Showing papers on "Quinone published in 1998"

Chemoprotective properties of phenylpropenoids, bis(benzylidene)cycloalkanones, and related Michael reaction acceptors: correlation of potencies as phase 2 enzyme inducers and radical scavengers.

Abstract: Induction of phase 2 enzymes (e.g., glutathione transferases, NAD(P)H:quinone reductase, glucuronosyltransferases, epoxide hydrolase) is a major strategy for reducing the susceptibility of animal cells to neoplasia and other forms of electrophile toxicity. In a search for new chemoprotective enzyme inducers, a structure−activity analysis was carried out on two types of naturally occurring and synthetic substituted phenylpropenoids: (a) Ar−CHCH−CO−R, where R is OH, OCH3, CH3, or Ar, including cinnamic, coumaric, ferulic, and sinapic acid derivatives, their ketone analogues, and chalcones; and (b) bis(benzylidene)cycloalkanones, Ar−CHC(CH2)n(CO)CCH−Ar, where n = 5, 6, or 7. The potencies of these compounds in inducing NAD(P)H:quinone reductase activity in murine hepatoma cells paralleled their Michael reaction acceptor activity (Talalay, P.; De Long, M. J.; Prochaska, H. J. Proc. Natl. Acad. Sci. U.S.A. 85, 1988, 8261−8265). Unexpectedly, the bis(benzylidene)cycloalkanones also powerfully quenched the luci...

Electrochemical Post-Self-Assembly Transformation of 4-Aminothiophenol Monolayers on Gold Electrodes

Abstract: Electrochemical oxidation of a self-assembled monolayer (SAM) of 4-aminothiophenol on polycrystalline gold electrodes leads to a complex voltammetric behavior characterized by an initial irreversible oxidation at ∼+0.77 V versus SSCE (sodium saturated calomel electrode) and the formation of a pseudostable surface redox couple at +0.53 V. The oxidized form of this couple is hydrolyzed in acidic solutions to another redox pair with the formal redox potential of ∼+0.3 V. We show that the oxidation leads to a radical−radical coupling reaction between two adjacent aminothiophenol molecules, yielding an electrode surface modified with 4‘-mercapto-4-aminodiphenylamine, the thiol derivative of a head-to-tail aniline dimer. The oxidized form of the dimer, quinone diimine, undergoes hydrolysis to the corresponding quinone monoimine and, eventually, to the original surface-bound 4-aminothiophenol and benzoquinone. The mechanism of the monolayer oxidation reaction has been elucidated by a variety of electrochemical a...

Indolequinone antitumor agents: correlation between quinone structure, rate of metabolism by recombinant human NAD(P)H:quinone oxidoreductase, and in vitro cytotoxicity.

Abstract: A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (NQO1) were studied. Thus 5-methoxyindolequinones were prepared by the Nenitzescu reaction, followed by functional group interconversions. The methoxy group was subsequently displaced by amine nucleophiles to give a series of amine-substituted quinones. Metabolism of the quinones by NQO1 revealed that, in general, compounds with electron-withdrawing groups at the indole 3-position were among the best substrates, whereas those with amine groups at the 5-position were poor substrates. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward non-small-cell lung cancer cells with either high NQO1 activity (H460) or no detectable activity (H596) was also studied in representative quinones. Compounds which were good substrates for NQO1 showed the highest selectivity between the two cell lines.

Inhibition of Nitric Oxide Formation by Neuronal Nitric Oxide Synthase by Quinones: Nitric Oxide Synthase as a Quinone Reductase†

Abstract: Inhibitory action of a variety of quinoid compounds on neuronal nitric oxide synthase (nNOS) activity was examined with a 20000g rat cerebellar supernatant preparation and purified nNOS. The inhibition of citrulline formation from l-arginine by quinones, which exhibit one-electron reduction potentials (E17) ranging between −240 and −100 mV, increased at a more positive one-electron reduction potential, suggesting that quinone appears to act as an electron acceptor for nNOS. Among the quinones tested, 9,10-phenanthraquinone (PQ), corresponding to an E17 value of −124 mV, exhibited the most potent inhibiton of citrulline formation (IC50 value = 10 μM). A kinetic study revealed that PQ is a competitive inhibitor with respect to NADPH, with a Ki value of 0.38 ± 0.12 μM, and a noncompetitive inhibitor with respect to l-arginine, with a Ki value of 9.63 ± 0.20 μM. Partial purification of the enzymes which are responsible for reducing PQ in 20000g supernatant of rat cerebellum by anion-exchange column chromatogr...

Indolequinone Antitumor Agents: Reductive Activation and Elimination from (5-Methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl Derivatives and Hypoxia-Selective Cytotoxicity in Vitro

Abstract: A series of indolequinones bearing a variety of leaving groups at the (indol-3-yl)methyl position was synthesized by functionalization of the corresponding 3-(hydroxymethyl)indolequinone, and the resulting compounds were evaluated in vitro as bioreductively activated cytotoxins. The elimination of a range of functional groups-carboxylate, phenol, and thiol-was demonstrated upon reductive activation under both chemical and quantitative radiolytic conditions. Only those compounds which eliminated such groups under both sets of conditions exhibited significant hypoxia selectivity, with anoxic:oxic toxicity ratios in the range 10-200. With the exception of the 3-hydroxymethyl derivative, radiolytic generation of semiquinone radicals and HPLC analysis indicated that efficient elimination of the leaving group occurred following one-electron reduction of the parent compound. The active species in leaving group elimination was predominantly the hydroquinone rather than the semiquinone radical. The resulting iminium derivative acted as an alkylating agent and was efficiently trapped by added thiol following chemical reduction and by either water or 2-propanol following radiolytic reduction. A chain reaction in the radical-initiated reduction of these indolequinones (not seen in a simpler benzoquinone) in the presence of a hydrogen donor (2-propanol) was observed. Compounds that were unsubstituted at C-2 were found to be up to 300 times more potent as cytotoxins than their 2-alkyl-substituted analogues in V79-379A cells, but with lower hypoxic cytotoxicity ratios.

Tyrosinase kinetics: failure of the auto-activation mechanism of monohydric phenol oxidation by rapid formation of a quinomethane intermediate

Abstract: When 3,4-dihydroxybenzylcyanide (DBC) is oxidized by mushroom tyrosinase, the first visible product, identified as the corresponding quinomethane, exhibits an absorption maximum at 480 nm. Pulse-radiolysis experiments, in which the o -quinone is formed by disproportionation of semiquinone radicals generated by single-electron oxidation of DBC, showed that the quinomethane ( A 480 6440 M -1 ·cm -1 ) is formed through the intermediacy of the o -quinone with a rate constant at neutral pH of 7.5 s -1 . The oxygen stoichiometry of the formation of the quinomethane by tyrosinase-catalysed oxidation of DBC was 0.5:1. On the basis of oxygen utilization rates the calculated V max was 4900 nmol·min -1 and the apparent K m was 374 µ M. The corresponding monohydric phenol, 4-hydroxybenzylcyanide (HBC), was not oxidized by tyrosinase unless the enzyme was pre-exposed to DBC, the maximum acceleration of HBC oxidation being obtained by approximately equimolar addition of DBC. These results are consistent with tyrosinase auto-activation on the basis of the indirect formation of the dihydric phenol-activating cofactor. The rapid conversion of the o -quinone to the quinomethane prevents the formation of the catechol by reduction of the o -quinone product of monohydric phenol oxidation from occurring in the case of the compounds studied. In the absence of auto-activation, the kinetic parameters for HBC oxidation by tyrosinase were estimated as V max 70 nmol·min -1 and K m 309 µ M. The quinomethane was found to decay with a rate constant of 2 k 38 M -1 ·s -1 , as determined both by pulse-radiolysis and tyrosinase experiments. The second-order kinetics indicate that a dimer is formed. In the presence of tyrosinase, but not in the pulse-radiolysis experiments, the quinomethane decay was accompanied by a steady-state oxygen uptake concurrently with the generation of a melanoid product measured by its A 650 , which is ascribed to the formation of an oligomer incorporating the oxidized dimer.

Combination of (acyl) carnitine and (hydro)quinone for use in skin care, effective e.g. against light-induced damage and inflammation

Abstract: An active agent combination comprises: (A) at least one of carnitine and acyl carnitine(s); and (B) at least one quinone and/or hydroquinone. An Independent claim is also included for cosmetic or dermatological preparations containing (A) and (B).

In Search of Molecular Rectifiers. The Donor−σ−Acceptor System Derived from Triptycenequinone and Tetrathiafulvalene

Abstract: Several donor−σ−acceptor compounds (8, 9, 13, and 14) have been synthesized that contain a sterically hindered quinone tethered by a tetramethylene chain to a substituted tetrathiafulvalene. Compounds 13 and 14 show a dramatic increase (≈450 mV) in the oxidation potential of the dipyrrolo-TTF unit, suggestive of considerable electron withdrawal through the σ-bridge. Monolayers of 9 and 14 are metastable at the air−water interface.

Paterno−Büchi Coupling of (Diaryl)acetylenes and Quinone via Photoinduced Electron Transfer

Abstract: Photoinduced coupling of an acetylene with a quinone in two wavelength regions (λDB and λCT) can be regioselective to yield a single quinone methide adduct when various diarylacetylenes (DA) and 2,6-dichlorobenzoquinone (DB) are used. Thus, the direct photoexcitation of DB at λDB = 355 nm or the specific activation of the 1:1 electron donor−acceptor complex [DA,DB] at λCT = 532 nm both lead to the transient ion-radical pair [DA•+,DB•-], which is established by time-resolved (ps,ns) spectroscopy. Competition between back electron transfer (kBET) and ion-radical pair collapse (kC) to the distonic adduct DA-DB, as described in Schemes 1 and 2, limits the quantum yields for both photochemical processes in Table 4. The biradical nature of the distonic adduct in Scheme 3 accommodates the various facets of acetylene reactivity and unique regioselectivity to yield the same quinone methide by both actinic processes. In a more general context, the electron-transfer mechanism established by the charge-transfer excit...

Characterization of the ubiquinone reduction site of mitochondrial complex I using bulky synthetic ubiquinones.

Abstract: A wide variety of alkyl derivatives of Q2 (6-geranyl-2, 3-dimethoxy-5-methyl-1,4-benzoquinone) and DB (6-n-decyl-2, 3-dimethoxy-5-methyl-1,4-benzoquinone), in which methoxy groups of the 2- and/or 3-positions of the quinone ring were replaced by other bulky alkoxy groups from ethoxy to butoxy, were prepared by novel synthetic procedures. Electron-accepting activities of the bulky quinones were investigated with bovine heart mitochondrial complex I and its counterpart of Paracoccus denitrificans(NDH-1) to elucidate structural and functional features of the quinone reduction site of the enzymes. The bulky quinone analogues served as sufficient electron acceptors from the physiological quinone reduction site of bovine complex I. Considering the very poor activities of even the ethoxy derivatives as substrates for other respiratory enzymes such as mitochondrial complexes II and III [He, D. Y., Gu, L. Q., Yu, L., and Yu, C. A. (1994) Biochemistry 33, 880-884], this result indicated that the quinone reduction site of bovine complex I is spacious enough to accommodate bulky exogenous substrates. In contrast to bovine complex I, bulky quinone analogues served as poor electron acceptors with Paracoccus NDH-1. These observations indicated that bovine complex I recognizes the substrate structure with poor specificity. The substituent effects in the 2- and 3-positions of the quinone ring on the electron-transfer activity with bovine complex I differed significantly between Q2 and DB series despite having the same total number of carbon atoms in the side chain. The inhibitory effect involving Q2 due to its geranyl side chain was markedly diminished by structural modifications of the quinone ring moiety. These findings indicate that the side chain plays a specific role in the redox reaction and that the quinone ring and side-chain moieties contribute interdependently to binding interaction. Moreover, structural dependency of the proton-pumping activity of the quinone analogues was comparable to that of the electron-transfer activity with bovine complex I, indicating that the mechanism of redox-driven proton-pumping does not differ depending upon the substrate structure.

Chemistry of ruthenium( II ) complexes of N-substituted 1,2-benzoquinone diimines. Synthesis, structure and redox properties‡

Abstract: A series of ruthenium complexes of N-aryl-1,2-benzoquinone diimine chelates [Ru(acac)2L] have been isolated via ruthenium promoted oxidative dimerization of arylamines. These compounds were obtained from the reaction of [Ru(acac)3] and arylamines. The crystal structure of one representative case has been determined to authenticate the formation of the compound from a heretofore unknown chemical transformation. The structural data revealed a planar diimine L. The two C–N (imine) and two conjugate C–C double bonds in the quinonoid ring are localized and are indicative of the bivalent state of the metal ion. A plausible reaction pathway is discussed. Extended Huckel calculations on [Ru(acac)2L] revealed that the metal–ligand overlap is high. The electronic transitions of the complexes are discussed based on the frontier MO diagram. There are multiple transitions in the range 1100 to 250 nm. The highly intense transition at ca. 520 nm has been assigned to a transition involving two heavily mixed metal–ligand orbitals. The diimine complexes undergo four successive one electron transfer processes. Two are metal centered, occurring at positive potentials, and two are ligand reductions at negative potentials. The E°298 values of all the four redox processes are dependent on the nature of substitution of the quinone diimine ligand. The structure and physicochemical properties of these complexes are compared with those of [Ru(acac)2(bqdi)] (bqdi = o-benzoquinone diimine) obtained from the reaction of [Ru(acac)3] and o-phenylenediamine.

Efficient total synthesis of (-)-ilimaquinone

Abstract: The total synthesis of (-)-ilimaquinone, a metabolite isolated from sea sponges, is described. The key step of the synthesis is the attachment of the quinone moiety to the drimane skeleton. Alkylation of enone 11 obtained in four steps from the readily available diketone 8, with tetramethoxybenzyl bromide 15 as the alkylating agent, led to addition product 16 in excellent yield. The presence of the tetramethoxybenzyl group induced stereoselective hydrogenation of the exo olefin 18, leading to the required isomer in a 9:1 ratio. Treatment of compound 21 with ceric ammonium nitrate (CAN) afforded formation of the quinone and deprotection of only one methyl ether in one step to furnish the desired ilimaquinone 1.

Methylene Arenium Cations via Quinone Methides and Xylylenes Stabilized by Metal Complexation

Abstract: The quinone methide (QM) rhodium complex of 3,5-bis(di-tert-butylphosphinomethyl)-2,6-dimethyl-4-methylene-3,5-cyclohexadien-1-one (L) (1) was protonated by trifluromethanesulfonic acid (triflic acid) at the quinonoid carbonyl group giving the unique methylene arenium complex (Cl)Rh[LH+]CF3SO3- (2). Complexes 2 and its (trimethyl)silyl analogue (3) were fully characterized spectroscopically, and complex 2 was also characterized by single-crystal X-ray analysis. The crystallographic studies on 2 have revealed that the positive charge is delocalized between the carbon atoms of the ring with most of it being at the para- and ortho-carbon atoms. The electron deficient QM complex (CO)Rh+[L] CF3SO3- (4), which has also been crystallographically characterized, is less basic, requiring excess of triflic acid to obtain the methylene arenium complex (CO)Rh+[LH+]2CF3SO3- (5), demonstrating a dramatic effect of the electron density on the metal center on the stability of the methylene arenium species. When 1 was reac...

Lignin–carbohydrate model compounds. Formation of lignin–methyl arabinoside and lignin–methyl galactoside benzyl ethers via quinone methide intermediates

Abstract: Model compounds for lignin–carbohydrate complexes (LCCs) were synthesized from β-O-4-type quinone methides and methyl glycosides of α-L-arabinofuranose and α-D-galactopyranose. Both monosaccharides reacted predominantly through primary hydroxy groups with the benzyl position of the dilignol but some secondary C-3 hydroxy groups of galactopyranosides also took part in ether-bond formation. Methyl α-L-arabinofuranosides were found to be more reactive than methyl α-D-galactopyranosides. LCC model-compound formation via quinone methides gave a mixture of four diastereomers. The diastereomers were isolated using silica gel and HPLC chromatography and all products were characterized by NMR spectroscopy.

Transition-metal complexes of terpyridine ligands with hydroquinone or quinone substituents‡

Abstract: The new ligands 4′-(2,5-dimethoxyphenyl)- (L1), 4′-(2,5-hydroxyphenyl)- (L2) and 4′-(1,4-benzoquinonyl)-2,2′∶6′,2″-terpyridine (L3) and a range of their transition-metal complexes have been prepared. The crystal and molecular structures of L1 and [CuL12][PF6]2 have been determined. Model reactions showed that the complexes [ML22]n+ can be derivatized with suitable organic reagents, suggesting they may be incorporated into multicomponent architectures using either ester or ether linkages. The chromophoric, magnetic and electrochemical properties of the complexes vary with transition metal and 4′ substituent. The hydroquinonyl-substituted [ML22]2+ and the quinonyl-substituted [ML32]2+ complexes can be electrochemically interconverted in the presence of weak acid and switching between hydroquinonyl and quinonyl 4′ substituents can significantly perturb physical properties of the bis(terpyridyl) transition-metal centre(s).

Reaction of beta-lapachone and related naphthoquinones with 2-mercaptoethanol: a biomimetic model of topoisomerase II poisoning by quinones.

Abstract: 1,2-Naphthoquinones, such as beta-lapachone, 4-alkoxy-1,2-naphthoquinones, and tetrahydrofuran-1,2-naphthoquinones, react rapidly with 2-mercaptoethanol in benzene to give 1,4-, 1,2-, 1,3- and 1,6-Michael-type adducts that are formed by the addition of the thiol group to the quinone ring. Menadione (2-methyl-1,4-naphthoquinone) reacts with the thiol reagent very slowly under the same reaction conditions. Although the formation of the adducts can be followed by 1H-NMR, attempts to isolate the adducts failed due to their retroconversion to the starting products. On addition of a Lewis acid, however, the adducts undergo cyclization reactions that give stable derivatives that can be isolated and characterized. Determination of the structures of the derivatives allowed for the identification of the adducts from which they originated. Thus, beta-lapachone and 2,3-dinordunnione underwent 1,4- and 1,2-Michael type additions to the quinone ring, while 4-pentyloxy-1,2-naphthoquinone underwent two simultaneous Michael additions to the quinone ring of the naphthoquinone. Menadione underwent a single 1,3-addition. The alkylation rates of the thiol group of 2-mercaptoethanol by the naphthoquinones parallel the naphthoquinones efficiencies in inducing DNA cleavage through DNA-bound topoisomerase II. These results support our hypothesis that the cytotoxic effect of the naphthoquinones derive, at least in part, from their alkylation of exposed thiol residues on the topoisomerase II-DNA complex.

Contrasting photoinduced electron-transfer properties of two closely related, rigidly linked porphyrin-quinone dyads

Abstract: Two closely related, rigidly linked porphyrin−naphthoquinone dyads have been prepared and studied using time-resolved fluorescence and absorption methods. Dyad 1, whose quinone carbonyl groups are relatively close to the porphyrin macrocycle, exhibits photoinduced electron-transfer rate constants that are virtually independent of solvent dielectric constant and temperature within the range 77−295 K. Dyad 2, which has a similar donor−acceptor linkage but whose quinone carbonyl groups are ∼2 A farther from the porphyrin, features photoinduced electron-transfer rate constants that decrease with decreasing solvent dielectric constant. Electron transfer in this molecule ceases at low temperatures. Photoinduced electron transfer in dyad 2 exhibits the usual dependence on free energy change and solvent reorganization observed in many similar porphyrin−quinone systems. The behavior of 1 may be attributed at least in part to the smaller separation of the porphyrin radical cation and the quinone radical anion, whic...