Use of sodium triacetoxyborohydride in the synthesis of nitroxide biradicals

Abstract

A family of nitroxide biradicals was synthesized for the purpose of creating terminal groups with high relaxivity for linkage to dendrimers for use as targeted MR contrast agents for articular cartilage. The structure of the nitroxide biradicals strongly influenced their MR relaxivities. The addition of a carbon atom between the nitroxyl rings and the bridging nitrogen increased the relaxivity of the nitroxide biradical by ∼14% over what was expected by doubling the relaxivity of the monomeric nitroxide. Conversely in nitroxide biradicals without the additional carbon atoms, steric hindrance restricted the relaxivity to ∼35% below what was expected by doubling the relaxivity of the monomeric nitroxide. Nitroxide biradicals that have a carbon atom incorporated between the nitroxyl rings and the bridging nitrogen exhibit MR relaxivity values ∼223% greater than that of the corresponding monomeric nitroxide. By linking these nitroxide biradicals to a dendrimer, it should be possible to synthesize targeted magnetic resonance contrast agents with higher relaxivities than dendrimer-linked nitroxides with single nitroxyl rings as terminal groups. These dendrimer-linked dinitroxides should be capable of differentiating normal and abnormal articular cartilage on the basis of the glycosaminoglycan concentration.