Photoredox chemistry with organic or transition metal agents has been reviewed in earlier years, but such is the pace of progress that we will overlap very little with earlier comprehensive reviews. ...This review first presents an overview of the area of research and then examines recent examples of C-C, C-N, C-O and C-S bond formations
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radical intermediates with transition metal and organic radical promoters. Recent successes with Birch reductions are also included. The transition metal chemistry will be restricted to photocatalysts based on the most widely used metals, Ru and Ir, but includes coupling chemistries that take advantage of low-valent nickel, or occasionally copper, complexes to process the radicals that are formed. Our focus is on developments in the past 10 years (2011-2021). This period has also seen great advances in the chemistry of organic photoredox reagents and the review covers this area. The review is intended to present highlights and is not comprehensive.
Visible light-activated reactions continue to expand and diversify. The example shown here is a Birch reduction achieved by organophotoredox reagents.
Based on simple ideas of electron-rich alkenes, exemplified by tetrakis(dimethylamino)ethene, TDAE, and on additional driving force associated with aromatization, families of very powerful neutral ...organic super-electron-donors (SEDs) have been developed. In the ground state, they carry out metal-free reductions of a range of functional groups. Iodoarenes are reduced either to aryl radicals or, with stronger donors, to aryl anions. Reduction to aryl radicals allows the initiation of very efficient transition-metal-free coupling of haloarenes to arenes. The donors also reduce alkyl halides, arenesulfonamides, triflates, and triflamdes, Weinreb amides, and acyloin derivatives. Under photoactivation at 365 nm, they are even more powerful and reductively cleave aryl chlorides. They reduce unactivated benzenes to the corresponding radical anions and display original selectivities in preferentially reducing benzenes over malonates or cyanoacetates. Additionally, they reductively cleave ArC–X, ArX–C (X = N or O) and ArC–C bonds, provided that the two resulting fragments are somewhat stabilized.
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, radical transformations have been far less successful. 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. Here we show how the combination of photoredox and asymmetric organic catalysis 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 (a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.
In case law, and in the associated academic literature, numerous judges and jurists have labelled parts of tort law 'anomalies'. This description - with its pejorative overtones - seemingly ...highlights a cause for concern about the state of the law. Yet closer analysis suggests otherwise. First, commentators mean different things when they speak of anomalies; only some of which provide genuine reasons for unease. Secondly, all but two of the aspects of tort law considered in this article that have been described as anomalous turn out to be no such thing. Finally, even those two remaining parts of tort law that have been labelled anomalies can be defended because (1) they have a great deal going for them in practical terms, and (2) the internal coherence of tort law (which they are thought to undermine) is not the unqualified good it is widely supposed to be.
Prostate cancer (PC) is a leading cause of death in men. Inflammation is one of the initiating processes whereby cells are trafficked into the tumor microenvironment by specific cytokines termed ...chemokines. This recruitment is complex and involves diverse leukocyte subsets with procancer and anticancer functions. Chemokines promote/abrogate proliferation of cancerous cells, block/aid apoptosis, and are instrumental/detrimental in cancer cell migration required for metastasis. Chemokines guide the release/transport of immune cells that serve as chaperones at sites of inflammation, and after subsequent activation, they lead to an immune response. The variety of immune cells recruited at the site of tumor initiation possess unique functions, and the plethora of chemokines released by each cell derived from a progenitor cell activated under a defined set of conditions dictates its specific role in cancer progression/regression. Geographic consequences that govern the climate and endemic diseases, along with the associated evolutionary effects that at times protect populations from one disease, could lead to genetic variations that determine a role for ethnicity and race in PC risk and susceptibility. Dysregulated expression or an imbalance in the homeostatic mechanisms associated with chemokines is implicated in PC. This review discusses the role of inflammation and chemokines in PC.
The visible-light-driven, phase-transfer-catalyzed, enantioselective perfluoroalkylation and trifluoromethylation of cyclic β-ketoesters is described. The photo-organocatalytic process, which occurs ...at ambient temperature and under visible light illumination, is triggered by the photochemical activity of in situ-generated electron donor–acceptor complexes, arising from the association of chiral enolates and perfluoroalkyl iodides. Preliminary mechanistic studies are reported.
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.
STAT5 in Cancer and Immunity Rani, Aradhana; Murphy, John J
Journal of interferon & cytokine research
36, Številka:
4
Journal Article
Recenzirano
Odprti dostop
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 (γ(c)) in their receptor complex. STAT5 critically mediates the biological actions of members of the γ(c) 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.
To examine the relative association between daily change in pain, fatigue, depressed mood, and cognitive function and 4 outcomes-positive affect and well-being, ability to participate in social roles ...and activities, upper extremity (UE) functioning, and lower extremity (LE) functioning.
Data analysis, multilevel mixed modeling.
General community.
Ambulatory adults (N=102) with multiple sclerosis.
Not applicable.
Customized short-forms of the Quality of Life in Neurological Disorders positive affect and well-being, UE functioning, and LE functioning item banks and the Patient-Reported Outcomes Measurement Information System ability to participate in social roles and activities item bank adapted for daily use and administered as end-of-day diaries.
Above and beyond the effects of demographic and clinical covariates, daily pain was associated with 3 of the 4 outcomes; days of higher than usual pain were related to lower same-day social participation (unstandardized β, B=-1.00; P=.002), UE functioning (B=-1.04; P=.01), and LE functioning (B=-.71; P=.04). Daily fatigue and depressed mood were independently related to daily positive affect and well-being; days of worse fatigue (B=-.54; P=.006) and depressed mood (B=-1.17; P<.0001) were related to lower same-day well-being.
The results indicate the role of fluctuations in symptoms in daily functioning and quality of life of individuals with multiple sclerosis. Daily increases in pain intensity are related to social and physical functioning, whereas increases in fatigue and depressed mood are related to lower daily well-being. Findings implicate a person-centered approach to monitoring and treating symptoms.
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.
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