Quantum chemical investigations of electronic properties, chemical reactivity, FTIR, thermodynamic behaviors and biological activity for some novel quercetin derivatives

Quercetin is a crucial natural bioactive substance present in many plants offering numerous health benefits. This computational study uses DFT calculations at the B3LYP/6-31G∗∗ level to computationally investigate novel quercetin derivatives modified by a tetra-amino acid sequence (Ser-Gly-Lys-Arg) in various structural forms including α-amino acids, β-amino acids, mixed-amino acids, and ketoacid. These modifications aim to improve the physicochemical and biological properties of quercetin providing a helpful framework for producing more potent bioactive compounds. Frontier molecular orbital analysis, molecular electrostatic potential mapping and reactivity indices reveal that β-amino acid and ketoacid derivatives exhibit enhanced electronic reactivity and thermodynamic stability relative to native quercetin. In addition, quantitative structure activity relationship (QSAR) descriptors and ADMET predictions are employed as comparative indicators to assess trends in polarity, solubility, and molecular permeability among the investigated compounds. The results highlight how peptide conjugation modulates the electronic and physicochemical properties of quercetin providing a rational computational basis for the future design of quercetin based peptidomimetic systems for further experimental investigation.