Amino acids as chelating ligands for platinum: enhanced stability in aqueous environment promoted by biocompatible molecules

25 July 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Platinum (II) based chemotherapeutics are a cornerstone in the treatment of many malignancies. However, their severe toxicity and dose-limiting side-effects have rooted efforts in the medicinal inorganic community to develop better drug candidates with higher selectivity for tumor tissues and less problematic side effects. In the current study, we developed a cytotoxic platinum (II) complex based on a Zeise’s salt substructure containing the nonsteroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA) as a ligand. Since the original complex displayed high reactivity against sulfur-containing biomolecules, the structure was optimized regarding its stability. Amino acids L-alanine, β-alanine and L-histidine were used as biocompatible chelating ligands to achieve this aim. Differences in the coordination sphere caused pronounced changes in the stability profiles of the Zeise-type precursor complexes 1-3. Of the tested systems, coordination with LAla through N in trans position to ethylene (N-trans) showed the most promising results and was employed to stabilize the previously published complex 5. The stability profiles of all complexes were evaluated by capillary electrophoresis and the biological activity was investigated in vitro in various tumor cell lines. To investigate the effect of the NSAID ligand on the mode-of-action, inhibition of cyclooxygenase enzymes was also tested. Platinum (II) complex 4 containing both the ASA and the Ala ligand showed improved stability and higher cytotoxicity, outperforming both 5 and 1, exhibiting a cytotoxic activity at 25 µM comparable to the reference drug cisplatin.


Zeise’s salt
amino acid ligand
capillary electrophoresis
acetylsalicylic acid

Supplementary materials

Supporting Information to: Amino acids as chelating ligands for platinum: enhanced stability in aqueous environment promoted by biocompatible molecules
Supporting Information: NMR characterization spectra, electropherograms, crystal data and structure refinements, NMR experiments set up, IRMPD data and supplementary biological data (PDF)


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.