Determination of the pKa and Concentration of NMR-Invisible Molecules and Sites Using NMR Spectroscopy
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide NMR spectroscopy is a very powerful tool for measuring the dissociation constants (p K a ) of molecules, requiring smaller quantities of samples of lower purity relative to potentiometric or conductometric methods. However, current approaches are generally limited to those molecules possessing favorable pH-dependent NMR properties. Typically, a series of 1D experiments at varying pH are performed, and the p K a is obtained by fitting the observed chemical shift of the analyte as a function of pH using nonlinear routines. However, the majority of polymers, biomolecules, and inorganic species do not present favorable NMR resonances. Either the resonances are not observable or too broad, or the unambiguous interpretation of the NMR data is impossible without resorting to complex 2D experiments due to spectral overlap. To overcome these fundamental limitations, we present a method to obtain the p K a values and concentrations of acidic species without their direct observation by NMR. We instead determine the quantity of acidic protons removed from the species along a concentration gradient of an organic base in a single 1 H chemical shift imaging experiment that can be run under automation. The p K a values are determined via simple linear plots, avoiding complex and potentially unreliable nonlinear fitting routines.
Source: Analytical Chemistry
Institutions: University of East Anglia, Norwich Research Park
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4404940894