Philippe Arnoux’s research while affiliated with Reactions and Chemical Engineering Laboratory and other places

In this work, we aimed at photocaging the well‐known anticancer agents dasatinib, ceritinib, gemcitabine, and combretastatin A4 with red‐light activatable 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY)‐based cages using a carbonate/carbamate linking strategy. Due to the synthetic challenges discussed in this article, we only obtained two target compounds, namely two caged ceritinib compounds. The latter were characterized in‐depth by nuclear magnetic resonance spectroscopy (NMR, 1H, COSY, 13C), high‐resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and their purity was evaluated by elemental analysis. Their photophysical characteristics were also measured including absorption and emission spectra, quantum yields, and lifetimes. Analysis of the products after irradiation of the compounds allowed us to make assumptions about the possible mechanism of the phototransformations. Moreover, we conducted biological studies to determine the phototoxicity indexes of A549 cancer cells. While the two compounds were found to be non‐toxic, the BODIPY precursors themselves were found to be highly toxic upon irradiation with phototoxicity indexes up to 1400.

In this work, we describe the synthesis of three new meso-arylporphyrins, named meso-tetrakis [4-(nicotinoyloxy)phenyl] porphyrin (H2TNPP), meso-tetrakis [4-(picolinoyloxy)phenyl] porphyrin (H2TPPP), and meso-tetrakis [4-(isonicotinoyloxy) phenyl] porphyrin (H2TIPP). These new synthesized meso-arylporphyrins are characterized using spectroscopic analysis: Fourier Transform Infrared Spectroscopy (FTIR) and One-dimensional Nuclear Magnetic Resonance (1D NMR), and mass spectrometry (MS). The photophysical studies (UV–visible absorption, singlet oxygen (¹O2) luminescence, and fluorescence emissions) demonstrate their potential uses as photosensitizers (PSs) in photodynamic therapy (PDT) applications. An in vitro investigation of the anti-fungal activity of H2TNPP, H2TPPP, and H2TIPP against Candida (C.) species (C. albicans, C. glabrata, and C. tropicalis) reveals that their minimum inhibitory concentration (MIC) values ranged from 1.25 to 5 mg/mL. In addition, their in vitro anti-fungal susceptibilities against three dermatophyte clinical isolates (Trichophyton rubrum, Microsporum canis, and Trichophyton mentagrophytes) are also evaluated and they demonstrate good anti-fungal activities. A molecular docking study of these meso-arylporphyrins as anti-fungal agents against C. tropicalis extracellular aspartic proteinases, Protein data Bank in Europe (PDBe code: 1J71) and Trichophyton rubrum Sialidases (PDBe code: 7P1D) underlines the possible interactions of H2TNPP, H2TPPP, and H2TIPP with the key amino acid residues of these fungal target proteins.

Phthalocyanine derivatives have attracted significant attention due to their unique chemical properties and applications in various fields, including photodynamic therapy. However, the synthesis and purification of phthalocyanines remain challenging. Among these derivatives, zinc(II) tetra, tert-butyl phthalocyanine (tert-ZnPc(II)) is noteworthy for its straightforward synthesis, making it a cost-effective option. tert-ZnPc(II) is often synthesized as a second-generation byproduct in the synthesis of asymmetric phthalocyanines when tert-butyl moieties are introduced to enhance the solubility of derivatives in a wide range of organic solvents. The practical applications of phthalocyanine derivatives depend mainly on their photophysical properties, which in turn influence key parameters such as absorption and fluorescence emission. This study investigates the ultraviolet-visible (UV-vis) absorption and fluorescence emission spectroscopies of tert-ZnPc(II), focusing on the impact of solvent polarity and the effect of different concentrations of water on UV-vis absorption behavior.

Can globular proteins be considered as Pickering emulsionstabilizers? In recent years, there has been a growing interest in the study of Pickering emulsions due to their unique properties. Among these, protein-stabilized Pickering emulsions have garnered significant attention, thanks to their environmentally friendly nature and wide-ranging applications across various industries. Pickering emulsions are typically classified separately from surfactant-stabilized emulsions due to their distinct stabilization mechanisms and remarkable resistance to coalescence. Although proteins have long been considered as particles in the context of Pickering emulsions, a debate still exists regarding their classification. In this work, we aim to address this debate by investigating the rheological and interfacial activity aspects of bovine serum albumine (BSA) proteins at silicone oil-water interfaces in the context of silicone oil-in-water emulsions. For rheological analysis and comparisons, emulsions were also formulated with surfactants and particles. Our results show that proteins can present both surfactantlike and particle-like behavior in terms of interfacial activity and microscopic structures with varying formulation parameters (pH). Rheological modelling, additionally, indicate similar behavior between emulsions with particles, surfactants and proteins. Thus, the challenge of categorizing proteins definitively as one or the other persists.

Immunogenic cell death (ICD), which converts tumor cells into their own vaccine, plays a pivotal role in the development of novel anti-cancer therapies. Here, a small series of osmium(II) polypyridyl complexes were synthesized and their biological activity in the dark and upon light irradiation against various cancer cell lines was studied. The compound Os2 (bearing two 4,7-diphenyl-1,10-phenanthrolines and one substituted bipyridine ligand) was discovered to be the most effective photosensitizer (PS) for photodynamic therapy (PDT) of this series through the photogeneration of 1O2 and •OH. In addition, Os2 was found to exhibit promising toxicity upon near-infrared (NIR) irradiation under both normoxia and hypoxia. These observations indicate that this PS is working through a mixture of Type-I and Type-II mechanisms. More interestingly, upon 740 nm irradiation, Os2 can stimulate a strong ICD response both in vitro and in vivo. A comprehensive immune analysis showed that mice vaccinated with Os2-treated CT26-luc cells boosted the systemic specific adaptive immune responses, including the activation of CD8+ T cells and reprograming of macrophages, leading to effective inhibition of tumor growth. Os2 is, to the best of our knowledge, the first photoactive osmium-based complex inducing ICD.

Photodynamic therapy is an accepted therapy cancer treatment. Its advantages encourage researchers to delve deeper. The use of nanoparticles in PDT has several advantages including the passive targeting of cancer cells. The aim of this article is to evaluate the effectiveness of AGuIX nanoparticles (activation and guiding of irradiation by X-ray) in the presence or absence of a photosensitizer, Photofrin, under illumination of 630 nm or under X-ray irradiation. The goal is to improve local tumor control by combining PDT with low-dose-X-ray-activated NPs in the treatment of locally advanced metastatic lung cancer. The study of the energy transfer, which occurs after excitation of Gd/Tb chelated in AGuIX in the presence of Photofrin, was carried out. We could observe the formation of singlet oxygen after the light or X-ray excitation of Gd and Tb that was not observed for AGuIX or Photofrin alone, proving that it is possible to realize energy transfer between both compounds.