Guido De Guidi

Photochemistry of 2-(3-benzoylphenyl)propionic acid(ketoprofen) Part 1A picosecond and nanosecond time resolved study inaqueous solution

The photochemistry of ketoprofen (KPF), 2-(3-benzoylphenyl)propionic acid, has been studied in aqueous solutions by time resolved (picosecond and nanosecond) spectroscopic techniques. Excited-state calculations were performed. The overall reactivity of the molecule was rationalized within a scheme in which the lowest triplet state can undergo intramolecular electron transfer and photoionization. The main pathway for the formation of the decarboxylated photoproducts was shown to involve intramolecular electron transfer and to pass through triplet biradicals.

Determination of superoxide dismutase-like activity of copper(II) complexes. Relevance of the speciation for the correct interpretation of in vitro O2- scavenger activity.

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.

PREPARATION, CHARACTERISATION AND PHOTOSENSITIVITY STUDIES OF SOLID DISPERSIONS OF DIFLUNISAL AND EUDRAGIT RS100 AND RL100

Solid dispersions of diflunisal (DIF) with Eudragit RS100 (RS) and RL100 (RL) with different drug-to-polymer ratios were prepared by a solvent method (coevaporates) and were characterised in the solid state in comparison with the corresponding physical mixtures. The work was aimed at characterising the interactions occurring between DIF and RS or RL polymers, along with their influence on the in-vitro drug-dissolution pattern. The findings suggest that the drug did not change its crystalline form within the polymer network. Drug dispersion in the polymer matrix strongly influences its dissolution rate, which appears slower and more gradual while increasing the polymer ratios. Moreover, DIF is known to be a photosensitive compound, and its photoproduct has been found to be a toxic agent. This can be evidenced by testing red blood cell membranes for their resistance to the osmotic shock induced by UVA irradiation in the presence of DIF. The presence of some DIF/RS coevaporates was shown to reduce significantly the drug photosensitization process towards cell membranes. This suggests the possibility of combining the design of a drug delivery system with a photoprotective strategy.

Potentiometric, spectroscopic and antioxidant activity studies of SOD mimics containing carnosine

Stability constant values and bonding details of the copper(II) complexes of the β-cyclodextrin functionalized with the carnosine dipeptide (β-alanyl-L-histidine) at its narrow (CDAH6) or at its wide (CDAH3) rim were determined in aqueous solution. The potentiometric and spectroscopic data (UV-vis, CD and EPR) show that the involvement of a secondary OH group induces drastic differences in the coordination properties of CDAH3, in comparison with those of CDAH6. Direct and indirect assays were carried out showing that the copper(II) complexes with the two cyclodextrin derivatives are SOD-mimics with high catalytic activity. In addition the complex species are scavenger compounds towards ˙OH radicals, giving rise to a particular kind of copper(II) complexes with a combined activity against two toxic radical species, O2˙− and ˙OH. The cyclodextrin moiety contributes to the scavenger activity, without damaging the cellular membranes of neuronal and red blood cells.

Photophysical Properties of Rufloxacin in Neutral Aqueous Solution

The photophysical properties of rufloxacin, 9‐fluoro‐2r3‐dihydro‐10‐(4‐methyl‐l‐pyrazinyl)‐7‐oxo‐7‐H‐pyri‐do[l,2,3‐de]‐l,4‐benzothiazin‐6‐carboxylic acid, a fluoroquinolone antibacterial drug exhibiting photosensitizing action toward biological substrates, were studied in aqueous solutions at neutral pH. The lowest excited electronic states of the zwitterion were characterized by both experimental techniques and theoretical methods. Steady‐state and time‐resolved emission, triplet‐state absorption and singlet oxygen production were investigated. The results indicate that the lowest excited singlet is a fluorescent, relatively long‐lived state (φr= 0.075, Tr≅ 4.5 ns) with an efficient intersystem crossing to the triplet manifold (φisc≅ 0‐7)‐ The lowest triplet is a long‐lived state (TT≅ 10 μs at 295 K in 0.01 M phosphate buffer), with properties that make it a good candidate for being the precursor of the photodecarboxylation of the drug. It is quenched by oxygen at a rate of 1.7 times 109M‐1 s‐1 and singlet oxygen is formed with a quantum yield of 0.32 in air‐saturated solutions.

Supramolecular photochemistry of 2-(3-benzoylphenyl)propionic acid (Ketoprofen). A study in the β-cyclodextrin cavity

The photochemistry of 2-(3-benzoylphenyl)propionic acid (Ketoprofen) has been studied in the β-cyclodextrin cavity by stationary and time-resolved (picosecond and nanosecond) spectroscopic techniques. Conformational calculations of the inclusion complex were performed. Induced circular dichroism was measured and theoretically interpreted. Photodecarboxylation was found to occur with lower quantum yield than in aqueous medium. An additional photoreaction was evidenced. A mechanism in which the lowest triplet state of the Ketoprofen–β-cyclodextrin inclusion complex undergoes both intramolecular electron transfer and hydrogen abstraction is proposed. Adducts of reduced ketoprofen with β-cyclodextrin are the likely photoproducts of the additional reaction channel.

Inhibition of photohemolysis by copper(II) complexes with Sod-like activity

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.

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

This review focuses on damage photosensitized by the fluoroquinolone (FQ) antibacterial drugs. Different models are employed to study biosubstrate photodamage mediated by FQs (organisms, cells, isolated biomolecules and super molecules). Being that the effect of environment (polarity of the medium, ions, pH, binding with bio‐molecules, etc.) is crucial in FQ photochemistry, photobiological reactions can be consequently dramatically influenced. Thus, the photosensitization processes induced by FQs are here discussed taking into account that such extensive and cross‐targeted pathological implications request an excursus covering photosensitization in systems of increasing molecular complexity. In vivo and in vitro evidences for photoallergy, phototoxicity, photomutagenesis and photocarcinogenesis mediated by FQs are discussed.

Photoinduced N-Demethylation of Rufloxacin and its Methyl Ester Under Aerobic Conditions¶

Abstract Irradiation of rufloxacin (RF) under aerobic conditions gives rise to N-demethylation of the piperazinyl ring, which is enhanced in aerated D2O. Two primary processes seem to be involved in RF N-demethylation: photoionization from 1RF and singlet oxygen generation from 3RF. Both processes may lead to the same key intermediates, namely, RF·+ and superoxide radical anion; coupling of these intermediates explains N-demethylation of RF via an iminium cation. Formation of the hydrated electron by a monophotonic process (with a quantum yield of 0.09) is detected along with 3RF (with a intersystem-crossing quantum yield ϕISC = 0.36) by laser flash photolysis. Studies performed on RF methyl ester give qualitatively similar results.

MOLECULAR MECHANISM OF DRUG PHOTOSENSITIZATION. IX. EFFECT OF INORGANIC IONS ON DNA CLEAVAGE PHOTOSENSITIZED BY NAPROXEN

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‐photoin‐duced 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 dis‐mutase‐like activity of copper.