ProtonTransfer Pathways, Energy Landscape, and Kineticsin Creatine–Water Systems.

We study the exchange processes ofthe metabolite creatine, whichis present in both tumorous and normal tissues and has NH2and NH groups that can transfer protons to water. Creatine produceschemical exchange saturation transfer (CEST) contrast in magneticresonance imaging (MRI). The proton transfer pathway from zwitterioniccreatine to water is examined using a kinetic transition network constructedfrom the discrete path sampling approach and an approximate quantum-chemicalenergy function, employing the self-consistent-charge density-functionaltight-binding (SCC-DFTB) method. The resulting potential energy surfaceis visualized by constructing disconnectivity graphs. The energy landscapeconsists of two distinct regions corresponding to the zwitterioniccreatine structures and deprotonated creatine. The activation energythat characterizes the proton transfer from the creatine NH2group to water was determined from an Arrhenius fit of rate constantsas a function of temperature, obtained from harmonic transition statetheory. The result is in reasonable agreement with values obtainedin water exchange spectroscopy (WEX) experiments. [ABSTRACT FROM AUTHOR]