Chemistry for the Future. Proceedings of the 29th IUPAC Congress, Cologne, Federal Republic of Germany, 5–10 June 1983

428 Pages·1984·24.96 MB·English

by  H. Grünewald (Eds.)

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INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY
in conjunction with
Gesellschaft Deutscher Chemiker
CHEMISTRY FOR THE FUTURE
Proceedings of the 29th IUPAC Congress
Cologne, Federal Republic of Germany, 5-10 June 1983
Edited by
H. GR٢NEWALD
Ver Jag Chemie GmbH
Weinheim, Federal Republic of Germany
PERGAMON PRESS
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First edition 1984
Library of Congress Cataloging in Publication Data
IUPAC Congress (29th : 1983 : Cologne, Germany)
Chemistry for the future.
At head of title: International Union of Pure and
Applied Chemistry in conjunction with Gesellschaft
Deutscher Chemiker.
I. Chemistry—Congresses. I. Gr٧newald, Η.
II. International Union of Pure and Applied Chemistry.
III. Gesellschaft Deutscher Chemiker. IV. Title.
QD1.I95 1983 540 83-23825
British Library Cataloguing in Publication Data
International union of pure and Applied Chemistry.
Congress f29th : 1983 : Cologne)
Chemistry for the future.—(IUPAC symposium series)
1. Chemistry—Congress
I. Title II. Gr٧newald, Η
III. Gesellschaft Deutscher Chemiker IV. Series
540 QDl
ISBN 0-08-029249-6
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Printed in Great Britain by A. Wheaton & Co. Ltd., Exeter
Scientific Committee
President:
R. Sammet
Secretary General:
W. Fritsche
Members:
Μ. Becke
Κ. Η. B٧chel
Η. Dφrfel
Μ. Eigen
Ε. O. Fischer
Ε. U. Franck
Ο. Glemser
Η. Hellmann
J. Thesing
Ε. Vogel
Η. G. Wagner
Κ. Weissermel
G. Wilke
INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY
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Cowley Centre, Oxford 0X4 3YF, UK
ix
CFF-A*
PREFACE
Chemistry as a science covers a wide spectrum of applications of increasing
importance for an ever growing mankind to meet the basic needs regarding food,
health, clothing and accommodation. It also plays an important role in world
economics. Behind these applications of chemical science which are clearly
visible and familiar to the general public lies considerable work in the
forefield to which the scientific chemical societies effectively contribute.
They promote the transfer of knowledge and experience by several appropriate
means. The International Union of Pure and Applied Chemistry is active for
that purpose in an international scope; with its incomparable work, including
continuing projects which have spanned many decades, it has contributed
substantially to the progress of chemistry.
One of the most effective means for the transfer of knowledge is undoubtedly
the Chemical Congress. The Gesellschaft Deutscher Chemiker (German Chemical
Society) on behalf of the National Adhering Organization Deutscher
Zentralausschuss fόr Chemie readily took over the preparation and organization
of the 29th IUPAC Congress which successfully took place from the 5th to the
10th of June 1983 in the Congress Centre in Cologne. The programme consisted
of 9 invited plenary lectures and 52 invited section main lectures by
prominent scientists as well as 160 discussion papers and 242 posters of high
scientific level. They covered New Advances in Inorganic Chemistry, in
Organic Chemistry, and in Physical and Theoretical Chemistry, Progress in the
Production of Chemical Basic Materials, Education in Chemistry, and a Joint
Symposium on Chemical Information.
The scientific world is grateful to Pergamon Press for taking over the task of
publishing the plenary and section main lectures of the 29th IUPAC Congress in
one representative volume in order to disseminate them beyond the Congress
participants from 36 countries, and provide a lasting documentation of the
results of this major international event in chemical science.
Wolfgang Fritsche
Secretary General,
Gesellschaft Deutscher Chemiker
Secretary General,
29th IUPAC Congress
xi
HOST-GUEST COMPLEXATION CHEMISTRY
Donald J. Cram
Department of Chemistry, University of California at Los Angeles,
Los Angeles, California 90024 USA
Abstract - The principles of complementarity and of preorganizaron have
been applied to the study of structural recognition in complexation. A
chiral host has been synthesized which by design complexes enantiomers of
a particular configuration of racemic amino acid or ester salts by selec­
tivity factors as high as 31. The same host catalyzes (with turnover)
the reaction with an electrophile of a complexed prochiral potassium-
carbon acid salt to produce a chiral product that is ^99% optically pure.
A mimic for the acylation of a serine esterase has been synthesized which
by collection and orientation of reactants accelerates a transacylation
rate by a factor of 10 11 over that observed for a noncomplexing model
compound. A host containing an enforced cavity lined with electron pairs
(a spherand) is reported which is the strongest known complexer of
lithium and sodium ions. This ligand system rejects all other metal
ions. Organization of this host during synthesis rather than during com­
plexation is shown to enhance binding by factors as high as > 10 12.
Hosts with enforced concave surfaces of molecular dimensions (cavitands)
have been prepared. Cell-like hosts have been designed that are
potentially capable of encapsulating organic molecules. The hosts and
complexes were designed with the help of scale molecular models, and
their structures confirmed with crystal structure and nuclear magnetic
resonance spectral techniques.
INTRODUCTION
The magnificent ability of genes, enzymes, immune systems, hormones, and pheromones to
interconvert organic compounds and regulate chemical traffic in organisms depends on struc­
tural recognition in complexation. The receptors and substrates of evolutionary origin
provide the organic chemist with both inspiration and challenge to design and synthesize
organic compounds which through structural recognition in complexation might perform chemi­
cal tasks never before carried out by compounds of nonevolutionary origin.
Hosts, the synthetic counterparts of biological receptors, are conveniently defined as
organic compounds containing convergently arranged binding sites. Guests, the synthetic
counterparts of substrates, possess divergently arranged binding sites. Host-guest com­
plexes are formed when the molecular shapes and binding sites of hosts and guests are
complementary. A complex is composed of a host and guest held together in a definite
structural relationship. The binding partners are attracted by hydrogen bonding, ion-
pairing, ion-dipole, pi-acid to pi-base, van der Waals forces, and by solvent liberation
phenomena (in water solution, hydrophobic binding). These forces are weak compared to the
strength of covalent bonds, so multiple contacts of binding sites of hosts and guests are
needed to structure most complexes.
Structural recognition in complexation depends upon unique complementary relationships
between potential complexing partners. Complementarity has geometric and electronic
features, both of which are subject to design when the host and guest are organic compounds.
Relationships between the binding free energies of complexes and the structures of the
complexing partners are now subject to systematic examination and rationalization.
This paper addresses the following questions. Can chiral hosts be designed and synthesized
to complex only one enantiomer of a racemate? Can chiral hosts be used to catalyze re­
actions that lead from prochiral starting materials to enantiomerically pure products? Can
hosts be designed that mimic some of the catalytic features of the serine esterases? Can
hosts be designed that show very high discrimination in complexing alkali metal ions? What
are the relationships between the free energies of binding of host to guest and the degree
to which each is conformationally organized for complexing prior to complex formation?
3
4 D. J. Cram
Can hosts with rigid concave surfaces of molecular dimensions be prepared? Can cell-like
hosts be designed that might encapsulate organic guests?
CHIRAL RECOGNITION IN COMPLEXATION
Scale molecular model examination suggested that chiral host ]_ and guest 2 should form
complex 3. The complex was synthesized, and its crystal structure 4 turned out to possess
the anticipated structure (Ref. 1). Host RR-5 was prepared, since molecular model exami­
nation suggested it should complex D-amino acid and ester salts, e.g., D-6, better than
their L-anantiomers. Thus 1_ should be the more stable complex. Solutions of racemic amino
acid and ester salts in water were extracted with chloroform solutions of RR-5, and the
layers were separated. The optical purity and configuration of the guest isolated from each
layer were determined. From the values obtained, the distribution constants for each
enantiomer were determined, as well as the differences in free energies of the diastereo-
meric complexes. Twelve different amino acids or esters were examined. In all cases,
guests of the D-configuration were the more complexed enantiomers by factors that ranged
from a high of 31 to a low of 2. The -Δ(Δ6°) values ranged from a high of 1.9 to a low of
0.4 kcal mol"1. The highest chiral recognition was observed with phenylglycine methyl ester
hexafluorophosphate salt (Ref. 2). An amino acid (or ester) resolving machine based on a
W-tube was designed, built, and run continuously for several days. The resolution is based
on chiral recognition of each enantiomer in ion transport through bulk liquid membranes
(Fig. 1). The two enantiomers of about 90% optical purity were obtained from this experi­
ment as applied to phenylglycine methyl ester hexafluorophosphate salt.
CH
3
2
3 4
R
5
l
+
H-N--H
Η PFef 6 7
Host-Guest Complexation Chemistry
RESOLVING MACHINE
Fig. 1 Amino acid and amino ester resolving machine
CHIRAL CATALYSIS
Chiral host RR-5> was also used as a turnover catalyst in the conversion of prochiral salt 8
as guest into chiral S-9 of about 99% optical purity. The catalyst turnover number was 10,
and the value for A(AG+T was ^2.0 kcal mol" 1. Formula iEMs a schematic representation show­
ing the charge and aryl group location in the plane of 8. This guest uniquely fits into
host 5^ to produce complex ]J0. In the complex, 8^_ is "sided" and the electrophile,
3-pentenone, approaches the carbanion only from the open side. The direction of the con-
figurational bias was predicted in advance of experiment through molecular model examination
(Ref. 4).
8' 10
6 D. J. Cram
PROGRESS TOWARD A SERINE ESTERASE MIMIC
Formula Y\_ represents the important components in the active sites of serine esterase
enzymes. Elucidations of their crystal structures inspired the design with the help of
molecular models of target host 12. We predict that 12 will catalyze the hydrolysis
of guests such as 13, and possibly amides as well.
Proton transfer
catalyst
11
In an incremental approach to 12, we synthesized host 14, and found that it complexed Jj5
(as a picrate) in chloroform with a binding free energy of -AG° = 13.2 kcal mol .l Two
views of the crystal structure of the complex 16 are shown in 17 and 18. The nucleophilic
primary hydroxyl group was introduced into the system by synthesizing 19. This host com­
plexed methyl ammonium and sodium picrates in chloroform with 12.7 and 13.6 kcal mol" 1
binding free energy, respectively (Ref. 5). Host J_9 was acylated by 20 to give complexed
ester 21 and £-nitrophenol. The kinetics of formation of 21 were measured in chloroform
and found to be first order in added RaN^NHClOi, buffer ratio. Thus the alkoxide ion is
the nucleophile. The rate of acylation of 19 was MO 11 faster than the rate for the non-
complexing model compound, 3-phenylbenzyl alcohol. However, when sodium Perchlorate was
added, the acylation rate of ]_9 was inhibited by several powers of 10. Thus the acylation
of 1_9, like that of serine esterases, is subject to competitive inhibition. These facts
demonstrate that collecting and orienting reactants through highly structured complexation
results in enormous rate acceleration. We anticipate that incorporation of the imidazole
and carboxylate groups as in target catalyst ]_2 will induce hydrolysis of acylated esters
and provide the catalyst turnover characteristic of enzymes (Ref. 6). The synthesis of 12
has not yet been accomplished.
Nucleophile
Proton transfer
12 13
CDCI
3]
25° 1
14 15 16
Host-Guest Complexation Chemistry 7
SPHERANDS AND THE PRINCIPLE OF PREORGANIZATION
Crystal structures of chorands (crowns) and cryptands show that they fold to fill their own
cavities (Ref. 1). Their complexation involves conformational reorganization and desolva-
tion of their binding sites. To assess the cost in binding free energy of guest organizing
and desolvating host, we designed and synthesized the spherands whose binding sites are
rigidly preorganized and shielded from solvation by a hydrocarbon shell. Their binding
free energies were then compared to conformationally mobile systems. The crystal structure
of prototypical spherand 22 is shown in 23. Those of their lithium and sodium ion complexes
are pictured in 2£ and 25. Notice that 22 has the rare property of containing a hole
defined by octahedrally-arranged oxygens whose twenty-four unshared electrons define the
boundaries of the hole. The hole is shielded from solvation by the supporting aryl groups
and the six methyl groups attached to the oxygens (Ref. 7).