Characterization of Collagen/Lipid Nanoparticle–Curcumin Cryostructurates for Wound Healing Applications

Curcumin‐loaded collagen cryostructurates have been devised for wound healing applications. Curcumin displays strong antioxidant, antiseptic, and anti‐inflammatory properties, while collagen is acknowledged for promoting cell adhesion, migration and differentiation. However, when curcumin is loaded directly into collagen hydrogels, it forms large molecular aggregates and clogs the matrix pores. A double‐encapsulation strategy is therefore developed by loading curcumin into lipid nanoparticles (LNP), and embedding these particles inside collagen scaffolds. The resulting collagen/LNP cryostructurates have an optimal fibrous structure with ≈100 µm average pore size for sustaining cell migration. Results show that collagen is structurally unaltered and that nanoparticles are homogeneously distributed amidst collagen fibers. Hydrogels soaked in saline buffer release about 20 to 30% of their nanoparticles content within 24 h, while achieved 100% release after 25 days. When exposed to NIH 3T3 fibroblasts, these hydrogels provide a satisfactory scaffold for cell interaction as early as 4 h after seeding, with no cytotoxic counter effect. These positive features make the collagen/lipid cryostructurates a promising material for further use in wound healing.     

Quenching of the Singlet and Triplet Excited States of Pterin by Amino Acids

Unconjugated oxidized pterins accumulate in the skin of patients suffering from vitiligo and, under UVA irradiation, photosensitize the oxidation of amino acids. In this work, we study the interaction of the singlet and triplet excited states of pterin (Ptr), the parent compound of oxidized pterins, with four oxidizable amino acids: tryptophan (Trp), tyrosine (Tyr), histidine (His) and methionine (Met). Steady‐state and time‐resolved fluorescence measurements and laser flash photolysis experiments were performed to investigate the quenching of the Ptr excited states by the amino acids in aqueous solution. The singlet excited states of Ptr are quenched by Met mainly via a dynamic process and by Trp via a combination of dynamic and static processes. His does not quench singlet excited states of Ptr, and quenching by Tyr could not be investigated due to the low solubility of this amino acid. The triplet excited states of Ptr are quenched by the four studied amino acids, and the corresponding bimolecular quenching rate constants are in the range of diffusion controlled limit. The assessment of the results in the context of the Ptr‐photosensitization of amino acids suggests that triplet excited state of Ptr is the species that initiates the photochemical processes.     

Sulfilimines as Versatile Nitrene Transfer Reagents: Facile Access to Diverse Aza‐Heterocycles

We herein report the unprecedented synthesis of diverse biologically important aza‐heterocycles by employing sulfilimines as nitrene transfer reagents. This class of sulfur‐based aza‐ylides had not been successfully used for gold nitrene transfer before. This work contains an efficient generation of α‐imino gold carbenes by N?S cleavage of sulfilimines. These gold carbenes undergo C?H insertion, cyclopropanation, and nucleophilic attack to form indoles (44 examples), 3‐azabicyclo[3.1.0]hexan‐2‐imines (24 examples), and imidazoles (3 examples). Our study represents a unique gold‐catalyzed reaction between alkynes and sulfur ylides, and also includes the first aza‐heterocycle synthesis that proceeds by intermolecular nitrene transfer followed by cyclopropanation of the α‐imino gold carbenes. Moreover, an unexpected synthesis of 4‐acylquinolines (3 examples) from 2‐acylphenyl sulfilimines and propargylic silyl ether derivatives by a 1,2‐hydride shift onto the α‐imino gold carbene and a subsequent Mukaiyama aldol cyclization was discovered.     

Reactivity of urethanes at high temperature: Transurethanization and side reactions

The reactivity of urethanes based on 1,6‐hexamethylene diisocyanate (HDI) and 4,4′‐methylene diphenyl diisocyanate (MDI) was investigated at temperatures between 190 °C and 235 °C. Diurethane model compounds end‐capped with either 1‐dodecanol (D‐core‐D) or 1‐hexadecanol (H‐core‐H) were mixed and annealed at high temperature. The core was either MDI or HDI. The transurethanization reaction was followed based on the formation of the compounds (H‐core‐D). The amount of H‐core‐D and of side products, which had formed after variable annealing times, were identified with ¹H NMR, FTIR, SEC, and MALDI‐TOF. Transurethanization was considerably faster for MDI‐based urethanes than for HDI‐based urethanes. Only traces of side products were formed during annealing of MDI‐based urethanes, whereas a significant amount of allophanates was formed from HDI‐based urethanes under the same conditions. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 621–629     

Self‐emulsion polymerization of amphiphilic monomers—a green route to synthesis of polymeric nanoscaffolds

Self‐emulsion polymerization (SEP), a green route developed by us for the polymerization of amphiphilic monomers, does not require any emulsifier or an organic solvent except that the water‐soluble initiators such as 2,2′‐azobis[2‐(2‐imidazolin‐2‐yl)propane]dihydrochloride (VA‐044) and potassium persulfate (KPS) are only used. We report here the polymer nanoscaffolds from a number of amphiphilic monomers, which can be used for in situ encapsulation of a variety of nanoparticles. As a demonstration of the efficacy of these nanoscaffolds, the synthesis of a biocompatible hybrid nanoparticle (nanohybrid), prepared by encapsulating Fe₃O₄ magnetic nanoparticle (Fe₃O₄ MNPs) in poly(2‐hydroxyethyl methacrylate) in water, for MRI application is presented. The nanohybrid prepared following the SEP in the form of an emulsion does not involve the use of any stabilizing agent, crosslinker, polymeric emulsifier, or surfactant. This water‐soluble, spherical, and stable nanohybrid containing Fe₃O₄ MNPs of average size 10 ± 2 nm has a zeta potential value of ?41.89 mV under physiological conditions. Magnetic measurement confirmed that the nanohybrid shows typical magnetic behavior having a saturation magnetization (Ms) value of 32.3 emu/g and a transverse relaxivity (r2) value of 29.97 mM^?1 s^?1, which signifies that it can be used as a T2 contrast agent in MRI. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019     

Proto‐Urea‐RNA (Wöhler RNA) Containing Unusually Stable Urea Nucleosides

The RNA world hypothesis assumes that life on Earth began with nucleotides that formed information‐carrying RNA oligomers able to self‐replicate. Prebiotic reactions leading to the contemporary nucleosides are now known, but their execution often requires specific starting materials and lengthy reaction sequences. It was therefore proposed that the RNA world was likely proceeded by a proto‐RNA world constructed from molecules that were likely present on the early Earth in greater abundance. Herein, we show that the prebiotic starting molecules bis‐urea (biuret) and tris‐urea (triuret) are able to directly react with ribose. The urea‐ribosides are remarkably stable because they are held together by a network of intramolecular, bifurcated hydrogen bonds. This even allowed the synthesis of phosphoramidite building blocks and incorporation of the units into RNA. Investigations of the nucleotides’ base‐pairing potential showed that triuret:G RNA base pairs closely resemble U:G wobble base pairs. Based on the probable abundance of urea on the early Earth, we postulate that urea‐containing RNA bases are good candidates for a proto‐RNA world.     

Directional Self‐Assembly of Fluorinated Star Block Polymer Thin Films Using Mixed Solvent Vapor Annealing

We demonstrate the directional alignment of perpendicular‐lamellae domains in fluorinated three‐armed star block polymer (BP) thin films using solvent vapor annealing with shear stress. The control of orientation and alignment was accomplished without any substrate surface modification. Additionally, three‐armed star poly(methyl methacrylate‐block‐styrene) [PMMA‐PS] and poly(octafluoropentyl methacrylate‐block‐styrene) were compared to their linear analogues to examine the impact of fluorine content and star architecture on self‐assembled BP feature sizes and interdomain density profiles. X‐ray reflectometry results indicated that the star BP molecular architecture increased the effective polymer segregation strength and could possibly facilitate reduced polymer domain spacings, which are useful in next‐generation nanolithographic applications. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 1663–1672     

C−I‐Selective Cross‐Coupling Enabled by a Cationic Palladium Trimer

While there is a growing interest in harnessing synergistic effects of more than one metal in catalysis, relatively little is known beyond bimetallic systems. This report describes the straightforward access to an air‐stable Pd trimer and presents unambiguous reactivity data of its privileged capability to differentiate C?I over C?Br bonds in C?C bond formations (arylation and alkylation) of polyhalogenated arenes, which typical Pd⁰ and Pd^I‐Pd^I catalysts fail to deliver. Experimental and computational reactivity data, including the first location of a transition state for bond activation by the trimer, are presented, supporting direct trimer reactivity to be feasible.     

Copper-Photocatalyzed Borylation of Organic Halides under Batch and Continuous-Flow Conditions

The copper-photocatalyzed borylation of aryl, heteroaryl, vinyl and alkyl halides (I and Br) was reported. The reaction proceeded using a new heteroleptic Cu complex under irradiation with blue LEDs, giving the corresponding boronic-acid esters in good to excellent yields. The reaction was extended to continuous-flow conditions to allow an easy scale-up. The mechanism of the reaction was studied and a mechanism based on a reductive quenching (Cu^I/Cu^I*/Cu⁰) was suggested.     

A New Class of Lanthanide Complexes with Three Ligand Centered Radicals: NMR Evaluation of Ligand Field Energy Splitting and Magnetic Coupling

Combination of three radical anionic Ph-BIAN ligands (Ph-BIAN=bis-(phenylimino)-acenaphthenequinone) with lanthanoid ions leads to a series of homoleptic, six-coordinate complexes of the type Ln(Ph-BIAN)₃. Magnetic coupling data were measured by paramagnetic solution NMR spectroscopy. Combining ¹H NMR with ²H NMR of partially deuterated compounds allowed a detailed study of the magnetic susceptibility anisotropies over a large temperature range. The observed chemical shifts were separated into ligand- and metal-centered contributions by comparison with the Y analogue (diamagnetic at the metal). The metal-centered contributions of the complexes with the paramagnetic ions could then be separated into pseudocontact and Fermi contact shifts. The latter is large within the Ph-BIAN scaffold, which shows that magnetic coupling is significant between the lanthanide ion and the radical ligand. Pseudocontact shifts were further correlated to structural data obtained from X-ray diffraction experiments. Ligand-field parameters were determined by fitting the temperature dependence of the observed magnetic susceptibility anisotropies. The electronic structure determined by this approach shows, that the Er and Tm analogues are candidates for single molecule magnets (SMM). These results demonstrate the possibilities for the application of NMR spectroscopy in investigations of paramagnetic systems in general and single molecule magnets in particular.