Helical foldamers constitute particularly relevant targets in the field of host-guest chemistry, be that as hosts or substrates. In this context, the strategies reported so far to control the dimensions and shape of foldamers mainly involve modifications of the skeleton through covalent synthesis. Herein, we prepared an oligopyridine dicarboxamide foldamer substituted by photo-active tetraphenylethylene units (TPE). We demonstrate that it is possible to toggle the length of a helical foldamer by two means. First, the elongation of foldamers can be tuned by adjusting the concentration, as demonstrated by DOSY NMR spectroscopy and X-ray diffraction analyses on both the single and the double helix structures. Secondly, and in a more original manner, a photo-induced protonation process triggered by TPE units promotes a novel pathway to unfold helical foldamers, leading to dramatic conformational and spectroscopic changes.

The phase inversion temperature method is one of the formulation processes to elaborate nanomedicine based on lipid nanoparticles. This process was used in numerous studies in literature, changing the nature of the ingredients to ensure good encapsulation efficiencies of various drugs. While the product quality attributes to develop various nanomedicines were largely explored, the process parameters remained unchanged from the first lipid nanoparticles designed with this process 25 years ago. It is always composed of 3 temperature cycles and a fast addition of cold water, creating an "irreversible shock" to obtain the lipid nanoparticle in suspensions. To date, the exact roles of these 2 steps remain unclear. We decided to explore their impact by changing the number of temperature cycles and by modifying the final addition of water (temperature, salinity, with or without). Using these various conditions, the size distribution and stability, the capacity of encapsulation and the cytotoxic property of the lipid nanoparticles were compared. It demonstrated the indispensableness of these parameters: at least 1 temperature cycle and rapid cooling and dilution of the mixture, to obtain the most performant nano- systems.

Helical foldamers constitute particularly relevant targets in the field of host-guest chemistry, be that as hosts or substrates. In this context, the strategies reported so far to control the dimensions and shape of foldamers mainly involve modifications of the skeleton through covalent synthesis. Herein, we prepared an oligopyridine dicarboxamide foldamer substituted by photo-active tetraphenylethylenes (TPE). We demonstrate that it is possible to toggle the length of a helical foldamer by two means. First, the elongation of foldamers can be tuned by adjusting the concentration, as demonstrated by DOSY NMR spectroscopy and X-ray diffraction analyses on both the single and the double helix structures. Secondly, and in a more original manner, a photo-induced protonation process triggered by TPE units promotes a novel pathway to unfold helical foldamers, leading to dramatic conformational and spectroscopic changes.

While benzothioxanthene imide (BTI) has shown promise in organic electronics and more recently in photodynamic therapy, its full potential remains yet undiscovered. In this context, this study repots the synthesis and characterization of aza derivatives in which the characteristic sulfur atom is replaced by an amino group. Adapted from the synthetic route of the BTI, a way was found to control the electronic structure of the radical intermediates, by means of a simple chemical modification. As a result, either the thermodynamically six-membered or the kinetically favored five-membered ring regioisomers can selectively be accessed. Photophysical rationalization of their structure-property relationships confirmed the richness, versatility and tunability of this class of rylene imide-based dyes.

Subtle chemical modifications of an intermediate can have significant impacts, since they usually considered to control the reactivity. In their Research Article, J. Zagranyarski, D. Lungerich, C. Cabanetos, and co-workers report the preparation of aza derivatives of the benzothixanthene imide. The intramolecular radical cyclization can be controlled by means of a simple methylation to either afford the thermodynamically favored six-membered or its kinetically favored five-membered ring regioisomers, exhibiting significant photophysical properties.

Nanoemulsions are metastable emulsions in the nanometric range which can be obtained using low-energy processes. A decade ago, it was demonstrated that a non-negligible amount of residual surfactant micelles may coexist with the oil nanodroplets in a model oil/surfactant system. Those micelles were called "wasted" micelles as they did not participate in the formation of the nanodroplets. Little attention has been focused on the potential presence or effect of such secondary structures in nanoemulsions used as drug delivery systems. Here, we present an extensive characterization of lipid nanocapsules, a nanoemulsion obtained from a medium-chain triglyceride mixed with a pegylated surfactant by a process comprising a temperature-dependent phase inversion followed by a cold-water quench. Lipid nanocapsules demonstrate a very good shelf stability. First, for clarity and academic purposes, we briefly present the pros and the cons of the various diffusion-based characterization techniques used i.e., multi-angle and single-angle dynamic light scattering, nanoparticle tracking analysis, fluorescence recovery after photobleaching, and diffusometry nuclear magnetic resonance. Then, combining all these techniques, we show that up to 40 wt% of the surfactant is not involved in the lipid nanocapsule construction but forms residual micellar structures. Those micelles also contain a small quantity of medium-chain triglyceride (2 wt% of the initial amount) and encapsulate around 40 wt% of a fluorescent dye originally dispersed in the oily phase.

Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications.

Carbohydrate–ferrocene conjugates show a splitting of all the 1H NMR signals of the substituted cyclopentadienyl. XRD of crystals seems to indicate that the R group could be responsible for the splitting of the NMR signals.

AbstractSynthesis of two new zinc porphyrin fluorescein dyads are reported here. The two chromophoric units are covalently linked by alkane or alkyne bond, which provides various degrees of flexibility. Conformational analysis as photophysical properties were performed both experimentally (NOESY experiments, lifetimes, ROS production…) and theoretically (DFT and TD‐DFT calculations). Comparison with triazole linker described in a precedent study highlighted that linkage nature determine conformational structure (folding/linearity) but do not significantly modify energy transfer between the two moieties involved in dyads.

The synthesis for monobrominated benzothioxanthene is reported, which is then employed in common palladium catalyzed coupling reactions for novel organic semiconductors.

Usually isolated from Garcinia (Clusiaceae) or Hypericum (Hypericaceae) species, some Polycyclic Polyprenylated AcylPhloroglucinols (PPAPs) have been recently reported as potential research tools for immunotherapy. Aiming at exploring the chemodiversity of PPAPs amongst Garcinia genus, a dereplication process suitable for such natural compounds has been developed. Although less sensitive than mass spectrometry, NMR spectroscopy is perfectly reproducible and allows stereoisomers distinction, justifying the development of 13C-NMR strategies. Dereplication requires the use of databases (DBs). To define if predicted DBs were accurate enough as dereplication tools, experimental and predicted δC of natural products usually isolated from Clusiaceae were compared. The ACD/Labs commercial software allowed to predict 73% of δC in a 1.25 ppm range around the experimental values. Consequently, with these parameters, the major PPAPs from a Garcinia bancana extract were successfully identified using a predicted DB.

A new C15-acetogenin, sagonenyne (20), exhibiting an unusual single tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia obtusa collected on the Corsican coastline. Its structure was established by detailed NMR spectroscopic analysis, mass spectrometry, and comparison with literature data. Twenty-three known compounds were identified in the same extract by means of column chromatography steps, using a 13C-NMR computer aided method developed in our laboratory. In addition to sesquiterpenes, which represent the main chemical class of this extract, diterpenes, sterols, and C15-acetogenins were identified. The crude extract was submitted to a cytotoxicity assay and was particularly active against THP-1 cells, a human leukemia monocytic cell line.

NMR diffusometry is a powerful but challenging method to analyze complex mixture. Each component diffuses differently, from the faster small species to the slower large species, corresponding to different signal attenuation. However, the method is highly sensitive to the quality of the acquired data and the performance of the processing used to resolve multiexponential signals influences. Adapting the signal decay sampling to the mixture composition is one way to improve the precision of the measure. In this work, we propose a prediction tool, based on the calculation of the Cramér-Rao lower bound to minimize the variance of diffusion coefficient estimation in order to determine the optimal number of diffusion gradient steps, the best diffusion gradient sampling (among linear, exponential, quadratic and sigmoidal ones) and the optimal maximum diffusion factor. The tool was validated experimentally on a unimer/micelle solution of sodium dodecyl sulfate and on Caelyx®, a commercial liposomal preparation containing a mixture of pegylated-liposomes and sucrose.

Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). To compete with other microorganisms in the environment, fungi have evolved sophisticated strategies, including the production of secondary metabolites with antimicrobial activity that may also help them to establish successfully within the respiratory tract of receptive hosts. Here, the culture filtrate from a human pathogenic strain of S. boydii was investigated searching for an antibacterial activity, mainly against the major CF bacterial pathogens. A high antibacterial activity against Staphylococcus aureus, including methicillin-resistant strains of this species, was observed. Bio-guided fractionation and analysis of the active fractions by nuclear magnetic resonance or by high-performance liquid chromatography and high-resolution electrospray ionization-mass spectrometry allowed us to identify boydone A as responsible for this antibacterial activity. Together, these results suggest that this six-membered cyclic polyketide could be one of the virulence factors of the fungus. Genes involved in the synthesis of this secreted metabolite are currently being identified in order to confirm the role of this polyketide in pathogenesis.

Modulations of the optical properties of a new porphyrin–fluorescein dyad were elucidated using experimental and theoretical techniques, with conformational rearrangements being studied.