Patrizio Salice

Assessment of Water-Soluble π-Extended Squaraines as One- and Two-Photon Singlet Oxygen Photosensitizers: Design, Synthesis, and Characterization

Singlet oxygen sensitization by organic molecules is a topic of major interest in the development of both efficient photodynamic therapy (PDT) and aerobic oxidations under complete green chemistry conditions. We report on the design, synthesis, biology, and complete spectroscopic characterization (vis-NIR linear and two-photon absorption spectroscopy, singlet oxygen generation efficiencies for both one- and two-photon excitation, electrochemistry, intrinsic dark toxicity, cellular uptake, and subcellular localization) of three classes of innovative singlet oxygen sensitizers pertaining to the family of symmetric squaraine derivatives originating from pi-excessive heterocycles. The main advantage of pi-extended squaraine photosensitizers over the large number of other known photosensitizers is their exceedingly strong two-photon absorption enabling, together with sizable singlet oxygen sensitization capabilities, for their use at the clinical application relevant wavelength of 806 nm. We finally show encouraging results about the dark toxicity and cellular uptake capabilities of water-soluble squaraine photosensitizers, opening the way for clinical small animal PDT trials.

Carbon nanotubes and organic solar cells

The use of carbon nanotubes in photovoltaics is still challenging due to different issues connected to their synthesis, purification, functionalization, processing and device integration. From this perspective at first we review on selected contributions dealing with the above issues; then we focus on the advantages and limitations of carbon nanotubes for the development of organic solar cells.

Photophysics of Squaraine Dyes: Role of Charge-Transfer in Singlet Oxygen Production and Removal

The unique optical properties of squaraines render these molecules useful for applications that range from xerography to photodynamic therapy. In this regard, squaraines derived from the condensation of nitrogen-based heterocycles and squaric acid have many promising attributes. Key solution-phase photophysical properties of six such squaraines have been characterized in this study. One feature of these molecules is a pronounced absorption band in the region approximately 600-720 nm that has significant spectral overlap with the fluorescence band (i.e., the Stokes shift is small). As such, effects of emission/reabsorption yield unique excitation wavelength dependent phenomena that are manifested in quantum yields of both fluorescence and sensitized singlet oxygen production. Comparatively small squaraine-sensitized yields of singlet oxygen production and, independently, large rate constants for squaraine-induced deactivation of singlet oxygen are consistent with a model in which there is appreciable intra- and intermolecular charge-transfer in the squaraine and squaraine-oxygen encounter complex, respectively. The results reported herein should be useful in the further development of these compounds for a range of oxygen-dependent applications.

Photooxidation and Phototoxicity of π-Extended Squaraines

This paper describes the synthesis of pi-extended squaraines and their photooxidation properties and gives an in-depth characterization of these molecules as photosensitizing agents. Squaraines show a strong absorption in the tissue transparency window (600-800 nm), and upon irradiation, they undergo a photooxidation process, leading to the formation of peroxide and hydroperoxide radicals according to a type I radical chain process. Confocal laser microscopy demonstrates that the designed squaraines efficiently internalize in the cytoplasm and not in the nucleus of the cell. In the dark, they are scarcely cytotoxic, but after irradition, they promote a strong dose-dependent phototoxic effect in four different cancer cells. In HeLa and MCF-7 cells, squaraines 4 and 5, thanks to their hydrocarbon tails, associate to the membranes and induce lipid peroxidation, as indicated by a marked increase of malonyldialdehyde after photodynamic treatment, in agreement with in vitro photooxidation studies. FACS, caspase-3/7 assays and time-lapse microscopy demonstrate that the designed squaraines cause cell death primarily by necrosis.

The continuous-flow cycloaddition of azomethine ylides to carbon nanotubes

This communication demonstrates a straightforward continuous-flow method for efficient exohedral functionalisation of carbon nanotubes which affords soluble samples in a much shorter time over conventional batch processing.

Enhanced neuronal cell differentiation combining biomimetic peptides and a carbon nanotube-polymer scaffold

Carbon nanotubes are attractive candidates for the development of scaffolds able to support neuronal growth and differentiation thanks to their ability to conduct electrical stimuli, to interface with cells and to mimic the neural environment. We developed a biocompatible composite scaffold, consisting of multi-walled carbon nanotubes dispersed in a poly-L-lactic acid matrix able to support growth and differentiation of human neuronal cells. Moreover, to mimic guidance cues from the neural environment, we also designed synthetic peptides, derived from L1 and LINGO1 proteins. Such peptides could positively modulate neuronal differentiation, which is synergistically improved by the combination of the nanocomposite scaffold and the peptides, thus suggesting a prototype for the development of implants for long-term neuronal growth and differentiation. From the clinical editor: The study describes the design and preparation of nanocomposite scaffolds with multi-walled carbon nanotubes in a poly-L-lactic acid matrix. This compound used in combination with peptides leads to synergistic effects in supporting neuronal cell growth and differentiation.

On the trade-off between processability and opto-electronic properties of single wall carbon nanotube derivatives in thin film heterojunctions

A flow functionalization route has been employed to derivatize single wall carbon nanotubes (SWCNTs) by thienylphenyl groups. The SWCNT derivatives in the most soluble fraction have been characterized by thermogravimetric analysis, DLS analysis, DFT calculations, and UV-vis-NIR, microRaman and IR spectroscopies to study the degree of functionalization, the concentration of SWCNTs in solution, the dimension of the aggregates in solutions, the density of defects, and the presence of the thienylphenyl groups. Thin-film heterojunctions made of SWCNT derivatives and poly(3-hexylthiophene) (P3HT) have been prepared by various methods employing the Langmuir–Schaefer technique, spin-coating and thermal annealing processes. By comparing the batch and the flow functionalizations, a trade-off between solubility, processability and the thin-film opto-electronic properties has been found as a result of the degree of functionalization.

Chemistry of Carbon Nanotubes in Flow

The covalent chemistry of carbon nanostructures has put forth a wide variety of interesting derivatives that widen their potential as functional materials. However, the synthetic procedures that have been developed to functionalize the nanostructures may require long reaction times and harsh conditions. In this paper, we study the continuous flow processing of single-wall carbon nanotubes with azomethine ylides and diazonium salts and demonstrate that this approach is effective to reduce reaction times and tune the properties of the functionalized carbon materials.

Synthesis and characterisation of a trithiocarbonate for the decoration of carbon nanostructures

A novel aldehyde-bearing trithiocarbonate has been synthesized and reacted with carbon nanostructures with different dimensionalities (nanotubes, fullerenes, graphite). The decoration of these carbon nanostructures with trithiocarbonate moieties should provide a powerful tool for the design of advanced carbon nanofillers.

Synthesis and Electronic Properties of 1,2‐Hemisquarimines and Their Encapsulation in a Cucurbit[7]uril Host

The synthesis of a new class of robust squaraine dyes, colloquially named 1,2-hemisquarimines (1,2-HSQiMs), through the microwave-assisted condensation of aniline derivatives with the 1,2-squaraine core is reported. In CH3CN, 1,2-HSQiMs show a broad absorption band with a high extinction coefficient and a maximum at around λ=530 nm, as well as an emission band centered at about λ=574 nm, that are pH dependent. Protonation of the imine nitrogen causes a redshift of both absorption and emission maxima, with a concomitant increase in the lifetime of the emitting excited state. Encapsulation of the chromophore into a cucurbit[7]uril host revealed fluorescence enhancement and increased photostability in water. The redox characteristics of 1,2-HSQiMs indicate that charge injection into TiO2 is possible; this opens up promising perspectives for their use as photosensitizers for solar energy conversion.