Pioneering investigations into organometallic electrochemistry

Recently there has been a large effort to take advantage of electrochemistry to develop and understand novel chemical processes and reactivity. This thesis contains investigations into the synthesis and electrochemical properties of three diverse organometallic systems. In chapter 2, the first experimental determination of a an unsupported AuII-AuII bond is reported. The electrochemical characterisation of gold(III) hydride, hydroxide and chloride pincer complexes based on a backbone of a doubly cyclometalated 2,6-bis(4’-tert-butylphenyl) pyridine ligand was performed, in which it was determined that upon reduction of the AuIII complexes, an unsupported AuII dimer is formed, confirmed by characterisation of an authentic sample of the dimer. Using digital simulation, the reduction potentials of the hydride and hydroxide along with the oxidation potential of the dimer were determined, allowing the construction of a Hess cycle, from which the bond energy of the gold-gold bond in the dimer and the difference of the Au-OH and Au-H bond energies could be estimated. In chapter 3, the redox non-innocent behaviour of the ligands in zinc(II) bis(formazanate) complexes is investigated. These complexes have been electrochemically characterised by cyclic voltammetry, showing remarkably facile reduction to a radical anion, and further reduction to a dianion. Simulation of the cyclic voltammetry recorded for these compounds yielded optimised values of formal potentials, E0, and electron transfer rate constants, k0. In chapter 4, the synthesis and electrochemical characterisation of the first known examples of triazole-substituted cymantrene and cyrhetrene complexes are reported. The compounds h5-(-phenyltriazol-1-yl)cyclopentadienyl tricarbonyl manganese(I), with a phenyl, 3-aminophenyl or 4-aminophenyl substituent on the 4-position of the triazole ring were prepared via the copper(I)-catalyzed azide-alkyne cycloaddition (1,3-CuAAC) reaction. Cyclic voltammetric characterization of the redox behavior of each of the three cymantrene–triazole complexes is presented together with digital simulations, in-situ infrared spectroelectrochemistry, and DFT calculations to extract the associated kinetic and thermodynamic parameters. The synthesis and characterisation of the rhenium(I) analogues of the phenyl and 4-amino triazole substituted complexes are also reported. In chapter 5, the use of diazirines as carbene precursors for carbon surface modification is investigated, via the synthesis and characterisation of diazirine derivatised cymantrene and cyrhetrene. The surface modification of glassy carbon electrodes was attempted via irradiation of the half-sandwhich diazirine bearing complexes, resulting in oxidation waves visible on the electrode by cyclic voltammetric analysis

The amino acid sensitive TOR pathway from yeast to mammals

AbstractThe target of rapamycin (TOR) is an ancient effector of cell growth that integrates signals from growth factors and nutrients. Two downstream effectors of mammalian TOR, the translational components S6K1 and 4EBP1, are commonly used as reporters of mTOR activity. The conical signaling cascade initiated by growth factors is mediated by PI3K, PKB, TSC1/2 and Rheb. However, the process through which nutrients, i.e., amino acids, activate mTOR remains largely unknown. Evidence exists for both an intracellular and/or a membrane bound sensor for amino acid mediated mTOR activation. Research in eukaryotic models, has implicated amino acid transporters as nutrient sensors. This review describes recent advances in nutrient signaling that impinge on mTOR and its targets including hVps34, class III PI3K, a transducer of nutrient availability to mTOR

Synthesis and characterization of redox active cyrhetrene–triazole click products

We report the synthesis and characterization of two new cyclopentadienyl tricarbonyl rhenium(I) (cyrhetrene) complexes modified with a 1,4-disubstituted 1,2,3-triazole moiety. The two compounds, (η5-[4-phenyltriazol-1-yl]cyclopentadienyl) tricarbonyl rhenium(I), and (η5-[4-(4-aminophenyl)triazol-1-yl]cyclopentadienyl) tricarbonyl rhenium(I), were structurally characterized using 1H and 13C NMR, ATR-IR spectroscopy, UV–vis spectroscopy, mass spectrometry and X-ray crystallography where appropriate. The electrochemical behaviour of these two cyrhetrene–triazole complexes was explored using cyclic voltammetry, whereupon we observed that irreversible oxidation of the pendant 4-substituted-triazole moiety occurs before any electron transfer at the metal centre. This redox behaviour is in stark contrast to that of the analogous manganese(I) cymantrene–triazole derivatives, recently reported by our group

Essay mills and other contract cheating services: to buy or not to buy and the consequences of students changing their minds

Abstract: Very few parts of the world have legislation that prohibits the operation or the promotion of contract cheating services. This means that commercial companies providing such services can formally register and operate in most countries. If a student enters into an agreement with a contract cheating provider, what rights do they have to change their mind and what are the risks if they choose to do so? This paper examines the question through legal, institutional and societal lenses, showing that although a student has the consumer rights to withdraw from a contract with an essay mill, they may also be putting their future at risk by doing so. Contract cheating providers are now embedded within many institutions, using sharp practices to connect with vulnerable customers, but are also perfectly placed to blackmail students or threaten to report them to their institution if they ask to cancel their order. The paper argues that, while not condoning the practice of contract cheating, supportive processes need to be in place to help students at risk as part of standard institutional duty of care. This must be backed up by institutional policy that considers academic integrity as a core value for all

Nicastrin Functions as a γ-Secretase-Substrate Receptor

Summaryγ-secretase catalyzes the intramembrane cleavage of amyloid precursor protein (APP) and Notch after their extracellular domains are shed by site-specific proteolysis. Nicastrin is an essential glycoprotein component of the γ-secretase complex but has no known function. We now show that the ectodomain of nicastrin binds the new amino terminus that is generated upon proteolysis of the extracellular APP and Notch domains, thereby recruiting the APP and Notch substrates into the γ-secretase complex. Chemical- or antibody-mediated blocking of the free amino terminus, addition of purified nicastrin ectodomain, or mutations in the ectodomain markedly reduce the binding and cleavage of substrate by γ-secretase. These results indicate that nicastrin is a receptor for the amino-terminal stubs that are generated by ectodomain shedding of type I transmembrane proteins. Our data are consistent with a model where nicastrin presents these substrates to γ-secretase and thereby facilitates their cleavage via intramembrane proteolysis