Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

The first ring‐forming thioboration reaction of C?C π bonds is reported. This catalyst‐free method proceeds in the presence of a commercially available external electrophilic boron source (B‐chlorocatecholborane) in good to high yields. The method is scalable and tolerates a variety of functional groups that are intolerant of other major borylation methods. The resulting borylated benzothiophenes participate in a variety of in situ derivatization reactions, showcasing that these borylated intermediates do not need to be isolated prior to downstream functionalization. This methodology has been extended to the synthesis of borylated dihydrothiophenes. Mechanistic experiments suggest that the operative mechanistic pathway is through boron‐induced activation of the alkyne followed by electrophilic cyclization, as opposed to S?B σ bond formation, providing a mechanistically distinct pathway to the thioboration of C?C π bonds.     

Ion trap mass spectrometry on a comet nucleus: the Ptolemy instrument and the Rosetta space mission

In May 2014, the Rosetta spacecraft is scheduled to rendezvous with the comet Churyumov-Gerasimenko ('67P'). One of the instruments on board the 'Lander' which will descend on to the surface of the comet is a miniaturised GC/MS system that incorporates an ion trap mass spectrometer, specially developed for isotope ratio analysis. This article describes the development and optimisation of the ion trap for this unique application, and presents a summary of the range of pre-programmed experiments that will contribute to the characterisation of the solid and volatile cometary materials.     

A photoimmobilisation strategy that maximises exploration of chemical space in small molecule affinity selection and target discovery

We show that the use of multiple photochemistries is necessary to ensure diverse immobilisation of small molecules for binding of polypeptides using phage display and antibody libraries.     

Neutral-ligand complexes of bis(imino)pyridine iron: synthesis, structure, and spectroscopy

A family of bis(imino)pyridine iron neutral-ligand derivatives, ((iPr)PDI)FeL(n) ((iPr)PDI = 2,6-(2,6-iPr2-C6H3N=CMe)2C6H3N), has been synthesized from the corresponding bis(dinitrogen) complex, ((iPr)PDI)Fe(N2)2. When L is a strong-field ligand such as tBuNC or a chelating alkyl diphosphine such as DEPE (DEPE = 1,2-bis(diethylphosphino)ethane), a five-coordinate, diamagnetic compound results with no spectroscopic evidence for mixing of paramagnetic states. Reducing the field strength of the neutral donor to principally sigma-type ligands such as tBuNH2 or THT (THT = tetrahydrothiophene) also yielded diamagnetic compounds. However, the 1H NMR chemical shifts of the in-plane bis(imino)pyridine hydrogens exhibit a large chemical shift dispersion indicative of temperature-independent paramagnetism (TIP) arising from mixing of an S = 1 excited state via spin-orbit coupling. Metrical data from X-ray diffraction establish bis(imino)pyridine chelate reduction for each structural type, while M?ssbauer parameters and NMR spectroscopic data differentiate the spin states of the iron and identify contributions from paramagnetic excited states.     

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.