Precisely Programmable Degradation and Drug Release Profiles in Triblock Copolyether Hydrogels with Cleavable Acetal Pendants.

Hydrogels hold significant promise as drug delivery systems due to their distinct advantage of sustained localized drug release. However, the challenge of regulating the initial burst release while achieving precise control over degradation and drug-release kinetics persists. Herein, we present an ABA-type triblock copolymer-based hydrogel system with precisely programmable degradation and release kinetics. The resulting hydrogels were designed with a hydrophilic poly(ethylene oxide) midblock and a hydrophobic end-block composed of polyethers with varying ratios of ethoxyethyl glycidyl ether and tetrahydropyranyl glycidyl ether acetal pendant possessing different hydrolysis kinetics. This unique side-chain strategy enabled us to achieve a broad spectrum of precise degradation and drug-release profiles under mildly acidic conditions while maintaining the cross-linking density and viscoelastic modulus, which is unlike the conventional polyester-based backbone degradation system. Furthermore, programmable degradation of the hydrogels and release of active therapeutic agent paclitaxel loaded therein are demonstrated in an in vivo mouse model by suppressing tumor recurrence following surgical resection. Tuning of the fraction of two acetal pendants in the end-block provided delicate tailoring of hydrogel degradation and the drug release capability to achieve the desired therapeutic efficacy. This study not only affords a facile means to design hydrogels with precisely programmable degradation and release profiles but also highlights the critical importance of aligning the drug release profile with the target disease.

Quantifying lysosomal glycosidase activity within cells using bis-acetal substrates.

Understanding the function and regulation of enzymes within their physiologically relevant milieu requires quality tools that report on their cellular activities. Here we describe a strategy for glycoside hydrolases that overcomes several limitations in the field, enabling quantitative monitoring of their activities within live cells. We detail the design and synthesis of bright and modularly assembled bis-acetal-based (BAB) fluorescence-quenched substrates, illustrating this strategy for sensitive quantitation of disease-relevant human α-galactosidase and α-N-acetylgalactosaminidase activities. We show that these substrates can be used within live patient cells to precisely measure the engagement of target enzymes by inhibitors and the efficiency of pharmacological chaperones, and highlight the importance of quantifying activity within cells using chemical perturbogens of cellular trafficking and lysosomal homeostasis. These BAB substrates should prove widely useful for interrogating the regulation of glycosidases within cells as well as in facilitating the development of therapeutics and diagnostics for this important class of enzymes.

Design, Synthesis, and Acid-Responsive Disassembly of Shell-Sheddable Block Copolymer Labeled with Benzaldehyde Acetal Junction.

Smart nanoassemblies degradable through the cleavage of acid-labile linkages have attracted significant attention because of their biological relevance found in tumor tissues. Despite their high potential to achieve controlled/enhanced drug release, a systematic understanding of structural factors that affect their pH sensitivity remains challenging, particulary in the consruction of effective acid-degradable shell-sheddable nanoassemblies. Herein, the authors report the synthesis and acid-responsive degradation through acid-catalyzed hydrolysis of three acetal and ketal diols and identify benzaldehyde acetal (BzAA) exhibiting optimal hydrolysis profiles in targeted pH ranges to be a suitable candidate for junction acid-labile linkage. The authors explore the synthesis and aqueous micellization of well-defined poly(ethylene glycol)-based block copolymer bearing BzAA linkage covalently attached to a polymethacrylate block for the formation of colloidally-stable nanoassemblies with BzAA groups at core/corona interfaces. Promisingly, the investigation on acid-catalyzed hydrolysis and disassembly shows that the formed nanoassemblies meet the criteria for acid-degradable shell-sheddable nanoassemblies: slow degradation at tumoral pH = 6.5 and rapid disassembly at endo/lysosomal pH = 5.0, while colloidal stability at physiological pH = 7.4. This work guides the design principle of acid-degradable shell-sheddable nanoassemblies bearing BzAA at interfaces, thus offering the promise to address the PEG dilemma and improve endocytosis in tumor-targeting drug delivery.

Effects of sunflower oil infusions of Asparagopsis taxiformis on in vitro ruminal methane production and biohydrogenation of polyunsaturated fatty acids.

Asparagopsis taxiformis inhibits ruminal methane (CH4) production due to its bromoform (CHBr3) content. The immersion of A. taxiformis in edible vegetable oils allows the extraction and stabilization of the highly volatile CHBr3 in the oil phase. The objectives of this study were to explore the effects of adding sunflower oils with increasing concentrations of CHBr3 on in vitro ruminal methanogenesis and biohydrogenation. Five batches of 48-h in vitro incubations were performed in 14 fermentation bottles, using rumen inocula collected shortly after the slaughter of young crossbred bulls and 1 g of dry matter (DM) from a total diet of mixed feed without added oil (control) or with 60 µL of sunflower oil per gram of DM as the substrate. The treatments were the CHBr3 content in the oil added: 0 µg (B0), 25 µg (B25), 50 µg (B50), 75 µg (B75), 100 µg (B100), and 150 µg (B150) of CHBr3 per gram of substrate DM. Organic matter (OM) degradability, total gas, CH4, volatile fatty acids (VFA), long-chain fatty acids, and dimethyl acetals (DMA) were analyzed at the end of each incubation. Data were analyzed with a model considering the treatments as the fixed effect and the run as a random block and using orthogonal contrasts. Degradability of OM was higher in the control group and was unaffected by CHBr3 concentration. Total gas production per gram of degraded OM was unaffected by treatments and averaged 205 ± 29.8 mL/g. Methane (mL) production decreased linearly with increasing CHBr3 concentrations, with 33%, 47%, and 87% reductions for B75, B100, and B150, respectively. Total VFA concentration was unaffected by oil inclusion but was reduced by 20% in CHBr3-containing treatments, although without any dose-response pattern. The molar percentage of acetate decreased linearly, whereas propionate and butyrate increased linearly with the increasing CHBr3 dosage. Including oil in the diet decreased the branched-chain fatty acids and DMA content. Increasing CHBr3 concentrations did not affect branched-chain fatty acids, but linearly increased most of the identified DMA. Adding oil to the control diet increased the 18:2n-6, whereas increasing the concentration of CHBr3 had no effect on 18:2n-6 but decreased linearly the 18:0 and increased the trans-18:1 isomers. The results obtained provide evidence that oil immersions of A. taxiformis can successfully inhibit ruminal production of CH4 in vitro at doses of 100 and 150 µg/g DM, and simultaneously modulate biohydrogenation.

Exploration and Development of Nitrone Chemistry.

Nitrones are widely used as 1,3-dipoles in organic synthesis, but control of their reactions is not always easy. This review outlines our efforts to make the reactions of nitrones more predictable and easier to use. These efforts can be categorized into (1) 1,3-nucleophilic addition reaction of ketene silyl acetals to nitrones, (2) geometry-controlled cycloaddition of C-alkoxycarbonyl nitrones, (3) stereo-controlled cycloaddition using double asymmetric induction, and (4) generation of nitrones by N-selective modification of oximes.

Shell-Sheddable Polymeric Micelles Alleviate Oxidative Stress and Inflammation for Enhanced Ischemic Stroke Therapy.

As a ROS scavenger, resveratrol exerts a neuroprotective effect by polarizing the M1 microglia to the anti-inflammatory M2 phenotype for ischemic stroke treatment. However, the obstruction of the blood-brain barrier (BBB) seriously impairs the efficacy of resveratrol. Herein, we develop a stepwise targeting nanoplatform for enhanced ischemic stroke therapy, which is fabricated by pH-responsive poly(ethylene glycol)-acetal-polycaprolactone-poly(ethylene glycol) (PEG-Acetal-PCL-PEG) and modified with cRGD and triphenylphosphine (TPP) on a long PEG chain and a short PEG chain, respectively. The as-designed micelle system features effective BBB penetration through cRGD-mediated transcytosis. Once entering the ischemic brain tissues and endocytosed by microglia, the long PEG shell can be detached from the micelles in the acidic lysosomes, subsequently exposing TPP to target mitochondria. Thus, the micelles can effectively alleviate oxidative stress and inflammation by enhanced delivery of resveratrol to microglia mitochondria, reversing the microglia phenotype through the scavenging of ROS. This work offers a promising strategy to treat ischemia-reperfusion injury.

Selective Peptide Cysteine Manipulation on Demand and Difficult Protein Chemical Synthesis Enabled by Controllable Acidolysis of N,S-Benzylidene Thioacetals.

Although solid-phase peptide synthesis combining with chemical ligation provides a way to build up customized polypeptides in general, many targets are still presenting challenges for the conventional synthetic process, such as hydrophobic proteins. New methods and strategies are still required to overcome these obstacles. In this study, kinetic studies of Cys/Pen ligation and its acidolysis were performed, from which the fast acidolysis of substituted N,S-benzylidene thioacetals (NBTs) was discovered. The study demonstrates the potential of NBTs as a promising Cys switchable protection, facilitating the chemical synthesis of peptides and proteins by efficiently disrupting peptide aggregation. The compatibility of NBTs with other commonly adopted Cys protecting groups and their applications in sequential disulfide bond formation were also investigated. The first chemical synthesis of the native human programmed death ligand 1 immunoglobulin V-like (PD-L1 IgV) domain was achieved using the NBT strategy, showcasing its potential in difficult protein synthesis.

Design of Cationic Lipids with Acetal Linkers: Conformational Preferences, Hydrolytic Stability, and High Drug-Loading Abilities.

Lipids are key constituents of numerous biomedical drug delivery technologies. Here, we present the design, synthesis and biophysical characterizations of a library of cationic lipids containing an acetal residue in their linker region. These cationic acetal lipids (CALs) were conveniently prepared through a trans-acetalization protocol from commercially available precursors. NMR studies highlighted the conformational rigidity at the acetal residue and the high hydrolytic stability of these CALs. Fluorescence anisotropy studies revealed that the CAL with a pyridinium headgroup (CAL1) formed highly cohesive vesicular aggregates in water. These structural and self-assembly features of the CAL1 allowed up to 196 % w/w loading of curcumin (Cur) as a representative hydrophobic drug. A reconstitutable formulation of Cur was obtained as a result, which could deliver the drug inside mammalian cells with very high efficiency. The hemocompatibility and cytocompatibility of CAL1 was significantly enhanced by creating a coating of polydopamine (PDA) onto its vesicular assemblies to produce hybrid lipid-polymer nanocapsules. This work demonstrates rapid access to the useful synthetic lipid formulations with high potential in drug and gene delivery applications.

Hydride-Abstraction-Initiated Catalytic Stereoselective Intermolecular Bond-Forming Processes.

The stereoselective intermolecular bond-forming reactions through the direct manipulation of ubiquitous yet inert C(sp3)-H bonds represent an important and long-standing goal in chemistry. In particular, developing such a stereoselective bimolecular transformation involving carbocation intermediates generated via site-selective hydride abstraction or formal hydride abstraction by organic oxidants would avoid the preinstallation of directing groups and is therefore attractive. Hydride-abstraction-initiated bimolecular transformations have received considerable attention, but existing examples lack stereoselective studies. Prevalent stereoselective studies typically suffer from the narrow substrate scope of specific and highly reactive N-aryl amines and diarylmethanes together with limited synthetic utility. This Account describes our recent advances in the development and synthetic application of hydride-abstraction-initiated stereoselective intermolecular C-C and C-H bond-forming processes with significantly expanded scopes involving structurally diverse N-acyl amines and ethers together with nitriles, esters, and perfluoroalkyl moieties.We first explored hydride-abstraction-initiated stereoselective intermolecular C-C bond-forming processes. Utilizing triarylmethyl cations or oxoammonium ions as hydride abstractors, we accomplished the diastereoselective oxidative C-H functionalization of structurally diverse N-acyl amines and ethers with a range of organoboranes and C-H components, efficiently installing a series of alkyl, alkenyl, aryl, and alkynyl species into the α-position of heteroatoms with good levels of diastereocontrol. Subsequently, we developed an "acetal pool" strategy as the toolbox to regulate the stability of cationic intermediates and the compatibility of organic oxidants with a delicate asymmetric catalysis system. Utilizing this strategy, we achieved the catalytic enantioselective oxidative C-H alkenylation, arylation, alkynylation, and alkylation of diverse N-acyl heterocycles with a range of boronates and C-H components. Simultaneously, we extended this strategy to the asymmetric oxidative C-H alkylation of ethers. Notably, the method allows solvents that are used daily, such as tetrahydrofuran, tetrahydropyran, and diethyl ether, to be facilely transformed to high-value-added optically pure bioactive molecules. We further expanded the scope of this challenging area from the C(sp3)-H bond adjacent to electron-donating heteroatoms to valuable electron-withdrawing functional groups including nitriles, esters, and perfluoroalkyl moieties for the stereoselective construction of single and vicinal quaternary carbon stereocenters, respectively.We studied hydride-abstraction-initiated catalytic asymmetric intermolecular C-H bond-forming processes, known as redox deracemization. Utilizing the acetal pool strategy, we reported the first redox deracemization of cyclic benzylic ethers. Later, we disclosed an aerobic one-pot deracemization of diverse α-amino acid derivatives with excellent functional group compatibility. We further achieved the deracemization of the tertiary stereogenic center adjacent to electron-withdrawing groups including perfluoroalkyl, cyano, and ester moieties, which are otherwise difficult to construct.

A Wide Range of Flavoring-Carrier Fluid Adducts Form in E-Cigarette Liquids.

A range of flavoring molecules are used in electronic cigarette liquids (e-liquids), some of which have been shown to form cyclic acetal adducts with e-liquid solvent components propylene glycol (PG) and vegetable glycerine (VG). The objective of this study was to identify the range of flavoring molecules which form adducts in e-liquid products. Common e-liquid flavoring molecules (N = 36) from a range of chemical class groups were exposed to PG, VG, or methanol and analyzed by GC-MS over a time frame of 4 weeks to identify possible reaction products. Adduct formation was observed, with 14 of the flavoring molecules reacting with methanol, 10 reacting with PG, and 10 reacting with VG. Furfural PG and VG acetals, valeraldehyde PG and VG acetals, veretraldehyde PG and VG acetals, p-anisaldehyde PG and VG acetals, and piperonal VG acetal were confirmed for the first time. Adducts formed by reaction with ketone-containing flavoring molecules were also observed for the first time. The presence of these acetals was confirmed in 32% of commercial e-liquid products analyzed (N = 142). This study has established a range of flavoring molecules which are able to react with solvent components PG and VG in e-liquids under standard storage conditions. These newly identified adducts need to be further assessed to determine their toxicological safety.

Increasing the Hydrophilicity of Cyclic Ketene Acetals Improves the Hydrolytic Degradation of Vinyl Copolymers and the Interaction of Glycopolymer Nanoparticles with Lectins.

Radical ring-opening polymerization (rROP) of cyclic ketene acetals (CKAs) with traditional vinyl monomers allows the synthesis of degradable vinyl copolymers. However, since the most commonly used CKAs are hydrophobic, most degradable vinyl copolymers reported so far degrade very slowly by hydrolysis under physiological conditions (phosphate-buffered saline, pH 7.4, 37 °C), which can be detrimental for biomedical applications. Herein, to design advanced vinyl copolymers by rROP with high CKA content and enhanced degradation profiles, we reported the copolymerization of 2-methylene-1,3,6-trioxocane (MTC) as a CKA with vinyl ether (VE) or maleimide (MI) derivatives. By performing a point-by-point comparison between the MTC/VE and MTC/MI copolymerization systems, and their counterparts based on 2-methylene-1,3-dioxepane (MDO) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), we showed negligible impact on the macromolecular characteristics and similar reactivity ratios, suggesting successful substitution of MDO and BMDO by MTC. Interestingly, owing to the hydrophilicity of MTC, the obtained copolymers exhibited a faster hydrolytic degradation under both accelerated and physiological conditions. We then prepared MTC-based glycopolymers, which were formulated into surfactant-free nanoparticles, exhibiting excellent colloidal stability up to 4 months and complete degradation under enzymatic conditions. Importantly, MTC-based glyconanoparticles also showed a similar cytocompatibility toward two healthy cell lines and a much stronger lectin affinity than MDO-based glyconanoparticles.

Acetal Formation of Flavoring Agents with Propylene Glycol in E-Cigarettes: Impacts on Indoor Partitioning and Thirdhand Exposure.

The widespread use of flavored e-cigarettes has led to a significant rise in teenage nicotine use. In e-liquids, the flavor carbonyls can form acetals with unknown chemical and toxicological properties. These acetals can cause adverse health effects on both smokers and nonsmokers through thirdhand exposure. This study aims to explore the impacts of these acetals formed in e-cigarettes on indoor partitioning and thirdhand exposure. Specifically, the acetalization reactions of commonly used flavor carbonyls in laboratory-made e-liquids were monitored using proton nuclear magnetic resonance (1H NMR) spectroscopy. EAS-E Suite and polyparameter linear free energy relationships (PP-LFERs) were employed to estimate the partitioning coefficients for species. Further, a chemical two-dimensional partitioning model was applied to visualize the indoor equilibrium partitioning and estimate the distribution of flavor carbonyls and their acetals in the gas phase, aerosol phase, and surface reservoirs. Our results demonstrate that a substantial fraction of carbonyls were converted into acetals in e-liquids and their chemical partitioning was significantly influenced. This study shows that acetalization is a determinant factor in the exposure and toxicology of harmful carbonyl flavorings, with its impact extending to both direct exposure to smokers and involuntary exposure to nonsmokers.

Current Standing on Radical Ring-Opening Polymerizations of Cyclic Ketene Acetals as Homopolymers and Copolymers with one another.

Radical Ring-opening polymerization (RROP) of cyclic ketene acetals (CKAs) emerges to be a valuable polymerization technique. In attracting more attention, RROP has seen a new spike in publications, which the authors will put into perspective. This review will hence address the progress made on the number of available CKAs and the synthetic strategies to get them. In grouping, the available monomers into distinct categories, the enormous variety of available CKAs will be highlighted. Polymerizations of CKAs without vinylenes have the potential to yield fully biodegradable polymers, which is why this kind of polymerization is the focus of this review. Detailing the current understanding of the mechanism, the various side reactions will be noted and also their effect on the overall properties of the final polymers. Current attempts to control the ring-retaining and branching reactions will be discussed as well. In addition to the polymerization itself, the available materials will be discussed as well as homopolymers, copolymers of CKAs, and block-copolymers with pure CKA-blocks have significantly widened the range of possible applications of materials from RROP. Altogether this review highlights the progress in the entire field of RROP just of CKAs to give a holistic overview of the field.

Dual-Dynamic Chemistries-Based Fast-Reprocessing and High-Performance Covalent Adaptable Networks.

Covalent adaptable networks (CANs) possess multiple functions including reprocessing (or recyclability), self-healing, welding, shape shifting, 3D printing, etc., due to the network rearrangement from dynamic bonds, and favorable performance from their cross-linked feature, and they are supposed to be as sustainable alternatives to thermosets. However, the thermal and mechanical properties, and stability of CANs are often sacrificed for rapid network rearrangement. In this paper, fast-reprocessing CANs with high performance are facilely constructed by in situ polymerization and dynamic cross-linking of styrene (St), maleic anhydride (MA), and acetal diol (BHAD). The rigid and hydrophobic polymer backbone endow the materials with high glass transition temperatures, mechanical performance, and water resistance. Besides, carboxylic group-catalyzed dual dynamic ester and acetal-based networks exhibit faster stress relaxation and realize extrusion reprocessing. This work provides an ingenious and simple strategy of construction of CANs combining rapid network rearrangement and excellent comprehensive performance, which is beneficial for the application of CANs.

Ring-Opening Polymerization of Cyclic Acetals: Strategy for both Recyclable and Degradable Materials.

To cope with the severe plastic waste crisis, massive efforts are made to develop sustainable polymer materials whose degradation involves a disposing and decomposing to small molecule (DDM) and/or a chemical recycling to monomer (CRM) process. Polyacetals, a type of pH-responsive polymers, are degradable under acidic conditions, while highly stable under neutral and basic circumstances. As for their synthesis, the cationic ring-opening polymerization (CROP) of cyclic acetals is an elegant and promising approach, though suffering from fatal side reactions and polymerization-depolymerization equilibrium. Recent development in CRM restimulates the interest in the long-forgotten CROP method due to its inherent depolymerization characteristics. In terms of the end-of-life options, polyacetals are recyclable materials with both DDM and CRM potentials. They not only expand the scope of materials for closed-loop recycling but also help to tune the degradation properties of traditional polyesters and polyolefins. This review aims to discuss the synthesis of various polyacetals by CROP and their degradation properties from the perspectives of 1) polymerization of cyclic acetals, dioxepins, and hemiacetal esters, 2) copolymerization of cyclic acetals with heterocyclic or vinyl monomers, and 3) degradation and recycling properties of the related polymers.

Pseudo-Enantiomeric Paraphaeolactones and Their Biosynthetic Derivatives from Paraphaeosphaeria sp. KT4192: A Proposition of a Favorskii Rearrangement for Their Biosynthesis.

Paraphaeolactones A1, A2, B1, and B2 (1-4, respectively), known arthropsadiol D (5), massariphenone (6) and its positional isomer 7, and massarilactones E (8) and G (9) were isolated from the culture broth of Paraphaeosphaeria sp. KT4192. Although the structural resemblance between 1 and 2 implies that these comprised a diastereomeric pair at the C-2 stereogenic center, electronic circular dichroism (ECD) spectral analyses revealed that they were pseudo-enantiomers possessing the common (2R)-configuration. Paraphaeolactones B1 and B2 (3 and 4) were the derivatives of 2, which equipped the 3-(1-hydroxy-2-oxopropyl)-4-methylcatechol moiety via an acetal bond at C-10. The relative configurations of their acetal carbons were elucidated by NOE experiments, and those of C-8' were deduced independently by ECD spectral analysis. The present study disclosed that 1-5, 8, and 9 contain a methylcyclohexene substructure with the same absolute configuration. This prompted us to reinvestigate the absolute configurations of known structurally related fungal metabolites, allowing us to conclude that the methylcyclohexene moieties of these natural products have the same absolute configuration despite the variety of configurations of other stereogenic centers. The plausible biosynthetic routes for 1-9 are discussed on the basis of the above conclusion. We propose a Favorskii rearrangement as the key transformation for biosyntheses of 1-4.

Efficient regioselective five-component synthesis of novel thiazolo[3,2-a]pyridine carbohydrazides and oxazolo[3,2-a]pyridine carbohydrazides.

Two new categories of fused pyridines include 2H-thiazolo[3,2-a]pyridine-6-carbohydrazides and 2H-oxazolo[3,2-a]pyridine-6-carbohydrazides have been successfully synthesized via five-component cascade reactions using 9-fluorenone, cyanoacetohydrazide, 1,1-bis(methylthio)-2-nitroethene, aromatic aldehydes and cysteamine hydrochloride or ethanol amine as starting materials. This new approach involves a subsequence of key steps: N,S-acetal or N,O-acetal formation, Knoevenagel condensation, Michael addition, tautomerization and N-cyclization. It also has some advantages, such as convenience of operation, tolerance of a wide diversity of functional groups, use of green solvent and ease of purification by washing the crude products with ethanol.

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.

Evaluation of polymethyl-methacrylate and acetal denture base resins processed by two different techniques before and after nano-chlorohexidine surface treatment.

BACKGROUND: Flexible denture base polymers have gained popularity in modern dentistry however, their biofilm formation tendency, adversely affecting the oral tissue heath, remains a concern. Consequently, this study aimed to evaluate surface roughness and biofilm formation tendency of two types of denture base resins manufactured with two techniques before and after surface coating with chlorohexidine (CHX) NPs. MATERIALS AND METHODS: Acetal (AC) and Polymethyl-methacrylate (PMMA) resins manufactured by conventional and CAD/CAM methods were shaped into disk (10 X 10 X 1 mm). They were dipped for 8 h and 24 h in colloidal suspension prepared by mixing aqueous solution of CHX digluconate and hexa-metaphosphate (0.01 M). Surface roughness, optical density (OD) of microbial growth media and biofilm formation tendency were evaluated directly after coating. Elutes concentrations of released CHX were evaluated for 19 days using spectrophotometer. Three-way ANOVA and Tukey's post-hoc statistical analysis were used to assess the outcomes. RESULTS: AC CAD/CAM groups showed statistically significant higher roughness before and after coating (54.703 ± 4.32 and 77.58 ± 6.07 nm, respectively). All groups showed significant reduction in OD and biofilm formation tendency after surface coating even after 19 days of CHX NPs release. CONCLUSIONS: Biofilm formation tendency was highly relevant to surface roughness of tested resins before coating. After CHX NPs coating all tested groups showed significant impact on microbial growth and reduction in biofilm formation tendency with no relation to surface roughness. Significant antimicrobial effect remained even after 19 days of NPs release and specimens storage.

N,O-Benzylidene Acetal Dipeptides (NBDs) Enable the Synthesis of Difficult Peptides via a Kinked Backbone Strategy.

Proteins with highly hydrophobic regions or aggregation-prone sequences are typically difficult targets for chemical synthesis at the current stage, as obtaining such type of peptides via solid-phase peptide synthesis requires sophisticated operations. Herein, we report N,O-benzylidene acetal dipeptides (NBDs) as robust and effective building blocks to allow the direct synthesis of difficult peptides and proteins via a kinked backbone strategy. The effectiveness and easy accessibility of NBDs have been well demonstrated in our chemical syntheses of various challenging peptides and proteins, including chemokine, therapeutic hormones, histone, and glycosylated erythropoietin.