A pentameric TRPV3 channel with a dilated pore.

Transient receptor potential (TRP) channels are a large, eukaryotic ion channel superfamily that control diverse physiological functions, and therefore are attractive drug targets1-5. More than 210 structures from more than 20 different TRP channels have been determined, and all are tetramers4. Despite this wealth of structures, many aspects concerning TRPV channels remain poorly understood, including the pore-dilation phenomenon, whereby prolonged activation leads to increased conductance, permeability to large ions and loss of rectification6,7. Here, we used high-speed atomic force microscopy (HS-AFM) to analyse membrane-embedded TRPV3 at the single-molecule level and discovered a pentameric state. HS-AFM dynamic imaging revealed transience and reversibility of the pentamer in dynamic equilibrium with the canonical tetramer through membrane diffusive protomer exchange. The pentamer population increased upon diphenylboronic anhydride (DPBA) addition, an agonist that has been shown to induce TRPV3 pore dilation. On the basis of these findings, we designed a protein production and data analysis pipeline that resulted in a cryogenic-electron microscopy structure of the TRPV3 pentamer, showing an enlarged pore compared to the tetramer. The slow kinetics to enter and exit the pentameric state, the increased pentamer formation upon DPBA addition and the enlarged pore indicate that the pentamer represents the structural correlate of pore dilation. We thus show membrane diffusive protomer exchange as an additional mechanism for structural changes and conformational variability. Overall, we provide structural evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.

Host-Guest Doping Modulated Afterglow Emission of Fluoroquinolones for Their Separation-Free Detection and Discrimination.

Detection and discrimination of fluoroquinolones (FQs) are crucial for food safety but remain a formidable challenge due to their minor differences in molecular structures and the serious interferences from food matrices. Herein, we propose an afterglow assay for the detection and discrimination of FQs through modulating their room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF) properties by a host-guest doping strategy. FQs were doped into the boric acid host, forming boronic anhydride structures and hydrogen bonds, which prompted the RTP and TADF performance of FQs by stabilizing their excited states, preventing triplet exciton quenching, and reducing the energy gap between singlet and triplet states. The FQs can be quantitatively detected through monitoring the afterglow intensity of host-guest systems, as low as 0.25 µg/mL. The differences in the afterglow intensity and emission lifetime allowed accurate discrimination of 11 types of FQs through pattern recognition methods. Aided by the delayed signal detection model of afterglow emission, the background signal and the interferences from food matrices were effectively eliminated, which endow the detection and discrimination of mixed FQs in commercial meat samples, without multiple-step separation processes.

Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage.

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

Effect of Brønsted Acids on the Activation of Mixed Anhydride/Mixed Carbonic Anhydride and C-Terminal-Free N-Methylated Peptide Synthesis in a Micro-Flow Reactor.

Amidations employing mixed (carbonic) anhydrides have long been favoured in peptide synthesis because of their cost-effectiveness and less waste generation. Despite their long history, no study has compared the effects of additives on the activation of mixed anhydrides and carbonic anhydrides. In this study, we investigated the amidation of mixed (carbonic) anhydride in the presence of a base and/or Brønsted acids. The use of NMI⋅HCl significantly improved the conversion of the mixed carbonic anhydride, while expediting nucleophilic attacks on the desired carbonyl group. In contrast, in the case of mixed anhydrides, neither the conversion nor the desired nucleophilic attack improved significantly. We developed a C-terminus-free N-methylated peptide synthesis method using mixed carbonic anhydrides in a micro-flow reactor. Fourteen N-alkylated peptides were synthesized in moderate to high yields (55-99 %) without severe racemization (<1 %). Additionally, a significant enhancement in the amidation between mixed carbonic anhydrides and bis-TMS-protected N-methyl amino acids with the inclusion of NMI⋅HCl was observed for the first time. In addition, we observed unexpected C-terminal epimerization of the C-terminus-free N-methyl peptides.

Utility of Triethyloxonium Tetrafluoroborate for Chloride Removal during Sarcosine N-Carboxyanhydride Synthesis: Improving NCA Purity.

The clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality making high-purity sarcosine N-carboxyanhydride (Sar-NCA) as monomer for its production inevitable. Within this report, we present the use of triethyloxonium tetrafluoroborate in Sar-NCA synthesis with focus on amino acid and chloride impurities to avoid the sublimation of Sar-NCAs. With a view towards upscaling into kilogram or ton scale, a new methodology of monomer purification is introduced by utilizing the Meerwein's Salt triethyloxonium tetrafluoroborate to remove chloride impurities by covalent binding and converting chloride ions into volatile products within a single step. The novel straightforward technique enables access to monomers with significantly reduced chloride content (<100 ppm) compared to Sar-NCA derived by synthesis or sublimation. The derived monomers enable the controlled-living polymerization in DMF and provide access to pSar polymers with Poisson-like molecular weight distribution within a high range of chain lengths (Xn 25-200). In conclusion, the reported method can be easily applied to Sar-NCA synthesis or purification of commercially available pSar-NCAs and eases access to well-defined hetero-telechelic pSar polymers.

Enhancing Mucoadhesive Properties of Gelatin through Chemical Modification with Unsaturated Anhydrides.

Gelatin is a water-soluble natural polyampholyte with poor mucoadhesive properties. It has traditionally been used as a major ingredient in many pharmaceuticals, including soft and hard capsules, suppositories, tissue engineering, and regenerative medicine. The mucoadhesive properties of gelatin can be improved by modifying it through conjugation with specific adhesive unsaturated groups. In this study, gelatin was modified by reacting with crotonic, itaconic, and methacrylic anhydrides in varying molar ratios to yield crotonoylated-, itaconoylated-, and methacryloylated gelatins (abbreviated as Gel-CA, Gel-IA, and Gel-MA, respectively). The successful synthesis was confirmed using 1H NMR, FTIR spectroscopies, and colorimetric TNBSA assay. The effect of chemical modification on the isoelectric point was studied through viscosity and electrophoretic mobility measurements. The evolution of the storage (G') and loss (G'') moduli was employed to determine thermoreversible gelation points of modified and unmodified gelatins. The safety of modified gelatin derivatives was assessed with an in vivo slug mucosal irritation test (SMIT) and an in vitro MTT assay utilizing human pulmonary fibroblasts cell line. Two different model dosage forms, such as physical gels and spray-dried microparticles, were prepared and their mucoadhesive properties were evaluated using a flow-through technique with fluorescent detection and a tensile test with ex vivo porcine vaginal tissues and sheep nasal mucosa. Gelatins modified with unsaturated groups exhibited superior mucoadhesive properties compared to native gelatin. The enhanced ability of gelatin modified with these unsaturated functional groups is due to the formation of covalent bonds with cysteine-rich subdomains present in the mucin via thiol-ene click Michael-type addition reactions occurring under physiologically relevant conditions.

Toward Synthetic Intrinsically Disordered Polypeptides (IDPs): Controlled Incorporation of Glycine in the Ring-Opening Polymerization of N-Carboxyanhydrides.

Intrinsically disordered proteins (IDPs) do not have a well-defined folded structure but instead behave as extended polymer chains in solution. Many IDPs are rich in glycine residues, which create steric barriers to secondary structuring and protein folding. Inspired by this feature, we have studied how the introduction of glycine residues influences the secondary structure of a model polypeptide, poly(l-glutamic acid), a helical polymer. For this purpose, we carried out ring-opening copolymerization with γ-benzyl-l-glutamate and glycine N-carboxyanhydride (NCA) monomers. We aimed to control the glycine distribution within PBLG by adjusting the reactivity ratios of the two NCAs using different reaction conditions (temperature, solvent). The relationship between those conditions, the monomer distributions, and the secondary structure enabled the design of intrinsically disordered polypeptides when a highly gradient microstructure was achieved in DMSO.

Facile Synthesis of High Molecular Weight Poly(ethylene glycol)-b-poly(amino acid)s by Relay Polymerization.

Poly(amino acid)s (PAAs) are one kind of favorable biopolymer that can be used as a drug or gene carrier. However, conventional ring-opening polymerization of PAAs is slow and needs a strict anhydrous environment with an anhydrous reagent as well as the product without enough high molecular weight (Mn), which limits the expanding of PAAs' application. Herein, we took BLG-NCA as the monomer to quickly synthesize one kind of high Mn amphiphilic copolymer, poly(ethylene glycol)-b-poly(γ-benzyl-l-glutamic acid) (PEG-PBLG), by relay polymerization with a simple one-pot method within 3 h in mild conditions (open air, moisture insensitive). In the polymerization process, ring-opening polymerization-induced self-assembly in sodium bicarbonate aqueous solution first occurred to obtain low Mn PEG-PBLG seeds without purification. Then γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) dichloromethane solution was added into PEG-PBLG seeds directly and stirred vigorously to form am emulsion; during this process, the amphiphilic PEG-PBLG seeds will anchor on the interface of DCM and water to ensure the concentration of α-helix rigid PBLG in DCM to maintain the following relay polymerization. Then, high Mn PEG-PBLG was obtained in mild conditions in one pot. We found that the α-helix rigid structure was essential for relay polymerization by studying the synthetic speed of amphiphilic copolymer with different secondary structures. MOE simulation results showed that PBLG and BLG-NCA tended to form a double hydrogen bond, which was beneficial to relay polymerization because of higher local concentrations that can produce more double hydrogen bonds. Our strategy can quickly obtain high Mn PEG-PBLG (224.9 KDa) within 3 h from PEG-NH2 and BLG-NCA in one pot and did not need an extra initiator. After deprotection, the poly(ethylene glycol)-b-poly(l-glutamate acid) (PEG-PGA) with high Mn as a second product can be used as an excellent antitumor drug carrier. The high Mn PEG-PGA can achieve an encapsulation rate of 86.7% and a drug loading rate of 47.3%, which is twice that of the low Mn PEG-PGA. As a result, the synthesis of PEG-PBLG by relay polymerization simplified the process of PEG-PAA polymerization and increased the Mn. In addition, this method opened a way to obtain other kinds of high Mn PEG-PBLG values in the future.

Dextran Macroinitiator for Synthesis of Polysaccharide-b-Polypeptide Block Copolymers via NCA Ring-Opening Polymerization.

Synthesis of polysaccharide-b-polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in N-carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran-b-polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis. In this strategy, regioselective (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the sole primary alcohol located at the C-6 position of the monosaccharide at the nonreducing end of linear dextran results in a carboxylic acid. This motif is then transformed into a tetraalkylammonium carboxylate, thereby generating the dextran macroinitiator. This macroinitiator initiates a wide range of NCA monomers and produces dextran-b-polypeptides with a degree of polymerization (DP) of the polypeptide up to 70 in a controlled manner (D < 1.3). This strategy offers several distinct advantages, including preservation of the original dextran backbone structure, relatively rapid polymerization, and moisture tolerance. The dextran-b-polypeptides exhibit interesting self-assembly behavior. Their nanostructures have been investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and adjustment of the structure of block copolymers allows self-assembly of spherical micelles and worm-like micelles with varied diameters and aspect ratios, revealing a range of diameters from 60 to 160 nm. Moreover, these nanostructures exhibit diverse morphologies, including spherical micelles and worm-like micelles, enabling delivery applications.

A Novel Hydrophobic Polyimide Film with Sag Structure Derived from Multi-Hybrid Strategy.

Polyimide (PI) film with hydrophilic greatly limits their application in the field of microelectronic device packaging. A novel hydrophobic PI film with sag structure and improved mechanical properties is prepared relying on the reaction between anhydride-terminated isocyanate-based polyimide (PIY) containing a seven-membered ring structure and the amino-terminated polyamide acid (PAA) via multi-hybrid strategy, this work named it as hybrid PI film and marked it as PI-PIY-X. PI-PIY-30 showed excellent hydrophobic properties, and the water contact angle could reach to 102°, which is 20% and 55% higher than simply PI film and PIY film, respectively. The water absorption is only 1.02%, with a decrease of 49% and 53% compared with PI and PIY. Due to that the degradation of seven-membered ring and generation of carbon dioxide led to the formation of sag structure, the size of sag structures is ≈16.84 and 534.55 nm for in-plane and out-plane direction, which are observed on surface of PI-PIY-30. Meanwhile, PI-PIY-30 possessed improved mechanical properties, and the tensile strength is 109.08 MPa, with 5% and more than 56% higher than that of pure PI and PIY film, showing greatly application prospects in the field of integrated circuit.

Polymerizable 2-Propionic-3-methylmaleic Anhydrides as a Macromolecular Carrier Platform for pH-Responsive Immunodrug Delivery.

The design of functional polymers coupled with stimuli-triggered drug release mechanisms is a promising achievement to overcome various biological barriers. pH trigger methods yield significant potential for controlled targeting and release of therapeutics due to their simplicity and relevance, especially upon cell internalization. Here, we introduce reactive polymers that conjugate primary or secondary amines and release potential drugs under acidic conditions. For that purpose, we introduced methacrylamide-based monomers with pendant 2-propionic-3-methylmaleic anhydride groups. Such groups allow the conjugation of primary and secondary amines but are resistant to radical polymerization conditions. We, therefore, polymerized 2-propionic-3-methylmaleic anhydride amide-based methacrylates via reversible addition-fragmentation chain transfer (RAFT) polymerization. Their amine-reactive anhydrides could sequentially be derivatized by primary or secondary amines into hydrophilic polymers. Acidic pH-triggered drug release from the polymeric systems was fine-tuned by comparing different amines. Thereby, the conjugation of primary amines led to the formation of irreversible imide bonds in dimethyl sulfoxide, while secondary amines could quantitatively be released upon acidification. In vitro, this installed pH-responsiveness can contribute to an effective release of conjugated immune stimulatory drugs under endosomal pH conditions. Interestingly, the amine-modified polymers generally showed no toxicity and a high cellular uptake. Furthermore, secondary amine-modified immune stimulatory drugs conjugated to the polymers yielded better receptor activity and immune cell maturation than their primary amine derivatives due to their pH-sensitive drug release mechanism. Consequently, 2-propionic-3-methylmaleic anhydride-based polymers can be considered as a versatile platform for pH-triggered delivery of various (immuno)drugs, thus enabling new strategies in macromolecule-assisted immunotherapy.

Maleidride biosynthesis - construction of dimeric anhydrides - more than just heads or tails.

Covering: up to early 2022Maleidrides are a family of polyketide-based dimeric natural products isolated from fungi. Many maleidrides possess significant bioactivities, making them attractive pharmaceutical or agrochemical lead compounds. Their unusual biosynthetic pathways have fascinated scientists for decades, with recent advances in our bioinformatic and enzymatic understanding providing further insights into their construction. However, many intriguing questions remain, including exactly how the enzymatic dimerisation, which creates the diverse core structure of the maleidrides, is controlled. This review will explore the literature from the initial isolation of maleidride compounds in the 1930s, through the first full structural elucidation in the 1960s, to the most recent in vivo, in vitro, and in silico analyses.

Synergic Heterodinuclear Catalysts for the Ring-Opening Copolymerization (ROCOP) of Epoxides, Carbon Dioxide, and Anhydrides.

The development of sustainable plastic materials is an essential target of chemistry in the 21st century. Key objectives toward this goal include utilizing sustainable monomers and the development of polymers that can be chemically recycled/degraded. Polycarbonates synthesized from the ring-opening copolymerization (ROCOP) of epoxides and CO2, and polyesters synthesized from the ROCOP of epoxides and anhydrides, meet these criteria. Despite this, designing efficient catalysts for these processes remains challenging. Typical issues include the requirement for high catalyst loading; low catalytic activities in comparison with other commercialized polymerizations; and the requirement of costly, toxic cocatalysts. The development of efficient catalysts for both types of ROCOP is highly desirable. This Account details our work on the development of catalysts for these two related polymerizations and, in particular, focuses on dinuclear complexes, which are typically applied without any cocatalyst. We have developed mechanistic hypotheses in tandem with our catalysts, and throughout the Account, we describe the kinetic, computational, and structure-activity studies that underpin the performance of these catalysts. Our initial research on homodinuclear M(II)M(II) complexes for cyclohexene oxide (CHO)/CO2 ROCOP provided data to support a chain shuttling catalytic mechanism, which implied different roles for the two metals in the catalysis. This mechanistic hypothesis inspired the development of mixed-metal, heterodinuclear catalysts. The first of this class of catalysts was a heterodinuclear Zn(II)Mg(II) complex, which showed higher rates than either of the homodinuclear [Zn(II)Zn(II) and Mg(II)Mg(II)] analogues for CHO/CO2 ROCOP. Expanding on this finding, we subsequently developed a Co(II)Mg(II) complex that showed field leading rates for CHO/CO2 ROCOP and allowed for unique insight into the role of the two metals in this complex, where it was established that the Mg(II) center reduced transition state entropy and the Co(II) center reduced transition state enthalpy. Following these discoveries, we subsequently developed a range of heterodinuclear M(III)M(I) catalysts that were capable of catalyzing a broad range of copolymerizations, including the ring-opening copolymerization of CHO/CO2, propylene oxide (PO)/CO2, and CHO/phthalic anhydride (PA). Catalysts featuring Co(III)K(I) and Al(III)K(I) were found to be exceptionally effective for PO/CO2 and CHO/PA ROCOP, respectively. Such M(III)M(I) complexes operate through a dinuclear metalate mechanism, where the M(III) binds and activates monomers while the M(I) species binds the polymer change in close proximity to allow for insertion into the activated monomer. Our research illustrates how careful catalyst design can yield highly efficient systems and how the development of mechanistic understanding aids this process. Avenues of future research are also discussed, including the applicability of these heterodinuclear catalysts in the synthesis of sustainable materials.

Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications.

Catalytic atroposelective syntheses of axially chiral compounds have stimulated extensive interest in multiple communities, such as synthetic chemistry, biochemistry, and materials science, because of the intriguing characteristics of atropisomerism. In particular, atropisomeric indole derivatives, which contain a kind of five-membered heterocyclic framework, are widely distributed in a number of natural alkaloids, biologically relevant compounds, chiral ligands, and chiral organocatalysts. Hence, the catalytic atroposelective synthesis of indole derivatives bearing axial chirality is of considerable importance and has become an emerging focus of research. However, there are substantial challenges associated with the atroposelective synthesis of indole derivatives, including remote ortho-substituents around the chiral axis, a lower barrier for rotation, and a weaker configurational stability than that of atropisomeric six-membered biaryls. Therefore, the development of effective strategies toward the catalytic atroposelective synthesis of indole derivatives has become an urgent task.In order to tackle these challenges and to accomplish the task, our group devised a unique strategy of designing indole-derived platform molecules and developing organocatalytic enantioselective transformations of such platform molecules to synthesize atropisomeric indole derivatives; asymmetric organocatalysis has tremendous advantages and was the research area recognized by the Nobel Prize in Chemistry in 2021. This Account summarizes our endeavors in the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality. In brief, we devised and developed a series of indole-derived platform molecules, such as indolylmethanols, (hetero)aryl indoles, oxindole-based styrenes, N-aminoindoles, and indole-based homophthalic anhydrides, by introducing different functional groups onto the indole ring to achieve new reactivity and modulate the reactive site of the indole ring. As a result, these indole-derived platform molecules possess versatile and unique reactivity and are capable of undergoing a variety of organocatalytic enantioselective transformations for preparing structurally diversified indole derivatives with axial chirality.We used these strategies to accomplish the atroposelective synthesis of plenty of indole derivatives with axial chirality, including (hetero)aryl indoles, alkene-indoles, oxindole-based styrenes, N-pyrrolylindoles, and isochromenone-indoles. In addition, we gave a thorough and detailed understanding of the designed reaction by investigating the reaction pathway and activation mode. More importantly, we studied the biological activity of some products and performed catalyst design on the basis of atropisomeric indole moieties, which are helpful for disclosing more applications of indole derivatives bearing axial chirality.In the future, the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality will indubitably remain a frontier topic in the research area of asymmetric catalysis and chiral indole chemistry despite challenging issues, for instance, the atroposelective synthesis of novel indole derivatives bearing an unconventional chiral axis, the development of atropisomeric indole derivatives into powerful catalysts or ligands, and the discovery of atroposelective indole derivatives as potent drug candidates. We hope our efforts summarized in this Account will encourage chemists worldwide to devise innovative strategies toward solving the challenging issues that remain in this field, thus promoting its development to a higher level.

An Efficient Light-Mediated Protocol for the Direct Amide Bond Formation via a Novel Carboxylic Acid Photoactivation Mode by Pyridine-CBr4.

The direct amide bond formation between a carboxylic acid and an amine still constitutes a challenging reaction for both academia and industry. We demonstrate herein that several pairs of amines (halogen bond acceptors) and organohalogen sources may be used for the photochemical amidation reaction under either UVA or sunlight irradiation. Our studies led to the identification of pyridine-CBr4 as an efficient agent to perform amide synthesis under LED 370 nm irradiation, avoiding super-stoichiometric quantities. An extended substrate scope was demonstrated, showing that the widely used amino and carboxyl protecting groups are compatible with this photochemical protocol, while a number of industrially interesting products and bioactive compounds were synthesized. Direct infusion-high resolution mass spectrometry studies suggest an unprecedented type of carboxylic acid activation mode upon irradiation, involving the generation of a symmetric anhydride, an active ester with pyridine N-oxide and a mixed anhydride with hypobromous acid.

Construction of Fully Substituted Cyclobutanes by Tandem Reaction of 1,4-Diyn-3-ols and Anhydrides.

A concise and efficient synthesis of fully substituted cyclobutane derivatives from 1,4-diyn-3-ols and anhydrides was developed. Mechanistic studies indicated that a tandem esterification, isomerization to give allenyl ester, and homointermolecular [2+2] cycloaddition might be involved. The features of this protocol are its operational practicality, mild reaction conditions, and high regio- and stereoselectivity, and it is a readily accessible gram-scale synthesis.

A new selective inhibitor for IMP-1 metallo-ß-lactamase, 3Z,5E-octa-3,5-diene-1,3,4-tricarboxylic acid-3,4-anhydride.

3Z,5E-Octa-3,5-diene-1,3,4-tricarboxylic acid-3,4-anhydride (ODTAA, 1) was isolated from Paecilomyces sp. FKI-6801 for its selective IMP-1 MBL inhibitory activity. The first total synthesis of 1 from the commercially available compound was achieved in 9 steps with 28% overall yield. Introduction of catechol to the maleic anhydride of 1 improved the IC50 toward IMP-1 MBL and the inhibitory activity against IMP-1 MBL-producing P. aeruginosa. Treatment of the maleic anhydride scaffold with amine showed that the ß-carbonyl-α,ß-unsaturated carboxylic acid moiety is required as a pharmacophore for IMP-1 MBL inhibition.

Transition Metal ß-Diketonate Adhesion Promoters in Epoxy-Anhydride Resin.

Epoxy to copper adhesion supports the reliability of numerous structures in electronic packaging. Compared to substrate pre-treatment, processing and cost considerations are in favor of adhesion promoters loaded in epoxy formulations. In this work, first row transition metal ß-diketonates present such a compelling case when added in epoxy/anhydride resins: over 30% (before moisture aging) and 50% (after moisture aging) enhancement in lap shear strength are found using Co(II) and Ni(II) hexafluoroacetylacetonate. From extensive X-ray photoelectron spectroscopy (XPS) analyses on the adhesively failed sample surfaces, increased population of oxygen-containing functional groups, especially esters, is linked to the adhesion improvement. Assisted by XPS depth profile on the fractured epoxy side and in situ Fourier-transform infrared spectroscopy (FTIR), the previously discovered latent cure characteristics endowed by the metal chelates interacting with phosphine catalysts are regarded pivotal for pacing the anhydride consumption and allowing interfacial esterification reactions to occur. Further examinations on the XPS binding energy shifts and dielectric properties of the doped epoxy also reveal metal-polymer coordination that contribute to the adhesion and moisture resistance properties. These findings should stimulate future research of functional additives targeting at cure kinetics control and polar group coordination ideas for more robust epoxy-Cu joints.

Elements of Eoarchean life trapped in mineral inclusions.

Metasedimentary rocks from Isua, West Greenland (over 3,700 million years old) contain 13C-depleted carbonaceous compounds, with isotopic ratios that are compatible with a biogenic origin. Metamorphic garnet crystals in these rocks contain trails of carbonaceous inclusions that are contiguous with carbon-rich sedimentary beds in the host rock, where carbon is fully graphitized. Previous studies have not been able to document other elements of life (mainly hydrogen, oxygen, nitrogen and phosphorus) structurally bound to this carbonaceous material. Here we study carbonaceous inclusions armoured within garnet porphyroblasts, by in situ infrared absorption on approximately 10-21 m3 domains within these inclusions. We show that the absorption spectra are consistent with carbon bonded to nitrogen and oxygen, and probably also to phosphate. The levels of C-H or O-H bonds were found to be low. These results are consistent with biogenic organic material isolated for billions of years and thermally matured at temperatures of around 500 °C. They therefore provide spatial characterization for potentially the oldest biogenic carbon relics in Earth's geological record. The preservation of Eoarchean organic residues within sedimentary material corroborates earlier claims for the biogenic origins of carbon in Isua metasediments.

Mechanism of water extraction from gypsum rock by desert colonizing microorganisms.

Microorganisms, in the most hyperarid deserts around the world, inhabit the inside of rocks as a survival strategy. Water is essential for life, and the ability of a rock substrate to retain water is essential for its habitability. Here we report the mechanism by which gypsum rocks from the Atacama Desert, Chile, provide water for its colonizing microorganisms. We show that the microorganisms can extract water of crystallization (i.e., structurally ordered) from the rock, inducing a phase transformation from gypsum (CaSO4·2H2O) to anhydrite (CaSO4). To investigate and validate the water extraction and phase transformation mechanisms found in the natural geological environment, we cultivated a cyanobacterium isolate on gypsum rock samples under controlled conditions. We found that the cyanobacteria attached onto high surface energy crystal planes ({011}) of gypsum samples generate a thin biofilm that induced mineral dissolution accompanied by water extraction. This process led to a phase transformation to an anhydrous calcium sulfate, anhydrite, which was formed via reprecipitation and subsequent attachment and alignment of nanocrystals. Results in this work not only shed light on how microorganisms can obtain water under severe xeric conditions but also provide insights into potential life in even more extreme environments, such as Mars, as well as offering strategies for advanced water storage methods.