3D-QSPR STUDY ON HYDROGEN BOND STRENGTH OF HYDROXAMIC ACIDS: KEY ROLE OF STERIC AND ELECTROSTATIC FACTORS USING THE kNN-MFAMETHOD

Hydrogen bonding is critical for drug efficacy, impacting factors like absorption, distribution, metabolism, and excretion (ADME) and receptor binding. Hydroxamic acids, low-toxicity, and therapeutically diverse compounds were tested for lipophilicity and hydrogen bond strength. LogP (2.5120-2.8383), hydrogen bond donor (HBD) strength (1.880-3.740), and acceptor (HBA) strength (0.8350-1.271) were calculated. For the prediction of HBD and HBA strengths, we employed k-nearest neighbor molecular field analysis (kNN-MFA), and the best predictions for HBD and HBA were obtained from SWkNN-MFA models. The 3D-QSPR models revealed that hydrogen bond strength was largely influenced by steric and electrostatic conditions. These data are valuable for engineering hydroxamic acid derivatives with improved hydrogen bonding interactions and enhanced therapeutic potential.