Anticancer metal complexes developed by adsorption to apatite as an indicator

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Clinical anticancer Pt(II) complexes such as cisplatin, carboplatin, and oxaliplatin commonly consist of 2N and 2C1 or 2O (carboxylate) as donor atoms. These Cl and O groups called "Leaving Group (LG)" have been believed to be less important because anticancer Pt(II) drugs attack the DNA base after dissociation of LG from the Pt(II) coordination. Recently LG has been studied as a tool of drug delivery system (DDS). Focusing recent increment of cancers metastasis to bone, we studied anionic Pt(II) complexes involving phosphate like group as LG and its affinity to hydroxyapatite (HA, C_<10>(PO_4)_6(OH)_2,) because HA is inorganic component of bone.Pt(DA)(LG) complexes (DA=(NH_3)_2, dach; LG=methylenediphosphonate (MDP), pyrophosphate (PP), inositolhexakisphosphate (IP6) were prepared from corresponding Pt(DA)I_2 by treatment of Ag^+ through chelate effect. Crystal structure of Pt(dach)(MDP) showed 2N(NH_2) and 2O(PO_3) coordination to Pt(II). These Pt(II) complexes were stable for hydrolysis in water and showed short half live time (t_<1/2>) in acidic solution. The crystal structure of Pt(dach)(MDP)-oligo DNA adduct revealed the monodentate coordination of Pt(dach) to guanine N7 and removal of MDP as LG. The typical property of these Pt(II) complexes was the excellent adsorption to HA, while cisplatin and carboplatin showed low adsorption. The adsorption fits Langmuir plot and its adsorption constant K depends on the number of P, so from the view of the adsorption the Pt(DA)(IP6) complexes were distinguished.Pt(DA)(LG) exhibited (1) new interaction mode with DNA; (2) good in vitro assay results; (3) good adsorption to HA.