ChemRxiv
Not a member yet
27047 research outputs found
Sort by
Non-Steady State Validation of Kinetic Models for Ethylene Epoxidation over Silver Catalysts
No full textKinetic modelling has been key to developing a mechanistic understanding of the epoxidation of ethylene to ethylene oxide over silver catalysts. However, models of varying active site and mechanistic complexity have all been able to recreate steady state activity and selectivity, leading to an ambiguity about the exact mechanism and nature of the active site. Herein, we validate three leading kinetic models for ethylene epoxidation over metallic silver catalysts by numerically recreating non-steady state Temporal Analysis of Products experiments. We find all of the models are able to very generally recreate the trends observed in the pulse experiments, but that only a two-site model modified to mimic the presence of a subsurface oxygen reservoir is able to accurately recreate the trends observed in a state-altering experiment over oxidised silver. Specific to this model is the inclusion of a nucleophilic oxygen species adsorbed on top of the surface oxide which acts as the active site for the selective oxidation of ethylene. This work exemplifies that while simplified single-site models for ethylene epoxidation are useful tools for broad screening, more complex models are required to capture the precise activity of the catalyst
Rapid glycan labelling with fluorogenic molecular rotor dyes and nucleic acid stains responding to changes of the cell surface
No full textHerein, we introduce a dual-labelling technique for covalent modification of cell surfaces with fluo-rescent molecular rotor (FMR) dyes and environmentally insensitive fluorescent dyes. For this pur-pose, we combined an improved method for chemical reactions on sialic acid residues with FMR-dye hydrazides including dyes commonly used to stain nucleic acids. Fluorescence of FMR dyes increases upon molecular crowding and with increasing viscosity providing options for fluorogenic labelling of cell surfaces and detecting changes of cell surfaces that, for example, affect molecular crowding or local viscosity. The method involves mild periodate oxidation of cell surface glycans followed by or-ganocatalyzed dye conjugation. Both steps are performed within a total of 15 min at 25 °C, avoiding cold stress of cells. We show labelling glycans with FMR dyes such as 9-(2-carboxy-2-cyanovinyl)julolidine (CCVJ) or Cyanine 3 (Cy3) and the nucleic acid stain thiazole orange (TO) pro-vides sufficiently strong signals to allow fluorescence microscopy imaging of surfaces of A549, HeLa and CEM cells. Measurements with mucin suggest that the close proximity to glycans induced upon formation of covalent bonds is very efficient in hindering FMR torsional motions. We demonstrate that the fluorescence of CCVJ and TO on cell surface glycans and isolated mucin is influenced by the action of the disulfide-cleaving agent TCEP. Co-labelling of cells with CCVJ and an environmentally insensitive AF568 dye revealed a TCEP-induced decrease in the intensity CCVJ fluorescence, which did not occur when the dye was studied in glycerol solution, consistent with a decrease of the fluores-cence lifetime determined by fluorescence lifetime imaging microscopy (FLIM). This indicates that glycan-bound FMR dyes respond to changes in friction that hinder dye intramolecular rotation, poten-tially enabling the detection of changes occurring to surfaces of epithelial cells during disease and therapeutic intervention
Charge regulation triggers condensation of short oligopeptides to polyelectrolytes
No full textElectrostatic interactions between charged macromolecules are ubiquitous in bio- logical systems and they are important also in materials design. Attraction between oppositely charged molecules is often interpreted as if the molecules had a fixed charge, which is not affected by their interaction. Less commonly, charge regulation is invoked to interpret such interactions, i.e., a change of the charge state in response to a change of the local environment. Although some theoretical and simulation studies suggest that charge regulation plays an important role in intermolecular interations, experi- mental evidence supporting such view is very scarce. In the current study, we used a model system, composed of a long polyanion interacting with cationic oligolysines, containing up to 8 lysine residues. We showed using both simulations and experiments that while these lysines are only weakly charged in the absence of the polyanion, they charge up and condense on the polycations if the pH is close to the pKa of the lysine side chains. We show that the lysines coexist in two distinct populations within the same solution: 1. practically non-ionized and free in solution; 2. highly ionized and condensed on the polyanion. Using this model system, we demonstrate under what conditions charge regulation plays a significant role in the interactions of oppositely charged macromolecules and generalize our findings beyond the specific system used here
A robust “bottom up” proteomics pipeline is integral for assessing protein structure using hydroxyl radical protein footprinting mass spectrometry.
No full textHydroxyl Radical Protein Footprinting (HRPF) monitors macromolecular structure and dynamics by utilizing hydroxyl radicals to probe the solvent-accessible side chains of proteins. Hydroxyl radicals form irreversible covalent bonds with protein side chains based on their solvent accessibility and intrinsic reactivity. Following labeling, bottom-up proteomics which involves protease digestion and liquid chromatography (LC-MS/MS) coupled with mass spectrometry, is routinely employed to detect and quantify the modified protein side chains. The HRPF technique has been a breakthrough in the field of structural biology, enabling the assessment of structures and interrelationships between proteins, protein-drug complexes or such macromolecular mixtures. It is now being extended to complex applications such as in-cell and in-vivo studies. This perspective focuses on detailing aspects of peptide separations technology in HRPF, with a particular emphasis on chromatography. The discussion further encompasses the HRPF methodology, its current limitations, recent developments, and proposed ideas for future developments for selected research fields
Template-Directed Synthesis of Strained meso-meso-Linked Porphyrin Nanorings
No full textStrained macrocycles display interesting properties, such as conformational rigidity, often resulting in enhance π-conjugation or enhanced affinity for non-covalent guest binding, yet they can be difficult to synthesize. Here we use computational modeling to design a template to direct the formation of an 18-porphyrin nanoring with direct meso-meso bonds between the porphyrin units. Coupling of a linear 18-porphyrin oligomer in the presence of this template gives the target nanoring, together with an unexpected 36-porphyrin ring by-product. Scanning tunneling microscopy (STM) revealed the elliptical conformations and flexibility of these nanorings on a Au(111) surface
Trivalent Cations Slow Electron Transfer to Macrocyclic Heterobimetallic Complexes
No full textIncorporation of secondary redox-inactive cations into heterobimetallic complexes is an attractive strategy for modulation of metal-centered redox chemistry, but quantification of the consequences of incorporating strongly Lewis acidic trivalent cations has received little attention. Here, a family of seven heterobimetallic complexes that pair a redox-active nickel center with La3+, Y3+, Lu3+, Sr2+, Ca2+, K+, and Na+ (in the form of their triflate salts) have been prepared on a heteroditopic ligand platform to understand how chemical behavior varies across the comprehensive series. Structural data from X-ray diffraction analysis demonstrate that the positions adopted by the secondary cations in the crown-ether-like site of the ligand relative to nickel are dependent primarily on the secondary cations’ ionic radii, and that the triflate counter-anions are bound to the cations in all cases. Electrochemical data, in concert with electron paramagnetic resonance (EPR) studies, show that nickel(II)/nickel(I) redox is modulated by the secondary metals; the heterogeneous electron transfer (ET) rate is diminished for the derivatives incorporating trivalent metals, an effect that is dependent on steric crowding about the nickel metal center and that was quantified here with a topographical free-volume analysis. As related analyses carried out here on previously reported systems bear out similar relationships that were not noted in prior work, we conclude that the placement and identity of both the secondary metal cations and their associated counter-anions can afford unique changes in the (electro)chemical behavior of heterobimetallic species
Biocatalytic enantioselective C(sp3)–H fluorination enabled by directed evolution of nonheme Fe enzymes
No full textDue to the scarcity of C–F bond forming enzymatic activities in nature and the contrasting ubiquity of organofluorine moieties in bioactive compounds, developing new biocatalytic fluorination reactions represents a preeminent challenge in enzymology,
biocatalysis, and synthetic biology. Additionally, catalytic asymmetric C(sp3)–H fluorination remains a challenging problem facing synthetic chemists. Although many nonheme Fe halogenases have been discovered to promote C(sp3)–H halogenation reactions, to date, efforts to convert these Fe halogenases to fluorinases have remained unsuccessful. We repurposed a plant-derived natural nonheme enzyme 1-aminocyclopropane-1-carboxylic
acid oxidase (ACCO) to catalyze unnatural enantioselective C(sp3)–H fluorination via a radical rebound mechanism. Directed evolution afforded C–H fluorinating enzyme
ACCOCHF displaying 200-fold higher activity, substantially improved chemoselectivity and excellent enantioselectivity, converting a range of substrates into enantioenriched
organofluorine products. Notably, almost all the beneficial mutations were found to be distal to the Fe centre, underscoring the importance of substrate tunnel engineering in nonheme Fe biocatalysis. Computational studies revealed that the radical rebound step with the
Fe(III)–F intermediate has an exceedingly low activation barrier of 3.4 kcal/mol, highlighting a new avenue to expand the catalytic repertoire of enzymes to encompass asymmetric C–F bond formation
Correlation Analysis in X-ray Photoemission Spectroscopy
No full textX-ray photoelectron spectroscopy (XPS) is a powerful technique for surface analysis, but such analysis can be hindered by uncertainty in modelling spectra. Often, many spectral models have a similar goodness of fit, and distinguishing between them can be impossible without additional information. A further challenge is found in interpreting spectra from samples consisting of multiple chemical compounds. We show here how correlation analysis can be used to interpret large XPS datasets. Correlations in atomic concentrations and binding energies of core lines can be interpreted within a framework of an underlying chemical model and this can yield additional information compared with analysis of each spectrum individually. We give examples of the usage of this analysis on some simple systems, and discuss the potential and limitations of the technique
A Bioinspired Non-heme FeIII−(O22−)−CuII Complex with a St = 1 Ground State
No full textCytochrome c oxidase (CcO) is a heme−copper oxidase (HCO) that catalyzes the natural reduction of oxygen to water. A pro-found understanding of some of the elementary steps leading to the intricate 4e−/4H+ reduction of O2 is presently lacking. A St = 1 FeIII−(O22−)−CuII (IP) intermediate is proposed to reduce the overpotentials associated with the reductive O−O bond rupture by allowing electron transfer from a tyrosine moiety without the necessity of any spin-surface crossing. Direct evidence of the in-volvement of IP in the HCO catalytic cycle is, however, missing. A number of heme-copper peroxido complexes have been pre-pared as synthetic models of IP; but all of them possess the catalytically non-relevant St = 0 ground state resulting from antiferro-magnetic coupling between the S = 1/2 FeIII and CuII centers. In a complete non-heme approach, we now report the spectroscopic characterization and reactivity of the FeIII−(O22−)−CuII intermediates 1 and 2, which differ only by a single −CH3 versus −H sub-stituent on the central amine of the tridentate ligands binding to copper. Complex 1 with an end-on peroxido core, and ferromag-netically (St=1) coupled FeIII and CuII centers performs H-bonding mediated O−O bond cleavage in presence of phenol to generate oxoiron(IV), copper(II) and PhO•. In contrast, the side-on peroxide complex 2, with a St = 0 ground-state is unreactive towards phenol. Thus, the implications for spin topology contributions to O−O bond cleavage, as proposed for the heme FeIII−(O22−)−CuII intermediate in CcO, can be extended to non-heme chemistry
Guideline for Elucidating Catalysts
No full textIn the last decades, numerous efforts have been made to replace metal catalysts with cheaper and earth-abundant alternatives or the complete exclusion of metals in cross-coupling reactions, maintaining high efficiency of the target transformation. However, follow-up studies often revealed the role of metal impurities in the catalytic process. Thus, active metal impurities lead to mechanistic misinterpretations, could initiate erroneous research directives, and can lead to severe reproducibility problems. Milestone precedents of impurity effect in cross-coupling reactions are well documented in the literature. Interestingly, this fallacy has occurred repeatedly over the years due to the lack of thorough mechanistic studies and the appropriate research study scheme for identifying the impurity effect. Herein, we propose a guideline elucidating the real catalyst of future catalytic transformations that could eliminate mechanistic misinterpretation and help exclude the role of impurities in novel catalytic processes. Although this guideline mainly focuses on problems related to trace transition metals, it also offers the base for more general catalyst research