Comparison of the Reactivities of Tyrosine–Proline-Based Dipeptides toward Acylation with Nitrophenyl Benzoates

The reactivities of the L-Tyr–L-Pro dipeptide and its analog with a hydroxymethyl group instead of carboxy group in the proline moiety were compared by studying the kinetics of their acylation with di- and trinitrophenyl benzoates and computer simulation of their molecular structures. The rate constants for the acylation of L-Tyr–L-Pro(CH2OH) in water–1,4-dioxane (40:60 by weight) in the temperature range 298–313 K (k298 = 0.065–2.219 L mol–1 s–1] were found to exceed the rate constants for the reactions with L-Tyr–L-Pro on average by a factor of ~5. The geometric, energetic, and electronic characteristics of the dipeptides were calculated at the DFT B3LYP/cc-pVTZ level of theory. The energy of the lone electron pair on the terminal amino nitrogen atom of the dipeptide and the LUMO energy of nitrophenyl benzoate can be used as descriptors for the construction of QSPR models to predict their reactivities in acyl transfer processes. In silico screening of the examined dipeptides and their benzoylated derivatives showed that these compounds are promising as potential medicines.