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

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.