Investigation of the effect of the N-oxidation process on the interaction of selected pyridine compounds with biomacromolecules: structural, spectral, theoretical and docking studies.

ABSTRACT

Two new N-oxide compounds, namely glycinium 2-carboxy-1-(λ1-oxidaneyl)-1λ4-pyridine-6-carboxylate-glycine-water (1/1/1), C2H6NO2+·C7H4NO5-·C2H5NO2·H2O or [(2,6-HpydcO)(HGLY)(GLY)(H2O)], 1, and methyl 6-carboxy-1-(λ1-oxidaneyl)-1λ4-pyridine-2-carboxylate, C8H7NO5 or 2,6-HMepydcO, 2, were prepared and identified by elemental analysis, FT-IR, Raman spectroscopy and single-crystal X-ray diffraction. The X-ray analysis of 1 revealed an ionic compound containing a 2,6-HpydcO- anion, a glycinium cation, a neutral glycine molecule and a water molecule. Compound 2 is a neutral compound with two independent units in its crystal structure. In addition to the hydrogen bonds, the crystal network is stabilized by π-π stacking interactions of the types pyridine-carboxylate and carboxylate-carboxylate. The thermodynamic stability and charge-distribution patterns for isolated molecules of 2,6-H2pydcO and 2,6-HMepydcO, and their two similar derivatives, pyridine-2,6-dicarboxylic acid (2,6-H2pydc) and dimethyl 1-(λ1-oxidaneyl)-1λ4-pyridine-2,6-dicarboxylate (2,6-Me2pydcO), were studied by density functional theory (DFT) and natural bond orbital (NBO) analysis, respectively. The ability of these compounds and their analogues to interact with nine selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS and Top II) was investigated using docking calculations.