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Biomimetic and Bioorganic Chemistry III Editors: E V6gtle, E. Weber With Contributions by M. Badertscher, E M. Menger, Y. Kanaoka, P. Portmann, E. Pretsch, G. Schmidt, I~ Tanizawa,M. Welti
With 52 Figures and 13 Tables
Springer-Verlag Berlin Heidelberg NewYork London Paris Tokyo
This series presents critical reviews of the present position and future trends in modern chemical research. It is addressed to all research and industrial Chemists who wish to keep abreast of advances in their subject. As a rule, contributions are specially commissioned. The editors and publishers will, however, always be pleased to receive suggestions and supplementary information. Papers are accepted for "Topics in Current Chemistry" in English.
I SBN 3-540-16724-2 Springer-Verlag Berlin Heidelberg New York ISBN 0-387-16724-2 Springer-Verlag New York Heidelberg Berlin Library of Congress Cataloging-in-Publication Data (Revised for vol. 2) Biomimetic and bioorganic chemistry. (Topics in current chemistry = Fortschritte der Chemischen Forschung; 128, 132, 136) Vot. 2 editedby F. V6gtle, E. Weber. Includes bibliographies and indexes. I. Biological chemistry - - Collected works. 2. Bioorganic chemistry - - Collected works. I. Cammann, Karl. II. V6gtle, F. (Fritz), 1939-. IlL Weber, E. IV. Series: Topics in current chemistry; 128, etc. QDI.F58 vol. 128 540s [574.19'2] 85-2804 [QP514.2] This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use, a fee is payable to "Verwertungsgesellschaft WOW', Munich.
© by Springer-Verlag Berlin Heidelberg 1986 Printed in GDR The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Typesetting and Offsetprinting: Th. Miintzer, GDR; Bookbinding: L~ideritz & Bauer, Berlin 2152/3020-543210
Table of Contents
Chemistry of Multi-Armed Organic Compounds F. M. Menger
. . . . . . . . . . . . . . . . . . . .
Calculation of Interaction Energies in Host-Guest Systems M. Badertscher, M. Welti, P. Portmann, E. Pretsch
....
17
Design of Biospecific Compounds which Simulate Enzyme-Substrate Interaction K. Tanizawa, Y. K a n a o k a . . . . . . . . . . . . . . . .
81
Recent Developments in the Field of Biologically Active Peptides . . . . . . . . . . . . . . . . . . . . .
109
Author Index Volumes 101-136 . . . . . . . . . . . . .
161
G. Schmidt
Table of Contentsof Volume 128
Biomimetic and Bioorganic Chemistry Solvation and Ordered Structure in Colloidal Systems G. Ebert Active Transport of Ions Using Synthetic Ionophores Derived from Macrocyclic Polyethers and the Related Compounds M. Okahara, Y. Nakatsuji Quantitative Structure-Reactivity Analysis of the Inclusion Mechanism by Cyclodextrins Y. Matsui, T. Nishioka, T. Fujita The Role of Molecular Shape Similarity in Specific Molecular Recognition T. Endo Macrocyclic Polyamines as Biological Cation and Anion Complexones - - An Application to Calculi Dissolution E. Kimura Micellar Models of Zinc Enzymes W. Tagaki, K. Ogino Chemical Basis of Ion Transport Specificity in Biological Membranes D. W. Urry Ion-Selective Bulk Membranes as Models for Biomembranes K. Cammann
Table of Contents of Volume 132
Biomimetic and Bioorganie Chemistry lI Molecular and Functional Aspects of Superoxide Dismutases A. G~irtner, U. Weser Hemoglobin Model -- Artificial Oxygen Carrier Composed of Porphinatoiron Complexes E. Tsuchida, H. Nishide Molecular Catalysis by Polyammonium Receptors F. P. Schmidtchen Complexatinn of Organic Molecules in Water Solution J. Franke, F. V6gtle
Chemistry of Multi-Armed Organic Compounds
Fredrie M. Menger D e p a r t m e n t o f Chemistry, Emory University, Atlanta, G e o r g i a 30322/U.S.A.
Table of Contents 1 Introduction
. . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 Multi-armed Polyethers
. . . . . . . . . . . . . . . . . . . . . . .
3 Multi-armed Compounds with Ion-Terminated Chains . . . . . . . . . . .
2 2 7
4 Neutral Multi-armed Materials . . . . . . . . . . . . . . . . . . . .
10
5 Polymer Systems . . . . . . . . . . . . . . . . . . . . . . . . . .
13
6 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . .
15
7 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . .
15
8 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
15
Topics in Current Chemistry, Vol. 136 i ~' Springer-Verlag, Berlin Heidelberg 1986
Fredric M. Menger
1 Introduction When chemists carry out a reaction in the laboratory, they hope that a suitable fraction of the molecular collisions will possess sufficient energy and the proper geometry for a successful transformation. If the reaction rate is slow, little can be done about increasing the percentage of successful hits. The best one can do is to increase the temperature and thereby increase the total number of collisions per unit time. This is a fairly crude procedure and not practical for biological systems which must operate within a well-defined and narrow temperature range. Thus, enzymes do not depend on highly inefficient random collisions, but function instead by collecting the necessary species in a "cavity" or "pocket" located on the protein surface. The correct orientation and distance, forced upon the reactive functionalities within this restricted volume, greatly accelerates reaction rates. Clearly, organic chemists must synthesize cavitybearing molecules in order to satisfactorily model enzymes. This paper deals with one particular type of "space-encompassing" compound: the multi-armed system. Our own interest in multi-armed compounds stems from work with micelles 1). Micelles are spherical aggregates of roughly 50-100 surfactant molecules each comprised of a polar head group and a long hydrocarbofi chain. A huge number of papers have been devoted to micellar reactions owing, in part, to their superficial resemblance to enzyme-catalyzed processes. Micelles bind compounds, for example, with association constants rivaling those for many enzymes and their substrates. Binding to micelles often leads to catalyzed reactions obeying Michaelis-Menten kinetics 2). Stereoselectivity is possible with micelles composed of chiral surfactants 3). Yet there is a rather serious disadvantage of micellar systems: to observe micellar effects, the surfactant concentration must exceed a critical micelle concentration. Otherwise, the surfactant exists entirely in the monomeric state. Thus, it is natural to think of tying the chains together by covalent linkages in order to prevent the chains from dissociating from each other. Such a multi-chain or "multi-armed" compound could behave like a micelle at all concentrations. The above paragraph reflects our original motivation for studying multi-armed species. Other investigators in the area undoubtedly had different reasons for constructing molecules with many appendages. Probably the likelihood of interesting and perhaps unique properties stimulated much of the research. And in all cases, I feel certain, the investigators were intrigued by the admittedly anthropormorphic resemblance of their systems to the human hand and its capability to grasp. Although this review is not exhaustive, the examples herein should serve to illustrate the important properties of multi-armed compounds as far as they are now known. A concise, almost compressed, format should provide the reader an overview with a minimum amount of reading time.
2 Multi-armed Polyethers In 1974 V6gtle and Weber published a paper entitled "Octapus Molecules" *). The paper describes a hexasubstituted benzene derivative (1 a) which shows "remarkable phenomenological parallelisms to the mode of food capture by an octopus using its suction pads." Compound (1 a), a water-insoluble oil, was found to be a powerful
Chemistry of Multi-Armed Organic Compounds
ligand for cations. Thus, a dichloromethane solution of ( l a ) is able to extract metal picrates (Li ÷, Na ÷, K ÷, Ca 2+, Mg z+ , etc.) from an aqueous phase (and do so more rapidly and completely than do the corresponding solutions of crown ethers). Neither (la) nor crown ethers are able to extract heavy-metal salts (CuC12, NiCI2, Ce(SO4)2, etc.) from water. R
R
R
I
I
1
d
:-7 :-7
I
I
R
I
R
R
la
The complexing ability of the multi-armed polyethers diminishes when (a) the arms are shortened so as to possess only two oxygens per arm and (b) the number of arms are successively reduced. This is illustrated with formula (1)-(4) (a) and (b). Apparently, the most stable complex forms when six chains residing on the same side of the benzene ring surround the metal ion. Three chains on the same side of the aromatic ring can best enclose a "cavity" favourable to metal ion complexation if the chains are in a 1,3,5 relationship [cf. (2)] as opposed to 1,2,3 [cf. (3)] or 1,2,4. Ligand properties for the 2-chain molecules are found only with the 1,2-isomer (4). R
R
1
°
R
R
R
R
2
R
R: c . 2 s / - V - - V - - x o _ o
/---k / - - k b : R = CH2S
0
OCH 3
3
04.9
g
t-'redric M. Mcl]ger
Steric overcrowding in (I a) is apparent from a broad a-methylene proton signal. Broadening, indicative of hindered internal rotation, varies with the nature of the arms: shorter arms impede rotation less than long ones R R,~ . . ~
R
..R
R
R
Signal broadening (e~-CH2)
R_C12 H25S m n- C~H9 S - CH3 S - -
Marked Moderate None
R
Fig. 1. 14 nmr characterization of (1 a)
(Fig. 1). Reducing the number of arms also decreases the crowing and hence the signal line-widths. V6gtle and co-workers 5) synthesized a host of neutral "tripod" and "tetrapod" ligands (6). Cation selectivity depends on the particular end-group R. When the endgroup is a quinolyloxy unit, the ligand binds Ba 2+ with an association constant close to 103 M-1 (at least an order of magnitude higher than that for the corresponding "dipod" ligand). When phthalimido is the end-group, one can form and isolate a solid complex with FeC13. Various other end-groups give solid complexes with ZnCI2, RbI, and Th(NO3)4.
5R
6 0
a'R= [ ~ N - 0
b'R=@ 0
Hyatt 6) attached six polyether chains onto a rigid and bowl-shaped cyclotriveratrylene framework (7). These chains are capable of surrounding a space which incorporates metal ions. The length of the polyether arms, --(CzH40--),R, does not appear to be particularly critical to binding as long as n > 1. For example, the derivatives with n = 2, 3, and 4 all bind Na + rapidly and strongly, and they all bind Mga+ slowly and weakly. On the other hand, the stereochemistry and conformational rigidity of the supporting framework does play a crucial role in binding. No complex is observed, for example, with an 8-armed analog shown with formula (8). Examination of molecular models show that conformationally mobile aromatic rings do not readily adopt a bowl-shaped configuration necessary for the chains to enclose a cavity. As a consequence, crown ether-like behavior is not observed. 4
Chemistryof Multi-ArmedOrganicCompounds
EtO~ 7 ~OEt
R O T O R
H3C."
3
R = ~C2H~OC2H~OC2H~OCH3
8
Montanari and co-workers 7) used °'polypode" ligands (9) as phase-transfer catalysts. Thus, a saturated aqueous solution of KI was stirred with n-octyl bromide in the presence of a multi-armed ligand; the resulting production of n-octyl iodide was followed by gas chromatography. Catalyst activity was found to vary with the hydrophobicity of the arms. When the chains are terminated by butyl groups, 72 hours
(n-CsHI~-OC2H ~OC2Hz.OC2H&OC2H~)2N ~ c / / N , , , c / N
( C2HLOC2H~OC2H&OC2Hz.On-CaH17}2
I II N%cIN I N { C2H~OC2Hz.OC2Hz.OC2Hz~Or) - C8H 17)2
9
Fredric M. Menger are required for an 82 ~ yield. When the chains are terminated by octyl groups, only 3 hours are needed for an 85 ~o yield. The latter efficiency approximates that of hexdecyltrimethylphosphonium bromide and certain cryptates. The authors speculate that an associative apolar interaction among the terminal alkyl groups leads to a relatively stable cavity within the polyoxymethylene chains which favors chelation of metal ions. Although the majority of compounds discussed in this paper have linear arms, cases are known in which a central unit bears multiple ring substituents. A good example (10) was investigated by Weber s). This material is highly soluble in water
/--5
(-o ,o-) 10 but relatively insoluble in nonpolar solvents such as chloroform. Interestingly, the properties of the compound resemble those of a surfactant: (a) Aqueous solutions of (10) foam; (b) Concentrating (10) in water elevates the viscosity until there is formed a reversible, opaque, and almost immobile gel; (c) Warming aqueous solutions of (10) causes clouding at 52-54 °C; (d) Light scattering experiments indicate the formation of micelles with a critical micelle concentration of 1.3 x 10 .4 M and an aggregation number of 50. Weber states that the surfactant-like behavior was unexpected, and the present author is likewise astonished. Undoubtedly, many other pleasant surprises lie in store for the octapus chemist.
Chemistry of Multi-Armed Organic Compounds
3 Multi-armed Compounds with Ion-Terminated Chains "'Tentacle" molecules having ion-terminated hydrocarbon chains that radiate from a central unit are relatively rare in the literature. Suckling 9) examined benzene-1,3,5tricarboxylic acid esterified with three [CH2]nNRa+ groups. The resulting tentacle molecule (11) forms complexes with small aromatics in acetonitrile but not in methanol.
C--O{CH2)11 N~ . . ~
/~--~c. o c~]~'c o{c.)~/-~--~ 0
0
11
For example, high-field NMR data demonstrate that at equimolar quantities of (11) and phenol (3.3 x 10 -3 M in acetonitrile), 85-90% of the phenol is bound. When phenol is in great excess over (11), several phenol molecules interact with each tentacle molecule. Binding ofp-nitrophenolate to (11) in acetonitrile occurs with a huge association constant: 1.7 × 106 M -I ! Suckling also found that when phenol is enmeshed in the arms of (11), the phenol becomes resistant to the normally rapid chlorination by t-butyl hypochlorite. Protection of labile compounds, such as drugs, through encapsulation constitutes only one of several potential uses of multi-armed systems. "Hexapus" (12), developed in our laboratory lo), also falls into the category of multi-armed compounds with ion-terminated chains. Six [CHz]loCOf chains project from a cyclotriveratrylene framework. Surprisingly, hexapus exhibits much less surface activity than single-chained fatty acid anions. Aqueous solutions of hexapus do not foam, and they possess surface tensions only slightly smaller than that of pure water. Apparently, the tendency of hexapus to absorb at the air-water interface is impaired by the difficulty of placing above the water phase both the hydrocarbon portion of the tails and the aromatic "cap".
ccH~l~o~ ~o~
(.CH2)1o
,i:;,, °
~ot
d
o
I
I
(CH2}1o (CH2)1o
0%
12
7
l--redric M. Menger
Hexapus in water solubilizes cholesterol, phenol blue (K ..... = 1.0 x 104 M 1), naphthalene, and hydrophobic esters. Thus, hexapus seems non-selective in its binding characteristics (just like micelles). "Universal" binding has the advantage that almost any water-insoluble compound can be "collected" by the host molecule without regard to subtle structural variations. On the other hand, potential catalysts based on hexapus and other multi-armed systems would not be expected to manifest high specificity. Flexible chains do not lend themselves to a precise fit. We were curious as to whether hexapus, where six chains are tied together covalently, would form aggregates in water as do single-chained fatty acid anions above a critical micelle concentration. Light scattering data show that hexapus does indeed assemble into small aggregates of about 9 for a total of 54 chains. Neither light scattering nor UV spectrophotometry reveals a critical micelle concentration for hexapus; if there is one, it must be extremely low (less than 1 x 10 -5 M). At present we do not know whether guest molecules bind among the chains of a single hexapus molecule or among the chains of several hexapus molecules within an aggregate. Whichever the case, it is clear that hexapus has a distinct advantage over micelles: binding occurs at all concentrations, not just above a certain critical concentration. We also investigated 11) three "trigapus" molecules (13)-(15). By themselves, the trigapus molecules are fairly mundane. Unlike c0-phenylalkanoic acids, they have no
O(CH2)loCOe
O(CH2)10COe
O(CH2)loCOe eO2C(CH2)loO'~O(CH 2)10COe
13
O(CH2)~oCO2e14:
15
critical micelle concentration, form only very small aggregates barely detectable by light scattering, and do not bind small organics in water. Covalent attachment of the chains obviously has a dramatic effect on the colloidal behavior of amphiphilic molecules. The most interesting properties of the trigapus molecules relate to their interaction with cationic surfactants such as decyltrimethylammonium bromide (DTAB). Small amounts of trigapus lower DTAB's critical micelle concentration 10-fold. It is as if trigapus "seeds" micellization of the cationic surfactant. Eow levels of trigapus also induce a huge growth in the size of DTAB micelles; thus, 1.3 mM trigapus elevates the aggregation number of DTAB micelles by at least an order of magnitude. Since these effects are not observed with trigapus and anionic surfactants, we presume that electrostatic attractions are critical to the phenomena. Murakami and co-workers 12) have carried out one of the most thorough investigations of multi-armed compounds with ion-terminated chains. In 1979 they reported the substrate-binding behavior of an azaparacyclophane (16) in which the hydrophobic cavity was deepened by substitution of long ion-terminated chains on the macrocyclicskeleton. Salient propertiesofthe cyclophane (16) include: (1) The compound has a critical micelle concentration of 3.2 x 10 -4 M. (2) (16) binds cationic and neutral dyes but not anionic ones. Thus, Rhodamine 6G and Quinaldine Red form 1 : 1 complexes with (/6) having association constants of about 5 x 103 M -1.
Chemistry of Multi-Armed Organic Compounds
--
t {H2~)10
/H2"-~CH2N!O~j~i~ eO 2C{CH2)ION"
\
/
N(CH2)10C02e
(([H2)1O
coe2 16
These bulky guests presumably reside in a cavity surrounded by the four aromatic rings of the cyclophane and the four alkyl branches. Since guests are incorporated into (16) below its critical micelle concentration, monomeric (16) provides an effective binding site apart from micellization processes. (3) Binding of p-nitrophenyl 3,5dimethylcyctohexylacetate to (16) inhibits the basic hydrolysis of the former by a factor of 147 relative to the rate without (16). The rate data obey "reverse" MichaelisMenten kinetics. (4) Hydrophobic spin probes, but not hydrophilic ones, bind to (16) and, as a consequence, have their rotational correlation times increased by as much as 3-fold. Hyperfine splitting constants do not, however, change on binding, suggesting that (16) associates only with the hydrophobic portion of the spin label while the nitroxide moiety remains outside in the water. One can readily imagine multi-armed compounds bearing catalytically active groups; such materials could conceivably emulate enzymes by binding substrates prior to an intramolecular-type catalytic process. An example of this sort, provided by Murakami and co-workers ~3), is shown under (17). The compound has two long alkyl chains terminated by cationic nitrogens; two other chains have, in addition, an imidazole ring with well-known catalytic properties toward ester hydrolysis. No
CH2IM
.
/
CH2
Me2[N@' I (H2C}1o CH2NC
/
,oo/92-,o\ ,
IMCH2Me2N(CH2)loN
\
C
/ (.CH2ho Me2~e
CH2IM 17
.
.N(CH2)10NMe 2CH2IM
Fredric M. Menger catalysis is observed with p-nitrophenyl esters of acids having eight carbons or less. On the other hand, fatty acid esters with chains of 10-16 carbons do indeed experience a catalyzed hydrolysis in the presence of (17). Since the C~4 substrate reacts the fastest among the esters, the authors state, "There must be a certain threshold for the length of the alkyl chain of the substrate in order to attain the most favorable arrangement of both the ester bond of an incorporated substrate and the catalystic group (or groups) of an octopus cyclophane; this is achieved with the substrate, p-nitrophenyl tetradecanoate." Although the selectivity is really quite small (the Clo-C16 esters differ by less than a factor of 3), the concept as embodied in the quote is an important one. Selectivity among similar compounds, and regioselectivity among similar functional groups in a single compound, remain a primary goal of all chemists engaged in the design of cavities.
4 Neutral Multi-armed Materials Tsukube 14) reported in 1984 a "multi-armed cyclam" (18) which has the ability to transport N H + cation through a chloroform layer (a so-called "liquid membrane"). Metal ions such as K + are not transported under similar conditions, a selectivity generally unobserved with the common crown ethers and cryptates. Since the transport rate decreases substantially when the furan rings terminating the pendant arms are
0
0 .~
18
replaced by benzene rings, the furan oxygens must play an important role in the complexation of NH4+ cation. Tsukube feels that the ability of the multi-armed cyclam to differentiate NH4+ from K + is probably not related to ion-size (which is similar for the two ions). Instead, he suggests that charge distribution (being tetrahedral for NH~+ and spherical for K +) is critical. CPK models indicate that the NH4+ cation can be wrapped tetrahedrally by its donating two hydrogen bonds to opposite ring nitrogens and two hydrogen bonds to furan oxygens. The furan-bearing crown (19), binds both NH4+ and K ÷ ; substitution of benzene for furan has, in this case, only a minor effect on the transport properties of the system. MacNicol and Wilson 15) synthesized a series of compounds (20) called "hexahosts". Such hexa-substituted benzenes can, on crystallization from suitable solvents, from a wide range of inclusion compounds. When Y = SPh, for example, a crystalline complex with CCI~ was isolated having a host-guest stoichiometry of 1 : 2. The CC14 is 10
Chemistry of Multi-Armed Organic Compounds
£o o) 19 slowly lost upon standing. Whereas the Y = C H 2 O P h and Y = CH2SPh compounds both retain toluene, no such behavior was observed with Y = CH2SePh. By far the largest number of inclusions compounds was obtained with the hexa-host having Y = CH2SC6H4-t-Bu- p. Cyclooctane, phenyl iodide, bromoform, etc. all yield relatively stable crystalline complexes with this material. y
Y=~SPh ~CH2OPh ~CH2SPh Y
2O
In more recent work, MacNicol and co-workers 16) described the first nitrogenbased hexa-host molecules (21). Although the derivative with R = COCHa (21a) shows no evidence of guest inclusion, the derivative with R = COCF3 (21b) gives 1 : 2 host: guest adducts with nitromethane, tetramethylurea, N,N-dimethylformamide, etc. One of the most interesting observations pertains to the complex between the fluorine-containing host and the amide (22). Only the thermodynamically less stable Z-form of the amide incorporates into the crystals. Thus, the host displays complete configurational selectivity !
~
H2Ph NR
I CH2
PhCH2--'NR--CH2~CH2--NR,CH2Ph PhCH2~NR--CH2"
T
"CH2--NR--CH2Ph
NR I
CH2Ph R= COCH3 21 b R = COCF3 11
Fredric M. Menger
BUrN/Me •
BUrN/Me
I
I
H./C~o E
o//C~H Z
22
Newkome and coiworkers 17) have recently developed an entirely new approach to multi-armed systems in their synthesis of "cascade" molecules. Rather than attaching chains to a central unit, they utilized a series of reactions which converted a single functional group into three functional groups. Each of the new functional groups can, in turn, be converted into three groups for a total of nine. Such a strategy could be continued to construct increasingly complex "tree-like" materials. A specific example, the synthesis of"[27]-arborol" (22), is given in Scheme 1. No doubt, intriguing new molecules are on the horizon.
/CH2OH CH3(CH2)4.CH2CHO
[,,,/~OCH2CO2CH3
~ R~C,~CH2OH \CH2OH
~-- R
j"
-)CH2CO2CH3 20020H3 (R=n- C5HI~)
/•%
2c2H5 O2C2H5 .CO2C2Hs
cOR ~ R
~
~
T
-O
CO2C2H5
%.
LORr
~/cO2C2H5 CO2C2H5 "~CO2C2H5 NHC(CH2OH)3 ONHC(CH2OH)3 ONHC (CH2OH)3 W ~OO I / / " ~ C O N HC(CH20 H)3 [ [ "CONHC(CH2OH)3 CONHC(CH2OH)3 ~C%
NHC(CH2OH)3
ONHC(CH2OH)3 ONHC(CH2OH)3
12
Chemistry of Multi-Armed Organic Compounds
5 Polymer Systems Thus far the discussion here has focused on compounds having multiple arms radiating from a small central unit such as a benzene, cyclotriveratrylene, or cyclophane ring. The number of such systems in the literature is, as yet, rather small. In contrast, there exists a vast body of data on polymeric chains bearing "arms" of various lengths. I have included a section on these polymers but obviously not with the intention of even superficially covering the subject. I merely wish to present four examples so that the interested organic and bio-organic chemist may, for comparison purposes," see how "arms" behave when they are covalently linked to a macromolecular backbone. Almost three decades ago, Strauss and co-workers 18) carried out classic work on "polysoaps" (23) comprised of poly-4-vinylpyridine which had been quaternized on up to 38 % of the nitrogens with n-dodecyl bromide; those nitrogens that escaped reaction with n-dodecyl bromide were then derivatized with ethyl bromide. Now addition of KBr to an aqueous solution of a polyelectrolyte normally decreases the viscosity. This is not true for the 38 % polysoap (23) where the viscosity increases with
~CH2~CH
~
C H 2 ~ C H
(~H2)11 CH3
~
CH2~CH~
(~H2)11 CH3
~H2 CH3
23
KBr until the solutions eventually gel. Viscosity data indicate that the polysoaps are far more compact than the random coils associated with ordinary polyelectrolytes in solution. In addition, the 38 % polysoap (23) forms intermolecular aggregates in solution owing to the "sticky" hydrophobic spots on its surface. Disaggregation induced by dilution is a slow process (taking several hours). If one decreases the percentage of dodecyl groups on the polymer (relative to ethyl groups), then it is possible to revert back from polysoap behavior to that of a typical polyelectrolyte. This change occurs over a rather narrow composition range, suggesting the existence of a "critical dodecyl group content" analogous to the critical micelle concentration for simple soaps. Cordes and co-workers tg) found that the alkaline hydrolysis of p-nitrophenyl hexanoate is subject to catalysis by polyvinylpyridine-based polysoaps. For example, kobs is increased from 0.1 min -1 to 1.4 min -1 in the presence of 5 x 10 -7 M 38% polysoap (23) (the same material used in the Strauss work). With 5 x 10 -7 M polymer having a 15 % dodecyl content, the rate is increased only 3 times above background. The simplest rationale for the kinetics invokes both hydrophobic and electrostatic forces. Thus, dodecyl chains on the polymer hydrophobicaUy bind p-nitrophenyl hexanoate to the polymer surface. Since the polymer possesses a high density of cationic nitrogens, hydroxide ions also accumulate at the polymer surface where they catalyze the hydrolysis of bound ester. Addition of nitrate ion to the aqueous reaction 13
Fredric M. Menger
mixture converts the polysoap-catalyzed process into a polysoap-inhibited one presumably because the nitrate displaces hydroxide counterions from the active sites. Klotz and co-workers zo) attached pendant butanoyl, hexanoyl, and dodecanoyl groups onto polyethylenimine (24), a highly branched water-soluble polymer containing approximately 25 % primary and tertiary nitrogens and 50% secondary nitrogens. Roughly 8-10 % of the residues of the polymer were acylated. The acylH2N (CH2CH2NH)× (CH2CH2NI)y(CH2CH2NH)z-/
CH2 ,
I
CH2
I
N--
I polyethylenimines are vastly more effective in binding a dye, methyl orange, than is serum albumin under comparable conditions. Thus, at a free methyl orange concentration of 10 -5 M, the dodecanoyl, hexanoyl, and butanoyl derivatives bind 100, 10, and 1 dye molecules, respectively, compared to a value less than unity for bovine serum albumin. The improvement over albumin is impressive since the protein contains nearly 40 % of nonpolar residues (although obviously not as long as a dodecyl chain). Urea (9.0 M) markedly reduces the binding affinity of the dodecanoyl-polyethylenimine. The dependence of binding on the dye concentration shows a strong cooperative interaction. In other words, each methyl orange anion creates, as it is bound, a new strong apolar site for additional binding. Finally, mention should be made of the polysoap-catalyzed decarboxylation of 6-nitrobenzisoxazole-3-carboxylate anion (Eq. 1) studied by Kunitake and co-workers 2tL This reaction is known to proceed faster in apolar solvents than polar ones.
-co2
N
O2N
O2N
e
'File polymers employed were (among others) partially dodecylated poly(2-ethyl-1vinylimidazole) (25). It was found that polymer containing 29 700dodecyl groups and 67 % ethyl groups catalyzes the decarboxylation 350-fold, whereas, a polymer with 9 % dodecyl groups and 83 % ethyl groups does not display significant catalysis. This kinetic behavior parallels the spectral shifts of bound methyl orange. When the dye --CH2--CH--
CH2--CH - - CH2-- C H - -
I
I
I
n- C12H25
n -C2Hs
n- C12H25
25 14
Chemistry of Multi-Armed Organic Compounds is b o u n d to the 29 % polymer, the )~maxshifts from 465 nm to 417 nm, attributable to a microenvironment less p o l a r than water. In contrast, the catalytically inactive 9 % polymer hardly perturbs the spectrum o f methyl orange. Since the catalytic efficacy o f the 29 % polymer exceeds that o f a conventional cationic micelle, tying chains together covalently can contribute positively to a rate process.
6 Concluding Remarks Attaching multiple arms to a central unit has been shown to impart interesting chemical and physical properties not always predictable from the properties o f the individual arms. Since the field o f multi-armed c o m p o u n d s is relatively undeveloped, there is obviously much r o o m for the imaginations of synthetically and physically inclined chemists to wander freely.
7 Acknowledgement This w o r k was supported by the N a t i o n a l Institutes o f Health and the Petroleum Research Fund.
8 References 1. 2. 3. 4. 5. 6. 7. 8. 9. t0. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
Menger, F. M.: Acc. Chem. Res. 12, 111 (1979) Menger, F. M., Portnoy, C. E.: J. Am. Chem. Soc. 90, 1875 (1968) Bunton, C. A., Robinson, L., Stam, M. F. : Tetrahedron Lett. 121 (1971) Vfgtle, F., Weber, E. : Angew. Chem. Int. Ed. Engl. 13, 814 (1974) V6gtle, F., Mfiller, W. M., Buhleier, E., Wehner, W. : Chem. Ber. 112, 899 (1979) Hyatt, J. A.: J. Org. Chem. 43, 1808 (1978) Fornasier, R., Montanari, F. : Tetrahedron Lett. 1381 (1976) Weber, E. : Angew. Chem. Int. Ed. Engl. 22, 616 (1983) Suckling, C. J. : J. Chem. Soc., Chem. Commun. 661 (t982) Menger, F. M., Takeshita, M., Chow, J. F.: J. Am. Chem. Soc. 103, 5938 (1981) Menger, F. M., Angel de Greiff, A.J., Jaeger, D. A.: J. Chem. Soc., Chem. Commuq. 543 (1984) Murakami, Y., Nakano, A., Miyata, R., Matsuda, Y. : J. Chem. Soc., Perkin I, 1669 (1979) Murakami, Y., Nakano, A., Akiyoshi, K., Fukuya, K. : ibid 2800 (1981) Tsukube, H.: Chem. Lett. 1961 (1984) MacNicol, D. D., Wilson, D. R.: J. Chem. Soc., Chem. Commun. 494 (1976) Freer, A. A., Gall, J. H., MacNicol, D. D.: ibid. 674 (1982) Newkome, G. R., Yao, Z , Baker, G. R., Gupta, V. K.: to be published in J. Org. Chem. Strauss, U. P., Gershfeld, N. L., Crook, E. H.: J. Phys. Chem 60 577 (1956) Rodulfo, T., Hamilton, J. A., Cordes, E. H.: J. Org. Chem. 39, 2281 (1974) Klotz, I. M., Royer, G. P., Sloniewsky, A. R. : Biochem. 8, 4752 (1969) Kunitake, T., Shinkai, S., Hirotsu, S. : J. Org. Chem. 42, 306 (1977)
15
Calculation of Interaction Energies in Host-Guest Systems
Martin Badertscher, Martin Welti, Pius Portmann and Ernii Pretsch Department of Organic Chemistry, Swiss Federal Institute of Technology, CH-8092 Ziirich, Switzerland
Table of Contents 1 Introduction
. . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 Ab Initio Calculations oflon-Ligand Interaction Energies . . . . . . . . . . 2.1 2.2 2.3 2.4 2.5 2.6
Introduction . . . . . . . . . The Supermolecule A p p r o a c h . . Basis Sets . . . . . . . . . . . Geometries . . . . . . . . . . Correlation Energy . . . . . . C o m p a r i s o n with the Experiment
. . . . . .
. . . . . .
. . . .
. . . .
. . . . . . . . . .
. . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . .
. . . . . .
. . . . . .
3 Treatment of Large Systems . . . . . . . . . . . . . . . . . . . . . . 3.1 3.2 3.3 3,4
Introduction . . . . . . . . . . . . . . . . . . . . . . . . Pair Potential Procedure . . . . . . . . . . . . . . . . . . . . Additive Model o f Gresh, Claverie and Pullman . . . . . . . . . . C o m p a r i s o n o f the Two Models . . . . . . . . . . . . . . . . .
4 Conformational Energy
5 Future Prospects
. . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . .
. . . .
18 18 18 19 19 63 67 67 68 68 68 71 73 74
75
6 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . .
76
7
76
References
. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17 Topics in Current Chemistry, Vol. 136 © Springer-Verlag, Berlin Heidelberg 1986
Martin Badertscheret al.
1 Introduction There is a strongly growing interest in designing and synthesizing host compounds for selected guests 1). Although results of simple model calculations z-3) have been applied for the development of ligand molecules for many years 4,5), merely a minor part of these works is based on theoretical considerations. In most cases the design is mainly intuitive and the sole tools used are molecular models. More elaborate theoretical calculations have only been applied since a few years as a design aid 6). In the last decade much experience was collected independently on the host-guest chemistry in the field of the theoretical description of one particular kind of hostguest interaction: ions as guests and small ligand molecules as hosts 7-lo). Possibilities and limitations of such calculations are quite well known now. In the first part of this article the corresponding results will be reviewed. On the basis of these fundamental calculations different models were suggested for the description of host-guest interaction energies of larger systems. These models will be presented in Chapter 3. Since, in most cases, hosts (and often also guests) may adopt different conformations in different complexes as well as in the uncomplexed state, the calculation of the interaction energies is of only limited use if the conformational energy is not considered. Therefore several approaches of conformational energy calculations will be discussed briefly. The main purpose of the present paper is to help judging the current possibilities and limitations of theoretical calculations on host-guest systems. In the last Chapter we will try to summarize the topic from this point of view. An enormous work done in the field of polypeptides and proteins by Scheraga and coworkers includes calculations of both conformational energies and enzyme-substrate interactions for this special class of compounds 11- ~3).This kind of calculations on host-guest systems is well documented elsewhere and is not considered within the scope of this article.
2 Ab initio Calculations of Ion-Ligand Interaction Energies 2.1 Introduction Various methods for the calculation of ion-ligand interaction energies were discussed in several excellent reviews 7-9) Therefore only a brief summary is given here. In some cases classical electrostatic models may suffice to predict correctly relative interaction energies and equilibrium geometries 7) This success seems to be a consequence of error compensation 7~. Using such an electrostatic model, the interaction energies of a water molecule with alkali metal cations were calculated 14) within a few percent deviation relative to the experimental values measured in the gas phase 15) But for realistic ionophores only a qualitative use of this model can be made because appropriate parameters are lacking 2). Molecular electrostatic potentials are accessible from quantum chemical calculations and have been used to calculate interaction energies of ions with small ligand molecules 16) (see also Sect. 3.3). In a series of papers various semiempirical quantum chemical procedures were examined for their usefulness to describe ion-ligand interactions (for a review see 7)). t8
Calculation o f Interaction Energies in Host-Guest Systems
The results were not very successful in several respects: wrong geometries, nonrealistic interaction energies and extremly overemphasized charge transfer were obtained 7). These techniques are thus unsuitable for a reliable investigation of ionligand interactions.
2.2 The Supermolecule Approach Interaction energies (E1nt) on the basis o f a b initio calculations are in general evaluated according to the so-called supermotecule approach: Ein t :
Ecomplex - E t l o s t - E(;uest
(l)
E denotes on the right hand of the expression the total energy of the system specified. The interaction energy is by several orders of magnitude smaller than the individual total energies. Some consequences of this fact are discussed in the following sections. A large number of complexes of alkali metal, alkaline earth metal and ammonium cations has been studied using this approach (see Table 1). Much less effort has been made in the field of anions as guests. Some of these results are collected in Table 2. In case of complexes consisting of more than two constituents it has been shown that three-body terms are of significant magnitudes 12o,121) i.e. : E~,,t(ABC) ~ Eh,t(AB) + Eh,,,(BC) + Eh,t(AC)
(2)
2.3 Basis Sets The reliability of the ab initio calculations depends heavily on the choice of the basis sets. In order to reduce computational demands very often small basis sets have to be applied. According to experience, some rules can be given for the compatibility of the basis set with a given problem 122). It is suggested that for molecular geometry optimizations and for the description of ion-ligand interactions minimal basis sets might be sufficient. In contrast, large basis sets are necessary for the computation of weak intermolecular interactions 136) Many results shown in Table 1 clearly indicate that too small basis sets like STO-3G or a minimal GLO basis are inadequate to calculate reliable interaction energies (see also 31~).Their application is however justified if only relative stabilities and approximate geometries are to be evaluated. False geometries have been obtained for hydrogen bonded systems using the STO-3G basis set 123,124) It is also known that geometry optimizations with too small basis sets may lead to non-realistic geometries especially if torsion angles or pyramidal structures are concerned 122). In any case well-balanced basis sets are absolutely necessary, i.e. the quality of the basis set should be similar for all atoms. A carefully selected small GTO basis set may give reliable results for the ion-ligand interaction energies 31,12s,126) However, error compensations are at least partly responsible for this success. Therefore an improvement of the basis set may lead to less accurate results 91). Nonbalanced small basis sets lead to large basis set superposition errors lZ6-12s) This error is caused by the fact that in the calculations of the complex the wave functions 19
~
Ligand
NH 3
NH 3
NH 3
NH 3
NH 3
NH 3
NH 3
NH 3
NH 3
NH 3
NH 3
NH 3
Ion
Li +
Li +
Li +
Li ÷
Li p
Li +
Ei +
Li +
Li +
Li +
Li +
Li +
H N Li H, Li H N Li H, Li H, Li H N Li H N Li H, Li
all
N
N
N
N
H N Li H, N Li all
atom
Basis set h uncontracted
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
GTO (6/1) (11/7/1) (7/1) 4-31G (7/1) (4) (9/5) (7/1) 6-31G* (7/1) 6-31G** (7/t) (4/1) (9/5/1) (7/1) (3) (7/3) 6G3G 4-31G 5-21G
6-31G*
G T O (4) G T O (9/5/1) G T O (10) G T O STO-3G G T O 6G3G G T O 3-21G
type
[3/1] [3/1] [5/3/1] [3/1] [l] [2/11
[3/1]
[3/1] [3] [5/3] [3/1]
[3/1] [5/4/1] [3/1]
[2] [4/2/1] [4]
contracted
experimental
assumed
experimental
experimental
experimental
experimental
experimental
experimental
* 3-21G geometry
* fully optimized
assumed
* STO-4G geometry, * not varied
Ligand geometry/ * Complex geometry ¢
197
235 188
196 Li ----N 193 Li-----N
200 Li--N
200 Li---N 200 Li--N 200 Li--N
227
23~
212
z17
182
167
z1~
211
177 174
217
zl)
207
189
20t
161
197
229
not given I95 Li--N 195 Li--N 200 Li--N 195 Li--N
187
169
190 Li ----N
aT)
E(Int) Ref. [kJ/ mole]
R [pm]
Table 1. A b initio SCF calculations on the complexes of alkali, alkaline earth metal and a m m o n i u m cations with uncharged ligands? The ligands are ordered according to their molecular mass. e~
~
tO
NH 3
NH 3
NH a
NH 3
NH 3
NH 3
2 NH a
4 NH a
4 NH a
5 NH a
6 NH 3
H20
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li ÷
Li +
H N Li H N Li H N Li H N Li H N Li H 0 Li
H N Li H N Li H N Li H, N Li
H N Li all
GLO GLO GLO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
(5) (10/5) (10/2) (3) (7/3) (7) (4) (7/3) (7) (4) (7/3) (7) (4) (7/3) (7) (4) (9/5/1) (10)
G T O (4) G T O (7/3) G T O (7/2) G L O (5) G L O (10/5) G L O (10/2) G T O (3) G T O (7/3) G T O (7) G T O 4-31G G T O (8/2)?
G T O (5/1) G T O (11/7/2) G T O (10/3) G T O 4-31G
[11 [3/1] [3/11 [11 [2/11 [3] [ll [2111 [2] ill [2/11 [21 [1] [2/11 [2] [21 [4/2/11 [4]
[3/11
[21 [4/21 [4/2] [ll [3/11 [3/11 [11 [2/11 [31
[3/1] [5/5/21 [4/31
* from Ref. 32)
STO-3G geometry * tetragonal, * part. optimized STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized
not specified
assumed
not specified
not specified
assumed
experimental
experimental
assumed
200 Li--N 184 Li--O
200 Li--N
200 Li--N
205 Li--N
not given
197 Li--N
192 Li--N
not given
198 Li--N
197 Li--N 201 Li--N
157
741
723
653
515
395
211
167
209
224
213
169
17,
29)
29)
29~
28,
2v,
2s)
28)
27)
26)
25)
24)
a
~.
m
=o
.~
o
~"
(3
Ligand
H20
HzO
H20
H20
H20
H20
HaO
HzO
H20
H20
H20
Ion
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Table 1. (continued)
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
GTO (11/2) GTO GTO GTO GTO GTO GTO GTO
H, O Li H, O Li H O Li H O Li H O ti n O Li H O
Li H 0 Li H O Li all
contracted
(11/7/2) (7/2/I) (6/1) (11/7/1) [3/1] [5/4/11
[5/2] [2/1] [4/2/1] [4/2]
(6/1) (11/7/1)
(11/2) (4/1) (9/5/1) (9/3) 3-21G
[5/2]
[2/21 [4/3/2] [5/2/1] [3/1] [5/4/1]
(6/2)
STO-3G STO-3G + 1 p orbital STO-3G 6G3G (3) [1] (7/3) [2/1] 6G3G (6/1) [2/1] (11/7/1) [4/3/1] (7/1) [3/1] (6/2) [4/2] (13/8/2/1) [8/5/2/1] (812/1) [5/2/1]
GTO STO-4G
all
uncontracted
type
atom
Basis set b
* fully optimized
not specified
experimental
fully optimized
not specified
assumed
fully optimized
experimental
experimental
experimental
STO-4G geometry
Ligand geometry/ * Complex geometry ~
185 Li--O 177 Li--O
183 Li--O
189 Li--O
189 Li--O
184 Li--O
189 Li--0
183 Li-.O
183 Li--O 170 Li--O 17.5 Li--O
[pm]
R
238
155
151
151
147
147
143
169
200
335
168
19}
36)
35)
33J
32)
32)
31)
31}
31)
30~
--E(Int) Ref. [kJ/ mole]
o
~g
tO
H20
H20
H20
H20
H20
H20
H20
H20
H20
H20
H:O
H20
H20
Li +
Li +
Li +
Li ÷
Li e
Li +
Li +
Li +
Li ÷
Li +
Li-~
Li +
Li +
H O Li H O Li H O Li H O Li H O Li
H O Li H O Li H,O Li H O Li H O Li H O Li all
all
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
(9/10) (9/2) (4) (9/5) (7/1) (3) (7/3) (7)
(4)
(9/10) (9/2) (3) (9/10) (9/2)
(3)
(7/3) (7) (3) (7/3) (7/2) (3/1) (7/3/2) (7/2) 4-31G
(3)
(7/3) 6G3G 4-31G 5-21G
(7/1) (3)
(6/1) (ll/7/l)
GTO 6-31G*
[1] [2/1] [2/1] [31 [4/2] [411] [41 [6/4] [7/11 [3] [5/31 [3/11 [11 [2/11 [3]
[4/2]
[4/2/2] ?
[3]? [7/31? [7]? [317 [7/3]? [7/21? [2/1]
[3/11 [5/4/11 [3/1] [11 [2/1]
not specified
experimental
experimenta I
experimental
experimental
experimental
assumed
assumed
assumed
experimental
assumed
experimental
* 3-21G geometry
182 Li--O
183 Li--O
183 Li--O
182 Li--O
181 Li--O
184 Li--O 180 Li---O
181 Li--O
178 Li--O
183 Li--O 181 Li--O
180 Li--O
177 Li--O
156
182
182
195
198
200
163
137
190
200
170
141
163
28)
40)
39)
39)
39)
38)
37)
37)
37)
23)
22)
20)
19)
,'7
~Z
O
g
O
¢3
ba
Ligand
H20
H20
H20
H20
H20
HzO
2 HzO
2 H20
2 H20
4 HzO
4 H20
Ion
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Table 1. (continued)
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
H, Li
H O Li H O Li
H O Li t! O Li all
O
GLO GLO GLO GLO GLO GLO GLO GLO GLO GTO
H O Li H O Li H O Li all
[2/1] [4/2/1] [4/I] [1] [2/1] [1] [1] [2/1] [11
[3/1]
contracted
(3) (7/3) (7) (4) (7/3) (7)
[1] [2/11 [3] [11 [2/1] [2]
6-31G** 6-31G** + sp orbital (6/1) [3/1] (11/7/1) [5/4/1] (11/3) [5/2] (3) [21 (7/3) [4/2] (7) [4] 4-31G
(4/1) (8/4/1) (8/1) (1) (2/1) (2) (1) (2/1) (2) 6-31G**
G T O 4-31G G T O (8/2)?
H, O Li
uncontracted
type
atom
Basis set u
STO-3G geometry * tetragonal, * part. optimized
not specified
* not optimized
assumed
experimental
* 6-31G* geometry
* 6-31G* geometry
experimental
* fully optimized
* fully optimized
not specified
Ligand geometry/ * Complex geometry ~
185 Li--O
182 Li--O
179 Li-O 180 Li--O
192 Li---O
given
not
183 Li--O not given
183 Li--O
185 Li--O
182 Li - - 0
R [pro]
608
494
390
370
283
151
166
137
100
145
195
mole]
29~
28~
4-4-~
37)
4-31
42)
g2)
41)
.41)
4q)
28~
- - E (Int) Ref.
[kJ/
0 g~
g
g
tO Lpl
5 H20
6 H20
HF
HF
HF
HCN
HCN
HCN
HCN
CH 2= NH
HN=NH
H2CO
H2CO
H2CO
H2CO
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li ÷
Li ÷
Li +
Li ÷
Li +
Li +
Li ÷
H
all
H C,O Li H C,O Li all
all
H C,N Li H C,N Li all
all
H,F Li all
all
O Li all
H
O Li
6-31G*
(4) (7/3) (7) (4) (7/3) (7) 3-21G
GTO
GTO GTO GTO GTO GTO GTO GTO
GTO
GTO GTO GTO GTO GTO GTO GTO
GTO
6-31G*
(9/5) (9) (2) (5/3) (4) 3-21G
(4)
6-31G*
(7/3/1) (6/1) (4/1) (9/5/1) (6/1) 6-31G*
(3/1)
6-31G*
G T O 4-31G G T O 5-21G G T O 3-21G
GTO
GTO GTO GTO GTO GTO GTO GTO
[3] [5/3] [51 [21 [3/21 [3]
[2/11 [4/2/11 [3/1] [3/11 [5/3/1] [3/11
[1] [2/1] [21 [11 [2/1] [21
* 3-21G geometry
* fully optimized
from Ref. 47)
from Ref. 47)
* 3-21G geometry
* 3-21G geometry
not specified
not specified
* 3-21G geometry
* fully optimized
experimental
* 3-21G geometry
STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized * fully optimized
180 Li--O 173 Li--O 173 Li--O
177 Li--O
196 Li--N 191 Li--N 196 Li--N
194 Li--N
200 Li--O 168 Li--F 168 Li--F 175 Li--F 191 Li--N 191 Li--N
190 Li--O
168
222
188
181
138
189
155
164
156
194
144
117
183
680
671
19)
19)
46)
46)
45)
45)
7)
7)
19)
19)
23)
19}
19)
29)
29)
,'7
O
O
=_
('3
to
H2CO
H2CO
H2CO
H2CO
H20
H2CO
H2CO
H2CO
4 H2CO
5 H2CO
Li ÷
Li +
Li +
Li +
Li +
Li ÷
Li ÷
Li +
Li +
Li +
6 HSO
Ligand
Ion
TaMe 1. (continued)
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
H C,O Li all H C,O Li H C,O Li H C,O Li
[1l [2/11 [21 [11 [2/1]
[2] [1] [2/1] [2]
(7) (4) (7/3) (7)
[31 [5/311] [3/1]
[3] [5/3] [3/1]
[21 [4/21 [4] [21 [4/2] [4]
contracted
(4) (7/3) (7) (4) (7/3)
(4) (9/S/l) (7/1) 6-31G
H G L O (5) C,O G L O (10/5) Li G L O (10) H G L O (5) C,O G L O (10/5) Li G L O (10) counterpoise corrected H G T O (4) C,O G T O (9/5) L~ G T O (7/1) all G T O STO-3G
G T O 4-31G G T O 5-21G G T O STO-3G
H, C, O Li all
uncontracted
type
atom
Basis set b
STO-3G geometry * tetragonal, * part. optimized STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized
* fully optimized
assumed
* fully optimized
assumed
* part. optimized
* part. optimized
* fully optimized
experimental
Ligand geometry/ * Complex geometry c
210 Li--O
200 Li--O
185 Li-O
182 Li--O 177 Li-O
given
not
178 Li - - O
180 Li--O
180 Li--O
given
not
176 Li--O
520
524
489
185
161
404
184
171
174
308
198
29)
29)
291
52) 53)
40)
51)
501
49~
48~
23)
[pml molel
- - E (Int) Ret:
[kJ/
R
".---1
all H C,O Li H C,O Li H,C,O Li
CH3--NH 2
CH3--NH 2
CHa--NH 2
CHa--NH 2
CH3--NH 2
CHa--NH 2
HN=O
NHz--NH 2
CHa--OH
CH3--OH
CHs--OH
CH3--OH
CH3--OH
NH2--OH
Li ÷
Li ÷
Li +
Li +
Li +
Li ÷
Li ÷
Li +
Li +
Li +
Li +
Li +
Li +
Li + all
all
all
all
H,C,N Li H,C,N Li H,C,N Li H,C,N Li H C,N Li all
all
CH3--NH 2
Li +
all
CH3--NH 2
Li +
(7/1) 4-31G
(9/5/1)
STO-3G 6G3G 4-31G (7/1) 6-31G* (7/1) 6-31G** (7/1) (4/1)
[3/1]
[1] [2/11 [31
(3) (7/3) (7) 4-31G (8/2)?
[1] [2/11
[3/11 [3/1] [5/3/11 [3/1]
[3/1]
[3/1]
(3) (7/3) 6G3G
GTO 6-31G*
GTO GTO GTO GTO GTO GTO GTO GTO
GTO 6-31G*
GTO 3-21G
GTO 6-31G*
GTO 6-31G*
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
GTO 6-31G*
GTO 3-21G
* 3-21G geometry
not specified
not specified
assumed
* 3-21G geometry
* fully optimized
* 3-21G geometry
* 3-21G geometry
experimental
experimental
experimental
experimental
experimental
assumed
* 3-21G geometry
* fully optimized
181 Li--O 178 Li--O
180 Li--O
not given
200 Li--N not given 182 Li--O 193 Li--N 176 Li-O 176 Li--O
195 Li--N 195 Li--N not given 195 Li--N 2OO Li--N 2OO Li--N
177
203
154
169
172
243
199
113
204
167
173
175
200
220
187
235
45)
28)
28)
22)
t9)
19)
45)
45)
25)
21)
21)
21~
21)
18)
19)
~9)
,'7
o
0=
g~
g~
to
Ligand
HO--OH
CH3--F
PH 3
PH 3
HzS
H2S
H2S
H2S
H2S
NH2--F
HO--F
HC1
HCl
HCl
CHy-CN
Ion
Li +
Li +
Li +
Li +
Li +
Li +
Li ÷
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Table 1. (continued)
G T O 6-31G* GTO GTO G T O STO-3G G T O (7/1) G T O 4-31G G T O (7/1) G T O 3-21G GOT G T O 4-31G G T O 5-21G G T O 6-31G* GTO GTO GTO G T O 4-31G G T O 5-21G G T O 3-21G
all all all H, S Li H, S Li all all H, S Li all all all all H, CI Li all
6-31G*
3-2lG
6-31G*
6-31G*
6-31G*
3-21G
6-31G*
GTO
all
uncontracted
type
atom
Basis set b
[3/1]
[3/1]
contracted
* fully optimized
experimental
* 3-21G geometry
* fully optimized
* 3-21G geometry
* 3-21G geometry
experimental
* 3-21G geometry
* fully optimized
experimental
experimental
* 3-21G geometry
* fully optimized
* 3-21G geometry
* 3-21G geometry
Ligand geometry/ * Complex geometry ¢
258 Li--P 220 Li--S 240 Li--S 244 Li--S 244 Li--S 249 Li--S 182 Li--F 178 Li F 245 Li--C1 245 Li--C1 241 Li--C1 188 Li N
189 Li--O 166 Li--F 258
R [pm]
226
74
57
68
105
t52
109
75
98
92
t84
109
119
146
156
mole]
19)
23)
19)
19}
45)
45)
55)
19)
7~
7)
19)
19)
45)
45)
- - E ( I n t ) Ref.
[kJ/
V
I'0
CH2-NH-CH 2
CH3--CHO
CH3--CHO
CH2-O-CH 2
~Hz-O-~H2
CH3--NH--CH 3
CHs--NH--CH 3
CHs--NH--CH 3
CHs--CHz--NH 2
HCO--NH 2
HCO--NH 2
HCO--NH 2
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
l,
!
~ H2-NH-ffHz
Li +
I
CHs--CN
Li +
t.
CHs--CN
Li +
H C,N,O Li
I.i
H C,N Li H C,N,O Li H C,N,O
all
H,C,N Li all
all
all
all
all
all
H C,N Li all
all
GTO GTO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO
GTO
GTO GTO GTO
GTO
GTO
GTO
GTO
GTO
GTO GTO GTO GTO
GTO
(4/2) (4/1) (1) (2/1) (2)
(3)
[2/11 [1]
[1]
[3] [4/2] [4/11
[1] [2/11
(3) (7/3) 6G3G
[11 [2/1]
[1] [2/1]
(3) (7/3) 6G3G
6-31G*
STO-3G 6G3G 3-21G
6-31G*
6-21G
6-31G*
3-21G
6-31G*
(3) (7/3) 6G3G 6-21G
6-31G*
assumed
experimental
assumed
assumed
* 3-21G geometry
* fully optimized
assumed
* fully optimized
* fully optimized
* 3-21G geometry
* fully optimized
* fully optimized
* fully optimized
assumed
* 3-21G geometry
175 Li--O
172 Li--O
not given
not given
180 Li--O not given 193 Li--N 193 Li--N
196 Li--N 171 Li--O 171 Li--O 172 Li--O
not given t 89 Li--N
188 Li--N
~9~
182
171
234
212
58)
22)
221
19)
231
t77
is)
213
56)
252
56)
19~
190
182
x9)
~6)
56)
22)
19)
245
198
253
169
188
7
m
0~
O
=_
o
Ligand
HCO--NH 2
HCO--NH 2
HCO--NH 2
2 HCO--Ntt 2
C H 3 - - C H 2.--OH
CH3--O.--CH 3
CH3--O--CH 3
CHs--O--CH 3
CHs--O--CH a
HCOOH
CHa--PH 2
Ion
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li ÷
Li +
Table 1. (Continued)
* fully optimized * 3-21G geometry experimental
G T O (3) GTO (7/3) GTO 6G3G GTO 3-21G GTO 6-31G* G T O STO-3G GrO GTO GTO GLO GLO GLO GTO
all all H C, O Li H C, O Li all
(3) (7/3) (5) (1) (2/1) (2) 3-21G
[11 [2/11 [11 [1] [2/1] [1]
[11 [2/11
* fully optimized
assumed
experimental
assumed
experimental
experimental
experimental
assumed
H C, O Li all
H
[317 [4/21 [4/1] [1] [2/1] [1] [2/1] [4/2/1] [4/1] [3] [4/2] [4/1]
C, N, O Li
(3) (6/3) 56/1) (1) (2/1) (2) (4/1) (8/4/1) (8/1) (3) (4/2) (4/1)
GTO GTO GTO GLO GLO GLO GLO GLO GLO GLO GLO GLO
contracted
H C,N, O Li H C,N,O Li H C,N,O Li
uncontracted
type
Ligand geometry/ * Complex geometry ¢
atom
Basis set b
175 Li - - O 256 Li--P
170 Li---O
not given 175 l,i-- O 175 Li--O 170 Li--O
not given 183 Li--O 219 Li--N
177 Li--O
172 Li--O
R [Pml
61)
326
136
171
63)
62)
19)
172
131
19)
22)
60)
59)
59)
242
175
431
218
162
219
mole]
58)
- - E (Int) Refi
~J/
t~
ta~
CH3--CI
(CH3)2CH--CN
CH3--CO--CH 3
CHs--CO--CH 3
H~=O
HC=O
Li +
Li ÷
Li +
Li +
Li +
N(CH3) 3
(CH3)zCH--NH 2
CH3--CO--NH2
Li +
Li +
2 H~=O HC=O
Li +
Li +
HC=O
H~=O
CH3--CI
Li ~
Li +
H C, O Li
CHs--SH
Li +
C,N Li H C,N,O Li
H
C,O Li H C,O Li H,C,N Li
H
H C, N Li H C,O Li all
all
all
all
all
CH3--SH
Li +
all
CH3--PH z
Li +
(3~
(7/3) (7/3) STO-3 ) 6G36
(2) (4)
(8/4) (8) (I) {2/0
(4)
(7/3) 6G3G 6-31G
(3)
(7/3) 6G3G
(3)
,,/3) GTO 6G3G GLO (1) GLO (2/1) GLO (2)
GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO GTO GTO
GTO GTO GTO GTO GTO GTO GTO
GTO 6-31G*
GTO 3-21G
GTO 6-31G*
GTO 3-21G
GTO 6-31G*
[1] [2/q [1]
[1] [2/1]
[31 [4/2] [4] [1] [2/1] [1] [21 [4/2] [4/1]
Ill [2/1]
[11 [2/1]
experimental
assumed
assumed
assumed
experimental
experimental
* fully optimized
assumed
assumed
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
* 3-21G geometry
I75 Li--O
not given
202 Li--O not given
not given
not given
176 Li--O not given
not given
256 Li--P 240 Li--S 240 Li--S 233 Li--C1 233 Li--C1
178
181
201
425
113
197
222
181
158
87
111
I00
121
131
67}
22)
18)
66)
65)
64)
52}
22)
221
19)
19)
19)
19)
19}
Go
T ©
:=
5"
~J
K
g~
~ t,~
* fully optimized * 3-21G geometry
GTO 3-21G GTO 6-31G* GTO GTO GTO GTO GTO GLO GLO GLO GTO GTO GTO
all all H C S Li all H C,O Li H C,N Li
CH3--S--CH 3
CH3--S--CH 3
CH3--S--CH 3
F--CO--F
CHO--CH2--CHO
(CH3)3C--NH
Li +
Li +
Li +
Li +
Li +
Li +
2
* 3-21G geometry
GTO 6-31G*
all
CH3--PH--CH s
Li +
(2) (3) (7/3) 6G3G
(2/1)
(1)
(7/3) (9/6) (5) 6-31G
(3)
* fully optimized
GTO 3-21G
all
CHs--PH--CH s
Li ÷
* fully optimized
OH
6-31G
HO--CO
Li +
[1] [2/11 [1] [1] [2/1]
[1] [2/1] [3/2] [11
assumed
not given
not given
182
200
105
not given * fully optimized
assumed
70
119
136
t48
148
195
271
155
213
22)
65}
52)
62)
19)
19)
19)
19)
52)
52)
68)
22)
- - E ( l n t ) Ref. [kJ/ mole]
243 Li--S
177 Li--O not given not given 255 Li--P 255 Li--P 237 Li--S 237 Li--S
175 Li--O
R [pm]
experimental
* fully optimized
assumed
GTO
NH2--CO--NH z
Li +
[1] [2/1] [1]
assumed
all
HCO--NH--CH 3
[11 [2/1]
(3) (7/3) 6G3G (1) (2/1) (2) 6-31G
GTO GTO GTO GLO GLO GLO GTO
contracted
H C, N, O Li H C,N,O Li all
Li +
3
HCO--NH--CH
Li ÷
uncontracted
Ligand geometry/ * Complex geometry ~ type
Basis set b
atom
Ligand
Ion
Table 1. (continued)
~a
HCO--N(CH3) z
CH3--CO--NH--CH
CH3--CHz--O--CH 2 - C H 3
CH3--CHz--O--CH2--CH 3
CH3--COO--CH 3
CsHsN (pyridine)
CHO--CH2--CH2--CHO
CH3--CH2--CH2--CO--NH
CH3--CO--N(CH3) z
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li +
Li ÷
3
HCO--N(CH3) 2
Li +
3
HCO--NH--CH2--CH
Li +
z
CH3--CH2--CO--NH
Li +
z
H C,N,O Li H C,N,O Li H C,N,O Li H C,N,O Li H C,N,O Li H C,O Li H C,O Li H C,O Li H C,N Li H C,O Li H C, N, O Li H C,N,O Li GLO GLO GLO GTO GTO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO (2/I) (2) (I) (2/1) (2) (3) (7/3) (5)
(1)
(7/3) 6G3G
(3)
(7/3) (5) (3) (7/3) 6G3G
(3)
(2/1) (2) (1) (2/1) (2) (3) (7/3) 6G3G
(1)
(7/3) 6G3G
(3)
(2/1) (2) (3) (7/3) 6G3G
(1)
[1] [211] [I] [11 [2/I1 [11 [11 [2/11 [1]
[11 [2II1
[11 [2/1] [I] [11 [2/11
assumed
experimental
assumed
assumed
assumed
experimental
assumed
experimental * not varied
experimental
assumed
[1] [2/11 [11 [2/1] [1] [11 [2/11 [1] [1] [2/11
assumed
experimental
.Ill [2/1] [11 [ll [2/1]
169 Li--O
I75 Li--O
not given
192 Li--N
given
not
172 Li--O
not given
175 . Li--O
not given
given
not
given
not
175 Li--O
189
191
236
179
172
135
181
180
169
223
221
187
62)
67)
65)
22)
22)
62)
22)
67)
69)
22)
22)
67)
o 5 ~z
5"
c) g~
CHs--CO--NH--CH2--CH 3
CH3--CO--N(CH3) 2
CHs--COO--CHz--CH s
CH3--O--CH2--CHz--O--CH 3
HC=S 2 HC[=S
CHa--(CH2)s--CO--NH 2
HCO--N(CHz--CHa) 2
NH2_CO--NH--CO
Li +
Li +
Li +
Li ÷
Li ÷
Li +
Li +
Li ~
NH 2
CH 3
C O - - N H - - C H 2 CH s
Ligand
Li +
Ion
t~.l~ Table 1. (continued)
H C, N, O Li H C, N, O Li H C, N, O Li H C, O Li H C, O Li H C S Li H C, N, O Li H C, N, O Li H C, N, O Li
atom
Basis setb
GTO GTO GTO GLO GLO GLO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GLO GLO GLO GTO GTO GTO GLO GLO GLO
type (3) (7/3) 6G3G (1) (2/1) (2) (3) (7/3) 6G3G (3) (7/3) 6G3G (3) (7/3) (5) (4) (7/3) (10/6) (7/3) (1) (2/1) (2) (3) (7/3) 6G3G (1) (2/1) (2)
uncontracted
[1] [2/1] [1]
[1] [2/1] [1] [2] [4/2] [5/4] [4/1] [1] [2/1] [1] [1] [2/1]
[1] [2/11
[1] [2/1] [1] [1] [2/1]
[1] [2/1]
contracted
experimental
assumed
experimental * not varied
assumed
assumed synperiplanar E(conf) = 30 k J/mole
assumed
assumed
experimental * not varied
assumed
Ligand geometry/ * Complex geometry ¢
180 Li--O
given
not
175 Li--O
213 Li O
178 Li--O
given
not
not given
175 Li--O
not given
269
232
193
87
244
178
232
185
231
22}
67)
66)
70)
22)
22}
67)
22)
g J/
[pm] mole]
-E (Int) Ref.
R
g
g
.=
.
.
.
.
1
Li +
Li +
Li +
Li +
Ihylnine
J
thymine
guanine
NH2-C==N--C---N
adenine
N-C(NHz)=C-N=CH
adenine
CH--N==C---NH
t
H
J
(20-NH-CH=C(CHa)-CO-NH
t
C O - N H-CH=(2((2H a ) - C O - N H
.
Li +
cytosine
cylosine
CH3--CO--N(CHa--CH3) 2
.
Li ÷
.
CH 3 - - C O - N ( C H 2-CH3) 2
.
Li +
l
.
C O - N =C(NH 2 ) - C H = C H - N H
.
Li +
.
~O-N=(2(NH2)-CH=CH-NHl
Li +
.
2 NH2--(20--NH--CO--NH 2
Li +
H GLO (1) C, N GLO (2/1) Li GLO (2) counterpoise corrected H GLO (1) (2, N, O GLO (2/1) Li GLO (2)
H GLO (1) C, N, O GLO (2/1) Li GLO (2) n GLO (1) C, N, O GLO (2/1) Li GLO (2) H GLO (1) C, N, O GLO (2/1) Li GLO (2) counterpoise corrected H GTO (3) C, N, O GTO (7/3) Li GTO 6G3G H GTO (3) C, N, O GTO (7/3) Li GTO (5) H GLO (1) (2, N, O GLO (~/1) Li GLO (2) H GLO (1) C, N, O GLO (2/1) Li GLO (2) counterpoise corrected H GLO (1) C, N GLO (2/1) Li GLO (2)
[1] [2/1] [1]
[1] [2/1] [1]
[1] [2/1] [1]
[11 [2/I] [1] [1] [2/1] [1] [I] [2/11 [1]
[1] [2/1]
[1] [2/1] [11 [1] [2/1] [1] [11 [2/1] [1]
experimental
experimental
experimental
experimental
experimental
assumed
assumed
experimental
experimental
experimental
192 Li,--O
185 Li--O
185 Li--O
176 Li--O
176 Li--O
170 Li--O
not given
195 Li--O
195 Li--O
not given
293
t94
212
168
188
193
238
242
270
302
72~
~3~
72~
7a)
v~)
62~
22)
73)
721
71)
a
5"
E" =_
]
|
C---NH
-
t
2
I
I
2
uncontracted
GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO
H C,O Li H C,O Li H C,O Li all GTO 6-31G* GTO, (6/1) GTO (11/7/1) GTO (12/6)
all H N Na
NH 3
NH3
Na ÷
(1) (2/1) (2) (1) (2/1) (2) (3) (7/3) (5) 3-21G
GTO STO-3G
all
Na +
z
type
H GLO (l) C, N , O GLO (2/1) Li GLO (2) counterpoise corrected H GLO (1) C,N GLO (2/1) Li GLO (2) H GLO (1) C,N GLO (2/1) Li GLO (2)
atom
Basis setb
NH 3
CH 2 - ( O - C H z - C H 2)2-O-CH 2
I
CH2-(O-CH 2-CH2)2-O-CH 2
CH3-O-CH z-CH2-O-CH 2
CH3-O-CHz-CHz-O-~H2
CHz-O-CH2-CH2-O-CH2
I
CH2-O-CH2-CH2-O-CH 2 CHa-O-CH2-CH2-O-~H2
CH3-NH-CH2-CH2-NH-CH
CH3-NH-CHz-CHz-NH-CH
C H 2 - N H - C H 2 - C H 2 - NH-CHg
CH2-NH-CH,-CH2-NH-CH
guanine
NHz-C==N-
I
LI
N H - ~ C O - C - N =CH
Ligand
N,a +
Li +
Li ÷
Li +
Li +
Li +
Li +
Li +
Ion
Table I. (continued)
[3/11 [5/4/1] [6/4]
[11 [2/11 [11 [11 [2/1t [1] [1] [2/1] [1]
[1] [2/11 [1] [1] [2/1] [1]
[11 [2/1] [11
contracted
experimental
* 3-21G geometry
geometry of complexed ligand * experimental * fully optimized
assumed * not varied
~/ssumed * part. optimized
assumed * not optimized
assumed * not varied
assumed * part. optimized
experimental
Ligand geometry/ * Complex geometry ~
240 Na-N
207 Li--O 230 Na--N 230 Na--N
204 Li--O
204 Li--O
180 Li--O
188 Li--N
188 Li--N
192 Li--O
R [pm]
116
136
172
317
68
241
923
376
517
262
20)
19)
19)
75)
74)
74)
61)
74)
74)
73)
--E(Int) Ref. [kJ/ motel
f0
g
L~
4 NH 3
5 NH 3
6 NH 3
H20
HzO
H:O
H20
H20
H20
H20
H20
HzO
H20
Na +
Na +
Na +
Na ~
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
H O Na H O Na H O Na H O Na all
H N Na H N Na H N Na H,O Na H,O Na H O Na H,O Na H,O Na GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
(4) [11 (7/3) [2/11 (10/3) [3/I] (4) [1] (7/3) [2/1] (10/3) [3/1] (4) [1] (7/3) [2/1] (10/3) [3/I] STO-3G STO-3G + 2p orbital STO-3G STO-3G reoptimized (3) [11 (7/3) [2/1] STO-3G reoptimized 4-31G STO-3G reoptimized 4-31G STO-3G + 2p orbital, reoptimized (6/2) [2/2] (11/7/2) [4/3/2] (13/8/2) [7/4/2] (6/1) [2/1] (1 I/7/1) [4/3/1] (13/8/1) [7/4/1] (6/1) [3/1] (11/7/1) [5/4/1] (14/8/1) [8/6/1] (4/1) [2/1] (9/5/1) [4/2/1] (11/7) [6/4] 3-21G * fully optimized
not specified
experimental
not specified
not specified
experimental
experimental
experimental
experimental
STO-3G geometry * tetragonal, * part. optimized STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized experimental
220 Na--O 212 Na--O
224 Na--O
225 Na--O
225 Na--O
215 Na--O 200 Na--O 220 Na--O
230 Na--N 200 Na--O 200 Na--O
230 Na--N
235 Na--N
173
113
105
105
100
138
175
121
126
178
628
585
509
19)
36)
34-)
76)
33)
31)
31)
31)
31)
3I)
29}
29)
29)
.=
,7" O
5"
c)
~
Ligand
H20
H20
H20
H20
4 H20
5 H20
6 H20
HF
HF
HC N
HCN
H2CO
Ion
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Table i. (continued)
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO 6-31G* GTO GTO 6-31G* GTO
H
O Na H,O Na H O Na H O Na H O Na H O Na all all all all all
[3/11 [5/4/]I
contracted
3-21G
3-2 !G
(12/6) [6/4] STO-3G STO-3G reoptimized (6/1) [2/1] (12/8/2) [5/8/2] (13/8/1) [7/4/1] (4) [1] (7/3) [2/1] (10/3) [3/1] (4) [t] (7/3) [2/1] (10/3) [3/1] (4) [1] (7/3) [2/1] (10/3) [3/1] 3-21G
(I I/7/I)
(6/1)
GTO 6-31G*
all
uncontracted
type
at,Jm
Basis set b
* fully optimized
* 3-21G geometry
* fully optimized
* 3-21G geometry
STO-3G geometry * tetragonal, * part. optimized STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized * fully optimized
experimental
not specified
experimental
* 3-21G geometry
Ligand geometry/ * Complex geometry ~
220 Na--O 203 Na--F 203 Na--F 224 Na--N 224 Na--N 208 Na--O
220 Na--O
210 Na--O
225 Na--O
220 Na--O 199 Na--O
212 Na--O
[pro]
R
159
115
145
87
131
594
552
477
102
170
104
118
19)
19)
19)
19)
19)
29)
29)
29)
78)
77~
2O)
19)
--E(Int) Ref. [k J/ mole]
co
HzCO
H2CO
4 H2CO
5 H2CO
6 H2CO
CH3--NH 2
CH3--NH 2
CH 3-OH
CH3--OH
CH3--F
CH3--F
PH 3
PH 3
H2S
H2S
HC1
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na ÷
Na + all
all
all
all
all
all
all
all
all
all
H C,O Na H C,O Na H C,O Na all
all
all
(7/3) (10/3) (4) (7/3) (10/3) (4) (7/3) (10/3) 3-21G
(4)
STO-3G
6-31G*
GTO
GTO
GTO
GTO
GTO
GTO
GTO
GTO
GTO
3-21G
6-31G*
3-21G
6-31G*
3-21G
6-31G*
3-21G
6-31G*
3-21G
G T O 6-31G*
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
GTO
GTO
[l] [2/1] [3/1] [1] [2/i] [3/1] [1] [2/1] [3/11
* fully optimized
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
* 3-21G geometry
STO-3G geometry * tetragonal, * part. optimized STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized * fully optimized
* fully optimized
* 3-21G geometry
230 Na--O 229 Na--N 229 Na--N 211 Na--O 211 Na--O 202 Na--F 202 Na--F 294 Na--P 294 Na--P 278 Na--S 278 Na--S 279 Na--C1
220 Na--O
210 Na--O
208 Na--O not given
51
52
74
74
86
105
144
121
172
132
169
464
441
387
141
121
19)
19)
19)
19)
19)
19)
19)
19}
19)
19)
19)
29)
29)
29)
48)
191
-v
e.. o
=_
-~
HC1
CH3--CN
CHz--CN
C,H z - N H - C H 2 L_ A
~H20-~H2
CH3--CHO
CH 3 CHO
CH3--NH--CH 3
CH3--NH--CH 3
HCO
CH3--O--CH 3
CH3--O
CH 3 O - - C H 3
CH3--O--CH 3
Na +
Na*
Na +
Na +
Na +
Na ~
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na*
CH 3
NH 2
Ligand
ton
Table 1. (continued)
6-21G geometry of Li complex 6-21G geometry of Li complex * fully optimized
GTO 6-21G GTO GTO G T O 6-31G* GTO GTO G L O (1) G L O (2/1) G L O (4/2) G T O 3-21G G T O 6-31G* GTO GTO G fO GTO GTO
all all all all all all H C, N, O Na all all H, C, O Na H C, O Na
STO-3G STO-3G reoptimized (3) [11 (7/3) [2/tl (9/6) [3/2]
6-31G*
3-21G
3-21G
6-21G
[1] [2/1] [2/1]
* 3-21G geometry
G T O 6-31G*
all
3-21G
experimental
experimental
* 3-21G geometry
* fully optimized
experimental
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
GTO
* 3-21G geometry
all
6-31G*
GTO
contracted
all
uncontracted
type
Ligand geometry/ * Complex geometry ~
atom
Basis set b R
202 Na--O
210 Na--O 210 Na O 2OO Na--O
given
not
279 N a CI 221 Na N 221 Na--N 225 Na--N 218 Na--N 206 Na O 206 Na--O 228 Na--N 228 Na N
[prn]
90
163
118
169
t31
125
163
I38
176
172
178
140
170
37
62)
61}
19~
19}
79~
19~
191
19~
56)
56~
19)
19)
19I
- - E ( l n t ) Ref. [kJ/ mole]
rj~
CH3--SH
CH3 - S H
CH3--CI
CH3--CI
HC=O
Na +
Na +
Na +
Na +
Na +
t
CH3--CO_NH 2
CH3--PH_CH 3
CH3--PH--CH a
CH3--S--CH 3
CHa--S--CH 3
CH3--S--CH 3
CHO--CH z-CHO
Na +
Na +
Na +
Na +
Na +
Na +
HC=O
HC=O
HC=O
Na +
Na +
CHa--PH2
Na +
I
CH3--PH2
Na +
H C S Na H C,O Na
all
all
all
H C,O Na H C,O Na H C,N,O Na all
all
GTO
all
(2/]) (4/2) 3-21G
(2/I) (4/2) (1)
(8/4) (11/7) (I)
(4)
3-21G
GTO GTO GTO GTO GLO GLO GLO
(2/]) (4/2)
(7/3) (9/6) (7/3) (1)
(3)
GTO 6-31G*
GTO
GTO 6-31G*
GLO GLO GLO GLO GLO GLO GLO GLO GLO GTO
GTO 6-31G*
3-2tG
GTO 6-31G*
GTO 3-21G
all all
GTO 6-31G*
all
3-21G
GTO
all
[1] [2/11 [3/2] [2/1] [11 [2/1] [2/1]
[3] [4/2] [6/4] Ill [2/i] [2/1t [11 [2/11 [2/1]
assumed
assumed
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
experimental
experimental
experimental
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
* 3-21G geometry
* fully optimized
given
not
254 Na--S
209 Na--O 288 Na--P 288 Na--P 269 Na--S 269 Na--S
not given
not given
291 Na--P 291 Na--P 273 Na--S 273 Na--S 264 Na--C1 264 Na--C1
175
57
84
101
105
108
142
110
158
58
84
71
90
92
98
65)
62)
19)
19)
19)
19)
67)
65)
64)
19)
19)
19)
19)
19)
19)
C~
e,. O
CH3--CH2--CO--NHz
CH3--CO--NH--CH 3
CH3--CHa--O--CH2--CH 3
CH3--COO--CH s
CHO - C H 2 - - C H 2 - - C H O
CH3--CH2--CH2--CO--NH 2
CH3--O~-CHz--CHz--O--CH 3
NH2--CO--NH--CO--NH 2
2 NH2--CO--NH--CO--NH 2
C O _ N =C(NHa)-CH_--CH_ NH k _ _ ............................... I
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
Na +
eylo~ine
Ligand
Ion
t,.~'l~ Table 1. (continued)
type GLO GLO GLO GTO GTO GTO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO
atom H C, N, O Na Ligand Na H C, O Na Ligand Na H C, 0 Na It C, N, O Na H C, O Na H C, N, O Na H C, N, O Na tt C, N, O Na
Basis set b contracted
(1) [1] (2/1) [2/11 (4/2) [2/1] STO-3G STO-3G reoptimized (3) [1] (7/3) [2/1] (7/3) [2/1] STO-3G STO-3G reoptimized (1) [1] (2/1) [2/11 (4/2) [2/1] (1) [1] (2/1) [2/11 (4/2) [2/I] (3) [1] (7/3) [2/1] (7/3) [2/1] (1) [11 (2/1) [2/11 (4/2) [2/1] (1) [t] (2/1) [2/1] (4/2) [2/1] (3) [ I] (7/3) [2/1] STO-3G reoptimized
uncontracted
assumed * not optimized
experimental
experimental
assumed synperiplanar E(conf) = 30 kJ/mole
experimental
assumed
part. optimized
experimental
part. optimized
experimental
Ligand geometry/ * Complex geometry c
not given 215 Na--O 230 Na--N
210 Na--O
212 Na--O
208 Na--O
not given
225 Na--O 199 Na--O
209 Na--O 195 Na--O
216
417
247
172
153
196
162
93
208
149
80)
71)
~)
70)
6"7)
6s)
77)
62)
77)
671
IPm] mole]
--E(Int) Ref.
[kJ/
R
cytosine
Na +
Na +
Na+
Na +
Na +
Na +
?.
thymine
I
-CH2
H
2
C H 2 - N H - C H 2 - C H ~- NH-CH_,
CH,-NH-CH,-CH,-NH-CH
guanine
NH2-C==N--C---NH
~H-CO-~-N=~H
guanine
NHa-C==N--C---N
~H-CO-~'-N=~H
adenine
N-C(NHz)=C-N=CH
adenine
,N,-C(NH2)=~-N=CH II / I CH--N==C---NH
ribose
HO-CH2-CH-CH(OH)-C[ H - O H
L
CO-N H-CH=C(CHa)-CO- NH
I
Na +
uracil
I
CHa--CO--N(CHz--CH3) 2
I
CO-NH-CH=CH- CO-NH
L
CO_N=C(NH2)_CH_-CH_ NH
Na +
Na +
Na +
[11 [2/1] [2/1]
[11 [2/1] [2/11
[11 GTO (7/3) [2/11 GTO STO-3G reoptimized
GTO (3)
H GLO (1) C,N,O GLO (2/1) Na GLO (4/2) counterpoise corrected H GLO (1) C,N GLO (2/1) Na GLO (4/2)
C,N,O Na
H
[1] [2/11 [2/11
GTO (3) [1] GTO (7/3) [2/1] GTO STO-3G reoptimized
H GLO (1) C,N GLO (2/1) Na GLO (4/2) counterpoise corrected
H C,N Na
H GLO (1) [11 C, N , O GLO (2/1) [2/11 Na GLO (4/2) [2/11 counterpoise corrected H GTO (3) Ill C,N,O GTO (7/3) [2/11 Na GTO STO-3G reoptimized H GTO (3) [11 C,N,O GTO (7/3) [2/1] Na GTO (7/3) [2/1] H GLO (1) [11 C,N,O GLO (2/1) [2/11 Na GLO (4/2) [2/1] counterpoise corrected H GTO (3) [1] C,O GTO (7/3) [2/1] Na not specified
assumed * pa~. optimized
experimental
assumed * not optimized
experimental
208 Na--N
182
225 210 Na--N
74)
73)
s0)
=.
o ~3
m .~ ~' g~'
"t g~
~" o
g~
215 Na--O 225 290 Na.-N
73)
s0)
sl)
73)
62)
soj
5"
132
110
146
122
139
138
73)
220 Na--N
215 Na--O
not given
experimental
assumed * not optimized
210 Na--O
201 Na--O
200 Na--O
220 191 Na- O
experimental
assumed
assumed * not optimized
experimental
c.
CH3-O-CH2-CH2-O-CH
NH 3
NH~
NH 3
NH 3
4 NH 3
5 NH 3
K+
K+
K*
K+
K+
CH2-(O-CH z-CH2)2-O-CH 2
CHH 2 - ( O 2- C H 2 - C1 H 2 ) 2 - O - ~
z
2
CH3-O-CHz-CH2-O-~H
z
t
2
-CH 2
-o-c.2-c.2-o5.2
CH2-O-CH2-CH2-O-CH
K +
Na+
Na +
Na+
CH3-NH -CH2-CHz-NH
Na +
CH3-NH-CH2-CH2-NH-CH
Ligand
Ion
Table 1. (continued)
type GLO GLO GLO GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
atom H C, N Na H C, O Na H C, O Na H C, O Na H, N K H Y K H N K H N K H N K H N K
Basis set b
(1) (2/1) (4/2) (1) (2/1) (4/2) (1) (2/1) (4/2) (3) (7/3) (7/4) 4-31G (14/9) (6/1) (I 1/7/1) (14/9/5) (4/1) (9/5/I) (14/9) (6/1) (11/7/1) (14/9) (4) (7/3) (13/6) (4) (7/3) (13/6)
uncontracted
[8/6] [3/1] [5/4/1] [8/4/2] [3/1] [5/3/1] [8/4] [3/1] [5/4/1] [8/4] [1] [2/1] [4/2] [t] [2/1] [4/2]
[11 [2/t 1 [2/1] [11 [2/I] [2/1] [1] [2/1] [2/1] [11 [2/1] [2/1]
contracted
STO-3G geometry * tetragonal, * part. optimized STO-3G geometry * pentagonal, * part. optimized
experimental
experimental
experimental
geometry of complexed ligand * experimental assumed
assumed * not varied
assumed * part. optimized
assumed * not varied
Ligand geometry/ * Complex geometry ~
28O K N
270 K--N
290 K--N
290 K--N
290 K--N
245 Na--O 278 K--N
228 Na--O
228 Na--O
208 Na--N
[pm]
R
403
333
77
81
77
101
343
42
247
79
29)
29)
21)
21)
20)
82)
75)
74)
74)
- - E (Int) Ref. [k J/ mole]
o
g
5
6 NH s
H2O
H2O
H20
HzO
H20
H20
H2O
H20
HzO
H20
H20
H20
K +
K+
K+
K+
K+
K+
K÷
K+
K+
K+
K+
K'
K+
H O K H O K H O K H,O K H O K H 0 K H O K H,O K
H N K H,O K H 0 K H,O K H,O K
GTO (4) [1] GTO (7/3) [2/t] GTO (13/6) [4/2] GTO STO-3G GTO STO-3G reoptimized GTO (3) [1] GTO (7/3) [2/1] STO-3G reoptimized GTO 4-31G GTO STO-3G reoptimized GTO 4-31G GTO STO-3G + 3p orbital, reoptimized GTO (6/2) [2/2] GTO (11/7/2) [4/3/2] GTO (17/1 I/2) [9/6/2] GTO (6/1) [2/1] GTO (11/7/1) [4/3/1] GTO (17/11/1) [ll/7/1] GTO (4/1) [2/1] GTO (9/5/1) [4/2/1] GTO (I4/9) [8/6] GTO 4-31G GTO (14/9) [8/6] GTO (6/1) [3/1] GTO (11/7/1) [5/4/1] GTO (14/9/5) [8/4/2] GTO (4/1) [3/11 GTO (9/5/1) [5/3/1] GTO (14/9) [8/4] GTO (6/1) [3/1] GTO (11/7/1) [5/4/1] GTO (14/9) [8/4] GTO STO-3G GTO STO-3G reoptimized not specified
experimental
experimental
experimental
assumed
not specified
not specified
not specified
experimental
experimental
experimental
STO-3G geometry * hexagonal, * part. optimized experimental
270 K--O 240 K--O
270 K--O
270 K--O
265 K--O 259 K--O
269 K--O
269 K--O
257 K-O 250 K--O 260 K--O
285 K--N 250 K--O
117
72
76
72
98
75
73
70
101
115
85
82
457
771
21~
211
20~
82)
36)
76)
33~
31)
31)
31)
29)
e,.
~Z
O
4 H20
5
6 H20
HCN
4 HzCO
5 HzCO
6 H2CO
CH 3 - N H 2
CH3--NH 2
CH3--NH 2
CH3--OH
K÷
K+
K+
K+
K+
K+
K÷
K*
K+
K+
K +
H20
Ligand
Ion
Table 1. (continued)
uncontracted (4) (7/3) (13/6) (4) (7/3) (13/6) (4) (7/3) (13/6) 4-31G (14/9) (4) (7/3) (13/6) (4) (7/3) (13/6) (4) (7/3) (13/6) 4-31G (14/9) (4/1) (9/5/1) (14/9) (6/1) (11/7/1) (14/9) 4-31G (14/9)
type GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
atom H O K H O K H O K H,C, N K H C,O K H C,O K H C, O K H,C,N K H C,N K H C,N K H,C,O K
Basis set b
[8t6]
[8/6] [3/1] [5/3/1] [8/4] [3/1] [5/4/1] [8/4]
[8/6] [1] [2/11 [4/2] [1] [2/1] [4/2] [1] [2/1] [4/2]
[1] [2/t] [4/2] [1] [2/1] [4/2] [1] [2/1] [4/2]
contracted
assumed * not varied
experimental * not varied
experimental
STO-3G geometry * tetragonal, * part. optimized STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized assumed
STO-3G geometry * tetragonat, * part. optimized STO-3G geometry * pentagonal, * part. optimized STO-3G geometry * hexagonal, * part. optimized assumed
Ligand geometry/ * Complex geometry ~
290 K--N 259 K--O
290 K--N
270 K--O 278 K--N
265 K--O
270 K--O
265 K--O 270 K--N
265 K--O
260 K--O
R [pm]
99
76
82)
21)
211
82)
96
79
29)
29)
29}
82)
291
29~
354
316
265
88
441
387
320
mole] 29)
- - E ( I n t ) Ref.
[kJ/
~m
4~
CHz--CN
CH3--NH--CH3
HCO--NH2
CH3--O--CH3
CH3--O--CH 3
H~=O HC=O"
CH3--CO--NH z
CHO--CH2--CHO
CH3--CO--NH--CH3
CH3--COO--CH3
CHO--CH2--CH2--CHO
NHz--CO--NH--CO--NH2
C H 2 - ( O - C H 2 - C H 2)2- O - .CH2 I I C H 2 - ( O - C H 2-CH2)2-O-CH2 NHa
K +
K +
K +
K +
K +
K +
K +
K +
K +
K +
K +
K +
K ÷
N~f
H2S
K +
H, S K H, C, N K H, C, N K Ligand K H, C, O K H, C, O K H C, O K H C, N, O K H C, O K Ligand K Ligand K H C, O K H C, N, O K H C, O K all GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO
4-3lG (14/9) [8/6] 4-31G (14/9) [8/6] 4-31G (14/9) [8/6] 4-31G (14/9) [8/6] 4-31G (14/9) [8/6] STO-3G STO-3G reoptimized (1) [1] (2/1) [2/1] (8/4) [3/21 (1) [1] (2/1) [2/11 (8/4) [3/2] (I) [11 (2/1) [2/1] (8/4) [3/2] STO-3G STO-3G reoptimized STO-3G STO-3G reoptimized (1) [1] (2/1) [2/1] (8/4) [3/21 (1) [1] (2/1) [2/11 (8/4) [3/21 (3) [1] (7/3) [2/1] (9/6) [3/2] STO-3G geometry of complexed ligand * experimental assumed
experimental
assumed
part. optimized
part. optimized
assumed
experimental * not varied
experimental
assumed * not varied assumed * not varied assumed * not varied assumed * not varied experimental
experimental
277 K--O 250 N--N
250 K--O
not given
not given 235 K--O 240 K--O
250 K--O
not given
330 K-.-~S 273 K--N 278 K--N 259 K--O 259 K--O 240 K--O
177
263
249
187
107
147
169
131
146
108
97
124
79
107
49
83)
75)
71)
65)
77)
77 t
65)
67)
64)
61)
82)
82)
82)
82)
r,,3
6
t~
O
=_
~.
c)
•G~ ~
GTO STO-3G GTO (3) GTO (7/3) GTO STO-3G GTO 4-31G GTO 3-21G GTO 6-31G*
H N, O all all all all
H20
HzO
H20
HzO
H20
NH~
NH2
NH2
NH4+
NH2
NH;
GTO STO-3G
all
4 NH 3
N.;
all
GTO STO-3G
5 NH 3
3 NH 3
NH;
all
NH 4
2 NH 3
NH2
GTO STO-3G
NH 3
NH;
hydrogen bond 4-31G
(10/5)
(3/1) (8/4/1) (5)? (5/1)?
all
NH 3
NH~
H GTO N GTO H GLO H7 GLO N GLO H7 is involved in all GTO
4 NH 3
NH 3
NHa~
GTO 4-31G
all
GTO STO-3G
NH 3
NH2
uncontracted
type
atom
Basis setb
all
Ligand
Ion
Table 1. (continued)
[1] [2/1]
[4/2]
[2/1] [4/2/11 [11 [2/11
contracted
* 3-21G geometry
* fully optimized
experimental
experimental
experimental
assumed
assumed
assumed
assumed
assumed
4-31G geometry
* part. optimized
* part. optimized
assumed
Ligand geometry/ * Complex geometry~
279 N--N 260 N--N 265 N--N 270 N--N 270 N---N 290 N--N 270 N--O 240 N--O 265 N--O 259 N--O 259 N--O
271 N--N
275 N--N 278 N--N
R [pro]
88)
88)
82
83)
84~
83)
311
84
83~
84~
84}
84)
87)
86)
85}
83~
142
ll8
156
95
524
475
481
407
310
112
151
118
131
--E(Int) Ref. [kJ/ mole]
,---
H20
H20
H20
H20
H20
H20
H20
H20
H20
H20
H20
H20
H20
H20
H20
NH +
NIq;
NH2
NH4+
NH;
NH;
NH;
NH;
NH, +
NH;
NH;
N H ,+
NH2
NHg
N H ,+
H20
GTO 4-31G
GTO 4-31G
GTO 6-31G*
H GTO (3/1) N,O GTO (8/4/t) H GTO (4/1) N,O GTO (9/5/1) H GTO (4/1) N,O GTO (9/5/I) counterpoise corrected H GTO (5/1) N,O GTO (10/6/1) H GTO (4/1) N,O GTO (9/5/2) H GTO (6/1) N,O GTO (11/7/2) H GTO (6/I) N,O GTO (ll/7/2) counterpoise corrected H GTO (4/1) N,O GTO (W5/I) H GTO (4/1) N,O GTO (9/5/1) H GTO (4/0 N,O GTO (9/5/1) H GTO (4/1) N,O GTO (9/5/1) counterpoise corrected H GTO (4) N,O GTO (9/5) H GTO (4) N,O GTO (9/5) counterpoise corrected
all
all
all
[21 [4/21
[4/2]
[2]
[2/1] [4/2/I] [2/11 [4/2/1] [2/1] [4/2/1] [2/11 [4/2/1]
[2/11 [3/2/2] [2/1] [4/3/2] [2/1] [4/3/21
[5/3/11
* * * *
same geometry as 2 entries above same geometry as 3 entries above
experimental
isolated partners fully optimized experimental
* fully optimized
experimental
experimental
assumed
assumed
assumed
[3/11
assumed
[2/11
* part. optimized
[3/2/11 [2/11 [3/2/1]
[412/11
[2/1]
experimental
experimental
* part. optimized
278 N--O 278 N--O 278 N--O
278 N--O 276 N--O 277 N--O 278 N--O
278 N--O 279 N--O 278 N--O
not given 268 N--O 268 N--O 271 N--O 278 N--O 279 N--O
105
91~
91}
91~
87
108
9~t
85
91~
91~
86
85
9m
9o~
77
77
s9~
591
s9~
82
83
84
59~
55)
98 86
38)
~
114 114
ss~
90
a
5.
0
Ligand
H20
H20
H20
2 H20
2H20
2 H20
2 H20
3"t-I20
3 H20
3 H20
4 H20
4 H20
4 H20
5 H20
6 H20
Ion
NH~
Nli~
NH,/~
NH~
NH4÷
NH~
NH~
NH~
NI-~
NH4+
NH~
NH, i+
NH~
NI-I~
N I-I,~
v,no Table 1. (continued)
GTO GTO 6-31G* GTO 6-31G* GTO 3-21G GTO 6-31G* GTO STO-3G GTO STO-3G GTO 3-21G GTO 6-31G* GTO STO-3G GTO 4-31G
all all all all all all all all all all all
3-21G
(4/1) (9/5/2) (4/1) (9/5/2) (5/1) ~10'~ % STO-3G
GTO GTO GTO GTO GTO GTO GTO
H N, O H N, O H N,O all
uncontracted
type
setb
atom
Basis
[2/1] [4/2/11 [2/1] [4/3/2] [3/1] [5/4/2]
contracted same geometry as 4 entries above same geometry as 5 entries above same geometry as 6 entries above experimental
experimental * not varied
experimental
* 3-21G geometry
* fully optimized
experimental
experimental
* 3-21G geometry
* fully optimized
* part.optimized
* 3-21G geometry
* fully optimized
* * * * * *
Ligand geometry/ * Complex geometry c
278 N---O 278 N--O 278 N---O 245 NO 266 N--O 259 N--O not given 272 N--O 259 N O 255 N--O 260 N--O 277 N--O 259 N--O 262 N--O 268 N--O
R
9t~ 91~ s3~ 84) ss~ ss~ 88~ 8s~ ss~ s3~ s4) s3) s4~ 88~ ss~ 8,~j 3s~
81 78 275
155 166 346 217 367
427 276 493 659
44t
255
9~
81
- - E ( I n t ) Ref. [kJ/ mole]
m
.=_
~g
HO--CH2--CH2--OH
NH3
H20
HzO
H20
H20
H20
H20
HCO--NH2
NCO_NH 2
H~=O
NH4+
Be++
Be + +
Be + +
Be + +
Be + +
Be + +
Be + +
Be + +
Be ++
Be ++
Be + +
HCOOH
NH~
2
I
HC=O
HC=O
HC=O
CH3--O--CH 3
NH,{~
H C,O Be H C,O Be H C,O Be
H O Be H O Be H O Be all
H O Be H,O Be all
all
all
all
all STO-3G
GLO GLO GLO GLO GLO GLO GTO GTO GTO
(1) (2/1) (2) (4) (8/4) (8) (4) (7/3) (7/3)
G T O (4) G T O (9/10) G T O (9/2) G T O (6/1) G T O (11/7/1) G T O (8) G T O (6/1) G T O (11/7/1) G T O (1 t/3) G T O 4-31G
G T O (4/1) G T O (9/5/1) G T O (9/3) G T O 4-31G not specified G T O 4-31G
G T O 4-31G
G T O STO-3G
G T O STO-3G
GTO
[11 [2/1] [1] [3] [4/2] [41 [2l [4/2] [4/11
[41 [6/4] [7/1] [2/11 [4/3/1] [2] [2/1] [4/3/1] [4/2]
[2/11 [4/2/1] [4/2[
assumed * part. optimized
experimental
experimental
experimental
not specified
not specified
experimental
experimental
* fully optimized
not specified
assumed
not specified
experimental
not specified
634
66}
64)
79)
4~)
824
594
95)
95)
39)
563
467
592
94)
not given 601
~
a6}
586
'~}
92)
198 686
9a)
92)
122
161
185 1350 Be--O
not given
not given
153 Be--O 148 Be--N
159 Be--O
156 Be--O
150 Be--O 156 Be--O 159 Be--O
not given 244 N--O not given 164 Be--N
¢D
.~.
5'
~"
= -~. O
t~ b~
CH3"-CH2--CO
CH 3- C H z
HC=S
Be ++
Be ++
Be + +
2 NH~--CO
H20
H20
H20
Be ++
Mg + *
Mg + +
Mg + +
NH
NH2--CO -NH
Be ++
HC=S
I
CH3_CO_NH 2
Be + ~
2
N(CHa)3
Be + +
CH2
Ligand
Ion
Table 1. (continued)
CO--NH 2
CO--NH 2
CO--NH2
NH 2
GLO GLO GLO GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO GTO GTO GTO
H C, N, O Be H C, N, O Be H C,N,O Be H C S Be H C, N, O Be H C, N, O Be H O Mg H, O Mg H, O Mg
contracted
(I) [11 (2/I) [2/1] (2) [1] (l) [1] (2/1) [2/1] (2) [1] (1) [1] (2/1) [2/11 (2) [1] (4) [2] (7/3) [4/21 (10/6) [5/41 (7/3) [4/1] (1) [11 (2/1) [2/1] (2) [1] (1) [1] (2/1) [2/1] (2) [1] (4) [2] (9/5) [4/2] (9/5) [4/2] STO-3G STO-3G + 2p orbital STO-3G STO-3G reoptimized
GTO 4-31G
all
uncontracted
type
atom
Basis set b
experimental
experimental
assumed
experimental
experimental
assumed * part. optimized
experimental
experimental
experimental
* not optimized
Ligand geometry/ * Complex geometry ~
691
676
649
799
967
795
192 355 Mg--O 180 490 Mg O 180 321 Mg O
not given
172 Be--O
210 lIl0 Be O
Be - O
144
145 Be--O
145 Be--O
164 Be N
molel
31)
96J
711
71)
66)
67)
t~7)
07j
--E(Int) Ref.
[kJ/
R
[pm]
g
~z
HzO
H20
H20
Hz O
6 HzO
HC=NH 2 t HC=NH
HC=O
Mg + ~
Mg+ +
Mg* *
Mg + +
Mg + +
Mg + +
Mg + +
H~=O
CH3--CO
HS--SH
Mg + +
Mg + +
HC=O
HC=O
2
HC=O
Mg+ +
Mg ++
H20
Mg ~ +
H~=O
H20
Mg + +
NH2
H O Mg H O Mg H, O Mg H, O Mg H C, N Mg H C, O Mg H C, O Mg H C, O Mg H C, N, O Mg H S Mg
H O Mg H, O Mg H, O Mg GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GYO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO GLO GLO GLO GTO GTO GTO
GTO GTO GTO GTO GTO GTO GTO
(3) [11 (7/3) [2/11 STO-3G reoptimized 4-31G STO-3G reoptimized 4-31G STO-3G + 2p orbital, reoptimized (4/1) [2/1] (9/5/1) [4/2/1] (11/7) [6/4] (4) [21 (7/3/1) [4/2/I] (10/7) [5/5] 4-31G (10/5) [6/4] 4-31G (10/5) [6/4] (4) [21 (7/3) [4/2] (10/6) [5/41 (4) [3] (8/4) [4/2] (11/7) [6/4] (1) [1] (2/1) [2/1] (4/2) [2/1] (4) [2] (7/3) [4/2] (10/6) [5/4] (1) [l] (2/l) [2/1] (4/2) [2/1] (4) [2] (7/3/1) [4/2/1] (10/6/l) [5/4/1] * optimized'?
experimental * not varied
planar
experimental
experimental
planar
assumed
* fully optimized
955
454
454
1390
not given 1659
185 444 Mg--O not given 3t7
not given not given
not given
not given 189 Mg--O 207 Mg---O not given
not specified
385
195 335 Mg--O
187 317 Mg--O 180 412 Mg--O 190 387 Mg--O
not specified
experimental
experimental
experimental
97}
ov~
,7~
{,5~
~4~
97}
9~
94)
97)
3m
3~}
31~
3~
e..
~Z
E
=_.
CH3 - C O - - N H - - C H 3
CHO--CH2--CHz--CHO
CH3--CH2--CH2--CO.-NH 2
CH3--CO--N(CH3) 2
Mg ++
Mg + +
Mg + +
Mg ++
NH2--CO--CH2--CO--NH 2
NHz - C O - - N H - - C O - . . N H 2
2 NHz--CO--NH---CO--NH 2
Mg+ +
Mg + +
Mg+ +
HC=S HC=S |
CH3-- CH2--CO--NH2
Mg + +
2
CHO--CH2 --CHO
Mg + +
Mg + +
Ligand
Ion
Table 1. (continued)
H C, O Mg H C, N, O Mg H C, N, O Mg H C, O Mg H C, N, O Mg H C, N, O Mg H C Mg, S H C, N, O Mg H C, N, O Mg H C, N, O Mg
atom
Basis setb
GLO GLO GLO GLO GLO GLO GTO GTO GTO GLO GLO GLO GLO GLO GLO GTO GTO GTO GTO GTO GTO GTO GTO GTO GLO GLO GLO GLO GLO GLO
type (1) (2/1) (4/2) (1) (2/1) (4/2) (3) (7/3) (7/4) (1) (2/1) (4/2) (1) (2/1) (4/2) (3) (7/3) (7/4) (4) (7/3) (10/6) (3) (7/3) (7/4) (1) (2/1) (4/2) (1) (2/1) (4/2)
uncontracted [1] [2/1] [2/1t [1] [2/1] [2/11 [1] [2/1] [2/l] [1] [2/1] [2/t] [1] [2/1] [2/1] [1] [2/1] [2/1] [2] [4/2] [5/4] [1] [2/1] [2/11 [1] [2/t] [2/1] [11 [2/11 [2/11
contracted
experimental
experimental
assumed
planar
assumed
experimental * not varied
assumed
assumed
experimental * not varied
assumed
Ligand geometry/ * Complex geometry ~
527
476
607
414
675
not given
1037
665 185 Mg O
187 Mg--O
421 177 Mg--O not 425 given
185 Mg-O
not given
175 Mg-O
464 185 Mg--O
not given
mole]
71~
7xl
9sj
9~)
9s~
671
651
0s~
~7~
65)
--E (Int) Ref.
lkJ/
R
lPm]
~o
e~
g,,n
K
I
fl
guanine
(CH3)2N-CO
H20
ICH3) 2 N - C O - C H 2
Mg+ + (CH3)z N - C O - C H 2
Ca + +
|
NH2-C==N--C--_NH
N H - C O - C - N =CH
adenine
CH--N==C---NH
I~-C(NH2)=~-N=~H
Mg + + (CH3)2 N - C O - ~ H 2
Mg + +
Mg + +
thymine
l
CO-NH-CH=CICH3)_CO_ N H
Mg + +
[
CHa--CO--CH(OH)--S--CH 3
Mg+ +
1
CH 3 - C H 2 --CH 2 - C O - N ( C H 3 ) 2
uracil
Mg + +
l.
I
CO-NH-CH=CH-CO-NH
cytosine
Mg + +
'
=C(NHz)-CH=CH_ N,H C O - N
Mg+ + H GLO (1) [11 C, N, O GLO (2/1) [2/1] Mg GLO (4/2) [2/1] counterpoise corrected H GTO (3) [1] C,N,O GTO (7/3) [2/1] Mg GTO STO-3G reoptimized H GTO (3) [11 C,N,O GTO (7/3) [2/1] Mg GTO (7/4) [2/1] H GTO (3) [11 C,N,O GTO (7/3) [2/1] S GTO (10/6) [3/2] Mg GTO STO-3G reoptimized H GLO (1) [1] C,N,O GLO (2/1) [2/1] Mg GLO (4/2) [2/1] counterpoise corrected H GLO (1) [ll C, N GLO (2/1) [2/1] Mg GLO (4/2) [2/1] counterpoise corrected H GLO (1) [1] C, N, O GLO (2/1) [2/1] Mg GLO (4/2) [2/11 counterpoise corrected H GTO (3) [11 C, N, O GTO (7/3) [2/1] Mg GTO (7/4) [2/1] H GTO (3) [11 C, N, O GTO (7/3) [2/1] Mg GTO (7/4) [2/1] H GTO (4) [2] O GTO (9/5) [4/2] Ca GTO (11/7) [6/4] 180 705 Mg--O 236 Ca--O
assumed assumed
242
182 691 Mg--O
225 210 Mg--N
220 132 Mg--N
210 122 Mg--O
410 197 200 Mg--O
174 431 Mg--O
434 175 Mg--O
19t 220 Mg--O
assumed
experimental
experimental
experimental
part. optimized; * distances Mg--O * optimized with * STO-3G basis set
assumed
experimental * not optimized
experimental
96)
98)
98)
73~
73}
73)
loo)
98i
99)
73)
e.
7' O
m
o
g
O
E"
g~
H20
H20
H20
H20
H20
H20
6 H2O
6 H20
HC=O
Ca + +
Ca + +
Ca + +
Ca ++
Ca + +
Ca + +
Ca + +
Ca + +
Ca + +
CHO--CHz--CHO
CHs--CO--NH--CH 3
Ca + +
Ca + +
HC=O
I
Ligand
Ion
Table 1. (continued)
O Ca H,O Ca H,O Ca H,O Ca H C,O Ca H C,O Ca H C,N,O Ca
H
G T O STO-3G G T O STO-3G reoptimized G T O (3) til G r O (7/3) [2/1] G T O STO-3G reoptimized G T O 4-31G G T O STO-3G reoptimized G T O 4-31G G T O STO-3G + 3p orbital, reoptimized G T O (4/1) [2/1] [4/2/1] G T O (9/5/1) G T O (14/9) [8/6] G T O 4-31G G T O (12/7) [8/6] G T O STO-3G G T O (14/9) [6/3] G T O 4-31G G T O (12/7) [8/6] G L O (1) [1] G L O (2/1) [2/1] G L O (8/4) [3/2] G L O (1) [1] G L O (2/1) [2/1] G L O (8/4) [3/2] G T O (3) [1] G T O (7/3) [2/1] G T O (9/6) [3/2]
contracted
H,O Ca H 0 Ca H,O Ca H, 0 Ca
uncontracted
type
atom
Basis set b
assumed
assumed
experimental
assumed
STO-3G geometry
* fully optimized
not specified
experimental
experimental
experimental
experimental
Ligand geometry/ * Complex geometry c
217 Ca--O
not given
not given
283
389
297
98~
65)
6~
9.~
,oo
94j
36)
31
31)
274
267
31~
3i)
213
197
- - E ( I n t ) Ref. [kJ/ mole
240 222 Ca O 230 not C a - - O given 230 1424 Ca--O 240 1272 Ca--O
230 Ca--O
230 Ca--O 230 Ca--O
220 Ca--O
R [pm]
g
~z
t~
NH 2 - C O - C H 2 - C O - N H
NH 2 - - C O - N H - C O - N H
Ca + +
Ca + +
2
2
Ca + +
Ca + +
Ca + +
"
!
|
(CH3)2N-CO
N-CO-~H 2
guanine
NH2--C==N--C---NH
ade.iae
CH--N==C---NH
II
N-C(N H ,)=C-N = C H
thymine
I
CO- NH-CH=C(CH 3)-CO-NH
Ca + +
t
CH 3--CH 2 - C H 2 - C O - N ( C H 3 ) 2
Ca + +
cytosine
O-N =C(NH2)-CH=CH-N, H
CH3--CO--N(CH3) 2
Ca + +
Ca + +
CHO---CHz--CH 2 - C H O
Ca ++
GLO (8/4)
counterpoise corrected H GLO (1) C, N GLO (2/1) Ca GLO (8/4) counterpoise corrected H GLO (1) C, N, O GLO (2/1) Ca GLO (8/4) counterpoise corrected H GTO (3) C, N, O GTO (7/3) Ca GTO (9/6)
Ca
H GLO (1) C, O GLO (2/1) Ca GLO (8/4) H GTO (3) C, N, O GTO (7/3) Ca GTO (9/6) H GTO (3) C, N, O GTO (7/3) Ca GTO (9/6) H GLO (1) C, N, O GLO (2/1) Ca GLO (8/4) H GLO (1) C, N, O GLO (2/1) Ca GLO (8/4) counterpoise corrected H GTO (3) C, N, O GTO (7/3) Ca GTO (9/6) H GLO (1) C, N, O GLO (2/1)
[11 [2/1] [3/2]
[11 [2/11 [3/21
01 [2/11 [3/21
[11 [2/1] [3/21 [1] [2/11 [3/21
[11 [2/1] [3/21 [1] [2/1] [3/2] [11 [2/1] [3/2] [1] [2/1] [3/21 [1] [2/11 [3/21
assumed
experimental
experimental
experimental
assumed
experimental
experimental
assumed
assumed
assumed
286
464
224 Ca--O
233 Ca--N
231 Ca--N
217 Ca--O
218 Ca--O
230 Ca-O
220 Ca--O
492
506
316
307
294
439
558
483 225 Ca --O
218 Ca--O
not given
98}
73)
73)
73)
98)
73)
71)
98)
98}
65)
£3
e-. t
5" ~Z
.=
5"
O
(CH3)zN-CO-~H 2
Ca + +
H C, N, O Ca
atom
Basis set b uncontracted
GTO (3) GTO (7/3) GTO (9/6)
type [1] [2/1] [312]
contracted
assumed
Ligand geometry/ * Complex geometry ¢
224 Ca-O
R [pro]
510
98)
- - E (Int) Ref. [kJ/ mole]
a CI and pseudopotential calculations are not included, neither are calculations on outer sphere complexes. Calculations improved by the same authors in subsequent publications using the same basis sets are omitted. h The notation GTO A (ot/3/~/6) [a/b/c/d] means : c¢s-type, fl p-type, 1' d-type, and ~ f-type Gaussian Type Orbitals are centered on atom A which are contracted to a s-type, b p-type, c d-type, and d f-type orbitals respectively. The notation STO-nG means: a minimal basis set o f Slater Type Orbitals is used each o f which is expanded into n simple Gaussians lt2.11~) The notation n-klG means: each inner shell is represented by a single basis function taken as a sum of n Gaussians while each valence orbital is split into inner and outer parts described by k and l Gaussians, respectively. Asterisks indicate additional polarization functions, For full description see: 3-21G: 114); 4-31G: ~ts, 116~; 5-21G: 117~; 6-21G: 114); 6-31G: HT); 6-31G* and 6-31G**: H8~ For 6G3G see is). The counterpoise correction procedure is described in 119). (See also 2.3.) c The position of the ion was optimized and the geometry of the ligand was not relaxed unless otherwise specified, Entries marked with an asterisk refer to the whole complex, those without to the uncomplexed ligand.
(CH3)zN-CO-CH2
Ligand
ion
Table 1. (continued)
Ligand
H20
HzO
HzO
HzO
HzO
2 HzO
2 H20
4 H~O
CH3--CN
2 CH3--CN
3 CHa--CN
4 CHa--CN
2 HCOOH
Ion
F-
F-
F
F-
F-
F
F-
F-
F-
F-
F
F-
F-
C, N
C, N
C, N
C, N
H C, O, V
F
H, F H, F H, F H,
H O, F all
all
H, O Li H O F H O, F H O F all
atom
Basis set
STO-4G ? (6/2) (11/7/2) (13/8/2) (6/1) (11/7/1) (6/1) (11/7/1) (13/8/1) 4-31G
uncontracted
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
4-31G 4-31G 4-31G 4-31G 4-31G 4-31G 4-31G 4-3tG (4/1) (9/5) + p orbital
+ p orbital
+ p orbital
[2/1] [4/21
[3/1] [5/4/1]
[2/11 [2/21 [4/3/2] [7/4/2] [3/1] [5/4/1] [2/1] [4/3/1] [7/4/1]
contracted
+ p orbital
GTO (6/1) GTO (11/7/1) GTO 4-31G
GTO 4-31G
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
type
Table 2. Ab ia;,'~o SCF calculations on some anion-ligand interactions. For details see Table 1.
* 4-31G geometry
4-31G geometry
4-31G geometry
4-31G geometry
* fully optimized
* not varied
experimental
* not varied
experimental
not specified
experimental
not specified
STO-4G geometry
Ligand geometry/ * Complex geometry R
104)
76
g ="
196 F--N 160 F--H
F--N
358
237
198
lo5)
~o4)
104~
=
c~
~"
g
3a)
481
~e~ ~" o
~.
103)
188
,o41
~
302
141
3s)
[68
179 F--N 186
lo2~
35)
101
98
33)
30)
99
133
--E(Int) Ref. [kJ/ mole]
F--N
251 F--O 248 F--O 248 F--O 255 F--O not given 170
251 F--O 251 F--O
240 F--O
[pm]
¢~
H20
H20
H20
H20
H20
H20
H20
CH3--OH
CH3--CN
2 CH3--CN
3 CH 3 CN
CI
C1-
C1-
C1-
CI-
CI-
C1-
CV
C1-
CI-
[
uracil
J
CO-NH-CH=CH-CO-NH
Ligand
C1-
Ion
Table 2. (continued)
O CI H 0 C1 H, C, O C1 H, C, N CI H, C, N C1 H, C, N Ct
H
all
n C, N, O F H O C1 H O C1 H, O CI all
atom
Basis set
GTO GTO GTO STO STO STO GTO GTO GTO GTO GTO GTO GTO GTO
contracted
(6/1) (12/8/2) (17/11/1) (2) (3/2) (5/4) 4-31G 4-31G + 4-31G 4-31G + 4-31G 4-31G + 4-31G 4-31G + p orbital
p orbital
p orbital
p orbital
[2/1] [5/8/21 [10/7/11
(4/1) [2/11 (9/5) [4/21 (9/5) [4/21 (6/2) [2/2] (11/7/1) [4/3/1] (17/11/2) [9/6/2] (6/1) [2/I] (11/7/2) [4/3/2] (17/10/1) [9/6/1] 4-31G 4-31G + p orbital 4-31G
uncontracted
GTO 4-31G
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
type
4-31G geometry
4-31G geometry
fully optimized part. optimized fully optimized
part. optimized
experimental
experimental
fully optimized part. optimized experimental
not specified
not specified
experimental * part. optimized
Ligand geometry/ * Complex geometry
304 C1--O 237 CI--H 345 CI--C 346 C1--C 350 C1--C
339 CI--O
331 CI--O 240 CI--H 315 C1--O 315 CI--O
331 CI--O
257 F--N
R [pm]
128
91
48
50
80
49
83
88
57
50
50
378
104)
104)
107)
108)
78)
38)
44)
107)
102)
33)
106)
--E(Int) Ref. [kJ/ mole]
?-
I::1
4 CH3--CN
HCOOH
CH3--COOH
(CH3)3C--OH
C6H5--NH2
C6Hs--OH
CHC13
HzO
H20
2 HzO
2 H20
3 HzO
4 H20
4 H20
C1-
CI-
C1-
C1-
CI-
CI-
C1-
Br-
Br-
Br-
Br-
Br-
Br
Br-
H, C, O CI H, C, O CI H, C, N C1 H, C, O C1 Ligand C1H O Br H O Br H O Br H O Br H O Br H O Br H O Br
C1
H, C, N C1 H, C, O
GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO GTO
4-3tG 4-31G + 4-31G 4-31G + 4-31G 4-31G + 4-31G 4-31G + 4-31G 4-31G + 4-31G 4-31G + 4-31G 4-31G + (4) (9/5) (14/11/5) (4/1) (9/5/1) (14/11/6) (4) (9/5) (14/11/5) (4/1) (9/5/1) (14/11/6) (4) (9/5) (14/11/5) (4) (9/5) (14/11/5) (4) (9/5) (14/11/5) [2] [4/2] [8/6/2] [2/1] [4/2/1] [8/6/3] [21 [4/2] [8/6/2] [2/1] [4/2/1] [8/6/3] [2] [4/2] [8/6/2] [2] [4/2] [8/6/21 [2] [4/2] [8/6/2]
p orbital
p orbital
p orbital
p orbital
p orbital
p orbital
p orbital
experimental * tetrahedral, * not optimized experimental * tetragonal
experimental
experimental * not varied
experimental
experimental * not varied
experimental
fully optimized * part. optimized fully optimized * part. optimized fully optimized * part. optimized fully optimized * part. optimized fully optimized * part. optimized fully optimized * part. optimized
4-31G geometry
349 Br--O
344 Br--O
345 Br--O
340 Br--O
340 Br--O
339 Br--O
339 Br--O
355 CI--C 222 CI--H 215 C1--H 244 CI--H 246 CI--H 227 C1--H 230 C1--H
213
215
172
101
122
54
64
69
77
47
49
72
92
158
109)
109)
109)
109)
109)
109)
109)
107)
107)
107)
107)
107)
107)
lOg)
¢¢
5"
h"
63
tO
Ligand uncontracted
GTO 4-31G
GTO 4-31G
all
all
HCO)i" 2 H20
HCO 3
HCO 3
3 H20
HzO
[3/1] [5/3/1] [1] [2/1] [1] [2/1]
contracted
STO-3G STO-3G + 3sp orbital 4-31G 4-31G + 3sp orbital
GTO GTO GTO GTO
H C, O H C, O
HCO:~" H20
GTO 4-31G
H2O
HCO 3
type
H GTO (4/1) C, 0 GTO (9/5/1) H GTO (3) C, O GTO (7/3) H GTO (3) C, O GTO (7/3) counterpoise corrected all GTO STO-3G
atom
Basis set b
all
HzO
HCO 3
HCOO- HzO
H C O 0 - H20
H C O 0 - H20
Ion
Table 2. (continued)
free H20 and ion fully optimized
free H20 and ion fully optimized free H20 and ion fully optimized free H20 and ion STO-3G geometry free HzO and ion 4-31G geometry * not varied free H20 and ion fully optimized
assumed
assumed
assumed
Ligand geometry/ * Complex geometry
300 O---O 285 273 0--0 289 278 276 0..--0
275 O--O 250 O--O 283 O--O 300 O--O
290 O--O 275 O--O
R [pm]
220
161
79
95
Illl
11i)
111)
111)
111)
103 86
11o)
110)
110)
69
92
80
- - E (Int) Ref. [kJ/ mole]
t~
~z
Calculation of Interaction Energies in Host-Guest Systems of the host and guest improve each other mutually. Thus Ecomple x [Eq. (1)] is calculated with a virtually larger basis than EHost and EGues t. Larger basis sets lead to more negative total energies. Ecomp~x is therefore too negative and the interaction energy will be overestimated if calculated according to Eq. (1). This effect was carefully analyzed lz3,~25.~26~. Well-balanced small basis sets which are insensitive to the basis set superposition error are now available ~29.~30) The basis set superposition error can be estimated using the counterpoise technique ~19~. In this method the energies EHost and Eau~st are calculated using the geometry and basis set applied for the complex but with zero charges on the nuclei of the guest and of the host, respectively. It is to be noted that the counterpoise calculation does not exactly eliminate the basis set superposition error. It overestimates the correction term and should not be applied in calculations using extended basis sets 145t The importance of polarization functions (like d-orbitals for C, O and N or porbitals for H) for the calculation of ion-ligand interaction energies was pointed out by several authors 7.17.19~. Nevertheles many results using well-balanced small basis sets without polarization functions are acceptable if interactions of ligands with alkali or alkaline earth metal ions are considered (see Tables 1 and 3). The importance of the polarization functions in the case of the ammonium-water interaction was demonstrated recently 91)
2.4 Geometries For an accurate description of the interaction energy the geometries of the host, the guest and of the complex should be optimized using large basis sets. In practice the time for the computation is prohibitively large except for small systems. A way to circumvent this problem is the use of experimental geometries of the host and guest and to search only for their optimal position and orientation in the complex. In the case of ion-ligand interactions as compiled in Tables 1 and 2 this procedure leads to satisfactory results. Geometry optimizations using small basis sets are problematic. The calculated geometries may strongly deviate from the experimentel ones. In a recent study of the H / O - - N H 2 complex, it was shown that the use of experimental geometries may be very satisfactory. The influence of geometry optimization on the calculated interaction energy is in this case insignificant if large basis sets are used, 91) but of significance in case of smaller basis sets 88t (see also Tables 1 and 3). In case of alkali and alkaline earth metal cations as guests, the calculated ionligand distances at the energy minimum depend on the basis set. An improvement of the basis set leads to an increase of the ion-ligand distance. For Li +--HzO and K +-H20 the optimal distances are 176 and 257 pm, if minimal Gaussian basis sets are used. The corresponding values are 189 and 269 pm with extended basis sets (see Table 1). Even these latter values are significantly lower than the sum of the ionic radii 132)and the van der Waals radius of the oxygen atom (218 pm for Li ÷ and 273 pm for K+). These remaining differences can be explained as a consequence of ligandligand repulsions in case of higher coordination number. Ionic radii and van der Waals radii allow, in general, a good approximation of the experimental results if the ions are fully coordinated. They overestimate, however, the optimal distance 63
M a r t i n B a d e r t s c h e r et al.
T a b l e 3. C o m p a r i s o n o f the e x p e r i m e n t a l e n t h a l p i e s o f i n t e r a c t i o n w i t h t h e c a l c u l a t e d i n t e r a c t i o n e n e r g i e s as g i v e n in T a b l e s 1 a n d 2. Ion
Ligand
Li +
NH 3
Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Li + Na + Na + Na + Na + Na + Na + Na + Na + K+ K+ K+
- - k H ( I n t ) (exp,) [k J / m o l e ]
Ref. (exp.) Ref. ( S C F )
169
13a) 13s) 13s) 135) 135~ 135) is) IS) 15) 15) is) 1341 134) 134) 13~) 136j J36) 1361 13a) 134~
164 162 2 NH 3 301 4 NH 3 458 5 NH 3 504 6 NH 3 543 H20 142 2 H20 250 4 H20 405 5 H20 464 6 H20 514 HCN 152 H2CO t 51 CH a-NH 2 172 CH 3-OH 159 CH3--F 128 CH3--CN 180 CH a-CHO 174 CHa--NH--CH 3 177 CH3--O--CH 3 165 CH3--CI 105 CHs--CO--CH 3 186 N(CH3) 3 176 CHa--S--CH 3 134 HCO--N(CHs) 2 209 C H 3 - C O O - - C H 3 184 pyridine 185 NH 3 122 4 NH 3 351
395 5t5 723 741 147 283 494 671 68'0 155 161 167 172 146 188 190 182 172 87 222 201 119 223 172 179 116 509
5 NH 3 6 NH 3 H20 4 H20 5 H~O 6 H20 NH 3
395 436 100 307 359 403 75 84 257 75 71
585 628 105 477 552 594 77
247 292 333 80 102 82 87 93 104
320 387 441 76 107 79 97
4 NH 3 H20
K+ K+ K+ K+ K+ K+ K+
4 H20 5 H20 6 H20 CH3--NH 2 CH3--CN CHs--NH--CH
NH~
NH 3
CH3--O--CH 3
3
113
64
--E(Int) (SCF)" [k J / m o l e ]
333 70 73
118
241 27) 2s) 29~ 29) 32~ 43) 2s) 29~ 29~ 7~ 4o) 21) 19) 45) 19) 19) 19t 19~
136)
19)
136) 134) 136) 136~ 136) 136) 13s)
52) 18) 191 22j 22) 22) 2o~
135}
291
~35) 13s) 15) 15~ i5) 15) 137) ~38) 138) 15~ 1391
29)
15) 15) 15) 137) 139) 137) 137) 14m 141)
29) 29~ 29)
142)
29)
34) 291
29) 29~ 20)
291
33) 76)
21)
82) 82)
s2) ss)
Calculation of Interaction Energies in Host-Guest Systems Table 3. (continued) Ion
Ligand
AH(Int) (exp.) [kJ/mole]
--E(Int) (SCF) a [kJ/mole]
Ref. (exp.) Ref. (SCF)
NH~-
2 NH 3
310
NH +
3 NH 3
NH~
4 NH 3
NH~
5 NH 3
NH + NH~ NH,~ NH~ NH~FFFFFFFC1-
HzO 2 HzO 3 H20 4 H20 5 H20 H20 2 H20 4 H20 CH 3 - C N 2 CH3 - C N 3 CHs--CN 4 CH3--CN H20
177 184 235 253 287 314 318 345 72 134 190 24t 282 97 167 281 67 121 170 213 55 62 59 56 107 151 177 155 90 59 72 81 64 53 104 t 52 198 66 128 185
141~ 142~ 1.1) 142~ t,~l) v*2) 141) 142) 141) 141) 141) 141) 141)
C1C1C1C1C1CICI C1 CICIC1BrBrBrBrHCO 3 HCO 3 HCO 3
CH 3 - O H CH 3 - C N 2 CH3--CN 3 CH3--CN 4 CH3--CN HCOOH CH 3 - C O O H (CH3)3C--OH C6Hs--NH 2 C6H s - O H CHC13 H20 2 H20 3 H20 4 H20 H20 2 H20 3 H20
407 475 481 524 78 166 217 276 493 99 302 481 76 141 198 237 50 50 48 91 128 158 92 72 49 47 77 69 54 I01 172 215 79 161 220
s4) ~) s3~ 8.~ s~ 91) ss) s8~ 8s) s4)
143)
33)
1,3) l,s) 1,~) 1.~) 1,**) 1~)
44~ 38) 104~ lo4) 104~
143)
33)
145) 14~) ia4~ la4) 144~ 144) 146) v~) 1,6) 143) 146) 1~) 143) 143) 1,3~ 143~ 147) 14v) l,v)
1o7~ lo4) 104) 104~ 104) 1o7) Io7~ to7~ lo7~ 107) 1o7) 1o9) io9~ io9) 1o9~ 111 111) 111~
104}
Calculated values obtained with the largest basis sets applied were selected. For details and for other calculations see Tables 1 and 2.
in case o f a 1 : 1 c o m p l e x w i t h a m o n o d e n t a t e ligand. T h e d i f f e r e n c e s are especially large f o r s m a l l c a t i o n s s u c h as Li ÷ a n d M g 2÷ 9s). I n line w i t h t h e s e c o n s i d e r a t i o n s , a decrease o f the metal-oxygen distances with decreasing coordination n u m b e r was d o c u m e n t e d r e c e n t l y b y c o m p a r i n g a large n u m b e r o f X - r a y s t r u c t u r e s o f alkali a n d a l k a l i n e e a r t h m e t a l c o m p l e x e s 133) 65
H20 ,.. NH 2
H20 ... Li +
H20 ... H20
Reaction
298 373 298 0 500
- - 18.0 18.0 --149.4 147.3 - - 78.1
AEscv
Temperature [K] AE e
--4.6 --4.6 2.1 --1.1 --6.6
AEcoru~ 9.2 9.2 8.8 5.6 13.0
AE °
7.9 9.2 1.7 0 14.3
A(AEv) ~
---3.8 --4.6 0 0 ---6.2
AEx
--3.8 --4.6 --3.8 0 --6.2
AEtT
2.5 --2.9 2.5 0 --4.2
APV
Table 4. Examples for the comparison of calculated interaction energies with measured enthalpies (all values in kJ/mol)
-
-
-- 72.4 + 1.7
148~
90,91)
33~
148~
148}
-- 15.1 ± 2.1 ---142.3 ± 8.4
15.5
Ref.
-- 16.3 --143.1 -- 142.8 74,0
--
AH~ v
e~
~"
Calculation of Interaction Energies in Host-Guest Systems 2.5 C o r r e l a t i o n E n e r g y A part of the electronic energy is not considered in case of ab initio SCF calculations since the electrons of different spins are treated as independent (uncorrelated) within the framework of this approach. If the corresponding energy (correlation energy) is of different magnitude in the complex and in its constituents, the correlation energy contribution to the interaction energy has to be evaluated. The intermolecular electron correlation (the dispersion interaction) was calculated or estimated for some cation-ligand interactions using configuration interaction (CI) calculations, perturbation theory or on the basis of a statistical model (see Table 4). Its contribution to the total interaction energy is less than 10 % throughout.
2.6 Comparison with the Experiment Intermolecular interactions in the gas phase have been measured in a series of cases using mass spectrometry 1~-147) From the temperature dependence of the equilibrium constants, besides the free energies, the enthalpies and the entropies of the involved reactions were evaluated. The corresponding data are useful for comparison with the results of theoretical calculations (see Table 3). In order to compare the calculated interaction energies with the measured reaction enthalpies, a series of contributions has to be taken into account. Concerning these correction terms some inconsistencies arise in the literature. Therefore the list of them is given here in detail according to Ref. 148). A H 298 AF298 Calc = ~ C a l c "~ A P V
(4)
AI2298 ~tEe0 -~- A ( A E e ) 298 q- A E ° + A(AE~) 298 + A~'298 -]- A E 298 L'Calc = --r
(5)
AE° is the calculated electronic interaction energy at 0 K. A(AEe)298 is the change in the calculated electronic interaction energy between 298 K and 0 K. This term is negligible unless electronically excited states are important. AE ° is the difference between the zero-point vibrational energies of reactants and product. A(AEv)298 is the change in the vibrational energy difference between 298 K and 0 K. AE298r is the difference in rotational energies of reactants and product. A E 298 is the translational energy change due to the change in the number of degrees of translational freedom. The calculation of the vibrational terms is straightforward but rather time consuming (see e.g. 149~). A-~298 and ~AF298 --r t can be approximated according to classical considerations as - - 1/2, RT for each degree of rotational and translational freedom lost due to complex formation. Assuming an ideal behavior, APV is equal to - - R T for a I : 1 host-guest association since 1 tool gas is lost by the complexation reaction. In Table 4 the calculated contributions for two simple 1:1 complexes are given, 67
Martin Badertscher et al,
3 Treatment of Large Systems 3.1 Introduction The computer time required for ab initio calculations is roughly proportional to the fourth power of the number of atomic basis functions used for the description of the molecular system. Ab initio calculations are thus not feasible today for host-guest systems with more than about 150--200 electrons. Supercomputers and vector processors will significantly lower the necessary CPU times 15o~but they alone probably cannot bring a breakthrough for systems larger than two or three times the ones which can be treated today. An increase in speed can be achieved by using pseudopotential calculations lZZ,151~ In these type of calculations the inner shell electrons are approximated with a potential and the problem is reduced to a valence electron problem. This technique is very powerful for heavy atoms but the time saving is not more than roughly 50 ~o for molecules containing first-row atoms only 152~. Ion-ligand interactions have been studied with pseudopotential calculations in several cases 153-157) In some cases, strange approximations were applied in order to circumvent the pr, suppress the growth of tumors when administered subcutaneously and orally and at the same time are effective against bacterial infections. (D) CH3 (CH2)5CO -- HNCHCOOH
(~H3 t (CH2)2COHNCHCO-- HNCHCOOH 1 (o) (0H2)3 1 H2NCHGOOH
I
(L)
(66)
(o)
4.7 Chlamydocins and Peptidylacivicins Chlamydocin 67, isolated as a cyclic tetrapeptide from culture broths of Diheterospora chlamydosporia by Closse et al. 163~in 1974, has 100 times the cytostatic activity of actinomycin D with respect to inhibition of cell growth in the mouse. Numerous chlamydocin derivatives have been synthesized by D. H. Rich et al. 164}
o
/o\ II /NH CH2-CH--C--(CH2)5--CH ~O
H
,~ ?H -CH2-4,Q~~ CH3 NH
(67)
1 CH3
The characteristic basic unit of the cyclopeptide is S-2-amino-S-9,10-epoxy-8oxodecanoic acid. U. Schmidt et al. have reported the synthesis of chlamydocin and epichlamydocin 165). One of the main problems in the treatment of cancer is always the high toxicity of cytostatics and their low selectivity against malignant cells. Attempts to develop prodrugs that are only activated in the vicinity of a tumor by a tumor-enzyme inhibition have been made with peptidylacivicins. Tumor cells contain high levels of plasmin-activator and therefore high protease-plasmin levels. According to Katzenellenbogen et al. 166) with the aid of AT-125 peptide 68 it should be possible to achieve the full effect of plasmin-activated prodrugs only in the cancer cells. D-VaI-Leu-Lys-NH-CH-COOH
(68) Ct
4.8 Bestatin Bestatin 69[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, which can either be obtained from culture broths of Streptomyces olivoreticuli as per H. Umezawa 134
Recent Developmentsin the Field of BiologicallyActivePeptides et al. 167) or by synthesis ~68), can be used in the treatment of malignant skin tumors.
(•)--CH2--CH-CH-CO-NH-CH-COOH I I NH 2 OH
I OH2
(69)
t
CH CH3/ N CH 3
5 Peptides of the Renin-Angiotensin System 5.1 Proteolytic Cascade of the Renin-Angiotensin System 169,170) Since the re,in-angiotensin system is involved in regulation of the blood pressure, antihypertensive substances are encountered among the peptides that exert an effect on this system. The mechanism of the renin-angiotensin system is illustrated in Fig. 10.
Asp--Arg --Val--Tyr --lie --His --Pro--Phe
Arg--Pro--Pro-Gly--Phe + Ser--Pro + Phe--Arg
Angiotensin II [ Angiotensin-Converting I ~ I I ............ Enzyme Asp--Arg--VaI--Tyr --lie--His-- Pro --Phe--His--Leu
Arg--Pro--Pro--Gly--Phe--Ser - Pro-Phe--Arg
Angiotensin 1
Bradykinin
Angiotensinogen
Kininogen
Fig. 10. Processingof angiotensinogen and kininogen
When the blood pressure is reduced, or during sympathetic stimulation, renin is secreted from the juxtaglomerular kidney cells. This enzyme liberates a biologically inactive decapeptide, angiotensin I, from the renin substrate (angiotensinogen) produced in the liver, with cleavage of a Leu-Leu or a Leu-Val bond (human). Under the influence o f a peptidyldipeptide hydrolase likewise present in plasma (angiotensinconverting enzyme = ACE), the biologically active angiotensin II is formed from angiotensin I by splitting-off of the C-terminal dipeptide His-Leu (Fig. 10). Angiotensin II has a contracting effect on the vascular smooth muscle and is the most powerful vasoconstrictor known. 135
Gunter Schmidt
5.2 Angiotensin H Antagonists and ACE Inhibitors Inhibition of the action of angiotensin II 70 has been achieved with many angiotensin I and II analogs (Fig. 11), in which, on the basis of structure-activity relationships, an essential function is attributed to the Phe 8 residue in stimulation of the receptor, while Tyr4 and His6 residues are thought to be important in the binding to the receptor. These angiotensin II-blockers (70-75) prevent the action of the effector peptide of the renin-angiotensin system on the target organ. Saralasin 71 is currently in use as an angiotensin-receptor antagonist in the treatment of hypertension, despite its partial agonistic effect. The disadvantages of 71 lie in the fact that it is administered i.v. and in its short biological half-life. (70) (7:) (72) (73) (74) (75)
Asp-Arg-Val-Tyr4-Ile-His6-Pro-Phe s Sar-Arg-Val-Tyr-Val-His-Pro-A|a Sar-Arg-Val-Tyr-lle-His-Pro-lle t 71,I721 Sar-Arg-Val-Tyr-lle-His-Pro-Thr 173) Sar-Arg-Val-Tyr-Ile-His-Pro-Ala 174~ Asp-Arg-Val-Tyr-Ile-His-Ala-Phe 17sj Fig. 11. Angiotensin II antagonists
The teprotide BPP9, (bradykinin-potentiating peptide) 76 and analogous BPP peptides 17o), which have been isolated from snake venom, are taken up by ACE in competition with the substrate angiotensin I with far greater affinity. pyroGlu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro
(76)
Converting enzyme (ACE) inhibitors 176) likewise prevent the formation of angiotensin II and are used in the treatment of renal and essential h}3~ertension. Examples of orally active ACE-inhibitors are: (2)-l-[(2S)-3-[N-(S)-mercapto-2-methylpropanoyllproline 170) (captopril 77), 1-[N-(S)- 1-carboxy-3-phenylpropyl]-L-alanyl-Lproline-l'-ethyl ester 177) (enalaprit 78), and 2-[N-[(S)-l-ethoxycarbonyI-3-phenylpropyl]-L-alanyl]-(lS,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid 178) (Hoe 498; 79).
CH3 ~
~
4C'"-H v
OH3
CX3OH
H
(77)
(78)
~
CH3H.....f~ H (79)
I36
COOH
COOH
Recent Developmentsin the Field of BiologicallyActivePeptides Today, captopril (Capoten ®) ranks among the most frequently used drugs in the treatment of hypertension. Enalapril (Xanef~) has been commercially available since 1985 as a second ACE inhibitor. The discovery of captopril started an avalanche of research into the synthesis of angiotensin-converting enzyme inhibitors. Some new developments should be mentioned at this point: 1. Tripeptide analogs of enalapril 80
179), e.g.
COOHCH3 'CX~--CO--UH~
Ii1"~O ~(k~....H H
(80)
COOH
2. t-Glutarylindoline-2-carboxylic acid derivatives 81 18o), e.g.
(81) COON 3. N-substituted y-D-glutamyl-cis-perhydroindoline-2-(S)-carboxylic acid 82 181), e.g.
(~)--CH2"-"O
CO i
% "-.,
(82)
COOH 4. Cilazapril = (1S,9S)-9-[(S)-l-ethoxycarbonyl-3-phenylpropylamino]-octahydro10-oxo-6-H-pyridazo-[ 1,2-a] [1,2] diazepine-carboxylic acid 83 182).
0
COOH (83)
.,c ooc
Lj'..#
5.3 Renin Inhibitors Another way of reducing the blood pressure via the renin-angiotensin system is to block the conversion of angiotensinogen into angiotensin I by inhibition of renin. Two different types ofrenin inhibitors are distinguished. 137
Gunter Schmidt
5.3.1 Substrate-Analogous Renin Inhibitors As a highly specific acid peptidase, renin cleaves the decapeptide angiotensin I from the N-terminal end of the substrate angiotensinogen (Fig. 12).
ACE
Renin
Asp-Arg-Val-Tyr-Ile- His-Pro-Phe-His-Leu-Val-Ile-His-X-Glu-Protein I
j
Angiotensin II [
-
1 Angiotensin I
t Angiotensinogen Fig. 12. Stepwise enzymatic cleavage of human angiotensinogen; X = peptide fragment of angiotensinogen
D e r i v a t i z a t i o n s in t h e N - t e r m i n a l s e q u e n c e o f h u m a n a n g i o t e n s i n o g e n led to w e a k l y a c t i v e r e n i n i n h i b i t o r s 183L A c c o r d i n g t o Szelke et al. 18,), h i g h l y a c t i v e s u b s t r a t e analogs with modified peptide linkage (--CHz--NH--) were formed by reduction o f t h e C O - - N H b o n d in L e u - L e u o r P h e - P h e ( T a b l e 2).
Table 2. Renin inhibitors with a modified peptide linkage; R = reduced peptide linkage Substrate sequence 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Plasma, human Asp Arg Vat Tyr Ile His Pro Phe His Leu Leu Val Tyr Ser ,,, ICso[M]K I
R His Pro Phe His Leu-Leu Val Tyr
1 × 10 -6
R
H-77
D-His Pro Phe His Leu-Leu Val Tyr
1 x 10 -6
R
His Pro Phe His Phe-Phe Val Tyr
8.2 × 10- v
R
His Pro Phe His Leu-Val lie His
1.9 × 10 -7
R
His Pro Phe His Leu-Val Ile Tyr
H-142
1 x 10 °~
Pro His Pro Phe His Leu-Val Ile His R Pro His Pro Phe His Leu-Val Ile His Lys
1.0 x 10 -8
Iva Val Val Sta-Ala-Sta
2.2 x 10 -5
Pepstatin
1.6 x 10 -8
T h e r e s u l t s o f in v i t r o a n d h u m a n v o l u n t e e r s t u d i e s s h o w t h a t t h e b e s t r e n i n i n h i b i t o r to d a t e is H-142. 138
Recent Developments in the Field of Biologically Active Peptides
5.3.2 Statine-Containing Renin Inhibitors Pepstatin 84, which was isolated from actinomycetes and which contains the unusual amino acid statine (Sta), inhibits renin and other acidic proteases.
,30 ?,3 CH
?,. CH 3 CH3
I
CH 3 CH3
x/
CH
CH
I
x/
c.,i c.i
,3\?,3
c.l
o.3j
I
y,o.
(84)
CO--NHCHCO--NHCHCO--NHCHCHCH2CO--NHCHCO--NHCHCHCH2CO2H Iva - -
Val
Val
Sta
Ala
Sta
By exchanging Leu~° for Sta in the N-terminal end of angiotensinogen, active renin inhibitors have been produced (Table 3) 185-188~. It is assumed that statine corresponds to the tetrahedral intermediate during the enzymatic hydrolysis of the Leu1°-Val1~ peptide linkage in angiotensinogen. Table 3. Inhibition of porcine renin by statine-containing substrate analogs, (*KM-value 183)) 6
7
8
9
10
11
12
13
ICso(M)
His--Pro--Phe--His--Leu-- Leu --VaI--Tyr His-Pro-Phe-His-Sta-Leu Phe-NH2 I v a - - H i s - - P r o - - P h e - - H i s - - S t a - - Leu - - Phe--NH2 B o c - - H i s - - P r o - - P h e - - H i s - - S t a - - Leu - - Phe-NH2 S t a - - Leu - - P h e - N H 2 H i s - - S t a - - L e u - - Phe--NH 2 P h e - - H i s - - S t a - - Leu ~ Phe--NH2 P r o - - P h e - - H i s - - S t a - - L e u - - Phe--NH2 lbu --His --Pro--Phe --His --Sta--NH2 Ibu -- His --Pro--Phe --His - - S t a - - Leu --NH2 I b u - - H i s - - P r o - - P h e - - H i s - - S t a - - L e u - - Phe--NH2 I b u - - H i s - - P r o - - P h e - - H i s - - S t a - - Ala - - Phe-NH2 I b u - - H i s - - P r o - - P h e - - H i s - - S t a - - Val m P h e - N H 2 I v a - - H i s - - P r o - - P h e - - H i s - - S t a - - lie - - Phe-NH2 B o c - - H i s - - P r o - - P h e - - H i s - - S t a - - Leu - - Tyr-NH2 B o c - H i s - - P r o - - P h e - - H i s - - S t a - - L e u - - Phe-OCH3 Iva--His--Pro--Phe--His--Sta--Leu--VaI--Phe--NH2 tva = isovaleroyl
(5.5x10-5) * 2.0x10 -a 3.1x10 -8 2.7x10 -8 2.0x10 -3 3 . 7 x t 0 -4 1.3x10 -6 2.0x10 -7 2.9 x 10-5 6.7x10 -7 4.3x10 -8 5.7x10 -8 1.2x10 -7 1.3x10 -7 2.6x10 -8 1.1 x l 0 -8 4.6x10 -5
Boc = tert- B u t o x y c a r b o n y l
Iva-His-Pro-Phe-His-Sta-Ile-Phe-NH 2 is so far the best statine-containing renin
inhibitor. According to Rich, new protease inhibitors were produced by replacing statine in pepstatin derivatives with (3S,4S)-4,8-diamino-3-hydroxyoctanecarboxylic acid (DAHOA) 85a 189a)or 4-amino-3-hydroxy-5-phenylpentanecarboxylic acid (AHPPA) 85b 189b, o)
~
H2
Iva--Vat--VaI--NH--CH ~
OC2H 5
Iva --Val-- NH--CH ~
HO "" ~H 0
HO
(85 a)
(85b)
Ala -- NH--CH 2 H O
139
Gunter Schmidt
L 364210 86 and analogous highly active renin inhibitors, which have a longer duration of action and greater stability in vivo owing to their improved polarity and solubility, have been produced by Merck & Co./USA 19o)
HsC2--O--CO--Phe--Hi O~H s--NH CO--Leu--NH-~cH2NH 2
(86)
It is not only of scientific but also of great commercial interest to develop new drugs active on renin-induced hypertension.
6 Plasma Kinins Plasma kinins are tissue hormones liberated from s-globulins of the blood plasma by kallikrein.
6.1 Bradykinin and Kallidin Bradykinin 87 and kallidin (Lys-bradykinin-decapeptide), which are split off from the kininogen in the plasma by trypsin and kallikrein respectively (Fig. 10), hardly differ in their pharmacological activity. The most important effect of the kinins is a dilation of the peripheral vessels, which leads to an improved blood flow, in the kidneys for example, and therefore increases diuresis. By acting on the formation of angiotensin II, kinins can contribute to the regulation of blood pressure. Moreover, kinins cause a contraction of the bronchial muscle. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
(87)
Bradykinin was first synthesized by Boissonnas et al. 191),since when many research groups have reported on bradykinin analogs 89~
6.2 Tachykinins (Fig. 13) The following active substances, known as tachykinins 192) which in contrast to the stow-acting kinins exert a rapid stimulating effect on the smooth muscle, are similar in their biological activities and their structure but differ in their origin. Eledoisin, which was discovered in the salivary glands of cephalopods from the Mediterranean by Erspamer in 1949, exerts an antihypertensive effect and acts as a spasmogen. A large number of eledoisin analogs have been prepared by Boissonnas et al. 193), Liibke et al. 194) Erspamer et al. 195), and Voelter et al. 196) Physalaemin 197,198), isolated by Erspamer in 1964 from the skin of American amphibians, has a strong vasodilating and antihypertensive action. 140
Recent Developments in the Field of Biologically Active Peptides
Uperolein, phyllomedusin, and kassinin, which Anastasi 199) isolated from frog skin, exhibit broad similarities with other tachykinins.
Pyr-Pro-Ser-Lys-Asp-Ala-Phe-Ile-Gly-Leu-Met-N H 2 Pyr-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-Gly-Leu-Met-NH2 Pyr-Ala-Asp-Pro-Lys-Thr-Phe-Tyr-Gly-Leu- Met -NH 2 Pyr-Pro-Asp-Pro-Asn-Ala-Phe-Tyr-Gly-Leu- Met-NH 2 Pyr - - Asn-Pro-Asn-Arg-Phe-Ile-Gly-Leu-Met-NH2 Asp-Val-Pro-Lys-Ser-Asp-Gln-Phe-Val-Gly-Leu-Met-NH 2
Eledoisin Physalaemin [Lys5,Thr6]Physalaemin Uperolein Phyllomedusin Kassinin
Asp-Glu-Pro-Lys-Pro-Asp-Gln-Phe-Val-Gly-Leu-Met- NH 2
[GluZ,ProS]Kassinin
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 Arg-His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2
Substance P Substance K
Fig. 13. Primary structures in the family of tachykinins; Pyr = pyroglutamic acid
Substances P and K can be considered as mammalian tachykinins in view of their unmistakable chemical relationship. Caerulein 88, which was isolated from skin extracts from the Australian tree frog Hyla caerula, has a longer-lasting antihypertensive activity than bradykinin or physalaemin. It causes a contraction of the gallbladder and bile ducts, and stimulates intestinal peristalsis. Caerulein analogs have been synthesized by Bernardi et al. 200, 201)
pyroGlu-Gln-Asp-Tyr-Thr-Gly-Tr~Met-As~Phe-NH 2
(88)
SO3H
7 Atrial Natriuretic Peptides (ANP or ANF) In 1983 de Bold et al. 202)first isolated an atrial peptide ANP-(6-3 3) from homogenates of rat atrial muscle and elucidated its structure (Fig. 14). In January 1984, K. Kangawa et al. prepared pure samples of the a-human atrial natriuretic peptide ~-h-ANP(6-33 Met ~7) zo3~ and of the hitherto longest-known natriuretic peptide containing 126 amino acids, 7-h-ANP 2o4), from human atrial tissue.
1 3 6 10 12 17 19 Leu--Ala --Gly--Phe--Arg --Set --Leu --Arg --Arg - S e t --Set --Cys --Phe--Gly--G~--Arg--Ile --Asp--Arg
I [
lie
f
1
S
Tyr--Arg--Phe--Ser--Asn--Cys--Gly--Leu--Gly--Ser_Gin_Ala_Gly 33 32 28 22
Fig. 14. Amino acid sequence of rat atrial natriuretic peptide 141
Gunter Schmidt Seidah et al. 205)isolated ANF-(1-33) from rat atria and synthesized a shorter ANF(8-33), which is identical with natural ANF-(3-33) in its biological activity. Needleman et al. 206)isolated atriopeptin I [ANF-(10-30) or AP I] and atriopeptin II [ANF-(10-32) or AP II], also from rat atrium extracts. S. P. Adams (Monsanto Compay) and P. Needleman (Washington University, St. Louis) synthesized the following atrial peptides by the solid-phase method zo7~ (Table 4).
Table 4. Biologicalactivity of ANF analogs ANF analogs
Relative activity in rabbit aorta assays
AP I AP II Ap3-19 Arg-Arg-AP II Ser-Leu-Arg-Arg-APII DesPhe22-Ap II DesSer1-AP II DesSer~-DesSerz-AP II DesSer2t-AP I
1.4 200 0.35 300 150 7.0 200 56 1.0
Table 4 shows that arginine residues at the N-terminal end increase the bioactivity. Tyr33 is not absolutely necessary, but all the other amino acids at the C-terminal are (see AP I). The ANF hormones, which derive from higher-molecular-weigh precursors (atriopeptigens), have diuretic properties, i.e. an administration of ANF in the rat increases diuresis and natriuresis (the release of Arg-vasopressin is inhibited) and at the same time the vessels are dilated, apparently by inhibition of catecholamines and angiotensin II. In addition, it has been shown that under volume loading the ANF peptides are released from the atria and develop their effects as hormones in renal, vascular, and other tissues. They can be considered as functional antagonists of the renin-angiotensin system. The antihypertensive properties of ANF could really represent a new therapeutic starting point in combatting hypertensive disease in man.
8 Thyroid Hormones (Calcitonins) Calcitonins (Fig. 15) with an N-terminal intrachain 23-membered disulfide ring were isolated independently by 4 different research groups, structurally clarified in 1968, and synthesized. Calcitonin causes the deposition of calicum phosphate in the skeleton by stimulation of the bone-forming cells, and hence reduces the levels of calcium and phosphate in the blood (hypocalcemia). Completely synthetic calcitonin products such as Salmcalcitonin (Sandoz Ltd., Switzerland)zos) Elcitonin (Toyo Jozo Co., Japan)209) and 142
Recent Developmentsin the Field of BiologicallyActivePeptides I
I
Bovine H.Cys-Ser-Asn-Leu-Ser-Thr-Cys-Val-Leu-Ser -AIa-Tyr-Trp-Lys-Asp-Leu1 I Salmon H.Cys.Ser_Asn-Leu-Ser-Thr-Cys-Val-Leu-Gly-Lys-Leu-Ser-Gln-Glu'Leu[ I Human H-Cys-Gly-Asn-Leu-Ser-Thr-Cys-Met -Leu-Gly-Thr-Tyr-Thr-Gln-Asp-PheBovine Asn-Asn-Tyr-His-Arg-Phe-Ser-Gly-Met-Gly-Phe-Gly-Pro-Glu-Thr-Pro-NH2 Salmon His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Thr-Gly-Ser-Gly-Thr-Pro-NH2 Human Asn-Lys-Phe-His-Thr-Phe-Pro-Gln-Thr-Ala-Ile-Gly-Val-Gly-Ala-Pro-NH2 Fig. 15. Primarystructures of calcitoninin various species [16-alanine]-Salmcalcitonin (Armour Pharmaceutical Co.) zl°~, are available for therapeutic use (bone atrophy).
9 Peptide Antibiotics Since the discovery of bacitracin 89 35 years ago and of gramicidin 90 211) in 1946, hundreds of peptide antibiotics have been synthesized. H I
S
CH3CH2--C--CH--'
