Synthesis and functionalization of nitrosyl rhenacarboranes towards their use as drug delivery vehicles

The compound [3,3,3-(CO)(3)-closo-Re(8-O(CH2)(2)OCH2CH2-3,1,2-C2B9H10)] has been synthesized and used as precursor to several nitrosyl rhenacarborane complexes with boron-bound B-O(CH2)(2)O(CH2)(2)-tethers to halo, amino and hydroxo functional groups. The last two in particular have afforded a pair of rhenacarborane derivatives, [3,3-(CO)(2)-3-NO-closo-Re(8-O(CH2)(2)O(CH2)(2)NH3-3,1,2-C2B9H10)]BF4 and [3,3-(CO)(2)-3-NO-closo-Re(8-O(CH2)(2)O(CH2)(2)OH-3,1,2-C2B9H10)], for potential use as drug-delivery vehicles. Bioconjugates tethering our delivery vehicles to amino acids or small peptides that are not readily transported across the blood brain barrier, either by means of membrane-based transport mechanisms or through passive diffusion, could make potential pharmacological agents for central nervous system infiltration. The final nitrosyl complexes are made following nucleophilic ring opening of the beta-boron-bound 1,4-dioxane moiety and our work has established that even with unprotected hydroxo and amino terminal groups, the metal can be selectively nitrosylated using [NO][BF4] without destroying the integrity of the B-O(CH2)(2)O(CH2)(2)X (X = OH, NH3) tether. (C) 2015 Elsevier B.V. All rights reserved.