Crystal structures of some small molecules of biological interest: implications for crystal engineering

Abstract

The thesis presents the results of X-ray crystallographic investigations of some drugs and heterocyclic compounds. The thesis is divided into four parts. PART-I Crystal structures of some derivatives of aminopyrimidines Chapter 1 Hydrogen bonding patterns in the crystal structures of trimethoprim 3,5-dinitro salicylate (1) and trimethoprim 4 chlorobenzoate monohydrate (2) In the title compounds 1 and 2, the carboxylate group of the 3,5-dinitosalicylate/ 4-chlorobenzoate anions makes a specific pair of Nand#61485;H???O hydrogen bonding with protonated nitrogen atom and 2-amino group hydrogen leading to a bimolecular cyclic ring motif (R22(8)) (heterosynthon). In compound 1, the TMP cations self assemble via Nand#61485;H???O hydrogen bonds. A typical intramolecular Oand#61485;H???O hydrogen bond is observed in the anion. In compound 2, the R22(8) motifs self-assemble through a DDAA (D = hydrogen bond donor and A = hydrogen bond acceptor) array of quadruple hydrogen bonds. This array is extended further on either side by Oand#61485;H???O hydrogen bonds, resulting in an array of six hydrogen bonds (DDDand#61655;AAA). The carboxylate groups of the 4-chlorobenzoate anions are bridged by the intervening water molecules (O1W) via Oand#61485;H???O hydrogen bonds resulting in a supramolecular chain.Chapter 2 Crystal structures of pyrimethamine 3,5-dinitrobenzoate [PMNDNB] and bis(pyrimethamine-5-chlorothiophene-2-carboxylate) [PMNCTC] newlinePyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine, PMN] is an antimalarial drug, which inhibits the dihydrofolate reductase enzyme (DHFR). PMN is also used along with other drugs for the treatment of opportunistic infections in patients with AIDS. In both the compounds, aminopyrimidine-carboxylate interaction has been observed (R22(8)). In compound 1, two inversion related PMN cations and 3,5-dinitrobenzoate anions are connected via pair of Nand#61485;H???O hydrogen bonds leading to a quadruple array of (DDAA) hydrogen bonds. The crystal structure is also stabilized by Cand#61485;H???O hydrogen bonds.