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"Murphy, John"
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Why are you shouting at us? : the dos and don'ts of behaviour management
Preparing to work in a tough school can be a nerve-wracking experience. Will there be gangs? What if none of the students do their homework? What will you do if faced with a physical threat? Here the authors set out 7 keys to successful behaviour management, through innovative approaches to teaching and learning.
Book
Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals
A combination of photoredox and asymmetric organic catalysis enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to construct quaternary carbon stereocentres with high fidelity.
Radical solution to quaternary stereogenic centre synthesis
Quaternary stereogenic centres — carbon atoms with four distinct carbon substituents attached — are found in many biologically active natural products. A central goal of modern organic chemistry is to develop new catalytic enantioselective carbon–carbon bond-forming strategies that can be used to generate such centres. These authors demonstrate how a combination of photoredox and asymmetric organic catalysis enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to set quaternary carbon stereocentres with high fidelity. This method appears to be the first application of iminium ion activation, a successful catalytic strategy for enantioselective polar chemistry, in the realm of radical reactivity.
An important goal of modern organic chemistry is to develop new catalytic strategies for enantioselective carbon–carbon bond formation that can be used to generate quaternary stereogenic centres. Whereas considerable advances have been achieved by exploiting polar reactivity
1
, radical transformations have been far less successful
2
. This is despite the fact that open-shell intermediates are intrinsically primed for connecting structurally congested carbons, as their reactivity is only marginally affected by steric factors
3
. Here we show how the combination of photoredox
4
and asymmetric organic catalysis
5
enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to obtain quaternary carbon stereocentres with high fidelity. Critical to our success was the design of a chiral organic catalyst, containing a redox-active carbazole moiety, that drives the formation of iminium ions and the stereoselective trapping of photochemically generated carbon-centred radicals by means of an electron-relay mechanism. We demonstrate the generality of this organocatalytic radical-trapping strategy with two sets of open-shell intermediates, formed through unrelated light-triggered pathways from readily available substrates and photoredox catalysts—this method represents the application of iminium ion activation
6
(a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.
Journal Article
STAT5 in Cancer and Immunity
Signal transducers and activators of transcription 5 (STAT5a and STAT5b) are highly homologous proteins that are encoded by 2 separate genes and are activated by Janus-activated kinases (JAK) downstream of cytokine receptors. STAT5 proteins are activated by a wide variety of hematopoietic and nonhematopoietic cytokines and growth factors, all of which use the JAK-STAT signalling pathway as their main mode of signal transduction. STAT5 proteins critically regulate vital cellular functions such as proliferation, differentiation, and survival. The physiological importance of STAT5 proteins is underscored by the plethora of primary human tumors that have aberrant constitutive activation of these proteins, which significantly contributes to tumor cell survival and malignant progression of disease. STAT5 plays an important role in the maintenance of normal immune function and homeostasis, both of which are regulated by specific members of IL-2 family of cytokines, which share a common gamma chain (γc) in their receptor complex. STAT5 critically mediates the biological actions of members of the γc family of cytokines in the immune system. Essentially, STAT5 plays a critical role in the function and development of Tregs, and consistently activated STAT5 is associated with a suppression in antitumor immunity and an increase in proliferation, invasion, and survival of tumor cells. Thus, therapeutic targeting of STAT5 is promising in cancer.
Journal Article
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
The focus of this review is to provide an overview of the field of organocatalysed photoredox chemistry relevant to synthetic medicinal chemistry. Photoredox transformations have been shown to enable key transformations that are important to the pharmaceutical industry. This type of chemistry has also demonstrated a high degree of sustainability, especially when organic dyes can be employed in place of often toxic and environmentally damaging transition metals. The sections are arranged according to the general class of the presented reactions and the value of these methods to medicinal chemistry is considered. An overview of the general characteristics of the photocatalysts as well as some electrochemical data is presented. In addition, the general reaction mechanisms for organocatalysed photoredox transformations are discussed and some individual mechanistic considerations are highlighted in the text when appropriate.
Journal Article
Recent Advances in C–H Functionalisation through Indirect Hydrogen Atom Transfer
The functionalisation of C–H bonds has been an enormous achievement in synthetic methodology, enabling new retrosynthetic disconnections and affording simple synthetic equivalents for synthons. Hydrogen atom transfer (HAT) is a key method for forming alkyl radicals from C–H substrates. Classic reactions, including the Barton nitrite ester reaction and Hofmann–Löffler–Freytag reaction, among others, provided early examples of HAT. However, recent developments in photoredox catalysis and electrochemistry have made HAT a powerful synthetic tool capable of introducing a wide range of functional groups into C–H bonds. Moreover, greater mechanistic insights into HAT have stimulated the development of increasingly site-selective protocols. Site-selectivity can be achieved through the tuning of electron density at certain C–H bonds using additives, a judicious choice of HAT reagent, and a solvent system. Herein, we describe the latest methods for functionalizing C–H/Si–H/Ge–H bonds using indirect HAT between 2018–2023, as well as a critical discussion of new HAT reagents, mechanistic aspects, substrate scopes, and background contexts of the protocols.
Journal Article
Start by believing : Larry Nassar's crimes, the institutions that enabled him, and the brave women who stopped a monster
\"From ESPN journalists whose investigation garnered a Peabody Award, the full devastating story of former physician Larry Nassar's serial abuse of America's elite gymnasts and others, revealing the win-at-all-costs culture in youth athletics and higher education that enabled him\"-- Provided by publisher.
Book
TORT'S HIERARCHY OF PROTECTED INTERESTS
It is widely accepted that tort law operates according to a hierarchy of protected interests. Some commentators suggest that this hierarchy can be put to dispositive uses in cases characterised by a clash of interests held respectively by the claimant and defendant (the inferior interest giving way). Others argue that thinking in terms of a hierarchy of interests sheds light on three unusual aspects of tort law: viz. the existence of torts that are actionable per se, the existence of strict liability torts, and the existence of actions in which injunctive relief is routinely awarded even though compensatory damages are tort law's default remedy. This article tests both claims. It concludes that an intuitively appealing hierarchy of interests can be identified, and that it might well possess dispositive significance all other things being equal. But it also observes that all other things are seldom equal, and that departures from the hierarchy occur for various reasons that can be clearly identified and which should be borne in mind when thinking about its dispositive utility. It also urges caution in making connections between the status of certain interests and the fact that they are protected by torts that are actionable per se, strict liability torts and torts in connection with which injunctions are awarded almost as a matter of course.
Journal Article