Quantum Chemical Modeling, Synthesis, Spectroscopic (FT-IR, Excited States, UV/VIS) Studies, FMO, QTAIM, ELF, LOL, NBO, NLO and QSAR Analyses of Nelarabine

Abstract

In this study, we report the results of experiments and density functional theory (DFT), time-dependent DFT, and quantitative structure-activity relationship (QSAR) analyses of (2R,3S,4S,5R)-2- (2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl) tetrahydrofuran-3,4-diol (nelarabine). The molecular geometry, vibrational modes, excited states, molecular electrostatic potential (MEP) maps were calculated and discussed. Frontier molecular orbitals (FMO), quantum theory of atoms in molecules (QTAIM), electron localization function (ELF), localized orbital locator (LOL), natural charge, natural bonding, orbital (NBO) analysis were conducted and discussed. Nonlinear optical (NLO) and thermodynamic parameters were determined and discussed. In addition, Fourier transform infrared (FT-IR) and ultraviolet/visible (UV-Vis) spectral parameters were calculated and were found to agree with experimental spectral parameters excellently. The physicochemical, pharmacokinetic, and pharmacodynamic profiles were determined. The applicability of nelarabine as an anticancer drug was investigated in terms of QSAR models, and positive conclusions were yielded.