Isomeric Co(ii) paraCEST agents as pH responsive MRI probes

Abstract

A newly discovered isomer of Co(II) (1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane = CCRM) produces four highly paramagnetically shifted chemical exchange saturation transfer (CEST) peaks. The 1,8-pendants of the complex are bound in a trans-arrangement to produce a Co(II) complex of increased kinetic inertness. The isomers have a stabilized Co(II) center (E_1/2 of 540 to 550 mV versus SHE). Both the 1,8 and the 1,4-isomer are excellent pH probes in solution and in tissue homogenate by virtue of their highly paramagnetically shifted amide protons. These isomers produce both a ratiometric pH readout as well as amide proton exchange rate constants that correlate to pH.