Manipulated Fluoro-Ether Derived Nucleophilic Decomposition Products for Mitigating Polarization-Induced Capacity Loss in Li-Rich Layered Cathode.

Electrolyte engineering is a fascinating choice to improve the performance of Li-rich layered oxide cathodes (LRLO) for high-energy lithium-ion batteries. However, many existing electrolyte designs and adjustment principles tend to overlook the unique challenges posed by LRLO, particularly the nucleophilic attack. Here, we introduce an electrolyte modification by locally replacing carbonate solvents in traditional electrolytes with a fluoro-ether. By benefit of the decomposition of fluoro-ether under nucleophilic O-related attacks, which delivers an excellent passivation layer with LiF and polymers, possessing rigidity and flexibility on the LRLO surface. More importantly, the fluoro-ether acts as "sutures", ensuring the integrity and stability of both interfacial and bulk structures, which contributed to suppressing severe polarization and enhancing the cycling capacity retention from 39 % to 78 % after 300 cycles for the 4.8 V-class LRLO. This key electrolyte strategy with comprehensive analysis, provides new insights into addressing nucleophilic challenge for high-energy anionic redox related cathode systems.

Hydrolysis Mechanism of Carbamate Methomyl by a Novel Esterase PestE: A QM/MM Approach.

Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: (Ⅰ) serine-initiated nucleophilic attack and (Ⅱ) C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps Ⅰ and Ⅱ, respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based kcat prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein-substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases.

Complete active space analysis of a reaction pathway: Investigation of the oxygen-oxygen bond formation.

Water nucleophilic attack is an important step in water oxidation reactions, which have been widely studied using density functional theory (DFT). Nevertheless, a single-determinant DFT picture may be insufficient for a deeper insight into the process, in particular during the oxygen-oxygen bond formation. In this work, we use complete active space self-consistent field calculations and describe an approach for a complete active space analysis along a reaction pathway. This is applied to the water nucleophilic attack at a Ru-based catalyst, which has successfully been used for efficient water oxidation and in silico design of new water oxidation catalysts recently.

NHCs as Neutral Donors towards Polyphosphorus Complexes.

The first adducts of NHCs (=N-heterocyclic carbenes) with aromatic polyphosphorus complexes are reported. The reactions of [Cp*Fe(η5 -P5 )] (1) (Cp*=pentamethyl-cyclopentadienyl) with IMe (=1,3,4,5-tetramethylimidazolin-2-ylidene), IMes (=1,3-bis(2,4,6-trimethylphenyl)-imidazolin-2-ylidene) and IDipp (=1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene) led to the corresponding neutral adducts which can be isolated in the solid state. However, in solution, they quickly undergo a dissociative equilibrium between the adduct and 1 including the corresponding NHC. The equilibrium is influenced by the bulkiness of the NHC. [Cp''Ta(CO)2 (η4 -P4 )] (Cp''=1,3-di-tert-butylcyclopentadienyl) reacts with IMe under P atom abstraction to give an unprecedented cyclo-P3 -containing anionic tantalum complex. DFT calculations shed light onto the energetics of the reaction pathways.

Synthesis of 3ß-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene and Reductive Nucleophilic Attack on a Branched Aliphatic Aldehyde.

3ß-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene, which has a double bond between C-9 and C-11 and a phenylsulfenyl group on the terminus of the side chain, is a potential synthetic intermediate for steroids with 9,11-unsaturation or 9,11-seco skeletons. We describe here the synthesis of the title compound from 17-ethylenedioxy-3-acetoxyandrosta-3,5-dien-11-one. The introduction of an ethylene unit to 3ß-tert-butyldimethylsiloxyandrosta-5,9(11)-dien-17-one by the action of ethyltriphenylphosphonium bromide under basic conditions resulted in an inseparable mixture of two stereoisomeric products (5 : 1). However, in the subsequent step, only the (Z)-isomer was susceptible to the Lewis acid-catalyzed ene reaction with formaldehyde, giving a stereochemically pure product with the desired configuration. Within three steps, the ene-product was derivatized to the title compound, with a total yield of 53% over seven steps. Reductive terminal anion formation by treatment with lithium di-tert-butylbiphenyl (LiDBB) and subsequent nucleophilic attack on a branched aliphatic aldehyde was demonstrated, with an eye toward the introduction of side chains, especially for steroids with oxygen functionality at C-23.

Rational Design Rules for Molecular Water Oxidation Catalysts based on Scaling Relationships.

Lowering the overpotential required for water oxidation is of paramount importance for the efficient production of carbon-neutral fuels. This article highlights the intrinsic influence of the water oxidation mechanism used by molecular catalysts on the theoretically achievable minimal overpotential, based on scaling relationships typically used for heterogeneous catalysts. Due to such scaling relationships, catalysts that operate through the water nucleophilic attack mechanism have a fundamental minimal overpotential of about 0.3 V, whereas those that follow the dinuclear radical oxo coupling mechanism should in principle be able to operate with a lower overpotential. Therefore, it is recommended to design catalysts operating through the latter mechanism to achieve very efficient water oxidation systems.

Recent Advances in the Synthesis of Heterocycles and Related Substances Based on α-Imino Rhodium Carbene Complexes Derived from N-Sulfonyl-1,2,3-triazoles.

In recent years, α-imino rhodium carbene complexes derived by ring-opening of N-sulfonyl-1,2,3-triazoles have attracted much attention from organic chemists. Many transformations of these species have been reported that involve, in most cases, nucleophilic attack at the carbene center of the α-imino rhodium carbene, facilitating the synthesis of a wide range of novel and useful compounds, particularly heterocycles. This Minireview mainly focuses on advances in the transformation of N-sulfonyl-1,2,3-triazoles during the past two years.

The Origin of Anti-Markovnikov Regioselectivity in Alkene Hydroamination Reactions Catalyzed by [Rh(DPEphos)](.).

The development of regioselective anti-Markovnikov alkene's hydroamination is a long-standing goal in catalysis. The [Rh(COD)(DPEphos)](+) complex is the most general and regioselective group 9 catalyst for such a process. The reaction mechanism for intermolecular hydroamination of alkenes catalyzed by [Rh(DPEphos)](+) complex is analyzed by means of DFT calculations. Hydroamination (alkene vs. amine activation routes) as well as oxidative amination pathways are analyzed. According to the computational results the operating mechanism can be generally described by alkene coordination, amine nucleophilic addition, proton transfer through the metal center and reductive elimination steps. The mechanism for the formation of the oxidative amination side product goes via a ß-elimination after the nucleophilic addition and metal center protonation steps. The origin of the regioselectivity for the addition process (Markovnikov vs. anti-Markovnikov additions) is shown to be not charge but orbitally driven. Remarkably, η(2) to η(1) slippage degree on the alkene coordination mode is directly related to the regioselective outcome.

Molecular mechanism of a hotdog-fold acyl-CoA thioesterase.

Thioesterases are enzymes that hydrolyze thioester bonds between a carbonyl group and a sulfur atom. They catalyze key steps in fatty acid biosynthesis and metabolism, as well as polyketide biosynthesis. The reaction molecular mechanism of most hotdog-fold acyl-CoA thioesterases remains unknown, but several hypotheses have been put forward in structural and biochemical investigations. The reaction of a human thioesterase (hTHEM2), representing a thioesterase family with a hotdog fold where a coenzyme A moiety is cleaved, was simulated by quantum mechanics/molecular mechanics metadynamics techniques to elucidate atomic and electronic details of its mechanism, its transition-state conformation, and the free energy landscape of the process. A single-displacement acid-base-like mechanism, in which a nucleophilic water molecule is activated by an aspartate residue acting as a base, was found, confirming previous experimental proposals. The results provide unambiguous evidence of the formation of a tetrahedral-like transition state. They also explain the roles of other conserved active-site residues during the reaction, especially that of a nearby histidine/serine pair that protonates the thioester sulfur atom, the participation of which could not be elucidated from mutation analyses alone.

Amide synthesis by nucleophilic attack of vinyl azides.

A method for the synthesis of amide-containing molecules was developed using vinyl azides as an enamine-type nucleophile towards carbon electrophiles, such as imines, aldehydes, and carbocations that were generated from alcohols in the presence of BF3 ⋅OEt2 . After nucleophilic attack of the vinyl azide, a substituent of the resulting iminodiazonium ion intermediate migrates to form a nitrilium ion, which is hydrolyzed to afford the corresponding amide.

Functionalization of a cyclo-P5 ligand by main-group element nucleophiles.

Unprecedented functionalized products with an η(4)-P5 ring are obtained by the reaction of [Cp*Fe(η(5)-P5)] (1; Cp*=η(5)-C5Me5) with different nucleophiles. With LiCH2SiMe3 and LiNMe2, the monoanionic products [Cp*Fe(η(4)-P5CH2SiMe3)](-) and [Cp*Fe(η(4)-P5NMe2)](-), respectively, are formed. The reaction of 1 with NaNH2 leads to the formation of the trianionic compound [{Cp*Fe(η(4)-P5)}2N](3-), whereas the reaction with LiPH2 yields [Cp*Fe(η(4)-P5PH2)](-) as the main product, with {[Cp*Fe(η(4)-P5)]2PH}(2-) as a byproduct. The calculated energy profile of the reactions provides a rationale for the formation of the different products.

Degradation of citrinin by different types of light and hydrogen peroxide.

Citrinin (CIT), a mycotoxin produced by Monascus, Penicillium, and other fungies, can contaminate red yeast rice and other foods, thus constraining their application and development. Exploring efficient degradation methods of citrinin is becoming as one of the hot research topics. In this study, the degradation of citrinin, irradiated by visible (Vis) light, ultraviolet (UV) light, and simulated sunlight alone, as well as in combination with hydrogen peroxide (light/H2O2), was investigated. The research demonstrates UV, Vis, and simulated sunlight all have a degree of degradation on citrinin, and the degradation efficiency correlates with light source and light intensity. Interestingly, when combined with 100 W Vis and 0.01 M H2O2, the citrinin degradation rate increases to 32%, compared to 1% and 5% achieved by Vis and H2O2 alone. Hydroxyl radicals, arising from the uniform cracking of H2O2 under Vis, were experimentally validated by electron spin resonance measurement and could accelerate the dissociation of citrinin by nucleophilic attacking. Employing the density functional theory, we deduced nucleophilic •OH mainly attack onto C8 and C5 site by comparing the electrophilic Parr functions (Pk+) value of main C atom of citrinin. This research presents a rapid and efficient degradation of citrinin by combining visible light with H2O2. PRACTICAL APPLICATION: This research presents a rapid and efficient method for the degradation of citrnin in red yeast rice and other citrnin containing products by combining visible light with H2O2.

Dramatic substituent effects on the mechanisms of nucleophilic attack on Se-S bridges.

The reactions of XSeSX, XSeSY, and YSeSX (X, Y = CH3, NH2, OH, F) with F(-) and CN(-) nucleophiles have been investigated by means of B3PW91/6-311+G(2df,p) and G4 calculations. In systems where the two substituents are not identical (XSeSY), the more stable of the two possible isomers corresponds to those in which the most electronegative substituent is attached to Se. Nucleophilic attack takes place at Se, independent of the nature of the nucleophile, with the only exception being XSeSF (X = CH3 , NH2 , OH), in which case the attack occurs at S. In agreement with recent results for disulfide and diselenide linkages, the mechanisms leading to Se-S bond cleavage are not always the more favorable ones because for highly electronegative substituents the most favorable process is fission of the chalcogen-substituent bond. These dissimilarities in the observed reactivity pattern as a function of the electronegativity of the substituents are due to the fact that the σ-type Se-S antibonding orbital, which for low-electronegative substituents is the lowest unnoccupied molecular orbital (LUMO), becomes strongly destabilized when the electronegativity of the substituent increases, and is replaced by an antibonding π-type Se-X (or S-X) orbital. In contrast, however, with what has been found for disulfide and diselenide derivatives, the observed reactivity does not change with the nature of the nucleophile. The activation strain model provides interesting insight into these processes, showing that in most cases the activation barriers are the consequence of subtle differences in the strain or in the interaction energies.

Stereocomplementary routes to hydroxylated nitrogen heterocycles: total syntheses of casuarine, australine, and 7-epi-australine.

Addition of lithiated 1-benzyloxyallene to a D-arabinose-derived cyclic nitrone occurred with perfect diastereoselectivity furnishing a bicyclic 1,2-oxazine derivative, which is an excellent precursor for pyrrolizidine alkaloids hydroxylated at C-7 with optional configuration at this stereogenic center. Depending on the stage of the N-O bond cleavage and ring re-closure, 7-hydroxypyrrolizidines with 7R or 7S configuration were obtained, as a result of completely selective addition reactions occurring complementarily at the bottom or top face of the endocyclic C-C double bond in six- and five-membered B rings, respectively. Applicability of these stereodivergent routes to obtain polyhydroxy pyrrolizidine alkaloids is demonstrated by the efficient syntheses of casuarine and australine as examples of the two classes of diversely configured 7-hydroxypyrrolizidine alkaloids. An alternative synthesis of australine and two strategies for the preparation of 7-epi-australine are also reported, which demonstrate that the stereoselectivity of hydride reduction of an exocyclic C-O double bond is independent of the ring size, occurring preferentially from the top face either in a six- or five-membered ring.

Reactivity of iron complexes containing monodentate aminophosphine ligands - Formation of four-membered carboxamido-phospha-metallacycles.

Treatment of [FeCp(CO)2Cl] with 1 equiv of the amidophosphine ligands Li[R2PNR'] (R = Ph, iPr, R' = iPr, tBu, Cy) afforded complexes of the type [FeCp(CO)(κ2(C,P)-(C = O)-NiPr-PPh2)] (1a), [FeCp(CO)(κ2(C,P)-(C = O)-NtBu-PPh2)] (1b), and [FeCp(CO)(κ2(C,P)-(C = O)-NCy-PiPr2)] (1c) in 40-50% yields. Complex 1a was also formed when [FeCp(CO)2(PPh2NHiPr)]+ (2) was reacted with 1 equiv of KOtBu. These complexes feature a four-membered carboxamido-phospha-ferracycle as a result of an intramolecular nucleophilic attack of the amidophosphine ligand on coordinated CO. Upon treatment of 1a with the electrophile [Me3O]BF4 the aminocarbene complex [FeCp(CO)(κ2(C,P) = C(OMe)-NiPr-PPh2)]+ (3) was obtained bearing an aza-phospha-carbene moiety. Upon treatment of cis,trans,cis-[Fe(CO)2(Ph2PNHiPr)2(Br)2] (4a) and cis,trans,cis-[Fe(CO)2(Ph2PNHtBu)2(Br)2] (4b) with KOtBu the carboxamido-phospha-ferracycles trans-[Fe(CO)2(κ2(C,P)-(C = O)-NiPr-PPh2)(Ph2PNHiPr)Br] (5a) and trans-[Fe(CO)2(κ2(C,P)-(C = O)-NtBu-PPh2)(Ph2PNHtBu)Br] (5b) were formed in moderate yield. Finally, representative structures were determined by X-ray crystallography.

Extein residues regulate the catalytic function of Spl DnaX intein enzyme by restricting the near-attack conformations of the active-site residues.

Intein enzymes catalyze the splicing of their flanking polypeptide chains and have found tremendous biotechnological applications. Their terminal residues form the catalytic core and participate in the splicing reaction. Hence, the neighboring N- and C-terminal extein residues influence the catalytic rate. As these extein residues vary depending on the substrate identity, we tested the influence of 20 amino acids at these sites in the Spl DnaX intein and observed significant variation of spliced product as well as N- and C-terminus cleavage product formation. We investigated the dependence of these reactions on the extein residues by molecular dynamics (MD) simulations on eight extein variants, and found that the conformational sampling of the active-site residues of the intein enzyme differed among these extein variants. We found that the extein variants that sample higher population of near-attack conformers (NACs) of the active-site residues undergo higher product formation in our activity assays. Ground state conformers that closely resemble the transition state are referred to as NACs. Very good correlation was observed between the NAC populations from the MD simulations of eight extein variants and the corresponding product formation from our activity assays. Furthermore, this molecular detail enabled us to elucidate the mechanistic roles of several conserved active-site residues in the splicing reaction. Overall, this study shows that the catalytic power of Spl DnaX intein enzyme, and most likely other inteins, depends on the efficiency of formation of NACs in the ground state, which is further modulated by the extein residues.

Waste-derived biocatalysts for pesticide degradation.

A green approach to produce a cellulose-derived biocatalyst containing hydroxamic acids targeted for the neutralization of toxic organophosphates is shown. The cellulose source, rice husk, is among the largest agricultural waste worldwide and can be strategically functionalized, broadening its sustainable application. Herein, rice husk was oxidized in different degrees, leading to carboxylic acid-based colloidal and solid samples. These were functionalized with hydroxamic acids via amide bonds and fully characterized. The hydroxamic acid derived biocatalysts were evaluated in the cleavage of toxic organophosphates, including the pesticide Paraoxon. Catalytic increments reached up to 107-fold compared to non-catalyzed reactions. Most impressively, the materials showed P atom-selectivity and recyclability features. This guarantees only one reaction pathway that leads to less toxic products, hereby, detoxifies. Overall, highly sustainable catalysts are presented, that benefits from waste source, its green functionalization and is successfully employed for the promotion of chemical security of threatening organophosphates. To the best of our knowledge, this is the first report of a hydroxamate-derived rice husk (selectively modified at the C6 of cellulose) and its application in organophosphates reaction.

Nucleophilic Activation of Sulfur Hexafluoride by N-Heterocyclic Carbenes and N-Heterocyclic Olefins: A Computational Study.

Sulfur hexafluoride (SF6 ) is considered as a potent greenhouse gas, whose effective degradation is challenging. Here we report a computational study on the nucleophilic activation of sulfur hexafluoride by N-heterocyclic carbenes and N-heterocyclic olefins. The result shows that the activation of SF6 is both thermodynamically and kinetically favorable at mild condition using NHOs with fluoro-substituted azolium and sulfur pentafluoride anion being formed. The Gibbs free energy barrier during the activation of SF6 has a linear relationship with the energy of HOMO of substrates, which could be a guideline for applying those compounds that feature higher energy in HOMO to activate SF6 in high efficiency.

Acidic pH Decreases the Endonuclease Activity of Initiator RepB and Increases the Stability of the Covalent RepB-DNA Intermediate while Has Only a Limited Effect on the Replication of Plasmid pMV158 in Lactococcus lactis.

Plasmid vectors constitute a valuable tool for homologous and heterologous gene expression, for characterization of promoter and regulatory regions, and for genetic manipulation and labeling of bacteria. During the last years, a series of vectors based on promiscuous replicons of the pMV158 family have been developed for their employment in a variety of Gram-positive bacteria and proved to be useful for all above applications in lactic acid bacteria. A proper use of the plasmid vectors requires detailed knowledge of their main replicative features under the changing growth conditions of the studied bacteria, such as the acidification of the culture medium by lactic acid production. Initiation of pMV158 rolling-circle replication is catalyzed by the plasmid-encoded RepB protein, which performs a sequence-specific cleavage on one of the parental DNA strands and, as demonstrated in this work, establishes a covalent bond with the 5'-P end generated in the DNA. This covalent adduct must last until the leading-strand termination stage, where a new cleavage on the regenerated nick site and a subsequent strand-transfer reaction result in rejoining of the ends of the cleaved parental strand, whereas hydrolysis of the newly-generated adduct would release the protein from a nicked double-stranded DNA plasmid form. We have analyzed here the effect of pH on the different in vitro reactions catalyzed by RepB and on the in vivo replication ability of plasmid pMV158. We show that acidic pH greatly impairs the catalytic activity of the protein and reduces hydrolysis of the covalent RepB-DNA adduct, as expected for the nucleophilic nature of these reactions. Conversely, the ability of pMV158 to replicate in vivo, as monitored by the copy number and segregational stability of the plasmid in Lactococcus lactis, remains almost intact at extracellular pHs ranging from 7.0 to 5.0, and a significant reduction (by ∼50%) in the plasmid copy number per chromosome equivalent is only observed at pH 4.5. Moreover, the RepB to pMV158 molar ratio is increased at pH 4.5, suggesting the existence of compensatory mechanisms that operate in vivo to allow pMV158 replication at pH values that severely disturb the catalytic activity of the initiator protein.

Combined computational and experimental studies on cysteine-sulfadiazine adduct formation.

The electrochemical characterization of sulfadiazine-cysteine (SD-CYS) adduct formation was performed in phosphate buffer (pH 7) on the basis of voltammetric current and peak potential measurements. Due to the association of cysteine with sulfadiazine, the reduction peak currents of mercuric and mercurous cysteine thiolates decreased and their peak potentials simultaneously shifted to less negative potentials. By using the current changes of mercurous cysteine thiolate, it was determined that cysteine and sulfadiazine are associated with a 1:1 stoichiometry with a conditional association constant of 1.99 ×104 M-1 . In addition to experimental studies, a computational approach was carried out to study the geometrical parameters, electron densities, and UV-Vis absorption spectra of sulfadiazine and SDCYS adduct in water. Calculated (B3LYP/6-311++G(d,p) level) and experimental UV-Vis absorption spectra of the compounds were found to be in good agreement in water. The computational study suggests that cysteine bound to the C(5) on the pyrimidine ring via SH-group nucleophilic attack. Computational results reveal that sulfadiazine and its derivatives effectively bind cysteine and may lead to new molecules/drugs to target cysteine.