Prediction of protonation constants of hydrazones and Schiff bases derived from pyridoxal 5′-phosphate, pyridoxal, 3-hydroxyisonicotinaldehyde and salicylic aldehyde

Abstract

Hydrazones and Schiff bases are potent metal chelators applied in various areas such as analytical chemistry and medicine because of their various biological activities, including antimicrobial, antitumor, analgesic, and anti-inflammatory action. The hydrazones and Schiff bases derived from aldehyde forms of the B6 vitamin are arguably the most biologically active representatives of these classes. Protonation constants associated with pharmacokinetic characteristics are among the most important properties of drug-like molecules as they affect their binding to proteins, membrane transport, excretion, etc. The present paper accumulates data on protonation constants of hydrazones and Schiff bases derived from pyridoxal, pyridoxal 5′-phosphate, 3-hydroxyisonicotinaldehyde, and salicylic aldehyde available in the literature. A novel simple chemometric model is constructed based on these data to describe the protolytic equilibria constants. The model proposed takes into account such molecular descriptors as molecular weight, number of hydrogen bond donors and acceptors, polarizable surface area, and log P. The contribution of ionic strength is also included in the model. The adequacy of the model and the statistical significance of separate parameters are studied using standard mathematical procedures. The protonation constants of five hydrazones derived from pyridoxal and hydrazides of isonicotinic, 2- and 3-furoic, 2- and 3-thiophenecarboxylic acids are determined experimentally in aqueous solution at T = 298.2 K, p = 0.1 MPa and I = 0.50 mol/L (NaCl) and compared with the model predictions. Protonation constants determined can be used further in studies of coordination equilibria of the hydrazones.