Addition Reactions Research Articles

Preparation of Mesoporous Cu2O Nanospheres for Green Synthesis in the Enantioselective Boron Conjugate Addition of α,β‐Unsaturated Chiral Compounds in Aqueous Phase

AbstractChiral organoboron compounds are essential intermediates in various significant reactions. However, there are still few efficient catalysts for their synthesis. This paper reports a novel catalytic material for chiral asymmetric boron conjugate addition reactions: mesoporous Cu2O nanospheres (M−Cu2O). M−Cu2O is approximately 0.55 μm, exhibiting dense and uniformly distributed worm‐like pores. It features a specific surface area of 15.7 m2/g and an average pore size of 14.3 nm. Under the conditions of Toluene:H2O=9:1, with a chiral ligand amount of 3.6 mol% and no additional base, it achieves a high yield (98% yield) and impressive enantioselectivity (99% ee) for the template substrate chalcone using only 3.0 mol% of the catalyst. Notably, the catalyst can be easily recovered and maintains robust catalytic performance after seven cycles, yielding 92% and an ee value of 90%. This work presents a mild and effective method for synthesizing chiral boron compounds in an aqueous phase, significantly enhancing the application potential of mesoporous copper oxide nanospheres.

Enhancing Electron Donor-Acceptor Complex Photoactivation with a Stable Perylene Diimide Metal-Organic Framework.

Electron donor-acceptor complexes are commonly employed to facilitate photoinduced radical-mediated organic reactions. However, achieving these photochemical processes with catalytic amounts of donors or acceptors can be challenging, especially when aiming to reduce catalyst loadings. Herein, we have unveiled a framework-based heterogenization approach that significantly enhances the photoredox activity of perylene diimide species in radical addition reactions with alkyl silicates by promoting faster and more efficient electron donor-acceptor complex formation. Besides offering broad substrate scope in alkene hydroalkylation, the newly developed heterogeneous photocatalysis substantially improves the catalyst turnover numbers in comparison to previous homogeneous photocatalytic systems and demonstrates outstanding catalyst recyclability. These research findings pave the way for the advancement of various efficient and practical organic transformations using framework-supported organocatalysts.

Access to Chiral Bridged Biaryls via Brønsted Acid-Catalyzed Asymmetric Addition of Alcohols to Fluoroalkylated Biaryl Oxazepines.

We disclose herein a chiral phosphoric-acid-catalyzed enantioselective addition reaction of alcohols to fluoroalkylated biaryl 1,3-oxoazepines, which furnished a wide range of bridged biaryls bearing a fluoroalkylated quaternary carbon stereocenter on the seven-membered ring in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee). Our method can be used for the modification of several natural products and bioactive molecules. Preliminary studies revealed that the products obtained in this reaction exhibit good in vitro bioactivities against two plant pathogens.

Highly Selective α-Addition and β-Conjugate Addition Products from Peptides Composed of α,β-Unsaturated γ-Amino Acids.

β-Addition products are common in conjugate addition reactions consisting of α,β-unsaturated carbonyl compounds. Here, we are reporting an uncommon α-addition product as a major product in the thioacetic acid conjugate addition reaction on a peptide consisting of (E)-α,β-unsaturated γ-amino acids. In addition, we observed highly diastereoselective β-addition products from the thiophenol and thioethanol conjugate addition reaction on peptides. In comparison, (E)-α,β-unsaturated γ-amino amides give both α- and β-addition products with thioacetic acid and only β-addition products in the thiophenol conjugate addition reaction. Further, the conformations of both α-addition and β-addition products were studied in single crystals as well as in solution. The peptide product with α-thioacetate addition (α,γ-disubstituted γ-amino acid) adopted a regular 12-helix conformation, whereas β-addition (β,γ-disubstituted γ-amino acid) products slightly distorted 12-helix conformation. A kink is observed at the site of β-addition in the 12-helix structures of all β-addition products. Overall, the uncommon and stereospecific conjugate addition reactions reported here can be explored to introduce diverse functional groups to the peptide backbone.

Facile fabrication of PEG-PPG block copolymer via Michael addition reaction and its successful application as all-solid-state electrolyte for rechargeable lithium metal batteries

Facile fabrication of PEG-PPG block copolymer via Michael addition reaction and its successful application as all-solid-state electrolyte for rechargeable lithium metal batteries

Rapid Synthesis of Primary Amides Using Ammonia Borane.

We report the rapid synthesis of primary amides by directly using commercially available ammonia borane (NH3·BH3), sodium hexamethyldisilazide (NaHMDS), and esters. The success of this protocol relies on NH3·BH3 as the nitrogen source being considerably more convenient and NaHMDS being an excellent proton abstractor but not participating in the nucleophilic addition reaction. The reaction had a wide substrate scope containing bioactive molecules, and most of the substrates were efficiently amidated over 90% yields.

Theoretical Study on the Kinetics of Secondary Oxygen Addition Reactions for N-Butyl Radicals.

Chemical kinetics for second oxygen addition reactions (·QOOH + O2) of long-chain alkanes are of great importance in low-temperature combustion technologies. However, kinetic data for key reactions of ·QOOH + O2 systems are often difficult to obtain experimentally and are primarily estimated or calculated by using theoretical methods. In this work, barrier heights (BHs), reaction energies (ΔEs), and relative energies (REs) of stationary points for key reactions of two representative ·QOOH + O2 systems in the low-temperature oxidation of n-butyl as well as pressure-dependent rate constants for the involved reactions are calculated with the high-level quantum chemical method CCSD(T)-F12b/CBS. These results can be employed in the development of low-temperature combustion mechanisms for n-butane and longer straight-chain alkanes. In addition, the performance of some quantum chemistry methods with a lower computational cost on BHs, ΔEs, and REs as well as rate constants is also investigated. Our results indicate that the maximum error on these energies with PNO-LCCSD(T)-F12a is within 1 kcal/mol, and rate constants with this method are in the best agreement with reference values, with a maximum relative error of about half the reference values. Due to its low computational cost and memory requirements, this method is strongly recommended for studying low-temperature combustion reactions involving larger hydrocarbon fuels.

Catalytic Asymmetric Addition and Substitution Reactions with Grignard Reagents: Do We Know It All?

Catalysis has been a cornerstone in organic synthesis, enabling a variety of highly efficient and selective C–C bond formation reactions, in particular enantioselective addition and substitution of Grignard reagents. Throughout time, we have gained significant understanding into how various factors, such as the influence of the metal source, the nature of the ligands, the substrates or temperature, affect these processes. Recent advances in computational chemistry have further enriched our understanding of this chemistry by elucidating the potential reaction mechanism and providing insight into the rate and enantio‐determining steps in these catalytic transformations. However, challenges persist, and aspects such as ligand optimisation, full mechanistic understanding and scalability remain underexplored. Computational methods, however, present a remarkable potential to surmount these enduring challenges.

Polydopamine nanoparticles loaded with sodium ferulate for targeted therapy of myocardial infarction in endothelial cells.

Myocardial infarction (MI) is a leading cause of heart failure and death in cardiovascular diseases. Most drug trials currently fail due to inadequate local drug activity and side effects. In this study, we developed a novel polydopamine (PDA) nano delivery system that carries sodium ferulate (SF) and is modified with RGD peptides (SF/RGD-PDA NPs) for precise targeted delivery. SF is a clinical adjuvant for cardiovascular and cerebrovascular diseases but lacks targeting and has a short half-life. PDA, known for its excellent biocompatibility and surface modifiability, serves as an effective carrier. SF was loaded onto PDA through π-π stacking, while RGD was attached via a Michael addition reaction, resulting in stable SF/RGD-PDA NPs with an average particle size of 206.13 nm. In vitro and in vivo studies indicate that this targeted formulation has good safety. Targeting studies showed a 2.19-fold increase in nanoparticle accumulation in the heart and a 5.94-fold increase in cellular uptake efficiency. Pharmacodynamic studies revealed a 1.45-fold increase in endothelial cell proliferation, a 1.46-fold increase in angiogenesis rate, and a significant reduction in MI area. These findings suggest that SF/RGD-PDA NPs can improve endothelial cell function and reduce MI area through targeted delivery.

Structure Matters: Tailored Graphitization of Carbon Dots Enhances Photocatalytic Performance.

The chemical structure and photoredox properties of carbon dots (CDs) are not yet fully understood. However, it has been reported that, by carefully choosing the starting materials and tuning their synthesis conditions, it is possible to obtain CDs with different chemical structures and therefore different photocatalytic performance. For this work, a family of different CDs was synthesized in Milli-Q water via a microwave-assisted protocol, using citric acid and urea as precursors. The syntheses were carried out at different times and temperatures to assess the impact of the synthetic parameters on the photocatalytic properties of the final materials. After extensive and accurate purification, the photocatalytic abilities of a selected subset of CDs were tested by performing a photocatalyzed atom transfer radical addition reaction. Among the tested CDs, the best performing ones were found to be those synthesized at the highest temperature, which were the most graphitic. A number of different characterization techniques were then used to evaluate the degree of graphitization of CDs and to elucidate the origin of their different photocatalytic performance.

Novel tetracycline-degrading enzymes from the gut microbiota of black soldier fly: Discovery, performance, degradation pathways, mechanisms, and application potential.

The antibiotic tetracycline (TC) is an emerging pollutant frequently detected in various environments. Although enzymatic remediation is a promising strategy for mitigating TC contamination, the availability of effective TC-degrading enzymes remains limited, and their mechanisms and applications are not fully understood. This study developed a comprehensive TC-degrading enzyme library from the gut microbiome of the highly TC-resistant saprophagous insect, black soldier fly larvae (BSFL), using an integrated metagenomic and comparative metatranscriptomic approach, identifying 105 potential novel TC-degradation genes. Bioinformatics analysis of 10 selected genes underscored the novelty of the identified enzymes. Among these, Trg2 demonstrated strong binding affinity and significant degradation capacity for TC. Key functional amino acid residues, including Thr231, Ala64, Ala82, Gly68, Gly79, and Ser81, were identified as essential for the interaction between TC and Trg2. Six TC degradation pathways were proposed, involving the transformation of TC into 19 metabolites through de-grouping, ring opening, oxidation, reduction, and addition reactions, effectively reducing TC toxicity. Furthermore, Trg2 exhibited resilience under harsh conditions, maintaining the capacity to remove about 45 % of the total TC in mariculture wastewater across eight successive batches. This study advances the understanding of TC degradation mechanisms and highlights the potential application of novel enzymes for bioremediation purposes.

Structural Regulation and Performance Enhancement of Carbon-Based Supercapacitors: Insights into Electrode Material Engineering.

The development of carbon-based supercapacitors is pivotal for advancing high energy and power density applications. This review provides a comprehensive analysis of structural regulation and performance enhancement strategies in carbon-based supercapacitors, focusing on electrode material engineering. Key areas explored include pore structure optimization, heteroatom doping, intrinsic defect engineering, and surface/interface modifications. These strategies significantly enhance electrochemical performance through increasing surface area, improving conductivity, facilitating charge transfer, introducing additional pseudocapacitive reactions, and optimizing the density of states at the Fermi level, among other mechanisms. After introducing these fundamental concepts, the review details various preparation methods and their effects on supercapacitor performance, highlighting the interplay between material structure and electrochemical properties. Challenges in scaling advanced fabrication techniques and ensuring the long-term stability of functionalized materials are discussed. Additionally, future research directions are proposed, emphasizing the development of cost-effective, scalable methods and interdisciplinary approaches to design next-generation supercapacitors, thereby meeting the growing demand for efficient and sustainable energy storage solutions.

Manganese(I)-Catalyzed Enantioselective Alkylation To Access P-Stereogenic Phosphines.

This work introduces a novel Mn(I)-catalyzed enantioselective alkylation methodology that efficiently produces a wide array of P-chiral phosphines with outstanding yields and enantioselectivities. Notably, the exceptional reactivity of Mn(I) complexes in these reactions is demonstrated by their effective catalysis with both typically reactive alkyl iodides and bromides, as well as with less reactive alkyl chlorides. This approach broadens the accessibility to various P-chiral phosphines and simplifies the synthesis of chiral tridentate pincer phosphines to a concise 1-2 step process, contrary to conventional, labor-intensive multistep procedures. Importantly, the development significantly expands the applicability of earth-abundant Mn(I)-based complexes beyond their recently established roles in catalytic hydrogenative and conjugate addition reactions, emphasizing the catalytic potential of Mn(I) complexes as a viable alternative to noble metal chemistry and, in some cases, even surpassing their performance.

Synthesis and characteristics of water-based, rosin-modified, polymerized oil based on dehydrated castor oil acid and zinc resinate.

In this study, we synthesized a water-based, rosin-modified, polymerized oil (WRPO) via an addition and polymerization reaction of dehydrated castor oil (DCO), rosin acid (RA), zinc resinate (ZR) and dehydrated castor oil acid (DCOA). Addition and polymerization reactions at 240 °C, followed by neutralization with ammonia, dissolution into butyl alcohol and subsequent dilution with water, were performed at varying DCOA contents of 10%, 20%, 30%, 35% and 40%. WRPO was mixed with butoxymethylmelamine (BMM), a curing agent, at a weight ratio of 80 : 20, and then cured for 2 hours at 130 °C. Structure and thermal characterizations of the prepared WRPOs were investigated via FTIR spectroscopy, 1H NMR spectroscopy and TGA. Characterization results indicated that when the contents of DCOA and ZR were 35% and 5%, respectively, the obtained WRPO exhibited fine water-dispersible stability and excellent physicochemical properties.

Defluorinative Hydroxylation Promoted by Silica to Access Optically Pure Hexahydrofuranocarbazole via [4+2] Addition Reaction

AbstractCrafting an efficient strategy for the synthesis of biologically active and functionally rich hexahydrofuranocarbazole is a highly desirable but demanding pursuit. This research elucidates a groundbreaking strategy involving an unanticipated defluorinative hydroxylation reaction facilitated by silica gel, yielding highly enantio‐ and diastereoselective hexahydrofuranocarbazole frameworks. This method results in the formation of five consecutive chiral centers, including three quaternary stereocenters and an all‐carbon spiro center, via an aminocatalytic asymmetric remote [4+2] addition process. The developed methodology allows for the construction of a diverse array of products (24 examples, up to >99 % ee and 17 : 1 dr), reflecting its notable substrate scope. Furthermore, we demonstrate the feasibility of gram‐scale synthesis and control experiments that underscore the methodological advancements and provide insights into the underlying mechanism.

Challenges in the Characterization and Purification of (Peptide)n-Calix[4]Resorcinarene Conjugates Synthesized via Thiol-Maleimide Reaction Using Liquid Chromatography

The separation and purification of molecular compounds and their functionalized derivatives is a common challenge in organic synthesis. In particular, calix[4]resorcinarenes present a high potential for chemical derivatization at their upper edge by aminomethylation reactions, and these compounds and their derivatives require appropriate analytical methodologies for their analysis, separation, and purification. In this study, C-tetra(propyl)calix[4]resorcinarene was synthesized and functionalized with maleimide groups by optimized aminomethylation reactions, obtaining a mixture of mono-, di-, tri-, and tetrasubstituted compounds. Initial separation by RP-HPLC with a core-shell column showed poorly resolved peaks, indicating a loss of separation efficiency. Therefore, a monolithic C18 column was used, which significantly improved the separation, thanks to its larger pore volume and continuous structure facilitating the diffusion of these bulky molecules, notably improving efficiency. Finally, the six compounds functionalized with maleimide groups were efficiently separated and enriched by RP-SPE by analytical method transfer, and the two peptides of six and the thirteen residues derived from LfcinB (20–25): RRWQWR were synthesized by SPPS-Fmoc/tBu and purified. These were modularly linked by the Michael thiol-maleimide addition reaction obtaining six (peptide)n-resorcinarene conjugates. The analytical method by RP-HPLC with a monolithic C18 column, the separation and purification by RP-SPE were used transversally in all the steps to obtain compounds with adequate purities and quantities. Finally, the antibacterial activities of the six conjugates were evaluated against E. coli and E. faecalis strains, and it was determined that three aminomethylated compounds and one monosubstituted conjugate showed activity against E. faecalis. Our work established a new modular conjugation strategy between calix[4]resorcinarenes and peptides by thiol-maleimide click chemistry, and a methodology of separation, purification, and enrichment for these products by RP-HPLC and RP-SPE, which permitted us to obtain quantities with purities appropriate for their characterization by NMR, LC-MS and antibacterial activity assays.

Recent Advances in Diversity-Oriented Synthesis of N-containing Organic Molecules Through Carbodiimide-based Reactions.

Carbodiimides (R-N=C=N-R) are well-known intermediates for the preparation of a variety of N-containing compounds, including heterocycles and amide linkages. Be-cause of their high reactivity and easy availability, carbodiimides have been broadly used as building blocks in the synthesis of structurally complex and diverse heterocyclic com-pounds in multi-component reactions (MCRs). Recent advances in diversity-oriented syn-thesis with carbodiimide-based MCRs are discussed in this minireview and are classified into different sections based on the key transformation involved in the reactions, such as heteroannulation and nucleophilic addition reactions which containing metal-catalyzed re-actions, multi-component reactions, and catalyst-free reactions subsections.

Controlled Synthesis of α‐Mono‐ and α,α‐Di‐Halogenated Ketones Through Coupling of Halogenated Diboromethanes with Carboxylic Acid Esters

Halogenated gem‐diboron reagents, as structurally unique gem‐diborylalkanes, are crucial in organic synthesis chemistry. Herein, we report a strategy with controlled synthesis of α‐mono‐ and α,α‐di‐halogenated ketones through nucleophilic addition reaction of halogenated diboromethanes with carboxylic acid esters. The substrate scope is broad and the nucleophilic addition reaction proceeds from a diverse range of carboxylic acid esters with bromo‐ or chloro‐diborylmethanes. Moreover, an intriguing heterocyclic compound has been serendipitously synthesized as well.

In Vitro, In Vivo, Ex Vivo Characterisation of Dihydroimidazotriazinones and Their Thermal Decomposition Course Studied by Coupled and Simultaneous Thermal Analysis Methods.

The biological and thermal properties of a class of synthetic dihydroimidazotriazinones were disclosed in this article for the first time. Molecules 1-6-as potential innovative antimetabolites mimicking bicyclic aza-analogues of isocytosine-were evaluated for their in vitro anticancer activity. Moreover, in vivo, in vitro, and ex vivo toxicity profiles of all the compounds were established in zebrafish, non-tumour cell, and erythrocyte models, respectively. Their antihaemolytic activity was also evaluated. Additionally, the thermal decomposition mechanism, path, and key thermal properties of heterocycles 1-6 were analysed. It was found that all the studied compounds revealed significant antiproliferative activities against tumour cells of the lung, cervix, ovary, and breast, as well as acute promyelocytic leukaemia cells, superior or comparable to that of an anticancer agent gemcitabine. Most of them were less toxic to non-tumour cells than this standard drug, and none had a haemolytic effect on red blood cells. All the tested heterocycles proved to be safer for zebrafish than a standard drug pemetrexed. Some exhibited the ability to inhibit oxidative haemolysis, suggesting their protective action on erythrocytes. The differential scanning calorimetry (DSC) analyses confirmed that all molecules melted within one narrow temperature range, proving their purity. The melting points depended solely on the type of substituent and increased as follows: 4 (R = 3-ClPh) < 2 (R = 4-CH3Ph) = 3 (R = 4-OCH3Ph) < 5 (R = 4-ClPh) = 1 (R = Ph) < 6 (R = 3,4-Cl2Ph). The thermogravimetry/differential thermogravimetry (TG/DTG) studies confirmed high thermal stability of all the investigated heterocycles in inert (>230 °C) and oxidising (>260 °C) atmospheres, which depended directly on the R. The pyrolysis process included one main decomposition stage and was connected with the emission of NH3, HCN, CH3CN, HNCO, alkane, alkene, aromatic fragments, CO2 (for all the compounds), and HCl (for the molecule with 3,4-Cl2Ph), which was confirmed by FTIR and QMS analyses. In turn, the oxidative decomposition process of the tested polyazaheterocycles took place in two main stages connected with the formation of the same volatiles as those observed in an inert atmosphere and additionally with the release of N2, NO, CO, and H2O. These results proved that the pyrolysis and oxidative decomposition run through the radical mechanism connected with the additional reactions between radicals and oxygen in synthetic air. The favourable biological and thermal properties of this class of dihydroimidazotriazinones imply their usefulness as potential pharmaceutics.

Development and Characterization of Hyaluronic Acid Graft-Modified Polydopamine Nanoparticles for Antibacterial Studies.

The problem of antibiotic abuse and drug resistance is becoming increasingly serious. In recent years, polydopamine (PDA) nanoparticles have been recognized as a potential antimicrobial material for photothermal therapy (PTT) due to their excellent photothermal conversion efficiency and unique antimicrobial ability. PDA is capable of rapidly converting light energy into heat energy under near-infrared (NIR) light irradiation to kill bacteria efficiently. In order to solve the problem of PDA's tendency to aggregate and precipitate, this study improved its stability by grafting hyaluronic acid (HA) onto the surface of PDA. Using dopamine and hyaluronic acid as raw materials, hyaluronic acid (HA) was grafted onto polydopamine (PDA) nanoparticles via self-polymerization and Michael addition reactions under alkaline conditions to obtain PDA-HA-modified nanoparticles. We confirmed the successful grafting of hyaluronic acid via scanning electron microscopy (SEM), Fourier infrared spectroscopy (FTIR), nuclear magnetic hydrogen spectroscopy (¹H NMR), ultraviolet-visible spectroscopy (UV-vis), Raman spectroscopy (Raman), and dynamic light scattering (DLS) methods. Scanning electron microscopy (SEM) was used to observe the surface morphology and nanostructure of the grafted materials, providing information on the morphology and size distribution of the materials. Near-infrared performance experiments showed that the temperature of the PDA-HA solution increased rapidly under near-infrared light irradiation, demonstrating an excellent photothermal conversion performance. Antimicrobial properties were assessed via the colony counting method, and typical Gram-positive bacteria S. aureus and Gram-negative bacteria E. coli were selected as model strains. The experimental groups were tested under dark conditions and near-infrared (NIR) light irradiation. PDA/HA showed significant photothermal properties under NIR light irradiation, resulting in a rapid increase in the surrounding temperature to a level sufficient to kill bacteria. Under NIR light irradiation, PDA/HA exhibited 100% antimicrobial efficacy against both S. aureus and E. coli, while antimicrobial efficacy was limited under dark conditions. This indicates that the antibacterial activity of PDA/HA is highly dependent on NIR light activation.