11B NMR Probes of Copper(II): Finding and Implications of the Cu2+-Promoted Decomposition of ortho-Carborane Derivatives

The development of noninvasive methodologies for the detection of d-block metal ions such as copper (Cu2+), zinc (Zn2+), and manganese (Mn2+) is important for understanding their biological roles and relationship with diseases. We have been interested in the use of B-11 NMR probes for the detection of d-block metal ions, because B-11 is an ultratrace element in living systems. o-Carboranes, which consist of ten boron and two carbon atoms, have been applied to numerous drugs and biological active agents. In this work, we found that the o-carborane-pendant cyclens (L-3-L-5) (cyclen = 1,4,7,10-tetraazacyclododecane) are decomposed in the presence of Mn2+ or Cu2+ in aqueous solution at neutral pH, accompanied by the release of 4-9 equiv. of B(OH)(3). Furthermore, it was found that o-carborane derivatives that contain hydroxyl groups instead of a cyclen unit also undergo decomposition in the presence of Cu2+ and the corresponding complexes such as Cu(bpy) to afford 10 equiv. of B(OH)(3), as confirmed by B-11 NMR spectroscopic analysis and an azomethine-H assay. These reactions are applied to B-11 MRI (magnetic resonance imaging) probes for Cu2+.