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)-(C 6 F 5 )(1-Mecyt)]ClO 4 [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)]CIO 4 [dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl; L′ = PPh 3 (M = Pd or Pt), DMSO (M = Pt)] have been obtained. Palladium and platinum complexes of the types cis-[M(C 6 F 5 ) 2 (1-Mecyt) 2 ] (M = Pd or Pt) and cis-[Pd(L′)(C 6 F 5 )(1-Mecyt) 2 ]ClO 4 (L′ = PPh 3 or t-BuNC) have also been prepared. The crystal structures of [Pd(bpzm*)(C 6 F 5 )(1-Mecyt)]ClO 4 , [Pt(dmba)(DMSO)(1-Mecyt)]ClO 4 , cis-[Pd(C 6 F 5 ) 2 (1-Mecyt) 2 ], and cis-[Pd(t-BuNC)(C 6 F 5 )(1-Mecyt) 2 ]ClO 4 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(C 6 F 5 ) 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 IC 50 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. © 2005 American Chemical Society.