Synthesis of stable platinum complexes containing carborane in a carrier group for potential BNCT agents

Abstract

A series of stable platinum complexes containing closo-carborane cages in a 'carrier group', which could be potentially utilized for boron neutron capture therapy (BNCT), was successfully synthesized and characterized by various spectroscopic methods. Two ortho-closo-carborane cages were connected to the 3,3' or 4,4'-positions of 2,2'-bipyridine through ester bonds to give three carborane-linked bipyridine ligands, 3,3'-(3-(1,2-dicarba-closo-dodecaborane-1-yl)propoxycarbonyl)-2,2'-bipyridine (3) and n,n'-(3-(1-methyl-1,2-dicarba-closo-dodecaborane-1-yl)propoxycarbonyl)-2,2'-bipyridine (n = 34; n = 4 5). The prepared ligands successfully replaced the labile benzonitrile groups of [Pt(PhCN)(2)Cl(2)] to afford three cisplatin analogs [Pt(L)Cl(2)] (L = 3-5). In order to increase their aqueous solubility, three carboplatin analogs, [Pt(L)(CBDCA), L = 4 and 5, CBDCA= 1,1-cyclobutanedicarboxylate] and [Pt(4)(oxalate)], were synthesized by employing [Pt(DMSO)(2)(CBDCA)] or [Pt(DMSO)(2)(oxalate)] as a starting platinum(II) source. Two platinum(IV) complexes [Pt(L)Cl(4), L = 4 and 5] were also successfully prepared from Na(2)[PtCl(6)]center dot 6H(2)O. All of the synthesized platinum complexes containing closo-carboranes exhibited excellent stability in both the solid and solution states and could be stored in air for several months. Even though the three closo-carborane ligands were successfully deboronated to the corresponding nido-mono anions by employing a mild degradation method involving CsF/ethanol, all attempts at the incorporation of nido-carborane-linked bipyridine into the platinum complexes failed, leading to the formation of black precipitates of reduced platinum.