Aldehyde Function Research Articles

Development of self-healing vanillin/PEI hydrogels for tissue engineering

Self-healing materials recover mechanical damages to expand the lifetime of the material provided. In this study, self-healing hydrogels have been successfully prepared using a novel and simple technique. Vanillin is a natural monomer, used as a bio-based cross-linker for UV-induced bonding and Schiff-base bonding. Methacrylate-functionalized vanillin (M-VAN) is covalently integrated with the polymer matrix. While M-VAN supports polymer matrix with its vinyl group, its aldehyde functionality helps the formation of dynamic covalent imine bonds via Schiff-base formation. The hydrogel showed excellent self-healing ability overnight under physiological conditions without external addition. In addition, the hydrogel surface was modified by collagen and its cell viability was investigated. The prepared scaffolds showed good cell viability of 124% and 163% compared to the control sample. The developed self-healing material reveals that it has possible uses for future biomedical applications and tissue engineering studies due to the self-healing mechanism taking place under ambient conditions.

Revealed pathways of furan ring opening and surface crosslinking in biobased polyfurfuryl alcohol

Poly(furfuryl alcohol) – (PFA) is a biobased thermoset known for its highly crosslinked structure. Bidimensional NMR (2D-NMR) was employed to give new insights on the complex structural organization in PFA with a special emphasis on the side structures resulting from furan ring-opening. Interestingly, the presence of aldehyde functions was for the first time clearly highlighted and quantified in PFA resins. Overall, the aldehydes account for about 20 % of the total carbonyls present in PFA. Results from HSQC and HMBC sequences allowed proposing two pathways for the furan ring opening reactions. The first one is an hydrolytic-ring opening leading to levulinic like species. The second one is rather an oxidative furan-ring opening leading to conjugated aldehydes. These conjugated aldehydes are prone to crosslink via Diel-Alder cycloadditions with furanic entities thus leading to crosslinking. At macroscopic scale, this newly proposed crosslinking pathway would explain the formation of the rigid shell formed at the external surfaces of PFA resins.

DFT, ADMET, molecular docking and molecular dynamics studies of pyridoxal

We report in silico studies of pyridoxal, which is of interest both as a precursor for further functionalization due to the presence of the aldehyde functionality, as well as a bioactive compound. So far, the crystal structure of pyridoxal has not been reported and, thus, we have optimized its structure both under water solvation and in gas phase using the DFT calculations. Under water solvation conditions the optimized structure of pyridoxal is 7.62 kcal/mol more favorable in comparison to that in gas phase. The DFT calculations were also applied to verify optical and electronic properties of the optimized structure of pyridoxal in water. The HOMO and LUMO were revealed to subtract a set of descriptors of the so-called global chemical reactivity as well as to probe pyridoxal as a potential corrosion inhibitor for some important metals used in implants. The title compound exhibits the best electron charge transfer from the molecule to the surface of Ni and Co. Some biological properties of pyridoxal were evaluated using the respective on-line tools. Molecular docking was additionally applied to study interaction of pyridoxal with some SARS-CoV-2 proteins as well as one of the monkeypox proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with nonstructural protein 15 (endoribonuclease) and Omicron Spike protein of SARS-CoV-2. Pyridoxal was found to be also active against the studied monkeypox protein. Interaction of pyridoxal with nonstructural protein 15 (endoribonuclease) was further studied using molecular dynamics simulation.

Mechanism and origins of cobalt-catalyzed ligand-controlled regiodivergent C-H functionalization of aldehydes with enynes.

The influence of the P-M-P bite angle in diphosphine ligands on selectivity has been observed in various catalytic reactions. A better understanding of the ligand bite angle concept is important for the rational design of efficient catalytic systems. In the present work, the mechanism of cobalt-catalyzed C-H functionalization of aldehydes with enynes and how the diphosphine ligands alter regioselectivity were investigated by density functional theory (DFT) calculations. The catalytic cycle is initiated by the oxidative cyclization of enynes rather than the oxidative addition of aldehydes. Regioselectivity arises from competing σ-bond metathesis and migratory insertion steps, in which the steric effects of diphosphine ligands are the dominant factors influencing the activation barriers. The calculations indicate that σ-bond metathesis is more challenging and its feasibility is highly dependent on the ligand bite angle. The improved mechanistic understanding will enable further design of transition-metal-catalyzed selective cyclization reactions.

Development of an α'-hydroxy enone for the aminocatalytic asymmetric formal conjugate addition of aldehydes to acrylates, vinyl ketones and acrolein.

Aminocatalytic asymmetric conjugate addition of aldehydes to Michael acceptors is a well established C-C bond forming methodology. However, various acrylic-type acceptors, including acrylic acid derivatives and acrolein, remain reluctant. Here we demonstrate that the internal H-bonding self-activation in α'-hydroxy enones allows them to react smoothly with enolizable aldehydes using commercially available aminocatalysts to afford adducts in good yields and high enantioselectivity. Straightforward conversion of the ketol moiety of these adducts into aldehyde, ketone and carboxylic acid functionalities offers an indirect, unified entry to products derived from acrolein, alkyl-vinyl ketones and acrylates, respectively.

NHC-catalyzed radical acylation of cycloalkyl silyl peroxides to access 1,6-,1,7-, and 1,8-diketones.

An unprecedented N-heterocyclic carbene (NHC)-catalyzed radical acylation of cycloalkyl silyl peroxides was developed using readily available aldehydes as the acylating agents. This protocol provides an exceptionally useful method for the efficient and rapid synthesis of long-chain 1,6-/1,7-/1,8-diketones, especially unsymmetrical ones. This strategy also has the advantages of mild conditions, good functional group compatibility, and potential applications in the late-stage functionalization of aldehydes with bioactive fragments and in the construction of long-chain complex bioactive molecules.

Carotenoid metabolites, their tissue and blood concentrations in humans and further bioactivity via retinoid receptor-mediated signalling.

Many epidemiological studies have emphasised the relation between carotenoid dietary intake and their circulating concentrations and beneficial health effects, such as lower risk of cardiometabolic diseases and cancer. However, there is dispute as to whether the attributed health benefits are due to native carotenoids or whether they are instead induced by their metabolites. Several categories of metabolites have been reported, most notably involving (a) modifications at the cyclohexenyl ring or the polyene chain, such as epoxides and geometric isomers, (b) excentric cleavage metabolites with alcohol-, aldehyde- or carboxylic acid-functional groups or (c) centric cleaved metabolites with additional hydroxyl, aldehyde or carboxyl functionalities, not counting their potential phase-II glucuronidated / sulphated derivatives. Of special interest are the apo-carotenoids, which originate in the intestine and other tissues from carotenoid cleavage by β-carotene oxygenases 1/2 in a symmetrical / non-symmetrical fashion. These are more water soluble and more electrophilic and, therefore, putative candidates for interactions with transcription factors such as NF-kB and Nrf2, as well as ligands for RAR-RXR nuclear receptor interactions. In this review, we discuss in vivo detected apo-carotenoids, their reported tissue concentrations, and potential associated health effects, focusing exclusively on the human situation and based on quantified / semi-quantified carotenoid metabolites proven to be present in humans.

Controlled Covalent Functionalization of ZIF-90 for Selective CO2 Capture & Separation.

Mixed Matrix Membranes (MMM) with enhanced selectivity and permeability are preferred for gas separations. The porous metal-organic frameworks (MOFs) materials incorporated in them play a crucial part in improving the performance of MMM. In this study, Zeolitic imidazolate frameworks (ZIF-90) are selected to fabricate Polyetherimide (PEI) MMMs owing to their lucrative structural and chemical properties. This work reports new controlled post-synthetic modifications of ZIF-90 (50-PSM-ZIF-90) with ethanolamine to control the diffusion and uptake of CO2. Physical and chemical properties of ZIF-90, such as stability and presence of aldehyde functionality in the imidazolate linker, allow for easy modulation of the ZIF-90 pores and window size to tune the gas transport properties across ZIF-90-based membranes. Effects of these materials were investigated on the performance of MMMs and compared with pure PEI membranes. Performance of the MMMs was evaluated in terms of permeability of different gases and selective separation of CO2 and H2 gas. Results presented that the permeability of all membranes was in the following order, i.e., P(H2) > P(CO2) > P(O2) > P(CH4) > P(C2H6) > P(C3H8) > P(N2), demonstrating that kinetic gas diffusion is the predominant gas transport mode in these membranes. Among all the membranes, permeability of pure PEI membrane was highest for all gases due to the uniform porous morphology. The pure PEI membrane showed highest permeability of H2, which is 486.5 Barrer, followed by 49 Barrer for O2, 29 Barrer for N2, 142 Barrer for CO2, 41 Barrer for CH4, 40 Barrer for C2H6 and 39.6 Barrer for C3H8. Results also confirm the superiority of controlled PSM-ZIF-90-PEI membrane over the pure PEI and ZIF-90-PEI membranes in CO2 and H2 separation performance. The 50-PSM-ZIF-90 PEI membrane exhibited a 20% increase in CO2 separation from methane and a 26% increase over nitrogen compared to the ZIF-90-PEI membrane. The 50-PSM-ZIF-90 PEI membrane showed 15% more H2/O2 separation and 9% more H2/CH4 separation than ZIF-90 PEI membrane. Overall, this study represents the role of controlled PSM in enhancing the property of new materials like ZIF and its application in MMMs fabrication to develop a promising approach for the CO2 capture and separation.

Second Generation Self‐Assembling Dendrimer Combining Supramolecular and Dynamic Covalent Chemistry

AbstractA monodisperse second generation self‐assembled dendrimer has been obtained combining supramolecular chemistry and dynamic covalent chemistry as orthogonal binding moieties. A branching unit 18 and a core 5 were connected via a heteroleptic terpyridine zinc complex exploiting the sterical hindrance of mesitylene units in the 6,6’’‐position of one of the terpyridines as the distinction between the ligands. Solubility problems could be solved by introduction of an ethylhexyl ether. The final sphere of the dendrimer was connected via imines, hydrazones and oximes, whereby the oxime made from O‐methylhydroxylamine (22) led to a complete turnover of all aldehyde functions. Furthermore, no amine signal was left and also no signals for a diffusion constant of the hydroxylamine 22 were observed. The successful formation of the dendrimers was analyzed by 1H NMR and DOSY NMR spectroscopy. Furthermore both, the first and second generation dendrimers could be detected by ESI HRMS.

Control over the Hydrophilicity in the Pores of Covalent Organic Framework Membranes for High-Flux Separation of Dyes from Water

Membrane separation is making substantial contributions to water purification. Particularly important is the pore-size control designed for molecular sieving. Regarding water permeation, filtration experiments accentuate the importance of hydrophilic pores in enhancing the water adsorption capacity, while hydrophobic pores enable low-friction water diffusion. To reach both the criteria, we herein precisely design the pore metrics and pore functionalities to prepare a covalent organic framework (COF), termed TUS-46, membrane. Credited with pore sizes befitting for size-selective molecular exclusion and negative electrostatic pore walls, the TUS-46 COF membrane shows excellent rejection performance toward anionic dyes. Attributed to the free aldehyde functionalities in the framework resulting from unbalanced stoichiometry, the TUS-46 COF membrane also shows a 10-fold higher water permeance compared to the analogue COF membrane without free aldehyde functionalities. In particular, the in situ construction of hydrophilic nanospaces partaking in high water uptake and hydrophobic nanospaces facilitating fast water diffusion in a single COF structure endows the TUS-46 membranes with unprecedentedly high water flux. The stoichiometric imbalance approach presented herein offers a different route to COF membrane fabrication and may impart with an unprecedented control handle on the permeability and separation selectivity of COF membranes.

Heterogeneous asymmetric β-C-H functionalization of aldehydes under O2 catalyzed by hydroxide-layered Fe(III) sites synergistic with confined interlayer amine

Asymmetric functionalization of inert β-C-H is one of the most powerful strategies in organic synthesis, but of great challenge in the efficient β-C-H activation and the enantioselective C-heteroatom formation. Here, this work proposes an elegant strategy for one-pot asymmetric β-C-H functionalization of aldehyde under O2 catalyzed by hydroxide-layered Fe(III) sites synergistic with confined interlayer amine through a cascade oxidation-addition process on L-proline intercalated Fe-containing layered double hydroxides (LDHs), in which the direct β-H elimination of aldehyde on hydroxide-layered Fe(III) sites with the two-electron abstraction promoted by the Fe(III):N coordination as the key step to efficiently oxidize the enamine. The major β-functionalized diastereomer in the asymmetric nitromethylation of 3-phenylpropanal has been afforded in a regioselectivity of up to >99%, a stereoselectivity of 90%, and a yield of 65% on L-proline intercalated Mg3.00Al0.47Fe0.45-LDHs.

Pd on cyclotriphosphazen-hexa imine decorated boehmite as an efficient catalyst for hydrogenation of nitro arenes under mild reaction condition

Cyclotriphosphazen-hexa imine ligand was prepared through successive reactions of phosphonitrilchloride trimer with 4-hydroxybenzaldehyde and (3-aminopropyl) triethoxy silane. The as-prepared ligand was then covalently grafted on boehmite to furnish an efficient support for the immobilization of Pd nanoparticles and synthesis of a novel heterogeneous catalyst for hydrogenation of nitro arenes. The catalytic tests revealed that the catalyst had excellent catalytic activity for hydrogenation of various nitro arenes with different steric and electronic features under mild reaction condition in aqueous media. Noteworthy, the catalyst was highly selective and in the substrates with ketone or aldehyde functionalities, reduction of nitro group was only observed. The catalyst was also recyclable and only slight loss of activity was detected after each recycling run. Hot filtration test also approved true heterogeneous nature of catalysis.

Antibacterial activity and molecular studies of non-symmetric POCOP-Pd(II) pincer complexes derived from 2,4-dihydroxybenzaldehyde (2,4-DHBA)

A series of non-symmetric POCOP-Pd(II) pincer complexes including an aldehyde group in the meta-position of the aromatic pincer-backbone were prepared and characterized. The molecular structure of complex 1-Pd was unambiguously determined by single crystal X-ray diffraction analysis, showing a square-planar geometry around the metal fragment and the presence of the aldehyde functionality at the pincer ligand backbone. The evaluation of the antibacterial activities of complexes 2-Pd and 3-Pd against gram-positive and gram-negative strains was performed. Complex 3-Pd was the most active against S. aureus ATCC 25923 strain with a MIC value of 8 µg∙mL−1. We also determined by molecular docking studies, that pincer complexes 2-Pd and 3-Pd may interact with some key bacterial enzymes such as KPC-2 and PBP2A.

Photoredox Catalyzed Thioformylation of Terminal Alkynes Using Nitromethane as a Formyl Source.

A photoredox thioformylation of terminal alkynes using nitromethane as a formyl anion equivalent, thereby leading to the synthesis of (E)-1,2-difunctionalized acrylaldehyde, has been described. The current strategy introduces an adaptable aldehyde function across an alkyne and offers a new route to synthesizing α-alkyl/aryl aldehydes.

C−H Activation Based Functionalization of Furfural Derivatives

AbstractFurfural and related compounds are building blocks of industrial interest, obtained from raw biomass. Their use as precursors of basic and fine chemicals has gained increasing attention as a green alternative to petroleum‐derived compounds. Several works have reported the functionalization of furfurals to obtain a wider range of chemicals, opening up new synthetic possibilities and applications, ranging from biofuels to pharmaceuticals. Among these works, processes based on C−H activation are the most attractive ones for their atom economy and the possibility to use non‐activated substrates. This minireview summarizes the reported methods of direct C−H functionalization of furfurals without prior modification of the redox state of the aldehyde function. In particular, the transition metal catalyzed functionalization of each bond of the heteroaromatic nucleus of these molecules is systematically discussed, as well as examples of C−H transformations of the aldehyde function.

Photocurable extended vanillin-based resin for mechanically and chemically recyclable, self-healable and digital light processing 3D printable thermosets

A vanillin-based photocurable resin was designed for circularity by incorporation of imine functionalities through a Schiff-base reaction between the aldehyde function of vanillin and amino group of ethylene diamine. Sufficient flexibility was provided by a short aliphatic segment introduced by reaction of vanillin with ethylene carbonate, while photocurability was obtained by subsequent methacrylation. The cured thermoset had good solvent resistance, relatively high glass transition temperature (∼75 °C) and good thermal stability with an onset of degradation above 300 °C. Due to the crosslinked structure and imine linkages, the thermoset expressed malleability, self-healing and thermal reprocessability. Furthermore, it could be chemically recycled by immersing in ethylene diamine, which activated transimination. The obtained oligomeric product with amine-terminal groups could be utilized for production of new thermoset films. Tensile testing illustrated similar elastic modulus for mechanically and chemically recycled thermosets, while a slight increase was observed for the self-healed samples, ascribable to a completion of the curing during the post-processing. At the same time elongation and stress at break slightly decreased. Finally, the suitability of the resin for the production of 3D objects by means of digital light processing (DLP) 3D printing was demonstrated.

A unified strategy for the total syntheses of eribulin and a macrolactam analogue of halichondrin B

A unified synthetic route for the total syntheses of eribulin and a macrolactam analog of halichondrin B is described. The key to the success of the current synthetic approach includes the employment of our reverse approach for the construction of cyclic ether structural motifs and a modified intramolecular cyclization reaction between alkyl iodide and aldehyde functionalities to establish the all-carbon macrocyclic framework of eribulin. These syntheses, together with our previous work on the total syntheses of halichondrin B and norhalichondrin B, demonstrate and validate the powerful reverse approach in the construction of cyclic ether structural motifs. On the other hand, the unified synthetic strategy for the synthesis of the related macrolactam analog provides inspiration and opportunities in the halichondrin field and related polycyclic ether areas.

An efficient Mn-catalyzed reductive carbonylation of aryl iodides to aryl aldehydes and their benzimidazole and benzoxazoles

The present study envisaged the development of an efficient protocol of Mn-catalyzed reductive carbonylation of aryl iodides to aryl aldehydes and their corresponding imidazole and oxazole derivatives, by using CO as a carbonyl source, in the presence of hydrosilanes and base [Na2CO3 and NaHCO3 (1:1)] under mild reaction conditions gave a series of aldehydes in good yields. This approach could be extended for further functionalization of aryl aldehydes and to their corresponding benzimidazole and benzoxazole derivatives with high efficiency.

Surface Functionalized Polyaniline Nanofibers:Chitosan Nanocomposite for Promoting Neuronal-like Differentiation of Primary Adipose Derived Mesenchymal Stem Cells and Urease Activity.

Bioscaffolds having electrically conducting polymers (CPs) have become increasingly relevant in tissue engineering (TE) because of their ability to regulate conductivity and promote biological function. With this in mind, the current study shows a conducting polyaniline nanofibers (PNFs) dispersed chitosan (Ch) nanocomposites scaffold with a simple one-step surface functionalization approach using glutaraldehyde for potential neural regeneration applications. According to the findings, 4 wt % PNFs dispersion in Ch matrix is an optimal concentration for achieving desirable biological functions while maintaining required physicochemical properties as evidenced by SEM, XRD, current-voltage (I-V) measurement, mechanical strength test, and in vitro biodegradability test. Surface chemical compositional analysis using XPS and ATR FT-IR confirms the incorporation of aldehyde functionality after functionalization, which is corroborated by surface energy calculations following the Van Oss-Chaudhury-Good method. Surface functionalization induced enhancement in surface hydrophilicity in terms of the polar component of surface energy (γiAB) from 6.35 to 12.54 mN m-1 along with an increase in surface polarity from 13.61 to 22.54%. Functionalized PNF:Ch scaffolds demonstrated improvement in enzyme activity from 67 to 94% and better enzyme kinetics with a reduction of Michaelis constants (Km) from 21.55 to 13.81 mM, indicating favorable protein-biomaterial interactions and establishing them as biologically perceptible materials. Surface functionalization mediated improved cell-biomaterial interactions led to improved viability, adhesion, and spreading of primary adipose derived mesenchymal stem cells (ADMSCs) as well as improved immunocompatibility. Cytoskeletal architecture assessment under differentiating media containing 10 ng/mL of each basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) revealed significant actin remodeling with neurite-like projections on the functionalized scaffolds after 14 days. Immunocytochemistry results showed that more than 85% of cells expressed early neuron specific β III tubulin protein on the functionalized scaffolds, whereas glial fibrillary acidic protein (GFAP) expression was limited to approximately 40% of cells. The findings point to the functionalized nanocomposites' potential as a smart scaffold for electrically stimulated neural regeneration, as they are flexible enough to be designed into microchanneled or conduit-like structures that mimic the microstructures and mechanical properties of peripheral nerves.

Annulative π-extension of 1-phenylsulfonyl-2/3-bromomethylindole via Zn(OTf)2-mediated domino reaction with thiophene analogs

The reaction of isomeric 2/3-bromomethylindoles containing masked aldehydic function with heteroarenes in the presence of Zn(OTf)2 as a catalyst in 1,2-DCE at room temperature led to the formation of benzo[b]-hetero annulated carbazoles.