Synthesis and Characterization of (OC-6-33)-Dichloridobis((4-(¹³C₂)ethoxy)-4-(¹³C₄)oxobutanoato)bis((¹⁵N)ethylamine)platinum(IV). Time-Dependent NMR Spectroscopy and HPLC-MS Investigations on its Stability in Cell Culture Medium

Author(s)

Thomas Maier, Bernhard K. Keppler, Mathea S. Galanski, Hristo P. Varbanov

Abstract

In order to investigate the stability of an experimental anticancer platinum(IV) prodrug in cell culture media, (OC-6-33)-dichloridobis((4-ethoxy)-4-oxobutanoato)bis(ethylamine)-platinum(IV) was synthesized with ¹⁵N labeled equatorial and fully ¹³C labeled axial ligands. The title compound as well as its stability in cell culture media was investigated in depth by ¹H, ¹³C, ¹⁵N, and ¹⁹⁵Pt one- and two-dimensional NMR spectroscopy as well as HPLC-MS. Different platinum(IV) compounds as a result of hydrolysis were detected in cell culture media as main species. Besides hydrolysis of one or both equatorial chlorido ligands, also hydrolysis of the ester moiety in the axial ligands and release of ethanol could be observed. The different mono and dihydroxidoplatinum(IV) species were proven by ¹⁹⁵Pt and ¹³C NMR spectroscopy as well as HPLC coupled to MS and HRMS. Reduction of the title compound to the corresponding platinum(II) analog or reaction of the complex with ingredients of the cell culture media were not observed. In cell culture medium supplemented with fetal calf serum (FCS), the formation of hydrolysis species was slowed down by a factor of two.

Organisation(s)

Department of Inorganic Chemistry

External organisation(s)

Research Cluster Translational Cancer Therapy Research, Leopold-Franzens-Universität Innsbruck, Trakia University, Vienna Doctoral School in Chemistry (DoSChem)

Journal

European Journal of Inorganic Chemistry

Volume

27

ISSN

1434-1948

DOI

https://doi.org/10.1002/ejic.202400348

Publication date

2024

Peer reviewed

Yes

Austrian Fields of Science 2012

104003 Inorganic chemistry, 104026 Spectroscopy

Keywords

ASJC Scopus subject areas

Inorganic Chemistry

Portal url

https://ucrisportal.univie.ac.at/en/publications/e18b7634-fe4e-4fe9-8ad8-bc4f29f58c04