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Tricyclic, bicyclic, and monocyclic compounds containing cyanoenones induce various anti-inflammatory and cytoprotective enzymes through activation of the Keap1/Nrf2/ARE (antioxidant response element) pathway. The potency of these compounds as Nrf2 activators was determined using a prototypic cytoprotective enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) in Hepa1c1c7 murine hepatoma cells. The electron affinity (EA) of the compounds, expressed as the energy of their lowest unoccupied molecular orbital [E (LUMO)], was evaluated using two types of quantum mechanical calculations: the semiempirical (AM1) and the density functional theory (DFT) methods. We observed striking linear correlations [r = 0.897 (AM1) and 0.936 (DFT)] between NQO1 inducer potency of these compounds and their E (LUMO) regardless of the molecule size. Importantly and interestingly, this finding demonstrates that the EA is the essentially important factor that determines the reactivity of the cyanoenones with Keap1.

Spectroscopic and chemical properties of γ-CD radicals, resulting from the abstraction by HO radicals of hydrogen atoms, have been investigated using pulse radiolysis. The reactions of γ-CD radicals with C60 in 2:1 γ-CD/C60 inclusion complexes have been studied in aqueous solutions. It has been demonstrated that the γ-CD radicals are reducing species producing C60- monoanion radicals, as well as doubly reduced C602-, well characterised by their absorption spectra in the near IR. The oxidation potential of γ-CD radical is estimated to be more negative than −390 mV vs. NHE. The kinetics of the C60 reduction by γ-CD radicals have been determined and compared with kinetics by other reducing species including the solvated electron (eaq-) and CO2- radicals. It was observed that the method of preparation of the 2:1 γ-CD/C60 inclusion complexes modifies the C60 reduction mechanism.

In search of a simple internal complexation of C 60 in cyclodextrins, six 2:1 cyclodextrin:[60]fullerene conjugates involving different types of linkers have been synthesised. Using spectrophotometry, laser flash photolysis and pulse radiolysis, we have investigated spectroscopic and photophysical properties of these 2:1 cyclodextrin [60]fullerene monoadduct conjugates ( CDF ), including ground and triplet state absorption spectra, triplet molar absorption coefficients ( e T ), quantum yields of triplet ( Φ T ) and singlet oxygen formation ( Φ Δ ) in water and toluene, in order to probe the possibility of 2:1 inclusion complexes of C 60 between two cyclodextrins. In water, the CDF spectroscopic and photophysical properties indicate hydrophobically driven self-assemblies of the amphiphilic conjugates into spherical micelles with no evidence for the presence of a 2:1 inclusion complex, while in toluene they show no sign of aggregation. It is observed that formation of aggregates in water does not prevent scavenging of HO radical by the C 60 moiety of the CD–C 60 conjugates.

Induction of phase 2 enzymes is a major strategy in chemoprotection against cancer. Inducers belong to nine different chemical classes. In this study we found that a measure of the tendency of 30 plant phenylpropenoids and synthetic analogs to release electrons correlates linearly with their potency in inducing the activity of NAD(P)H:quinone reductase (NQO1), a prototypic phase 2 cancer-protective enzyme. The tendency to release electrons was determined by the energy of the highest occupied molecular orbital (EHOMO), calculated by simple quantum-mechanical methods. The correlations observed establish a clear conclusion: the smaller the absolute EHOMO of an agent, A, i.e., the lower its reduction potential, E(A +/A), the stronger is its electron donor property and the greater its inducer potency. The finding of this redox ranking of the inducers demonstrates the possibility of controlling and predicting the genetic expression of an enzymatic defense against cancer by xenobiotics via one physicochemical parameter, the reduction potential, E(A +/A).

Absorption spectra of the pyrrolidine N -mTEG (mTEG=CH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 OCH 3 ) mono-adduct and eight bis-adducts of C 60 were studied in the 230–800 nm spectral range. The five-membered ring adducts contain an apex nitrogen atom. A theoretical discussion in terms of the effective electronic structures and transitions of these species shows that a filiation between spectra of C 60 , and its pyrrolidine mono- and bis-adduct derivatives can be expected and rationalised. Allowed transitions in the ultraviolet are related to fullerene core electronic transitions and are observed to be little affected in energy and in transition strength by the mono-adduct, apart from band splitting or broadening associated with the lowered molecular symmetry with respect to C 60 , whereas in the visible region, the transitions related to C 60 forbidden transitions are significantly modified by the adduct. The bis-adducts have similar general spectral behaviour to that of the mono-adduct, with differences that reflect the relative position of the two addends but are found to be not dependent on membership of any of the three formal symmetry groups into which the bis-adducts can be classified. The second pyrrolidine adduct reinforces the perturbation of the forbidden and, to a lesser extent, the allowed transitions of the fullerene core. From a comparison with the spectra of C 60 [C(COOEt) 2 ] and its bis-adducts, it was concluded that the N atom in the pyrrolidine five-membered ring adduct is a less efficient blocker of through-bond and/or through-space communication than the sp 3 carbon atom in Bingel–Hirsch methanofullerenes.

A new methanofullerene, C 61 (poly(aryl)acetylene) 2 , where the mono-adduct contains dendrimer units, has been studied with respect to its photophysical properties. The visible absorption and the emission spectra, the triplet molar extinction coefficient as well as the near unity value of the quantum yield of singlet oxygen production upon photoexcitation reveal characteristics in keeping with other methanofullerenes previously studied, where the addend species is not an electron donating group. The results indicate that, even when the methanofullerene is photoexcited, this large addend does not electronically communicate through the methano bridge neither through space. Photophysical properties of methanofullerenes can thus be preserved when they are functionalised with such addends.

The fluorescence spectra, quantum yields and lifetimes of C70 and a pseudo-dihydro derivative (C70R) have been measured in a wide range of solvents at room temperature. This information is important for the development of reverse saturable absorbers. Phosphorescence spectra and phosphorescence lifetimes were also measured at low temperature. The fluorescence is subject to quenching by halogenated compounds. The eAciency of quenching follows the order I > Br Cl. The nature of the quenching is shown to vary, with chlorinated compounds exhibiting static quenching of fullerene fluorescence, owing to nonfluorescent complex formation, whilst those compounds containing bromine and iodine exhibit dynamic quenching due to the external heavy-atom eAect, that increases the intersystem crossing rate constant in the fluorophore‐perturber complex. This constant is evaluated by an original method from the bimolecular quenching rate constants. The phosphorescence quantum yield of both fullerenes at 77 K slightly increases in the presence of iodobenzene, in spite of a strong decrease in phosphorescence lifetime. The marked increase of the intersystem crossing rate constant in concentrated solutions owing to the external heavy-atom eAect is of interest for the application of fullerenes as fast-responding optical limiters (reverse saturable absorbers) of intense laser pulses, even in cases where the triplet quantum yield is of the order of unity. ” 2001 Elsevier Science B.V. All rights reserved.

Using pulse radiolysis and laser flash photolysis, we have investigated the reactions of the deleterious species, e(-)(aq), HOz, O(2)(*)(-) and O(2)((1)Delta(g)) with 10 water-soluble cyclopropyl-fused C(60) derivatives including a mono-adduct dendro[60]fullerene (d) and C(60) derivatives based on C(60)[C(COOH)(2)](n=2-6), some of which are known to be neuroprotective in vivo. The rate constants for reactions of e(-)(aq) and HOz lie in the range 0.5-3.3 x 10(10) M(-1) s(-1). The d and bis-adduct monoanion radicals display sharp absorption peaks around 1000 nm (epsilon = 7 000-11 500 M(-1) cm(-1)); the anions of the tris-, tetra-, and penta-adduct derivatives have broader, weaker absorptions. The monohydroxylated radicals have their most intense absorption maxima around 390-440 nm (epsilon = 1000-3000 M(-1) cm(-1)). The anion and hydroxylated radical absorption spectra display a blue-shift as the number of addends increases. The radical anions react with oxygen (k approximately 10(7)-10(9) M(-1) s(-1)). The reaction of O(2)(*)(-) with the C(60) derivatives does not occur via an electron transfer. The rate constants for singlet oxygen reaction with the dendrofullerene and eee-derivative in D(2)O at pH 7.4 are k approximately 7 x 10(7) and approximately 2 x 10(7) M(-1) s(-1) respectively, in contrast to approximately 1.2 x 10(5) M(-1) s(-1) for the reaction with C(60) in C(6)D(6). The large acceleration of the rates for electron reduction and singlet oxygen reactions in water is due to a solvophobic process.

Using semi-empirical AM1 calculation and 6.31G∗ basis sets, we have calculated the energy of the highest-occupied molecular orbital (E HOMO ) for anti-inflammatory 4,5-diarylpyrroles which have been shown to have inhibitory activity on cyclooxygenase COX-2, an inducible enzyme expressed during inflammation. We have found a correlation between the E HOMO of a molecule and its COX-2 inhibition. However, no correlation was observed between E HOMO and the inhibition efficiency of cyclooxygenase-1 (COX-1), the constitutively expressed enzyme, protective to the organism. This result suggests that the inhibitions of the two isoforms follow different molecular mechanisms.

The purpose of the present work has been to seek a correlation of potential predictive value, demonstrating redox control of cytotoxicity toward human nasopharynx carcinoma (KB) cells by seven 5-hydroxy-7-methoxyflavones, together with two glycoside derivatives, all extracted from Lethedon tannaensis. In this approach, redox control is characterized by a physicochemical parameter expressing quantitatively the relative electron-donating power of the flavones, this parameter being the second order rate constant, kdelta, for quenching of singlet oxygen O2 (1deltag). This rate constant kdelta is usually related to the ability of a given molecule D to donate an electron and, thus, with the reduction potential E of the couple (D*+/D). Our results show that the flavone toxicity is linearly correlated with ease of oxidation: the higher the rate constant of reaction with singlet oxygen, the easier the oxidation, the less positive or more negative the reduction potential ((D*+/D), the higher the cytotoxicity. The results suggest new screening strategies to identify and improve potential antitumor drugs.

Using a simple quantum mechanical method, we calculated the energy of the highest-occupied molecular orbital (E(HOMO)) of three groups of anti-inflammatory compounds, and we have found correlations between E(HOMO) of these molecules and experimental data previously reported on (1) inhibition of sheep-vesicular-gland prostaglandin cyclooxygenase by phenolic compounds, (2) inhibition of prostaglandin cyclooxygenase in mouse macrophages by salicylates, benzoates and phenols, and (3) peroxyl-radical scavenging and radioprotection of a bacterial virus by NSAID drugs, including metiazinic acid, sulindac, D-penicillamine, piroxicam, indomethacin, benoxaprofen, and aspirin. Our correlations using a systematic evaluation of the HOMO energies can be of predictive value in the search for new anti-inflammatory drugs as well as for new radioprotectors.

The ground-state absorption spectrum of C 76 was measured in toluene solution over the interval 300–1100 nm. Pulse radiolysis and laser flash photolysis have been used to determine properties of the lowest triplet-state of C 76 in benzene, including the triplet difference spectrum between 310 and 1100 nm, the difference and absolute molar absorption coefficients at 840 nm (e=4460 and 5730 M −1 cm −1 , respectively), the quantum yield of triplet formation ( Φ T =0.03±0.01) and the quantum yield for C 76 -sensitized formation of singlet oxygen in aerated benzene ( Φ Δ =0.04±0.01). Our results suggest that the S 1 –T 1 interval is smaller than in C 60 . The strongly lipophilic nature of C 76 , coupled with its low triplet and sensitized singlet oxygen yield, suggests its use as a carrier for delivery of highly polar drugs to hydrophobic sites and tissues without phototoxic sensitization.

Ground and triplet state spectroscopic and photophysical properties of C60H18 and C60H36 have been studied using the complementary techniques of nanosecond pulse radiolysis and laser flash photolysis to determine triplet-triplet (T-T) absorption spectra, triplet lifetimes, T-T molar absorption coefficients and triplet quantum yields, in particular for C60H18. The spectroscopic and photophysical propperties of C60H18 are similar to those of an sp2 network species such as C60. whereas those of C60H36 resemble benzene. No T-T absorption was observed for C60H36 at λ > 300 nm, so that its triplet state parameters could not be measured. The most probable assignment of the C60H36 samples studied, on the basis of vibrational and electronic spectra and structure, is to an S6 symmetry isomer, but the lowest energy T and D3d isomers are not entirely excluded. Our partially hydrogenated fullerene samples were prepared by a transfer hydrogenation method. Other preparation techniques may have produced other isomers of these species, thus accounting for some differences in reported spectroscopic results.

The ground state and lowest triplet state properties of three hydrofullerenes, C60H2, C60H4 and [1-methylsuccinate-4-methyl-cyclohexadiene-2,3]buckminsterfullerene, have been investigated in toluene at room temperature. Their visible ground state absorption spectra are compared to those of methanofullerenes and methanolfulleroids. The triplet properties, including the absorption spectrum between 300 and 800 nm, molar absorption coefficient, quantum yield of formation and quantum yield for the photosensitized production of O 2 ( 1 Δ g ) , are compared to those of other C60 derivatives.

Experiments were caried out to confirm the existence of nanoampere mm-2 currents photoinduced in bilayer lipid membranes (≈40 A width) containing C60 or C70 fullerenes and to explore possible mechanism of electron transport in these model light harvesting and conversion systems. Thermodynamic considerations indicate the electron transfer occurs via reduction of fullerene triplets. This supported by triplet quenching experiments. No photocurrent change was observed when an ionic gradient was imposed on the membrane or when its ionic permeability was modified. This is consistent with an eletron-hopping mechanism. The following parameters were varied: membrane thickness, fullerenes concentration, applied membrane potential, light intensity and intermittency. The results indicate that electron transport is mediated by fullerene aggregates that span the membrane and that light excitation can either enhance or diminish fullerene aggregation and electron transfer, according to its intensity.

Pulse radiolysis and laser flash photolysis have been used to determine properties of the lowest triplet state of C70 in benzene at room temperature, including its absorption spectrum between 300 and 1620 nm, its molar absorption coefficients (ϵT=3800 dm3 mol−1 cm−1 at 970 nm) and its quantum yield of formation in benzene T=0.76±0.15. Measurements were also made of the quantum yield Δ=0.82±0.15 for the C70 sensitised formation of O2(1Δg). Transition assignments, oscillator strengths, and optical limiting properties of C70 are discussed.

Pulse radiolysis and, to a lesser extent, laser flash photolysis have been used to determine properties of the lowest triplet of C 60 in benzene at room temperature, including its absorption spectrum between 300 and 1600 nm, its molar absorption coefficient (ϵ T = 20200 ± 2000 dm 3 mol −1 cm −1 at 750 nm) and its quantum yield of formation (Φ T = 0.88 ± 0.15). The features of the triplet spectrum are assigned according to the triplet transition energies based on molecular orbital calculations previously reported; the strong band at 750 nm is attributed to the 2 3 G u -1 3 T 2g transition. Implications of the results are discussed, including those related to C 60 as an optical limiting material.

Four transient species have been detected in the time scale 10−9 to 10 seconds following pulse radiolysis of dimethyl sulphoxide.

1. 1. Semiquinone anion minus quinone (Q − -Q) and neutral semiquinone minus quinone (QH-Q) difference spectra have been measured for plastoquinone-9, ubiquinone-10 and ubiquinone-0, using pulse radiolysis in methanolic solution. The difference spectra were used to determine the absolute spectra of each semiquinone. 2. 2. The (Q − -Q) difference spectrum for plastoquinone-9 is similar to the difference spectrum detected at a time less than 20 ns after flash excitation of the photosynthetic light reaction Photosystem II in spinach chloroplasts [Stiehl, H. H. and Witt, H. T., (1968) Z. Naturforsch. 23b, 220–224; Witt, H. T. (1971) Q. Rev. Biophys. 4, 365–477]. 3. 3. The ubiquinone Q − -Q spectra are similar to difference spectra found on illumination of reaction centre preparations from Rhodopseudomonas spheroides and Rhodospirillum rubrum [Slooten, L. (1972) Biochim. Biophys. Acta 275, 208–218; Clayton, R. K. and Straley, S. C. (1972) Biophys , J. 12, 1221–1234]. Ubiquinone has been suggested to be closely associated with the primary electron acceptor of bacterial photosynthesis. 4. 4. Rate constants were measured for formation of semiquinones by reaction of e staggered− staggeredCH 3 OH , ĊH 2 OH and ĊH 2 O − with quinone, and for the decays of the neutral semiquinones. The semiquinone anions were stable for seconds. The ubisemiquinone-6 anion reacts only slowly with oxygen, k ≈ 10 3 M −1 · s −1 . 5. 5. The effect of substituents upon semiquinone physicochemical properties is discussed.

Nanosecond flash photolysis has been carried out on benzophenone solutions in benzene and acetonitrile in presence of oxygen- and sulfur-containing reductants such as anisole, thioanisole, dibutyl sulfide and methyl 2-octyl ether. The quantum yield of ketyl formation is compared to previous results on the quantum yields of the final benzophenone disappearance. This comparison is also related to previous data on benzophenone reduction by nitrogen-containing reductants such as amines and amides and suggests a general mechanism for benzophenone photoreduction by heteroatom-containing donors.

The triplet—triplet absorption spectra, quantum efficiencies of intersystem crossing, triplet extinction coefficients, and triplet energy levels of 1,6-diphenyl-1,3,5-hexatriene, and 1,8-diphenyl-1,3,5,7-octatetraene, in ethanol and benzene have been obtained. The quantum efficiencies of intersystems crossing are found to be less than 0.03 for both molecules in both solvents, indicating that the excited singlet is efficiently deactivated by internal conversion and flourescence emission. The triplet—triplet absorption spectra and the triplet energy level of 1,6-diphenyl-1,3,5,hexatriene are compared with previous results in other solvent systems.

Oscillator strengths for triplet-triplet transitions in fluid solution are reported. From these results and from a comparison with previous work, experimental support is provided for the constancy of triplet-triplet oscillator strengths under various solvent and temperature conditions.

Pulse radiolysis of o- m-, and p-xylene mesitylene and and pseudocumene give rise to three main absorption spectra at about 600,400 and 320 nm. Those transients might be correlated to an excimer state (600nm) a biradical (320 nm) a triplet state (400 nm).