Oxidation peroxide-mediated

DNA damage by iron chelators has been shown by Cragg et al. [84]. These authors showed that various iron chelators affected the hydrogen peroxide-mediated DNA damage in iron-loaded liver cells in different ways. Thus, desferrithiocin was protective and desferri-oxamine had no effect, while l,2-dimethyl-3-hydroxypyrid-4-one (LI) enhanced oxidative DNA damage. It has been suggested that the oxidative effect of LI depended on stoichiometry of Fe—LI complexes. 

In the first of these techniques the lanthanoid complex (33) (5-8 mol%) is used as the organometallic activator in cumene hydroperoxide or tert-butyl hydrogen peroxide-mediated oxidation of chalcone (epoxide yield 99 % 99 % ee) or the ketone (34) (Scheme 20)[1001. 

Gupta, M. P., Evanoff, V., and Hart, C. M., 1997, Nitric oxide attenuates hydrogen peroxide-mediated injury to pordne pulmonary artery endothelial cells, Am. J. Physiol. 272 LI 133-1141. 

There are no available data on the formation of hydroperoxides derived from DNA within cells. This is likely explained, at least partly, by the fact that DNA is a poorer target than proteins for OH radical as observed upon exposure of mouse myeloma cells to ionizing radiation . However, indirect evidence for DNA peroxidation within cells may be inferred from the measurement of final degradation products that may derive from thymine and guanine hydroperoxidation as the result of oxidation reactions mediated by OH radical and O2, respectively (Sections n.A.2 and n.E.2). It may be pointed out that the measurement of oxidized bases and nucleosides within DNA has been the subject of intense research during the last decade and accurate methods are now available . This includes DNA extraction that involves the chaotropic Nal precipitation step and the use of desferrioxamine to chelate transition metals in order to prevent spurious oxidation of overwhelming nucleobases to occur . HPLC coupled to electrospray ionization... 

Yin J, Chu JW, Ricci MS, Brems DN, Wang DI, Trout BL. Effects of antioxidants on the hydrogen peroxide-mediated oxidation of methionine residues in granulocyte colony-stimulating factor and human parathyroid hormone fragment 13-34. Pharm Res 2004 21 (12) 2377—2383. 

Scheme 51. Di-tert-butyl peroxide-mediated oxidative dimerization of a chiral phenol precursor to the magistophorenes.

Knepp, V. M., Whatley, J. L., Muchnik, A., and Calderwood,T. S. (1996), Identification of antioxidants for prevention of peroxide-mediated oxidation of recombinant human ciliary neurotrophic factor and recombinant human nerve growth factor, J. Parenteral Sci. Technol., 50,163-171. 

Hirvonen a, Tuhkanen T, Kalliokoski P (1996) Removal of Chlorinated Ethylenes in Contaminated Ground Water by Hydrogen Peroxide Mediated Oxidation Processes, Environ. Technol. 17 263-272. 

For oxidation, different stressing schemes can be used, and this depends generally on the structure of the drug substance (active component) autooxidation, metals, peroxide-mediated, peroxy-mediated, bubbled oxygen, and pressurized oxygen. Auto-oxidation involves a free radical initiator such as AIBN (2,2 -azobisisobutyronitrile) or AMVN (2,2 -azobis(2,4-dimethylvaleronitrile) to initiate oxidation [37] and has been used to mimic long-term room temperature degradation related to oxidation. The concentration... 

The nitro-substituted seleninic acid 103a was also found [531 to be an effective catalyst for the hydrogen peroxide mediated oxidative conversion of aromatic hydrazones 107 into nitriles 108 (Eq. 21). However, oxidation of hexanal dimethylhydrazone with this system gave only the parent aldehyde. 

K. Merker et al. Hydrogen peroxide-mediated protein oxidation in young and old human MRC-5 fibroblasts, Arch Biochem Biophys. 175 (2000) 50-54. 

As mentioned previously, oxidative degradation pathways can be complex, and it is useful to consider the chemistry of oxidative degradation. The oxidative degradation of pharmaceuticals has been discussed in the literature,23-27 and we assert that there are three major pathways, (1) autoxidation or radical-mediated oxidation, (2) peroxide-mediated, and (3) photochemically induced (see Table 5). Traditionally, dilute aqueous peroxide solutions have been used for oxidative stress testing of pharmaceuticals. Landmark papers by Boccardi23 24 in 1992 and 1994 identified autoxidation as the major oxidative degradation pathway for pharmaceuticals. Boccardi showed that the use of radical initiators such as... 

In some methods, the final mixture is acidified slightly to stop the reaction, and the intensity of the yellow chro-mophore is measured at 400 nm. In stronger acid solution, the color becomes pink, with maximum absorbance at 540 nm, and both sensitivity and stability are improved. Other approaches to measurement of the H2O2 produced include the peroxide-mediated oxidative coupMng of 3-methyl 2-benzothia2olinone hydrazone (MBTH) with N,N-dimethyl-aniline (DMA) catalyzed by peroxidase or the oxidative coupHng of p-aminophenazone (PAP) to phenoi. Both procedures have been automated. The... 

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