Conformational Isomerism of the Host as a Factor in Molecular Recognition in Host–Guest Inclusion Complexes: Example of Tris(5-acetyl-3-thienyl)methane

Abstract

The tripod molecule tris(5-acetyl-3-thienyl)methane (TATM) is a flexile 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 guest have been reported to form inclusion complexes. Five different types of crystal structure (all racemic), with nine different guests, have been reported in the literature and structural information is available for 17 crystallographically independent TATM molecules; most of the guests are disordered. Our analysis of this (substantial but, nevertheless, incomplete) database shows that each group of crystallographically isomorphous structures contains a particular TATM conformer with characteristic torsion angles about the bonds between methane carbon and the three thienyl rings (τ1, τ2 and τ3); the range of torsion angles in a particular structural group does not exceed 10°. 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 conformations not being found. So far three different types of conformer have been encountered for the TATM molecule considered as an entity. A necessary condition for the occurrence of a particular conformer type is that the torsion angles τ1, τ2 and τ3 are such that ring H atoms should not approach more closely than (say) 2.4 Å, 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 solution will contain a Boltzmann distribution of host conformers, the distribution depending on temperature but not on the nature of the solvent. Under suitable temperature and solubility conditions, the solvent will crystallize together with the appropriate conformer to form the inclusion complex-nuclei formed at this recognition stage, then grow into crystallites of the inclusion complex. The perturbed Boltzmann distribution (depleted in appropriate conformer) will continuously revert to its equilibrium form by conversion of the non-appropriate into the appropriate conformer as the crystallization proceeds.