Visualization of lignification in flax stem cell walls with novel click-compatible monolignol analogs.

Introduction: As an essential part of plant cell walls, lignin provides mechanical support for plant growth, enhances water transport, and helps to defend against pathogens. As the most abundant natural aromatic-based renewable resource on earth, its biosynthesis has always been a research focus, and it is still currently under study. Methods: In this study, the p-coumaryl alcohol analog (HALK) and the coniferyl alcohol analog (GALK) containing an alkyne group at the ortho position were synthesized and applied to lignification in vivo and in vitro. The incorporation of these novel lignin monomers was observed via fluorescence imaging. Results and Discussion: It was found that the two monolignol analogs could be incorporated in dehydrogenated polymers (DHPs) in vitro and in flax cell walls in vivo. The results showed that as the cultivation time and precursor concentration varied, the deposition of H and G-type lignin exhibited differences in deposition mode. At the subcellular scale, the deposited lignin first appears in the cell corner and the middle lamella, and then gradually appears on the cell walls. Furthermore, lignin was also found in bast fiber. It was demonstrated that these new molecules could provide high-resolution localization of lignin during polymerization.

Novel Methods for the Formation of Free Carbyne Radicals in Solution.

Carbyne free radicals RC⋮ (RC) are usually associated with high-energy processes, thus research on their preparation, chemical reactivity, and prevalence under mild conditions is scarce. Recently, it was reported that metallo-complexes containing CR ligands may undergo spontaneous degradation in aqueous solutions to produce free RC radicals. These highly reactive species may react with each other to form the corresponding alkyne and other products. The reaction of 1,1,1 halo-carbo-hydrates with Cr(II) ions also forms RC radicals under mild conditions. Herein, we report two additional synthetic routes that produce free RC radicals under mild conditions. First, the reaction between metallic zinc and acetic anhydride produces 2-butyne and several other C2, C3, and C4 compounds. Isotopic-labeling experiments indicate that the formation of 2-butyne results from an inter-molecular reaction in which two RC moieties from two acetic anhydride molecules combine in solution. In addition, the degradation of the tri-molybdenum complex [Mo3(H3CC≡CCH3)(OAc)(H2O)2Br7], in which a 2-butyne ligand is coordinated to the Mo3 framework in a µ3-η2 (⊥) binding mode in aqueous solution produces several C2, C3, C4 and C5 molecules. This indicates the formation of free CH3C radicals by a homolytic cleavage of the carbon-carbon triple bond.

Radical-Mediated Trifunctionalization Reactions.

Synthetic radicals have intrinsic power for cascading and multifunctional reactions to construct diverse molecular scaffolds. In the previous review series, we covered 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6-, and 1,7-difunctionalizations, addition followed by cyclization reactions, and cycloaddition-initiated difunctionalizations. Presented in this paper are radical addition-initiated trifunctionalization reactions of alkenes, alkynes, and their derivatives. After the initial radical addition, there are different pathways, such as group or hydrogen atom transfer, cyclization, and radical coupling, to complete the second and third functionalizations.

One-Stage Pathway from Hollongdione to C17-Alkyne and Vinyl Chloride Following Mannich Bases and Carboxylic Acid.

Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2-5 were determined by X-ray analysis.

Optical Fiber-Assisted Printing: A Platform Technology for Straightforward Photopolymer Resins Patterning and Freeform 3D Printing.

Light-based 3D printing techniques represent powerful tools, enabling the precise fabrication of intricate objects with high resolution and control. An innovative addition to this set of printing techniques is Optical Fiber-Assisted Printing (OFAP) introduced in this article. OFAP is a platform utilizing an LED-coupled optical fiber (LOF) that selectively crosslinks photopolymer resins. It allows change of parameters like light intensity and LOF velocity during fabrication, facilitating the creation of structures with progressive features and multi-material constructs layer-by-layer. An optimized formulation based on allyl-modified gelatin (gelAGE) with food dyes as photoabsorbers is introduced. Additionally, a novel gelatin-based biomaterial, alkyne-modified gelatin (gelGPE), featuring alkyne moieties, demonstrates near-visible light absorption thus fitting OFAP needs, paving the way for multifunctional hydrogels through thiol-yne click chemistry. Besides 2D patterning, OFAP is transferred to embedded 3D printing within a resin bath demonstrating the proof-of-concept as a novel printing technology with potential applications in tissue engineering and biomimetic scaffold fabrication, offering rapid and precise freeform printing capabilities.

Metal-Free, PPA-Mediated Fisher Indole Synthesis via Tandem Hydroamination-Cyclization Reaction between Simple Alkynes and Arylhydrazines.

A new variant of Fisher indole synthesis involving Bronsted acid-catalyzed hydrohydrazination of unactivated terminal and internal acetylenes with arylhydrazines is reported. The use of polyphosphoric acid alone either as the reaction medium or in the presence of a co-solvent appears to provide the required balance for activating the C-C triple bond towards the nucleophilic attack of the hydrazine moiety without unrepairable reactivity loss of the latter due to competing amino group protonation. Additionally, the formal hydration of acetylenes to the corresponding ketones occurs under the same conditions, making it an alternative approach for generating carbonyl groups from alkynes.

Heteroatoms-Stabilized Single Palladium Atoms on Amorphous Zeolites: Breaking the Tradeoff between Catalytic Activity and Selectivity for Alkyne Semihydrogenation.

As a fundamental industrial catalytic process, the semihydrogenation of alkynes presents a challenge in striking a balance between activity and selectivity due to the issue of over-hydrogenation. Herein, we develop an efficient catalytic system based on single-atom Pd catalysts supported on boron-containing amorphous zeolites (Pd/AZ-B), achieving the tradeoff breaking between the activity and selectivity for the selective hydrogenation of alkynes. Advanced characterizations and theoretical density functional theory calculations confirm that the incorporated B atoms in the Pd/AZ-B can not only alter the geometric and electronic properties of Pd atoms by controlling the electron migration from Pd but also mitigate the interaction between alkene and the catalyst supports. This boosts the exceptional catalytic efficacy in the semihydrogenation of phenylacetylene to styrene under mild conditions (298 K, 2 bar H2), achieving a recorded turnover frequency (TOF) value of 24198 h-1 and demonstrating 95% selectivity to styrene at full conversion of phenylacetylene. By comparison, the heteroatom-free amorphous zeolite-anchored Pd nanoparticles and the commercial Lindlar catalyst have styrene selectivities of 73% and 15%, respectively, under identical reaction conditions. This work establishes a solid foundation for developing highly active and selective hydrogenation catalysts by controllably optimizing their electronic and steric properties.

Copper(I)-Catalyzed Formal [4 + 2] Cyclocondensation of ortho-Hydroxybenzyl Alcohol, Aromatic Terminal Alkynes, and Sulfonyl Azides: An Alternative Approach to 2-Sulfonyliminocoumarins.

In this paper, an alternative and efficient copper(I)-catalyzed synthesis of 2-sulfonyliminocoumarins is developed through a three-component reaction of ortho-hydroxybenzyl alcohol, alkynes, and p-toluenesulfonyl azide. The proposed route for access to the 2-iminocoumarin ring involves a [4 + 2] hetero-Diels-Alder reaction between ortho-quinone methide and ketenimine intermediates generated in situ.

Single-Crystal Cage Framework with High Selectivity and Reversibility in Fullerene Binding.

Host-guest chemistry, a pivotal branch of supramolecular chemistry, plays an essential role in understanding and constructing complex structures through non-covalent interactions. Organic molecular cages, characterized by their intrinsic confined cavities, can selectively bind a variety of guest molecules. Their host-guest chemistry has been well studied in the solution phase, and several attempts have been made to encode well-defined molecular architectures into solid-state polymeric materials. However, only limited studies have explored their potential in the solid state, where their lack of robustness and less ordered networks significantly hinder practical applications. Herein, we report the synthesis of a single-crystal cage framework and a systematic study of its host-guest chemistry, spanning from the solution state to the solid state. Our studies reveal that the host-guest interactions inherent to the cage are successfully maintained in the solid-state polymeric material. Furthermore, the framework's robustness allows for the guest molecules (fullerene) to be released triggered by an organic acid (trifluoroacetic acid), with subsequent regeneration of the framework through an organic base (triethylamine) treatment. Our findings represent the first synthesis of a robust, single-crystal cage framework exhibiting highly selective and reversible host-guest chemistry, thus showing great potential towards molecular separation application.

Post-Synthetic Modification of Calix[4]arene Framework by Iridium-Mediated Alkyne Insertion into an Inert C-C Bond: A Novel Strategy for Unsymmetrical Macrocycles.

As a novel synthetic method for unsymmetrical macrocycles, we herein developed a post-synthetic modification of calix[4]arenes by insertion of a terminal alkyne into an inert C(methylene)-C(aryl) bond of the macrocyclic framework. In this transformation, C-iridated calix[4]arenes, readily synthesized through C-H bond activation of the parent calix[4]arene, undergoes C(methylene)-C(aryl) bond cleavage followed by insertion of an alkyne to provide a ring-expanded calix[4]arene complex. Removal of the iridium metal from the resulting complex was readily accomplished by a simple treatment with an acid. The developed sequential method affords novel unsymmetrical, monofunctionalized macrocyclic compounds via 3 steps from the parent calix[4]arene in good yield. The unique unsymmetrical structures of the alkyne-inserted macrocycles were evaluated by X-ray single crystal analyses. On the basis of theoretical calculations, we propose a reaction mechanism involving an uncommon C-C bond cleavage step through δ-carbon elimination for the ring enlargement process.

The development of 177Lu-DOTA-CC-PSMA following a unified "Click Chemistry" protocol of synthesizing metal nuclide-conjugated radiopharmaceuticals.

BACKGROUND: Currently, the synthesis pathway of metal nuclide-labeled radiopharmaceuticals is mainly divided into two steps: first, connecting the chelator with the target molecule, and second, labeling the metal nuclide to the chelator. However, the second step of the reaction to label the metal nuclide requires high temperature (90-100 °C), which tends to denature and inactivate the target molecule, leading to loss of biological activities, especially the targeting ability. A feasible solution may be the click chemistry labeling method, which consists of reacting a metal nuclide with a chelating agent to generate an intermediate and then synthesizing a radiopharmaceutical agent via the click chemistry intermediate and the target molecule-alkyne compound. In this study, through the click chemistry of 177Lu-DOTA-N3 with prostate-specific membrane antigen (PSMA)-alkyne compound, 177Lu-labeled PSMA-targeted molecular probe was synthesized and evaluated for its potential to be cleared from the bloodstream and rapidly distributed to tissues and organs, achieving a high target/non-target ratio. 177Lu-PSMA-617 was utilized as an analogue for comparison in terms of synthesizing efficiency and PSMA-targeting ability. RESULTS: A novel 177Lu-labeled PSMA radioligand was successfully synthesized through the click chemistry of 177Lu-DOTA-N3 with PSMA-alkyne compound, and abbreviated as 177Lu-DOTA-CC-PSMA, achieving a radiochemical yield of 77.07% ± 0.03% (n = 6) and a radiochemical purity of 97.62% ± 1.49% (n = 6) when purified by SepPak C18 column. Notably, 177Lu-DOTA-CC-PSMA was characterized as a hydrophilic compound that exhibited stability at room temperature and commendable pharmacokinetic properties, such as the superior uptake (19.75 ± 3.02%ID/g at 0.5 h) and retention (9.14 ± 3.16%ID/g at 24 h) within xenografts of 22Rv1 tumor-bearing mice. SPECT/CT imaging indicated that radioactivity in both kidneys and bladder was essentially eliminated after 24 h, while 177Lu-DOTA-CC-PSMA was further enriched and retained in PSMA-expressing tumors, resulting in the high target/non-target ratio. CONCLUSION: This study demonstrated the potential of click chemistry to unify the synthesis of metal radiopharmaceuticals, and 177Lu-DOTA-CC-PSMA was found for rapid clearance and appropriate chemical stability as a PSMA-targeted radioligand.

Embedding Single Pd Atoms on NiGa Intermetallic Surfaces for Efficient and Selective Alkyne Hydrogenation.

Catalytic removal of alkynes is essential in industry for producing polymer-grade alkenes from steam cracking processes. Non-noble Ni-based catalysts hold promise as effective alternatives to industrial Pd-based catalysts but suffer from low activity. Here we report embedding of single-atom Pd onto the NiGa intermetallic surface with replacing Ga atoms via a well-defined synthesis strategy to design Pd1-NiGa catalyst for alkyne semi-hydrogenation. The fabricated Pd1Ni2Ga1 ensemble sites deliver remarkably higher specific mass activity under superb alkene selectivity of >96 % than the state-of-the-art catalysts under industry-relevant conditions. Integrated experimental and computational studies reveal that the single-atom Pd synergizes with the neighbouring Ni sites to facilitate the σ-adsorption of alkyne and dissociation of hydrogen while suppress the alkene adsorption. Such synergistic effects confer the single-atom Pd on the NiGa intermetallic with a Midas touch for alkyne semi-hydrogenation, providing an effective strategy for stimulating low active Ni-based catalysts for other selective hydrogenations in industry.

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction.

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine.

An Organic Molecular Mimetic Metal-Free Heterogeneous Catalyst for Electrocatalytic Alkyne Semihydrogenation.

The direct construction of metal-free catalysts on conductive substrates for electrocatalytic organic hydrogenation reactions is significant but still unexplored. Here, learning from the homogeneous molecular catalysts, an organic molecular mimetic metal-free heterogeneous catalyst is designed and constructed in situ on a graphite flake electrode via a mild electrochemical oxidation‒reduction relay strategy. The as-prepared -COOH- and -OH-functionalized metal-free catalyst exhibits an electrocatalytic alkyne semihydrogenation performance with a 72% Faradaic efficiency, 99% selectivity and 96% yield of the alkene product, which is comparable to that of noble metal catalysts. The removal of these oxygen-containing groups leads to negligible activity. The experimental and calculation results reveal that the origin of the high activity can be assigned to the -COOH and -OH groups on graphite. A flow electrolytic cell delivers ten grams of hydrogenated products with 81% Faradaic efficiency. This metal-free catalyst is also suitable for gas-phase acetylene semihydrogenation and other electrocatalytic hydrogenation reactions.

Cyclic Peptide Conjugate Vaccines and Physically Mixed Cyclic Peptide Vaccines for Subcutaneous Immunization.

Immune stimulants (adjuvants) enhance immune system recognition to provide an effective and individualized immune response when delivered with an antigen. Synthetic cyclic deca-peptides, co-administered with a toll-like receptor targeting lipopeptide, have shown self-adjuvant properties, dramatically boosting the immune response in a murine model as a subunit peptide-based vaccine containing group A Streptococcus peptide antigens.Here, we designed a novel peptide and lipid adjuvant system for the delivery of group A Streptococcus peptide antigen and a T helper peptide epitope. Following linear peptide synthesis on 2-chlorotrityl chloride resin, the linear peptide was cleaved and head-to-tail cyclized in solution. The selective arrangement of amino acids in the deca-peptide allowed for selective conjugation of lipids and/or peptide antigens following cyclisation. Using both solution-phase peptide chemistry and copper-catalyzed azide-alkyne cycloaddition reaction were covalently (and selectively) ligated lipid and/or peptide antigens onto the cyclic deca-peptide core. Subcutaneous administration of the vaccine design to mice resulted in the generation of a large number of serum immunoglobulin (Ig) G antibodies.

Transition Metal-Catalyzed Dual C-H Activation/Annulation Reactions Involving Internal Alkynes.

Recently, transition metal-catalyzed ortho-C-H bond activation/annulations involving two internal alkyne molecules have been extensively used to synthesize highly substituted polycyclic aromatic scaffolds. Such reactions have emerged as a powerful atom and step-economical strategy for the assembly of multifunctional bioactive molecules. In this context, we focused on the recent achievements of dual C-H bond activation/annulations, as well as functionalization reactions involving diaryl/alkyl alkynes.

Gold trifluoromethyl complexes as efficient regioselective catalysts in alkyne hydration.

Gold (III) complexes containing trifluromethyl ligands are efficient catalyst in the hydration of alkynes, operating at low catalyst loadings, without additives, using environmentally friendly solvents and at mild conditions (60 ºC). Hydration of terminal and internal alkynes provide the corresponding ketones in quantitative yields without special precautions as dry solvents or inert atmospheres. Remarkably, hydration of asymmetric internal alkynes proceeds with moderate to notable regioselectivities, providing mixtures of the two possible isomers with ratios up to 90:10.

Structure-activity relationship study of nitrogen signaling factors.

We have synthesized 10 analogs of oxylipins, which are nitrogen signaling factors (NSFs) that mediate cell-to-cell communication in the fission yeast Schizosaccharomyces pombe, and evaluated their structure-activity relationships with the aim of developing molecular probes for NSFs. We found that the OH or OAc group at C10 could be replaced with a compact amide (17) or carbamate (19). Introducing an alkyne as a detection tag at C10 led to decreased, though still sufficient, activity. Introducing an alkyne at the C18 position showed a similar trend, suggesting tolerance is relatively low even for compact functional groups such as alkynes. Although introduction of a diazirine moiety as a photoreactive group at the C5 position decreased the activity, we found that introducing diazirine at the C13 position was acceptable, and compound 38 exhibited potent NSF activity. These findings will be helpful in the development of molecular probes for NSFs.

Recent Advancements in Metal-Catalyst-Free Multicomponent Radical Sulfonylation of Alkynes.

Vinyl sulfones are crucial building blocks in synthetic chemistry and core structural units of pharmaceutically active molecules, thus extensive investigations have been conducted on the construction of these skeletons. In contrast to the classical synthetic approaches, the radical sulfonylation of alkynes for producing vinyl sulfones has garnered considerable interest because of its mild conditions and high efficiency. Radical sulfonation of alkynes typically begins with the sulfonyl radical attacking the alkynes, followed by further functionalization. Moreover, the association of metal-catalyst-free systems with multicomponent reactions (MCRs) offers an environmentally friendly pathway for efficiently constructing complex scaffolds from readily available partners. However, there is no comprehensive review summarizing the advancements in metal-catalyst-free multicomponent radical sulfonylation of alkynes. Hence, we provide a categorical overview based on the objects of sulfonylation of alkynes (hydrosulfonylation, carbosulfonylation, aminosulfonylation, oxysulfonylation, sulfosulfonylation, selenosulfonylation, and iodosulfonylation), along with interpretations of the reaction mechanisms.

Multicomponent Synthesis of 3(2H)-Furanones Initiated by Copper(II)-Catalyzed Alkyne-Carbonyl Cross Metathesis.

The cooperative Lewis and Brønsted acid catalysis makes convergent synthesis of 3(2H)-furanones through a three-component coupling of 1,3-diynes, alkyl glyoxylates and water. Control experiments support that Lewis acid-catalyzed highly chemo-, regio- and stereoselective alkyne-carbonyl metathesis of 1,3-diynes and alkyl glyoxylates might be the initial step of this multicomponent annulation. Further chemo- and regioselective hydration of the alkyne-carbonyl metathesis product and subsequent oxa-Michael addition promoted by Brønsted acid results in the formation of two C-O bonds of the five-membered oxygen heterocycle.