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Thiol‐water proton exchange of glutathione, cysteine, and N ‐acetylcysteine: Implications for CEST MRI
Author(s) -
Chen Johnny,
Yadav Nirbhay N.,
StaitGardner Timothy,
Gupta Abhishek,
Price William S.,
Zheng Gang
Publication year - 2020
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.4188
Subject(s) - chemistry , thiol , glutathione , cysteine , catalysis , proton , acetylcysteine , antioxidant , biochemistry , physics , quantum mechanics , enzyme
Amide‐, amine‐, and hydroxyl‐water proton exchange can generate MRI contrast through chemical exchange saturation transfer (CEST). In this study, we show that thiol‐water proton exchange can also generate quantifiable CEST effects under near‐physiological conditions (pH = 7.2 and 37°C) through the characterization of the pH dependence of thiol proton exchange in phosphate‐buffered solutions of glutathione, cysteine, and N ‐acetylcysteine. The spontaneous, base‐catalyzed, and buffer‐catalyzed exchange contributions to the thiol exchange were analyzed. The thiol‐water proton exchange of glutathione and cysteine was found to be too fast to generate a CEST effect around neutral pH due to significant base catalysis. The thiol‐water proton exchange of N ‐acetylcysteine was found to be much slower, yet still in the fast‐exchange regime with significant base and buffer catalysis, resulting in a 9.5% attenuation of the water signal at pH 7.2 in a slice‐selective CEST NMR experiment. Furthermore, the N ‐acetylcysteine thiol CEST was also detectable in human serum albumin and agarose phantoms.