Determination of microscopic acid?base parameters from NMR?pH titrations

Abstract

The theory and practice of proton microspeciation based on NMR-pH titrations are surveyed. Principles of bi-, tri-, tetra-, and n-protic microequilibrium systems are discussed. Evaluation methods are exemplified by case studies on bi- and tetraprotic biomolecules. Selection criteria and properties of 'reporter' NMR nuclei are described. Literature data on complete microspeciations of small ligands and site-specific basicity characterizations of peptides and proteins are critically reviewed.

Potentiometric Determination of Phytic Acid and Investigations of Phytate Interactions with Some Metal Ions

“…The magnitude of the interaction between metal ions and chelating agents is defined by the corresponding equilibrium constants, and nowadays most of them are determined experimentally by spectrophotometry, potentiometry and other techniques (NMR) in combination with computational analysis of data. 18 Protonation of phytates and/or determination of stability constants with metallic ions are the subject of numerous publications. 1,12,19 With help of computerized programs determination of such data becomes easier and published constants are nowadays of high precision, which was not the case by data published in the classical monographs on stability constants, [20][21] where data frequently scatter between different methods and sources for more orders of magnitude.…”

Physicochemical Profiling in Drug Research and Development

“…Thus, this methodology has become the chief approach of microspeciation as reviewed recently [34]. The acid/base profiling of imatinib [66] and cetirizine [33], measured by NMR/pH titration was reported.…”

“…The theory and practice of proton microspeciation based on NMR-pH titration and data in the literature on complete microspeciation of small ligands including drugs have recently been surveyed [34]. …”

pH-Free Measurement of Relative Acidities, Including Isotope Effects

“…Consequently an NMR titration can be adapted to simultaneously measure the difference in acid dissociation constants (pK a ) of two or more structurally similar compounds ( 12 ). The NMR titration is capable of high precision and accuracy, and it can be carried 3 out without the necessity of measuring pH.…”