A Method for the Measurement of Site-Specific Tautomeric and Zwitterionic Microspecies Equilibrium Constants

Abstract

We describe a method for the individual measurement of simultaneously occurring, unimolecular, site-specific “microequilibrium” constants as in, for example, prototropic tautomerism and zwitterionic equilibria. Our method represents an elaboration of that of Nygren et al. (Anal. Chem. 1996, 68, 1706−10), which thereby becomes generalized and improves the accuracy. Specifically, by making spectral measurements as a function of temperature, we demonstrate the ability to determine site-specific microenthalpies unambiguously. Analysis proceeds via multivariate nonlinear regression modeling of, for example, the Gibbs−Helmholtz relation. Additional determinations of macroscopic equilibrium constants as a function of temperature, in combination with the previously determined microenthalpies, in turn enables the determination of all remaining site-specific thermodynamic parameters, i.e., microentropies, micro free energies, and/or microequilibrium constants, and moreover allows us to resolve and measure the spectra of tautomeric isocoulombers. To our knowledge, we have hereby devised the first such universally applicable and accurate measurement method on record.

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

“…Sophisticated assumptions are being developed even today (see, e.g., ref. [113] for UV pH titrations), leading hopefully to more profound understanding of microequilibrium systems and improved microconstant determination strategies in the future.…”

Reactions of Hydroxypyridines with 1-Chloro-2,4,6-trinitrobenzene − Product Structure, Kinetics, and Tautomerism

“…[29] In the cases of 3-hydroxypyridine and 3-hydroxy-6-methylpyridine, the products of the attack on the oxygen atom (14,16) The structures of 14, 16, 18, and 19 were assigned on the basis of 1 H and 13 C NMR spectral data. [30] The structures of 18 and 19 agree with those found in 1 H-1 H NOE experiments and shows considerable enhancement of both the 2-H and 6-H (18% and 14%) signals of 18, and of 2-H (23%) and 6-CH 3 (6%) of 19.…”

“…Cationic and anionic forms 4 and 6 [16] are clearly possible intermediates on the tautomeric pathway. It is possible to depict 5 in a formally neutral oxo form.…”

“…The nitro groups are not equivalently oriented with respect to the phenyl ring, the dihedral angles between the planes involving N(12), N(14), and N(16) and that of the benzene ring being 41.4(2), 5.6(2), and 25.5(3)°, respectively. Ϫ Packing is consistent with van der Waals interactions.…”

Solvent Effects on Tautomeric and Microscopic Protonation Constants of Glycine in Different Aqueous Solutions of Methanol and Ethanol

“…A few efforts have been devoted to determining protonation microconstants of some amino acids using different methods [1][2][3][4][5]. Nevertheless, there is still little information in the literature about the effect of organic solvents (or their aqueous mixtures) on protonation microconstants of amino acids [6].…”