Ca vs. Ba electrochemical detection by two disubstituted ferrocenyl chalcone chemosensors. Study of the ligand-metal interactions in CH3CN

We show here that the disubstituted ferrocenyl chalcones 1 and 2 are good electrochemical sensors for calcium and barium in CH₃CN. However, these two triflate salts are detected in a different way by both ligands. To clarify this point, a thorough and informative NMR study of the ligand-salt interactions is presented. The unusual shapes of the titration curves obtained depend on both the ligand and cation used. For example, they illustrate that ligand 1 mainly interacts with the metal by its CO functions, while ligand 2 also interacts by its azacrown groups. These curves also reflect complex equilibriums in solution involving several ligand-salt adducts detected by mass spectrometry. To evaluate the strength of these interactions, the association constants of all the species formed have been determined by fitting the NMR data. It is noteworthy that changing the diethylamino groups in molecule 1 by the azacrown residue enhances the selectivity for the calcium salt, as pointed out by the value of the association constant of the 2Ca²⁺ species. The synthesis of the protonated counterparts 3 and 4 was useful to clarify the electrochemical behaviour of 1 and 2. Although the two ligand-salt interactions present several common points, the whole results obtained allow us to propose an original explanation for the difference observed between the Ca²⁺ and Ba²⁺ electrochemical sensing.     

Two electroactive ferrocenyl chalcones as original optical chemosensors for Ca and Ba cations in CH3CN

The optical study of ferrocenyl ligands 1-2 is presented, and reveals several interesting points. Contrary to their monosubstituted counterparts, these ligands exhibit fluorescence properties in acetonitrile. They can detect calcium, and also barium, by four different techniques: NMR, electrochemistry, UV-Vis absorption spectroscopy and fluorimetry in the same solvent. Each ligand detects both salts in the same manner by UV-Vis absorption and by fluorimetry. The response depends on the nature of the N terminal groups of the ligand. In each case, the ligand-calcium interaction is complex and involves 3-5 species in equilibrium in solution. Their association constants have been determined by fitting the UV-Vis data. Remarkably, for 2 and the calcium salts, nearly the same set of association constants can be used to fit not only the UV-Vis data obtained with calcium triflate (in a restricted range of concentration) or with calcium perchlorate, but also the NMR data obtained with calcium triflate. Interestingly, these results strengthen the fact that, in this family of compounds, the azacrown derivatives are less sensitive to high calcium triflate concentrations than their simple N-alkyl homologues. It is noteworthy that the complex non-monotonous fluorescence behaviour of compounds 1 and 2 upon Ca²⁺ or Ba²⁺ addition is quite original for ferrocenyl chalcones. These ligands constitute scarce examples of multi-signalling fluorescent ferrocenyl chemosensors for Ca²⁺ and Ba²⁺ cations in CH₃CN.     

Chemical end-grafting of homogeneous polystyrene monolayers on mica and silica surfaces

Homogeneous polystyrene monolayers covalently end-attached on mica and silica surfaces were obtained using a "graft to" methodology. The grafting was achieved via nucleophilic substitution between silanol groups (Si-OH) containing surface and monochlorosilyl terminated polystyrene (PS). Different parameters, such as surface activation, grafting reaction time, polymer concentration, nature of solvent, and presence of catalyst, were investigated to determine the optimal conditions for creating very homogeneous and stable polymer monolayers. Ellipsometry, atomic force microscopy (AFM), surface forces apparatus (SFA), and contact angle measurements were used to characterize the polymer-grafted layers. An efficient plasma activation procedure was established to create a maximum number of silanol groups on mica surfaces without increasing the surface roughness. Surface reactivity was investigated by grafting trimethylchlorosilane (TMS) on OH-activated mica and silica. The maximum TMS surface coverage on activated mica is similar to that observed for silica. The stability of covalently attached TMS and PS layers in toluene and water were investigated. Both grafted layers (TMS and PS) partially detached from the mica and silica surfaces when immersed in water. Hydrolysis of the siloxane bond between the monochlorosilyl groups and the surface is the most probable cause of layer degrafting. The degrafting was much slower with the long PS polymer chains, compared to the small TMS molecules, which may act as a protective layer against hydrolysis.     

Treatment of intralocular diseases with poly(ortho ester)‐based drug delivery systems

A poly(ortho ester) (POE) has been investigated as a carrier for controlled delivery in intraocular therapy. The intraocular biocompatibility of POE was assessed in the rabbit after intravitreal as well as suprachoroidal injections. In both cases, the injection was feasible and reproducible, and the tolerance of POE was good, with no clinical or cellular signs of inflammation. The polymer degraded slowly within 2 to 3 weeks, with total bioresorption. POE allowed to sustain the release of an antifibroblastic agent in a model of glaucoma filtering surgery in the rabbit. A formulation based on POE and 5‐fluorouracil was administered to prevent the failure of the surgery. This POE formulation was effective in inhibiting the fibrotic response, allowing a local and controlled release of a small amount of the antiproliferative drug, while reducing its toxicity. Based on these results, POE appears to be a promising carrier for sustained drug delivery in treatment of intraocular affections.     

Fungicidal Activity of Recombinant Javanicin against Cryptococcus neoformans Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes

The occurrence of Cryptococcus neoformans, the human fungal pathogen that primarily infects immunocompromised individuals, has been progressing at an alarming rate. The increased incidence of infection of C. neoformans with antifungal drugs resistance has become a global concern. Potential antifungal agents with extremely low toxicity are urgently needed. Herein, the biological activities of recombinant javanicin (r-javanicin) against C. neoformans were evaluated. A time-killing assay was performed and both concentration- and time-dependent antifungal activity of r-javanicin were indicated. The inhibitory effect of the peptide was initially observed at 4 h post-treatment and ultimately eradicated within 36 to 48 h. Fungal outer surface alteration was characterized by the scanning electron microscope (SEM) whereas a negligible change with slight shrinkage of external morphology was observed in r-javanicin treated cells. Confocal laser scanning microscopic analysis implied that the target(s) of r-javanicin is conceivably resided in the cell thereby allowing the peptide to penetrate across the membrane and accumulate throughout the fungal body. Finally, cryptococcal cells coped with r-javanicin were preliminarily investigated using label-free mass spectrometry-based proteomics. Combined with microscopic and proteomics analysis, it was clearly elucidated the peptide localized in the intracellular compartment where carbohydrate metabolism and energy production associated with glycolysis pathway and mitochondrial respiration, respectively, were principally interfered. Overall, r-javanicin would be an alternative candidate for further development of antifungal agents.     

Porphyrin-Based Thin-Film Molecular Materials with Highly Adjustable Nanoscale Porosity and Permeability Characteristics

Mesoporous thin films based on neutral, porphyrin-bridged, tetrarhenium “square” compounds (metallacycles) display permeability to molecules smaller than the dimensions of an individual square cavity, but blocking behavior toward larger species (see schematic representation). The characteristic permeant size cutoff can be systematically and predictably manipulated by decorating the walls of the porphyrin square with axially bound, mono-, bi-, and tetradentate ligands.     

Inclusion complexes of a nucleotide analogue with hydroxypropyl-beta-cyclodextrin

Bis(tbutyl-S-acyl-2-thioethyl)-AraCMP (UA911) is a mononucleotide prodrug developed to overcome some of the cellular resistance to cytotoxic deoxynucleosides analogues. Its use for in vivo studies is limited due to its poor solubility in water. Thus, 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) was proposed to solubilize UA911 in water, in order to obtain concentrations needed for in vivo experiments. A molar ratio of HP-β-CD: UA911 of 3:1 was sufficient to obtain complete solubilization of the prodrug. The corresponding inclusion complex was characterized by differential scanning calorimetry and ¹H NMR spectroscopy study provided a definitive proof of the formation of the inclusion complex. The complex retained its cytotoxic activity as shown by in vitro cell survival assays on murine leukemia cells, and was evaluated in vivo. HP-β-CD is therefore suitable for the preparation of adequate solutions for the study of the antitumoral activity of nucleotide prodrugs such as UA911.     

The Influence of N‐Heterocyclic Carbenes (NHC) on the Reactivity of [Ru(NHC)4H]+ With H2, N2, CO and O2

The five‐coordinate ruthenium N‐heterocyclic carbene (NHC) hydrido complexes [Ru(IiPr₂Me₂)₄H][BAr^F₄] ( 1 ; IiPr₂Me₂=1,3‐diisopropyl‐4,5‐dimethylimidazol‐2‐ylidene; Ar^F=3,5‐(CF₃)₂C₆H₃), [Ru(IEt₂Me₂)₄H][BAr^F₄] ( 2 ; IEt₂Me₂=1,3‐diethyl‐4,5‐dimethylimidazol‐2‐ylidene) and [Ru(IMe₄)₄H][BAr^F₄] ( 3 ; IMe₄=1,3,4,5‐tetramethylimidazol‐2‐ylidene) have been synthesised following reaction of [Ru(PPh₃)₃HCl] with 4–8 equivalents of the free carbenes at ambient temperature. Complexes 1 – 3 have been structurally characterised and show square pyramidal geometries with apical hydride ligands. In both dichloromethane or pyridine solution, 1 and 2 display very low frequency hydride signals at about δ ?41. The tetramethyl carbene complex 3 exhibits a similar chemical shift in toluene, but shows a higher frequency signal in acetonitrile arising from the solvent adduct [Ru(IMe₄)₄(MeCN)H][BAr^F₄], 4 . The reactivity of 1 – 3 towards H₂ and N₂ depends on the size of the N‐substituent of the NHC ligand. Thus, 1 is unreactive towards both gases, 2 reacts with both H₂ and N₂ only at low temperature and incompletely, while 3 affords [Ru(IMe₄)₄(η²‐H₂)H][BAr^F₄] ( 7 ) and [Ru(IMe₄)₄(N₂)H][BAr^F₄] ( 8 ) in quantitative yield at room temperature. CO shows no selectivity, reacting with 1 – 3 to give [Ru(NHC)₄(CO)H][BAr^F₄] ( 9 – 11 ). Addition of O₂ to solutions of 2 and 3 leads to rapid oxidation, from which the Ru^III species [Ru(NHC)₄(OH)₂][BAr^F₄] and the Ru^IV oxo chlorido complex [Ru(IEt₂Me₂)₄(O)Cl][BAr^F₄] were isolated. DFT calculations reproduce the greater ability of 3 to bind small molecules and show relative binding strengths that follow the trend CO ? O₂ > N₂ > H₂.     

A Nanoscale Molecular Switch Triggered by Thermal,Light, and Guest Perturbation

Bottoms up! A discrete metallo‐supramolecular nanoball (see picture), synthesized by using “bottom‐up” methodologies, uniquely undergoes a solvent‐sensitive, physically addressable electronic spin switching. The switching occurs by thermal, light, or solvent perturbation, where importantly it can be switched “on” or “off” by green or red laser irradiation, respectively.