Synthesis, characterization, and cytotoxicity of trimethylplatinum(IV) complexes with 2-thiocytosine and 1-methyl-2-thiocytosine ligands

The reaction of [PtMe3(MeOH)(bpy)][BF4] (1) with the thionucleobases 2-thiocytosine (SCy, 2) and 1-methyl-2-thiocytosine (1-MeSCy, 3) resulted in the formation of the complexes [PtMe3(bpy)(SCy-κS)][BF4] (4) and [PtMe3(bpy)(1-MeSCy-κS)] [BF4] (5), respectively. The complexes were characterized by 1H and 13C NMR spectroscopy as well as by single-crystal X-ray analyses of 4 · MeOH and 5. In 4 · MeOH two strong hydrogen bonds (N4–H⋯N3′: N4⋯N3′ 2.976(7) Å) between the thiocytosine ligands give rise to base pairing thus forming dinuclear cations [{PtMe3(bpy)(SCy-κS)}2]2+. In both complexes the platinum atom is octahedrally coordinated [PtC3N2S] by three methyl ligands, the 2,2′-bipyridine ligand and the κS coordinated nucleobase (configuration index: OC-6-33). The structural investigations gave evidence that the sulfur atoms of the nucleobase ligands in 4 · MeOH and 5 have to be regarded as sp3 and sp2 hybridized, respectively. Thus, the ligand in 4 · MeOH has to be considered as the deprotonated thiol-amino form of thiocytosine being reprotonated at N1. In complex 5 the 1-MeSCy is coordinated in its thione-amino form. DFT-calculations of the base-paired dinuclear cation in 4 as well as of 4 itself gave proof of the strength of the hydrogen bond (8.5 kcal/mol) and exhibited that cation–anion interactions influence the conformation of the complex. In vitro cytotoxicity studies of 4 and 5 using nine different human tumor cell lines revealed moderate cytotoxic activity.

Reactions of [PtMe3(MeOH)(bpy)][BF4] with the thionucleobases 2-thiocytosine (SCy) and 1-methyl-2-thiocytosine (1-MeSCy) resulted in the formation of the base-paired dinuclear complex [{PtMe3(bpy)(SCy-κS)}2] [BF4]2 (see figure) and the monomeric complex [PtMe3(bpy)(1-MeSCy-κS)][BF4], respectively. The thionucleobases are coordinated to the platinum through the exocyclic sulfur atom, which has to be regarded as sp3 and sp2 hybridized, respectively.Figure optionsDownload as PowerPoint slide