Living species are continuously subjected to all extrinsic forms of reactive oxidants and others that are produced endogenously. There is extensive literature on the generation and effects of reactive oxygen species (ROS) in biological processes, both in terms of alteration and their role in cellular signaling and regulatory pathways. Cells produce ROS as a controlled physiological process, but increasing ROS becomes pathological and leads to oxidative stress and disease. The induction of oxidative stress is an imbalance between the production of radical species and the antioxidant defense systems, which can cause damage to cellular biomolecules, including lipids, proteins and DNA. Cellular and biochemical experiments have been complemented in various ways to explain the biological chemistry of ROS oxidants. However, it is often unclear how this translates into chemical reactions involving redox changes. This review addresses this question and includes a robust mechanistic explanation of the chemical reactions of ROS and oxidative stress.

Hydrogen peroxide (H2O2) is a compound involved in some mammalian reactions and processes. It modulates and signals the redox metabolism of cells by acting as a messenger together with hydrogen sulfide (H2S) and the nitric oxide radical (•NO), activating specific oxidations that determine the metabolic response. The reaction triggered determines cell survival or apoptosis, depending on which downstream metabolic pathways are activated. There are several ways to produce H2O2 in cells, and cellular systems tightly control its concentration. At the cellular level, the accumulation of hydrogen peroxide can trigger inflammation and even apoptosis, and when its concentration in the blood reaches toxic levels, it can lead to bioenergetic failure. This review summarizes existing research from a chemical perspective on the role of H2O2 in various enzymatic pathways and how this biochemistry leads to physiological or pathological responses.

Classically, superoxide anion O2•− and reactive oxygen species ROS play a dual role. At the physiological balance level, they are a by-product of O2 reduction, necessary for cell signalling, and at the pathological level they are considered harmful, as they can induce disease and apoptosis, necrosis, ferroptosis, pyroptosis and autophagic cell death. This revision focuses on understanding the main characteristics of the superoxide O2•−, its generation pathways, the biomolecules it oxidizes and how it may contribute to their modification and toxicity. The role of superoxide dismutase, the enzyme responsible for the removal of most of the superoxide produced in living organisms, is studied. At the same time, the toxicity induced by superoxide and derived radicals is beneficial in the oxidative death of microbial pathogens, which are subsequently engulfed by specialized immune cells, such as neutrophils or macrophages, during the activation of innate immunity. Ultimately, this review describes in some depth the chemistry related to O2•− and how it is harnessed by the innate immune system to produce lysis of microbial agents.

In recent years, much interest has been generated by the idea that nitrosative stress plays a role in the aetiology of human diseases, such as atherosclerosis, inflammation, cancer, and neurological diseases. The chemical changes mediated by reactive nitrogen species (RNS) are detrimental to cell function, because they can cause nitration, which can alter the structures of cellular proteins, DNA, and lipids, and hence, impair their normal function. One of the most potent biological nitrosative agents is peroxynitrite (ONOO−), which is produced when nitric oxide (•NO) and superoxide (•O2−) are combined at extremely rapid rates. Considering the plethora of oxidations by peroxynitrite, this makes peroxynitrite the most prevalent nitrating species responsible for protein, DNA, and lipids nitration in vivo. There is biochemical evidence to suggest that the interactions of the radicals NO and superoxide result in the formation of a redox system, which includes the reactions of nitrosation and nitration, and is a component of the complex cellular signalling network. However, the chemistry involved in the nitration process with peroxynitrite derivatives is poorly understood, particularly for biological molecules, such as DNA, proteins, and lipids. Here, we review the processes involved in the nitration of biomolecules, and provide a mechanistic explanation for the chemical reactions of NOS and nitrosative stress. This study reveals that these processes are based on a surprisingly simple and straightforward chemistry, with a fascinating influence on cellular physiology and pathology.

This review discusses the formation of hypochlorous acid HOCl and the role of reactive chlorinated species (RCS), which are catalysed by the enzyme myeloperoxidase MPO, mainly located in leukocytes and which in turn contribute to cellular oxidative stress. The reactions of RCS with various organic molecules such as amines, amino acids, proteins, lipids, carbohydrates, nucleic acids, and DNA are described, and an attempt is made to explain the chemical mechanisms of the formation of the various chlorinated derivatives and the data available so far on the effects of MPO, RCS and halogenative stress. Their presence in numerous pathologies such as atherosclerosis, arthritis, neurological and renal diseases, diabetes, and obesity is reviewed and were found to be a feature of debilitating diseases.