Photoprotection by carotenoids during photosynthesis: motional dependence of intramolecular energy transfer.

A new carotenoporphyrin has been prepared in which a synthetic carotenoid is joined to a tetraarylporphyrin through a flexible trimethylene linkage. This molecule exists primarily in an extended conformation with the carotenoid chromophore far from the porphyrin pi-electron system. In benzene solution, where large-amplitude molecular motions are rapid, the molecule can momentarily assume less stable conformations which favor triplet energy transfer, and quenching of the porphyrin triplet by the carotenoid is fast. In a polystyrene matrix or frozen glass such motions are slow, and energy transfer cannot compete with other pathways for depopulating the triplet state. These observations help establish the requirements for biological photoprotection.

Mechanism of action in a 4,5-diarylpyrrole series of selective cyclo-oxygenase-2 inhibitors.

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.

Molecular orbital theory applied to the study of nonsteroidal anti-inflammatory drug efficiency.

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.

Redox regulation of tumor cell toxicity by flavones from Lethedon tannaensis.

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.

Reactions of e(-)(aq), CO(2)(*)(-), HO(*), O(2)(*)(-) and O(2)((1)delta(g)) with a dendro[60]fullerene and C(60)[C(COOH)(2)](n) (n = 2-6).

Using pulse radiolysis and laser flash photolysis, we have investigated the reactions of the deleterious species, e(-)(aq), HO&z.rad;, 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 HO&z.rad; 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.

DNA-photocleavage agents.

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.

Photophysical properties of the ground and triplet state of four multiphenylated [70]fullerene compounds.

The particular chromophoric structure of C(70)Ph(10), which consists of two cage-centered π-electron systems, makes its photophysical properties an exception to those found for other phenylated [70]fullerenes C(70)Ph(2n) (n=2-4). For these other C(70)Ph(2n) species, their intrinsic photophysical properties undergo smooth transitions as a function of n.

Deactivation of singlet molecular oxygen by organo-selenium compounds exhibiting glutathione peroxidase activity and by sulfur-containing homologs.

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.

Singlet molecular oxygen quenching by saturated and unsaturated fatty-acids and by cholesterol.

The rate constants of molecular singlet oxygen quenching by saturated and unsaturated fatty-acids and by cholesterol-membrane critical components - membrane critical components - have been measured by time resolved detection of the 1270 nm phosphorescence of singlet molecular oxygen [O2(1deltag)]. We have determined (i) an increment of 5.7 x 10(2)M(-1)s(-1) per -CH2- in C6D6 and CD3OD for saturated fatty acids between C4 and C20, (ii) an increment of 3 x 10(4)M(-1)s(-1) per non-conjugated cis-double bond for C18 unsaturated fatty acids, identical in C6D6 and DC3OD, (iii) a lower quenching rate constant by a factor of 2.7 for the trans-C16 and trans-C18 as compared to the corresponding cis-monounsaturated fatty acids, (iv) a rate constant of O2x(1deltag) quenching by cholesterol of 5.7 x 10(4)M(-1)s(-1) in benzene. These rate constants are compared to those obtained for other membrane cellular components.

Quantum yields of triplet and O2(1 delta g) formation of 4-thiouridine in water and acetonitrile.

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.

Photophysical properties of 2-nitro-5,10,15,20-tetra-p-tolylporphyrins.

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.

[Correlation of the rates of singlet oxygen inactivation by phenols and their efficacy in the inhibition of neoplasms induced by benzo(a)pyrene]. / Corrélation entre les vitesses de désactivation de l'oxygène singulet par les phénols et leur efficacité dans l'inhibition de néoplasies induites par le benzo (a) pyrène.

Prooxidant states, characterised by an increase in the intracellular concentration of activated forms of oxygen, are able to promote tumors. The inhibitory effects of synthetic phenolic compounds added to the diet of mice on benzo(a)pyrene-induced neoplasia of the forestomach have been determined by Wattenberg et al. The efficiency of this inhibition has been estimated quantitatively for each phenol, using the ratio R of the number of tumors per mouse in the treated group over the number of tumors per mouse in the control group. We have observed a linear correlation between the antitumoral efficiency (1-R) and the logarithm of the rate of quenching of singlet oxygen, k, y, by this family of phenols, log k being itself correlated with the half-wave oxidation potential of the phenols. These correlations suggest a charge transfer mechanism for the inhibition of neoplasia induced by benzo(a)pyrene, B(a)P. It should be pointed out that singlet oxygen can be generated via enzymatic reactions in the dark and thus might play a role in the formation of the ultimate carcinogenic metabolite B(a)P-7, 8-dihydroxy-9, 10-epoxide. The correlations described emphasize the interest in scaling the inhibitors of mutagenicity induced by polycyclic aromatic hydrocarbons with respect to their oxidation potentials. Our result is a first step towards a better understanding of the molecular reactions involved in chemically-induced neoplasia and in its prevention.

Redox properties of phenols, their relationships to singlet oxygen quenching and to their inhibitory effects on benzo(a)pyrene-induced neoplasia.

The inhibitory effects of synthetic phenolic compounds on benzo(a)pyrene-induced neoplasia of the mouse forestomach have been measured by Wattenberg et al. 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 by benzo(a)pyrene. The correlations described provide a theoretical basis for scaling the inhibitors of mutagenicity induced by polycyclic aromatic compounds in terms of their oxidation potentials.

One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C.

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 x 10(8) 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.

Orientation and linear dichroism characteristics of porphyrin-DNA complexes.

The linear dichroism spectra of complexes of tetrakis(N-methyl-4-pyridinio)prophine (H2TMpyP) and its zinc(II) derivative (ZnTMpyP) with DNA oriented in a flow gradient have been investigated. The dichroism of H2TMpyP determined within the Soret band and the Qy band system is consistent with an intercalative conformation in which the plane of the porphyrin ring system is nearly parallel to the planes of the DNA bases. In the case of ZnTMpyP on the other hand, the porphyrin ring system is inclined at angles of 62-67 degrees with respect to the axis of the DNA helix. The pyridyl groups in both cases are characterized by a low degree of orientation with respect to the axis of the helix. In contrast to H2TMpyP which does not significantly affect the degree of alignment of the DNA in the flow gradient, the binding of ZnTMpyP causes a significant decrease (about 50% for a base pair/ZnTMpyP ratio of 20) in the intrinsic dichroism at 260 nm due to the oriented DNA bases; the binding of ZnTMpyP to DNA either gives rise to regions of higher flexibility or causes bends or kinks at the binding sites. Increasing the ionic strength has little influence on the linear dichroism of the ZnTMpyP-DNA complexes, but the number of molecules bound at intercalation sites diminishes in the case of the H2TMpyP-DNA complexes; the accompanying changes in the linear dichroism characteristics suggest that external H2TMpyP complexes are formed at the expense of intercalation complexes.(ABSTRACT TRUNCATED AT 250 WORDS)