Specifically Generated Radicals

Introducing in the 5 -position a T-containing nucleotide labeled with deuterium at either C(l ) C(2 ) or C(4 ) showed only a marked kinetic isotope effect (KIE = 3.9) when labeled at C(l ). It has been concluded that the observed effects must be due to an H-abstraction of the Thy-5-peroxyl radical from the neighboring C(l ) position. A kinetic isotope effect is only observed when there is a competing reaction. This competing reaction has not yet been identified. However, some information has been obtained by generating specifically the C(l ) radical within a short ODN [reactions (11) and (12) Hwang et al. 1999], 

The 2-dRL lesion and the 3 -fragment resulting from reaction (13) were identified by mass spectrometry. The bona fide intermediate (in brackets) expected to be formed upon treatment with a base such as piperidine was not observed, but the p,6-elimination product [reaction (14)] and an adduct of the amine [reaction (15)] were identified. 

For studying mechanistic aspects of DNA strand breakage starting from the C(4 ) radical, ODNs substituted by a phenylselenide group at C(4 ) were photo- 

---

There are many chemical methods for generating radicals reported in the hterature that do not involve conventional initiators. Specific examples are included in References 64—79. Most of these radical-generating systems carmot broadly compete with the use of conventional initiators in industrial polymer apphcations owing to cost or efficiency considerations. However, some systems may be weU-suited for initiating specific radical reactions or polymerizations, eg, grafting of monomers to cellulose using ceric ion (80). 

In this section, the reactions undergone by radicals generated in the initiation or chain transfer processes are detailed. Emphasis is placed on the specificity of radical-monomer reactions and other processes likely to take place in polymerization media under typical polymerization conditions. The various factors important in determining the rate and selectivity of radicals in addition and... 

Lipid peroxidation has often been regarded simply as an undesirable side reaction, but it is also a normal part of metabolism. Initiated by enzymatically generated radicals, peroxidation occurs as specific metabolic pathways, such as the arachidonate cascade, which leads to a variety of local hormones and other substances (Eq. 21-16).254 2563... 

It is usually assumed that an H-abstraction at C(5 ) by OH (see, however, below) leads to the C(5 ) radical which adds to C(8) [e.g., reaction (221) for details of this reaction see below, where experiments that lead to the specific generation of this radical are discussed]. In a disproportionation reaction with other radicals, the cyclonucleoside (cyclonucleotide) is formed [reaction (221)]. In competition, the C(5 ) radical maybe oxidized giving rise to the 5 -aldehyde [reaction (220)]. 

Single- and double-strand scission of DNA, together with hydroxylation of constituent bases, are changes characteristic of oxygen-radical attack on DNA. An important mechanism is site-specific hydroxyl-radical generation, catalysed... 

Albumin (50-60 mg/ml) Albumin, one of the most important proteins in human plasma, is able to bind copper(II) tightly and iron weakly. Copper(II) bound to albumin is still effective in generating radical species in the presence of hydrogen peroxide. Thus macromolecules functioning by this mechanism are called sacrificial antioxidants, since the hydroxyl radical is generated locally on the protein and reacts at the specific site (Halli-well, 1988). The binding of copper ions to albumin may represent a protective mechanism overall, since the damaged albumin can be quickly replaced. 

A complexing agent should not be used in metallo-protein formulations, where the protein subunits are held by the metal.The EDTA, in rare instances, can increase the oxidation rate due to binding of the EDTA-metal complex to protein, resulting in site-specific generation of radicals. ... 

Most tetraalkylstannanes similarly usually react by Sh2 at a hydrogen centre, but alkyltin halides and similar derivatives react by an Sh2 process at the tin centre, for example reaction 3-3. These reactions are useful for generating specific alkyl radicals for ESR and similar studies,2 and are discussed in Section 5.3.6 and 11.4. Photoexcited carbonyl compounds react in the same way. 

---