Structure and Bonding in Some Highly Reactive Species

7 STRUCTURE AND BONDING IN SOME HIGHLY REACTIVE SPECIES 

Although these species do not necessarily contain heteroatoms, the structures and bonding in some highly reactive species are most conveniently considered here. 

When carbon-carbon bonds are broken, there are two ways in which this can occur. The first is described as homolytic cleavage, where one of the electrons of the carbon-carbon bond 

FIGURE 4.12 Homolytic cleavage of a carbon-carbon bond. 

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Structure and Bonding in Some Highly Reactive Species... 

The splitting of a Cl2 molecule is an initiation step that produces two highly reactive chlorine atoms. A chlorine atom is an example of a reactive intermediate, a short-lived species that is never present in high concentration because it reacts as quickly as it is formed. Each Cl- atom has an odd number of valence electrons (seven), one of which is unpaired. The unpaired electron is called the odd electron or the radical electron. Species with unpaired electrons are called radicals or free radicals. Radicals are electron-deficient because they lack an octet. The odd electron readily combines with an electron in another atom to complete an octet and form a bond. Figure 4-1 shows the Lewis structures of some free radicals. Radicals are often represented by a structure with a single dot representing the unpaired odd electron. 

Bioactivation to a free radical intermediate has been implicated in the teratological mechanism for a number of xenobiotics, including phenytoin and structurally-related AEDs, benzo[a]pyrene, thalidomide, methamphetamine, valproic acid, and cyclophosphamide (Fantel 1996 Wells et al. 2009 Wells and Winn 1996). Unlike in the case of most CYPs, the embryo-fetus has relatively high activities of PHSs and lipoxygenases (LPOs), which via intrinsic or associated hydroperoxidase activity can oxidize xenobiotics to free radical intermediates (Fig. 10) (Wells et al. 2009). These xenobiotic free radical intermediates can in some cases react with double bonds in cellular macromolecules to form covalent adducts, or more often react directly or indirectly with molecular oxygen to initiate the formation of potentially teratogenic reactive oxygen species (ROS). 

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