Quantum chemical studies of chitosan nanoparticles as effective drug delivery systems for 5-fluorouracil anticancer drug

Using DFT functionals (B3LYP and M06-2X), eight configurations for the adsorption of 5-fluorouracil drug (F1.1) drug on chitosan nanocarrier (CHIT) have been investigated in aqueous solution. The solvation and binding energies were examined in solution (water) and gas phases. The energetic stability of eight configurations (CHIT/ FU1-8) were demonstrated by the negative values of binding energies. The solvation energies displayed that the solubility of FU drug rises in the vicinity of CHIT nanocarrier which is an essential factor for applicability of a nanocarrier. The quantum molecular descriptors showed that the toxicity of FU in eight configurations decreases to some extent and its reactivity increases. The AIM analysis for CHIT/FU1-8 demonstrated that the hydrogen bonds play important roles in the noncovalent functionalization of CHIT with FU. The covalent Functionalization was examined through Schiff base formation. Two mechanisms were investigated and it was found that proton transfer could take place through three intermediates. (C) 2020 Elsevier B.V. All rights reserved.