Abstract
The review is devoted to the influence of the hydrogen isotope–deuterium on biological models of organisms and the biological activity of pharmaceutical substances.
 The positions of the influence of deuterium on the properties of active pharmaceutical ingredients and excipients are examined from different perspectives. The first position reflects an increase in the kinetic isotope effect (KIE) in processes involving known pharmaceutical substances in aqueous solutions with a deuterium/protium ratio (D/H) below natural. For the first time, the dose-response diagram shows the identity of deuterium with essential trace elements, when a deficiency and excess of an element reduces the organism's vitality. Improved kinetic characteristics are demonstrated for the molecular and organism levels of different hierarchical gradations. In particular, they consist in the possibility of increasing the dissolution rate of substances by influencing the carbohydrate mutarotation processes and the optical activity of chiral substances, increased accumulation of essential elements in medicinal plants and other processes associated with a possible change in metabolic pathways in the cell and the organism as a whole.
 The second considered position of the influence of deuterium is associated with the use of deuterated substances–new compounds or obtained by substitution of protium in known protium analogues. The KIE is presented, which is expressed in a decrease in the biotransformation rate as a result of deuteration, it allows predicting a rapid development of the new direction in the development of drugs. Having an identical therapeutic effect, deuterated analogs provide improved pharmacokinetic characteristics, such as reduced toxicity, blocked epimerization of optically active substances, and a change in the mechanisms of biotransformation. The obtained results make it possible to predict the mechanisms of the effect of deuterium on the biochemical transformations of pharmaceutical substances in the organism.
Highlights
The atom of the most common hydrogen isotope, protium 1H, has one proton and one electron
The purpose of this review is to summarize information on the effect of the deuterium/protium ratio on living model objects of different hierarchical levels using these data for the analysis of pharmaceutical substances and aqueous solutions with a modified isotopic composition of D/H
While the use of deuterium in drug development is steadily increasing, the number of issues regarding the use of this bioisosteric replacement is not decreasing
Summary
The atom of the most common hydrogen isotope, protium 1H, has one proton and one electron. Deuterium D (2H) is a heavier natural isotope of hydrogen with the atomic mass equal to 2 and, unlike protium, it has one neutron in the atomic nucleus [1]. Deuterium is used in the nuclear power industry as a neutron moderator in reactors, as well as a stable indicator in chemical and biological models and studies of the mechanisms of various processes [4]. Deuterated compounds, which are identical in size and structure, are obtained by replacing protium with deuterium in the molecule. Due to the higher strength of carbon-deuterium (C-D) chemical bonds vs carbon-protium (C-H), the properties of deuterated compounds change, for example, the reaction rates with their participation are lower [5]
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