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

Dalton Trans. 2009 Jul 7:(25):4978-86. doi: 10.1039/b823193a. Epub 2009 May 8.

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] x 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / chemistry
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Boranes / chemical synthesis
  • Boranes / chemistry*
  • Boron Neutron Capture Therapy*
  • Carboxylic Acids / chemistry
  • Chlorides / chemistry
  • Cisplatin / analogs & derivatives*
  • Cisplatin / chemical synthesis
  • Crystallography, X-Ray
  • Humans
  • Ions / chemistry
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Platinum Compounds / chemistry*

Substances

  • Antineoplastic Agents
  • Boranes
  • Carboxylic Acids
  • Chlorides
  • Ions
  • Platinum Compounds
  • 2,2'-Dipyridyl
  • Cisplatin