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The smart grid is a product of the advances in computer and communication technology and power electronics that creates a more resilient, reliable and one that supports a two-way flow of electricity and information. The smart grid enables more uptake of the variable renewables like wind, solar and variable loads like the plug-in cars and improves the efficiency of power systems and facilitate several products and services supported by the grid like automatic healing and re-routing of power in case of a fault and demand side management. The deployment and use of smart grids will enhance the realization of shared goals of grid stakeholders, promote energy security, enable economic growth, and help in the mitigation of climate change.

The Levelized Costs of Energy/Electricity (LCOE) is widely used to compare different power generation technologies by considering the various fixed and variable costs as a single cost metric. The levelized cost of electricity (LCOE) measures the average net present cost of generating electric power over the power plants entire life. As a metric, the levelized cost of energy does not capture all costs that affect the cost of electricity like the system costs. For accuracy of cost analysis, the LCOE is modified to account for other costs e.g., system levelized cost which considers externalities. The value-adjusted levelized cost of electricity (VALCOE) is a metric developed by the International Energy Agency (IEA) that captures the cost and value to the electricity system since the same amount of power may be less or more valuable during peak demand. The levelized cost of storage (LCOS) is another metric applied in comparing alternative energy storage systems for specific energy scenarios i.e. long-term, short-term, and medium-term storage. Another related metric is the Levelized avoided cost of energy (LACE) which n captures information about how the grid operates without the new power plant or storage facility entering service making it more complex than LCOE or LCOS, but more insightful. The value-adjusted levelized cost of electricity (VALCOE) captures both cost and value to the electricity system. Another metric, the Levelized Full System Costs of Electricity (LFSCOE), metric is used to analyze the costs incurred to supply the entire energy market with one power source plus storage presented as one value just like the levelized cost of energy (LCOE). Therefore, the levelized cost of energy (LCOE) metric is universally accepted as a tool for preliminary cost evaluations of generation technologies, but for accurate and reliable assessment, various modifications of the levelized cost of energy/electricity must be applied.

Diesel power plants use diesel engines as prime movers powered mainly by heavy fuel oil or industrial diesel oil and with potential for conversion to gas engines or dual fuel engines. The global concerns over prices of diesel and heavy fuel oil and energy related greenhouse gas emissions have created demand for natural gas as an alternative fuel for power generation by diesel power stations. This study involved a performance analysis of an operating diesel power plant and its potential conversion to dual fuel engine power plant. Dual fuel engines have reduced fuel costs and greenhouse gas emissions since natural gas is the cleanest fossil fuel. For a conventional diesel engine to run on diesel, the fuel injection system is modified to handle gas and a mixture of gas and diesel. Other modifications are the introduction of an electronic control unit, reduction in air fuel ratio, installation of a fuel mixer, and reduction of compression ratio. The conversion requires provision for natural gas storage facilities and supply system which were introduced in the proposed design modification. The study showed that dual fuel engine power plants have better performance indicators like lower specific fuel consumption, higher indicated and brake thermal efficiency, cheaper power produced, less emissions per unit power and thus reduced environmental impact. Conversion to dual fuel engines will reduce the cost of electricity generation, reduce emissions particularly Sulphur dioxide while accommodating fuel flexibility like use of biofuel to substitute diesel.

Biogas is a renewable energy resource that can play a leading role in the sustainable energy transition through green electricity generation. Biogas can be converted to electricity and renewable fuels through different technologies and prime movers. Prime movers that can be used for biogas power generation include gas and steam turbines, diesel engines, Otto cycle engines, Stirling engines as well as direct conversion in fuel cells. Since biogas has high octane rating, it can be used directly or with minimal modifications in spark ignition or petrol engines, but needs several modifications for use in dedicated diesel biogas engines or dual fuel engines and bi engines. The dual fuel mode which uses biomethane or biogas and diesel requires little or no engine modifications unlike the conversion to a dedicated gas engine. The performance of biogas prime movers is greatly enhanced if enriched biogas or biomethane is used in place of raw biogas. Other than use in various engines, biogas can be cleaned and used in fuel cells and manufacture of renewable hydrogen. As renewable natural gas, biogas in the form of biomethane can be injected to the natural gas grids for domestic and industrial application as natural gas substitute in applications which include power generation.

The Sugar industry faces several sustainability challenges due to dumping of excess global production which cause stiff competition for high cost sugar producers like Kenya. Through diversification into cogeneration and ethanol production, sugar companies in high cost producing countries can remain competitive and survive in the market. In this study, the technical and economic feasibility of ethanol production is done for the case of Nzoia Sugar Company in Kenya whose milling capacity is 3000 tons of cane per day (TCD). Molasses is taken through a series of stages starting with pretreatment, followed by fermentation and distillation to produce ethanol. The ethanol formed is then transferred to the distillation columns for fractionation to remove water and hence have ethanol rich product. Through further distillation and molecular sieve dehydration the purity and quality of the final ethanol product is enhanced. The main equipment for the process includes the fermenter, boilers, condensers, and distillation columns, design to suit the product characteristics and design capacity of the plant. The analysis showed that ethanol production by a 3000 TCD sugar factory is a profitable venture. The study showed that investment is both technically and economically feasible and will improve the financial performance and sustainability of the sugar factory in a competitive market environment. Therefore, diversification into ethanol production is an important strategy in sustaining the sugar industry in a competitive global market.

Kenyan sugar factories are facing challenges in the market from low cost sugar producers as a result of high cost of production. As a result, a number of factories have closed down while operating factories are struggling with cash flow problems. Diversification into both ethanol and export cogeneration is a promising solution to the challenges. In this study, the feasibility of export electricity generation for a Nzoia sugar factory in Western Kenya is undertaken. The 3000 tons of cane per day crushing capacity (TCD) factory has effective generation capacity of 2.8 MW for own internal consumption against installed capacity of 7 MW. The study showed that the factory can develop a continuous power plant of 15 megawatts (MW) but modernization of the factory is necessary to reduce steam consumption mainly by replacing steam turbine drives with electric drives, increase generation efficiency by use of a condensing extraction turbine. The three boilers which are over 30 years old should be replaced with more efficient modern boilers of steam pressure between 45–60 bars. A well negotiated power purchase agreement that captures the challenges facing the factory should then be signed with a utility company to avoid the challenges in implementation due to external factors.

Waste heat recovery systems convert the thermal energy in waste fluid streams into useful work. Diesel engine cogeneration systems are waste recovery systems using technologies and devices with main elements being the diesel engine prime movers, the electric generator, Rankine cycle steam turbine, exhaust heat recovery boiler super heaters, and control and instrumentation devices. Diesel engines exhaust significant recoverable heat energy that can be converted to extra electricity using a Rankine cycle plant. In this study, the cogeneration potential of an operating diesel engine power plant was established. The cogeneration potential of a 119.7 MW operating power plant in Kenya is established. The study showed that subject to limits imposed by presence of sulphur in fuel and hence existence of sulphur dioxide in the exhaust, each engine of capacity 17.1 MWe has recoverable thermal energy of about 1.33 MWth while the whole plant with seven engines is about 9.3 MWth for the 7 engines at plant optimum loading conditions which can generate 8.5 MWe extra electricity under optimum conditions. The study recommends the development of up to 9 MWe Rankine cycle steam turbine-based cogeneration power plant. Diesel power plant cogeneration is a technically and economically viable strategy to increase the generation efficiency of diesel power plants and reduce the pollution intensity and financial performance of the diesel power plant leading to reduction in cost of power and higher return on investment for investors.

PurposeTo investigate the trends, prevalence and distribution of ocular trauma in a Zimbabwean Tertiary Teaching Hospital (Parirenyatwa).MethodA hospital-based retrospective cross-sectional study was conducted at the Parirenyatwa Group of Hospitals, Sekuru Kaguvi Eye Department in Harare, Zimbabwe, to review medical records of patients with ocular trauma visiting for treatment at the outpatient department between January 2017 and December 2021. Information on patients' demographics, presenting visual acuity, type of ocular trauma, and the number of eyes affected were collected and analysed using descriptive and inferential statistics.ResultsA total of 863 patients (1007 eyes) were identified to have experienced ocular trauma of one kind or another, with the youth (18-35 years) reporting with most cases (331, 38.4%). About 71.2% of patients were classified as having open-globe injuries and of that number, 90% were caused by blunt trauma, while the rest were caused by penetrating, intraocular, and perforating injuries. Patients with open-globe injuries were about 10 times more likely to develop blindness than those with closed-globe injuries after adjusting for age and gender, and this was statistically significant (ARR = 9.65, 95% CI: 5.53-16.84, p < 0.001). The prevalence of distance vision impairment due to ocular trauma was 60.1% (95% CI: 56.8%-63.4%), with majority resulting in blindness (22.0%, 95% CI: 19.4%-24.9%).ConclusionThere is a high prevalence of open-globe injuries in Zimbabwe with blunt trauma being the most significant cause. This suggests the need to promote and intensify public eye health awareness and sensitisation on safety strategies for the prevention of ocular trauma throughout the country.

Plastics are cheap, lightweight, and durable and can be easily molded into many different products, shapes, and sizes, hence their wide applications globally, leading to increased production and use. Plastic consumption and production have been growing since its first production in the 1950s. About 4% of global oil and gas production is being used as feedstock for plastics, and 3–4% is used to provide energy for their manufacture. Plastics have a wide range of applications because they are versatile and relatively cheap. This study presents an in-depth analysis of plastic solid waste (PSW). Plastic wastes can be technically used for oil production because the calorific value of the plastics is quite comparable to that of oil, making this option an attractive alternative. Oil can be produced from plastic wastes via thermal degradation and catalytic degradation, while gasification can be used to produce syngas. Plastic pyrolysis can be used to address the twin problem of plastic waste disposal and depletion of fossil fuel reserves. The demand for plastics has continued to rise since their first production in the 1950s due to their multipurpose, lightness, inexpensiveness, and durable nature. There are four main avenues available for plastic solid waste treatment, namely, reextrusion as a primary treatment, mechanical treatment as secondary measures, chemical treatment as a tertiary measure, and energy recovery as a quaternary measure. The pyrolysis oil has properties that are close to clean fuel and is, therefore, a substitute to fresh fossil fuel for power generation, transport, and other applications. The study showed that plastic wastes pyrolysis offers an alternative avenue for plastic waste disposal and an alternative source of fossil fuel to reduce the total demand of virgin oil. Through plastic pyrolysis, plastic wastes are thermally converted to fuel by degrading long-chain polymers into small complex molecules in the absence of oxygen, making it a technically and economically feasible process for waste plastic recycling. The process is advantageous because presorting is not required, and the plastic waste can be directly fed without pretreatment prior to the process. Products of plastic pyrolysis are pyrolysis oil, a hydrocarbon-rich gas, with a heating value of 25–45 MJ/kg, which makes it ideal for process energy recovery. Hence, the pyrolysis gas can be fed back to the process to extract the energy for the process-heating purpose, which substantially reduces the reliance on external heating sources.

Sugar industries have huge potential to contribute to the sustainable energy transition through electricity generation and production of biofuels. Sugar-producing countries generate huge volumes of sugarcane bagasse as a byproduct of sugarcane production. In this study, the performance of an operating traditional sugar factory is analyzed for electricity generation and export potential. The study presents characteristics and energy potential of modern and traditional sugar factories. The challenges facing a traditional sugar mill are inefficient boilers, less efficient and back pressure steam turbines, and wasteful and inefficient use of steam turbine drives as prime movers instead of modern electric drives for the mills and cane knives. Others are the use of inefficient and energy intensive cane mill rollers instead of the diffusers which have low energy requirements. It was demonstrated that the cogeneration potential of sugar factory is quite significant but currently underutilized. Sugar factories can make significant contribution towards mitigation of greenhouse gas emission mitigation through supply of green electricity to the public grid. The study showed that the factory uses very old and inefficient boilers aged over 39 years which contributes to poor performance and low electricity generation capacity. Modernization is required to increase the generation and electricity export capacity through investment in new and modern high-pressure boilers, replacement of inefficient back pressure boilers (BPSB) with more efficient condensing extraction turbines (CEST), and reduction of factory steam consumption by electrification of mills and cane knife turbine drives among other measures. This study showed that the 3,000 TCD factory can invest in a 15 MW power plant based on current average factory performance indicators and more if the throughput and overall performance is close to design parameters.

Abstract The long gestation period, high upfront costs and the risks in the development of central geothermal power plants are the main reasons for the slow rate of geothermal electricity growth and its contribution to the global electricity mix. The overall objective of this study was to make a comparison between central geothermal power plants and wellhead power plants in the delivery of geothermal electricity projects. The study showed that wellhead power plants are generally less efficient compared to central power plants because of higher specific steam consumption, but are financially attractive because of the quicker return on investment, early electricity generation and the lower financial risks. The study showed that permanent wellhead power plants are a better option for geothermal wells with too low or too high steam pressure compared to others in the steam field. Temporary use of wellhead power plants as opposed to their permanent use is preferred when only limited time is available between the commissioning of a wellhead plant and the commissioning of a central power plant in the same steam field. Technical, operational and environmental challenges, including higher specific steam consumption and lower efficiency than central power plants as well as absence of geothermal fluid reinjection system make wellhead plants less economical and less sustainable in resource use. It can thus be concluded that wellhead power plants can reduce the long wait to generate geothermal electricity and make an early return on investment for investors. Both central and wellhead power plants have relatively higher capacity factor than many other power plants and so can be used to supply base load electricity for the grid or off-grid power supply. This study is a review of the central and wellhead power plants and additionally provides policy guidelines in the execution of geothermal electricity projects either as central or wellhead power plants for grid electricity generation.

The greatest sustainability challenge facing humanity today is the greenhouse gas emissions and the global climate change with fossil fuels led by coal, natural gas and oil contributing 61.3% of global electricity generation in the year 2020. The cumulative effect of the Stockholm, Rio, and Johannesburg conferences identified sustainable energy development (SED) as a very important factor in the sustainable global development. This study reviews energy transition strategies and proposes a roadmap for sustainable energy transition for sustainable electricity generation and supply in line with commitments of the Paris Agreement aimed at reducing greenhouse gas emissions and limiting the rise in global average temperature to 1.5°C above the preindustrial level. The sustainable transition strategies typically consist of three major technological changes namely, energy savings on the demand side, generation efficiency at production level and fossil fuel substitution by various renewable energy sources and low carbon nuclear. For the transition remain technically and economically feasible and beneficial, policy initiatives are necessary to steer the global electricity transition towards a sustainable energy and electricity system. Large-scale renewable energy adoption should include measures to improve efficiency of existing nonrenewable sources which still have an important cost reduction and stabilization role. A resilient grid with advanced energy storage for storage and absorption of variable renewables should also be part of the transition strategies. From this study, it was noted that whereas sustainable development has social, economic, and environmental pillars, energy sustainability is best analysed by five-dimensional approach consisting of environmental, economic, social, technical, and institutional/political sustainability to determine resource sustainability. The energy transition requires new technology for maximum use of the abundant but intermittent renewable sources a sustainable mix with limited nonrenewable sources optimized to minimize cost and environmental impact but maintained quality, stability, and flexibility of an electricity supply system. Technologies needed for the transition are those that use conventional mitigation, negative emissions technologies which capture and sequester carbon emissions and finally technologies which alter the global atmospheric radiative energy budget to stabilize and reduce global average temperature. A sustainable electricity system needs facilitating technology, policy, strategies and infrastructure like smart grids, and models with an appropriate mix of both renewable and low carbon energy sources.

Geothermal energy has a significant role to play in the global transition to renewable and low-carbon energy systems because of its ability to supply steady and flexible electricity particularly for baseload demand because of its cost competitiveness compared to fossil fuel energy options. However, geothermal faces a challenge of long project development times with conventional power plant taking an average of 5–10 years and with high risks associated with drilling of unproductive wells which discourage private investment and quick deployment. Although geothermal energy has a huge potential for power generation, it currently contributes less than 1% of global electricity generation capacity. The generation capacity grew from 8.7 GWe in 2005 to 15.61 GWe at the end of the year 2020, representing average annual growth of 4.01%. The overall objective of this study was to determine the potential, features and application of wellhead power plants in electricity generation both to complement and substitute central powerplants. It was established that wellhead power plants can be used on temporary basis during the project development or permanently as grid connected or off grid generation facilities. With current technology, wellhead generators of up to 15 MW capacity can be installed on well pads of production wells for temporary or permanent electricity supply. Wellhead generators can facilitate optimum resource utilization especially for wells with unique conditions like too high or too low pressure and temperature compared to others in the same steam. They are generally inferior to central power plants due to lack of economies of scale hence higher unit cost of power. Successful adoption of wellhead powerplants for faster electrifications calls for state support and incentives in terms of subsidies, development of electricity gid, attractive feed in tariffs and tax incentives without which they won't compete favorably against the conventional central powerplants. Generally, wellhead powerplants can make geothermal electricity projects more feasible with reduced barriers in investment and early electricity and revenue generation for investors. However, investment on temporary basis makes reasonable economic sense if the time between drilling the first productive well and completion of a central plant is more than one year. Incentives like high feed in tariffs and tax incentives may be necessary to make them competitive against the superior conventional powerplants.

Biogas is competitive, viable, and generally a sustainable energy resource due to abundant supply of cheap feedstocks and availability of a wide range of biogas applications in heating, power generation, fuel, and raw materials for further processing and production of sustainable chemicals including hydrogen, and carbon dioxide and biofuels. The capacity of biogas based power has been growing rapidly for the past decade with global biogas based electricity generation capacity increasing from 65 GW in 2010 to 120 GW in 2019 representing a 90% growth. This study presents the pathways for use of biogas in the energy transition by application in power generation and production of fuels. Diesel engines, petrol or gasoline engines, turbines, microturbines, and Stirling engines offer feasible options for biogas to electricity production as prme movers. Biogas fuel can be used in both spark ignition (petrol) and compression ignition engines (diesel) with varying degrees of modifications on conventional internal combustion engines. In internal combustion engines, the dual-fuel mode can be used with little or no modification compared to full engine conversion to gas engines which may require major modifications. Biogas can also be used in fuel cells for direct conversion to electricity and raw material for hydrogen and transport fuel production which is a significant pathway to sustainable energy development. Enriched biogas or biomethane can be containerized or injected to gas supply mains for use as renewable natural gas. Biogas can be used directly for cooking and lighting as well as for power generation and for production of Fischer-Tropsch (FT) fuels. Upgraded biogas/biomethane which can also be used to process methanol fuel. Compressed biogas (CBG) and liquid biogas (LBG) can be reversibly made from biomethane for various direct and indirect applications as fuels for transport and power generation. Biogas can be used in processes like combined heat and power generation from biogas (CHP), trigeneration, and compression to Bio-CNG and bio-LPG for cleaned biogas/biomethane. Fuels are manufactured from biogas by cleaning, and purification before reforming to syngas, and partial oxidation to produce methanol which can be used to make gasoline. Syngas is used in production of alcohols, jet fuels, diesel, and gasoline through the Fischer-Tropsch process.

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.

We introduce a 10-fs hyperspectral source architecture for facilitating nonlinear spectroscopy with multi-color sequences of arbitrarily shaped 10-fs UV/Vis, near-IR, and mid-IR pulses. Design principles and initial experimental results are provided.

Phosphorus fluoride exchange (PFEx) is a catalytic click reaction that involves exchanging high oxidation state P-F bonds with alcohol and amine nucleophiles, reliably yielding P-O- and P-N-linked compounds. Here, we describe steps for preparing a phosphoramidic difluoride and performing two sequential PFEx reactions to yield a phosphoramidate through careful catalyst selection. We then detail procedures for handling and quenching potentially toxic P-F-containing compounds to ensure user safety when conducting PFEx reactions. For complete details on the use and execution of this protocol, please refer to Sun et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Cold Spring Harbor Laboratory. Published by Elsevier Inc. All rights reserved.)

Accelerated SuFEx Click Chemistry (ASCC) is a powerful method for coupling aryl and alkyl alcohols with SuFEx-compatible functional groups. With its hallmark favorable kinetics and exceptional product yields, ASCC streamlines the synthetic workflow, simplifies the purification process, and is ideally suited for discovering functional molecules. We showcase the versatility and practicality of the ASCC reaction as a tool for the late-stage derivatization of bioactive molecules and in the array synthesis of sulfonate-linked, high-potency, microtubule targeting agents (MTAs) that exhibit nanomolar anticancer activity against multidrug-resistant cancer cell lines. These findings underscore ASCC's promise as a robust platform for drug discovery., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Phosphorus Fluoride Exchange (PFEx) represents a cutting-edge advancement in catalytic click-reaction technology. Drawing inspiration from Nature's phosphate connectors, PFEx facilitates the reliable coupling of P(V)-F loaded hubs with aryl alcohols, alkyl alcohols, and amines to produce stable, multidimensional P(V)-O and P(V)-N linked products. The rate of P-F exchange is significantly enhanced by Lewis amine base catalysis, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). PFEx substrates containing multiple P-F bonds are capable of selective, serial exchange reactions via judicious catalyst selection. In fewer than four synthetic steps, controlled projections can be deliberately incorporated along three of the four tetrahedral axes departing from the P(V) central hub, thus taking full advantage of the potential for generating three-dimensional diversity. Furthermore, late-stage functionalization of drugs and drug fragments can be achieved with the polyvalent PFEx hub, hexafluorocyclotriphosphazene (HFP), as has been demonstrated in prior research., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

The impact of click chemistry was recently recognized with the 2022 Nobel Prize in Chemistry. The breadth of areas where click chemistry has accelerated discovery is prodigal. In one of the most written about subjects in chemistry over recent years, this short perspective zones in on a small fragment of what we, the authors, consider are some of the most critical developments in synthetic chemistry, which have expanded access to the click chemistry toolbox. In addition, we touch upon areas within medicinal chemistry and novel approaches to drug discovery enabled by click chemistry, where we believe there is untapped potential for biological function to be found and exploited., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

We present the synthesis of 1,1-bis(fluorosulfonyl)-2-(pyridin-1-ium-1-yl)ethan-1-ide, a bench-stable precursor to ethene-1,1-disulfonyl difluoride (EDSF). The novel SuFEx reagent, EDSF, is demonstrated in the preparation of 26 unique 1,1-bissulfonylfluoride substituted cyclobutenes via a cycloaddition reaction. The regioselective click cycloaddition reaction is rapid, straightforward, and highly efficient, enabling the generation of highly functionalized 4-membered ring (4MR) carbocycles. These carbocycles are valuable structural motifs found in numerous bioactive natural products and pharmaceutically relevant small molecules. Additionally, we showcase diversification of the novel cyclobutene cores through selective Cs 2 CO 3 -activated SuFEx click chemistry between a single S-F group and an aryl alcohol, yielding the corresponding sulfonate ester products with high efficiency. Finally, density functional theory calculations offer mechanistic insights about the reaction pathway., (© 2023 Wiley-VCH GmbH.)

The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here, we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), as well as vancomycin-resistant S. aureus (VRSA). The shapeshifting modality of the dimers is powered by a triazole-linked bullvalene core, exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis. The new shapeshifting antibiotics are not disadvantaged by the common mechanism of vancomycin resistance resulting from the alteration of the C-terminal dipeptide with the corresponding d-Ala-d-Lac depsipeptide. Further, evidence suggests that the shapeshifting ligands destabilize the complex formed between the flippase MurJ and lipid II, implying the potential for a new mode of action for polyvalent glycopeptides. The SVDs show little propensity for acquired resistance by enterococci, suggesting that this new class of shapeshifting antibiotic will display durable antimicrobial activity not prone to rapidly acquired clinical resistance.

A concise semi-synthesis of the Aspidosperma alkaloids, (-)-jerantinine A and (-)-melodinine P, and derivatives thereof, is reported. The novel compounds were shown to have potent activity against MDA-MB-231 triple-negative breast cancer cells. Furthermore, unbiased metabolomics and live cell reporter assays reveal (-)-jerantinine A alters cellular redox metabolism and induces oxidative stress that coincides with cell cycle arrest., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Sulfur Fluoride Exchange (SuFEx) is a click reaction par excellence that has revolutionized multiple research fields. In this Primer, we delve into the essential elements of SuFEx operation, catalysis, and SuFExable connective hubs. We also explore the cutting-edge applications of SuFEx in drug development, polymer science, and biochemistry. Additionally, we examine the potential limitations and promising prospects for this versatile click reaction., Competing Interests: Competing interests Details of patents covering material related to the content of this Primer can be found in the supplementary information.

Diversity Oriented Clicking (DOC) is a discovery method geared toward the rapid synthesis of functional libraries. It combines the best attributes of both classical and modern click chemistries. DOC strategies center upon the chemical diversification of core "SuFExable" hubs-exemplified by 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs)-enabling the modular assembly of compounds through multiple reaction pathways. We report here a range of stereoselective Michael-type addition pathways from SASF hubs including reactions with secondary amines, carboxylates, 1 H -1,2,3-triazole, and halides. These high yielding conjugate addition pathways deliver unprecedented β-substituted alkenyl sulfonyl fluorides as single isomers with minimal purification, greatly enriching the repertoire of DOC and holding true to the fundamentals of modular click chemistry. Further, we demonstrate the potential for biological function - a key objective of click chemistry - of this family of SASF-derived molecules as covalent inhibitors of human neutrophil elastase.

SuFEx click chemistry is a powerful method designed for the selective, rapid, and modular synthesis of functional molecules. Classical SuFEx reactions form stable S-O linkages upon exchange of S-F bonds with aryl silyl-ether substrates, and while near-perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of accelerated SuFEx click chemistry (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2-tert-butyl-1,1,3,3-tetramethylguanidine; BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S-O bond linkages in a single step; often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol % and, in congruence with click-principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science., (© 2021 Wiley-VCH GmbH.)

The hydration of carbon-carbon triple bonds is an important and atom economic synthetic transformation. Herein, we report a mild and selective method for the catalytic Markovnikov hydration of (E)-aryl enynes to the corresponding enones, mediated through the bench-stable aminium salt, tris(4-bromophenyl)ammoniumyl hexachloroantimonate (TBPA). The chemoselective and diastereoselective method proceeds under neutral metal-free conditions, delivering excellent product yields from terminal and internal alkyne units. The synthesis of biologically important (E)-3-styrylisocoumarins, including a formal synthesis of the natural product achlisocoumarin III, demonstrates the utility of this novel transformation.

Diversity Oriented Clicking (DOC) is a unified click-approach for the modular synthesis of lead-like structures through application of the wide family of click transformations. DOC evolved from the concept of achieving "diversity with ease", by combining classic C-C π-bond click chemistry with recent developments in connective SuFEx-technologies. We showcase 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click-cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click-library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3- and 1,5-dipoles; while reaction with cyclic dienes yields several three-dimensional bicyclic Diels-Alder adducts. Growing the library to 278 discrete compounds through late-stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well-plates-demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The boom in growth of 1,4-disubstituted triazole products, in particular, since the early 2000's, can be largely attributed to the birth of click chemistry and the discovery of the Cu I -catalyzed azide-alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1-substituted-1,2,3-triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click-inspired protocol for the synthesis of 1-substituted-1,2,3-triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal-free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1-substituted-1,2,3-triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1-substituted triazolium sulfonyl fluoride salts., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sulfur fluoride exchange (SuFEx) has emerged as the new generation of click chemistry. We report here a SuFEx-enabled, agnostic approach for the discovery and optimization of covalent inhibitors of human neutrophil elastase (hNE). Evaluation of our ever-growing collection of SuFExable compounds toward various biological assays unexpectedly revealed a selective and covalent hNE inhibitor: benzene-1,2-disulfonyl fluoride. Synthetic derivatization of the initial hit led to a more potent agent, 2-(fluorosulfonyl)phenyl fluorosulfate with IC 50 0.24 μM and greater than 833-fold selectivity over the homologous neutrophil serine protease, cathepsin G. The optimized, yet simple benzenoid probe only modified active hNE and not its denatured form., Competing Interests: The authors declare no conflict of interest.

SuFEx (Sulfur Fluoride Exchange) is a modular, next generation family of click reactions, geared towards the rapid and reliable assembly of functional molecules. This review discusses the growing number of applications of SuFEx, which can be found in nearly all areas of modern chemistry; from drug discovery to materials science.

We report here the development of a suite of biocompatible SuFEx transformations from the SOF 4 -derived iminosulfur oxydifluoride hub in aqueous buffer conditions. These biocompatible SuFEx reactions of iminosulfur oxydifluorides (R-N=SOF 2 ) with primary amines give sulfamides (8 examples, up to 98 %), while the reaction with secondary amines furnish sulfuramidimidoyl fluoride products (8 examples, up to 97 %). Likewise, under mild buffered conditions, phenols react with the iminosulfur oxydifluorides (Ar-N=SOF 2 ) to produce sulfurofluoridoimidates (13 examples, up to 99 %), which can themselves be further modified by nucleophiles. These transformations open the potential for asymmetric and trisubstituted linkages projecting from the sulfur(VI) center, including versatile S-N and S-O connectivity (9 examples, up to 94 %). Finally, the SuFEx bioconjugation of iminosulfur oxydifluorides to amine-tagged single-stranded DNA and to BSA protein demonstrate the potential of SOF 4 -derived SuFEx click chemistry in biological applications., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

SuFEx is a new-generation click chemistry transformation that exploits the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx-based procedure for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new process involves rapid S-F exchange with trifluoromethyltrimethylsilane (TMSCF 3 ) upon activation by potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative mechanism is proposed involving nucleophilic displacement of S-F by the trifluoromethyl anion via a five-coordinate intermediate. The utility of late-stage SuFEx trifluoromethylation is demonstrated through the synthesis and selective anticancer properties of a bis(trifluoromethyl)sulfur oxyimine., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Technologies that enable surface modification are in high demand and are critical for the implementation of new functional materials and devices. Here, we describe the first modification of a carbon surface (in this case carbon fiber) using the sulfur-fluoride exchange (SuFEx) reaction. The parent sulfur (VI) fluoride moiety can be installed directly to the surface via electrochemical deposition of the fluorosulfate phenyldiazonium tetrafluoroborate salt, or by 'SuFExing' a phenol on the carbon surface followed by treatment of the material with SO 2 F 2 ; similar to a 'graft to' or 'graft from' functionalization approach. We demonstrate that these SuFEx-able surfaces readily undergo exchange with aryl silyl ethers, and that the subsequent sulfate linkages are themselves stable under electrochemical redox conditions. Finally, we showcase the utility of the SuFEx chemistry by installing a pendant amino group to the fiber surface resulting in interfacial shear strength improvements of up to 130 % in epoxy resin., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The constraints of minute reactant amounts and the impossibility to remove any undesired surface-bound products during monolayer functionalization of a surface necessitate the selection of efficient, modular and orthogonal reactions that lead to quantitative conversions. Herein, we explore the character of sulfur-fluoride exchange (SuFEx) reactions on a surface, and explore the applicability for quantitative and orthogonal surface functionalization. To this end, we demonstrate the use of ethenesulfonyl fluoride (ESF) as an efficient SuFEx linker for creating "SuFEx-able" monolayer surfaces, enabling three distinct approaches to utilize SuFEx chemistry on a surface. The first approach relies on a di-SuFEx loading allowing dual functionalization with a nucleophile, while the two latter approaches focus on dual (CuAAC-SuFEx/SPOCQ-SuFEx) click platforms. The resultant strategies allow facile attachment of two different substrates sequentially on the same platform. Along the way we also demonstrate the Michael addition of ethenesulfonyl fluoride to be a quantitative surface-bound reaction, indicating significant promise in materials science for this reaction., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

A convenient method for the synthesis of 1,2,4-triazol-3-imines through a selective, formal, 1,3-dipolar cycloaddition of organo-cyanamide ions with nitrile imine dipoles is reported. Hydrolysis of the 1,2,4-triazol-3-imines yields the corresponding 1,2,4-triazol-5-ones. A stepwise mechanism, supported by DFT calculations, is invoked to explain the reaction selectivity.

The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.

We demonstrate 1,2-dibromoethane-1-sulfonyl fluoride (DESF) as a bench-stable and readily accessible precursor to the robust SuFEx connector, 1-bromoethene-1-sulfonyl fluoride (BESF). The in situ generation of BESF from DESF opens up several new reaction profiles, including application in the syntheses of unprecedented 3-substituted isoxazole-5-sulfonyl fluorides, 1-substituted-1H-1,2,3-triazole-4-sulfonyl fluorides, 2-amino-1-bromoethane-1-sulfonyl fluorides and 4-bromo-β-sultams in good to excellent yields. These new modules comprise a pendant sulfonyl fluoride handle, which further undergoes facile and selective SuFEx reactions with a selection of aryl silyl ethers to generate stable and useful sulfonate connections.

Modular polyketide synthases (PKSs) produce numerous structurally complex natural products that have diverse applications in medicine and agriculture. PKSs typically consist of several multienzyme subunits that utilize structurally defined docking domains (DDs) at their N and C termini to ensure correct assembly into functional multiprotein complexes. Here we report a fundamentally different mechanism for subunit assembly in trans-acyltransferase (trans-AT) modular PKSs at the junction between ketosynthase (KS) and dehydratase (DH) domains. This mechanism involves direct interaction of a largely unstructured docking domain (DD) at the C terminus of the KS with the surface of the downstream DH. Acyl transfer assays and mechanism-based crosslinking established that the DD is required for the KS to communicate with the acyl carrier protein appended to the DH. Two distinct regions for binding of the DD to the DH were identified using NMR spectroscopy, carbene footprinting, and mutagenesis, providing a foundation for future elucidation of the molecular basis for interaction specificity.

Thionyl tetrafluoride (SOF 4 ) is a valuable connective gas for sulfur fluoride exchange (SuFEx) click chemistry that enables multidimensional linkages to be created via sulfur-oxygen and sulfur-nitrogen bonds. Herein, we expand the available SuFEx chemistry of SOF 4 to include organolithium nucleophiles, and demonstrate, for the first time, the controlled projection of sulfur-carbon links at the sulfur center of SOF 4 -derived iminosulfur oxydifluorides (R 1 -N=SOF 2 ). This method provides rapid and modular access to sulfonimidoyl fluorides (R 1 -N=SOFR 2 ), another array of versatile SuFEx connectors with readily tunable reactivity of the S-F handle. Divergent connections derived from these valuable sulfonimidoyl fluoride units are also demonstrated, including the synthesis of sulfoximines, sulfonimidamides, and sulfonimidates., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mapping the interaction sites between membrane-spanning proteins is a key challenge in structural biology. In this study a carbene-footprinting approach was developed and applied to identify the interfacial sites of a trimeric, integral membrane protein, OmpF, solubilised in micelles. The diazirine-based footprinting probe is effectively sequestered by, and incorporated into, the micelles, thus leading to efficient labelling of the membrane-spanning regions of the protein upon irradiation at 349 nm. Areas associated with protein-protein interactions between the trimer subunits remained unlabelled, thus revealing their location., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and pharmaceutically important drugs. We report here the development of "SuFExAmide": a new sulfur-fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene-1,3-disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron-deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sulfur(VI) fluoride exchange (SuFEx) is a new family of click chemistry based transformations that enable the synthesis of covalently linked modules via S VI hubs. Here we report thionyl tetrafluoride (SOF 4 ) as the first multidimensional SuFEx connector. SOF 4 sits between the commercially mass-produced gases SF 6 and SO 2 F 2 , and like them, is readily synthesized on scale. Under SuFEx catalysis conditions, SOF 4 reliably seeks out primary amino groups [R-NH 2 ] and becomes permanently anchored via a tetrahedral iminosulfur(VI) link: R-N=(O=)S(F) 2 . The pendant, prochiral difluoride groups R-N=(O=)SF 2 , in turn, offer two further SuFExable handles, which can be sequentially exchanged to create 3-dimensional covalent departure vectors from the tetrahedral sulfur(VI) hub., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vancomycin has long been considered a drug of last resort. Its efficiency in treating multiple drug-resistant bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), has had a profound effect on the treatment of life-threatening infections. However, the emergence of resistance to vancomycin is a cause for significant worldwide concern, prompting the urgent development of new effective treatments for antibiotic resistant bacterial infections. Harnessing the benefits of multivalency and cooperativity against vancomycin-resistant strains, we report a Click Chemistry approach towards reengineered vancomycin derivatives and the synthesis of a number of dimers with increased potency against MRSA and vancomycin resistant Enterococci (VRE; VanB). These semi-synthetic dimeric ligands were linked together with great efficiency using the powerful CuAAC reaction, demonstrating high levels of selectivity and purity., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Correction for 'The growing applications of click chemistry' by John E. Moses et al., Chem. Soc. Rev., 2007, 36, 1249-1262.

Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.

Natural products with anti-cancer activity play a vital role in lead and target discovery. We report here the synthesis and biological evaluation of the plant-derived alkaloid, piperlongumine and analogues. Using a Horner-Wadsworth-Emmons coupling approach, a selection of piperlongumine-like compounds were prepared in good overall yield from a novel phosphonoacetamide reagent. A number of the compounds displayed potent anti-cancer activity against colorectal (HCT 116) and ovarian (IGROV-1) carcinoma cell lines, via a mechanism of action which may involve ROS generation. Contrary to previous reports, no selective action in cancer cell (MRC-5) was observed for piperlongumine analogues.