Tautomeric ratio and prototropic equilibrium constants of tenoxicam, a 1H and 13C NMR theoretical and experimental study.

The determination of the micro-equilibrium prototropic constants is often a tough task when the tautomeric ratio favors one of the species or when the chemical exchange is not slow enough to allow the quantitative detection of the tautomeric species. There are just few experimental methods available to reveal the constants of the tautomeric micro-equilibriums; its applicability depends on the nature of the tautomeric system. A combination of experimental and quantum chemistry calculated (1)H and (13)C NMR chemical shifts is presented here to estimate the population of the species participating in the tautomeric equilibriums of the tenoxicam, an important anti-inflammatory drug.

Antihypertensive and antiarrhythmic properties of a para-hydroxy[bis(ortho-morpholinylmethyl)]phenyl-1,4-DHP compound: comparison with other compounds of the same kind and relationship with logP values.

A new para-hydroxy[bis(ortho-morpholinylmethyl)]phenyl-1,4-DHP substituted compound, (4-(4-hydroxy-3,5-bis(morpholin-4-ylmethyl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester, LQM300), with antihypertensive and antiarrhythmic properties, has been synthesized. Four pKa values of this compound have been determined with the aid of the program SQUAD, at pseudo-physiological conditions (T = 37 degrees C and I = 0.15 M) by UV spectrophotometry and at T = 25 degrees C and I = 0.

Determination of pKa values of tenoxicam from 1H NMR chemical shifts and of oxicams from electrophoretic mobilities (CZE) with the aid of programs SQUAD and HYPNMR.

In this work it is explained, by the first time, the application of programs SQUAD and HYPNMR to refine equilibrium constant values through the fit of electrophoretic mobilities determined by capillary zone electrophoresis experiments, due to the mathematical isomorphism of UV-vis absorptivity coefficients, NMR chemical shifts and electrophoretic mobilities as a function of pH. Then, the pK(a) values of tenoxicam in H(2)O/DMSO 1:4 (v/v) have been obtained from (1)H NMR chemical shifts, as well as of oxicams in aqueous solution from electrophoretic mobilities determined by CZE, at 25 degrees C. These values are in very good agreement with those reported by spectrophotometric and potentiometric measurements.