Quinones reduction potentials

Many mitomycin analogues have been prepared by partial synthesis, and two of them have received clinical trials.Unexpected toxicity has led to their withdrawal, however. The present clinical candidates. BMY-25067 and KT 6149. contain disulfide sulxstituents on the 7-amino group. Control of the quinone reduction potential is especially. stre.ssed in analogue. studies, because reduction is the key step in bioactivation of the.se molecules. - ... 

No correlation between quinone reduction potential or hydrocarbon ionization potential and complex stability. 

It must be noted that in contrast to the early work cited above, in which correlations were carried out with Op, for which Pr is 50, best results for most substituted quinone oxidation-reduction potentials show a Pr value of about... 

The continuing interest in bioreductive alkylation is largely due to the clinical success of mitomycin C and the low reduction potentials observed in many tumors.9 The low reduction potentials favor the quinone to hydroquinone conversion necessary for bioreductive alkylation. Hypoxia due to low blood flow3 and/or the unusually high expression of the quinone two-electron reducing enzyme DT-diaphorase in some histological cancer types10-14 contribute to the tumor s tendency to reduce quinones. 

It is known that the reduction potentials of quinones are related to the aromatic stabilization of the parent conjugated systems. In an attempt to relate the annulenediones 171,177, and 178 to the tetradehydro[18]annuIene system Breslow and coworkers63 have studied their electrochemical reduction by cyclic voltammetry. These diones can easily be reduced to the corresponding dianions, e.g. 171 - 179. These... 

Fig. 6 A linear correlation of the reduction potentials Ertd (V versus SCE) with the gas-phase electron affinities EA (eV) of various nitrobenzenes and quinones. Reproduced with permission from Ref. 70.

Competition between dioxygen and quinones depends on the one-electron reduction potentials of quinones [29], and therefore, quinones may inhibit or stimulate superoxide production. 

There are two kinds of redox interactions, in which ubiquinones can manifest their antioxidant activity the reactions with quinone and hydroquinone forms. It is assumed that the ubiquinone-ubisemiquinone pair (Figure 29.10) is an electron carrier in mitochondrial respiratory chain. There are numerous studies [235] suggesting that superoxide is formed during the one-electron oxidation of ubisemiquinones (Reaction (25)). As this reaction is a reversible one, its direction depends on one-electron reduction potentials of semiquinone and dioxygen. 

Most quinone reductions go through an intermediate radical or semiquinone stage, usually revealed by a one-electron step in the redox potential.100 The radical formed by the reduction of compound VI is especially stable, probably because of the additional involvement of the benzoyl group.101 The ordinary semiquinones are more stable in basic solution since some of the resonance structures of the neutral radical involve separation of charges. 

Qrunones can accept one or two electrons to form the semiquinone anion (Q ") and the hydroquinone dianion (Q ). Single-electron reduction of a quinone is catalyzed by flavoenzymes with relatively low substrate selectivity (Kappus, 1986), for instance NADPH cytochrome P-450 reductase (E.C. 1.6.2.3), NADPH cytochrome b5 reductase (E.C. 1.6.2.2), and NADPH ubiquinone oxidoreductase (E.C. 1.6.5.3). The rate of reduction depends on several interrelated chemical properties of a quinone, including the single-electron reduction potential, as well as the number, position, and chemical characteristics of the substituent(s). The flavoenzyme DT-diphorase (NAD(P)H quinone acceptor oxidoreductase E.C. 1.6.99.2) catalyzes the two-electron reduction of a quinone to a hydroquinone. 

Quinones with higher reduction potential react faster that those with lower reduction potential. 1,2-Benzoquinones are also reduced to the corresponding bis-silylated hydroquinones. 

Q = quinones) have been measured by pulse radiolysis methods. From the results a self-exchange rate constant of 1.1 x 10 s and a reduction potential of -1-0.048 V vs. NHE for Os /Os have been... 

The half-wave reduction potentials for a series of annelated 1,4 naphthoquinones (102-106) increase upon alkylation, and decrease as ring size decreases (Table 13). The more cathodic reduction potentials of 2,3-dimethylnaphtho-l,4-qui-none (106, 0.846 V) and l,2,3,4-tetrahydro-9,10-anthroquinone (105,0.854 V) as compared to 1,4-naphthoquinone (0.685 V) are expected from inductive electron donation of alkyl groups. A decrease in reduction potential from 105 to 2,3-cyclobutanaphtho-l,4-quinone (103) (0.695 V) as ring size decreases is observed such that the reduction potential of 103 is only slightly higher than the parent 1,4-naphthoquinone. 

HO2 and 02 have characteristic absorption spectra with s ax 140 mol at 225 nm [83] and Smav = 189 mol at 245 nm [85], respectively, which are sufficiently intense to permit their reactions to be followed by direct observation in pulse radiolysis experiments. Both radicals are relatively unreactive with organic molecules [83], abstracting only weakly bonded hydrogen atoms in, for example, ascorbic acid, cysteine, and hydroquinone. Oj undergoes reversible electron transfer in its reaction with quinones (Q), which was used to establish its reduction potential [86] ... 

In the ESR spectra of some related trimethylsilyl benzoquinone derivatives, as with the ketyls, the spin density in the quinone ring increases for trimethylsilyl substitution and decreases for alkyl substitution, consistent with the electron-accepting ability of the trimethylsilyl group. This ability is also manifested in the reduction potentials of the compounds (65). The ESR data for the trimethylsily ketyls and for the trimethylsilyl benzoquinone anion radicals are summarized in Table IX. 

Another redox switchable system is based on dyad 21 in which 2-chloro-1,4-naphthoquinone is covalently attached to 5-dimethyl-aminonaphthalene via a non-conjugated spacer. The intrinsic fluorescence of the dansyl excited state in dyad 21 is strongly quenched, due to the intramolecular electron transfer from the excited dansyl to the adjacent quinone acceptor. However, the fluorescence can be switched on by addition of a reducing agent. Apart from chemical switching, the fluorescence of dyad 21 can also be switched electrochemically. This can be realized using a photoelec -trochemical cell, and the solution starts to fluoresce upon application of a reductive potential.31... 

The chemistry of the transition metals including chromium(III) with these ligands has been the subject of a recent and extensive review,788 with references to the early literature. The close relationship between the catechol (180), semiquinone (181) and quinone (182) complexes may be appreciated by considering the redox equation below (equation 44). 789 The formal reduction potentials for the chromium(III) complexes (183-186 equation 45) are +0.03, -0.47 and -0.89 V (vs. SCE in acetonitrile) respectively. 

Numerous studies have been made of the relationship between halfcell reduction potentials and the structures of quinones. As might be expected, the potentials are greatest when the resonance stabilization associated with formation of the aromatic ring is greatest. 

Ronald Breslow and his collaborators have given some attention to the problem of estimating the degree of destabilization of cyclobutadiene with respect to nonconjugated models. They have concluded from electrochemical measurements of oxidation-reduction potentials of the system 37 38, of which only the quinone 38 has the cyclobutadiene fragment, that the C4H4 ring is destabilized by some 12-16 kcal mole-1 and so is definitely antiaromatic.15... 

Intermolecular light-induced electron transfer to acceptors (quinones and nitro-benzenes) complexes in a /(-cyclodextrin linked to a porphyrin has been studied and the dependence of electron transfer efficiency upon the reduction potential of the acceptor was examined 72). 

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