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

•Synthesis of lipophilic nitrosyl rhenacarborane drug delivery vehicles with boron-functionalized diether tethers.•Vehicle tethers designed with amino or hydroxyl functional groups for amide or ester tethering to amino acids and peptides.•Tethering chains able to withstand conditions of metal nitrosylation without the need for protecting group strategies.

The compound has been synthesized and used as precursor to several nitrosyl rhenacarborane complexes with boron-bound B–O(CH2)2O(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)2O(CH2)2NH3-3,1,2-C2B9H10)]BF4 and [3,3-(CO)2-3-NO-closo-Re(8-O(CH2)2O(CH2)2OH-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 β-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)2O(CH2)2X (X = OH, NH3) tether.

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