Intermediates of N-Heterocyclic Carbene (NHC) Dimerization Probed in the Gas Phase by Ion Mobility Mass Spectrometry: C−H⋅⋅⋅:C Hydrogen Bonding Versus Covalent Dimer Formation

N-Heterocyclic carbenes (NHCs, :C ) can interact with azolium salts ( C−H⁺ ) by either forming a hydrogen-bonded aggregate ( CHC⁺ ) or a covalent C−C bond ( CCH⁺ ). In this study, the intramolecular NHC–azolium salt interactions of aromatic imidazolin-2-ylidenes and saturated imidazolidin-2-ylidenes have been investigated in the gas phase by traveling wave ion mobility mass spectrometry (TW IMS) and DFT calculations. The TW IMS experiments provided evidence for the formation of these important intermediates in the gas phase, and they identified the predominant aggregation mode (hydrogen bond vs. covalent C−C) as a function of the nature of the interacting carbene–azolium pairs.     

Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file

The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.     

Crown Ethers and Phase Transfer Catalysis in Polymer Chemistry

Abstract

This paper is the first half of a two part review on the applications of crown ethers, cryptands, glymes and various onium ion salts to polymer chemistry. Part 1 surveys the use of these phase transfer catalysts (PTC's) in the synthesis and modification of macromolecules. Applications to ring-opening and vinyl polymerizations generally have involved solubilization and activation by PTC's of organic and inorganic salts which serve as anionic initiators. Change in the polymerization rates, polymer yields and product microstructure often resulted from association of the PTC with the active chain end.

Polymer modification and functionalization reactions have been enhanced by the use of PTC's. Macromolecular substrates have included both soluble and insoluble polymers, although the most popular have been the readily-available Merrifield resins. Generally these two-phase reactions have involved polymer solutions interacting with insoluble reagents or insoluble polymers reacting with the reagent solution. Some of the groups incorporated have been thiols, nitriles, carboxylic acids, esters, and crown ether analogs themselves. Most of this work has aimed at synthesis of polymer derivatives which can serve as chelating agents, catalysts and reagents in subsequent reactions. In almost all cases described, phase transfer catalysis offers definate advantages in selectivity and yield over conventional methods. The outline below gives the general subject areas of both Part 1 and Part 2; the latter will be published shortly.     

Integration of the 1,2,3‐Triazole “Click” Motif as a Potent Signalling Element in Metal Ion Responsive Fluorescent Probes

In a systematic approach we synthesized a new series of fluorescent probes incorporating donor–acceptor (D‐A) substituted 1,2,3‐triazoles as conjugative π‐linkers between the alkali metal ion receptor N‐phenylaza‐[18]crown‐6 and different fluorophoric groups with different electron‐acceptor properties (4‐naphthalimide, meso‐phenyl‐BODIPY and 9‐anthracene) and investigated their performance in organic and aqueous environments (physiological conditions). In the charge‐transfer (CT) type probes 1 , 2 and 7 , the fluorescence is almost completely quenched by intramolecular CT (ICT) processes involving charge‐separated states. In the presence of Na⁺ and K⁺ ICT is interrupted, which resulted in a lighting‐up of the fluorescence in acetonitrile. Among the investigated fluoroionophores, compound 7 , which contains a 9‐anthracenyl moiety as the electron‐accepting fluorophore, is the only probe which retains light‐up features in water and works as a highly K⁺/Na⁺‐selective probe under simulated physiological conditions. Virtually decoupled BODIPY‐based 6 and photoinduced electron transfer (PET) type probes 3 – 5 , where the 10‐substituted anthracen‐9‐yl fluorophores are connected to the 1,2,3‐triazole through a methylene spacer, show strong ion‐induced fluorescence enhancement in acetonitrile, but not under physiological conditions. Electrochemical studies and theoretical calculations were used to assess and support the underlying mechanisms for the new ICT and PET 1,2,3‐triazole fluoroionophores.     

Reaction with SO3 in Ionic Liquids: The Example of K2(S2O7)­(H2SO4)

The ionic liquid 1‐butyl‐3‐methylimidazolium hydrogensulfate, [bmim]HSO₄, turned out to be resistant even to strong oxidizers like SO₃. Thus, it should be a suitable solvent for the preparation of polysulfates at low temperatures. As a proof of principle we here present the synthesis and crystal structure of K₂(S₂O₇)(H₂SO₄), which has been obtained from the reaction of K₂SO₄ and SO₃ in [bmim]HSO₄. In the crystal structure of K₂(S₂O₇)(H₂SO₄) (orthorhombic, Pbca, Z = 8, a = 810.64(2) pm, b = 1047.90(2) pm, c = 2328.86(6) pm, V = 1978.30(8) ų) two crystallographically unique potassium cations are coordinated by a different number of monodentate and bidentate‐chelating disulfate anions as well as by sulfuric acid molecules. The crystal structure consists of alternating layers of [K₂(S₂O₇)] slabs and H₂SO₄ molecules. Hydrogen bonds between hydrogen atoms of sulfuric acid molecules and oxygen atoms of the neighboring disulfate anions are observed.     

Combined QCM-D/GE as a tool to characterize stimuli-responsive swelling of and protein adsorption on polymer brushes grafted onto 3D-nanostructures

A combined setup of quartz crystal microbalance and generalized ellipsometry can be used to comprehensively investigate complex functional coatings comprising stimuli-responsive polymer brushes and 3D nanostructures in a dynamic, noninvasive in situ measurement. While the quartz crystal microbalance detects the overall change in areal mass, for instance, during a swelling or adsorption process, the generalized ellipsometry data can be evaluated in terms of a layered model to distinguish between processes occurring within the intercolumnar space or on top of the anisotropic nanocolumns. Silicon films with anisotropic nanocolumnar morphology were prepared by the glancing angle deposition technique and further functionalized by grafting of poly-(acrylic acid) or poly-(N- isopropylacrylamide) chains. Investigations of the thermoresponsive swelling of the poly-(N-isopropylacrylamide) brush on the Si nanocolumns proved the successful preparation of a stimuli-responsive coating. Furthermore, the potential of these novel coatings in the field of biotechnology was explored by investigation of the adsorption of the model protein bovine serum albumin. Adsorption, retention, and desorption triggered by a change in the pH value is observed using poly-(acrylic acid) functionalized nanostructures, although generalized ellipsometry data revealed that this process occurs only on top of the nanostructures. Poly-(N-isopropylacrylamide) is found to render the nanostructures non-fouling properties.     

Two-loop virtual top-quark effect on Higgs-boson decay to bottom quarks

In most of the mass range encompassed by the limits from the direct search and the electroweak precision tests, the Higgs boson of the standard model preferably decays to bottom quarks. We present, in analytic form, the dominant two-loop electroweak correction, of O(GF2mt4), to the partial width of this decay. It amplifies the familiar enhancement due to the O(GFmt2) one-loop correction by about +16% and thus more than compensates the screening by about -8% through strong-interaction effects of order O(alphasGFmt2).