Oxidation/Reduction of Biomolecules

Electrons are the currency of the chemical world. In an analogy with the financial world, from the perspective of the chemical species, reduction is like income (that is deposited) and oxidation is like a payment. As in the financial world, deposits and payments are made throughout the day and night resulting in a functioning economy. Although deposits are generally preferred over payments, as a consumer we balance our expenditures (payments) to meet our income (deposits). Unlike the financial world, the chemical world does not print currency when it is running low, instead the chemical world follows strict conservation of matter. The analogy breaks down when we look at the details of the oxidation-reduction reactions. Because electrons have a strong tendency to pair with each other, the transfer of electrons between chemical species is generally considered in terms of electron pairs. When a single electron is taken away from a chemical species (chemical oxidation), this results in an unbalanced situation forming what is called a free radical (a chemical species with an unpaired electron). Free radicals can also from 1-electron reduction. Free radicals formed from chemical oxidation, frequently have a very strong tendency to re-acquire the lost electron. Free radicals formed from chemical reduction, frequently have a very strong tendency to give up the gained electron. For this reason free radicals, formed through either oxidation or reduction, are considered dangerous since they can take electrons away from or give electrons to very important biomolecules like DNA, proteins, lipids, and other bioactive chemicals. Although these introductory statements about free radicals present them as harmful, this is not always the case.

II.1 General Introduction. The loss of an electron from a chemical species is referred to as oxidation; the gain of an electron by a chemical species is called reduction. The commonly used acronyms to remember these terms are: LEO-GER for Loss of Electron is Oxidation – Gain of Electron is Reduction or OIL RIG for Oxidation Is Loss Reduction Is Gain. Oxidation-reduction chemistry, also known as redox chemistry, is further complicated by the terms reducing agent and oxidizing agent. A reducing agent is a chemical species that reduces another chemical species; in the process the reducing agent becomes oxidized. Likewise, an oxidizing agent is a chemical species that oxidizes another chemical species; in the process the oxidizing agent becomes reduced. An example of a redox reaction is shown below:

Fe(s) + Cu2+(aq) → Fe3+(aq) + Cu(s) Eq. 1

First off, this equation is not balanced. Please balance the redox equation below (recall that you must balance element and electrons):

___ Fe(s) + ___ Cu2+(aq) → ___ Fe3+(aq) + ___ Cu(s) Eq. 2

In this example, Fe(s) is being oxidized and Cu2+(aq) is being reduced; Fe(s) is the reducing agent and Cu2+(aq) is the oxidizing agent. We often think of these redox reactions in terms of oxidation - reduction half reactions shown in Eq 3. and Eq. 4:

Fe(s) → Fe3+(aq) + 3e- (oxidation half rxn) Eq. 3

Cu2+(aq) + 2e- → Cu(s) (reduction half rxn) Eq. 4

The addition of the two half reactions (including the stoichieometric coefficients) results in the cancellation of the electrons generating the overall balanced redox reaction (Eq. 2).

Eq. 1 says that if you put a piece of iron metal in a copper (II) solution (like copper chloride – CaCl2) then you will form copper metal. Is this true? According to the activity series of metals presented in general chemistry (see Chemistry Reference Document), Fe(s) is more reactive then Cu(s), therefore in a solution that contains Fe(s) and Cu2+(aq), Fe(s) will react to form Fe3+(aq) with the resulting electrons going to reduce Cu2+(aq) to Cu(s). The concept of the activity series can be further reinforced by considering the most stable metals (also the least reactive metals) such as silver, platinum, and gold and the least stable metals (also the most reactive metals) such as the alkali metals and the alkaline earth metals. On earth we DO find native silver, platinum, and gold, but we DO NOT find native sodium instead we find Na+ salts. When considering Eq. 2, as the reaction starts the solution will contain Fe(s), Fe3+(aq), Cu(s), and Cu2+(aq). Since Fe(s) is more reactive then Cu(s), the Fe(s) will react and products will form. If I may digress to the previous financial analogy where electrons were equated to money, Fe(s) is a shopper, Cu2+(aq) is the merchant, Fe3+(aq) is the broke shopper, and Cu(s) is the merchant who has no more goods to sell. The stoichiometery of this reaction can be viewed as the amount of money the shopper is able to spend and the amount of money the merchant can accept based on the amount of goods they are able to sell.

We can be more quantitative and use the standard reduction potentials (see Chemistry Reference Document). Note that each redox reaction has one oxidation reaction and one reduction reaction, but the tabulated values are only for the reduction potentials. We can lookup the reduction half reactions (inverse of Eq. 3 and Eq. 4): Ered (V) Fe3+(aq) + 3e- → Fe(s) -0.036 Cu2+(aq) + 2e- → Cu(s) +0.34

To compensate for the oxidation reaction (Eq. 3), we need to reverse the iron reduction potential to make it oxidation and in doing so we change the sign of the Ered. In additon, if there is a stoichiemetric coefficient, we need to multiple the potential by that value:

Eredox (V) 2x [Fe(s) → Fe3+(aq) + 3e-] 2x [+0.036] = 0.072 V 3x [Cu2+(aq) + 2e- → Cu(s)] 3x [+0.34] = 1.02 V

Adding together the potentials we arrive at 1.092V. If this redox reaction potential is a positive value, then the reaction will proceed as written. If the reaction was written as;

Fe3+(aq) + Cu(s) → Fe(s) + Cu2+(aq),

then the overall redox potential for this reaction would be –1.092 V and hence would not proceed as written (in fact you could assume the reverse reaction would occur). When using tabulated redox potentials, it is important that you pay close attention to the details of the table contents that state the standard conditions that apply and the reference potential (in this case the standard hydrogen electrode - SHE).

You might find yourself asking how does one determine the reduction potential for a given chemical species. In general redox potentials can be determined using cyclic voltameetry. See: http://www-biol.paisley.ac.uk/marco/Enzyme_Electrode/Chapter1/Cyclic_Voltammetry1.htm

Let us consider an example more related to molecules of biological origin, like ascorbic acid and α-tocopherol, also known as vitamin C and E, respectively and glutathione (in the figure below the label is “reduced” glutathione. This is an indication that the thiol moiety is an R–S-H. There is also “oxidized” glutathione where the thiol moiety is R-S-S-R, this is clearly a bad/unclear naming convention).