Oxidative stress

Chemists and biologists typically define oxidative stress as an imbalance, particularly in biological cells, between the rate of formation and/or concentration of 'oxygen free radicals' (or 'reactive oxygen species') — potent 'oxidizing' (electron capturing) atoms or molecules — and their elimination or 'neutralization' by 'antioxidants' — 'reducing' (electron donating) molecules — the imbalance characterized by an excess of the former or a deficiency of the latter, leading to an alteration of a cell's 'redox' state towards the 'oxidized' state. The concept of oxidative stress occupies central importance in biology, as it applies, depending on circumstances, either to physiological phenomena essential for optimal functioning of organisms or to pathophysiological phenomenona, such as cardiovascular diseases, cancer and other clinical disease states, as well as to considerations of the mechanisms underlying aging.

In the definition of oxidative stress given above, the terms embraced by single quotes will require further discussion before any practical understanding of the concept can emerge. Accordingly, we will try to explicate those sub-concepts in turn, and relate them in a synthesis of the concept of oxidative stress.

Free radicals

In this section we will elaborate on the following assertions about free radicals:

• A free radical is any chemical species capable of independent existence — hence the term ‘free’ — that contains one or more unpaired electrons.
• An unpaired electron is one that occupies an atomic or molecular orbital without an accompanying electron of opposite spin.
• A superscript dot is usually used to denote the unpaired electron.
• Radicals can form in many ways, in both industrial and biological systems.
• A full understanding of free radical chemistry requires understanding concepts from quantum chemistry:

• Covalent bonding
• Spin quantum numbering
• Atomic orbitals
• Pauli principle
• Molecular orbital
• Hund’s law

Chemists define a 'free radical' as an atom or molecule that has one or more unpaired electron, whereas all its other electrons exist as pairs. The qualifier 'free' denotes the independent existence of the species with one or more unpaired electrons, and many biological chemists drop the term as they consider only those radicals which can exist independently, however briefly.

Consider the most common variety (a.k.a., isotope) of hydrogen atom, which comprises a nucleus consisting of one proton, a positively charged particle, and one electron, a negatively charged particle, the latter occupying a surrounding electron shell, having no sub-shells, a shell that has the intrinsic capacity to hold two electrons. We can symbolize it as H•, or H^•. For quantum mechanical reasons relating to a kind of stability, so to speak, the hydrogen atom tends to behaves as if it wanted two electrons in that shell, specifically a pair of electrons 'spinning' in opposite directions. Accordingly, the hydrogen atom tends to react with another hydrogen atom like itself, one with an oppositely spinning electron in its only electron shell, such that the two hydrogen nuclei share the two electrons in the shell, binding the two atoms together in what chemists refer to as a molecule with a 'covalent bond'. We can symbolize the hydrogen molecule as H:H. Or it may satisfy its reluctance to possess an unpaired electron, and simply donate its electron to some other electron-eager atom or molecule, and continue its existence as a hydrogen ion, H⁺.

Referring then to our definition of 'free radical', or just 'radical', we can recognize the hydrogen atom, H^•, as a radical. We will see that other radicals, too, may either lose an electron, or gain one, through transfer or sharing, depending on circumstances.

A few helpful definitions:

Definition Representative Examples Comments      OXIDATION      -- loss of electrons -- (oxidation = 'de-electronation') -- gain of oxygen -- K → K+ + e- O2•- → O2 + e- C + O2 → CO2 oxidation of a potassium atom to a potassium ion oxidation of a superoxide radical to an oxygen molecule oxidation of carbon to carbon dioxide; the more electronegative oxygen has greater share of electrons REDUCTION -- gain of electrons -- (reduction = 're-electronation') -- gain of electrons with a hydrogen nucleus -- -- loss of oxygen -- Cl + e- → Cl- O2 + e- → O2•- C +2H2 → CH4 CO2 + C → 2CO reduction of a chloride atom to a chloride ion reduction of an oxygen molecule to a superoxide radical reduction of a carbon atom to a methane molecule (the carbon atom gains electrons it shares with a hydrogen nucleus) reduction of carbon dioxide to carbon monoxide; concomitant oxidation of carbon to carbon monoxide