Modified-amino acid/peptide pyrimidine analogs: synthesis, structural characterization and DFT studies of N -(pyrimidyl)gabapentine and N -(pyrimidyl)baclofen

In this manuscript, we report the synthesis and structural characterization of two new pyrimidine amino acid modified derivatives: N -(pyrimidyl)gabapentin (pyr-gabapentin) (1) and N -(pyrimidyl)baclofen (pyr-baclofen) (2) and the spectroscopic characterization of γ-lactam subproducts. Both compounds 1 and 2 crystallize in the monoclinic system with Pc (1) and P 2 1 / n (2) space groups. We have analyzed the supramolecular assemblies observed in their solid-state architecture since they can be considered as minimalistic models of protein–DNA in terms of binding synthons. In particular, we have studied the H-bonding interactions between the carboxylate and the aminopyridine ring forming the recurrent R22(8) motifs that are observed in both compounds. Moreover, unconventional π-stacking interactions in 1 and halogen bonding in 2 have been also described and studied energetically using DFT calculations. The interactions have been rationalized by using several computational methods like molecular electrostatic potential (MEP) surfaces, Bader's theory of “atoms-in-molecules” (QTAIM) and the noncovalent interaction (NCI) index.