Formation of Cisplatin Adducts with the Epigenetically Relevant Nucleobase 5-Methylcytosine


Annika Menke, Romeo C. A. Dubini, Peter Mayer,Petra Rovó, and Lena J. Daumann

Eur. J. Inorg. Chem., 2020

With about 4 % abundance in the genome 5‐methylcytosine (5mC) is one of the most important epigenetic modifications. Change in DNA hypermethylation levels has even been linked to resistances to cisplatin treatment of cancer cells. This work aimed at the synthesis and full characterization of 5mC‐cisplatin adducts as well as for the examination of possible side‐reactions and transformations. We report the first X‐ray crystal structure of a cis‐[PtCl(5mC)(NH3)2]Cl complex and the formation of [PtCl(5mC)(NH3)2]+ and [PtCl(5mC)2(NH3)]+ with HR‐ESI mass spectrometry. Further, we explore complex formation and dynamics using 1H, 195Pt, and DOSY NMR spectroscopy. UV/Vis absorption and EPR spectroscopy also confirmed the formation of trace amounts of paramagnetic Pt‐blue species. In the process, a hemiprotonated 5mC dimer, 5mC5mCH+, reminiscent of the “i‐motif” in DNA tetramers, was structurally characterized.