Summary. The study of reactions of oxidative transformation of biologically active substances under the action of hypochlorite ions (OC1) is of interest for practical medicine and pharmacy. It has recently been established that hypochlorous acid (HOC1), containing a highly active oxidizing group - hypochlorite ion, is formed in the body and is the main protective component of the immune system against bacteria and viruses. In the human body, hypochlorite ions are able to simulate the oxidative function of liver cytochrome P-450, due to which solutions of hypochlorite ions are used as a drug, including infusion.
In the present work, for the first time, a kinetic study of the oxidation of pentoxifylline with hypochlorite ions was carried out at various temperatures and concentrations of both reagents in aqueous solutions with physiological pH. A rate law is proposed that describes the kinetics of the process. It has been established that the reaction has the first order both in terms of the oxidizing agent and in terms of the substrate. It has been experimentally shown that a change in the ionic strength of the medium does not have a noticeable effect on the oxidation rate. The reaction rate constant at pH 7.4 and a temperature of 37°C k=33.45x10-2 l/(molxs). The activation parameters were determined: activation energy E = 29.20 kJ/mol, activation enthalpy AH*=26.62 kJ/mol, activation entropy A8*=-168.59 J x mol-1 x K-1, Gibbs energy DO *=78.89 kJ/mol. A reaction mechanism has been proposed.
The conducted experimental studies and the obtained kinetic results can be the basis for further study of the oxidative conversion of drugs by hypochlorite ions, as well as for the use of hypochlorite ions in clinical toxicology in case of overdose or poisoning with pentoxifylline and other substances.
Key words: hypochlorite ions, pentoxifylline, oxidation kinetics, mechanism.
abstract. The studying of the reactions of oxidative transformation of biologically active substances affected by hypochloriteions (OCl) is of interest for applied medicine and pharmacy. Recently it has been established that hypochlorous acid (HOCl), containing a highly active oxidizing group - hypochlorite ion, is formed in the human organism and is the basic protectivecomponent of the immune system against bacteria and viruses. In the human body hypochlorite ions are capable of modeling oxidizing function of liver cytochrome P-450, thanks to this fact hypochlorite ions solutions are used as drugs even intravenously.
In the present work the kinetic study of oxidation reaction of pentoxifylline by means of hypochlorite ions at various temperatures and concentrations of both reagents in water solutions with physiologic value of pH was conducted for the first time. The rate law which describes the kinetics of the process was offered. The reaction was determined to have the first order both according to the oxidizer, and the substrate. It was experimentally shown, that the change of ionic force of the medium didnot exert any marked influence on the rate of oxidation. The rate constant of the reaction at pH 7.4 and the temperature 37X wasfound to be k=33.45x 10-2 l/( molxs). Activation parameters were found to be: energy of activation Ea=29.20 kJ/mol, enthalpy ofactivation AH*=26.62 kJ/mol, entropy of activation AS*=-168.59 Jxmol-1xK-1, Gibbs' energy AG *=78.89 kJ/mol. The reaction mechanism was proposed.
The conducted experimental studies and the obtained kinetic results can serve as a basis for further investigation of oxidative transformation of medicinal substances with hypochlorite ions, and also for the use of hypochlorite ions in clinical toxicology in case of overdosage or pentoxifylline and other substances poisoning.
Substances containing highly active hypochlorite ions (chlorine lime, chloramine B and chloramine T, hypochlorites of alkali and alkaline earth metals) are widely used in scientific research and in laboratory practice in many reactions as oxidizing agents, in medicine as disinfectants and antiseptics.
The most important among this group of substances is sodium hypochlorite. According to the publication, sodium hypochlorite is one of the hundred most important chemical compounds. And this is no coincidence.
Hypochlorite is used as a household and industrial bleach and disinfectant, a water purifier and disinfectant, and an oxidizing agent for many industrial chemical production processes. As a bactericidal and sterilizing agent, it is used in the food industry and agriculture.
Hypochlorite ions play a special role in medicine. Recently, new chemical and biological properties of these ions have been discovered: it turned out that hypochlorous acid containing hypochlorite ions is not a foreign substance for the body and is formed in human blood with the participation of enzymes - myeloperoxidase or eosinophil peroxidase in the presence of chloride ions and hydrogen peroxide according to the reaction: H2O2+Cl^OCl-+H2O. The hypochlorite ions formed in this way have been found to be the main components of the body's defense against bacteria and viruses. This discovery aroused great interest in chemical and biological research in this area.
Fundamental research in this direction by scientists from the Research Institute of Physicochemical Medicine and the Research Institute of Electrochemistry (Yu.M. Lopukhin, A.I. Archakov, V.I. Sergienko, G.F. Grinberg, Yu.B. Vasiliev, A.M. Skundin, O. A. Azizova, A. K. Martynov, M. A. Murina, O. M. Panasenko, etc.) eventually led to the creation of functioning models of enzymatic systems that are close in their efficiency and selectivity to the systems of a living organism, the development of basis of equipment and means for use in various fields of medicine: resuscitation, surgery, toxicology, gynecology, pulmonology, urology, phthisiology, dentistry, etc. Dosage forms for external and internal use (including hypochlorite solutions for injections).
As a result of the research, it was found that hypochlorite solutions model the oxidative (detoxifying) function of liver cytochrome P-450 and the oxidative (phagocytic) function of neutrophilic leukocytes. These solutions have a detoxifying effect on tissue decay products, turning them into non-toxic compounds, similar to cytochrome P-450. The oxidized compound is always better soluble in water, therefore, it is easier than the original compound to be involved in other metabolic transformations or excreted from the body by excretory organs. Hypochlorite ions effectively inactivate bilirubin, creatinine, urea, fibrinogen degradation products and other substances in the blood. The effect of the "native substance" makes it possible to explain the high efficiency of the use of hypochlorite and its good tolerance by the body. In this regard, hypochlorite solutions are successfully used in the treatment of destructive pancreatitis, hepatic and renal insufficiency, poisoning, including drugs.
For many years, the Department of General, Physical and Colloidal Chemistry of Vitebsk State Medical University has been conducting experimental and theoretical studies using hypochlorite ions to study the oxidative transformation of biologically active substances.
With the beginning of the widespread use of hypochlorite ions in many fields of medicine in pharmacology and pharmacotherapy, the subjects of study were the transformation of medicinal substances in the human body when interacting with endogenous and exogenous hypochlorite ions, as well as the entire article at the link - https://core.ac.uk/download/pdf/53877308.pdf