Free Radicals and Antioxidants

Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions

We present a new continuum solvation model based on the quantum mechanical charge density of a solute molecule interacting with a continuum description of the solvent. The model is called SMD, where the "D" stands for "density" to denote that the full solute electron density is used without defining partial atomic charges. "Continuum" denotes that the solvent is not represented explicitly but rather as a dielectric medium with surface tension at the solute-solvent boundary. SMD is a universal solvation model, where "universal" denotes its applicability to any charged or uncharged solute in any solvent or liquid medium for which a few key descriptors are known (in particular, dielectric constant, refractive index, bulk surface tension, and acidity and basicity parameters). The model separates the observable solvation free energy into two main components. The first component is the bulk electrostatic contribution arising from a self-consistent reaction field treatment that involves the solution of the nonhomogeneous Poisson equation for electrostatics in terms of the integral-equation-formalism polarizable continuum model (IEF-PCM). The cavities for the bulk electrostatic calculation are defined by superpositions of nuclear-centered spheres. The second component is called the cavity-dispersion-solvent-structure term and is the contribution arising from short-range interactions between the solute and solvent molecules in the first solvation shell. This contribution is a sum of terms that are proportional (with geometry-dependent proportionality constants called atomic surface tensions) to the solvent-accessible surface areas of the individual atoms of the solute. The SMD model has been parametrized with a training set of 2821 solvation data including 112 aqueous ionic solvation free energies, 220 solvation free energies for 166 ions in acetonitrile, methanol, and dimethyl sulfoxide, 2346 solvation free energies for 318 neutral solutes in 91 solvents (90 nonaqueous organic solvents and water), and 143 transfer free energies for 93 neutral solutes between water and 15 organic solvents. The elements present in the solutes are H, C, N, O, F, Si, P, S, Cl, and Br. The SMD model employs a single set of parameters (intrinsic atomic Coulomb radii and atomic surface tension coefficients) optimized over six electronic structure methods: M05-2X/MIDI!6D, M05-2X/6-31G, M05-2X/6-31+G, M05-2X/cc-pVTZ, B3LYP/6-31G, and HF/6-31G. Although the SMD model has been parametrized using the IEF-PCM protocol for bulk electrostatics, it may also be employed with other algorithms for solving the nonhomogeneous Poisson equation for continuum solvation calculations in which the solute is represented by its electron density in real space. This includes, for example, the conductor-like screening algorithm. With the 6-31G basis set, the SMD model achieves mean unsigned errors of 0.6-1.0 kcal/mol in the solvation free energies of tested neutrals and mean unsigned errors of 4 kcal/mol on average for ions with either Gaussian03 or GAMESS.

Free Radicals in Biology and Medicine

The new edition of this well-established book is thoroughly revised and gives a comprehensive account of the role of free radicals, other reactive species (RS), and antioxidants in life, health, and disease. Chapter 1 reviews how oxygen (O2) is used by living organisms, why it can be toxic, and introduces the concept of oxygen radicals and other RS; their chemistry is detailed in Chapter 2, especially for superoxide, hydroxyl radical (including Fenton chemistry), peroxynitrite, nitric oxide, ozone, and singlet O2, with emphasis on their redox properties. Subsequent chapters detail what antioxidants can be made in vivo (e.g. superoxide dismutases, peroxiredoxins) and which can come from diet (e.g. vitamins E and C, carotenoids, and polyphenols such as the flavonoids) and how they work in vivo. The role of RS in cell proliferation, senescence, and death (e.g. by apoptosis, necrosis, or intermediate forms) is presented. Methods for measuring RS are described in detail, including electron paramagnetic resonance and biomarker determination. Useful roles for RS (e.g. cell signalling, phagocyte action), as well as systems in which they cause particular problems (e.g. premature babies, the eye, the ear) are presented. Acute and chronic inflammation are used to illustrate both roles There is a comprehensive description of the role of RS in human diseases, from cancer to heart disease to dementia, in the ageing process, and in the toxicity of many agents, from ethanol to carbon tetrachloride to paraquat. Therapeutic agents active against RS are reviewed in detail, including NADPH oxidase inhibitors, N-acetylcysteine, and Ebselen.

Free Radicals in Biology and Medicine

(1990). Free Radicals in Biology and Medicine. International Journal of Radiation Biology: Vol. 58, No. 4, pp. 725-725.

First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid

The body encloses a complex antioxidant defence grid that relies on endogenous enzymatic and non-enzymatic antioxidants. These molecules collectively act against free radicals to resist their damaging effects to vital biomolecules and ultimately body tissues. Based on their response to general free radical invasion, they can be categorized into first, second, third and even fourth line defense antioxidants. The role and effectiveness of the first line defense antioxidants which basically include superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) is important and indispensable in the entire defense strategy of antioxidants, especially in reference to super oxide anion radical (*O2) which is perpetually generated in normal body metabolism, particularly through the mitochondrial energy production pathway (MEPP). A lot has been published concerning antioxidants and their significance in preventing oxidative stress and the attendant cellular damage, howbeit with paucity of awareness on the fundamental role of SOD, CAT and GPX. The present review tends to articulate important information on SOD, CAT and GPX as first line defense antioxidant enzymes.

The Biology of Oxygen Radicals

The reactive superoxide radical, O2-, formerly of concern only to radiation chemists and radiobiologists, is now understood to be a normal product of the biological reduction of molecular oxygen. An unusual family of enzymes, the superoxide dismutases, protect against the deleterious actions of this radical by catalyzing its dismutation to hydrogen peroxide plus oxygen.

Free radicals in biology and medicine