COMMUNICATIONS
calculation with an active space of 45 configurations. All calculations
were carried out with Gaussian94.[19]
[13] R. Huisgen, Angew. Chem. 1970, 82, 783 ± 820; Angew. Chem. Int. Ed.
Engl. 1970, 9, 751 ± 762.
[14] a) J. Cioslowski, P. Piskorz, M. Schimeczek, G. Boche, J. Am. Chem.
Soc., submitted; b) G. Boche, M. Schimeczek, J. Cioslowski, P. Piskorz,
J. Org. Chem., submitted.
[15] MP2(full) with 6-31 G(d)[18] for C and H; ECP and (4s,4p,1d)/
[3s,3p,1d] for iodine. Charges quoted are AIM charges, cf. R. W. F.
Bader, Atoms in Molecules: A Quantum Theory, Clarendon Press,
Oxford 1994.
ethers show that the formation of macrocyclic hosts is based to
a large degree on enthalpy advantages (macrocyclic effect).[2]
Entropic contributions to the formation of noncovalent
bonds are one of the most often invoked problems in
molecular recognition, and until now they were among the
least predictable factors. Systematic analyses of free energies
of association DGcplx of many supramolecular associations
show little dependence of DGcplx on the presence of single
bonds in either host or guest molecule, and DDGcplx contri-
butions from the different binding sites are generally addi-
tive.[3] However, most of the investigated complexes were
constructed so as to avoid the presence of many freely
rotatable bonds. This also holds for the few studies of
noncovalent intramolecular interactions, which also show
little strengthening upon rigidification of the underlying
frameworks.[4] In the gas phase one expects rotational entropy
contributions DSrot of 13 ± 21 Jmol 1 K 1 per single bond.[5, 6] If
the rotations were completely frozen upon complex forma-
tion, which is expected only if rigid covalent bonds are
formed,[6] the corresponding loss of free energy DDGrot would
[16] J. J. McDouall, K. Peasley, M. A. Robb, Chem. Phys. Lett. 1988, 148,
183 ± 196.
[17] P. Schwerdtfeger, M. Dolg, W. H. E. Schwarz, G. A. Bowmaker,
P. D. W. Boyd, J. Chem. Phys. 1989, 91, 1762 ± 1774.
[18] a) R. Krishnan, J. S. Binkley, R. Seeger, J. A. Pople, J. Chem. Phys.
1980, 72, 650 ± 654; b) T. Clark, J. Chandrasekhar, G. W. Spitznagel,
P. von R. Schleyer, J. Comp. Chem. 1983, 4, 294 ± 301.
[19] Gaussian94 from Gaussian Inc., Pittsburgh, PA, 1995.
[20] a) W. F. Bailey, J. J. Patricia, T. T. Nurmi, W. Wang, Tetrahedron Lett.
1986, 27, 1861 ± 1864; b) A. Schmidt, G. Köbrich, R. W. Hoffmann,
Chem. Ber. 1991, 124, 1253 ± 1258; c) P. Beak, T. J. Musick, C. Liu, T.
Cooper, D. J. Gallagher, J. Org. Chem. 1993, 58, 7330 ± 7335, and
references quoted.
[21] Such a possibility was explicitly discussed for the sulfoxide ± lithium
exchange reaction: G. Theobald, W. H. Okamura, Tetrahedron Lett.
1987, 28, 6565 ± 6568.
[22] This may also apply to reactions ascribed to a 1,1-dilithioalkene,[23] as
suggested by A. Maercker.[24]
1
be 3.9 ± 6.4 kJmol at room temperature. For noncovalent
interactions Williams et al. assume a value between 2 and
6 kJmol 1 per restricted bond.[7]
Unfortunately these numbers translate into a large un-
certainty of prediction. The presence of only two nonrestrict-
ed bonds[8] in host and guest would correspond to differences
[23] J. Barluenga, M. A. Rodriguez, P. J. Campos, J. Am. Chem. Soc. 1988,
110, 5567 ± 5568.
[24] A. Maercker, B. Bös, Main Group Metal Chem. 1991, 14, 67 ± 71.
1
in the association constant K of between 2 and 11m .
Therefore, it seems to be essential to obtain experimental
values for the change of free energy DGcplx associated with the
presence of single bonds in host ± guest complexes. Surpris-
ingly, there were no studies till now in which the number of
single bonds in supramolecular complexes was systematically
varied. We chose a series of a,w-diamides as hydrogen-bond
donors[9] and a,w-dicarboxylates as acceptors.[10] The tetrabu-
tylammonium salts of the latter are soluble in chloroform. The
functional groups were connected by spacers of different
length and flexibility (Scheme 1). The advantage of these
chloroform-soluble compounds is that interactions other than
hydrogen bonds are suppressed, and problems in the mea-
surements, such as self-association and salt effects, are
minimized.
Stabilities of Hydrogen-Bonded Supra-
molecular Complexes with Various Numbers of
Single Bonds: Attempts To Quantify a Dogma
in Host ± Guest Chemistry**
Frank Eblinger and Hans-Jörg Schneider*
It is generally accepted that optimal preorganization for
molecular recognition requires an optimal geometric fit
between convergent binding sites A(H), A'(G), B(G),
B'(G), etc. of host and guest molecules H and G.[1] If binding
sites within host and/or guest are connected by single bonds,
this can give rise to enthalpy or strain penalties if a transoid
fragment must convert into a gauche conformation for an
optimal orientation of binding sites. At the same time the
presence of freely rotatable single bonds can lead to a loss of
rotational freedom on complexation, which is generally
regarded as a major drawback of, for instance, open-chain
versus macrocyclic receptors. However, systematic analyses of
complexes with crown and open-chain poly(ethylene glycol)
The initially prepared amides of long-chain fatty acids were
only sparingly soluble in chloroform, probably owing to strong
dispersive interactions between the alkyl chains in the solid
state. Therefore, derivatives with the bulky and more
spherical adamantyl group were prepared from the corre-
sponding adamantyl acid chloride and, as expected, were
sufficiently soluble in chloroform. Dilution experiments with
these amides in CDCl3 in which the chemical shift of the NH
protons was monitored gave dimerization constants K <
1
30m , so that at least 85% of the monomer was present in
[*] Prof. Dr. H.-J. Schneider, Dipl.-Chem. F. Eblinger
FR 11.2 Organische Chemie der Universität des Saarlandes
D-66041 Saarbrücken (Germany)
the observed concentration range ( ꢀ 5 Â 10 3 m). Equilibrium
constants were determined according to ref. [11] and gave a
satisfactory fit to a 1:1 model for the association between host
and guest monomers (e.g., Figure 1). The spacers were chosen
to allow contact between the corresponding binding sites
without buildup of substantial strain; this was checked by
computer-aided molecular modeling (Figure 2). All amide
groups and the alkyl chains can retain their transoid
Fax: ( 49)681-302-4105
[**] Supramolecular Chemistry, Part 76. This work was supported by the
Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
Industrie. We thank Prof. A. Yatsimirski, UNAM Mexico, for
literature references and valuable comments. Part 75: A. Roigk, R.
Hettich, H.-J. Schneider, Inorg. Chem. 1998, in press.
826
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3706-0826 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1998, 37, No. 6