Deuterated pH Probes Based on Ketoglutarate for Magnetic Resonance

Deuterium is an atom with spin-1 that is currently generating substantial interest to develop drugs, new materials, and probes for metabolic analysis in nuclear magnetic resonance (NMR). Here, we are describing the feasibility of designing deuterated probes for the investigation of pH. The detection of pH, particularly extracellular pH, is relevant to investigating cancer, as tumors often display a low extracellular pH. We investigate deuterated ketoglutarate, a natural metabolite, and its diethyl ester derivative to assess pH, as it provides a chemical blueprint in its equilibrium with water for successful pH measurements using ketoacids. In addition to pH sensing, our findings suggest potential utilization of deuterated ketoglutarate esters for monitoring mitochondrial tricarboxylic acid metabolism by analyzing deuterium incorporation into the cycle's intermediates.