CONFORMATIONAL ISOMERISM OF THE HOST AS A FACTOR IN MOLECULAR RECOGNITION IN HOST-GUEST INCLUSION COMPLEXES - EXAMPLE OF TRIS(5-ACETYL-3-THIENYL)METHANE

The tripod molecule tris(5-acetyl-3-thienyl)methane (TATM) is a flexil e molecule, i.e. one that can occur in many conformationally isomeric states (conformers), which forms host-guest inclusion complexes with a large variety of guests (solvents). Some 40-odd different types of gu est have been reported to form inclusion complexes. Five different typ es of crystal structure (all racemic), with nine different guests, hav e been reported in the literature and structural information is availa ble for 17 crystallographically independent TATM molecules; most of th e guests are disordered. Our analysis of this (substantial but, nevert heless, incomplete) database shows that each group of crystallographic ally isomorphous structures contains a particular TATM conformer with characteristic torsion angles about the bonds between methane carbon a nd the three thienyl rings (tau(1), tau(2) and tau(3)); the range of t orsion angles in a particular structural group does not exceed 10 degr ees. Conformers are in addition distinguished via the stereochemistry of the acetyl group; there are approximately equal numbers of examples with carbonyl oxygen syn or anti to ring sulfur, intermediate conform ations not being found. So far three different types of conformer have been encountered for the TATM molecule considered as an entity. A nec essary condition for the occurrence of a particular conformer type is that the torsion angles tau(1), tau(2) and tau(3) are such that ring h ydrogens should not approach more closely than (say) 2.4 Angstrom, but this is not sufficient as considerably larger distances are found in some conformer types. Crystallization of the inclusion complex from a particular solvent can be envisaged to occur as follows. The TATM solu tion will contain a Boltzmann distribution of host conformers, the dis tribution depending on temperature but not on the nature of the solven t. Under suitable temperature and solubility conditions, the solvent w ill crystallize together with the appropriate conformer to form the in clusion complex-nuclei formed at this recognition stage, then grow int o crystallites of the inclusion complex. The perturbed Boltzmann distr ibution (depleted in appropriate conformer) will continuously revert t o its equilibrium form by conversion of the non-appropriate into the a ppropriate conformer as the crystallization proceeds.