Hydrogen atom abstraction pathway determination

Steenken et al. have concluded that in double-stranded DNA direct hydrogen atom abstraction from 2 -deoxyribose by G(-H) radical is very unlikely due to steric hindrance effects and a small thermodynamic driving force [94]. The EPR studies performed in neutral aqueous solutions at room temperature have shown that, in the absence of specific reactive molecules, the lifetime of the G(-H) radical in double-stranded DNA is as long as -5 s [80]. Therefore, the fates of G(-H) radicals are mostly determined by the presence of other reactive species and radicals. Thus, the G(-H) radical can be a key precursor of diverse guanine lesions in DNA. In the next section we begin from a discussion of the site-selective generation of the G(-H) radical in DNA, and then continue with a discussion of the reaction pathways of this guanine radical. 

Anionic chromium hydride complexes proved to be efficient hydrogen atom donors. Newcomb determined PPN+ HCr(CO)5 to be an efficient radical initiator and reducing agent for radicals and determined the kinetics of the hydrogen abstraction reaction [214]. In line with the observation that 3d metal complexes are much more prone to radical pathways than the corresponding 4d and 5d complexes, an increase of the extent of competing S -pathways for the bromide abstraction was found for molybdenum and tungsten complexes compared to the chromium complex. 

According to Singleton et al. (1989) and Butkovskaya et al. (2004), hydrogen atom abstraction from the carboxyl group (pathway la) is the preferred pathway. A branching ratio of (64 17) % has been determined between 249 and 300 K (Butkovskaya et al., 2004). 

In addition to the spectroscopic investigations, there have been attempts to obtain structural and stereochemical information about radicals by chemical means.25 The approach generally taken is to generate radicals by one of the methods discussed in the next section at a carbon where stereochemistry can be determined. As an example, we may cite the experiment shown in Equation 9.6, in which an optically active aldehyde is heated in the presence of a source of radicals.26 The reaction follows the chain pathway indicated in Scheme 1 the loss of chirality indicates that the radical is either planar or, if pyramidal, undergoes inversion rapidly with respect to the rate (on the order of 10s sec-1) at which it abstracts a hydrogen atom from another molecule of aldehyde. 

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