Catalysis driven by an amyloid-substrate complex.

Amine modification through nucleophilic attack of the amine functionality is a very common chemical transformation. Under biorelevant conditions using acidic-to-neutral pH buffer, however, the nucleophilic reaction of alkyl amines (pKa ≈ 10) is not facile due to the generation of ammonium ions lacking nucleophilicity. Here, we disclose a unique molecular transformation system, catalysis driven by amyloid-substrate complex (CASL), that promotes amine modifications in acidic buffer. Ammonium ions attached to molecules with amyloid-binding capability were activated through deprotonation due to the close proximity to the amyloid catalyst formed by Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH2 (NL6), derived from islet amyloid polypeptide (IAPP). Under the CASL conditions, alkyl amines underwent various modifications, i.e., acylation, arylation, cyclization, and alkylation, in acidic buffer. Crystallographic analysis and chemical modification studies of the amyloid catalysts suggested that the carbonyl oxygen of the Phe-Gly amide bond of NL6 plays a key role in activating the substrate amine by forming a hydrogen bond. Using CASL, selective conversion of substrates possessing equivalently reactive amine functionalities was achieved in catalytic reactions using amyloids. CASL provides a unique method for applying nucleophilic conversion reactions of amines in diverse fields of chemistry and biology.

Toward High-Performance Mg/S Batteries with M4-Assisted Mg(AlCl4 )2 /PYR14TFSI/DME Electrolyte and MoS2 @CMK/S Cathode.

Rechargeable magnesium batteries (RMBs) are considered as one of the most promising candidates for next-generation batteries. However, the popularization of RMBs is seriously plagued due to the lack of suitable non-nucleophilic electrolytes and the passivation of Mg anode. Herein, a novel non-nucleophilic electrolyte is developed by introducing (s)-1-methoxy-2-propylamine (M4) into themagnesium aluminum chloride complex (MACC)-like electrolyte. The as-synthesizes Mg(AlCl4 )2 -IL-DME-M4 electrolyte enables robust reversible cycling of Mg plating/stripping with low overpotential, high anodic stability, and ionic conductivity (8.56 mS cm-1 ). These features should be mainly attributed to the in situ formation of an MgF2 containing Mg2+ -conducting interphase, which dramatically suppresses the passivation and parasitic reaction of Mg anode with electrolyte. Remarkably, the Mg/S batteries assemble with as-synthesize electrolyte and a new type MoS2 @CMK/S cathode deliver unprecedented electrochemical performance. Specifically, the Mg/S battery exhibited the highest reversible capacity up to 1210 mAh g-1 at 0.1 C, excellent rate capability and satisfactory long-term cycling stability with a reversible capacity of 370 mAh g-1 (coulombic efficiency of ≈100%) at 1.0 C for 600 cycles. The study findings provide a novel strategy and inspiration for designing efficient non-nucleophilic Mg electrolyte and suitable sulfur-host materials for practical Mg/S battery applications.

HFIP-Mediated Desulfinative Friedel-Crafts Cyclobutenylation Reaction.

In 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP), gem-bis(triflyl)cyclobutenes, which can be prepared by the (2+2) cycloaddition reaction of Tf2C=CH2 with alkynes, underwent desulfination to generate the corresponding cyclobutenyl cation. This unique reactivity was successfully applied to the Friedel-Crafts type cyclobutenylation reaction of several (hetero)aromatic compounds.

Transition-Metal-Free Synthesis of 2-Substituted Benzo[cd]Indoles via the Reaction of 1-Halo-8-lithionaphthalenes with Nitriles.

A simple and effective organolithium approach to the synthesis of 2-substituted benzo[cd]indoles from peri-dihalonaphthalenes and nitriles has been developed. The reaction proceeds via a surprisingly easy intramolecular aromatic nucleophilic substitution facilitated by the "clothespin effect". The discovered transformation provides good isolated yields, allows usage of an extensive range of nitriles, and demonstrates a good substituents tolerance. UV-absorption and NMR spectra of the obtained benzo[cd]indoles and their protonated forms demonstrated exclusive protonation to the indole nitrogen atom even in the presence of two NMe2 groups in positions 5 and 6 (i. e. "proton sponge" moiety).

Metal-Free, Hindered, Regioselective Access to Multifunctional Groups Diarylamines via SN Ar Substitution of P-Nitroso Aromatic Methyl Ether by Arylamines.

Multifunctional groups diarylamines, an innovative product, efficiently produced from arylamines and p-nitrosoanisole derivatives by intermolecular SN Ar under weak acid conditions. This SN Ar proceeds under mild reaction conditions, and more significantly, the substrates involved do not necessarily require strong electron-withdrawing groups. Moreover, this SN Ar is characterized by resistance to space crowding, tolerance to halogen and nitroso functional groups, and high regioselectivity. Mechanistic observations suggest that the SN Ar is the result of the transfer of the positive charge center of the protonated nitroso group to the p-methoxy group.

Enhanced Photocatalytic Ozonation Using Modified TiO2 With Designed Nucleophilic and Electrophilic Sites.

Photocatalytic ozonation is considered to be a promising approach for the treatment of refractory organic pollutants, but the design of efficient catalyst remains a challenge. Surface modification provides a potential strategy to improve the activity of photocatalytic ozonation. In this work, density functional theory (DFT) calculations were first performed to check the interaction between O3 and TiO2-OH (surface hydroxylated TiO2) or TiO2-F (surface fluorinated TiO2), and the results suggest that TiO2-OH displays better O3 adsorption and activation than does TiO2-F, which is confirmed by experimental results. The surface hydroxyl groups greatly promote the O3 activation, which is beneficial for the generation of reactive oxygen species (ROS). Importantly, TiO2-OH displays better performance towards pollutants (such as berberine hydrochloride) removal than does TiO2-F and most reported ozonation photocatalysts. The total organic carbon (TOC) removal efficiency reaches 84.4 % within two hours. This work highlights the effect of surface hydroxylation on photocatalytic ozonation and provides ideas for the design of efficient photocatalytic ozonation catalysts.

Halogen and Chalcogen Activation by Nucleophilic Catalysis.

The high utility of halogenated organic compounds has prompted the development of numerous transformations that install the carbon-halogen motif. Halogen functionalities, deemed as "functional and functionalizable" molecules due to their capacity to modulate diverse internal properties, constitute a pivotal strategy in drug discovery and development. Traditional routes to these building blocks have commonly involved multiple steps, harsh reaction conditions, and the use of stoichiometric and/or toxic reagents. With the emergence of solid halogen carriers such as N-halosuccinimides, and halohydantoins as popular sources of halonium ions, the past decade has witnessed enormous growth in the development of new catalytic strategies for halofunctionalization. This review aims to provide a nuanced perspective on nucleophilic activators and their roles in halogen activation. It will highlight critical discoveries in effecting racemic and asymmetric variants of these reactions, driven by the development of new catalysts, activation modes, and improved understanding of chemical reactivity and reaction kinetics.

Dual Basicity and Nucleophilicity of Organosodium Reagents in Benzylic C-H Additions of Toluenes to Diarylethenes and Ketones.

Profiting from the dual high basicity and nucleophilicity of organosodium complexes, here we report the stepwise lateral metalation of a wide range of alkyl arenes (MeAr), mediated by hydrocarbon-soluble NaCH2SiMe3 ⋅ PMDETA (PMDETA=N,N,N',N'',N''-pentamethyldiethylenetriamine), followed by nucleophilic addition to diarylethenes of the newly generated NaCH2Ar ⋅ PMDETA complexes. This method grants access to a range of functionalised hydrocarbons in excellent yields and can be upgraded to catalytic regimes when using trans-stilbene, a 10 mol% of the alkyl sodium base and toluene as a solvent. Extending this approach to aromatic ketones leads to the formation of stilbenes under mild reaction conditions, resulting from the deprotonative coupling of toluenes with ketones. Combining spectroscopic studies with the trapping and characterisation of key reaction intermediates, mechanistic insights have been gained, advancing the understanding of coordination effects in organosodium chemistry, and shedding light on their special reactivity profiles.

Copper(II)-Catalyzed Amination of Aryl Chlorides in Aqueous Ammonia.

Anilines are ubiquitous in bio-active compounds and their synthesis can be achieved via metal-catalyzed cross-coupling reactions involving aryl halides. We describe an unusual, yet simple, CuII-catalyzed system for the amination of aryl chlorides in pure aqueous ammonia with 2.5 mol% catalyst loading under non-inert conditions. Different from previous systems, the reaction proceeds even without an additional organic solvent. Copper(II) sulfate in combination with 4,7-dimethoxy-1,10-phenanthroline enabled the amination of several aryl chlorides containing electron-neutral, -donating and -withdrawing groups to the corresponding anilines with good to excellent yields. The upscaling potential of the procedure has been shown by the synthesis at 50 mmol scale. The reaction proceeds as one of the rare cases of a CuII-assisted coupling, in contrast to the typical CuI-CuIII intermediates postulated for most Ullmann-type coupling reactions. The copper(II) center allows for a nucleophilic substitution pathway, enabled by the deprotonation of coordinated ammonia.

Computational Insights into SN 2 and Proton Transfer Reactions of CH3 O- with NH2 Y and CH3 Y.

Bimolecular nucleophilic substitution (SN 2) reactions have been extensively studied in both theory and experiment. While research on C-centered SN 2 reactions (SN 2@C) has been ongoing, SN 2 reactions at neutral nitrogen (SN 2@N) have received increased attention in recent years. To recommend methods for dynamics simulations, the comparison for the properties of the geometries, vibrational frequencies, and energies is done between MP2 and six DFT functional calculations and experimental data as well as the high-level CCSD(T) method for CH3 O- +NH2 Cl/CH3 Cl reactions. The relative energy diagrams at the M06 method for CH3 O- with CH3 Y/NH2 Y reactions (Y=F, Cl, Br, I) in the gas and solution phase are explored to investigate the effects of the leaving groups, different reaction centers, and solvents. We mainly focus on the computational of inv-SN 2 and proton transfer (PT) pathways. The PT channel in the gas phase is more competitive than the SN 2 channel for N-center reactions, while the opposite is observed for C-centered reactions. Solvation completely inhibits the PT channel, making SN 2 the dominant pathway. Our study provides new insight into the SN 2 reaction mechanisms and rich the novel reaction model in gas-phase organic chemistry.

CO Oxidation Mechanism of Silver-Substituted Mo/Cu CO-Dehydrogenase - Analogies and Differences to the Native Enzyme.

The aerobic oxidation of carbon monoxide to carbon dioxide is catalysed by the Mo/Cu-containing CO-dehydrogenase enzyme in the soil bacterium Oligotropha carboxidovorans, enabling the organism to grow on the small gas molecule as carbon and energy source. It was shown experimentally that silver can be substituted for copper in the active site of Mo/Cu CODH to yield a functional enzyme. In this study, we employed QM/MM calculations to investigate whether the reaction mechanism of the silver-substituted enzyme is similar to that of the native enzyme. Our results suggest that the Ag-substituted enzyme can oxidize CO and release CO2 following the same reaction steps as the native enzyme, with a computed rate-limiting step of 10.4 kcal/mol, consistent with experimental findings. Surprisingly, lower activation energies for C-O bond formation have been found in the presence of silver. Furthermore, comparison of rate constants for reduction of copper- and silver-containing enzymes suggests a discrepancy in the transition state stabilization upon silver substitution. We also evaluated the effects that differences in the water-active site interaction may exert on the overall energy profile of catalysis. Finally, the formation of a thiocarbonate intermediate along the catalytic pathway was found to be energetically unfavorable for the Ag-substituted enzyme. This finding aligns with the hypothesis proposed for the wild-type form, suggesting that the creation of such species may not be necessary for the enzymatic catalysis of CO oxidation.

Recent Advancement on the Indirect or Combined Alternative Thiocyanate Sources for the Construction of S-CN Bonds.

The process of thiocyanation is a notable chemical conversion owing to the extensive range of applications associated with thiocyanate compounds in the field of organic chemistry. In past centuries, the thiocyanation reaction incorporated metal thiocyanates or thiocyanate salts as sources of thiocyanate, which are environmentally detrimental and undesirable. In recent literature, there have been numerous instances where combined or indirect alternative sources of thiocyanate have been employed as agents for thiocyanation, showcasing their noteworthy applications. The present literature review focuses on elucidating the ramifications associated with the utilization of indirect or combined alternative sources of thiocyanate in various thiocyanation reactions.

Total synthesis of Comfreyn A and structural analogues via two photochemical key steps.

In this work the influence of o-fluorine substituents on the photo-dehydro-Diels-Alder (PDDA) reaction was investigated and the findings of this study were applied to the total synthesis of natural products. The reactant molecules consisted of two alkyl arylpropiolates, connected by a suberic acid tether and bearing fluorine substituents in each of the o-positions. While quantum chemical calculations suggested that a fluorine substituent prevents an attack of the adjacent carbon atom in the second C-C bond forming step of the PDDA reaction, this attack took place nevertheless. The subsequent fluoride elimination, assisted by protic solvents or trialkylsilanes, resulted in an "Umpolung" of the 4-position of the cycloallene intermediate enabling the introduction of nucleophiles at this position. The nucleophilic replacement of the second fluorine substituent could also be triggered photochemically. After removal of the tether, the two arene moieties stand nearly perpendicular to each other and a selective excitation of the naphthalene moiety was possible. This led to an intramolecular photoinduced electron transfer (PET) followed by a nucleophilic replacement of the fluoride according to a SR+N1Ar* mechanism. The formed phenolic hydroxyl group underwent spontaneous lactonization with the adjacent ester group. Based on these results, the first total synthesis of the lignan Comfreyn A and some structural analogues were developed.

Double difunctionalization of vinyl ether tethered nucleophile with electron-deficient alkene in two-molecule photoredox system.

Double difunctionalization of a vinyl ether tethered hydroxy or carbamoyl group with electron-deficient alkenes such as acrylonitrile or acrylic esters was achieved by visible-light irradiation in a two-molecule photoredox system. Use of anhydrous acetonitrile solution as a solvent promoted both dimerization of the radical cation of electron-rich alkene with electron-rich alkene and intramolecular nucleophilic addition to generate an electron-rich radical that was added to electron-deficient alkene to furnish the double difunctionalized product. A variety of electronically differentiated rich and deficient alkenes were used in the photoreaction; a simple construction of a complex carbon framework containing acetal from simple alkenes was successful under mild conditions.

Controllable Pyridine N-Oxidation-Nucleophilic Dechlorination Process for Enhanced Dechlorination of Chloropyridines: The Cooperation of HCO4- and HO2.

Dechlorination of chloropyridines can eliminate their detrimental environmental effects. However, traditional dechlorination technology cannot efficiently break the C-Cl bond of chloropyridines, which is restricted by the uncontrollable nonselective species. Hence, we propose the carbonate species-activated hydrogen peroxide (carbonate species/H2O2) process wherein the selective oxidant (peroxymonocarbonate ion, HCO4-) and selective reductant (hydroperoxide anion, HO2-) controllably coexist by manipulation of reaction pH. Taking 2-chloropyridine (Cl-Py) as an example, HCO4- first induces Cl-Py into pyridine N-oxidation intermediates, which then suffer from the nucleophilic dechlorination by HO2-. The obtained dechlorination efficiencies in the carbonate species/H2O2 process (32.5-84.5%) based on the cooperation of HCO4- and HO2- are significantly higher than those in the HO2--mediated sodium hydroxide/hydrogen peroxide process (0-43.8%). Theoretical calculations confirm that pyridine N-oxidation of Cl-Py can effectively lower the energy barrier of the dechlorination process. Moreover, the carbonate species/H2O2 process exhibits superior anti-interference performance and low electric energy consumption. Furthermore, Cl-Py is completely detoxified via the carbonate species/H2O2 process. More importantly, the carbonate species/H2O2 process is applicable for efficient dehalogenation of halogenated pyridines and pyrazines. This work offers a simple and useful strategy to enhance the dehalogenation efficiency of halogenated organics and sheds new insights into the application of the carbonate species/H2O2 process in practical environmental remediation.

Role of Nitrogenous Functional Group Identity in Accelerating 1,2,3-Trichloropropane Degradation by Pyrogenic Carbonaceous Matter (PCM) and Sulfide Using PCM-like Polymers.

Groundwater contamination by 1,2,3-trichloropropane (TCP) poses a unique challenge due to its human toxicity and recalcitrance to degradation. Previous work suggests that nitrogenous functional groups of pyrogenic carbonaceous matter (PCM), such as biochar, are important in accelerating contaminant dechlorination by sulfide. However, the reaction mechanism is unclear due, in part, to PCM's structural complexity. Herein, PCM-like polymers (PLPs) with controlled placement of nitrogenous functional groups [i.e., quaternary ammonium (QA), pyridine, and pyridinium cations (py+)] were employed as model systems to investigate PCM-enhanced TCP degradation by sulfide. Our results suggest that both PLP-QA and PLP-py+ were highly effective in facilitating TCP dechlorination by sulfide with half-lives of 16.91 ± 1.17 and 0.98 ± 0.15 days, respectively, and the reactivity increased with surface nitrogenous group density. A two-step process was proposed for TCP dechlorination, which is initiated by reductive ß-elimination, followed by nucleophilic substitution by surface-bound sulfur nucleophiles. The TCP degradation kinetics were not significantly affected by cocontaminants (i.e., 1,1,1-trichloroethane or trichloroethylene), but were slowed by natural organic matter. Our results show that PLPs containing certain nitrogen functional groups can facilitate the rapid and complete degradation of TCP by sulfide, suggesting that similarly functionalized PCM might form the basis for a novel process for the remediation of TCP-contaminated groundwater.

Metal-free internal nucleophile-triggered domino route for synthesis of fused quinoxaline [1,4]-diazepine hybrids and the evaluation of their DNA binding properties.

An unprecedented metal-free synthesis of fused quinoxaline 1,5-disubstituted-[1,4]-diazepine hybrids have been reported under mild conditions through a domino intermolecular SNAr followed by an internal nucleophile-triggered intramolecular SNAr pathway. Our strategy offers the flexibility for the introduction of a broad variety of functionalities at the N-1 position of fused diazepine moiety by using suitable diamine tails to design structurally diverse scaffolds. The DNA binding properties of representative quinoxaline diazepine hybrids were studied using UV-vis absorbance and EtBr displacement assay and were found to be governed by the functionalities at the N-1 position. Interestingly, compound 11f containing the N-1 benzyl substitution demonstrated significant DNA binding (KBH âˆ¼ 2.15 ± 0.25 × 104 M-1 and Ksv âˆ¼ 12.6 ± 1.41 × 103 M-1) accompanied by a bathochromic shift (Δλ âˆ¼ 5 nm). In silico studies indicated possible binding of diazepine hybrid 11f at the GC-rich major groove in the ct-DNA hexamer duplex and showed comparable binding energies to that of ethidium bromide. The antiproliferative activity of compounds was observed in the given order in different cell lines: (HeLa > HT29 > SKOV 3 > HCT116 > HEK293). Lead compound 11f demonstrated maximum cytotoxicity (IC50 value of 13.30 µM) in HeLa cell lines and also caused early apoptosis-mediated cell death in cancer cell lines. We envision that our work will offer newer methodologies for the construction of fused quinoxaline 1,5-disubstituted-[1,4]-diazepine class of molecules.

Synthesis and Photovoltaic Performance of ß-Amino-Substituted Porphyrin Derivatives.

New ß-amino-substituted porphyrin derivatives bearing carboxy groups were synthesized and their performance as sensitizers in dye-sensitized solar cells (DSSC) was evaluated. The new compounds were obtained in good yields (63-74%) through nucleophilic aromatic substitution reactions with 3-sulfanyl- and 4-sulfanylbenzoic acids. Although the electrochemical studies indicated suitable HOMO and LUMO energy levels for use in DSSC, the devices fabricated with these compounds revealed a low power conversion efficiency (PCE) that is primarily due to the low open-circuit voltage (Voc) and short-circuit current density (Jsc) values.

Sequential Nucleophilic Aromatic Substitution Reactions of Activated Halogens.

Building blocks have been identified that can be functionalised by sequential nucleophilic aromatic substitution. Some examples are reported that involve the formation of cyclic benzodioxin and phenoxathiine derivatives from 4,5-difluoro-1,2-dinitrobenzene, racemic quinoxaline thioethers, and sulfones from 2,3-dichloroquinoxaline and (2-aminophenylethane)-2,5-dithiophenyl-4-nitrobenzene from 1-(2-aminophenylethane)-2-fluoro-4,5-dinitrobenzene. Four X-ray single-crystal structure determinations are reported, two of which show short intermolecular N-O…N "π hole" contacts.

Simplified Synthesis of Poly(ethyleneimine)-Modified Silica Particles and Their Application in Oligosaccharide Isolation Methods.

There are great challenges in the field of natural product isolation and purification and in the pharmacological study of oligosaccharide monomers. And these isolation and purification processes are still universal problems in the study of natural products (NPs), traditional Chinese medicine (TCM), omics, etc. The same polymer-modified materials designed for the special separation of oligosaccharides, named Sil-epoxy-PEI and Sil-chloropropyl-PEI, were synthesized via two different methods and characterized by scanning electron microscopy combined with energy spectrum analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential as well as surface area analysis, etc. Several nucleotide/nucleoside molecules with different polarities and selectivities were successfully isolated in our laboratory using stainless-steel columns filled with the synthesized material. In addition, the separation of saccharide probes and oligosaccharides mixtures in water extracts of Morinda officinalis were compared in HILIC mode. The results showed that the resolution of separations for the representative analytes of the Sil-epoxy-PEI column was higher than for the Sil-chloropropyl-PEI column, and the developed stationary phase exhibited improved performance compared to hydrothermal carbon, amide columns and other HILIC materials previously reported.