Artificial metalloenzymes are created by incorporating an organometallic catalyst within a host protein. The resulting hybrid can thus provide access to the best features of two distinct, and often ...complementary, systems: homogeneous and enzymatic catalysts. The coenzyme may be positioned with covalent, dative, or supramolecular anchoring strategies. Although initial reports date to the late 1970s, artificial metalloenzymes for enantioselective catalysis have gained significant momentum only in the past decade, with the aim of complementing homogeneous, enzymatic, heterogeneous, and organic catalysts. Inspired by a visionary report by Wilson and Whitesides in 1978, we have exploited the potential of biotin−avidin technology in creating artificial metalloenzymes. Owing to the remarkable affinity of biotin for either avidin or streptavidin, covalent linking of a biotin anchor to a catalyst precursor ensures that, upon stoichiometric addition of (strept)avidin, the metal moiety is quantitatively incorporated within the host protein. In this Account, we review our progress in preparing and optimizing these artificial metalloenzymes, beginning with catalytic hydrogenation as a model and expanding from there. These artificial metalloenzymes can be optimized by both chemical (variation of the biotin−spacer−ligand moiety) and genetic (mutation of avidin or streptavidin) means. Such chemogenetic optimization schemes were applied to various enantioselective transformations. The reactions implemented thus far include the following: (i) The rhodium-diphosphine catalyzed hydrogenation of N-protected dehydroaminoacids (ee up to 95%); (ii) the palladium-diphosphine catalyzed allylic alkylation of 1,3-diphenylallylacetate (ee up to 95%); (iii) the ruthenium pianostool-catalyzed transfer hydrogenation of prochiral ketones (ee up to 97% for aryl-alkyl ketones and ee up to 90% for dialkyl ketones); (iv) the vanadyl-catalyzed oxidation of prochiral sulfides (ee up to 93%). A number of noteworthy features are reminiscent of homogeneous catalysis, including straightforward access to both enantiomers of the product, the broad substrate scope, organic solvent tolerance, and an accessible range of reactions that are typical of homogeneous catalysts. Enzyme-like features include access to genetic optimization, an aqueous medium as the preferred solvent, Michaelis−Menten behavior, and single-substrate derivatization. The X-ray characterization of artificial metalloenzymes provides fascinating insight into possible enantioselection mechanisms involving a well-defined second coordination sphere environment. Thus, such artificial metalloenzymes combine attractive features of both homogeneous and enzymatic kingdoms. In the spirit of surface borrowing, that is, modulating ligand affinity by harnessing existing protein surfaces, this strategy can be extended to selectively binding streptavidin-incorporated biotinylated ruthenium pianostool complexes to telomeric DNA. This application paves the way for chemical biology applications of artificial metalloenzymes.
During the early part of 2020, there has been an abundance of critically important research on Covid-19 from medical, epidemiological and virological disciplines. There is now an urgent need for ...sociologists to engage theoretically and empirically on the social impact of issues related to Covid-19. As we have moved further into 2020, governments around the world have imposed different types of restrictions on social life, in order to quell the spread of Covid-19 and 'flatten the curve'. These have included imposing various degrees of social isolation and restrictions on things like social gatherings, travel, sport and leisure activities, and going to work/school/ university. This commentary explores the ways in which different branches of social theory can shed light on the implications of Covid-19 restrictions for social life 'as we know it'. The broad fields of social theory in the commentary cover concepts such as risk, trust, fear, uncertainty and happiness. The process of developing the social theory driven research agenda contained within this commentary took a rather unusual route - it started by re-reading Jean-Paul Sartre's ideas on existentialism, which led to me painting a visual sociology of Covid-19 (an image of my painting is provided), and ultimately to this piece.
Summary
Objective
The objective of this study is to compare the effects of high‐intensity interval training (HIIT) and moderate‐intensity continuous training (MICT) for improvements in body ...composition in overweight and obese adults.
Methods
Trials comparing HIIT and MICT in overweight or obese participants aged 18–45 years were included. Direct measures (e.g. whole‐body fat mass) and indirect measures (e.g. waist circumference) were examined.
Results
From 1,334 articles initially screened, 13 were included. Studies averaged 10 weeks × 3 sessions per week training. Both HIIT and MICT elicited significant (p < 0.05) reductions in whole‐body fat mass and waist circumference. There were no significant differences between HIIT and MICT for any body composition measure, but HIIT required ~40% less training time commitment. Running training displayed large effects on whole‐body fat mass for both HIIT and MICT (standardized mean difference −0.82 and −0.85, respectively), but cycling training did not induce fat loss.
Conclusions
Short‐term moderate‐intensity to high‐intensity exercise training can induce modest body composition improvements in overweight and obese individuals without accompanying body‐weight changes. HIIT and MICT show similar effectiveness across all body composition measures suggesting that HIIT may be a time‐efficient component of weight management programs.
The biotin–streptavidin technology offers an attractive means to engineer artificial metalloenzymes (ArMs). Initiated over 50 years ago by Bayer and Wilchek, the biotin–(strept)avidin techonology ...relies on the exquisite supramolecular affinity of either avidin or streptavidin for biotin. This versatile tool, commonly referred to as “molecular velcro”, allows nearly irreversible anchoring of biotinylated probes within a (strept)avidin host protein. Building upon a visionary publication by Whitesides from 1978, several groups have been exploiting this technology to create artificial metalloenzymes. For this purpose, a biotinylated organometallic catalyst is introduced within (strept)avidin to afford a hybrid catalyst that combines features reminiscent of both enzymes and organometallic catalysts. Importantly, ArMs can be optimized by chemogenetic means. Combining a small collection of biotinylated organometallic catalysts with streptavidin mutants allows generation of significant diversity, thus allowing optimization of the catalytic performance of ArMs. Pursuing this strategy, the following reactions have been implemented: hydrogenation, alcohol oxidation, sulfoxidation, dihydroxylation, allylic alkylation, transfer hydrogenation, Suzuki cross-coupling, C–H activation, and metathesis. In this Account, we summarize our efforts in the latter four reactions. X-ray analysis of various ArMs based on the biotin–streptavidin technology reveals the versatility and commensurability of the biotin-binding vestibule to accommodate and interact with transition states of the scrutinized organometallic transformations. In particular, streptavidin residues at positions 112 and 121 recurrently lie in close proximity to the biotinylated metal cofactor. This observation led us to develop a streamlined 24-well plate streptavidin production and screening platform to optimize the performance of ArMs. To date, most of the efforts in the field of ArMs have focused on the use of purified protein samples. This seriously limits the throughput of the optimization process. With the ultimate goal of complementing natural enzymes in the context of synthetic and chemical biology, we outline the milestones required to ultimately implement ArMs within a cellular environment. Indeed, we believe that ArMs may allow signficant expansion of the natural enzymes’ toolbox to access new-to-nature reactivities in vivo. With this ambitious goal in mind, we report on our efforts to (i) activate the biotinylated catalyst precursor upon incorporation within streptavidin, (ii) minimize the effect of the cellular environment on the ArM’s performance, and (iii) demonstrate the compatibility of ArMs with natural enzymes in cascade reactions.
Palladium-catalyzed cross-coupling reactions have emerged as one of the most versatile tools in organic chemistry. Extensive efforts were made to adapt these reactions to aqueous media, not only for ...the purpose of environmental conservation but also to expand the scope, increase the efficiency and implement bio-compatible protocols. Among different palladium cross-coupling reactions, the Heck reaction turned out to be the most challenging in an aqueous environment. This led to various original developments in catalyst design. This review summarizes the different approaches pursued to perform Heck reactions in neat water as well as aqueous mixtures. Both, homogeneous and immobilized catalysts, including nanoparticles are presented herein.
Graphical Abstract
The palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of organic halides with boronic acids is one of the most versatile methods for the synthesis of biaryls. Green chemistry is a rapidly ...developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. When designed properly, clean chemical technology can be developed in water as a reaction medium. The technologies generated from such green chemistry endeavours may often be cheaper and more profitable. This review covers the literature on palladium-catalysed the Suzuki–Miyaura cross-coupling reaction in water.
Graphical Abstract
Emerging organic contaminants (EOCs) detected in groundwater may have adverse effects on human health and aquatic ecosystems. This paper reviews the existing occurrence data in groundwater for a ...range of EOCs including pharmaceutical, personal care, ‘life-style’ and selected industrial compounds. The main sources and pathways for organic EOCs in groundwater are reviewed, with occurrence data for EOCs in groundwater included from both targeted studies and broad reconnaissance surveys. Nanogram-microgram per litre concentrations are present in groundwater for a large range of EOCs as well as metabolites and transformation products and under certain conditions may pose a threat to freshwater bodies for decades due to relatively long groundwater residence times. In the coming decades, more of these EOCs are likely to have drinking water standards, environmental quality standards and/or groundwater threshold values defined, and therefore a better understanding of the spatial and temporal variation remains a priority.
► First review to focus on EOCs in groundwater. ► A large range (n>180) of EOCs are detected in groundwater. ► Significant concentrations (102–104ng/L) for a range of EOCs, including endocrine disruptors. ► Groundwater EOC occurrence is poorly characterised compared to other freshwater resources.
A large range of emerging organic contaminants are now being detected in groundwater as a result of recent and historical anthropogenic activities.
Hydrogen technologies have experienced cycles of excessive expectations followed by disillusion. Nonetheless, a growing body of evidence suggests these technologies form an attractive option for the ...deep decarbonisation of global energy systems, and that recent improvements in their cost and performance point towards economic viability as well. This paper is a comprehensive review of the potential role that hydrogen could play in the provision of electricity, heat, industry, transport and energy storage in a low-carbon energy system, and an assessment of the status of hydrogen in being able to fulfil that potential. The picture that emerges is one of qualified promise: hydrogen is well established in certain niches such as forklift trucks, while mainstream applications are now forthcoming. Hydrogen vehicles are available commercially in several countries, and 225 000 fuel cell home heating systems have been sold. This represents a step change from the situation of only five years ago. This review shows that challenges around cost and performance remain, and considerable improvements are still required for hydrogen to become truly competitive. But such competitiveness in the medium-term future no longer seems an unrealistic prospect, which fully justifies the growing interest and policy support for these technologies around the world.
Hydrogen has been 'just around the corner' for decades, but now offers serious alternatives for decarbonising global heat, power and transport.
Compressed sensing (CS) decoding algorithms can efficiently recover an N -dimensional real-valued vector x to within a factor of its best k-term approximation by taking m = O(klogN/k) measurements y ...= Phi x . If the sparsity or approximate sparsity level of x were known, then this theoretical guarantee would imply quality assurance of the resulting CS estimate. However, because the underlying sparsity of the signal x is unknown, the quality of a CS estimate \mathhat x using m measurements is not assured. It is nevertheless shown in this paper that sharp bounds on the error ||x - \mathhat x ||lN2 can be achieved with almost no effort. More precisely, suppose that a maximum number of measurements m is preimposed. One can reserve 10 log p of these m measurements and compute a sequence of possible estimates (\mathhat xj)j=1p to x from the m -10logp remaining measurements; the errors ||x - \mathhat xj ||lN2 for j = 1, ..., p can then be bounded with high probability. As a consequence, numerical upper and lower bounds on the error between x and the best k-term approximation to x can be estimated for p values of k with almost no cost. This observation has applications outside CS as well.
Now that it is possible to achieve measurement and control fidelities for individual quantum bits (qubits) above the threshold for fault tolerance, attention is moving towards the difficult task of ...scaling up the number of physical qubits to the large numbers that are needed for fault-tolerant quantum computing. In this context, quantum-dot-based spin qubits could have substantial advantages over other types of qubit owing to their potential for all-electrical operation and ability to be integrated at high density onto an industrial platform. Initialization, readout and single- and two-qubit gates have been demonstrated in various quantum-dot-based qubit representations. However, as seen with small-scale demonstrations of quantum computers using other types of qubit, combining these elements leads to challenges related to qubit crosstalk, state leakage, calibration and control hardware. Here we overcome these challenges by using carefully designed control techniques to demonstrate a programmable two-qubit quantum processor in a silicon device that can perform the Deutsch-Josza algorithm and the Grover search algorithm-canonical examples of quantum algorithms that outperform their classical analogues. We characterize the entanglement in our processor by using quantum-state tomography of Bell states, measuring state fidelities of 85-89 per cent and concurrences of 73-82 per cent. These results pave the way for larger-scale quantum computers that use spins confined to quantum dots.
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