Crystallographic studies of some small molecules of biological interest implications for crystal engineering

Abstract

Crystal engineering in other terms can be also called as the application of supramolecular chemistry to the solid state. It requires the understanding of intermolecular forces amongst which hydrogen bond plays the vital role of becoming the most reliable design element in the construction of supramolecular architectures. Forty one crystals have been prepared and their crystal structures have been investigated. A detailed analysis of the supramolecular architectures and molecular packing has been undertaken which includes organic salts, cocrystals, polymorphs, etc. The present study has got immense importance in biological systems and the design of molecular solids. A brief overview of supramolecular chemistry, crystal engineering and the intermolecular forces is given in chapter 1. Chapter 2 presents a series of cocrystals/ salts involving 2-amino-4,6-dimethyl pyrimidine and 2-amino-4,6- dimethoxy pyrimidine which produces eight 1:1 co-crystals, three 2:1 and five 1:1 salts through O-H···N/ N-H···O or N?H+···O-/N?H···O-hydrogen bonds respectively. The occurrence of the R22(8) synthon is predominant in all the cases and it is only in the next level of organization that these compounds differ significantly by forming different types of larger synthons with the order of priority as follows: linear heterotetrameric synthongtcyclic heterotetrameric synthongt trimeric synthon. Further the analysis of salt/co-crystal formation based on pKa value calculation indicates that 2-amino-4,6-dimethyl pyrimidine tends to be a more predictable and reliable co-crystal former in comparison with its anologue 2-amino-4,6-dimethoxy pyrimidine. The primary hypothesis of chapter 3 in the formation of isostructural cocrystals is based on the chloro/methyl exchange. A series of 17 co-crystals involving 2-amino-4-chloro-6-methyl pyrimidine and 2-amino-4,6-dimethyl pyrimidine have been synthesized where the anologues differ only with respect to chlorine and methyl groups.