Salvatore Sortino

Photoactivated nanomaterials for biomedical release applications

The achievement of nanomaterials able to release therapeutic agents in a controlled fashion is a major challenge in the burgeoning field of nanomedicine. Light represents the most elegant and non-invasive trigger to deliver bio-active compounds on demand since it allows the accurate control of three key factors determining the therapeutic outcome including site, timing and dosage. Recent breakthroughs in nanotechnology offer the opportunity to characterize, manipulate and organize matter at the nanometre scale, controlling the size and shape of the resulting nanomaterials and greatly improving the biocompatibility and the cellular uptake efficiency. This feature article illustrates some recent advances in the fabrication of light-triggered nanomaterials for biomedical delivery, describing representative examples from our laboratory and others, underlying the logical design and highlighting the potential applications in some major areas such as drug and gene release, photodynamic and photothermal therapy.

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.

Fast and Stable Photochromic Oxazines for Fluorescence Switching

The stringent limitations imposed by diffraction on the spatial resolution of fluorescence microscopes demand the identification of viable strategies to switch fluorescence under optical control. In this context, the photoinduced and reversible transformations of photochromic compounds are particularly valuable. In fact, these molecules can be engineered to regulate the emission intensities of complementary fluorophores in response to optical stimulations. On the basis of this general design logic, we assembled a functional molecular construct consisting of a borondipyrromethene fluorophore and a nitrospiropyran photochrome and demonstrated that the emission of the former can be modulated with the interconversion of the latter. This fluorophore-photochrome dyad, however, has a slow switching speed and poor fatigue resistance. To improve both parameters, we developed a new family of photochromic switches based on the photoinduced opening and thermal closing of an oxazine ring. These compounds switch back and forth between ring-closed and -open isomers on nanosecond-microsecond timescales and tolerate thousands of switching cycles with no sign of degradation. In addition, the attachment of appropriate chromophoric fragments to their switchable oxazine ring can be exploited to either deactivate or activate fluorescence reversibly in response to illumination with a pair of exciting beams. Specifically, we assembled three dyads, each based on either a borondipyrromethene or a coumarin fluorophore and an oxazine photochrome, and modulated their fluorescence in a few microseconds with outstanding fatigue resistance. The unique photochemical and photophysical properties of our fluorophore-photochrome dyads can facilitate the development of switchable fluorophores for superresolution imaging and, ultimately, provide valuable molecular probes for the visualization of biological samples on the nanometer level.

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.

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.

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.

An engineered nanoplatform for bimodal anticancer phototherapy with dual-color fluorescence detection of sensitizers

A multifunctional nanoplatform with four-in-one photoresponsive functionalities has been achieved through the co-encapsulation of two chromo-fluorogenic components within biocompatible polymeric nanoparticles. This engineered nanoconstruct efficiently delivers different photosensitizers in melanoma cells, which can be detected through their dual-color fluorescence, and induces amplified cell mortality due to the simultaneous photogeneration of singlet oxygen and nitric oxide.

The Photochemistry of Flutamide and its Inclusion Complex with β-Cyclodextrin. Dramatic Effect of the Microenvironment on the Nature and on the Efficiency of the Photodegradation Pathways¶

Abstract The photochemistry of the anticancer drug flutamide (FM), 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propan-amide, in homogeneous media and in the β-cyclodextrin (β-CD) cavity has been investigated. The photoreactivity of the free molecule has been rationalized on the basis of an intramolecular nitro to nitrite rearrangement followed by cleavage of the nitrite intermediate. The twisted geometry of the nitro group with respect to the aromatic plane plays a key role in triggering such a photoprocess. Incorporation of FM in the β-CD cavity leads to dramatic effects on both the efficiency and the nature of the photochemical deactivation pathways of the guest molecule. A 20-fold increase in the FM photodecomposition quantum yield and the formation of photoproducts originated by both reduction of the nitro group and cleavage of the amide bond were observed in the presence of the macrocycle. Such a behavior cannot be attributed exclusively to the micropolarity of β-CD and/or to its role as a reactant. The induced circular dichroism spectra and the nature of the photoproducts formed in these experimental conditions provide indications that the photoreactivity in the β-CD microenvironment could likely be mediated by structural changes of FM upon complexation.