Substituent‐Driven Modulation of Electronic Properties in Acrylonitrile Derivatives: A Combined Study on NLO Response and DNA ‐Binding Affinity via ECT Analysis

Abstract

This study presents a systematic investigation into the substituent‐driven modulation of the electronic, optical, and biological properties of two methoxy ‐substituted acrylonitrile derivatives, denoted as C‐1 ( m ‐CF 3 substituted) and C‐2 ( p ‐CH 3 substituted). While experimental data revealed a striking parity in their optical band gaps ( E g  = 3.3 eV in DMSO), their distinct electronic profiles prompted a deeper theoretical probe to differentiate their microscopic performances. Density Functional Theory (DFT) calculations at the B3LYP/6–311++G(d,p) level for ground‐state properties and B3LYP/6–311G(d,p) for TD‐DFT calculations were employed to elucidate the underlying electronic mechanisms. Natural Bond Orbital (NBO) analysis demonstrated that both systems exhibit efficient intramolecular charge transfer (ICT) across the acrylonitrile bridge. Furthermore, range‐separated hybrid DFT calculations (CAM‐B3LYP/6–311++G(d,p)) were performed to accurately evaluate the non‐linear optical (NLO) responses without global hybrid overpolarization artifacts. The calculations revealed comparable, robust first‐order hyperpolarizabilities () for both derivatives ( for C‐1 and for C‐2 in DMSO), significantly exceeding the benchmark urea threshold. To explore the theoretical quantum‐chemical reactivity profiles of these chromophores, Electrophilicity Charge Transfer (ECT) analysis was utilized to model their charge‐transfer tendencies with DNA bases. The results indicate that the electron‐withdrawing group in C‐1 enhances its electrophilic character, suggesting a higher charge‐accepting propensity toward nucleophilic bases. By correlating photophysical response with theoretical charge‐transfer descriptors, this work provides crucial mechanistic insights into the design of multifunctional materials suitable for non‐linear optical (NLO) applications and electronic structure tuning.