Purines reduction potential

Base stacking will further modulate the reduction potentials. Initial calculations show that pyrimidines flanked by other pyrimidines, like in 3 -TTT-5 or 3 -TCT-5 sequences, are most easily reduced. Incorporation of a purine base close to the pyrimidine, however, seems to make the pyrimidine reduction more difficult [40]. 

Gua has the lowest reduction potential among the four nucleobases (Table 10.2), and hence it is preferentially oxidized to its radical cation (for the calculation of ionization potentials of the DNA bases see Close 2004 Crespo-Hernandez et al. 2004), and this property makes Gua and its derivatives to stick out of the other nucleobases with respect to its different free-radical chemistry. In contrast, Thy and Cyt are good electron acceptors, while the purines are only poor ones in comparison (for the calculation of electron affinities, see Richardson et al. 2004). This is of special importance in the effects caused by the absorption of ionizing radiation by DNA. 

Purines. In general, -OH readily adds to double bonds but undergoes ET reactions only very reluctantly (Chap. 3.2). This also applies to purines despite their relatively low reduction potentials (Table 10.2). Thus, G- which is formed in the reaction of OH with dGuo has a short-lived -OH-adduct rather than G-+ as precursor (Candeias and Steenken 2000), and the H-abstraction that could also lead to G (for theoretical calculations see Mundy et al. 2002) does not occur to any significant extent. 

Faraggi M, Klapper MH (1993) Reduction potentials determination of some biochemically important free radicals. Pulse radiolysis and electrochemical methods. J Chim Phys 90 711-744 Faraggi M, Klapper MH (1994) One electron oxidation of guanine and 2 -deoxyguanosine by the azide radical in alkaline solutions. J Chim Phys 91 1062-1069 Faraggi M, Broitman F, Trent JB, Klapper MH (1996) One-electron oxidation reactions of some purine and pyrimidine bases in aqueous solutions. Electrochemical and pulse radiolysis studies. J Phys Chem 100 14751-14761... 

Although molybdenum and tungsten enzymes carry the name of a single substrate, they are often not as selective as this nomenclature suggests. Many of the enzymes process more than one substrate, both in vivo and in vitro. Several enzymes can function as both oxidases and reductases, for example, xanthine oxidases not only oxidize purines but can deoxygenate amine N-oxides [82]. There are also sets of enzymes that catalyze the same reaction but in opposite directions. These enzymes include aldehyde and formate oxidases/carboxylic acid reductase [31,75] and nitrate reductase/nitrite oxidase [83-87]. These complementary enzymes have considerable sequence homology, and the direction of the preferred catalytic reaction depends on the electrochemical reduction potentials of the redox partners that have evolved to couple the reactions to cellular redox systems and metabolic requirements. 

The electron affinities (EA) of the nucleobases have not been determined experimentally. Calculated values for the vertical and adiabatic EA obtained by scaling experimental and calculated values for other aromatic molecules are summarized in Table 1 [33a]. The vertical values follow the order U>T>C>A>G, with U having the largest (most positive) EA. The calculated adiabatic EA for C is less positive than the values for T or U. Chen and Chen [36] have asserted that the electron affinities of the purines are larger than those of the pyrimidines. However, this claim appears to be based upon questionable reduction potential measurements (see p. 114). The nucleobase anion radicals are estimated to be stabilized by c. 3 eV in aqueous solution. 

Professors Wiley, J. M. Robinson, and S. Ehdaie at the University of Texas in Permian Basin measured the reduction potentials of purines and pyrimidines. Wiley obtained NICI data for the chloroethylenes and purines and pyrimidines. The post-doctoral and doctoral students at the Wentworth laboratory in the 1990s were Gerard Gremaud, Huamin Cai, Janardhan Madabushi, J. Dojahn, and Kefu... 

Mode of action. The precise mode of action of carbamazepine has not been fully established. It has been shown to stabilize both pre- and postsynaptic neurons by blocking the use and frequency-dependent sodium channels. While this is probably its main action, the blockade of the glutamate NMDA ionotropic receptors also leads to a reduction in the influx of sodium and calcium ions into the neuron. The net effect of these changes is a reduction in the sustained high-frequency repetitive firing of the action potentials which characterize epileptic activity. There is also evidence that carbamazepine blocks purine, noradrenaline, serotonin and muscarinic acetylcholine receptors which probably accounts for the use of carbamazepine as a mood stabilizing agent. 

Purine exhibits two 2e diffusion-controlled irreversible reduction waves in aqueous buffered medium (over the pH range 2-12), corresponding to sequential reduction of the N(1)=C(6) and N(3) -C(2) bonds (Scheme 23). The potential required for initial addition of an electron to purine is so much higher than for pyrimidine 153) that the free radical species formed is instantaneously reduced, the result being a two-electron wave. Elving et al.15,36,99,153> proposed that the initial reduction step (wave I) of purine involves a very rapid protonation of N( 1) and successive one-electron transfer to the N(1)=C(6) bond, with formation of 1,6-dihydropurine (Scheme 23). Subsequent reduction of the N(3) = C(2) bond (corresponding to wave II) apparently proceeds by a similar mechanism (Scheme 23), with presumed formation of 1,3,4,6-tetrahydropurine, but this has not been experimentally established. 

Of some relevance to this review is adenine, which is a component of nucleic acids, and of key nucleotide coenzymes like NAD". This base, and its nucleosides and nucleotides 35>, exhibit a single reduction wave, with about the same total current as the parent purine, of the magnitude expected for a 4e process15,153). On controlled-potential electrolysis, however, it undergoes a 6e reduction to give the same product as does purine in its overall 4e reduction 15,35,36 153), as shown in Scheme 25. The reduction of adenine is accompanied by catalytic hydrogen evolution, so that it is not possible to determine directly the number of electrons involved. 

On addition of weak proton donors, such as water and benzoic acid l64), the le reduction product is further reduced at the potential of its formation, due to production of more readily reduced protonated species, so that reduction attains the level of a 4e process at a mole ratio of acid to purine of 4 (the total faradaic for these purines in aqueous media is 4). In the presence of a strong acid (perchloric), purine and 6-methylpurine exhibit two 2e waves and other 6-substituted purines a simple 4e wave. The effect of substitution at the 6-position on ease of reducibility is the same in neutral 164) and protonated purines 155). 

The 2, 3 -dideoxy-3 -C-(phosphonomethyl)nucleosides (38) of the five common nucleotide bases have been prepared by a condensation of the nucleobases with 1,2-di-O-acetyl-S-O-benzoyl-3-deoxy-3-(methoxyphosphorylmethyl)-6-D-ribofuranose (39). Conversion to the deoxyribose derivative was accomplished by reduction of the 2 -thionocarlKHUite and hydrolysis of the phosphonic ester groups using bromotrimethylsilane. 9-(l-Deoxy-l-phosphono-B-D-p(5CO-furanosyl)-l,9-dihydro-67f-purin-6-one (40, Scheme 4) has been prepared as a potential transition state inhibitor of purine nucleoside phosphorylase. The crucial step in the synthesis involved the carixm-phosphorus bond formation by reaction of the hemiacetal (41) with triethyl-phosphite. Nucleotide (40) proved to be very susceptible to hydrolysis of the glycosidic bond (half-life of thirty-nine minutes, pH 7), but showed weak inhibitory activity (K- = 26 /iM) against purine nucleoside phosphorylase. 

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