Surface‐Guided Formation of an Organocobalt Complex

Organocobalt complexes represent a versatile tool in organic synthesis as they are important intermediates in Pauson–Khand, Friedel–Crafts, and Nicholas reactions. Herein, a single‐molecule‐level investigation addressing the formation of an organocobalt complex at a solid–vacuum interface is reported. Deposition of 4,4′‐(ethyne‐1,2‐diyl)dibenzonitrile and Co atoms on the Ag(111) surface followed by annealing resulted in genuine complexes in which single Co atoms laterally coordinated to two carbonitrile groups undergo organometallic bonding with the internal alkyne moiety of adjacent molecules. Alternative complexation scenarios involving fragmentation of the precursor were ruled out by complementary X‐ray photoelectron spectroscopy. According to density functional theory analysis, the complexation with the alkyne moiety follows the Dewar–Chatt–Duncanson model for a two‐electron‐donor ligand where an alkyne‐to‐Co donation occurs together with a strong metal‐to‐alkyne back‐donation.     

Peptide-based SAMs that resist the adsorption of proteins

In this paper we present a modular approach for the fabrication of surfaces to characterize protein-protein interactions. The approach is based on azido peptides with an optimized sequence which are then thiol-functionalized using an alkynyl thiol and "click" chemistry. From these peptide thiols we fabricated SAMs on gold to evaluate the protein resistance, using surface plasmon resonance spectroscopy, toward streptavidin, bovin serum albumin (BSA), and fibronectin.     

Mechanisms of Cysteine-Lysine Covalent Linkage—The Role of Reactive Oxygen Species and Competition with Disulfide Bonds**

Recently, a new naturally occurring covalent linkage was characterised, involving a cysteine and a lysine, bridged through an oxygen atom. The latter was dubbed as the NOS bond, reflecting the individual atoms involved in this uncommon bond which finds little parallel in lab chemistry. It is found to form under oxidising conditions and is reversible upon addition of reducing agents. Further studies have identified the bond in crystal structures across a variety of systems and organisms, potentially playing an important role in regulation, cellular defense and replication. Not only that, double NOS bonds have been identified and even found to be competitive in relation to the formation of disulfide bonds. This raises several questions about how this exotic bond comes to be, what are the intermediates involved in its formation and how it competes with other pathways of sulfide oxidation. With this objective in mind, we revisited our first proposed mechanism for the reaction with model electronic structure calculations, adding information about the reactivity with alternative reactive oxygen species and other potential competing products of oxidation. We present a network with more than 30 reactions which provides one of the most encompassing pictures for cysteine oxidation pathways to date.     

Towards a Precise NMR Quantification of Acute Phase Inflammation Proteins from Human Serum

Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N-glycans, respectively. Diffusion-edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins. Conventionally determined concentrations of acute phase glycoproteins correlate well with distinct features in NMR spectra (R² up to 0.9422, p-value <0.001), allowing the simultaneous quantification of several acute phase inflammation proteins. Overall, a proteo-metabolomics NMR signature of significant diagnostic potential is obtained within 10–20 min acquisition time. This is exemplified in serum samples from COVID-19 and cardiogenic shock patients showing significant changes in several acute phase proteins compared to healthy controls.     

UHV Studies of Methanol Decomposition on Mono‐ and Bimetallic CoPd Nanoparticles Supported on Thin Alumina Films

Bimetallic nanoparticles often turn out to be superior to the corresponding monometallic systems with respect to their catalytic properties. To study such effects for the methanol decomposition reaction, model catalysts were prepared by physical vapor deposition of Pd and Co under ultrahigh‐vacuum (UHV) conditions. Monometallic Pd and Co particles as well as CoPd core–shell particles were generated on an epitaxial alumina film grown on NiAl(110). The interaction with methanol is examined by temperature‐programmed desorption of methanol and carbon monoxide and by X‐ray photoelectron spectroscopy. The decomposition of methanol proceeds in two reaction pathways independent of the particle composition: complete dehydrogenation towards carbon monoxide and hydrogen, and C? O bond scission yielding carbon deposits. Pd is the most active material studied here. The relative importance of the two channels varies for the different particle systems: on Pd dehydrogenation is preferred, whereas the C? O bond cleavage is more pronounced on Co. The bimetallic clusters show a moderate performance for both pathways. Carbon deposition poisons the model catalysts by blocking the adsorption sites for methoxide, which is the first intermediate product during methanol decomposition. In particular on Co, large amounts of carbon deposits can also be caused by dissociation of the final product of the dehydrogenation pathway, carbon monoxide. A comparison with the results of methanol decomposition on Co, Pd, and CoPd catalysts in continuous‐flow reactors demonstrates that the findings of the present UHV study are relevant for catalytic performance under high‐pressure conditions.     

Synthesis and evaluation of novel pyridine based PLG tripeptidomimetics

Analogues of the pyridine based PLG (Pro-Leu-Gly-NH(2)) peptidomimetic were synthesized and evaluated as dopamine modulating agents. Modifications in the position corresponding to the leucine side chain in PLG afforded derivatives , and , substituted with H, Me and Bn instead of the isobutyl group, respectively. Changes in the proline residue produced derivative , substituted with a symmetrical piperidine ring instead of the pyrrolidine ring and , in which the pyrrolidine ring is connected to the pyridine ring via a hydroxymethyl group instead of a keto function. The peptidomimetics were tested for their ability to enhance the maximal effect of N-propylapomorphine (NPA) at dopamine D2 receptors in the functional cell-based R-SAT assay. Compounds , , and , produced a statistically significant increase in the maximal NPA response at 10 nM (117 +/- 6%, 118 +/- 6%, and 116 +/- 3%, respectively), which is similar to the effect of PLG in this assay, whereas was able to potentiate the response to a similar extent at 1 nM concentration (115 +/- 5%). All derivatives produced a bell-shaped dose-response curve and none of the compounds were active at the D2 receptor alone, which indicates that the mechanism behind the activity of both the pyridine based mimetics and PLG is the same. Interestingly, l-Pro-d-Leu-Gly-NH(2) was found to be more potent than PLG and produced a 119 +/- 1% increase in the NPA response at 1 nM.     

Critical exponents for line tension and dipole density difference from lipid monolayer domain boundary fluctuations

The potential physiological relevance of liquid-liquid phase separation in lipid membranes to the formation and stability of "lipid rafts" in cellular plasma membranes has prompted extensive investigation of the physical chemistry underlying these phenomena. In this contribution, the line tension (gamma) and dipole density differences ( micro) between demixed fluid phases of monolayers comprised of dimyristoylphosphatidylcholine (DMPC) and dihydrocholesterol (DChol) were investigated by measuring the two-dimensional thermal fluctuations of domain boundaries visualized by the inclusion of a fluorescent tracer lipid. These parameters are essential determinants of domain stability, and their quantification will yield an increased understanding of the physical processes responsible for aspects of lateral phase separation. Employing an extensive data set, the surface pressure dependence of gamma and mu was determined at three different monolayer compositions (30%, 35%, and 40% DChol). Both parameters were found to decrease with a power law dependence as the surface pressure approached the phase transition pressure (pi t), in agreement with previous measurements. Additionally, photobleaching effects and domain size influence were quantified and found to be small in our system. We suggest that the method of flicker spectroscopy can be helpful in identifying line-active compounds.