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 = 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.

Synthesis and Supramolecular Studies of Chiral Boronated Platinum(II) Complexes: Insights into the Molecular Recognition of Carboranes by β‐Cyclodextrin

“…The ITC data clearly demonstrate that b-CD possesses a high affinity for (R/S)-(1-4)·2 NO 3 , for which K eq for the 1:1 host guest adducts is approximately one order of magnitude larger than the 1:2 or 2:1 systems. In the former case, with the exception of (S)-4·2 NO 3 (vide infra), the binding affinities were comparable to values de- 3 15. The higher-order interactions (with the exception of (R)-1·2 NO 3 in which DH/DG = 0.62 and ÀTDS/DG = 0.38) were also strongly enthalpically favoured with the DH/ DG ratios ranging from 4.4 to 1.4 and DS < 0.…”

“…[14] The second step has also been observed in Pt II complexes containing 2,2'-bipyridinepropoxylcarbonyl(1,2-closo-carboranyl) ligands, for which deboronation either before or after metal complexation resulted in immediate reduction of the metal centre and decomposition of the complex. [15] In the present study, it is likely the closo-to nido-carborane transformation is triggered by the pyridyl ligand acting as a nucleophile. Indeed, the first reported intermediate in the selective deboronation of 1,2-closo-carborane used pyridine as a nucleophile.…”

N,O-Type Carborane-Based Materials

“…The phenomenon is attributed to the electron density being withdrawn from the boron cluster upon metal complexation. There are, however, some reports, mainly dealing with Pt II complexes where deboronation seems to occur prior to metal complexation and most probably due to the nucleophilicity of the ligand itself [67,68].…”

An amphiphilic block copolymer conjugated with carborane and a NIR fluorescent probe for potential imaging-guided BNCT therapy

“…The LET range is limited to a diameter of 5-9 μm which is in accord with the size of a single cell. [11][12][13][14] However, carborane compounds are generally hydrophobic substances which cannot be dispersed in aqueous solution. A higher total dose can be received than that of the adjacent normal tissues resulting from a greater concentration of 10 B in tumor cells.…”