GIAO-NMR spectroscopy of the xanthine’s structures in water solution using S-MC/QM methodology: an evaluation of the DFT-functionals’ efficiency

Abstract

In this work, we report results for the structural solute–solvent, electrical and magnetic properties of xanthine derivatives: caffeine, paraxanthine and theophylline, considering the effects of polarization in water that represents the achievement of electrostatic balance between solute and solvent. For this procedure, we performed atomistic computer simulations based on iterative and sequence applications of Classical Monte Carlo Simulations and Quantum Mechanics (S-QM/MM). We employ additional calculations using DFT to calculate the chemical shielding of xanthine molecules in the liquid environment, comparing the efficiency of various DFT-exchange and correlation functionals (B3LYP, CAM-B3LYP, BHandHLYP and PBE1PBE). The hydrogen bonds between the solute and the solvent were analyzed and the contribution of this structural property to the NMR spectrum was also carefully considered. Additionally, supramolecular models for xanthine-water in solution were also evaluated with the aim of evaluating whether such models can contribute to a better description of the magnetic signatures of carbon and hydrogen atoms.