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 IV — active and inactive forms of irinotecan

Marek Štekláč, Martin Breza *

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

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

Abstract: Structures of irinotecan (CPT-11) in neutral lactone, neutral carboxyl, and anionic carboxylate forms in singlet ground states and of their complexes with Cu(II) in doublet ground states are optimized using B3LYP/6-311G* treatment. Metal ion affinities (MIA), Cu charges and Laplacians of Cu-ligand bond critical points of possible CPT active sites are evaluated. The formation of Cu(II) complexes with the anionic carboxylate ligand leads to the release of CO2 that can cause a decrease in the concentration of the active lactone form due to equilibria between all forms of the drug. MIA values and electron density transfer to Cu increase in the sequence lactone < neutral carboxyl < anionic carboxylate. Both neutral forms of irinotecan exhibit lower MIA values than those of camptothecin, unlike the anionic carboxylate form.

Keywords: copper(II), cytotoxicity, DFT calculations, electron structure, molecular modelling

Acta Chimica Slovaca, Vol. 16, No. 1, 2023, pp. 1—11, DOI: 10.2478/acs-2023-0001