Theoretical investigation on structural, topological, electronic, optoelectronic, nonlinear optical (NLO) properties and in silico molecular docking of some quercetin derivatives

This study investigates the structural, electronic, nonlinear optical (NLO), and optoelectronic properties of quercetin derivatives using density functional theory at the BPV86/6-311G(d,p) level, with dispersion corrections included to enhance reliability. NLO analysis revealed that the derivatives exhibited higher fist-order hyperpolarizability than urea, with the top derivatives of Q4 (47.40 × 10^–30 esu) and Q20 (46.02 × 10^–30 esu) showing values of 1.7 to 3.4 times higher than the p-NA benchmark, making them promising NLO compounds. The strong local electric fields observed for Q14 and Q15 at 7.542 and 7.334 × 10⁹ V m⁻¹ highlight their potential for optoelectronic applications. The HOMO–LUMO energy gap varied between 2.268 and 3.861 eV owing to significant O–H•••O hydrogen bonding, which also influenced chemical reactivity. Topological analysis based on atoms in molecules (AIM) theory confirmed the presence of strong hydrogen bonds, where the strongest interaction is observed for H26•••O19 in Q5. Our results of the molecular docking against breast cancer targets (EGFR, PI3Kα, and ERα) demonstrated strong binding affinities, where the Q19 and Q14 outperformed the reference drugs alpelisib and fulvestrant. Notably, Q4 and Q show binding energies of − 8.3 and − 9.0 kcal mol⁻¹ against EGFR, exceeding gefitinib (− 7.2 to − 8.3 kcal mol⁻¹); Q1 and Q19 achieve − 8.4 and − 9.3 kcal mol⁻¹ against PI3Kα, outperforming alpelisib; and Q18 and Q14 reach − 9.1 and − 9.5 kcal mol⁻¹ against ERα, exceeding fulvestrant. Our findings suggest that quercetin derivatives are promising multifunctional candidates for NLO and anticancer applications.