chemosensors Perspective Oxidative Free Radicals and Other Species: Selective Messengers with a Reactive Capacity for Unselective Tissue Damage Pankaj Vadgama   Citation: Vadgama, P. Oxidative Free Radicals and Other Species: Selective Messengers with a Reactive Capacity for Unselective Tissue Damage. Chemosensors 2021, 9, 89. https://doi.org/10.3390/ chemosensors9050089 Academic Editor: Khiena Z. Brainina Received: 26 March 2021 Accepted: 22 April 2021 Published: 24 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). School of Engineering and Materials Sciences, Queen Mary University of London, Mile End Road, London E14NS, UK; p.vadgama@qmul.ac.uk Abstract: Oxygen and nitrogen free radicals (RONS) form an exceptionally reactive molecular assembly within eukaryote cells. This perspective article gives a combined overview of different facets of research covering molecular reactivity, resultant tissue damage and final tissue outcomes as they relate to major disease. There is an emphasis on cardiovascular disease, as the damage processes are best liked to the pathology. The overriding importance of inflammation in driving damage across all tissues is highlighted. Brief coverage is also provided of measurement approaches, respectively for antioxidant status, using potentiometry, and voltammetry for selected target species. Whilst damage due to RONS is a common focus, the fundamental importance of RONS to biological signalling is also covered here as an indispensable basis for life. The article thus provides a global overview of this topic for anyone wishing to understand the current status across multiple fronts. Keywords: free radicals; ROS; nitric oxide; superoxide; cell signaling; mitochondria; antioxi- dants; hormesis 1. Introduction The aim of this perspective article is to provide a clinical context for the series of sen- sors papers in the journal’s Special Issue “Electrochemical Sensors for Antioxidant/Oxidant Activity Monitoring”. Hard-wired into our life on earth as oxygen dependent eukaryote organisms is the need to deal with the consequences of generating energy from conversion of the oxygen diradical to water. The cellular mitochondrial machine that achieves this is an exceptional immobilised phase redox system, that takes a series of intermediate energetic steps to final oxygen reduction in its inner surface. However, through this, it sets up a con- tinuous outward flow of reactive oxygen species (ROS), which emanate from the nanopores of its outer membrane. Our appreciation of free radical chemistry is partly derivative of radiation biology, and so naturally emphasises ROS as a damage causing agency. Cellular co-existence with ROS from the inception of eukaryotic life has also meant not only that biology has exceptional countermeasures to mitigate free radical damage, the antioxidant system, but more remarkably, it has harnessed ROS for signalling purposes [1,2]. As such, these reactive species have become fully integrated into the biochemical information shar- ing systems of the cell, and without them, life would not be possible. Their special utility is that they are highly reactive at low concentrations, broad in their molecular interactions, require no catalytic facility and have very short half-lives. These intrinsic properties are, however, conditioned by the specific biological matrix [3–5]. Thus, whilst slower reacting H 2 O 2 has a half-life of 10 -3 s, it drops to 10 -8 s in the presence of tissue catalase. For the more reactive O 2 .- free radical, the already short half-life of 10 -9 s drops to a remarkable 10 -15 s in the presence of tissue superoxide dismutase (SOD). The non-radical H 2 O 2 still has a sufficiently fast reaction kinetics and is able to operate as an efficient signalling molecule; this it does mostly through oxidative reactions with protein thiol residues at rate constants that show a varying repertoire from 10 0 –10 7 M -1 s -1 . Chemosensors 2021, 9, 89. https://doi.org/10.3390/chemosensors9050089 https://www.mdpi.com/journal/chemosensors