Not the usual suspect - an unexpected organometallic product during the synthesis of cytotoxic platinum(II) complexes

Author(s)
Thomas Maier, Judith Wutschitz, Natalie Gajic, Michaela Hejl, Klaudia Cseh, Sebastian Mai, Michael A Jakupec, Mathea S Galanski, Bernhard K Keppler
Abstract

The reaction of (1R,2R)-(cyclohexane-1,2-diamine)dichloridoplatinum(II) with maleic acid unexpectedly resulted in the formation of an organometallic platinum(II) complex featuring a C,O-coordinating ligand. Additionally, a small series of close derivatives with increasing lipophilicity was synthesized. All complexes were fully characterized by multinuclear one- and two-dimensional (1H, 13C, 15N, and 195Pt) NMR spectroscopy, high resolution mass spectrometry, and in one case by X-ray diffraction. The lipophilicity and the impact on the DNA secondary structure as well as the cytotoxic properties in three human cancer cell lines (A549, SW480, and CH1/PA-1) were investigated. Unexpectedly, no clear-cut trend in cytotoxicity was observed with increasing lipophilicity. Also unexpectedly, the complexes showed only a low potential to inhibit cancer cell growth and no sign of interaction with DNA, in sharp contrast to the parent drug oxaliplatin, which seems to be caused by the low reactivity of the investigated compounds.

Organisation(s)
Department of Inorganic Chemistry, Department of Theoretical Chemistry, NMR Centre
External organisation(s)
Vienna Doctoral School in Chemistry (DoSChem), University of Vienna
Journal
Dalton Transactions
Volume
52
Pages
16326-16335
No. of pages
10
ISSN
1477-9226
DOI
https://doi.org/10.1039/d3dt01736b
Publication date
2023
Peer reviewed
Yes
Austrian Fields of Science 2012
104003 Inorganic chemistry, 301904 Cancer research
ASJC Scopus subject areas
Inorganic Chemistry
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/db2a5240-8e3c-413c-abf6-23d4b18018fd