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Abréviations et acronymes : CNRS : Centre national de la recherche scientifique CEA : Commissariat à l’énergie atomique, devenu en 2010 Commissariat à l’énergie atomique et aux énergies alternatives (CEAEA) Inra : Institut national de la recherche agronomique ISMO : Institut des sciences moléculaires d’Orsay MNHN : Muséum national d’histoire naturelle SIRLaF : Société internationale de radiobiologie de langue française ERO : Espèces réactives de l’oxygène ROS : Reactive Oxygen Species Genèse ...

La parabole des aveugles de Pieter Brueghel, exergue de l’exposition du Louvre inspirée de l’essai de Jacques Attali : « Une brève histoire de l’avenir ». En 1943, Thomas Watson (1874-1956) le « chairman » de l’International Business Machines (IBM) écrivait: « I think there is a world market for maybe five computers ». En 1960, la France ne disposait que de quelques machines IBM 704, toutes rapidement saturées : pour le secteur public, les universités, l’Institut Henri Poincaré, le laboratoi...

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.

Quelques fructueuses collaborations du groupe Magat et de certains de ses successeurs sont décrites brièvement. Elles résultent des interactions avec des spectroscopistes, des physico-chimistes, des photochimistes, des photobiologistes et des médecins de nombreux laboratoires français et étrangers. This article briefly presents some of the fruitful collaborations of the Magat group and some of his successors among which spectroscopists, physical-chemists, photochemists, photobiologists, radiobiologists and doctors of medicine active in numerous laboratories in Paris and abroad.

A large number of molecules referred to here as M, several of which are extracted from plants, belong to different chemical classes and exhibit chemoprotective activity against carcinogenesis and inflammation in rodents and in vitro cell culture. The aim of this article is to review and analyse our previous investigations on linear correlations observed between physicochemical parameters of the tested molecules M and their biological efficacies measured in vivo and/or in vitro. The principal physicochemical parameters studied characterise the energy required to oxidise M into M•+, E(M•+/M), namely its first vertical ionisation potential, and the energy liberated by the addition of an electron to M, i.e. its vertical electron affinity. These physicochemical properties were determined experimentally using diverse techniques and theoretically using mainly semiempirical (AM1) and density functional theory (DFT) quantum mechanical methods.

DIBAL-H-mediated demethylation provides a novel method to access secondary-rim functionalized γ-cyclodextrin. 2

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.

Cancer-preventive activity by exogenous molecules can be mediated by enhancing the expression of cytoprotective enzymes [e.g, glutathione- S-transferase (GST) or NAD(P)H-quinone oxidoreductase 1 (NQO1)] via antioxidant-response elements (AREs) present in the promoter regions of their genes. Previously, potency of induction of NQO1 has been linearly correlated with the ability to release an electron from different classes of inducers, including diphenols, phenylpropenoids, and flavonoids. In the present work, we focus on the induction of NQO1 by diphenols, which we consider as a model underlying the mechanisms of action of other phenolic inducers such as phenylpropenoids and flavonoids. A two-step mechanism of NQO1 activation is proposed involving (i) oxidation of diphenol inducers to their quinone derivatives and (ii) oxidation of two highly reactive thiol groups by these quinones of a protein involved in NQO1 induction. These two putative routes are supported by linear correlations between the inducer potencies and the redox properties of diphenols and of their corresponding quinones. The linear correlations demonstrate the possibility to predict the enhanced gene expression of enzymatic defenses by diphenols from quantum mechanical calculations (i) of the ability of diphenols to release electrons and (ii) of the electron affinity of their corresponding quinones.

We have synthesised nine monomeric azaheterofullerene (AZA) derivatives, RC(59)N, with a wide variety of different side chains R and investigated their spectroscopic and photophysical properties in toluene and o-dichlorobenzene (ODCB). Measurements include their ground-state absorption spectra, molar absorption coefficient (epsilon(G)), fluorescence spectra, fluorescence quantum yields (Phi(F)), singlet-state lifetimes (tau(F)), triplet-state absorption spectra, triplet molar absorption coefficients (epsilon(T)), singlet oxygen (Phi(Delta)), and triplet state (Phi(T)) quantum yields. The replacement of a carbon by a nitrogen atom in the C(60) sphere strongly affects most of the spectroscopic and photophysical properties. The chemical nature of the R moiety has definite effects on these properties in contrast with minor effects on the chemical nature of the addends in [6,6]-ring bridged monoadduct methano[60]fullerene derivatives. These effects concern properties of the ground state, singlet excited state, and triplet states of our nine RC(59)N derivatives and in particular the values of photophysical parameters epsilon(G), epsilon(T), Phi(Delta), and Phi(T), which are significantly lower than those of analogous monoadduct [6,6]-ring bridged methano[60]fullerene derivatives.

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.

The results of a laser flash photolysis investigation of a dendritic methano[60]fullerene octadeca-acid (DA) and its tert-butyl ester (DE) are reported. DE possesses photophysical properties typical of a [60]fullerene mono-adduct with a singlet oxygen quantum yield approaching unity in toluene and a triplet absorption spectrum with a maximum at 710 nm. In methanol DA also possesses properties typical of a [60]fullerene mono-adduct, but in aqueous solution its photophysical behaviour shows a degree of aggregation that is a function of pH and concentration. At pH 7.4 and higher, Coulombic repulsion between de-protonated carboxylate groups reduces the propensity to aggregation and dilute solutions (

For a group of seven isomeric N-mTEG[60]fulleropyrrolidine bis-adducts (mTEG = CH2CH2OCH2CH2OCH2CH2OCH3), the quantum yields of singlet oxygen (O2, 1Δg) production and the maximum triplet molar absorption coefficients were found to be separately correlated with the shortest distances and with the number of bonds connecting the two addends on the fullerene sphere.

International audience; To resolve conflicting results in the literature, we determine quantitatively the properties of the lowest triplet excited state of water soluble 2:1 host:guest complexes of C$_{60}$ embedded in $\gamma$-cyclodextrin ($\gamma$-CD/C$_{60}$) using laser flash photolysis. The results show that the triplet excited state characteristics of $\gamma$-CD/C$_{60}$ in aqueous solutions are very similar to those observed for C$_{60}$ in organic solvents. Moreover oxygen, in contrast with non-gaseous solutes, can reach the proximity of C$_{60}$ embedded in 2:1 $\gamma$-CD inclusion complexes. In addition, photodestruction quantum yields have been determined for C$_{60}$ in toluene and for C$_{60}$ in $\gamma$-CD inclusion complexes in water.

Laser flash photolysis and pulse radiolysis have been used to determine properties of the lowest triplet state of a series of water-soluble malonic acid derivatives of C60 , C60[C(COOH)2]n with n = 2–6, in water at pH 7.4. Similar studies were carried out on the corresponding ethyl esters, C60[C(COOEt)2]n with n = 1–6, in the non-polar solvents, benzene or toluene. The properties include the T–T absorption spectra, the triplet molar absorption coefficients and the quantum yields of formation, ΦT and ΦΔ of the triplet and of singlet oxygen, respectively. This study shows a general tendency of the λmax of the T–T absorption spectra, and of the ΦΔ values to decrease with increasing number of addends. For regioisomers, the spectroscopic and photophysical parameters are modulated with the pattern of addition. The ΦΔ quantum yields for the acids in aqueous solution are systematically lower than those of the ethyl esters in toluene. The lower ΦΔ values observed for the acids in aqueous solution, and to a lesser extent for the esters in benzonitrile, can be interpreted as due to the presence of solute clusters in polar solvents.

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.

Redox reactions of endogenous and exogenous sulphur-containing compounds are involved in protection against oxidative damage arising from the incidence and/or treatment of many diseases, including cancer. We have investigated, via pulse radiolysis, the one-electron oxidation of ergothioneine, a molecule with antioxidant properties which is detected at millimolar concentrations in certain tissues and fluids subject to oxidative stress, including erythrocytes and plasma. The spectrum of the transient species, assigned to the product of one-electron oxidation, observed after reaction of ergothioneine with the oxidizing radicals OH•, N3• and CCl3O2• has a maximum absorption at 520 nm and is very similar to that obtained by oxidation of analogous molecules such as 2-mercaptoimidazole, 1-methyl-2-mercaptoimidazole, S-methyl- and S,N-dimethyl-ergothioneine. In the presence of vitamin C, the oxidized form of ergothioneine is repaired by a rapid reduction (k = 6.3×108 M-1·s-1) producing ascorbyl radicals. This co-operative interaction between ergothionine and ascorbate, similar to that previously observed between vitamin E and ascorbate, may contribute to essential biological redox protection.

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.

A study was made of the solubilization of C[sub 60] in various solvents and systems of biological interest, i.e., octanols, micelles, and liposomes, using visible-UV absorption spectroscopy as a diagnostic tool. The state of incorporation of C[sub 60] molecules in micellar and colloidal liposome solutions was monitored using a number of spectroscopic criteria of solute-solvent and solute-solute interactions based on comparison with spectra obtained in alkane and octanol solvents and from thin films of C[sub 60]. Spectral red shifts and intensity modifications of C[sub 60] absorption and C[sub 60] aggregation are discussed in terms of environment-dependent physical parameters. The results indicate that C[sub 60] can be dispersed in micellar solutions of Triton X-100 and Triton X-100 R-S, the fullerene molecules being localized in the inner hydrophobic part of the micelles. C[sub 60] was shown to be incorporated, mainly as aggregates, into phosphatidylcholine liposome colloidal solutions. It is concluded that micellar and liposome solutions can be prepared which could be used to transfer individual C[sub 60] molecules, or groups of molecules, to biological cells. 38 refs., 9 figs., 2 tabs.

DNA topoisomerases, enzymes involved in DNA replication and transcription, are known as targets for anticancer drugs. Among the various types of topoisomerase inhibitors, flavones (F) have been identified as promising compounds. In this study, it is shown that the potency of flavones acting as topoisomerase I inhibitors can be ranked according to their redox properties and their 3D structure. Linear correlations were observed between the topoisomerase I inhibition activity exerted by five flavones (chrysin, apigenin, kaempferol, fisetin, quercetin) and experimental and theoretical redox parameters of F. Moreover, theoretical calculations of the dihedral angle O(1)-2-1'-2' in the flavone molecules indicate the importance of their structural and steric features in their potency as topoisomerase I inhibitors. It is suggested that the flavones might interact with the DNA-topoisomerase I complex after their oxidation into quinones via autoxidation, enzymatic oxidation, or reactions with reactive oxygen species. Our investigation opens a new strategy quantitatively based on redox and 3D structural parameters in the search for the most active flavones as anticancer drug candidates inhibiting topoisomerase I.

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.

Transient electronic spectra of mono-hydroxylated fullerene radicals, initially derived from water soluble malonic acid derivatives (C60[C(COOH)2]n, n = 2–6) reacting with hydroxyl radical at a diffusion-controlled rate, show a unimolecular growth in absorption on a timescale of 0.1–1 ms. It is suggested that the reason for this slower growth is migration of the hydroxy group to a more stable position. Semi-empirical molecular orbital (AM1 and PM3) calculations on the symmetry-distinct C60[C(COOH)2]3OH− anions derived from two most abundant tris(malonate)s demonstrate a relation between Coulson’s free valence index for radical attack at a particular position and the stability of the corresponding product. They also suggest that after attack of the hydroxyl radical at the first encountered double bond, migration subsequently takes place to the position of highest free valence.

Transient electronic spectra of mono-hydroxylated fullerene radicals, initially derived from water soluble malonic acid derivatives (C60[C(COOH)2]n, n = 2–6) reacting with hydroxyl radical at a diffusion-controlled rate, show a unimolecular growth in absorption on a timescale of 0.1–1 ms. It is suggested that the reason for this slower growth is migration of the hydroxy group to a more stable position. Semi-empirical molecular orbital (AM1 and PM3) calculations on the symmetry-distinct C60[C(COOH)2]3OH− anions derived from two most abundant tris(malonate)s demonstrate a relation between Coulson’s free valence index for radical attack at a particular position and the stability of the corresponding product. They also suggest that after attack of the hydroxyl radical at the first encountered double bond, migration subsequently takes place to the position of highest free valence.

Electron affinity (EA) and electrophilicity index (omega) of 16 synthetic triterpenoids (TP), previously identified as inducers of cytoprotective enzymes and as inhibitors of cellular inflammatory responses, have been calculated by the molecular orbital method. Linear correlations were obtained by plotting the values of EA, as well as those of omega versus (i) the potencies of induction of NAD(P)H quinone reductase (NQO1, EC 1.6.99.2), a cytoprotective enzyme, expressed via the concentration of TP required to double the specific activity of NQO1 (CD value) and (ii) the values of their anti-inflammatory activity expressed via the IC-50 of TP for suppression of upregulation of inducible nitric oxide synthase (iNOS, EC 1.14.13.39), both previously experimentally determined. The observed correlations demonstrate quantitatively for a series of triterpenoids that their electrophilicity is a major factor determining their potency as inducers of the cytoprotective phase 2 response and as inhibitors of inflammatory processes.

A variety of molecular triads and dyads consisting of covalently linked carotenoid (C) andor porphyrin (P) moieties have been prepared and studied with transient absorption and time-resolved fluorescence techniques. Diporphyrins of the type P A -P B and C-P A -P B triads demonstrate interporphyrin singlet-singlet energy transfer with rate constants ranging from 8.1×10 8 to 2.3×10 10 s −1 . Interporphyrin photoinitiated electron transfer is observed in molecules possessing sufficient thermodynamic driving force to produce P A •+ -P B •− and C-P A •+ -P B •− charge-separated states. The electron-transfer rate constant increases with increasing reaction free energy change for the molecules studied, and rate constants up to 3.5×10 9 s −1 and quantum yields up to 0.68 were measured. The carotenodiporphyrin triad systems undergo a subsequent electron-transfer step to give final C •+ -P A -P B •− states

The quantum yield of triplet formation, phi T, and that of the photosensitized formation of singlet molecular oxygen, phi delta, were determined for a rare nucleoside, 4-thiouridine (4t-Urd), in water and in acetonitrile, using singlet molecular oxygen phosphorescence, laser-induced optoacoustics and time-resolved thermal lensing. These yields, phi T and phi delta, the latter in aerated solutions, were found to be, respectively, in water: 0.67 +/- 0.17 and 0.18 +/- 0.04 and in acetonitrile: 0.61 +/- 0.15 and 0.50 +/- 0.20. The fraction of the 4t-Urd triplet molecules quenched by oxygen leading to singlet molecular oxygen, S delta, was calculated to be between 0.7 and unity in both solvents, this value being indicative of a pi pi*character for the lowest triplet state of 4t-Urd.

Tetraarylporphyrins substituted with nitro groups at beta-pyrrolic positions are potential candidates for electron-accepting pigments in model systems for photosynthesis. The photophysics of 2-nitro-5,10,15,20-tetra-p-tolylporphyrin and its zinc analog have been studied in order to evaluate this potential. The ground state absorption spectrum, the triplet-triplet absorption spectrum, the fluorescence emission spectrum, and associated photophysical parameters have been determined. The molecules have short singlet lifetimes and anomalous temperature- and solvent-dependent emission spectra which are consistent with the formation of an intramolecular charge transfer state of the type P+.-NO2-. in which the nitro group is twisted about its bond to the porphyrin, relative to the ground state conformation.

A series of five 3-nitroflavones were tested for their ability to inhibit the formation of colon aberrant crypt foci (ACF) induced by a s.c. injection of azoxymethane (C2H6N2O) in rats. Our aim was to relate the electron-donating effects of the 3-nitroflavones as characterized by their Hammett substitution constants with their efficacy in inhibiting ACF. In a first assay (initiation, protocol A) the 3-nitroflavone as well as the 4'-substituted nitro-, methoxy-, fluoro-, and hydroxy-3-nitroflavones were continuously present in the diet. In a second assay (postinitiation, protocol B) they were given for a period of 4 weeks after the last azoxymethane injection. The different substituents of the 3-nitroflavones at the 4'-position spanned a spectrum of Hammett constants (sigma(p+)), going from +0.79 for the electron-withdrawing group, NO2, to -0.92 for the electron-donating group, OH. For both protocols the percentages of inhibition plotted versus the Hammett substitution constants showed a linear correlation, the most efficacious ACF inhibition being produced by the molecules with the most electron-donating substituents. Moreover, the nitroflavones were not only chemoprotective during initiation of the ACF, but also therapeutic in the postinitiation progression assay. The above correlations may be of predictive value in the search for new chemoprotective agents. The overall molecular mechanism of the inhibition of ACF by the 3-nitroflavones under study appears to involve redox reactions.

The aim of the present study was to develop an analytical method for measuring amounts of a dendro[60]fullerene (DF) which is a highly water-soluble [60]fullerene derivative. We tried to define a straightforward methodology using capillary zone electrophoresis, a method which, to our knowledge, has not yet been used to that purpose. Preliminary assays showed that DF has almost the same mobility than the electroosmotic flow (EOF) but in the opposite direction. Attempts were carried out to reduce the EOF and positive results were obtained by adding hydroxypropylcellulose to the background electrolyte. In order to define optimal operating conditions, a Taguchi experimental plan was used to study simultaneously the effects of the main parameters that are pH, ionic strength, methanol amount and hydroxypropylcellulose concentration. Two parameters are of the utmost importance as to their effect on the migration time and separation efficiency: pH and ionic strength whose actions are opposite.

This review describes recent advances in the development of DNA- photocleavage agents. Major mechanisms of photosensitized DNA photocleavage are presented and the most popular categories of compounds are considered, which include metal complexes and many organic functional derivatives. DNA-targeted conjugates of photosensitizers are also described and discussed

Aggregation of C60 and of three C60 derivatives in phosphatidylcholine liposome model membranes was studied via photophysical investigations. The triplet properties of these fullerenes, including the absorption spectrum between 400 and 900 nm, molar absorption coefficient, quantum yield of formation and/or quantum yield for the photosensitised production of 1O2 were determined in benzene solution and in liposomes. One of the derivatives was a cyclopropyl-fused hexa-addended C60 containing as addend C(CO2C18H37)2 (1). The other two derivatives were cyclohexyl-fused C60 with leucine (2) or hydrophilic acidic (3) mono-addend functionalisation. The synthesis of derivative 2, by thermal extrusion of sulfur dioxide from the corresponding sulfone in the presence of C60, is described. [60]Fullerene and derivative 1 show no T–T absorption in liposomes, although they do so in benzene solution (with a low triplet quantum yield for hexa-addended 1). The absence of triplet–triplet absorption in liposomes is indicative of fullerene aggregation. By contrast, the amphiphilic mono-addend derivatives 2 and 3 present appreciable T–T absorption in liposomes, although less marked than in benzene solution. Mono-addend functionalisation therefore appears to be an interesting way to prevent or diminish fullerene aggregation. Moreover, in this type of derivatisation most of the photophysical properties of pristine [60]fullerene are retained.

The three [6,6]-ring bridged methanofullerenes 1, 2, and 3 were synthesized; their ground-state absorption spectra in toluene and cyclohexane solutions are presented and possible assignments discussed. Although these three molecules are very different, they have very similar triplet–triplet spectra and near-unity values for the quantum yield for O2(1Δg) production by energy transfer from the triplet states, implying that the quantum yield of triplet production is approximately 1.

Due to its hydrophobic character, the hydrocarbon core of ultrathin phospholipid bilayer membranes lends itself to the insertion of fullerenes. When doped with C 60 these membranes are photoconducting, the photoconductivity being affected by the presence of quenchers of the excited triplet state such as oxygen. The photoconductivity involves trans-membrane electron transfer; its dependence on C 60 concentration and on the excitation wavelength suggests the participation of small aggregates in the membrane. As derived from time-resolved triplet absorption and fluorescence quenching measurements, the suggested mechanism makes more precise (i) the role of the aggregates which might act as a collecting antenna for the benefit of the monomers, and (ii) the role of the monomers which have a much higher yield of photoinduced triplet state formation than the aggregates.

The bimolecular rate constants (k) of quenching of molecular singlet oxygen 1O2 (1 delta g) by organo-selenium compounds exhibiting glutathione peroxidase activity and by sulfur analogs have been determined by time resolved phosphorescence detection of 1O2 in CD3OD and C6D6, with no solvent effect. The rate constants of quenching by the Se-containing compounds were found to be approximately one order of magnitude higher than those of the S-containing homologs. A linear correlation was observed between log k and the Hammett constant omega ortho with p = -0.89, the rate constant being higher for molecules with an electron-donating substituent and lower for those with an electron-withdrawing substituent. This observation is consistent with the involvement of a charge transfer complex in the deactivation of singlet oxygen.

The inhibitory effects of synthetic phenolic compounds on benzo(a)pyrene-induced neoplasia of the mouse forestomach have been measured by Wattenberg et al6 The efficiency of this inhibition has been estimated for each phenol, using R, the ratio of the number of tumors per mouse in the protected group over the number of tumours per mouse in the control group. We have observed a linear correlation between the chemoprotection efficiency R and the logarithm of the rate of quenching of singlet oxygen. k. by this family of phenols, log k being itself correlated with the one-electron oxidation potential of the phenols. These correlations suggest a charge transfer mechanism for the inhibition of neoplasia induced hy benzo(a)py-rene. The correlations described provide a theoretical basis for scaling the inhibitors of mutagenicity induced by polycyclic aromatic compounds in terms of their oxidation potentials

Thermodynamic and kinetic aspects of intramolecular electron-transfer reactions in carotenoporphyrin dyads and carotenoid-porphyrin-quinone triads have been studied by using pulse radiolysis and cyclic voltammetry. Rapid (