The use of free radicals in the treatment of disease The ground state is the most stable form of the molecule existence. If for a particular atom every electron in the outermost shell has a complementary electron spinning in the opposite direction then that atom is in the ground state…
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For example, they can react with other molecules (M1) and steal an electron from them. The reacting radical (R1.) transforms into a ground state molecule (M2) and the formation of a new radical takes place (R2.)(Scheme 1) ( Fieser and Fieser, 1966 ). Scheme 1: Typical reaction of radicals (Nesmeianov and Nesmeianov, 1970). The first type of free radicals is thermodynamically unstable particles. These are the molecular fragments similar in structure to CH3. ,C2H5. and their derivatives. Next, atoms with one unpaired atom also fall under the definition of radicals. For example, H. ,Na. ,Cl. . And the last group of radicals are the thermodynamically stable radicals. As an example of this group triarylmethyl (a) and semiquinones (b) can be put forward (Scheme 2). Stabilisation of the radical in these structures are realised through delocalisation of the unpaired electron. Nitrogen oxides (NO, NO2) can also be classified as radicals as they possess an unpaired electron. Odd electron of the hydrogen atom is an s electron. In case of chlorine, or any carbon based radical it is a p radical. Scheme 2: Triarylmethyl and semiquinones based radicals (Nesmeianov and Nesmeianov, 1970). If the radical is stable then it usually does not participate in the reactions described on scheme 1. Such radicals cannot sustain chain reactions but can stop them. They have the ability to remove free radicals from the system and consequently serve as inhibitors of chain reactions. All the described particles are paramagnetic due to their uncompensated spin, what can be detected using magnetic balance (in case of stable particles) or electron paramagnetic resonance (if the concentration of the studied compound is too small or it is unstable) (Nesmeianov and Nesmeianov, 1970). Free radicals have the ability to damage cells. Respiration and the immune system reaction to the infection are the ways which lead to generation of free radicals in the body. Environment factors, such as food, pollutants and drugs that are used, also contribute to the formation of radicals. Once produced, radicals damage lipids, proteins, nucleic acids and other tissue macromolecules. They also have been proven to play a major role in aging and lead to a series of diseases, including cancer. The amount of free radicals in the body is regulated through the use of antioxidants which donate an electron, thereby transform a free radical into a stable molecule. A number of enzymes are able to act as antioxidants, including catalase, superoxide dismutase and glutathione peroxidase. The list of antioxidants can be continued by mentioning selenium, beta-carotene and both vitamins C and E (Brown, 1999; Huang, 2000). Because of the mentioned destructive properties of free radicals they can be used to treat cancer. A number of methods utilises free radicals. The method that has been used for decades is radiation therapy. The first case of using radiation therapy in the USA is dated 1896 when Emil Grubbe used X-rays to treat cancer. The discovery of radium and polonium in the end of the nineteenth century gave radiotherapy a push for further advancement. In the mid-1900s radium was substituted by radioactive caesium and cobalt. Later, with the development of various forms of tomography it became possible for physicians to selectively target tumours. This led to fewer side effects and more effective treatment. Depending on the position of the radiation source there are three types of
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