Experimental and theoretical elucidation of structural and antioxidant properties of vanillylmandelic acid and its carboxylate anion.

Vanillylmandelic acid (VMA), an important metabolite of catecholamines that is routinely screened as tumor marker, was investigated by the various spectroscopic techniques (IR, Raman, UV-Vis, antioxidant decolorization assay and NMR). Structures optimized by the employment of five common functionals (M05-2X, M06-2X, B3LYP, CAM-B3LYP, B3LYP-D3) were compared with the crystallographic data. The M05-2X functional reproduced the most reliable experimental bond lengths and angles (correlation coefficient >0.999). The importance of intramolecular hydrogen bonds for structural stability was discussed and quantified by the NBO analysis. The most prominent bands in vibrational spectrum were analyzed and compared to the experimental data. The positions of the carbon and hydrogen atoms in NMR spectra were well reproduced. The differences in UV-Vis spectrum were investigated by adding the explicit solvent and by performing NBO and QTAIM analyses. The discrepancy in the two spectra of about 50nm could be explained by the solvent effect on carboxyl group. The most probable antioxidant activity mechanism was discussed for VMA and its carboxylate anion. The Molecular Docking study with the C - reactive protein additionally proved that variety of functional groups present in VMA and its anion allowed strong hydrogen and hydrophobic interactions.