New Palladium(II) and Platinum(II) Complexes with the Model Nucleobase 1-Methylcytosine: Antitumor Activity and Interactions with DNA

Palladium and platinum complexes with the model nucleobase 1-methylcytosine (1-Mecyt) of the types [Pd(N−N)(C6F5)(1-Mecyt)]ClO4 [N−N = bis(3,5-dimethylpyrazol-1-yl)methane (bpzm*), bis(pyrazol-1-yl)methane (bpzm),
N,N,N‘,N‘-tetramethylethylenediamine (tmeda), or 2,2‘-bipyridine (bpy)] and [M(dmba)(L‘)(1-Mecyt)]ClO4 [dmba =
N,C-chelating 2-(dimethylaminomethyl)phenyl; L‘ = PPh3 (M = Pd or Pt), DMSO (M = Pt)] have been obtained.
Palladium and platinum complexes of the types cis-[M(C6F5)2(1-Mecyt)2] (M = Pd or Pt) and cis-[Pd(L‘)(C6F5)(1-Mecyt)2]ClO4 (L‘ = PPh3 or t-BuNC) have also been prepared. The crystal structures of [Pd(bpzm*)(C6F5)(1-Mecyt)]ClO4, [Pt(dmba)(DMSO)(1-Mecyt)]ClO4, cis-[Pd(C6F5)2(1-Mecyt)2], and cis-[Pd(t-BuNC)(C6F5)(1-Mecyt)2]ClO4
have been established by X-ray diffraction. There is extensive hydrogen bonding (N−H···O, C−H···F or C−H···O)
in all the compounds. There are also intermolecular π−π interactions between pyrimidine rings of adjacent chains
in [Pd(C6F5)2(1-Mecyt)2]. DNA adduct formation of the new complexes synthesized was followed by circular dichroism
and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on
plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the new complexes against the
tumor cell line HL-60. At a short incubation time (24 h) almost all new complexes were more active than cisplatin.