Synthesis of stable platinum complexes containing carborane in a carrier group for potential BNCT agents.
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.
Yoo
Jeongsoo
J
Department of Molecular Medicine and Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea. yooj@knu.ac.kr
Do
Youngkyu
Y
D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001880:Boranes / Q000138:chemical synthesis / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy; D002264:Carboxylic Acids / Q000737:chemistry; D002712:Chlorides / Q000737:chemistry; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D018360:Crystallography, X-Ray; D006801:Humans; D007477:Ions / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017671:Platinum Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D001880:Boranes; D002264:Carboxylic Acids; D002712:Chlorides; D007477:Ions; D017671:Platinum Compounds; D015082:2,2'-Dipyridyl; D002945:Cisplatin