Mild Conditions Research Articles

Plasmon-Mediated Organic Photoelectrochemistry Applied to Amination Reactions.

Organic electrochemistry is currently experiencing an era of renaissance, which is closely related to the possibility of carrying out organic transformations under mild conditions, with high selectivity, high yields, and without the use of toxic solvents. Combination of organic electrochemistry with alternative approaches, such as photo-chemistry was found to have great potential due to induced synergy effects. In this work, we propose for the first time utilization of plasmon triggering of enhanced and regio-controlled organic chemical transformation performed in photoelectrochemical regime. The advantages of the proposed route is demonstrated in the model amination reaction with formation of C-N bond between pyrazole and substituted benzene derivatives. Amination was performed in photo-electrochemical mode on the surface of plasmon active Au@Pt electrode with attention focused on the impact of plasmon triggering on the reaction efficiency and regio-selectivity. The ability to enhance the reaction rate significantly and to tune products regio-selectivity is demonstrated. We also performed density functional theory calculations to inquire about the reaction mechanism and potentially explain the plasmon contribution to electrochemical reaction rate and regioselectivity.

Regioselective Cobalt(II) Catalyzed C-H Functionalization and [3 + 2] Annulation of N-Arylguanidines with 1,3-Diynes.

8-Quinolinyl directed N-arylguanidines were subjected to cobalt(II) catalyzed C-H functionalization/1,3-diyne annulation under mild conditions to afford 40 alkynylated indole guanidines in 34% to 92% yields. The scope of the substrates was explored. The reported procedure is mostly regioselective and tolerates various functional groups in the substrates. The regioselectivity of the reactions was assessed with the aid of multinuclear NMR spectroscopy and X-ray crystallography. Competition and labeling experiments were carried out to support the proposed mechanism.

Visible Light Photoredox-Catalyzed Formyl/Carboxylation of Activated Alkenes with Glyoxylic Acid Acetals and CO2.

A photoredox-catalyzed sequential α-formyl/carboxylation of alkenes with glyoxylic acid acetals and CO2 has been developed to afford a range of masked γ-formyl esters in good yields, which could be readily transformed into diverse compounds, such as γ-formyl ester, hemiacetal, and 1,4-diol. This reaction features mild conditions, readily available starting materials, and operational simplicity.

Hydrogen on Colloidal Gold Nanoparticles.

Colloidal gold nanoparticles (AuNPs) have myriad scientific and technological applications, but their fundamental redox chemistry is underexplored. Reported here are titration studies of oxidation and reduction reactions of aqueous AuNP colloids, which show that the AuNPs bind substantial hydrogen (electrons + protons) under mild conditions. The 5 nm AuNPs are reduced to a similar extent with reductants from borohydrides to H2 and are reoxidized back essentially to their original state by oxidants, including O2. The reactions were monitored via surface plasmon resonance (SPR) optical absorption, which was shown to be much more sensitive to surface H than to changes in solution conditions. Reductions with H2 occurred without pH changes, demonstrating that hydrogenation forms surface H rather than releasing H+. Computational studies suggested that an SPR blueshift was expected for H atom addition, while just electron addition likely would have caused a redshift. Titrations consistently showed a maximum redox change of the 5 nm NPs, independent of the reagent, corresponding to 9% of the total gold or ∼30% hydrogen surface coverage (∼370 H per AuNP). Larger AuNPs showed smaller maximum fractional surface coverages. We conclude that H binds to the edge, corner, and defect sites of the AuNPs, which explains the stoichiometric limitation and the size effect. The finding of substantial and stable hydrogen on the AuNP surface under mild reducing conditions has potential implications for various applications of AuNPs in reducing environments, from catalysis to biomedicine. This finding contrasts with the behavior of bulk gold and with the typical electron-focused perspective in this field.

Easy Access to Functionalized Indolines and Tetrahydroquinolines via a Photochemical Cascade Cyclization Reaction.

Herein, the development of a light-mediated synthesis of functionalized indolines and tetrahydroquinolines is reported. These structural motifs are considered as highly valuable targets, attributed to their widespread occurrence in pharmaceuticals and natural products. The gold-mediated approach offers a direct route to functionalized indolines in yields of up to 81% under mild photochemical conditions. Thereby, easily accessible Boc-protected N-aryl-allylamine and homoallylamine derivatives were reacted with sp3-hybridized haloalkanes in an intermolecular cascade cyclization reaction. A broad scope of substrates, including a variety of different substituents on the aromatic backbone as well as various haloalkanes, could be utilized. Indoline derivatives, which are functionalized in position 2, are also accessible by applying ortho-allylic anilines. Moreover, the synthetic appeal was demonstrated for a total synthesis of the anti-inflammatory agent AN669 in three reaction steps in an overall yield of 64%.

Copper-Nitroxyl-Catalyzed α-Oxygenation of Cyclic Secondary Amines Including Application to Late-Stage Functionalization.

Cyclic secondary amines are prominent subunits in pharmaceutical compounds. Methods for direct functionalization of N-unprotected/unsubstituted piperidines and related heterocycles have limited precedent despite their potential to impact medicinal chemistry and organic synthesis. Herein, we report a Cu/nitroxyl co-catalyzed method for direct conversion of cyclic secondary amines to the corresponding lactams via aerobic dehydrogenation and oxidative coupling with water. The mild reaction conditions tolerate diverse functional groups, enabling application to molecules that cover broad chemical space. The method is showcased in selective functionalization of building blocks and complex molecules, including late-stage functionalization of bromodomain inhibitors.

Efficient Decoupled Electrolytic Water Splitting in Acid through Pseudocapacitive TiO2.

Water electrolysis remains a key component in the societal transition to green energy. Membrane electrolyzers are the state-of-the-art technology for water electrolysis, relying on 80°C operation in highly alkaline electrolytes, which is undesirable for many of the myriad end-use cases for electrolytic water splitting. Herein, an alternative water electrolysis process, decoupled electrolysis, is described which performed in mild acidic conditions with excellent efficiencies. Decoupled electrolysis sequentially performs the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER), at the same catalyst. Here, H+ ions generated from the OER are stored through pseudocapacitive (redox) charge storage, and released to drive the HER. Here, decoupled electrolysis is demonstrated using cheap, abundant, TiO2 for the first time. To achieve decoupled acid electrolysis, ultra-small anatase TiO2 particles (4.5nm diameter) are prepared. These ultra-small TiO2 particles supported on a carbon felt electrode show a highly electrochemical surface area with a capacitance of 375Fg-1. When these electrodes are tested for decoupled water splitting an overall energy efficiency of 52.4% is observed, with excellent stability over 3000 cycles of testing. This technology can provide a viable alternative to membrane electrolyzers-eliminating the need for highly alkaline electrolytes and elevated temperatures.

Synthesis of β,β-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of β,β-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

Electrochemical Reductive Cross-Coupling of Alkyl or Alkenyl Halides with gem-Difluoroalkenes.

Herein, we describe an electroreductive cross-electrophile coupling protocol for the construction of valuable monofluoroalkenes from easily accessible alkyl or alkenyl halides with gem-difluoroalkenes. The reaction can be conducted under sustainable and mild conditions delivering valuable and functionalized monofluoroalkenes with excellent Z-selectivity. The protocol's most notable advantage is the in situ release of nickel catalyst from the inexpensive electrodes without the addition of extra hazardous metal catalyst and superstoichiometric reductant.

Rh-Catalyzed α-Arylation of Cyclic 1,3-Dicarbonyls with Benzocyclobutenols Enabled by a Cyclic Iodonium Ylide Strategy.

To date, the general and catalytic α-arylation of cyclic 1,3-dicarbonyls remains elusive. We now report the first Rh-catalyzed α-arylation of cyclic 1,3-dicarbonyls with benzocyclobutenols through a cyclic iodonium ylide strategy. Our strategy represents a good solution for the previously challenging α-arylation of cyclic 1,3-dicarbonyls with sterically demanding aryl partners, which is especially appropriate for structurally unique heteroaromatic 1,3-dicarbonyls. Our approach features mild conditions, readily available starting materials, high yields, excellent functional group-tolerance, and simple operation, providing expedient access toward medically important 2-aryl (hetero)cyclic 1,3-dicarbonyls. The practicality of this approach is demonstrated by the gram-scale synthesis, one-pot synthesis, and numerous downstream transformations.

Synthesis of Perdeuterated Alkyl Amines/Amides with Pt/C as Catalyst under Mild Conditions.

A convenient method for the synthesis of perdeuterated alkyl amides/amines is disclosed. Perdeuterated acetyl amides can be achieved by a hydrogen-deuterium (H/D) exchange protocol with Pt/C as a catalyst and D2O as a deuterium source under mild conditions. After removal or reduction of the acetyl group, this protocol can provide perdeuterated primary, secondary, and tertiary amines, which are difficult to achieve via other methods.

Biomimetic syntheses of myrtucommulones K-L and N, and callistiviminenes F-H

A concise and collective biomimetic synthesis of myrtucommulones K-L and N, as well as callistiviminenes F-H, has been achieved utilizing a mild Me2AlCl-mediated hetero-Diels-Alder reaction as a pivotal step, all in only three steps without the need for protecting groups from readily available compounds. This approach exhibits excellent regioselectivity and good diastereoselectivity, operates under exceptionally mild conditions, and delivers good yields. Furthermore, this synthesis has led to the revision of the structure of myrtucommulone L.

Three-Component Assembly of Dihydropyrrolo[3,4-e][1,3]thiazines from Elemental Sulfur, Maleimides, and 1,3,5-Triazinanes.

A three-component reaction for the synthesis of dihydropyrrolo[3,4-e][1,3]thiazines has been developed. Elemental sulfur, maleimides, and 1,3,5-triazinanes are assembled together through sulfuration/nucleophilic attack in N-methylpyrrolidin-2-one (NMP) under mild conditions. A small amount of NaHCO3 is important for the activation of the reaction. In this method, sulfur plays a dual role in thiazine ring formation, while triazinanes are utilized as three-atom synthons in the annulation reaction.

Nickel–Nitrogen–Carbon (Ni–N–C) Electrocatalysts Toward CO2 electroreduction to CO: Advances, Optimizations, Challenges, and Prospects

Electrocatalytic reduction of CO2 into high energy‐density fuels and value‐added chemicals under mild conditions can promote the sustainable cycle of carbon and decrease current energy and environmental problems. Constructing electrocatalyst with high activity, selectivity, stability, and low cost is really matter to realize industrial application of electrocatalytic CO2 reduction (ECR). Metal–nitrogen–carbon (M–N–C), especially Ni–N–C, display excellent performance, such as nearly 100% CO selectivity, high current density, outstanding tolerance, etc., which is considered to possess broad application prospects. Based on the current research status, starting from the mechanism of ECR and the existence form of Ni active species, the latest research progress of Ni–N–C electrocatalysts in CO2 electroreduction is systematically summarized. An overview is emphatically interpreted on the regulatory strategies for activity optimization over Ni–N–C, including N coordination modulation, vacancy defects construction, morphology design, surface modification, heteroatom activation, and bimetallic cooperation. Finally, some urgent problems and future prospects on designing Ni–N–C catalysts for ECR are discussed. This review aims to provide the guidance for the design and development of Ni–N–C catalysts with practical application.

Determinants of Disease Progression in Bangladeshi COVID-19 Patients: A Cross-sectional Survey

Background Coronavirus disease 2019 (COVID-19) shows a wide range of clinical manifestations, including asymptomatic presentation to severe pneumonia, acute respiratory distress syndrome, and respiratory failure. Although COVID-19 disease progression was studied elsewhere, it is largely unknown in Bangladesh. Methods We conducted this cross-sectional study in November 2020 to January 2021 on patients diagnosed with COVID-19 confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Pearson chi-square tests were used to assess the disease progressions across selected variables. A logistic regression model was used to assess the associated factors of COVID-19 infection for explanatory variables. All statistics were performed using the Stata software version 14.0 (Stata corporation, college station, Texas, USA). Results A total of 384 of respondents were involved in the survey. Of participants, most males (73%), unmarried (69%), aged 18 to 35 years during survey, and lived in urban community (73%). Overall, 41% of patients were in asymptotic condition, 44% were in mild condition, while 17% were moderate to severe conditions. Male patients and patients over 50 years had severe symptoms, accounting for 52% and 50%, respectively. Nearly half of business persons and office employees had severe symptoms. Almost all married patients (98%) had severe symptoms. The severity of symptoms was also higher for patients living in urban areas (79%), smoking (95%), and not physically active (52%). Patients with diabetes, asthma/COPD, and cancer were significantly associated with severe stage of COVID-19 (p≤0.05). Patient’s age, gender, smoking status, diabetics, working conditions significantly affect Covid-19 disease progression. Conclusion The study found that 7.03% of patients had severe, 9.11% had moderate and 40.36% had asymptomatic conditions. The heterogenic association between the disease progressions with age, sex, residence, marital status, smoking habits, diabetes, physical exercise, working conditions, sedentary lifestyles. Findings highlight the idea of using vulnerability ratings for each risk factor related to disease progression.

Durable and Robust Antibacterial Polypropylene Hernia Mesh for Abdominal Wall Defect Repair.

Polypropylene (PP) mesh is commonly used in repairing abdominal wall hernia (AWH). However, the use of synthetic prosthesis comes with the risk of developing a prosthetic infection, resulting in delayed healing, secondary surgery, and potentially increased mortality. To address these issues, a facile surface functionalization strategy for PP mesh based on phytic acid (PA) and polyhexamethylene guanidine (PHMG) was constructed through a one-step co-deposition process, referred to as the PA/PHMG coating. The development of PA/PHMG coating is mainly attributed to the surface affinity of PA and the electrostatic interactions between PA and PHMG. The PA/PHMG coating could be completed within 4 h under mild conditions. The prepared PA/PHMG coatings on PP mesh surfaces exhibited desirable biocompatibility toward mammalian cells and excellent antibacterial properties against the notorious "superbug" methicillin-resistant Staphylococcus aureus (MRSA) and tetracycline-resistant Escherichia coli (TRE). The PA/PHMG-coated PP meshes showed killing ratios of over 99% against MRSA in an infected abdominal wall hernia repair model. Furthermore, histological and immunohistochemical analysis revealed a significantly attenuated degree of neutrophil infiltration in the PA/PHMG coating group, attributed to the decreased bacterial numbers alleviating the inflammatory response at the implant sites. Meanwhile, the pristine PP and PA/PHMG-coated meshes showed effective tissue repair, with the PA/PHMG coating group exhibiting enhanced angiogenesis compared with pristine PP meshes, suggesting superior tissue restoration. Additionally, PP meshes with the highest PHMG weight ratio (PA/PHMG(3)) exhibited excellent long-term robustness under phosphate-buffered saline (PBS) immersion with a killing ratio against MRSA still exceeding 95% after 60 days of PBS immersion. The present work provides a facile and promising approach for developing antibacterial implants.

Decarboxylative Nucleophilic Fluorination of Aliphatic Carboxylic Acids.

Herein, we present a decarboxylative nucleophilic fluorination of carboxylic acids with a silver catalyst. This strategy enables the synthesis of a myriad of diverse and valuable fluorinated motifs under mild conditions, demonstrating good functional-group tolerance and utility in late-stage functionalization. In contrast to traditional electrophilic fluorination, this nucleophilic method utilizes a more readily available nucleophilic fluorinating reagent, providing substantial advantages in terms of cost efficiency, broad substrate scope, and functional-group compatibility.

Photoredox/Bismuth Relay Catalysis Enabling Reductive Alkylation of Nitroarenes with Aldehydes.

The effective transition metal-free photoredox/bismuth dual catalytic reductive dialkylation of nitroarenes with benzaldehydes has been reported. The nitroarene redution through visible light-driven photoredox catalysis was integrated with subsequent reductive dialkylation of anilines under bismuth catalysis to enable the cascade reductive alkylation of nitroarenes with carbonyls. Salient features of this relay catalysis system include mild reaction conditions, no requirement for transition metal catalysts, easy handling, step-economy, and high selectivity.

Engineering non-conventional yeast Rhodotorula toruloides for ergothioneine production

BackgroundErgothioneine (EGT) is a distinctive sulfur-containing histidine derivative, which has been recognized as a high-value antioxidant and cytoprotectant, and has a wide range of applications in food, medical, and cosmetic fields. Currently, microbial fermentation is a promising method to produce EGT as its advantages of green environmental protection, mild fermentation condition, and low production cost. However, due to the low-efficiency biosynthetic process in numerous cell factories, it is still a challenge to realize the industrial biopreparation of EGT. The non-conventional yeast Rhodotorula toruloides is considered as a potential candidate for EGT production, thanks to its safety for animals and natural ability to synthesize EGT. Nevertheless, its synthesis efficiency of EGT deserves further improvement.ResultsIn this study, out of five target wild-type R. toruloides strains, R. toruloides 2.1389 (RT1389) was found to accumulate the highest EGT production, which could reach 79.0 mg/L at the shake flask level on the 7th day. To achieve iterative genome editing in strain RT1389, CRISPR-assisted Cre recombination (CACR) method was established. Based on it, an EGT-overproducing strain RT1389-2 was constructed by integrating an additional copy of EGT biosynthetic core genes RtEGT1 and RtEGT2 into the genome, the EGT titer of which was 1.5-fold increase over RT1389. As the supply of S-adenosylmethionine was identified as a key factor determining EGT production in strain RT1389, subsequently, a series of gene modifications including S-adenosylmethionine rebalancing were integrated into the strain RT1389-2, and the resulting mutants were rapidly screened according to their EGT production titers with a high-throughput screening method based on ergothionase. As a result, an engineered strain named as RT1389-3 was selected with a production titer of 267.4 mg/L EGT after 168 h in a 50 mL modified fermentation medium.ConclusionsThis study characterized the EGT production capacity of these engineered strains, and demonstrated that CACR and high-throughput screening method allowed rapid engineering of R. toruloides mutants with improved EGT production. Furthermore, this study provided an engineered RT1389-3 strain with remarkable EGT production performance, which had potential industrial application prospects.

Eco-evolutionary dynamics of cooperative antimicrobial resistance in a population of fluctuating volume and size

Abstract Antimicrobial resistance to drugs (AMR), a global threat to human and animal health, is often regarded as resulting from a cooperative behaviour. Moreover, microbes generally evolve in volatile environments that, together with demographic fluctuations (birth and death events), drastically alter population size and strain survival. Motivated by the need to better understand the evolution of AMR, we study a population of time-varying size consisting of two competing strains, one drug-resistant and one drug-sensitive, subject to demographic and environmental variability. This is modelled by a binary carrying capacity randomly switching between mild and harsh environmental conditions, and driving the fluctuating volume (total amount of nutrients and antimicrobials at fixed concentration), and thus the size of the community (number of resistant and sensitive cells). We assume that AMR is a shared public good when the concentration of resistant cells exceeds a fixed {\it concentration cooperation threshold}, above which the sensitive strain has a growth advantage, whereas resistant cells dominate below it. Using computational means, and devising an analytical treatment (built on suitable quenched and annealed averaging procedures), we fully characterise the influence of fluctuations on the eco-evolutionary dynamics of AMR, and notably obtain specific strain fixation and long-lasting coexistence probabilities as a function of the environmental variation rate and cooperation threshold. We find that microbial strains tend to coexistence, but demographic fluctuations eventually lead to the extinction of resistant or sensitive cells for small or large values of the concentration cooperation threshold, respectively. This also holds for dynamic environments, whose specific properties determine the extinction timescale.