KINETIC ISOTOPIC EFFECT: STATIC RAYLEIGH EQUATION AND BASIC DYNAMIC ISOTOPE EQUATION FOR THE SUBSTRATE IN THE DESCRIPTION OF NITRITE-DEPENDENT ANAEROBIC OXIDATION OF METHANE

The article analyzes the results of modeling the dynamics of nitrite-dependent methane oxidation (N-DAMO) by Methylomirabilis oxyfera microorganisms using the standard isotope dynamic equations. Without specifying a specific function of the rate of the process, the traditional static Rayleigh equation is derived from the basic dynamic isotope equation. Thus, the equation of the 1st order in terms of the substrate is only a special case in the derivation of the Rayleigh equation. It was shown that the dominant fractionation of carbon isotopes occurs in the process of the microbiological reaction of anaerobic oxidation of methane by nitrite, and not in the physical process of mass transfer of dissolved methane into the gas phase. In contrast to the static Rayleigh equation, the dynamic description of the process of fractionation of stable isotopes is important when describing the parallel transformations of the substrate.

Role of stable hydrogen isotope variations in water for drug dissolution managing

In the present work, we provide the results of defining by utilizing Laser diffraction spectroscopy, the kinetic isotopic effect of solvent and constant of dissolution rate κ, s−1 of аn active pharmaceutical ingredient (API) in water with a different content of a stable _2^1{\rm{H}} isotope on the basis of the laws of first-order kinetics. This approach is based on the analysis of the light scattering profile that occurs when the particles of the dispersion phase in the aquatic environment are covered with a collimated laser beam. For the first time, the dependence of the rate of dissolution is demonstrated not only on the properties of the pharmaceutical substance itself (water solubility mg/ml, octanol–water partition coefficient log P oct/water, topological polar surface area, Abraham solvation parameters, the lattice type), but also on the properties of the solvent, depending on the content of stable hydrogen isotope. We show that the rate constant of dissolution of a sparingly hydrophobic substance moxifloxacin hydrochloride (MF · HCl) in the Mili-Q water is: k=1.20±0.14∙10−2 s−1 at 293.15 K, while in deuterium depleted water, it is k=4.24±0.4∙10−2 s−1. Consequently, we have established the development of the normal kinetic isotopic effect (kH/kD >1) of the solvent. This effect can be explained both by the positions of the difference in the vibrational energy of zero levels in the initial and transition states, and from the position of water clusters giving volumetric effects of salvation, depending on the ratio D/H. The study of kinetic isotopic effects is a method that gives an indication of the mechanism of reactions and the nature of the transition state. The effect of increasing the dissolution of the API, as a function of the D/H ratio, we have discovered, can be used in the chemical and pharmaceutical industries in the study of API properties and in the drug production through improvement in soluble and pharmacokinetic characteristics.

Cyclization of O-benzoylbenzamidoxime derivatives in water-alcohol media

O-Benzoylated benzamidoximes give 1,2,4-oxadiazoles (yields above 90%) in water-alcoholic media of pH = 2.45 to 6.20. The cyclization rate has been studied with 28 derivatives containing different substituents. The reaction is accelerated by electron-donor substituents at 4-position of benzamidoxime and by electron-acceptor substituents at 4'-position of benzoyl. The dependence of the rate constants vs σ values of the substituents fulfils the two-parameter Hammett equation at a 99% probability level. The activation parameters have been determined, and effects of polarity of medium, kinetic isotopic effect, and the reaction mechanism are discussed.