Acetal Bonds Research Articles

Injectable Dendrimer Hydrogel Delivers Melphalan in Both Conjugated and Free Forms for Retinoblastoma.

We report the successful synthesis of an injectable dendrimer hydrogel (DH) carrying melphalan, a clinical drug for retinoblastoma treatment, in both conjugated and free forms. Polyamidoamine (PAMAM) dendrimer generation 5 (G5) is surface-modified with an acid-sensitive acetal-dibenzocyclooctyne linker and then undergoes azide-alkyne cycloaddition with melphalan-PEG-N3 conjugate to form G5-acetal-melphalan. During the DH gelation between G5-acetal-melphalan and PEG-diacrylate, free melphalan is added, resulting in a hydrogel (G5-acetal-melphalan-DH/melphalan) that carries the drug in both conjugated and free forms. Melphalan is slowly released from G5-acetal-melphalan-DH/melphalan, with the conjugated melphalan released more quickly at pH 5.3 due to acid-triggered acetal bond cleavage. The formulation's in vitro safety and efficacy were established on human corneal epithelia (HCE-2) and retinoblastoma cells (Y79). In an in vivo Y79 tumor xenograft model of retinoblastoma, intratumorally injected G5-melphalan-DH formulation prolonged tumor suppression. This injectable, multimodal, pH-responsive formulation shows promise for intravitreal injection to treat retinoblastoma.

Capturing Enzyme-Loaded Diblock Copolymer Vesicles Using an Aldehyde-Functionalized Hydrophilic Polymer Brush.

Compared to lipids, block copolymer vesicles are potentially robust nanocontainers for enzymes owing to their enhanced chemical stability, particularly in challenging environments. Herein we report that cis-diol-functional diblock copolymer vesicles can be chemically adsorbed onto a hydrophilic aldehyde-functional polymer brush via acetal bond formation under mild conditions (pH 5.5, 20 °C). Quartz crystal microbalance studies indicated an adsorbed amount, Γ, of 158 mg m-2 for vesicle adsorption onto such brushes, whereas negligible adsorption (Γ = 0.1 mg m-2) was observed for a control experiment conducted using a cis-diol-functionalized brush. Scanning electron microscopy and ellipsometry studies indicated a mean surface coverage of around 30% at the brush surface, which suggests reasonably efficient chemical adsorption. Importantly, such vesicles can be conveniently loaded with a model enzyme (horseradish peroxidase, HRP) using an aqueous polymerization-induced self-assembly formulation. Moreover, the immobilized vesicles remained permeable toward small molecules while retaining their enzyme payload. The enzymatic activity of such HRP-loaded vesicles was demonstrated using a well-established colorimetric assay. In principle, this efficient vesicle-on-brush strategy can be applied to a wide range of enzymes and functional proteins for the design of next-generation immobilized nanoreactors for enzyme-mediated catalysis.

Concise Synthesis of 11-Noriridoids via Pauson-Khand Reaction.

Iridoids, which are a class of monoterpenoids, are attractive synthetic targets due to their diversely substituted cis-fused cyclopenta[c]pyran skeletons. Additionally, various biological activities of iridoids raise the value of synthetic studies on this class of compounds. Here, our synthetic efforts toward 11-noriridoids; (±)-umbellatolide B (6), (±)-10-O-benzoylglobularigenin (9) and 1-O-pentenylaucubigenin (34) are described. For the efficient synthesis of target compounds, common synthetic intermediates (tricyclic enones 17 and 26) were prepared by the Pauson-Khand reaction. The cleavage of the acetal bond on the tricyclic enones and 1,2-reduction introduced the two hydroxy groups on the cyclopentane ring of the core scaffold. Furthermore, the C3-C4 olefin part was constructed by the syn-elimination of a thiocarbonate moiety to obtain 34. The developed synthetic routes for 6, 9, and 34 will be useful for the preparation of iridoid analogs that have a polyfunctionalized core skeleton.

Electronic effects of substituents on the properties of recyclable epoxy resins containing aromatic acetal groups

Both environmental and economic concerns are pioneering the development of recyclable thermosetting polymers. In this study, three liquid acetal-containing di-epoxide monomers (ADEs) with different para-substituted (-OCH3, -Cl and –NO2) phenyl groups were synthesized. The refractive indices and viscosities of the three di-epoxide liquids increase in the sequence of ADE-3 (-OCH3), ADE-1 (-Cl) and ADE-2 (-NO2). Once cured with methylhexahydrophthalic anhydride, the three cured ADEs exhibit high glass transition temperatures (181–218 °C). Due to the presence of dynamic acetal bonds, all three cured ADEs are reprocessable, repairable, weldable, and degradable. Interestingly, the electronic effect of the substituents on the phenyl group significantly impacts the structural configuration, reprocessability and degradation behaviors of the resultant cured ADEs. As the electron-withdrawing effect of the substituents on the phenyl group increases, the stress relaxation rates of the cured ADEs decrease at the same temperature. Under optimized reprocessing conditions, the reprocessed ADE-1 (-Cl) and ADE-2 (-NO2) resins show the highest (117 %) and lowest (67 %) retention rates for tensile strength, respectively. The degradation rates of the three cured ADEs in the acidic solutions decrease with increasing the electron-withdrawing effect of the substituent on the phenyl group. Finally, a di-epoxide curing system based on ADE-3 was applied to prepare carbon fiber-reinforced composites, and nondestructive recovery of the carbon fibers was attained by degradation of the resin matrix.

Superior Epoxy Vitrimer Containing Acetal and Disulfide Bonds for Achieving High Mechanical Properties, Reprocessability, and Degradability

Superior Epoxy Vitrimer Containing Acetal and Disulfide Bonds for Achieving High Mechanical Properties, Reprocessability, and Degradability

Dynamic covalent bonds of hemiacetals and acetals enables reprocessability and raw material recyclability of high performance cellulosic thermosetting resins

Despite covalent adaptable networks (CANs) imparting the reprocessing performance of crosslinked polymers, due to reversible bond exchange of the dynamic covalent bonds; it is still a huge challenge to design catalyst-free, fast reprocessing, controlled degradation and raw material recycling biomass base CANs. Here, for the first time, we prepared cellulose CANs base on hemiacetal and acetal bonds (ACCs) via aldehyde and hydroxyl reaction of the dialdehyde crosslinker with hydroxypropyl cellulose (HPC). By regulating the crosslink density and chemical structure of the crosslinked network, ACCs exhibit tunable thermal and mechanical properties. The crosslinked network structure of the ACCs benefits from the rapid bond exchange of the hemiacetal and acetal bonds at elevated temperatures, which allows for rapid stress relaxation and thus, superior reprocessing properties. In addition, it was found that the dynamic exchange of acetals in the ACCs is influenced by the chain length and flexibility of the crosslinker. Moreover, ACCs possess good degradation and cellulose feedstock recycling properties due to the acid sensitivity of the acetal bonds. This work provides an effective solution to the problems of resource waste caused by petroleum-based thermoset plastics.

Study on the mechanism of lignin and lignin-carbohydrate complex hydrolysis under alkaline conditions by density functional theory

Lignin hydrolyzes during alkali-heat pretreatment of lignocellulose, due to the cleavage of covalent linkages between lignin and lignin-carbohydrate complex. Various structure of lignin monomers are responsible of the complicated hydrolysis mechanism of lignin and lignin-carbohydrate complex. This study used density functional theory to reveal the hydrolysis mechanism of lignin with various substituents and lignin-carbohydrates complex with different linkages. The results indicated that the SN2 reaction was observed to take place in the lignin. Methoxy groups and methyl group had an insignificant influence on hydrolysis reaction pathway of lignin, whereas the presence of a methyl group on the α-carbon atom had a hindering effect on the nucleophilic attack during alkaline pretreatment. The lignin-carbohydrate complex with different linkage showed a significant difference in hydrolysis reaction pathway. Additionally, the reaction energy barrier of ester bond hydrolysis was lowest among the hydrolysis of ester bond, phenyl glycosidic bond, benzyl ether bond, γ-ester bond, coumarin ester bond and acetal bond under alkaline condition. This study provides valuable insights into the process control, reactor design, and performance enhancement for lignocellulose pretreatment.

Bio-spiroacetal polyurethane covalent adaptive network with close-loop recycling, self-healing and reprocessability

Conventional polyurethanes from non-renewable resources have been widely used for their excellent mechanical properties and thermal stability, which are difficult to be reprocessed and recycled due to the permanent crosslinked networks. In this study, dynamic acetal bonds were synthesized using bio-based vanillin and then embedded in polymer with castor oil to construct bio-based recyclable polyurethane. The ratio of castor oil to bio-spiroacetal diols was varied to control the thermodynamics and mechanical performance of bio-based polyurethanes. Experimental results of dynamic mechanical analysis, differential scanning calorimetry, tensile test and stress relaxation test suggested that a decrease in the content of acetal diols as a hard segment, led to a decrease in the glass transition temperature and tensile strength. Additionally, the activation energy initially increased and then decreased. The reversibility of the acetal structure endowed green polyurethane materials with the ability of reprocessing, self-repairing and closed-loop recycling.

Potential Wound Dressing with Antibacterial Effect from Cross‐Linked Polyvinyl Alcohol/Sodium Caseinate/CuO NP Electrospun Mat

AbstractIn this study, nanofibers were produced from Polyvinyl alcohol (PVA)/Sodium Caseinate (SoCAS)/Copper Oxide nanoparticle (CuO NP) mixtures by electrospinning method. Nano surfaces were cross‐linked by immersion in a Glutaraldehyde (GLA) bath. Electrospun mats are designed as modern wound dressings with antibacterial effects for exuding wounds. The cross‐linking process by dipping has thickened a bit of nanofiber diameter by creating a coating effect on fiber surface. The increase of acetal bonds and decrease of hydroxyl groups in structure by cross‐linking have improved thermal properties of nanofibers. The increase in melting enthalpy has also improved mechanical properties of mats. The mixture of semicrystalline PVA and SoCAS has increased breaking stress of nanostructure. Besides, the CuO NP additive improved the breaking strength and elongation behavior of mats. It was stated that cross‐linked nanofibers swelled without dissolving in distilled water and contained water‐repellent groups. The CuO NP supplementation delayed the growth of Escherichia coli (E. coli). However, it was observed that antibacterial effect against Staphylococcus aureus (S. aureus) was higher than against E. coli. It was reported that 5 % CuO NP‐doped nanofiber can be used as a wound dressing, owing to its high fibroblast cell viability at 24th and 48th hours and 99.48 % antibacterial activity against S. aureus.

Facile extraction of lignin-carbohydrate complexes from bamboo with formic acid aqueous solution under moderate conditions

The extraction of lignin-carbohydrate complexes (LCC) while preserving the majority of the interconnecting bonds poses a formidable challenge in characterizing the structure and exploring further applications. In this study, a straightforward approach was proposed to extract LCC from bamboo by precisely adjusting formic acid aqueous solution concentrations (70 % to 100 %) and reaction temperatures (40 to 100 °C) under normal pressure. Notably, employing a 90 % formic acid aqueous solution at 100 °C for 2 h led to an impressive LCC yield of 24.47 %. Moreover, all the LCC samples demonstrated exceptional homogeneity with a polydispersity index ≤ 1.97. Nuclear magnetic resonance analysis revealed the presence of phenyl glycosidic, benzyl ether, benzyl ester, and acetal bonds within the extracted LCC, with phenyl glycosidic bonds serving as the predominant linkages. The LCC samples displayed notable antioxidant capacity, as evidenced by their high DPPH free radical scavenging index of 1.28.

Controlling Adsorption of Diblock Copolymer Nanoparticles onto an Aldehyde-Functionalized Hydrophilic Polymer Brush via pH Modulation.

Sterically stabilized diblock copolymer nanoparticles with a well-defined spherical morphology and tunable diameter were prepared by RAFT aqueous emulsion polymerization of benzyl methacrylate at 70 °C. The steric stabilizer precursor used for these syntheses contained pendent cis-diol groups, which means that such nanoparticles can react with a suitable aldehyde-functional surface via acetal bond formation. This principle is examined herein by growing an aldehyde-functionalized polymer brush from a planar silicon wafer and studying the extent of nanoparticle adsorption onto this model substrate from aqueous solution at 25 °C using a quartz crystal microbalance (QCM). The adsorbed amount, Γ, depends on both the nanoparticle diameter and the solution pH, with minimal adsorption observed at pH 7 or 10 and substantial adsorption achieved at pH 4. Variable-temperature QCM studies provide strong evidence for chemical adsorption, while scanning electron microscopy images recorded for the nanoparticle-coated brush surface after drying indicate mean surface coverages of up to 62%. This fundamental study extends our understanding of the chemical adsorption of nanoparticles on soft substrates.

Catalyst-free readily dual-recyclable acetal-based covalent adaptable cellulose networks

Despite covalent adaptable networks (CANs) imparting the favorable features of crosslinked polymers, as well as the functionality of reprocessing, reshaping and welding, due to exchange reaction enabled topology changes; it is still a huge challenge to design catalyst-free, fast reprocessing, controlled degradation and polymer recyclable biomass base CANs. Herein, for the first time, acetal-based covalent adaptable cellulose networks (ACCs) were utilized to synthesize readily reconstructable cellulose-based thermosets with mechanical tunability. ACCs were synthesized via catalyst-free “click” addition of cellulose and divinyl ether without releasing small molecule byproducts. Different crosslinking densities and crosslinkers were used to explore the structure-property relationship, the mechanical and thermal properties of the ACCs were strongly influenced by these factors. ACCs can obtain enhanced tensile strength or elongation at break by changing the structure of the crosslinker. Furthermore, the reworking, welding and shape memory properties of these ACCs, based on the dynamic exchange reaction of acetal bonds, were investigated. In addition, these ACCs can be degraded under acidic conditions, and closed-loop utilization of polymer was possible. Thus, ACCs can be mechanically and chemically double-cycled, which will contribute to solving the white pollution problem and resource waste as a new class of sustainable plastics.

Synthesis, characterization, and antibacterial effect of St. John's wort oil loaded chitosan hydrogel

Hydrogels prepared with natural and synthetic polymers were found to be applicable for the development of resistance against some Gram positive and negative bacterial species. Numerous studies have shown that chitosan polymers can be advantageous to be used in medicine due to their high antibacterial activity. In this study, biocompatible yellow cantorone oil doped hydrogels (chitosan/poly(vinyl alcohol) based) with antimicrobial properties were synthesized. The structural, morphological, swelling and mechanical properties of these biocompatible hydrogels prepared by double crosslinking were investigated and characterized. FTIR spectroscopy showed the appearance of new imine and acetal bonds due to both covalent cross-linking. In vitro cytotoxicity evaluation revealed that hydrogels showed weak cytotoxic effect. In the antimicrobial evaluation, it was determined that the hydrogel containing only chitosan showed better antimicrobial effect against Escherichia coli, Pseudomonas auriginosa, Staphylococcus aureus and Enterococcus faecalis bacteria than the one containing St. John's Wort oil. The antibacterial effect of polyvinyl alcohol/chitosan hydrogel was low. In our wound healing study, chitosan hydrogel loaded with yellow St. John's Wort oil was more effective in reducing wound size.

Linkage-Editing Pseudo-Glycans: A Reductive α-Fluorovinyl-C-Glycosylation Strategy to Create Glycan Analogs with Altered Biological Activities.

The acetal (O-glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore C-glycosides are of interest as more stable analogs. We hypothesized that, if the O-glycoside linkage plays a vital role in glycan function, the biological activities of C-glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans). We designed three types of pseudo-glycans with CH2 and CHF linkages, which resemble the O-glycoside linkage in terms of bond lengths, angles, and bulkiness, and synthesized them efficiently by means of fluorovinyl C-glycosylation and selective hydrogenation reactions. Application of this strategy to isomaltose (IM), an inducer of amylase expression, and α-GalCer, which activates iNKT cells, resulted in the discovery of CH2-IM, which shows increased amylase production ability, and CHF-α-GalCer, which shows activity opposite that of native α-GalCer, serving as an antagonist of iNKT cells.

Castor oil-derived polyurethane networks multiple recyclability based on reversible dynamic acetal bond

Making polyurethanes (PUs) from castor oil (CO) is severely constrained because they cannot be recycled due to the irreversibly cross-linked structure.

Flexible, shape-editable wood-based functional materials with acetal linkages.

A flexible, shape-editable transparent wood (ATW) composite containing acetal linkages was prepared simultaneously through free radical polymerization and addition reaction between vinyl ether bonds and hydroxyl groups. In this system, the anisotropic hierarchical structure of wood acted as a reinforced skeleton, the flexible chain segment ensured flexibility at room temperature, and the dynamic acetal bonds were responsible for the shape memory and editability under relatively mild conditions, verifying the expanding applications of functionalized wood-based materials.

Design of remoldable, shape-memory, welded biomass composites based on the acetal bond of the cellulose chain

The growing environmental concern over petrochemical-based plastics continuously promotes the exploration of green and sustainable biomass-based covalent adaptable networks composites (CANs). Compared with petrochemical products, cellulose and its derivatives have overwhelming superiority in terms of availability, cost and biodegradability; nevertheless, CANs using the abundant acetal bonds in the cellulose chain rather than elaborately designing other types of dynamic covalent bonds still have not received sufficient attention. Herein, we report acetal-based cellulose covalent adaptable networks (ACC) synthesized with poly(ethylene glycol) diglycidyl ether as the crosslinker for hydroxypropyl cellulose and tetrabutylammonium bromide (TBAB) as an accelerant. For the first time, exchangeability of the cellulose chain acetal reversible bonds at elevated temperature have been demonstrated to endow ACC reprocessability, shape memory and welding. The TBAB has been used as an accelerant of dynamic exchange for acetal bonds first and its accelerating mechanism and advantages have also been investigated. In addition, the thermal, mechanical and hydrophilic properties of ACC can be adjusted by simply adjusting the raw material ratio and the ACC has excellent chemical and biodegradability. Hence, ACC will provide new ideas for solving white pollution and building new CANs.

The effect of different cyclic substituents on the properties of recyclable acetal-containing epoxy resins

Vitrimers represent an emerging field warranting comprehensive investigation into fundamental aspects of dynamic covalent bond design. Herein, three acetal-containing cycloaliphatic epoxides (ACEs) with different cyclic substituents (cyclopentyl, furyl, and phenyl groups) were synthesized. These three liquid ACEs have different viscosities and refractive indices. After curing with anhydride, the cured ACEs show elevated glass transition temperature of up to 189 °C, and superior tensile strengths of up to 71 MPa. Interestingly, the dangling groups attached to the acetal bonds have a significant impact on the structure dynamics, reprocessability, degradation rates and hot wet aging resistance of cured ACEs. The effect of different dangling groups on the dynamic behaviors of acetal bonds was verified by small molecular modeling reactions. Among them, the epoxy resin containing the furyl group shows the fastest stress relaxation rate at the same temperature. The epoxy resin containing the phenyl group has the highest retention of tensile strength after reprocessing or hot wet aging, while the epoxy resin containing the cyclopentyl group exhibits the fastest degradation rate in various acid solutions. These cured ACEs can also be effectively repaired and welded owing to their dynamic structures. These noteworthy discoveries provide essential insights for understanding the structure-property relationship of acetal-containing recyclable thermosetting polymers.

Exploration of the Linkages between Lignin and Carbohydrates in Kraft Pulp from Wheat Straw Using a 13C/2H Isotopic Tracer.

To further our understanding of the change in association between lignin and carbohydrates after kraft pulping, isotope-labeled kraft pulp (KP) was prepared using 13C and D double-isotope-labeled wheat straw, and it was subjected to enzymatic hydrolysis and ionic liquid treatment to explore the linkages between lignin and carbohydrate complexes in wheat straw. Isotope abundance determination showed that 13C and D abundances in the experimental groups were substantially higher than those in the control group, indicating that the injected exogenous coniferin-[α-13C], coniferin-[γ-13C], and d-glucose-[6-D2] were effectively absorbed and metabolized during wheat internode growth. Solid-state CP/MAS 13C-NMR spectroscopy showed that lignin was mainly linked to polysaccharides via acetal, benzyl ether, and benzyl ester bonds. Kraft pulp (KP) from the labeled wheat straw was degraded by cellulase. The obtained residue was fractionated using the ionic liquid DMSO/TBAH to separate the cellulose-lignin complex (KP-CLC) and xylan-lignin complex (KP-XLC). X-ray diffractometer determination showed that the KP-CLC regenerated cellulose type II from type I after the ionic liquid conversion. The 13C-NMR spectrum of Ac-En-KP-CLC showed that the cellulose-lignin complex structure was chemically bonded between the lignin and cellulose through acetal and benzyl ether bonds. The 13C-NMR spectrum of En-KP-XLC showed a lignin-hemicellulose complex structure, wherein lignin and xylan were chemically bonded by benzyl ether and acetal bonds. These results indicate that the cross-linking between lignin and carbohydrates exists in lignocellulosic fibers even after kraft pulping.

Acid-degradable magnolol-containing polymeric prodrug micelles for enhanced gastric cancer therapy

Magnolol shows promise as an effective anti-tumor therapeutic agent. Nevertheless, the clinical application of this agent is constrained by its inherent water insolubility and diminished stability. In the present investigation, we have developed a new approach to address these limitations by creating an acid-responsive amphiphilic polymeric prodrug (PMag) that contains acetal bonds and magnolol, and can self-assemble into polymeric micelles (PMag-Ms) in aqueous solutions. We conducted in vitro release studies and observed that the micelles rapidly released magnolol at an acidic pH of 5.0, but only released minimal amounts of magnolol at a neutral pH of 7.4. In vitro investigations performed on gastric cancer cells elucidated that PMag-Ms selectively induced cell apoptosis and G1 phase cell cycle arrest, exhibiting higher efficacy than magnolol alone. Furthermore, in vivo studies confirmed that PMag-Ms exhibited superior inhibition of tumor growth, favorable biocompatibility with organs, increased accumulation in tumor tissues, and enhanced targeting efficiency compared to magnolol. Pharmacokinetic analysis also revealed that PMag-Ms had a longer half-life and extended duration of action in vivo. These results highlight the potential of the synthesized acid-degradable PMag-Ms as a promising therapeutic option for gastric cancer.