One pot synthesis of Curcumin-NSAIDs prodrug, spectroscopic characterization, conformational analysis, chemical reactivity, intramolecular interactions and first order hyperpolarizability by DFT method

Abstract

A novel Curcumin-NSAIDs prodrug 4-((1E, 3Z, 6E)-3-hydroxy-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,3-trienyl)-2-methoxyphenyl-2-(4-isobutylphenyl) propanoate (2) derivative was synthesized by Steglich esterification in high yield and characterized with the help of 1H, 13C NMR, 1H–1H COSY, UV, FT-IR spectroscopy and mass spectrometry. The molecular geometry of synthesized compound was calculated in ground state by Density functional theory (DFT/B3LYP) using two different basis set 6-31G (d, p) and 6-311G (d, p). Conformational analysis of 2 was carried out to determine the most stable conformation. Stability of the molecule as a result of hyperconjugative interactions and electron delocalization were analysed using Natural bond orbital (NBO) analysis. Intramolecular interactions were analysed by AIM (Atom in molecule) approach. Global and local reactivity descriptors were calculated to study the reactive site within molecule. The electronic properties such as HOMO and LUMO energies were calculated using time dependent Density Functional Theory (TD-DFT). The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). First hyperpolarizability value has been calculated to describe the nonlinear optical (NLO) property of the synthesized compound. Molecular electrostatic potential (MEP) for synthesized compounds have also been determined to check their electrophilic or nucleophilic reactivity.