Mechanism of hydroxylation

The mechanism of hydroxylation of heterocyclic compound has not been studied, but the mechanistic aspects of hydroxylation of homocyclic compounds may again serve as a basis for discussion. 

Nomiyama K, T Tanizaki, H Ishibashi, K Arizono, R Shinohara (2005) Production mechanism of hydroxylated PCBs by oxidative degradation of selected PCBs using TiOj in water and estrogenic activity of their intermediates. Environ Sci Technol 39 8762-8769. 

Smith RV, PJ Davis, AM Vlark, SK Prasatik (1981) Mechanism of hydroxylation of biphenyl by Cunningha-mella echinulata. Biochem J 196 369-371. 

IV. Mechanism of Hydroxylation A. Reaction of Hred with Dioxygen... 

FIGURE 24.1 Mechanism of hydroxylation and reduction of substrates by cytochrome P-450. (From TD Porter, MJ Coon. J Biol Chem 266 13469-13472, 1991. With permission.)... 

Ogliaro F, Harris N, Cohen S, et al. A model rebound mechanism of hydroxylation by cytochrome P450 stepwise and effectively concerted pathways, and their reactivity patterns. J Am Chem Soc 2000 122(37) 8977-8989. 

The mechanism of hydroxylation by the bacterial monooxygenase has been resolved to show four main steps in the sequence of cytochrome P-450 reactions (Fig. 1). 

Good, D.A., Hanson,]., Francisco, ].S., Li, Z., andjeong, G.-R. Kinetics and reaction mechanism of hydroxyl radical reaction with methyl formate, J. Phys. Chem. A, 103(50) 10893-10898, 1999. 

Mitchell, North Carolina, Air Waste, 43, 1074-1083 (1993). Arakaki, T., C. Anastasio, P. G. Shu, and B. C. Faust, Aqueous-Phase Photoproduction of Hydrogen Peroxide in Authentic Cloud Waters Wavelength Dependence, and the Effects of Filtration and Freeze-Thaw Cycles, Atmos. Environ., 29, 1697-1703 (1995). Arakaki, T., and B. C. Faust, Sources, Sinks, and Mechanisms of Hydroxyl Radical ( OH) Photoproduction and Consumption in Authentic Acidic Continental Cloud Waters from Whiteface Mountain, New York The Role of the Fe(r) (r = II, III) Photochemical Cycle, . /. Geophys. Res., 103, 3487-3504 (1998). Atkinson, R., D. L. Baulch, R. A. Cox, R. F. Hampson, Jr., J. A. Kerr, M. J. Rossi, and J. Troe, Evaluated Kinetic and Photochemical... 

F. Ogliaro, N. Harris, S. Cohen, M. Filatov, S. R de Visser, and S. Shaik, A Model Rebound Mechanism of Hydroxylation by Cytochrome P450. Stepwise and Effectively Concerted Pathways, and Their Reactivity Patterns, J. Am. Chem. Soc. 2000,122, 8977. Calculations explain puzzling aspects of cytochrome P450 hydroxylation reactions in terms of two, different, reactive spin states of the enzyme. 

Suzuki, K. T. Gomi, and E. Itagaki, Intermediate and mechanism of hydroxylation of orffco-iodophenol by salicylate hydroxylase , J. Biochem. (Tokyo), 109, 791-797 (1991). 

It is now generally understood that the mechanism of hydroxylation by cytochrome P-450 proceeds by two successive one-electron reduction steps of the heme center, transforming dioxygen into a peroxide species bonded to iron (Scheme l).73,78 Well-defined steps (25) - (31) involve (a) the formation of a high-spin Fein-enzyme-substrate complex (26) (b) one-electron reduction of (26) to a high-spin ferrocytochrome (27) (c) addition of dioxygen to form a superoxo-Fe111 complex (28) and (d) one-electron reduction of the superoxo complex to a peroxide complex (29). 

The deuterium KIE of 2.5 0.1, observed at 297 K in the cleavage of tributyltin allylsulphinate with [2H]TFA in toluene435 (equation 227) has been interpreted as suggesting a rigid compact and reactant-like early TS, and as confirming the concerted retro-ene mechanism of thermal desulphination of allylsulphinic acid (equation 228). The mechanism of hydroxyl radical-induced decarboxylation of 2-(alkylthio)ethanoic acid... 

Hildenbrand K, Schulte-Frohlinde D (1989) E.S.R. studies on the mechanism of hydroxyl radical-induced strand breakage of polyuridylic add. Int J Radiat Biol 55 725-738 Hildenbrand K, Schulte-Frohlinde D (1997) Time-resolved EPR studies on the reaction rates of per-oxyl radicals of poly(acrylic acid) and of calf thymus DNA with glutathione. Re-examination of a rate constant for DNA. Int J Radiat Biol 71 377-385 Hildenbrand K, Mirtsch S, Schulte-Frohlinde D (1993) H-NMR studies of y-irradiated polynucleotides and DNA in N20-saturated aqueous solutions. Release of undamaged and modified bases. Radiat Res 134 283-294... 

The superoxide oxide radical interacts with nitric oxide to produce peroxynitrite at a rate which three times faster than the rate at which superoxide dismutase utilizes superoxide (Beckman, 1994). Peroxynitrite is capable of diffusing to distant places in neural cells where it induces lipid peroxidation and may be involved in synaptosomal and myelin damage (Van der Veen and Roberts, 1999). After protonation and decomposition, peroxynitrite produces more hydroxyl radicals. This mechanism of hydroxyl radical generation is not dependent on redox active metal ions and may be involved in initiating lipid and protein peroxidation in vivo (Warner et al., 2004). 

The mechanism of hydroxylation has been discussed from the standpoint of anionic, cationic, or free-radical substitution, as opposed to the perhydroxylation mechanism. Smith122 has shown that free-radical substitution can explain the findings better than can anionic or cationic hydroxyl substitution, but the preferred explanation at present is perhydroxylation.123 124 Robinson, Smith and Williams123 have suggested that the following events occur in the metabolism of nitrobenzene. 

In more general terms, a review of product yields and distributions in radical hydroxylations shows that a great variety of yields and selectivities can be achieved by careful manipulation of experimental conditions. Occasionally, formation of biphenyl, which is often regarded as indicating the presence of a radical-based process, can be completely suppressed. Therefore, it is very risky to make statements about the mechanism of hydroxylation based solely on product distributions and without thorough mechanistic investigations [11]. 

J. Llano et al., Mechanism of hydroxyl radical addition to imidazole and subsequent water elimination. J. Phys. Chem. B 103, 5598-5607 (1999)... 

The reaction of ozone and hydrogen peroxide in its ionic form and photolysis of both oxidants constitute the initiation reactions leading to a mechanism of hydroxyl radical formation in water. This mechanism is basically the same for all these advanced oxidation systems, whereas the main differences lie in the initiating steps. These oxidation technologies have been applied for the treatment of pollutants in water for more than two decades. 

It is evident that the studies with tritiated proline do not permit definite conclusions about the mechanism of hydroxylation further information is needed about the labeling of the proline used and possible isotope effects. It is probable that there is some randomization of label during tritiation of 3,4-dehydroproline (40), and apparently also some racemization. Thus, we have observed that the tritiated proline preparations contain 10 to 20% D-proline and that oxidation by D-amino acid oxidase releases significant amounts of tritiated water. 

Although we must tentatively put aside the question of the detailed chemical mechanism of hydroxylation, the present data appear to provide insight into the relationship between hydroxylation and collagen synthesis. Thus, we may first consider a mechanism as shown below, based on the suggestion of Stetten. 

Connors TA, Cox PJ, Farmer PB, et al. 1974. Observations on the mechanism of hydroxylation of cyclophosphamide by rat liver microsomes The metabolism of cyclophosphamide-4-d2. Biomed Mass Spectrom 1 130-136. 

---