Synthesis of stable platinum complexes containing carborane in a carriergroup 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 = 3 4; n = 4 5). The prepared ligands successfully replaced the labile benzonitrile groups of [Pt(PhCN)₂Cl₂] to afford three cisplatin analogs [Pt(L)Cl₂] (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)Cl₄, L = 4 and 5] were also successfully prepared from Na₂[PtCl₆]·6H₂O. 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.