Proton Transfer Pathways, Energy Landscape, and Kinetics in Creatine鈥揥ater Systems

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• 作者：Olga Ivchenko ; Chris S. Whittleston ; Joanne M. Carr ; Petra Imhof ; Steffen Goerke ; Peter Bachert ; David J. Wales
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：February 27, 2014
• 年：2014
• 卷：118
• 期：8
• 页码：1969-1975
• 全文大小：344K
• 年卷期：v.118,no.8(February 27, 2014)
• ISSN：1520-5207

文摘

We study the exchange processes of the metabolite creatine, which is present in both tumorous and normal tissues and has NH₂ and NH groups that can transfer protons to water. Creatine produces chemical exchange saturation transfer (CEST) contrast in magnetic resonance imaging (MRI). The proton transfer pathway from zwitterionic creatine to water is examined using a kinetic transition network constructed from the discrete path sampling approach and an approximate quantum-chemical energy function, employing the self-consistent-charge density-functional tight-binding (SCC-DFTB) method. The resulting potential energy surface is visualized by constructing disconnectivity graphs. The energy landscape consists of two distinct regions corresponding to the zwitterionic creatine structures and deprotonated creatine. The activation energy that characterizes the proton transfer from the creatine NH₂ group to water was determined from an Arrhenius fit of rate constants as a function of temperature, obtained from harmonic transition state theory. The result is in reasonable agreement with values obtained in water exchange spectroscopy (WEX) experiments.