Titrations without the Additions: The Efficient Determination of p Ka Values Using NMR Imaging Techniques

Analytical Chemistry
Matthew WallaceJonathan A Iggo

Abstract

It can be very informative to acquire NMR spectra of a sample as a function of the solution pH. Examples can be found in the design of host-guest complexes or in the determination of the p Ka values of organic molecules. In the conventional procedure, a series of spectra must be recorded and the pH of the sample adjusted manually between successive NMR measurements. As an alternative to this laborious procedure, we demonstrate how controlled pH gradients may be established in 5 mm NMR tubes and analyzed using standard NMR equipment in a "single shot" experiment. Using 1H NMR imaging techniques and a set of NMR pH indicator compounds, we are able to measure the pH of a sample as a function of position along a pH gradient. We are thus able to obtain the necessary set of 1H NMR spectra as a function of pH from a single sample in a single NMR experiment. As proof of concept, we demonstrate how the technique may be employed for the determination of the p Ka values of small organic molecules. We are able to measure p Ka values from 1 to 11 to within 0.1 units of their literature values. The method is robust to variations in the setting of the pH gradients and can be readily implemented through an automated sample changer.

References

Dec 14, 1979·Biochemical and Biophysical Research Communications·K Lintner, S Fermandjian
Nov 1, 1996·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·J J AckermanJ L Evelhoch
Mar 8, 2003·Analytical Chemistry·Karl BoxDerek Reynolds
Aug 9, 2003·Journal of the American Chemical Society·Amalia AggeliNeville Boden
Jun 25, 2004·Journal of Chromatography. a·Salwa K PooleColin F Poole
Dec 2, 2004·Journal of the American Chemical Society·Ronger LinKam Piu Ho
Mar 6, 2007·Annual Review of Biochemistry·John A T Young, R John Collier
Sep 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kazumasa Sakurai, Yuji Goto
Apr 10, 2008·Journal of Biomolecular NMR·Olga K BaryshnikovaBrian D Sykes
Jun 9, 2009·Applied and Environmental Microbiology·Christian L LauberNoah Fierer
Oct 17, 2009·Chemical Reviews·Junyan Han, Kevin Burgess
Dec 21, 2010·Journal of Pharmaceutical and Biomedical Analysis·Gábor Orgován, Béla Noszál
Feb 14, 2013·Nature Communications·Kyle L MorrisDave J Adams
Apr 6, 2013·Chemistry : a European Journal·Pablo Trigo-MouriñoRoberto R Gil
Sep 3, 2013·Analytical Chemistry Insights·Jetse ReijengaBram Teunissen
Jan 28, 2014·Journal of Pharmaceutical and Biomedical Analysis·Jacqueline BezençonBeat Ernst
Dec 6, 2014·Chemical Communications : Chem Comm·T NiklasM John
Mar 27, 2015·Protein Science : a Publication of the Protein Society·Carolyn A FitchLawrence P McIntosh
Aug 28, 2015·Soft Matter·Matthew WallaceDave J Adams
Nov 18, 2015·Biopolymers·Yoshio MurogaShigeru Shimizu
Oct 13, 2016·Metabolomics : Official Journal of the Metabolomic Society·Gregory D TredwellTimothy M D Ebbels
Nov 16, 2017·Talanta·Ting LiPengchi Deng

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