Thiazole–Carbonyl Interactions: A Case Study Using Phenylalanine Thiazole Cyclic Tripeptides

Abstract

Natural as well as synthetic thiazole/oxazole peptides have shown widespread pharmacological and metal binding properties. Herein, phenylalanine- and tyrosine derived thiazole-containing cyclic tripeptides were synthesized, and the influence of the solvent on the supramolecular assembly in the solid state was investigated. Striking influences of the solvent on the solid state structure were observed. S···O interactions between the sulfur of a thiazole ring and a carbonyl moiety of an amide showing an average distance of 3.1 Å which is much smaller than the sum of the van der Waals radii predominantly mediate the crystal structure. To get deeper insights into this kind of interaction, two model systems consisting of thiazole and acetyl-N-methylamide were studied using the MP2/6-311G++(3df,3dp) level of theory. Theoretical calculations revealed that these interactions are associated with an average energy gain of about 16 kJ/mol in comparison with the separated species.