Revealing the contributions of DFT to the spectral interpretation for an amino benzoyl thiourea derivative: Insights into experimental studies from theoretical perspectives, and biological evaluation

Abstract

2-Amino-N-(phenylcarbamothioyl)benzamide (APCB), an amino benzoyl thiourea derivative, was synthesized via ring opening nucleophilic substitution reaction. Various spectroscopic techniques, including UV-Vis, FT-IR, and NMR spectroscopy, were used to fully characterize the synthesized thiourea derivative. A comprehensive theoretical study was conducted utilizing density functional theory (DFT) and the B3LYP functional along with 6-311++G(d,p) basis sets to justify the experimental results. NMR chemical shifts were computed, illustrating that the molecule exhibits several intramolecular hydrogen bonds influencing proton assignment. Furthermore, the experimental UV-Vis spectrum was interpreted by incorporating time-dependent density functional theory (TD-DFT) calculations for numerous singlet excited states. Thus, both single and mixed transitions are disclosed. Moreover, DFT calculations were employed for frontier molecular orbitals (FMOs) analysis, non-linear optical (NLO) properties, and calculated thermodynamic functions. The reactivity of different sites is precisely assigned by implementing the molecular electrostatic potential map analysis and the Fukui functions. In addition, the non-covalent interaction was visualized through the reduced density gradient (RDG) function, confirming the existence of N–H⋯O intramolecular H-bond interaction. In contrast, a localized orbital locator (LOL) function explains the various covalent interactions in the molecule. Molecular docking properties and drug-likeness calculations were implemented according to Lipinski's five principles. In terms of biological evaluation, the lead molecule was evaluated as a novel VEGFR-2 inhibitor (IC₅₀ = 35.78 ± 3.06 μM) for treating breast cancer (IC₅₀ = 177.180 ± 5.760 μM). Overall, our study highlights the power of DFT calculations to interpret the spectral data of a synthetic amino benzoyl thiourea derivative, a versatile building block for functional compounds with tailored properties and applications.