Sandra Monti

Photophysics and photochemistry of fluoroquinolones

The photobehavior of fluoroquinolone antibiotics, one of the most successful classes of drugs in therapeutic applications, has recently been the object of increasing interest due to the finding of their phototoxic and photocarcinogenic properties. The main results obtained for a series of structurally related, representative fluoroquinolone drugs is reviewed. Both activation of oxygen and various degradation pathways have been identified and the effects of medium and structure have been rationalized. The results can help in the understanding of the photochemistry occurring in biological environments and in the assessing of the correlation between structural characteristics and biological photodamage.

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.

Photoprocesses of photosensitizing drugs within cyclodextrin cavities

Recently some interest has been focused on the photobehavior of CD-drug inclusion complexes in relation to the problem of the biological photosensitization by drugs. This review is dedicated to the illustration of the mechanistic aspects of the photoprocesses occurring in some non-steroidal anti-inflammatory drugs (NSAIDs), with photosensitising side effects, within CD cavities. It is shown how the photobehavior of the CD-drug associates can help to model the photoreactivity of the drugs in biological sites. The limitations for the use of CDs as protective systems for the clinical administration of photosensitising drugs is also evidenced.

Multifaceted Photoreactivity of 6-Fluoro-7-aminoquinolones from the Lowest Excited States in Aqueous Media: A Study by Nanosecond and Picosecond Spectroscopic Techniques

Nanosecond and picosecond absorption and emission spectroscopic techniques were applied to the investigation of the reactivity from the lowest excited states of some 6-fluoro-7-piperazino-4-quinolone-3-carboxylic acids (FQs) in aqueous media at neutral pH, in the absence and presence of different sodium salts. Following the detection of various transients, we proposed a mechanism for the cleavage of the carbon-fluorine bond that proceeded through different reaction pathways, dependent on the molecular structure and the characteristics of the medium. The drug lomefloxacin (LOM), a 6,8-difluoroquinolone derivative, underwent heterolytic cleavage of the C8-F bond from the excited singlet state. With the 6-monofluoroquinolone norfloxacin (NOR) and the corresponding 1,8-naphthyridinone enoxacin (ENX), the lowest singlet state was not significantly reactive and an important deactivation channel was intersystem crossing (ISC) to the triplet manifold. The lowest triplet state underwent cleavage of the C6-F bond through a solvent mediated process possibly via a cyclohexadienyl anionic adduct. In the presence of sulfite or phosphate buffer a novel defluorination mechanism, induced by electron transfer from the inorganic anions to the FQ triplet state, was observed. The correlation between the transients observed and the final photoproducts in the different media was elucidated.

The cis → trans photoisomerization of azobenzene: an experimental re-examination

Abstract The quantum yields O t for the cis → trans photoisomerization of azobenzene have been redetermined in various solvents. As for the reverse process, there is a quantum yield dependence on the excitation wavelength. Reasons for the discrepancy with previous reported values are briefly discussed.

pH Effects on the Spectroscopic and Photochemical Behavior of Enoxacin: A Steady-State and Time-Resolved Study

The spectroscopic and photochemical behavior of Enoxacin (ENX), 1‐ethyl‐6‐fluoro‐1,4‐dihydro‐4‐oxo‐7‐(1‐piperazinyl)‐1,8‐naphthyridine‐3‐carboxylic acid, has been investigated in aqueous solutions between pH 3.5 and pH 12. The absorption and emission properties of ENX are strongly affected by pH. The fluorescence quantum yield, 4 x 10−3 at pH 3.5, increases by a factor of two on going to neutral pH while a strong reduction is observed at alkaline pH. The photodegradation quantum yield also depends on pH, being maximum in neutral conditions (ca 0.04). Nanosecond flash photolysis experiments confirm that the yield of absorbing transients is maximum at neutral pH while it decreases to zero at acid and alkaline pH. These results indicate that both the dissociation of the carboxylic group and the protonation of the piperazinyl residues are key steps for the formation of the photochemically active form of ENX. Loss of F− by heterolytic cleavage of the C–F bond is proposed to occur from the triplet state of the zwitterion with formation of a carbocation. A path for the evolution of this intermediate to the final product is also proposed.

Photodecarboxylation of Ketoprofen in Aqueous Solution. A Time-resolved Laser-induced Optoacoustic Study¶

Abstract The photodecarboxylation reaction of 2-(3-benzoylphenyl)propionate (ketoprofen anion, KP−) was studied in water and in 0.1 M phosphate buffer solutions in the pH range 5.7–11.0 by laser-induced optoacoustic spectroscopy (LIOAS, T range 9.5–31.6°C). Upon exciting KP− with 355 nm laser pulses under anaerobic conditions, two components in the LIOAS signals with well-separated lifetimes were found (τ1 < 20 ns; 250 < τ2 < 500 ns) in the whole pH range, whereas a long-lived third component (4 < τ3 < 10 μs) was only detected at pH ≤ 6.1. The heat and structural volume changes accompanying the first step did not depend on pH or on the presence of buffer. The carbanion resulting from prompt decarboxylation within the nanosecond pulse (<10 ns) drastically reduces its molar volume ([−18.9 ± 2.0] cm3/mol) with respect to KP−and its enthalpy content is (256 ± 10) kJ/mol. At acid pH (ca 6), a species is formed with a lifetime in the hundreds of ns. The enthalpy and structural volume change for this species with respect to KP− are (181 ± 15) kJ/mol and (+0.6 ± 2.0) cm3/mol, respectively. This species is most likely a neutral biradical formed by protonation of the decarboxylated carbanion, and decays to the final product 3-ethylbenzophenone in several μs. At basic pH (ca 11), direct formation of 3-ethylbenzophenone occurs in hundreds of ns involving a reaction with the solvent. The global decarboxylation reaction is endothermic ([45 ± 15] kJ/mol) and shows an expansion of (+14.5 ± 0.5) cm3/mol with respect to KP−. At low pH, the presence of buffer strongly affects the magnitude of the structural volume changes associated with the intermolecular proton-transfer processes of the long-lived species due to reactions of the buffer anion with the decarboxylated ketoprofen anion.

Water-Soluble Naphthalene Diimides as Singlet Oxygen Sensitizers

Bromo- and/or alkylamino-substituted and hydrosoluble naphthalene diimides (NDIs) were synthesized to study their multimodal photophysical and photochemical properties. Bromine-containing NDIs (i.e., 11) behaved as both singlet oxygen ((1)O2) photosensitizers and fluorescent molecules upon irradiation at 532 nm. Among the NDIs not containing Br, only 12 exhibited photophysical properties similar to those of Br-NDIs, by irradiation above 610 nm, suggesting that for these NDIs both singlet and triplet excited-state properties are strongly affected by length, structure of the solubilizing moieties, and pH of the solution. Laser flash photolysis confirmed that the NDI lowest triplet excited state was efficiently populated, upon excitation at both 355 and 532 nm, and that free amine moieties quenched both the singlet and triplet excited states by intramolecular electron transfer, with generation of detectable radical anions. Time-resolved experiments, monitoring the 1270 nm (1)O2 phosphorescence decay generated upon laser irradiation at 532 nm, allowed a ranking of the NDIs as sensitizers, based on their (1)O2 quantum yields (ΦΔ). The tetrafunctionalized 12, exhibiting a long-lived triplet state (τ ~ 32 μs) and the most promising absorptivity for photodynamic therapy application, was tested as efficient photosensitizers in the photo-oxidations of 1,5-dihydroxynaphthalene and 9,10-anthracenedipropionic acid in acetonitrile and water.

Gaining an insight into the photoreactivity of a drug in a protein environment: a case study on nalidixic acid and serum albumin.

The binding of nalidixic acid (NA) with human and bovine serum albumin (HSA and BSA) in buffer solution at pH 7.4 was investigated using circular dichroism (CD), UV absorption and fluorescence spectroscopy. Global analysis of multiwavelength spectroscopic data afforded the equilibrium constants of the most stable noncovalent drug/protein adducts of 1:1 and 2:1 stoichiometry and their individual CD, UV absorption, and fluorescence spectra. The primary binding site of the drug was located in subdomain IIIA (Sudlow Site II), whereas the secondary one was assigned to subdomain IIA. Conformational and CD calculations afforded the binding geometries. In the complexes, the fluorescence of the protein was strongly quenched by energy transfer and that of the drug was suppressed by electron transfer. Laser flash photolysis at 355 nm evidenced the formation of a radical pair consisting of a tyroxyl radical (lambdamax = 410 nm) and a reduced nalidixate anion radical NA(2-)* (lambdamax = 640 nm) with quantum yield of 0.4-0.5. Strong evidence was obtained that the process that involves Tyr411 in HSA (Tyr409 in BSA). A further transient with lambdamax approximately 780 nm observed in HSA was attributed to oxidation of the -(S200-S246)- bridge upon electron transfer to NA(-)*. Decay of the confined radical pairs occurred with rates approximately 10(7) s(-1). Formation of covalent drug-protein adducts in mixtures irradiated at lambdairr> 324 nm was proved using HPLC with fluorescence detection.

Host–Guest Interactions in Fe(III)-Trimesate MOF Nanoparticles Loaded with Doxorubicin

Doxorubicin (DOX) entrapment in porous Fe(III)-trimesate metal organic frameworks (MIL-100(Fe)) nanoparticles was investigated in neutral Tris buffer via UV-vis absorption, circular dichroism (CD), and fluorescence. The binding constants and the absolute spectra of the DOX-MIL-100(Fe) complexes were determined via absorption and fluorescence titrations. A binding model where DOX associates as monomer to the dehydrated Fe3O (OH)(H2O)2 [(C6H3)(CO2)3]2 structural unit in 1:1 stoichiometry, with apparent association constant of (1.1 to 1.8) × 10(4) M(-1), was found to reasonably fit the experimental data. Spectroscopic data indicate that DOX binding occurs via the formation of highly stable coordination bonds between one or both deprotonated hydroxyl groups of the aglycone moiety and coordinatively unsaturated Fe(III) centers. Complete quenching of the DOX fluorescence and remarkable thermal and photochemical stability were observed for DOX incorporated in the MIL-100(Fe) framework.