Facile Protocol for Water-Tolerant “Frustrated Lewis Pair”-Catalyzed Hydrogenation

Despite rapid advances in the field of metal-free, “frustrated Lewis pair” (FLP)-catalyzed hydrogenation, the need for strictly anhydrous reaction conditions has hampered wide-scale uptake of this methodology. Herein, we report that, despite the generally perceived moisture sensitivity of FLPs, 1,4-dioxane solutions of B(C6F5)3 actually show appreciable moisture tolerance and can catalyze hydrogenation of a range of weakly basic substrates without the need for rigorously inert conditions. In particular, reactions can be performed directly in commercially available nonanhydrous solvents without subsequent drying or use of internal desiccants

Novel B(Ar')2(Ar'') hetero-tri(aryl)boranes: a systematic study of Lewis acidity

A series of homo- and hetero-tri(aryl)boranes incorporating pentafluorophenyl, 3,5-bis(trifluoromethyl)phenyl, and pentachlorophenyl groups, four of which are novel species, have been studied as the acidic component of frustrated Lewis pairs for the heterolytic cleavage of H2. Under mild conditions eight of these will cleave H2; the rate of cleavage depending on both the electrophilicity of the borane and the steric bulk around the boron atom. Electrochemical studies allow comparisons of the electrophilicity with spectroscopic measurements of Lewis acidity for different series of boranes. Discrepancies in the correlation between these two types of measurements, combined with structural characterisation of each borane, reveal that the twist of the aryl rings with respect to the boron-centred trigonal plane is significant from both a steric and electronic perspective, and is an important consideration in the design of tri(aryl)boranes as Lewis acids

Exploring structural and electronic effects in three isomers of tris{bis(trifluoromethyl)phenyl}borane: Towards the combined electrochemical-frustrated Lewis pair activation of H2

Three structural isomers of tris{bis(trifluoromethyl)phenyl}borane have been studied as the acidic com- ponent of frustrated Lewis pairs. While the 3,5-substituted isomer is already known to heterolytically cleave H2 to generate a bridging-hydride; ortho-substituents in the 2,4- and 2,5-isomers quench such reactivity through electron donation into the vacant boron pz orbital and steric blocking of the boron centre; as shown by electrochemical, structural and computational studies. Electrochemical studies of the corresponding borohydrides identify that the two-electron oxidation of terminal-hydrides occurs at more positive potentials than observed for [HB(C6F5)3]−, while the bridging-hydride oxidizes at a higher poten- tial still, comparable to that of free H2

Synthesis, Photochemical, and Redox Properties of Gold(I) and Gold(III) Pincer Complexes Incorporating a 2,2′:6′,2″-Terpyridine Ligand Framework

Reaction of [Au(C6F5)(tht)] (tht = tetrahydrothiophene) with 2,2′:6′,2″-terpyridine (terpy) leads to complex [Au(C6F5)(η1-terpy)] (1). The chemical oxidation of complex (1) with 2 equiv of [N(C6H4Br-4)3](PF6) or using electrosynthetic techniques affords the Au(III) complex [Au(C6F5)(η3-terpy)](PF6)2 (2). The X-ray diffraction study of complex 2 reveals that the terpyridine acts as tridentate chelate ligand, which leads to a slightly distorted square-planar geometry. Complex 1 displays fluorescence in the solid state at 77 K due to a metal (gold) to ligand (terpy) charge transfer transition, whereas complex 2 displays fluorescence in acetonitrile due to excimer or exciplex formation. Time-dependent density functional theory calculations match the experimental absorption spectra of the synthesized complexes. In order to further probe the frontier orbitals of both complexes and study their redox behavior, each compound was separately characterized using cyclic voltammetry. The bulk electrolysis of a solution of complex 1 was analyzed by spectroscopic methods confirming the electrochemical synthesis of complex 2

Endothelial Cell Thrombin Receptors and PAR-2 TWO PROTEASE-ACTIVATED RECEPTORS LOCATED IN A SINGLE CELLULAR ENVIRONMENT

Human endothelial cells express thrombin receptors and PAR-2, the two known members of the family of protease-activated G protein-coupled receptors. Because previous studies have shown that the biology of the human thrombin receptor varies according to the cell in which it is expressed, we have taken advantage of the presence of both receptors in endothelial cells to examine the enabling and disabling interactions with candidate proteases likely to be encountered in and around the vascular space to compare the responses elicited by the two receptors when they are present in the same cell and to compare the mechanisms of thrombin receptor and PAR-2 clearance and replacement in a common cellular environment. Of the proteases that were tested, only trypsin activated both receptors. Cathepsin G, which disables thrombin receptors, had no effect on PAR-2, while urokinase, kallikrein, and coagulation factors IXa, Xa, XIa, and XIIa neither substantially activated nor noticeably disabled either receptor. Like thrombin receptors, activation of PAR-2 caused pertussis toxin-sensitive phospholipase C activation as well as activation of phospholipase A2, leading to the release of PGI2. Concurrent activation of both receptors caused a greater response than activation of either alone. It also abolished a subsequent response to the PAR-2 agonist peptide, SLIGRL, while only partially inhibiting the response to the agonist peptide, SFLLRN, which activates both receptors. After proteolytic or nonproteolytic activation, PAR-2, like thrombin receptors, was cleared from the endothelial cell surface and then rapidly replaced with new receptors by a process that does not require protein synthesis. Selective activation of either receptor had no effect on the clearance of the other. These results suggest that the expression of both thrombin receptors and PAR-2 on endothelial cells serves more to extend the range of proteases to which the cells can respond than it does to extend the range of potential responses. The results also show that proteases that can disable these receptors can distinguish between them, just as do most of the proteases that activate them. Finally, the residual response to SFLLRN after activation of thrombin receptors and PAR-2 raises the possibility that a third, as yet unidentified member of this family is expressed on endothelial cells, one that is activated by neither thrombin nor trypsin

Interactions of Mast Cell Tryptase with Thrombin Receptors and PAR-2

Tryptase is a serine protease secreted by mast cells that is able to activate other cells. In the present studies we have tested whether these responses could be mediated by thrombin receptors or PAR-2, two G-protein-coupled receptors that are activated by proteolysis. When added to a peptide corresponding to the N terminus of PAR-2, tryptase cleaved the peptide at the activating site, but at higher concentrations it also cleaved downstream, as did trypsin, a known activator of PAR-2. Thrombin, factor Xa, plasmin, urokinase, plasma kallikrein, and tissue kallikrein had no effect. Tryptase also cleaved the analogous thrombin receptor peptide at the activating site but less efficiently. When added to COS-1 cells expressing either receptor, tryptase stimulated phosphoinositide hydrolysis. With PAR-2, this response was half-maximal at 1 nM tryptase and could be inhibited by the tryptase inhibitor, APC366, or by antibodies to tryptase and PAR-2. When added to human endothelial cells, which normally express PAR-2 and thrombin receptors, or keratinocytes, which express only PAR-2, tryptase caused an increase in cytosolic Ca2+. However, when added to platelets or CHRF-288 cells, which express thrombin receptors but not PAR-2, tryptase caused neither aggregation nor increased Ca2+. These results show that 1) tryptase has the potential to activate both PAR-2 and thrombin receptors; 2) for PAR-2, this potential is realized, although cleavage at secondary sites may limit activation, particularly at higher tryptase concentrations; and 3) in contrast, although tryptase clearly activates thrombin receptors in COS-1 cells, it does not appear to cleave endogenous thrombin receptors in platelets or CHRF-288 cells. These distinctions correlate with the observed differences in the rate of cleavage of the PAR-2 and thrombin receptor peptides by tryptase. Tryptase is the first protease other than trypsin that has been shown to activate human PAR-2. Its presence within mast cell granules places it in tissues where PAR-2 is expressed but trypsin is unlikely to reach

An Electrochemical Study of Frustrated Lewis Pairs: A Metal-free Route to Hydrogen Oxidation

[Image: see text] Frustrated Lewis pairs have found many applications in the heterolytic activation of H(2) and subsequent hydrogenation of small molecules through delivery of the resulting proton and hydride equivalents. Herein, we describe how H(2) can be preactivated using classical frustrated Lewis pair chemistry and combined with in situ nonaqueous electrochemical oxidation of the resulting borohydride. Our approach allows hydrogen to be cleanly converted into two protons and two electrons in situ, and reduces the potential (the required energetic driving force) for nonaqueous H(2) oxidation by 610 mV (117.7 kJ mol(–1)). This significant energy reduction opens routes to the development of nonaqueous hydrogen energy technology

“Janus” Calixarenes: Double-Sided Molecular Linkers for Facile, Multianchor Point, Multifunctional, Surface Modification

We herein report the synthesis of novel “Janus” calix[4]arenes bearing four “molecular tethering” functional groups on either the upper or lower rims of the calixarene. These enable facile multipoint covalent attachment to electrode surfaces with monolayer coverage. The other rim of the calixarenes bear either four azide or four ethynyl functional groups, which are easily modified by the copper(I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC), either pre- or postsurface modification, enabling these conical, nanocavity reactor sites to be decorated with a wide range of substrates to impart desired chemical properties. Redox active species decorating the peripheral rim are shown to be electrically connected by the calixarene to the electrode surface in either “up” or “down” orientations of the calixarene