11B NMR sensing of d-block metal ions in vitro and in cells based on the carbon-boron bond cleavage of phenylboronic acid-pendant cyclen (cyclen = 1,4,7,10-tetraazacyclododecane).

Noninvasive magnetic resonance imaging (MRI) including the "chemical shift imaging (CSI)" technique based on (1)H NMR signals is a powerful method for the in vivo imaging of intracellular molecules and for monitoring various biological events. However, it has the drawback of low resolution because of background signals from intrinsic water protons. On the other hand, it is assumed that the (11)B NMR signals which can be applied to a CSI technique have certain advantages, since boron is an ultratrace element in animal cells and tissues. In this manuscript, we report on the sensing of biologically indispensable d-block metal cations such as zinc, copper, iron, cobalt, manganese, and nickel based on (11)B NMR signals of simple phenylboronic acid-pendant cyclen (cyclen = 1,4,7,10-tetraazacyclododecane), L(6) and L(7), in aqueous solution at physiological pH. The results indicate that the carbon-boron bond of L(6) is cleaved upon the addition of Zn(2+) and the broad (11)B NMR signal of L(6) at 31 ppm is shifted upfield to 19 ppm, which corresponds to the signal of B(OH)(3). (1)H NMR, X-ray single crystal structure analysis, and UV absorption spectra also provide support for the carbon-boron bond cleavage of ZnL(6). Because the cellular uptake of L(6) was very small, a more cell-membrane permeable ligand containing the boronic acid ester L(7) was synthesized and investigated for the sensing of d-block metal ions using (11)B NMR. Data on (11)B NMR sensing of Zn(2+) in Jurkat T cells using L(7) is also presented.