Spatial structure and conformations of hydrazones derived from pyridoxal 5′-phosphate and 2-, 3-pyridinecarbohydrazide in the light of NMR study and quantum chemical calculations

Hydrazones derived from pyridoxal 5′-phosphate and hydrazides of 2-, 3-pyridinecarboxylic acids has a significant degree of conformational freedom in the solution and can take 16 configurations, at least. These conformers differ in the total energy and has different population. • Conformations of pyridoxal 5′-phosphate derived hydrazones are studied; • Intramolecular motions are correlated with each other; • Phosphate group rotation induces the rotation of PLP moiety as a whole; • 2- and 3-pyridinyl residues rotate differently due to steric repulsion. Coordination properties and biological activity of the compounds depend significantly on their capability of taking the conformation, most appropriate for complex formation or binding to the target biomolecule. The hydrazones formed by B 6 vitamers, pyridoxal, and pyridoxal 5′-phosphate, are known for their metal chelating ability closely related to their beneficial and adverse effects on living cells. The conformational behavior of two hydrazones derived from pyridoxal 5′-phosphate and 2-,3-pyridinecarbohydrazide is studied utilizing quantum chemistry and NMR techniques. Four possible rotations resulting in different rotamers are analyzed: phosphate group, pyridoxal 5′-phosphate rotation, carbonyl group, and 2- or 3-pyridinyl rotation. Ground states energies, rotation barriers, as well as the structural peculiarities of different species, were estimated on the B3LYP/6-311G++(d,p) level of the density functional theory, while the proportion of different rotamer groups was evaluated from the experimental 1D NOESY measurements.