Synthesis of functional derivatives of [B12H12]2- anion for boron neutron capture therapy, radiodiagnostics and radioimmunotherapy
Abstract: Functional derivatives of dodecahydro-closo-dodecaborate anion [B12H12]2- are potential candidates for medical application in boron neutron capture therapy for cancer and as linkers for the introduction of radiohalogen label into biomolecules for radioimmunodiagnostics and radioimmunotherapy.In this study, new approaches for the synthesis of functional derivatives of the closo-dodecaborate anion were developed and a series of novel functional derivatives were prepared. The alkylation of [B12H11]2- gave the corresponding alkoxy derivatives [B12H11]2- which can be used for synthesis of functional derivatives by functional group interconversion reactions.A series of derivatives containing functional groups attached to the boron cage through long aliphatic chains [B12H11O(CH2)4X]2- (X = OH, NH2, COOH,CH(NH2)COOH) were prepared by ring-opening reactions of the tetramethylene oxonium derivative [B12H11O(CH2)4]- with different nucleophiles.The reaction of [B12H11NH3]- with aldehydes followed by reduction of the Schiff bases formed was used for synthesis of a series of derivatives containing functional groups attached to the boron cage through an aromatic ring [B12H11NH2CH2C6H4-4-X]- (X = NH2, COOH, NCS). The structures of (Bu4N)[B12H11NH=CHC6H4-4-NMe2] and (Bu4N)[B12H11NH=CHC6H4-2-OMe] were determined by single crystal X-ray diffraction.A new method for the synthesis of the carbonyl derivative [B12H11CO]-, a potential synthon for the synthesis of new derivatives with boron-carbon bonds, was elaborated.A new approach to synthesis of water-soluble carboranes using the closo-dodecaborate cage as a hydrophilic substituent was proposed. The double-cage molecules synthesized [ o-, m-, and p-CB10H10(CH2)4OB12H11]2- can be used for the attachment to biomolecules via the carbon atom of the carborane cage using earlier developed methods.
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