Acta Chimica Slovaca (ACS) publishes papers on fundamental and applied aspects of chemistry, biochemistry, chemical technology, chemical engineering and process control, biotechnology and food technology. Welcome are also topics which include chemical aspects of materials, physical chemistry and chemical physics, analytical chemistry, macromolecular chemistry and biomedical engineering.

DFT studies of camptothecins cytotoxicity III: camptothecin, irinotecan and SN-38

Marek Štekláč, Martin Breza *

Department of Physical Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, SK-81237, Bratislava, Slovakia

E-mail: * martin.breza@stuba.sk

Abstract: Geometries of camptothecin, irinotecan, SN-38, and of their hypothetical Cu(II) complexes were optimized at the B3LYP/6-311G* level of theory. Their electron structure, evaluated in terms of Mulliken population analysis and Quantum Theory of Atoms-in-Molecule, was subsequently related to in vitro cytotoxicity. Electron density transfer from the relevant active sites to Cu decreases in the sequence irinotecan > SN-38 > camptothecin. The absolute values of their metal-ligand interaction energies exhibit the same trend. Discrepancy with the least relative in vitro cytotoxicity of irinotecan can be explained by differences in its pharmacokinetics.

Keywords: Copper(II) probe, Cu2+-ligand interaction energy, cytotoxicity estimation, electronic structure

Acta Chimica Slovaca, Vol. 15, No. 1, 2022, pp. 72—84, DOI: 10.2478/acs-2022-0009