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Free radical pathology.

OVER the past several years free radical pathology, especially as it pertains to experimentally induced cerebral lesions, has been the subject of renewed interest in several investigative laboratories. Its possible role in the development of ischemic cerebral lesions, i.e., stroke, is suggested. For most chemicals, the electron orbitals are filled with paired electrons, which spin in opposite directions and cancel each other's magnetic fields. For a free radical, however, the outer orbital has a lone, unpaired electron, which spins unopposed. In most cases, this unpaired electron creates an extremely unstable electronic distribution and the free radical is quite reactive. The pattern of its chemical reactions is referred to as "anti-Markovnikov" as opposed to the usual pattern of organic reactions known as "Markovnikov." Many compounds can be converted into a free radical state by x-ray or ultraviolet irradiation, or by chemical agents known as initiators. The most significant aspect of radical chemistry is a marked alteration in the size and shape of the molecules, leading to altered function of the chemicals involved. The physical-chemical properties of molecular oxygen (O2) are central to the theory of free radical pathology. First, the molecular structure of O2 is such that it can be written as having a covalent double bond, O = O, or as being a diradical, O-O. It is this diradical characteristic that provides 02 with the potential to undergo initiation and addition reactions. Reactions such as those depicted in figure 1 are typical of the free radical reactions that occur in the classic rancidification of fats. The presence of iron complexes or copper complexes can catalyze further radical reactions, as shown in figure 2. Molecular oxygen is 7 to 8 times more soluble in nonpolar media than in polar media, a characteristic that significantly affects the structure of the plasma membrane. Quite simplified, the plasma membrane is a bimolecular leaflet of phospholipids, with hydrophobic, hydrophilic, and amphipathic substances interdigitated into and interacting with the leaflet by hydrophobic and ionic forces. As shown in figure 3,