Synthesis, structural characterization and DFT study of N-(pyrimidyl)-omega-amino acids/peptide: beta-alanine, gamma-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid and glycylglycine

In this manuscript we report the synthesis and structural characterization of five pyrimidine amino acid/peptide modified derivatives: N-(2-pyrimidyl)-beta-alanine (pyr-beta-Ala) (1), N-(2-pyrimidyl)-gamma-aminobutyric acid (pyr-GABA) (2), N-(2-pyrimidyl)-5-aminovaleric acid (pyr-5A-Val) (3), N-(2-pyrimidyl)-6-aminohexanoic acid (pyr-6A-Hex) (4) and N-(2-pyrimidyl)glycylglycine (pyr-GlyGly) (5), as well as the corresponding nitrate salts of the protonated pyr-GABA (2a), pyr-5A-Val (3a) and pyr-6A-Hex (4a). The presence of two types of hydrogen bond donor/acceptor groups (carboxylic acid and aminopyrimidine) allows the formation of "head-to-tail " or "head-to-head " 1D supramolecular polymers in the solid state, which have been studied using DFT calculations. The analysis of such assemblies and binding modes is relevant since they can be considered as minimalistic models of interactions between the side chain of aspartic or glutamic amino acids and pyrimidine bases. Apart from the H-bonding networks, other assemblies like antiparallel pi-stacking and anion center dot center dot center dot pi-hole dimers have been also studied and compared. The noncovalent interactions have been rationalized using molecular electrostatic potential (MEP) surfaces and Bader's quantum theory of "atoms-in-molecules " (QTAIM) and reduced density gradient (RDG) computational tools.