Structural and QTAIM electronic assessment of Thiamazole adsorption on the transition metal doped fullerenes as a potential smart drug delivery platform

Adsorption of Thiamazole (TZOL, a medication to treat hyperthyroidism) on the transition metal (TM) doped fullerenes (MF) is investigated to gain insight into the potential development of a smart drug delivery platform. In this computational study, molecular models of adsorbed TZOL on TM-doped and undoped fullerenes were optimized and their structural and electronic features were evaluated using density functional theory (DFT) and the quantum theory of atoms in molecules (QTAIM). The TM-doped models were created by substituting a carbon atom of the original fullerene (F) with a metal atom of the first row of transition metals, yielding ten different MF models. TZOL adsorbate (TZOL@MF) showed stronger interaction through its sulphur group binding to the doped metal in comparison to the original carbon fullerene, i.e. TZOL@F. Our calculations indicate that the most stable conjugate system was TZOL on the vanadium-doped fullerene (TZOL@VF) with a free energy of -37.78 kcal/mol followed by Mn-doped fullerene (-36.86 kcal/mol) while that of all undoped fullerene is -9.18 kcal/mol. The impact of water on the stability of TZOL@MFs was investigated and results show that aqueous phases are even more stable than the gaseous phase, again, with TZOL@VF being the most stable of the conjugate adsorbate/adsorbent pair. Frontier molecular orbital analysis showed significant changes of electronic environment from the MF adsorbent to the TZOL@MF conjugated models. HOMO and LUMO levels and their gap energy detected the variations of electronic environment upon adsorption of TZOL, making this system a potential drug delivery platform capable of detection of loaded and released drug molecules.