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Nature Communications Mar 2021Effective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from...
Effective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.
Topics: Animals; Cell Proliferation; Cicatrix; Disease Models, Animal; Extracellular Matrix; Female; Fibroblasts; Hydrogels; Imines; Male; Mice; Rabbits; Signal Transduction; Skin; Sus scrofa; Transforming Growth Factor beta; Wound Healing
PubMed: 33723267
DOI: 10.1038/s41467-021-21964-0 -
Chemical Reviews Jun 2021The merging of click chemistry with discrete photochemical processes has led to the creation of a new class of click reactions, collectively known as photoclick... (Review)
Review
The merging of click chemistry with discrete photochemical processes has led to the creation of a new class of click reactions, collectively known as photoclick chemistry. These light-triggered click reactions allow the synthesis of diverse organic structures in a rapid and precise manner under mild conditions. Because light offers unparalleled spatiotemporal control over the generation of the reactive intermediates, photoclick chemistry has become an indispensable tool for a wide range of spatially addressable applications including surface functionalization, polymer conjugation and cross-linking, and biomolecular labeling in the native cellular environment. Over the past decade, a growing number of photoclick reactions have been developed, especially those based on the 1,3-dipolar cycloadditions and Diels-Alder reactions owing to their excellent reaction kinetics, selectivity, and biocompatibility. This review summarizes the recent advances in the development of photoclick reactions and their applications in chemical biology and materials science. A particular emphasis is placed on the historical contexts and mechanistic insights into each of the selected reactions. The in-depth discussion presented here should stimulate further development of the field, including the design of new photoactivation modalities, the continuous expansion of λ-orthogonal tandem photoclick chemistry, and the innovative use of these unique tools in bioconjugation and nanomaterial synthesis.
Topics: Click Chemistry; Cycloaddition Reaction; Imines; Nitriles; Photochemistry; Tetrazoles
PubMed: 33104332
DOI: 10.1021/acs.chemrev.0c00799 -
Current Opinion in Chemical Biology Apr 2017Imine reductases (IREDs) have emerged as a valuable new set of biocatalysts for the asymmetric synthesis of optically active amines. The development of bioinformatics... (Review)
Review
Imine reductases (IREDs) have emerged as a valuable new set of biocatalysts for the asymmetric synthesis of optically active amines. The development of bioinformatics tools and searchable databases has led to the identification of a diverse range of new IRED biocatalysts that have been characterised and employed in different synthetic processes. This review describes the latest developments in the structural and mechanistic aspects of IREDs, together with synthetic applications of these enzymes, and identifies ongoing and future challenges in the field.
Topics: Amination; Biocatalysis; Imines; Oxidation-Reduction; Oxidoreductases
PubMed: 28038349
DOI: 10.1016/j.cbpa.2016.11.022 -
Trends in Biochemical Sciences Oct 2019Metabolic networks are webs of integrated reactions organized to maximize growth and replication while minimizing the detrimental impact that reactive metabolites can... (Review)
Review
Metabolic networks are webs of integrated reactions organized to maximize growth and replication while minimizing the detrimental impact that reactive metabolites can have on fitness. Enamines and imines, such as 2-aminoacrylate (2AA), are reactive metabolites produced as short-lived intermediates in a number of enzymatic processes. Left unchecked, the inherent reactivity of enamines and imines may perturb the metabolic network. Genetic and biochemical studies have outlined a role for the broadly conserved reactive intermediate deaminase (Rid) (YjgF/YER057c/UK114) protein family, in particular RidA, in catalyzing the hydrolysis of enamines and imines to their ketone product. Herein, we discuss new findings regarding the biological significance of enamine and imine production and outline the importance of RidA in controlling the accumulation of reactive metabolites.
Topics: Amines; Catalysis; Heat-Shock Proteins; Humans; Hydrolysis; Imines; Ketones; Metabolic Networks and Pathways; Ribonucleases
PubMed: 31103411
DOI: 10.1016/j.tibs.2019.04.011 -
International Journal of Molecular... Mar 2024Fluorinated imines (Schiff bases) and fluorinated hydrazones are of particular interest in medicinal chemistry due to their potential usefulness in treating... (Review)
Review
Fluorinated imines (Schiff bases) and fluorinated hydrazones are of particular interest in medicinal chemistry due to their potential usefulness in treating opportunistic strains of bacteria that are resistant to commonly used antibacterial agents. The present review paper is focused on these fluorinated molecules revealing strong, moderate or weak in vitro antibacterial activities, which have been reported in the scientific papers during the last fifteen years. Fluorinated building blocks and reaction conditions used for the synthesis of imines and hydrazones are mentioned. The structural modifications, which have an influence on the antibacterial activity in all the reported classes of fluorinated small molecules, are highlighted, focusing mainly on the importance of specific substitutions. Advanced research techniques and innovations for the synthesis, design and development of fluorinated imines and hydrazones are also summarized.
Topics: Hydrazones; Anti-Bacterial Agents; Imines; Schiff Bases; Bacteria
PubMed: 38542315
DOI: 10.3390/ijms25063341 -
International Journal of Molecular... Oct 2022An operationally convenient Zn-catalyzed synthesis of alcohols by the reduction of aldehydes, ketones, and ,-unsaturated aldehydes/ketones is reported. It is a rare...
An operationally convenient Zn-catalyzed synthesis of alcohols by the reduction of aldehydes, ketones, and ,-unsaturated aldehydes/ketones is reported. It is a rare example of using mild and sustainable HBpin as a reductant for catalytic reduction of carbonyl compounds in the absence of acid or base as hydrolysis reagent. The reaction is upscalable and proceeds in high selectivity without the formation of boronate ester by-products, and tolerates sensitive functionalities, such as iodo, bromo, chloro, fluoro, nitro, trifluoromethyl, aminomethyl, alkynyl, and amide. The Zn(OAc)/HBpin combination has been also proved to be chemoselective for the C=N reduction of imine analogs.
Topics: Aldehydes; Ketones; Imines; Reducing Agents; Alcohols; Catalysis; Zinc; Esters; Amides
PubMed: 36293541
DOI: 10.3390/ijms232012679 -
Molecules (Basel, Switzerland) Jul 2022A number of imines, including 12 new compounds, previously not reported in the literature, derived from variously fluorinated benzaldehydes and different anilines or...
A number of imines, including 12 new compounds, previously not reported in the literature, derived from variously fluorinated benzaldehydes and different anilines or chiral benzylamines were synthesized by a solvent-free mechanochemical method, which was based on the manual grinding of equimolar amounts of the substrates at the room temperature. In a very short reaction time of only 15 min, the method produced the expected products with good-to-excellent yields. The yields were comparable or significantly higher than those reported in the literature for the imines synthesized by other methods. Importantly, the conditions used for the reactions with aniline derivatives also resulted in the high yields of imines obtained from chiral benzylamines, and can be extended to the synthesis with other similar amines. Structures of all imines were confirmed by NMR spectroscopy: H, C and F. For four compounds, X-ray structures were also obtained. The synthetic approach presented in this paper contributes to the prevention of environmental pollution and can be easily extended for larger-scale syntheses. The mechanochemical solvent-free method provides a convenient strategy particularly useful for the preparation of fluorinated imines being versatile intermediates or starting material in the synthesis of drugs and other fine chemicals.
Topics: Amines; Benzaldehydes; Benzylamines; Imines; Magnetic Resonance Spectroscopy
PubMed: 35889430
DOI: 10.3390/molecules27144557 -
Journal of Inorganic Biochemistry Dec 2020With a growing interest in utilizing visible light to drive biocatalytic processes, several light-harvesting units and approaches have been employed to harness the... (Review)
Review
With a growing interest in utilizing visible light to drive biocatalytic processes, several light-harvesting units and approaches have been employed to harness the synthetic potential of heme monooxygenases and carry out selective oxyfunctionalization of a wide range of substrates. While the fields of cytochrome P450 and Ru(II) photochemistry have separately been prolific, it is not until the turn of the 21st century that they converged. Non-covalent and subsequently covalently attached Ru(II) complexes were used to promote rapid intramolecular electron transfer in bacterial P450 enzymes. Photocatalytic activity with Ru(II)-modified P450 enzymes was achieved under reductive conditions with a judicious choice of a sacrificial electron donor. The initial concept of Ru(II)-modified P450 enzymes was further improved using protein engineering, photosensitizer functionalization and was successfully applied to other P450 enzymes. In this review, we wish to present the recent contributions from our group and others in utilizing Ru(II) complexes coupled with P450 enzymes in the broad context of photobiocatalysis, protein assemblies and chemoenzymatic reactions. The merging of chemical catalysts with the synthetic potential of P450 enzymes has led to the development of several chemoenzymatic approaches. Moreover, strained Ru(II) compounds have been shown to selectively inhibit P450 enzymes by releasing aromatic heterocycle containing molecules upon visible light excitation taking advantage of the rapid ligand loss feature in those complexes.
Topics: Biocatalysis; Cytochrome P-450 Enzyme System; Electron Transport; Imines; Ruthenium Compounds
PubMed: 32979791
DOI: 10.1016/j.jinorgbio.2020.111254 -
Accounts of Chemical Research Oct 2021Redox reactions that take place in enzymes and on the surfaces of heterogeneous catalysts often require active sites that contain multiple metals. By contrast, there are... (Review)
Review
Redox reactions that take place in enzymes and on the surfaces of heterogeneous catalysts often require active sites that contain multiple metals. By contrast, there are very few homogeneous catalysts with multinuclear active sites, and the field of organometallic chemistry continues to be dominated by the study of single metal systems. Multinuclear catalysts have the potential to display unique properties owing to their ability to cooperatively engage substrates. Furthermore, direct metal-to-metal covalent bonding can give rise to new electronic configurations that dramatically impact substrate binding and reactivity. In order to effectively capitalize on these features, it is necessary to consider strategies to avoid the dissociation of fragile metal-metal bonds in the course of a catalytic cycle. This Account describes one approach to accomplishing this goal using binucleating redox-active ligands.In 2006, Chirik showed that pyridine-diimines (PDI) have sufficiently low-lying π* levels that they can be redox-noninnocent in low-valent iron complexes. Extending this concept, we investigated a series of dinickel complexes supported by naphthyridine-diimine (NDI) ligands. These complexes can promote a broad range of two-electron redox processes in which the NDI ligand manages electron equivalents while the metals remain in a Ni(I)-Ni(I) state.Using (NDI)Ni catalysts, we have uncovered cases where having two metals in the active site addresses a problem in catalysis that had not been adequately solved using single-metal systems. For example, mononickel complexes are capable of stoichiometrically dimerizing aryl azides to form azoarenes but do not turn over due to strong product inhibition. By contrast, dinickel complexes are effective catalysts for this reaction and avoid this thermodynamic sink by binding to azoarenes in their higher-energy cis form.Dinickel complexes can also activate strong bonds through the cooperative action of both metals. Norbornadiene has a ring-strain energy that is similar to that of cyclopropane but is not prone to undergoing C-C oxidative addition with monometallic complexes. Using an (NDI)Ni complex, norbornadiene undergoes rapid ring opening by the oxidative addition of the vinyl and bridgehead carbons. An inspection of the resulting metallacycle reveals that it is stabilized through a network of secondary Ni-π interactions. This reactivity enabled the development of a catalytic carbonylative rearrangement to form fused bicyclic dienones.These vignettes and others described in this Account highlight some of the implications of metal-metal bonding in promoting a challenging step in a catalytic cycle or adjusting the thermodynamic landscape of key intermediates. Given that our studies have focused nearly exclusively on the (NDI)Ni system, we anticipate that many more such cases are left to be discovered as other transition-metal combinations and ligand classes are explored.
Topics: Coordination Complexes; Imines; Ligands; Molecular Structure; Nickel; Oxidation-Reduction; Pyridines
PubMed: 34565142
DOI: 10.1021/acs.accounts.1c00424 -
Journal of the American Chemical Society Apr 2021A cross-selective aza-pinacol coupling of aldehydes and imines has been developed to afford valuable β-amino alcohols. This strategy enables chemoselective conversion...
A cross-selective aza-pinacol coupling of aldehydes and imines has been developed to afford valuable β-amino alcohols. This strategy enables chemoselective conversion of aliphatic aldehydes to ketyl radicals, in the presence of more easily reduced imines and other functional groups. Upon carbonyl-specific activation by AcI, a photoinitiated Mn catalyst selectively reduces the resulting α-oxy iodide by an atom transfer mechanism. The ensuing ketyl radical selectively couples to imines, precluding homodimerization by a classical reductive approach. In this first example of reductive, ketyl coupling by atom transfer catalysis, Zn serves as a terminal reductant to facilitate Mn catalyst turnover. This new strategy also enables ketyl radical couplings to alkenes, alkynes, aldehydes, propellanes, and chiral imines.
Topics: Aldehydes; Amino Alcohols; Aza Compounds; Catalysis; Free Radicals; Imines; Magnesium; Oligopeptides; Oxidation-Reduction; Stereoisomerism
PubMed: 33830738
DOI: 10.1021/jacs.1c00886