TY  - JOUR
AU  - Köcher, Simone S.
AU  - Düwel, Stephan
AU  - Hundshammer, Christian
AU  - Glaser, Steffen J.
AU  - Schilling, Franz
AU  - Granwehr, Josef
AU  - Scheurer, Christoph
TI  - Ab Initio Simulation of pH-Sensitive Biomarkers in Magnetic Resonance Imaging
JO  - The journal of physical chemistry  / A A, Molecules, spectroscopy, kinetics, environment & general theory
VL  - 122
IS  - 40
SN  - 1520-5215
CY  - Washington, DC
PB  - Soc.66306
M1  - FZJ-2018-06542
SP  - 7983 - 7990
PY  - 2018
AB  - An ab initio simulation scheme is introduced as a theoretical prescreening approach to facilitate and enhance the research for pH-sensitive biomarkers. The proton 1H and carbon 13C nuclear magnetic resonance (NMR) chemical shifts of the recently published marker for extracellular pH, [1,5–13C2]zymonic acid (ZA), and the as yet unpublished (Z)-4-methyl-2-oxopent-3-enedioic acid (OMPD) were calculated with ab initio methods as a function of the pH. The influence of the aqueous solvent was taken into account either by an implicit solvent model or by explicit water molecules, where the latter improved the accuracy of the calculated chemical shifts considerably. The theoretically predicted chemical shifts allowed for a reliable NMR peak assignment. The pKa value of the first deprotonation of ZA and OMPD was simulated successfully whereas the parametrization of the implicit solvent model does not allow for an accurate description of the second pKa. The theoretical models reproduce the pH-induced chemical shift changes and the first pKa with sufficient accuracy to establish the ab initio prescreening approach as a valuable support to guide the experimental search for pH-sensitive biomarkers.
LB  - PUB:(DE-HGF)16
C6  - pmid:30222345
UR  - <Go to ISI:>//WOS:000447471400006
DO  - DOI:10.1021/acs.jpca.8b04665
UR  - https://juser.fz-juelich.de/record/857551
ER  -