| Derivatives of [closo-B12(OH12] 2-, known as "closomers," have been well studied and can be synthesized through standard organic reactions. These closomers are discrete, have closely spaced radial substituents and exhibit controllable solubility. Furthermore, the B12 core displays low toxicity. As such, closomers are ideal candidates as scaffolds in drug design. Twelvefold conjugation of therapeutics to the B12 core has advanced profoundly in recent years. The efficacy of such B12 closomeric drug delivery systems relies heavily on targeted delivery of therapeutics to desired sites through the use of directing groups such as antibodies and peptides. Targeted delivery can be accomplished by differentiating the vertices of the B12 core such that orthogonal functions may be selectively conjugated to both targeting moieties and therapeutics.;[Closo-B12(OH)11OPO3H] 3- represents the first closomer having two different functionalizable substituents. It exhibits stability to high temperatures and prolonged exposure to aqueous acidic and basic conditions at varying temperatures. The conjugation of a linker to the free phosphate is investigated. The compound, [ closoB12(OAc)10O2PO2] 3-, a unique closomer containing a cyclic phosphate, has been isolated.;[Closo-B12(OH)11O(CH 2CH2O)7CH2CH2N3] 2-, represents the first closomer to have eleven free vertex alcohols and one vertex coupled to a linker having a terminal orthogonal function available for conjugation. Conjugation of the linker to a directing biomolecule is discussed and requires further investigation. |
