The electrophilic aromatic substitution of a C–H bond of benzene is one of the archetypal transformations of organic chemistry. In contrast, the electron-rich π-system of benzene is highly resistant ...to reactions with electron-rich and negatively charged organic nucleophiles. Here, we report that this previously insurmountable electronic repulsion may be overcome through the use of sufficiently potent organocalcium nucleophiles. Calcium n-alkyl derivatives—synthesized by reaction of ethene, but-1-ene, and hex-1-ene with a dimeric calcium hydride—react with protio and deutero benzene at 60°C through nucleophilic substitution of an aromatic C–D/H bond. These reactions produce the n-alkyl benzenes with regeneration of the calcium hydride. Density functional theory calculations implicate an unstabilized Meisenheimer complex in the C–H activation transition state.
Although many cellular processes depend upon enzymatic reactions, protein-protein interactions (PPIs) mediate a large number of important regulatory pathways and thus play a central role in disease ...development. In order to understand and selectively inhibit cellular signalling pathways, there is a pressing need for small molecules that target PPIs, particularly in the context of pharmaceutical development. This tutorial review will introduce the relevance of PPIs to chemical biology and highlight the key challenges in designing inhibitors. Some of the successes using conventional approaches to the identification of small-molecule PPI inhibitors will be highlighted, and also the reasons why these approaches have not always proven successful. Several general approaches tailored to particular protein topologies are emerging for the design of scaffolds that inhibit PPIs-these will form the major content of this review. Finally a summary of the challenges to be faced in developing inhibitors of PPIs into drug leads and how these challenges may differ from those encountered with enzyme-like targets will be given.
A Stable Calcium Alumanyl Schwamm, Ryan J.; Coles, Martyn P.; Hill, Michael S. ...
Angewandte Chemie,
March 2, 2020, Volume:
59, Issue:
10
Journal Article
Peer reviewed
Open access
A seven‐membered N,N′‐heterocyclic potassium alumanyl nucleophile is introduced and utilised in the metathetical synthesis of Mg−Al and Ca−Al bonded derivatives. Both species have been characterised ...by experimental and theoretical means, allowing a rationalisation of the greater reactivity of the heavier group 2 species implied by an initial assay of their reactivity.
AlCan Wrap: The Reaction of a seven‐membered cyclic alumanyl anion with a β‐diketiminato calcium tetraphenylborate provides facile access to a stable, but highly reactive, calcium alumanyl.
Artificial photosynthesis relies on the availability of synthetic photocatalysts that can drive CO2 reduction in the presence of water and light. From the standpoint of solar fuel production, it is ...desirable that these photocatalysts perform under visible light and produce energy-rich hydrocarbons from CO2 reduction. However, the multistep nature of CO2-to-hydrocarbon conversion poses a significant kinetic bottleneck when compared to CO production and H2 evolution. Here, we show that plasmonic Au nanoparticle photocatalysts can harvest visible light for multielectron, multiproton reduction of CO2 to yield C1 (methane) and C2 (ethane) hydrocarbons. The light-excitation attributes influence the C2 and C1 selectivity. The observed trends in activity and selectivity follow Poisson statistics of electron harvesting. Higher photon energies and flux favor simultaneous harvesting of more than one electron from the photocharged Au nanoparticle catalyst, inducing the C–C coupling required for C2 production. These findings elucidate the nature of plasmonic photocatalysis, which involves strong light-matter coupling, and set the stage for the controlled chemical bond formation by light excitation.
Molecular Main Group Metal Hydrides Roy, Matthew M D; Omaña, Alvaro A; Wilson, Andrew S S ...
Chemical reviews,
10/2021, Volume:
121, Issue:
20
Journal Article
Peer reviewed
This review serves to document advances in the synthesis, versatile bonding, and reactivity of molecular main group metal hydrides within Groups 1, 2, and 12-16. Particular attention will be given to ...the emerging use of said hydrides in the rapidly expanding field of Main Group element-mediated catalysis. While this review is comprehensive in nature, focus will be given to research appearing in the open literature since 2001.
Dehydrocoupling reactions between the boranes HBpin and 9‐borabicyclo3.3.1nonane and a range of amines and anilines ensue under very mild reaction conditions in the presence of a simple ...β‐diketiminato magnesium n‐butyl precatalyst. The facility of the reactions is suggested to be a function of the Lewis acidity of the borane substrate, and is dictated by resultant pre‐equilibria between, and the relative stability of, magnesium hydride and borohydride intermediates during the course of the catalysis.
BoNd‐forming catalysis: Dehydrocoupling reactions between the boranes HBpin and 9‐borabicyclo3.3.1nonane, and a range of amines and anilines ensue under very mild reaction conditions in the presence of a simple β‐diketiminato magnesium n‐butyl precatalyst. The reaction is facilitated by the Lewis acidity of the borane substrate, and is dictated by resultant pre‐equilibria between magnesium hydride and borohydride.
The most exciting hypothesis in cognitive science right now is the theory that cognition is embodied. Like all good ideas in cognitive science, however, embodiment immediately came to mean six ...different things. The most common definitions involve the straight-forward claim that "states of the body modify states of the mind." However, the implications of embodiment are actually much more radical than this. If cognition can span the brain, body, and the environment, then the "states of mind" of disembodied cognitive science won't exist to be modified. Cognition will instead be an extended system assembled from a broad array of resources. Taking embodiment seriously therefore requires both new methods and theory. Here we outline four key steps that research programs should follow in order to fully engage with the implications of embodiment. The first step is to conduct a task analysis, which characterizes from a first person perspective the specific task that a perceiving-acting cognitive agent is faced with. The second step is to identify the task-relevant resources the agent has access to in order to solve the task. These resources can span brain, body, and environment. The third step is to identify how the agent can assemble these resources into a system capable of solving the problem at hand. The last step is to test the agent's performance to confirm that agent is actually using the solution identified in step 3. We explore these steps in more detail with reference to two useful examples (the outfielder problem and the A-not-B error), and introduce how to apply this analysis to the thorny question of language use. Embodied cognition is more than we think it is, and we have the tools we need to realize its full potential.
β‐Diketiminato (BDI) calcium alkyl derivatives undergo hydrogenolysis with H2 to regenerate (BDI)CaH2, allowing the catalytic hydrogenation of a wide range of 1‐alkenes and norbornene under very mild ...conditions (2 bar H2, 298 K). The reactions are deduced to take place with the retention of the dimeric structures of the calcium hydrido‐alkyl and alkyl intermediates via a well‐defined sequence of Ca−H/C=C insertion and Ca−C hydrogenation events. This latter deduction is strongly supported by DFT calculations (B3PW91) performed on the 1‐hexene/H2 system, which also indicates that the hydrogenation transition states display features which discriminate them from a classical σ‐bond metathesis mechanism. In particular, NBO analysis identifies a strong second order interaction between the filled α‐methylene sp3 orbital of the n‐hexyl chain and the σ* orbital of the H2 molecule, signifying that the H−H bond is broken by what is effectively the nucleophilic displacement of hydride by the organic substituent.
Hydrogen gets nuked: Hydrogenation of dimeric β‐diketiminato calcium alkyls occurs by nucleophilic attack and heterolysis of the H−H bond.
Super-Resolution Imaging and Plasmonics Willets, Katherine A; Wilson, Andrew J; Sundaresan, Vignesh ...
Chemical reviews,
06/2017, Volume:
117, Issue:
11
Journal Article
Peer reviewed
This review describes the growing partnership between super-resolution imaging and plasmonics, by describing the various ways in which the two topics mutually benefit one another to enhance our ...understanding of the nanoscale world. First, localization-based super-resolution imaging strategies, where molecules are modulated between emissive and nonemissive states and their emission localized, are applied to plasmonic nanoparticle substrates, revealing the hidden shape of the nanoparticles while also mapping local electromagnetic field enhancements and reactivity patterns on their surface. However, these results must be interpreted carefully due to localization errors induced by the interaction between metallic substrates and single fluorophores. Second, plasmonic nanoparticles are explored as image contrast agents for both superlocalization and super-resolution imaging, offering benefits such as high photostability, large signal-to-noise, and distance-dependent spectral features but presenting challenges for localizing individual nanoparticles within a diffraction-limited spot. Finally, the use of plasmon-tailored excitation fields to achieve subdiffraction-limited spatial resolution is discussed, using localized surface plasmons and surface plasmon polaritons to create confined excitation volumes or image magnification to enhance spatial resolution.
Conspectus Plasmonic nanostructures have garnered widescale scientific interest because of their strong light–matter interactions and the tunability of their absorption across the solar spectrum. At ...the heart of their superlative interaction with light is the resonant excitation of a collective oscillation of electrons in the nanostructure by the incident electromagnetic field. These resonant oscillations are known as localized surface plasmon resonances (LSPRs). In recent years, the community has uncovered intriguing photochemical attributes of noble metal nanostructures arising from their LSPRs. Chemical reactions that are otherwise unfavorable or sluggish in the dark are induced on the nanostructure surface upon photoexcitation of LSPRs. This phenomenon has led to the birth of plasmonic catalysis. The rates of a variety of kinetically challenging reactions are enhanced by plasmon-excited nanostructures. While the potential utility for solar energy harvesting and chemical production is clear, there is a natural curiosity about the precise origin(s) of plasmonic catalysis. One explanation is that the reactions are facilitated by the action of the intensely concentrated and confined electric fields generated on the nanostructure upon LSPR excitation. Another mechanism of activation involves hot carriers transiently produced in the metal nanostructure by damping of LSPRs. In this Account, we visit a phenomenon that has received less attention but has a key role to play in plasmonic catalysis and chemistry. Under common chemical scenarios, plasmonic excitation induces a potential or a voltage on a nanoparticle. This photopotential modifies the energetics of a chemical reaction on noble metal nanoparticles. In a range of cases studied by our laboratory and others, light-induced potentials underlie the plasmonic enhancement of reaction kinetics. The photopotential model does not replace other known mechanisms, but it complements them. There are multiple ways in which an electrostatic photopotential is produced by LSPR excitation, such as optical rectification, but one that is most relevant in chemical media is asymmetric charge transfer to solution-phase acceptors. Electrons and holes produced in a nanostructure by damping of LSPRs are not removed at the same rate. As a result, the slower carrier accumulates on the nanostructure, and a steady-state charge is built up on the nanostructure, leading to a photopotential. Potentials of up to a few hundred millivolts have been measured by our laboratory and others. A photocharged nanoparticle is a source of carriers of a higher potential than an uncharged one. As a result, redox chemical reactions on noble metal nanoparticles exhibit lower activation barriers under photoexcitation. In electrochemical reactions on noble metal nanoparticles, the photopotential supplements the applied potential. In a diverse set of reactions, the photopotential model explains the photoenhancement of rates as well as the trends as a function of light intensity and photon energy. With further gains, light-induced potentials may be used as a knob for controlling the activities and selectivities of noble metal nanoparticle catalysts.
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