Palladium and platinum complexes with HmtpO (where HmtpO = 4,7-dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5a]pyrimidine, an analogue of the natural ocurring nucleobase hypoxanthine) of the types [M(dmba)(PPh3)(HmtpO)]ClO4 (dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl; M = Pd or Pt], [Pd(N-N)(C6F5)(HmtpO)]ClO4 [N-N = 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (Me(2)bpy), or N,N,N',N'-tetramethylethylenediamine (tmeda)] and cis-[M(C6F5)(2)(HmtpO)(2)] (M = Pd or Pt) (head-to-head atropisomer in the solid state) have been obtained. Pd(II) and Pt(II) complexes with the anion of HmtpO of the types [Pd(tmeda)(C6F5)(mtpO)], [Pd(dmba)(mu-mtpO)](2), and [NBu4](2)[M(C6F5)(2)(mu-mtpO)](2) (M = Pd or Pt) have been prepared starting from the corresponding hydroxometal complexes. Complexes containing simultaneously both the neutral HmtpO ligand and the anionic mtpO of the type [NBu4][M(C6F5)(2)(HmtpO)(mtpO)] (M = Pd or Pt) have been also obtained. In these mtpO-HmtpO metal complexes, for the first time, prototropic exchange is observed between the two heterocyclic ligands. The crystal structures of [Pd(dmba)(PPh3)(HmtpO)](+), cis-[Pt(C6F5)(2)(HmtpO)(2)]center dot acetone, [Pd(C6F5)(tmeda)(mtpO)]center dot 2H(2)O, [Pd(dmba)(mu-mtpO)](2), [NBu4](2)[Pd(C6F5)(2)(mu-mtpO)](2)center dot CH2Cl2 center dot toluene, [NBu4](2)[Pt(C6F5)(2)(mu-mtpO)](2)center dot 0.5(toluene), and [NBu4][Pt(C6F5)(2)(mtpO)(HmtpO)] have been established by X-ray diffraction. Values of IC50 were calculated for the new platinum complexes cis-[Pt(C6F5)(2)(HmtpO)(2)] and [Pt(dmba)(PPh3)(HmtpO)]ClO4 against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR), lung (NCl-H460), and breast cancers (T47D). At 48 h incubation time, both complexes were about 8-fold more active than cisplatin in T47D and show very low resistance factors against an A2780 cell line, which has acquired resistance to cisplatin. The DNA adduct formation of cis-[Pt(C6F5)(2)(HmtpO)(2)] and [Pt(dmba)(PPh3)(HmtpO)]ClO4 was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by these platinum complexes on plasmid DNA pBR322 were also obtained.