[Show abstract][Hide abstract] ABSTRACT: This paper deals with the photosensitizing activity of FLQs towards two different biosubstrates, membrane and DNA. The in vitro phototoxic activity of these drugs vs. DNA presents peculiar features with respect to that vs. membranes, probably due to a specific binding of the drugs to the double helix and to the operativeness of different photosensitization mechanisms with the two types of biosubstrates. A description of the UVA photochemistry and the photosensitizing properties of two significant examples in the FLQ family is reported. The investigated compounds are Enoxacin, 1-ethyl-6-fluoro-1,4-dihydro-4- oxo-7-[1-piperazinyl]-1,8-naphtyridine-3-carboxilic acid and Rufloxacin, 9-fluoro-2,3-dihydro-10-4Ã‚Â´-methyl- 1Ã‚Â´-piperazinyl-7-oxo-7H-pyrido[1,2,3Ã¢ÂˆÂ’de]-1,4-benzothiazine-6-carboxylic acid.
International Journal of Photoenergy 01/1999; · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Copper(II), at very low levels of concentration, modulates the distribution of tolmetin stable photoproducts as well as inhibits the DNA cleavage photoinduced by the drug, via a highly efficient electron transfer process with the main transient species generated in the tolmetin photolysis.
Chemical Communications 01/1999; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The inhibitory effect of Cu2+, Mn2+, Co2+, and I- on naproxen-induced photohemolysis was investigated. In order to better understand this effect, these ions were also tested for lipid peroxidation and protein crosslinking, which are among the main processes involved in erythrocyte membrane damage. The overall results support the hypothesis that metal cations act via a redox scavenging of the radicals which are produced on the lipid component of the membrane. This process occurs through hydrogen abstraction operated by photogenerated naproxen radicals. Moreover, copper can also act as a superoxide anion scavenger: its decay is noxious in photohemolysis, whereas it is not in lipid peroxidation. Metal cations, besides, are not able to scavenge protein crosslinking. On the other hand, iodide is able to reduce both processes because it acts as a heavy atom, favoring intersystem crossing to the unreactive triplet state of the drug, thus reducing naproxen photolysis and, as a consequence, the amount of the damaging species produced. This mechanism was supported by luminescence experiments performed in the absence and in the presence of iodide.
Journal of Inorganic Biochemistry 10/1996; 63(4):253-63. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photocleavage of DNA induced by naproxen and the correlated protective effect by some inorganic ions have been considered. The presence of a DNA complex is suggested and only associated naproxen seems to be responsible for the cleavage, for which the quantum yield of single strand breaks was calculated. The inorganic ions I-, Mn2+, Co2+ and Cu2+ decrease naproxen-photoinduced DNA cleavage. Iodide acts by a heavy atom mechanism, thus inhibiting naproxen photolysis and decreasing the amount of free radicals responsible for the photocleavage both in aerobic and anaerobic conditions. Metallic ions protect only within a range of concentrations, as for higher amounts damaging processes are observed. The protective efficiency of cations decreases with the increase of free drug concentration in the bulk of the solution, due to their involvement in the scavenging of naproxen radicals generated by photolysis of the free drug. In the presence of EDTA the cations show a better protective action. The most likely hypothesis is an inhibiting effect on the damaging processes via a redox cycle. The different behaviors of copper and of the two other cations can be justified by the influence of redox potentials of free and complexed metals and by the superoxide dismutase-like activity of copper.
Photochemistry and Photobiology 05/1996; 63(4):455-62. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The photosensitizing properties of tolmetin, 5-(p-toluoyl)-1-methyl-2-pyrrolyacetic acid (TLM), have been studied in vitro following the lysis of erythrocytes in phosphate buffer suspensions irradiated with UVA light in the presence of the drug. It was found that the phototoxic properties of the drug are negligible in nitrogen and significant in aerated medium, but that they decrease in oxygen-saturated solution. The investigation of the drug photolysis showed that TLM undergoes photodecarboxylation to p-tolyl 1,2-dimethyl-5-pyrrolyl ketone in nitrogen and to p-tolyl 1-methyl-2-hydroxymethyl-5-pyrrolyl ketone and 5-(p-toluoyl)-1-methyl-2-pyrrole carbaldehyde in air. These photoproducts also undergo photodegradation. The comparison between the photohaemolysis and photolysis results and the effect of suitable additives such as sodium azide, mannitol, butylated hydroxy-anisole, reduced glutathione, superoxide dismutase and copper (II) suggest that the phototoxicity of TLM can be attributed essentially to singlet oxygen in the first step and to its photoproducts when they accumulate and compete with the starting drug in light absorption. Their phototoxic effect is much higher with respect to that of TLM, as shown by comparison of the doses needed to attain 50% photohaemolysis.
Journal of Photochemistry and Photobiology B Biology 09/1995; 29(2-3):125-33. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Phosphate buffer suspensions of unilamellar liposomes of phosphatidylcholine were irradiated with UVC (254 nm) and UVB (300 nm) light. The irradiation provoked lipid peroxidation and liposome lysis with release of entrapped glucose-6-phosphate. At the same intensity of absorbed light, the photochemical effect at 254 nm is higher than at 300 nm. The addition of copper(II) and manganese(II) reduced both the peroxidation and the lysis. The copper showed an inhibitory effect only on the process provoked by the 254 nm irradiation, whereas the manganese was efficient both at 254 and 300 nm. The results are interpreted with a mechanism of peroxidation and quenching, involving photoformation of peroxyl radicals that are scavenged by manganese(II) and copper(I), with consequent breaking of the radical chain and reduction of the peroxidation rate. The copper(I), which is the active species, can be formed only at 254 nm by electron capture. The experimental data fit the kinetic equations obtained by the proposed mechanism by means of computer software.
Journal of Inorganic Biochemistry 08/1995; 59(1):1-13. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Unilamellar liposomes (LH) of phosphatidylcholine (PC), dispersed in phosphate buffer at pH 7 (PB), underwent lipid peroxidation and lysis with release of entrapped glucose-6-phosphate when irradiated with UVA light in the presence of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KPF) or 2-(6-methoxy-2-naphthyl)propionic acid (naproxen, NAP), which were used as photosensitizers. Lipid photoperoxidation and consequent lysis were reduced when copper(II), up to 5 microM, was present in the irradiated samples. Suitable experiments were performed to evidence the species responsible for the lipid peroxidation, the copper effect on the drug photodegradation, and the mechanism of the copper antioxidant activity. The overall results suggest that the photoperoxidation was probably initiated by organic radicals obtained from the irradiation of KPF and NAP and the inhibition by copper could be attributed to its interaction with the peroxyl radicals of the drug and/or the liposomes, breaking the propagation of the radical chain.
Journal of Inorganic Biochemistry 03/1995; 57(2):115-25. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Red blood cell lysis photosensitized by Ketoprofen, 2-(3-benzoxyphenyl)propionic acid (KPF), was investigated in the presence of some copper(II) complexes with linear and cyclic dipeptides as well as functionalized beta-cyclodextrins with SOD-like activity with the aim of ascertaining their protective activity towards the photoinduced cell damage. The comparison between the decrease of photolytic activity caused by these complexes and their superoxide dismutase activity showed an appreciable correlation. The correct determination of species existing in experimental conditions was obtained through a simulation approach based on the knowledge of the stability constants of the complexes.
Journal of Inorganic Biochemistry 07/1994; 54(4):257-65. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Red blood cell lysis photosensitized by Suprofen (SPF) and the photolysis of the drug were investigated. The photohemolysis process occurs at a higher rate in anaerobic than aerobic conditions. The effect of additives demonstrates the involvement of free radicals and, to a lesser extent, singlet oxygen and hydroxyl radicals in the process. Photolysis of the drug at 310-390 nm in deaerated buffered solutions (pH 7.4) leads to a decarboxylation process with the formation of p-ethylphenyl 2-thienyl ketone (I), whereas in aerated solutions formation of photoproduct I and of the photoproducts p-acetylphenyl 2-thienyl ketone (II) and p-(1-hydroxyethyl)phenyl-2-thienyl ketone (III) occurs. The photodegradation products, which were separated and characterized, show a moderate lytic and photolytic activity. The rate of SPF photodegradation decreases in the presence of oxygen and increases in the presence of hydrogen donors. The overall results lead us to propose a mechanism of SPF photodegradation and a hemolysis scheme in which cell damage is provoked principally by the direct attack of drug radicals and secondarily by singlet oxygen and hydroxyl radicals.
Journal of Photochemistry and Photobiology B Biology 06/1994; 23(2-3):125-33. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The inclusion in cyclodextrins (CDx) of phenylethylenethioamide (PETA) and naphthylethylenethioamide (NETA) was investigated. For PETA, the UV, induced circular dichroism and nuclear magnetic resonance (NMR) spectra show that the molecule forms an inclusion compound (1 : 1) with α-CDx. From the variation of the absorption spectrum with increasing CDx concentration, the constants of the inclusion equilibrium (450 M−1 and 130 M−1 respectively for the trans and cis isomers) were calculated. The spectroscopic data suggest that for the trans isomer the inclusion involves the double bond, whereas for the cis isomer only the aromatic ring is included. The photochemical results are consistent with this model. Indeed, on irradiation, trans—cis photoisomerization is retarded by the α-CDx cavity (φt-c = 0.13), whereas cis—trans photoisomerization is favoured slightly (φc-t = 0.31): the cavity alters the decay ratio of the twisted state to the ground trans and cis states. For NETA, only the trans isomer forms an inclusion compound with β-CDx as shown by the dependence of the UV spectra on the β-CDx concentration and by the enhancement of fluorescence. The value of the inclusion constant is 270 M−1. However, the trans—cis quantum yield is not influenced by inclusion: only the naphthyl ring is encapsulated and the rotation around the ethylene group probably occurs outside the cavity.
Journal of Photochemistry and Photobiology A: Chemistry. 12/1993; 76(s 1–2):127–133.
[Show abstract][Hide abstract] ABSTRACT: The superoxide dismutase activity of several copper(II) complexes of linear and cyclic dipeptides has been measured. The results of a classic indirect method (xanthine-xanthine oxidase) have been compared with those obtained by generation of the superoxide radical through 2-(3-benzoylphenyl)propionic acid (ketoprofen) photolysis. A simulation approach, based on the knowledge of the stability constants of the different complex species existing in experimental conditions, has allowed us to obtain the correct speciation and to use these data to calculate the pertinent catalytic constants.
Journal of Inorganic Biochemistry 07/1993; 50(4):273-81. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathways of photoreactivity of some nonsteroidal antiinflammatory drugs (NSAID), i.e. propionic acid derivatives indicated in a clinical picture as phototoxic and/or photoallergic, are discussed in a general oversimplified scheme. The NSAID photosensitizing activity, estimated from the ability to induce red blood cell lysis, was found to be dependent on the quantum yield of decarboxylation, which in turn determines the superoxide anion formation, on free radical reactivity and on singlet oxygen production efficiency. An investigation into the NSAID photoinduced cell damage in erythrocytes from various mammalian species, erythrocyte ghosts and unilamellar liposomes, evidenced the role played by membrane proteins and phospholipids. To inhibit phototoxic effects, some systems, including β-cyclodextrin and cupric Ion and its complexes with bio-functionalized ligands, were considered for their ability in protecting cell membranes from the damage, which is photoinduced by superoxide anion, free radicals and singlet oxygen.
[Show abstract][Hide abstract] ABSTRACT: Red blood cell lysis photosensitized by carprofen (CPF) was investigated. The photohemolysis process was observed in both aerobic and anaerobic conditions. Irradiation (310-390 nm) of buffered CPF solutions at pH 7.4 in deaerated conditions leads to a dehalogenation process via intermediate radicals with formation of the compound 2-(2-carbazolyl)propanoic acid (I) in the presence of hydrogen donors. Irradiation of I produces decarboxylation via free radicals and the formation of a stable decarboxylated compound, 2-ethylcarbazole (II). The photodegradation products I and II do not show lytic activity. The dechlorinated product I shows photosensitizing ability which was studied in the presence of the red blood cells in both aerated and deaerated solution. When carried out in the presence of additives, the observed photohemolysis suggests the involvement of free radicals and singlet oxygen in the membrane damage induced by both CPF and photoproduct I irradiation, whereas there is no evidence of any role for hydroxyl radicals. Superoxide anion is involved only in the photosensitization process induced by photoproduct I.
Journal of Photochemistry and Photobiology B Biology 04/1993; 17(3):239-46. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A parallel investigation of the photochemistry of [Ru(CNCH3)5(pyridine-4-aldehyde-4-nitrophenylhydrazone)](BF4)2 and of the organic ligand was carried out at various excitation wavelengths in different solvents. The intraligand syn—anti isomerization was the only photoreaction observed in the complex; it was found that the quantum yields decrease with the excitation wavelength and with solvent polarity and remain unaltered in the presence of triplet quenchers. The only effects produced by ruthenium coordination were a decrease in the quantum yields of isomerization and an increase in the fluorescence quantum yields. The syn—anti isomerization sensitized by 2′-acetonaphthone occurred with almost the same quantum yields in the free and the coordinated ligand.The thermal back reaction anti → syn was observed and the kinetic data were calculatedA mechanism which involves rotation in the excited states via an adiabatic pathway was proposed for the direct photoisomerization of the free and bound ligand, taking into account the effects of the irradiation wavelengths, the solvents and the coordination on the quantum yields of isomerization and fluorescence.
Journal of Photochemistry and Photobiology A Chemistry 11/1989; 50(1):75–82. · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Red blood cell lysis photosensitized by ketoprofen (KPF) was investigated. The photohemolysis was inhibited by butylated hydroxyanisole, reduced glutathione, superoxide dismutase and mannitol, and was unaffected by sodium azide; the presence of oxygen markedly enhanced the lysis. Photohemolysis was also observed under anaerobic conditions. Ketoprofen, irradiated in aqueous buffer solution at pH 7.4, underwent a decarboxylation process via intermediate radicals, leading to the compounds (3-benzoylphenyl)ethane, (3-benzoylphenyl)ethyl hydroperoxide, (3-benzoylphenyl)ethanol and (3-benzoylphenyl)ethanone under aerobic conditions and only to the compound (3-benzoylphenyl)ethane under anaerobic conditions. The four photoproducts showed lytic activity, particularly high for the alcohol and hydroperoxide. The overall results suggest for KPF-photosensitized hemolysis a molecular mechanism involving free radicals, superoxide anion and sensitizer photodegradation products.
Photochemistry and Photobiology 10/1989; 50(3):359-65. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Red blood cell lysis photosensitized by naproxen was investigated. The photohemolysis rate was enhanced by deuterium oxide and inhibited by butylated hydroxyanisole, reduced glutathione, sodium azide and superoxide dismutase. Photohemolysis was also observed under anaerobic conditions. In the absence of red cells the irradiation of deaerated solutions underwent a decarboxylation process via intermediate radicals, while under aerobic conditions photo-oxidation leading to the photoproduct 6-methoxy-2-acetonaphthone occurred. A molecular mechanism involving free radicals and singlet oxygen as important intermediates and consistent with the overall results is proposed.
Journal of Photochemistry and Photobiology B Biology 05/1989; 3(2):223-35. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The irradiation of the complex Ru(CNCH3)5 (4-styrylpyridine)(BF4)2 in CH2Cl2 resulted in the trans-cis isomerization of the coordinated organic molecule. Comparison with the free ligand indicated that the coordination offered some advantages, in that it shifted absorption towards longer wavelengths and increased the quantum yields of isomerization. This increase can be interpreted in two ways: (i) the ruthenium acts as a heavy atom and increases the intersystem crossing efficiency and thus the quantum yields; (ii) the coordination raises the n-π* levels and thus deprives the excited molecule of a non-radiative decay route with retention of configuration.
Journal of Photochemistry and Photobiology A Chemistry 03/1989; 46(3):295-300. · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Irradiation of [Ru(CNCH3)6]2+ at 254 nm induced release of CNCH3 and formation of the monosolvated cation [Ru(CNCH3)5(NCCH3)]2+ in acetonitrile and of the dimeric cation [Ru2(CNCH3)10]4+ in H2O and in CH2Cl2. The photochemical products were isolated as tetrafluoroborate salts and characterized by elemental analysis, conductivity measurements, and 1H NMR, UV and IR spectroscopy. The dimeric cation [Ru2(CNCH3)10]4+ was photochemically stable, but reacted thermally with acetonitrile to give the mixed complex [Ru(CNCH3)5− (NCCH3)]2+, which underwent conversion into the dimeric species when irradiated in an inert solvent. The overall quantum yields of the photoprocesses were determined under various experimental conditions. The results are consistent with a mechanism in which the primary photochemical step consists in a dissociation of the starting complex into a free molecule of CNCH3 (or NCCH3) and a pentacoordinate intermediate, which undergoes fast thermal reactions to give the final products.
[Show abstract][Hide abstract] ABSTRACT: Direct irradiation of acetonitrile solutions of Fe(CNCH3)4(CN)2 in both CT and LF bands leads to gradual ligand-solvent substitution and the solvated intermediates Fe(CNCH3)3(NCCH3(CN)2 and Fe(CNCH3)2(NCCH3(CN)2 are formed in two subsequent steps. The quantum yield of the first step of photosolvation (ϕ = 0.5) is independent of the wavelength of irradiation. Benzophenone is a high energy triplet donor for this compound, and sensitizes the photosolvation with a limit quantum yield of 0.56. The results point to the same reactive triplet state for the direct and the sensitized reaction.
Journal of Organometallic Chemistry - J ORGANOMET CHEM. 01/1986; 315(1):73-77.
[Show abstract][Hide abstract] ABSTRACT: The salt Fe(bipy)(CNCH3)4(BF4)2 reacts with an excess of hydrazine in CH3CN to give the dicarbene complex cis-Fe(bipy)(CNCH3)2(C4H10N4)(BF4)2. The reaction is of pseudo first-order, and obeys the rate law kobs = k[N2H4]. The rate constant k and the activation parameters have been calculated, and a mechanism is proposed. On irradiation in acetonitrile, both Fe(bipy)(CNCH3)42+ and the dicarbene complex undergo a process of replacement of coordinated CH3CN by solvating CH3NC, the reaction involving an initial photochemical step which gives a monosolvated intermediate. In the case of Fe(bipy)(CNCH3)42+ a subsequent fast thermal step gives a bisolvated intermediate in equilibrium with the monosolvated species, so that a photostationary equilibrium is attained. In the case of the dicarbene complex a second photochemical step leads to a stable bisolvated compound. For both compounds the quantum yields of the photochemical steps, calculated at 254 and 350 nm, increase with the exciting radiation energy, and this is consistent with the hypothesis of a dissociative mechanism for the photosolvation.
Journal of Organometallic Chemistry 07/1985; 289(1):81–90. · 2.30 Impact Factor