Stereospecific reactions and interactions in tri-ortho-thymotide clathrates

The emphasis in this paper is on the interpretation of physicochemical phenomena occurring in tri-ortho-thymotide (TOT) clathrates in the light of crystallographic data. Enantiomeric discrimination of guest included in the cage P3₁21 clathrates, first suggested by H. M. Powell, has been studied for about twenty guest molecules. Practical applications include preparative resolution and determination of the absolute configuration of guest molecules via TOT clathrates. The observation of similar position and orientation within the cage of stereochemically related guests, provides a clue for the chiral discrimination in terms of crystallographic data. The influence of different factors (guest size, crystallographic disorder, etc.) is analyzed, as well as the difficulties in obtaining a precise assignment of the chirality of host/guest interactions. TOT clathrates including stilbene and cinnamic acid as guest undergo photoisomerization reactions whose pathway is different from that observed in solution or in the pure guest crystal, due to the different microenvironment around the olefinic molecule. It is shown that symmetry, as well as crystallographic disorder, is the most important factors governing these phenomena. The analysis of these factors bears similarities with the problems arising in chiral discrimination. In particular, the flexibility of the TOT molecule is probably strongly correlated with the physicochemical phenomena so far studied, as well as with the large variety of crystal forms. The comparison of the TOT molecular configurations in five different crystallographic environments allows a critical discussion on the pertinent molecular parameters which reflect the TOT flexibility.