LC-MS/MS Analysis and Comparison of Oxidative Damages on Peptides Induced by Pathogen Reduction Technologies for Platelets

Pathogen reduction technologies (PRT) are photochemical processes that use a combination of photosensitizers and UV-light to inactivate pathogens in platelet concentrates (PCs), a blood-derived product used to prevent hemorrhage. However, different studies have questioned the impact of PRT on platelet function and transfusion efficacy, and several proteomic analyses revealed possible oxidative damages to proteins. The present work focused on the oxidative damages produced by the two main PRT on peptides. Model peptides containing residues prone to oxidation (tyrosine, histidine, tryptophane, and cysteine) were irradiated with a combination of amotosalen/UVA (Intercept process) or riboflavin/UVB (Mirasol-like process). Modifications were identified and quantified by liquid chromatography coupled to tandem mass spectrometry. Cysteine-containing peptides formed disulfide bridges (R-SS-R, ?2 Da; favored following amotosalen/UVA), sulfenic and sulfonic acids (R-SOH, +16 Da, R-SO₃H, +48 Da, favored following riboflavin/UVB) upon treatment and the other amino acids exhibited different oxidations revealed by mass shifts from +4 to +34 Da involving different mechanisms; no photoadducts were detected. These amino acids were not equally affected by the PRT and the combination riboflavin/UVB generated more oxidation than amotosalen/UVA. This work identifies the different types and sites of peptide oxidations under the photochemical treatments and demonstrates that the two PRT may behave differently. The potential impact on proteins and platelet functions may thus be PRT-dependent.

Crystallization of the $${\text{Mn}}^{{\text{II}}}[12{\text{-MC}}_{{\text{Mn}}^{{\text{III}}}{\text{(N)shi}}}{\text{-}}4]^{2+}$$ Mn II [ 12 -MC Mn III (N)shi - 4 ] 2 + Structure with 1,2,4-Triazolate from Methanol

Journal of Chemical Crystallography - The metallacrown (MC) dimer complex {MnII(OAc)(1,2,4-trz) $$[12{\text{-MC}}_{{\text{Mn}}^{{\text{III}}}{\text{(N)shi}}}{\text{-}}4]$$...     

Atom‐Economic,Regiodivergent, and Stereoselective Coupling of Imidazole Derivatives with Terminal Allenes

New Rh‐ and Pd‐catalyzed regiodivergent and stereoselective intermolecular coupling reactions of imidazole derivatives with mono‐substituted allenes are herein reported. Using a Rh^I/Josiphos system, perfect regioselectivities and high enantiomeric excess were obtained, while a Pd^II/dppf system gave linear products with high regioselectivities and high E/Z selectivities. This method permits the atom economic synthesis of valuable branched and linear allylic imidazole derivatives.     

Synthesis and Surface‐Spectroscopic Characterization of Photoisomerizable glyco‐SAMs on Au(111)

Photoisomerizable glyco‐SAMs (self‐assembled monolayers), utilizing synthetic azobenzene glycoside derivatives were fabricated. The ultimate goal of this project is to assay the influence of the 3D arrangement of sugar ligands on cell adhesion, and eventually make cell adhesion photoswitchable. However, it is a prerequisite for any biological study on the spatial conditions of carbohydrate recognition, that photoisomerization of the surface molecules can be verified. Here, we employed IRRAS and XPS to spectroscopically characterize glyco‐SAMs. In particular and unprecedented to date, we prove reversible E→Z→E isomerization of azobenzene glycoside‐terminated SAMs.     

Direct X‐ray Observation of Trapped CO2 in a Predesigned Porphyrinic Metal–Organic Framework

Metal–organic frameworks (MOFs) are emerging microporous materials that are promising for capture and sequestration of CO₂ due to their tailorable binding properties. However, it remains a grand challenge to pre‐design a MOF with a precise, multivalent binding environment at the molecular level to enhance CO₂ capture. Here, we report the design, synthesis, and direct X‐ray crystallographic observation of a porphyrinic MOF, UNLPF‐2, that contains CO₂‐specific single molecular traps. Assembled from an octatopic porphyrin ligand with [Co₂(COO)₄] paddlewheel clusters, UNLPF‐2 provides an appropriate distance between the coordinatively unsaturated metal centers, which serve as the ideal binding sites for in situ generated CO₂. The coordination of Co^II in the porphyrin macrocycle is crucial and responsible for the formation of the required topology to trap CO₂. By repeatedly releasing and recapturing CO₂, UNLPL‐2 also exhibits recyclability.     

Cooperative,Reversible Self‐Assembly of Covalently Pre‐Linked Proteins into Giant Fibrous Structures

We demonstrate a simple bioconjugate polymer system that undergoes reversible self‐assembling into extended fibrous structures, reminiscent of those observed in living systems. It is comprised of green fluorescent protein (GFP) molecules linked into linear oligomeric strands through click step growth polymerization with dialkyne poly(ethylene oxide) (PEO). Confocal microscopy, atomic force microscopy, and dynamic light scattering revealed that such strands form high persistence length fibers, with lengths reaching tens of micrometers, and uniform, sub‐100 nm widths. We ascribe this remarkable and robust form of self‐assembly to the cooperativity arising from the known tendency of GFP molecules to dimerize through localized hydrophobic patches and from their covalent pre‐linking with flexible PEO. Dissipative particle dynamics simulations of a coarse‐grained model of the system revealed its tendency to form elongated fibrous aggregates, suggesting the general nature of this mode of self‐assembly.     

Hollow Spheres of Iron Carbide Nanoparticles Encased in Graphitic Layers as Oxygen Reduction Catalysts

Nonprecious metal catalysts for the oxygen reduction reaction are the ultimate materials and the foremost subject for low‐temperature fuel cells. A novel type of catalysts prepared by high‐pressure pyrolysis is reported. The catalyst is featured by hollow spherical morphologies consisting of uniform iron carbide (Fe₃C) nanoparticles encased by graphitic layers, with little surface nitrogen or metallic functionalities. In acidic media the outer graphitic layers stabilize the carbide nanoparticles without depriving them of their catalytic activity towards the oxygen reduction reaction (ORR). As a result the catalyst is highly active and stable in both acid and alkaline electrolytes. The synthetic approach, the carbide‐based catalyst, the structure of the catalysts, and the proposed mechanism open new avenues for the development of ORR catalysts.     

The rheological properties of hydrogenated castor oil crystals

The present study focuses on the rheological performance of a surfactant-rich aqueous suspension containing hydrogenated castor oil (HCO) crystals. HCO can be typically crystallized in five distinct shapes: spherically shaped, irregularly shaped, star-shaped (also called rosettes), short needles, and thick or thin fibers. The effect of the differences in shape on the rheological performance is studied, and the rheological properties are compared to the behavior of other triacylglycerol’s (TAG) suspensions. A suspension of TAG crystals usually behaves as a colloidal gel wherein a colloidal gel is defined as a network of flocs, with each floc being an aggregate of smaller subunits. All of these surfactant-rich aqueous suspensions of HCO crystals behaved according to a colloidal gel in the transient regime, independent of the studied crystal shapes, except the long thin fibers at a concentration above 0.1 wt% HCO transitioning from a heterogeneous fractal rod network to a homogeneous rod network, shifting from a colloidal gel to a glass.     

Covalent Adaptable Networks with Tunable Exchange Rates Based on Reversible Thiol–yne Cross‐Linking

The design of covalent adaptable networks (CANs) relies on the ability to trigger the rearrangement of bonds within a polymer network. Simple activated alkynes are now used as versatile reversible cross‐linkers for thiols. The click‐like thiol–yne cross‐linking reaction readily enables network synthesis from polythiols through a double Michael addition with a reversible and tunable second addition step. The resulting thioacetal cross‐linking moieties are robust but dynamic linkages. A series of different activated alkynes have been synthesized and systematically probed for their ability to produce dynamic thioacetal linkages, both in kinetic studies of small molecule models, as well as in stress relaxation and creep measurements on thiol–yne‐based CANs. The results are further rationalized by DFT calculations, showing that the bond exchange rates can be significantly influenced by the choice of the activated alkyne cross‐linker.     

Selective Interactions of O-Methylated Flavonoid Natural Products with Human Monoamine Oxidase-A and -B

A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were characterized for their interaction with human monoamine oxidases (MAO-A and -B) in vitro. Compounds 1, 2, and 5 showed selective inhibition of MAO-A, while 4 and 6 showed selective inhibition of MAO-B. Compound 3 showed ~2-fold selectivity towards inhibition of MAO-A. Binding of compounds 1–3 and 5 with MAO-A, and compounds 3 and 6 with MAO-B was reversible and not time-independent. The analysis of enzyme-inhibition kinetics suggested a reversible-competitive mechanism for inhibition of MAO-A by 1 and 3, while a partially-reversible mixed-type inhibition by 5. Similarly, enzyme inhibition-kinetics analysis with compounds 3, 4, and 6, suggested a competitive reversible inhibition of MAO-B. The molecular docking study suggested that 1 selectively interacts with the active-site of human MAO-A near N5 of FAD. The calculated binding free energies of the O-methylated flavonoids (1 and 4–6) and chalcones (2 and 3) to MAO-A matched closely with the trend in the experimental IC_50′s. Analysis of the binding free-energies suggested better interaction of 4 and 6 with MAO-B than with MAO-A. The natural O-methylated flavonoid (1) with highly potent inhibition (IC₅₀ 33 nM; Ki 37.9 nM) and >292 fold selectivity against human MAO-A (vs. MAO-B) provides a new drug lead for the treatment of neurological disorders.