Abstract

This study presents a comprehensive experimental and computational study of 4-methoxy-N-methyl-N-(naphthalen-1-ylmethyl)aniline as a novel anti-angiogenic molecular scaffold with relevant optoelectronic properties. The compound was synthesized and fully characterized by H-1 and C-13 NMR spectroscopy, single-crystal X-ray diffraction, and thermogravimetric analysis, revealing a noncentrosymmetric monoclinic crystal structure stabilized by C-H & centerdot;& centerdot;& centerdot; pi interactions and high thermal stability of up to 220 degrees C. Density Functional Theory calculations at the M06-2X/6-311++G(d,p) level showed a moderate HOMO-LUMO gap (131.20 kcal mol(-)& sup1;) and a donor-rich aromatic framework with limited intramolecular pi-conjugation. Nonlinear optical analysis indicated a moderate dipole moment (2.37 D), enhanced polarizability (47.57 & times; 10(-)& sup2;(4) esu), and modest first-order hyperpolarizability, consistent with the absence of a strong push-pull system. However, the molecular rigidity, low polarizability anisotropy, and efficient field-induced charge redistribution give rise to a significant second-order hyperpolarizability (gamma = 80.30 & times; 10(-)& sup3;(6) esu), supporting its potential for third-order nonlinear optical applications. Molecular docking and molecular dynamics simulations revealed stable binding within the VEGFR-2 catalytic site through key interactions with Asp1046, Ala1050, and Asn923, consistent with the stabilization of a DFG-out-like inactive conformation. Cell viability assays in human dermal fibroblasts demonstrated high biocompatibility (>80% viability at 50 & micro;M), highlighting this scaffold as a promising candidate that combines selective VEGFR-2 targeting, low cytotoxicity, and a structurally driven third-order optoelectronic potential.