Magnesium(I) Reduction of Aluminum(III) Hydride Complexes: Generation of Mixed Valence Aluminum (AlI /Al0 ) Hydride Cluster Compounds, [Al6 H8 (NR3 )2 {Mg(ß-diketiminate)}4 ].

Reduction of a range of amido- and aryloxy-aluminum dihydride complexes, e.g. [AlH2 (NR3 ){N(SiMe3 )2 }] (NR3 =NMe3 or N-methylpiperidine (NMP)), with ß-diketiminato dimagnesium(I) reagents, [{(Ar Nacnac)Mg}2 ] (Ar Nacnac=[HC(MeCNAr)2 ]- , Ar=mesityl (Mes) or 2,6-xylyl (Xyl)), have afforded deep red mixed valence aluminum hydride cluster compounds, [Al6 H8 (NR3 )2 {Mg(Ar Nacnac)}4 ], which have an average Al oxidation state of +0.66, the lowest for any well-defined aluminum hydride compound. In the solid-state, the clusters are shown to have distorted octahedral Al6 cores, having zero-valent Al axial sites and mono-valent AlH2 - equatorial units. Several novel by-products were isolated from the reactions that gave the clusters, including the Mg-Al bonded magnesio-aluminate complexes, [(Ar Nacnac)(Me3 N)Mg-Al(µ-H)3 [{Mg(Ar Nacnac)}2 (µ-H)]]. Computational analyses of one aluminum hydride cluster revealed its Al6 core to be electronically delocalized, and to possess one unoccupied, and six occupied, skeletal molecular orbitals.

Fabrication and Functionalisation of Nanocarbon-Based Field-Effect Transistor Biosensors.

Nanocarbon-based field-effect transistor (NC-FET) biosensors are at the forefront of future diagnostic technology. By integrating biological molecules with electrically conducting carbon-based platforms, high sensitivity real-time multiplexed sensing is possible. Combined with their small footprint, portability, ease of use, and label-free sensing mechanisms, NC-FETs are prime candidates for the rapidly expanding areas of point-of-care testing, environmental monitoring and biosensing as a whole. In this review we provide an overview of the basic operational mechanisms behind NC-FETs, synthesis and fabrication of FET devices, and developments in functionalisation strategies for biosensing applications.

The distribution, ecology and predicted habitat use of the Critically Endangered angelshark (Squatina squatina) in coastal waters of Wales and the central Irish Sea.

The angelshark (Squatina squatina) has the northernmost range of any angel shark species, but there is limited information on its distribution, habitat use and ecology at higher latitudes. To address this, Angel Shark Project: Wales gathered 2231 S. squatina records and 142 anecdotal resources from fishers, coastal communities and archives. These spanned the coastal waters of Wales and the central Irish Sea and were dated from 1812 to 2020, with 97.62% of records within 11.1 km (6 nm) of the coast. Commercial, recreational and charter boat fishers provided the majority of S. squatina records (97.18%), with significantly more sightings from three decades (1970s, 1980s and 1990s) and in the months of September, June, August and July (in descending order). The coastal area between Bardsey Island and Strumble Head had the most S. squatina records (n = 1279), with notable concentrations also found in Carmarthen Bay, Conwy Bay and the Outer Severn Estuary. Species distribution models (SDM) identified four environmental variables that had significant influence on S. squatina distribution, depth, chlorophyll-a concentration, sea surface temperature (SST) and salinity, and these varied between the quarters (Q) of the year. SDM model outputs predicted a larger congruous area of suitable habitat in Q3 (3176 km2 ) compared to Q2 (2051 km2 ), with suitability along the three glacial moraines (Sarn Badrig, Sarn-y-Bwch and Sarn Cynfelyn) strongly presented. Comparison of modelled environmental variables at the location of S. squatina records for each Q identified reductions in depth and salinity, and increases in chlorophyll-a and SST when comparing Q2 or Q3 with Q1 or Q4. This shift may suggest S. squatina are making seasonal movements to shallow coastal waters in Q2 and Q3. This is supported by 23 anecdotal resources and may be driven by reproductive behaviour, as there were 85 records of S. squatina individuals ≤60 cm in the dataset, inferred as recently born or juvenile life-history stages. The results have helped fill significant evidence gaps identified in the Wales Angelshark Action Plan and immediate next research steps are suggested.

Reduction of tert-butylphosphaalkyne and trimethylsilylnitrile with magnesium(I) dimers.

We report on the reactivity of magnesium(I) dimers, [Mg(nacnac)]2 (nacnac = HC[C(Me)N(2,6-iPr2C6H3)]2 ([DippLMg]2) and HC[C(Me)N(2,4,6-Me3C6H2)]2 ([MesLMg]2)), towards the phosphaalkyne tBuCP. The steric profile of the magnesium(I) dimer results in selectivity for different products. The larger diisopropylphenyl derivative yields exclusively the monomeric dimagnesiated phosphaalkene [DippLMg]PC(tBu)([DippLMg]) (1), while the mesityl derivative facilitates reductive coupling of two phosphaalkyne equivalents to give access to the 1,3-diphosphacyclobutadienediide [MesLMg]2[(tBu)2C2P2](2). The reactivity differs in coordinating solvents such as THF, which allowed for the observation of C-P coupled products. For sake of comparison, reactions of magnesium(I) compounds with Me3SiCN were carried out. In contrast to the reactions involving tBuCP, these afforded 1,3-diazabutadienediyl complexes via reductive coupling and silyl migration processes.

Photochemically Activated Dimagnesium(I) Compounds: Reagents for the Reduction and Selective C-H Bond Activation of Inert Arenes.

The photochemical activation of dimagnesium(I) compounds, and subsequent high yielding, regioselective reactions with inert arenes are reported. Irradiating benzene solutions of [{(Ar Nacnac)Mg}2 ] (Ar Nacnac=[HC(MeCNAr)2 ]- ; Ar=2,6-diisopropylphenyl (Dip) or 2,4,6-tricyclohexylphenyl (TCHP)) with blue or UV light, leads to double reduction of benzene and formation of the "Birch-like" cyclohexadienediyl bridged compounds, [{(Ar Nacnac)Mg}2 (µ-C6 H6 )]. Irradiation of [{(Dip Nacnac)Mg}2 ] in toluene, and each of the three isomers of xylene, promoted completely regio- and chemo-selective C-H bond activations, and formation of [(Dip Nacnac)Mg(Ar')] (Ar'=meta-tolyl; 2,3-, 3,5- or 2,5-dimethylphenyl), and [{(Dip Nacnac)Mg(µ-H)}2 ]. Fluorobenzene was cleanly defluorinated by photoactivated [{(Dip Nacnac)Mg}2 ], leading to biphenyl and [{(Dip Nacnac)Mg(µ-F)}2 ]. Computational studies suggest all reactions proceed via photochemically generated magnesium(I) radicals, which reduce the arene substrate, before C-H or C-F bond activation processes occur.

Sterically controlled reductive oligomerisations of CO by activated magnesium(i) compounds: deltate vs. ethenediolate formation.

An extremely bulky, symmetrical three-coordinate magnesium(i) complex, [{(TCHPNacnac)Mg}2] (TCHPNacnac = [{(TCHP)NCMe}2CH]-, TCHP = 2,4,6-tricyclohexylphenyl) has been prepared and shown to have an extremely long Mg-Mg bond (3.021(1) Å) for such a complex. It was shown not to react with either DMAP (4-dimethylaminopyridine) or CO. Three unsymmetrical 1 : 1 DMAP adducts of less bulky Mg-Mg bonded species have been prepared, viz. [(ArNacnac)Mg-Mg(DMAP)(ArNacnac)] (ArNacnac = [(ArNCMe)2CH]- Ar = 2,6-xylyl (Xyl), mesityl (Mes) or 2,6-diethylphenyl (Dep)), and their reactivity toward CO explored. Like the previously reported bulkier complex, [(DipNacnac)Mg-Mg(DMAP)(DipNacnac)] (Dip = 2,6-diisopropylphenyl), [(DepNacnac)Mg-Mg(DMAP)(DepNacnac)] reductively trimerises CO to give a rare example of a deltate complex, [{(DepNacnac)Mg(µ-C3O3)Mg(DMAP)(DepNacnac)}2]. In contrast, the two smaller adduct complexes react with only two CO molecules, ultimately giving unusual ethenediolate complexes [{(ArNacnac)Mg{µ-OC(H)[double bond, length as m-dash]C(DMAP-H)O}Mg(ArNacnac)}2] (Ar = Xyl or Mes). DFT calculations show the latter reactions to proceed via reductive dimerizations of CO, and subsequent intramolecular C-H activation of Mg-ligated DMAP by "zig-zag" [C2O2]2- fragments of reaction intermediates. Calculations also suggest that magnesium deltate complexes are kinetic products in these reactions, while the magnesium ethenediolates are thermodynamic products. This study shows that subtle changes to the bulk of the reacting 1 : 1 DMAP-magnesium(i) adduct complexes can lead to fine steric control over the products arising from their CO reductive oligomerisations. Furthermore, it is found that the more activated nature of the adduct complexes, relative to their symmetrical, three-coordinate counterparts, [{(ArNacnac)Mg}2], likely derives more from the polarisation of the Mg-Mg bonds of the former, than the elongated nature of those bonds.

The complex reactivity of ß-diketiminato magnesium(i) dimers towards pinacolborane: implications for catalysis.

Reactions between the borane, HBpin (pin = pinacolato), and three magnesium(i) dimers, [{(ArNacnac)Mg-}2] (ArNacnac = [(ArNCMe)2CH]-; Ar = xylyl (Xyl), mesityl (Mes) or 2,6-diethylphenyl (Dep)), have been carried out in 2 : 1, 5 : 1 and 20 : 1 ratios. In all cases, NMR spectroscopic studies have revealed complex mixtures of many known and novel products from these reactions. From extracts of the crude reaction mixtures, low yields of ten compounds, representing six different types of complexes between ß-diketiminato magnesium fragments and boron containing ligands, have been isolated and crystallographically characterised. These include unprecedented examples of compounds in which the γ-carbon of the ß-diketiminate ligand has been activated by boron hydride fragments. In addition, boryloxide (OBpin), borate ([B(pin)2]- or [(pin)BH2]-), B-O bond ruptured [pinBH2]-, a diborane(5) dianion, or BH3 have been shown to be incorporated into the isolated complexes. The complexity of the products of the reported reactions are discussed in light of recently published patents and papers which report that magnesium(i) dimers act as efficient catalysts, or as pre-catalysts to well defined catalysts, for the hydroboration of a variety of unsaturated substrates by HBpin. Our results strongly suggest that magnesium(i) dimers are not catalysts in these reactions, and that there are many more potential (pre-)catalysts that are generated in these reactions, than have previously been reported.

Acyclic 1,2-dimagnesioethanes/-ethene derived from magnesium(i) compounds: multipurpose reagents for organometallic synthesis.

Reactions of three magnesium(i) dimers, [{(ArNacnac)Mg-}2] (ArNacnac = [(ArNCMe)2CH]-; Ar = xylyl (Xyl), mesityl (Mes) or 2,6-diethylphenyl (Dep)), with either 1,1-diphenylethylene (DPE), α-methylstyrene (MS), trans-stilbene (TS) or diphenylacetylene (DPA) led to the 1,2-addition of the Mg-Mg bond across the substrate, giving rise to the 1,2-dimagnesioethanes, [{(XylNacnac)Mg}2(µ-DPE)], [{(DepNacnac)Mg}2(µ-MS)], [{(ArNacnac)Mg}2(µ-TS)] (Ar = Mes or Dep); and a 1,2-dimagnesioethene, [{(MesNacnac)Mg}2(µ-DPA)]. The reactions involving the 1,1-substituted alkenes are shown to be readily redox reversible, in that the reaction products are in equilibrium with a significant proportion of the starting materials at room temperature. Variable temperature NMR spectroscopy and a van't Hoff analysis point to low kinetic barriers to these weakly exergonic reactions. [{(MesNacnac)Mg}2(µ-DPE)] and [{(MesNacnac)Mg}2(µ-DPA)] behave as 1,2-di-Grignard reagents in their reactions with very bulky amido-zinc bromides, yielding the first examples of a 1,2-dizincioethane, [(L*Zn)2(µ-DPE)] (L* = -N(Ar*)(SiPri 3); Ar* = C6H2Me{C(H)Ph2}2-4,2,6), and a 1,2-dizincioethene, [(TBoLZn)2(µ-DPA)] (TBoL = -N(SiMe3){B(DipNCH)2}, Dip = 2,6-diisopropylphenyl), respectively. Divergent reactivity is shown for [{(MesNacnac)Mg}2(µ-DPE)], which behaves as a two-electron reducing agent when treated with amido-cadmium and amido-magnesium halide precursors, yielding the cadmium(i) and magnesium(i) dimers, [PhBoLCdCdPhBoL] (PhBoL = -N(SiPh3){B(DipNCH)2}) and [L†MgMgL†] (L† = -N(Ar†)(SiMe3); Ar† = C6H2Pri{C(H)Ph2}2-4,2,6), respectively. A further class of reactivity for [{(MesNacnac)Mg}2(µ-DPE)] derives from its reaction with the bulky amido-germanium chloride, L*GeCl, which gives a magnesio-germane, presumably via intramolecular C-H activation of a highly reactive magnesiogermylene intermediate, [:Ge(L*){Mg(MesNacnac)}]. [{(MesNacnac)Mg}2(µ-DPE)] can be considered as acting as a two-electron reducing, magnesium transfer reagent in this reaction.

On the Viability of Catalytic Turnover via Al-O/B-H Metathesis: The Reactivity of ß-Diketiminate Aluminium Hydrides towards CO2 and Boranes.

A series of ß-diketiminate stabilized aluminium hydrides of the type (Nacnac)Al(R)H has been synthesized offering variation in the auxiliary R substituent and in the Nacnac backbone. These show significant variation in the nature of the Al-H bond: electron-donating R groups give rise to weaker (and presumably more hydridic) Al-H bonds, leading to enhanced rates of reactivity towards CO2 . The resulting κ1 -formate complexes (Nacnac)Al(R){OC(O)H} have been isolated and their reactivity towards B-H-containing reductants probed. In the case of HBpin no reaction is observed (even under forcing conditions), while the more reactive boranes HBcat and {H(9-BBN)}2 ultimately yield boryloxy complexes of the type (Nacnac)Al(R)(OBX2 ) (X2 =cat, 9-BBN). However, no hint of Al-O/B-H metathesis is observed even under forcing conditions. With BH3 ⋅SMe2 the major product is a related boryloxy system, although (uniquely) in this case a minor product is observed which contains an Al-H bond. We hypothesize that (Nacnac)Al(R)(κ2 -BH4 ) is formed (despite the unfavourable thermodynamics of Al-O/B-H metathesis) due to the additional driving force provided by coordination of the strongly Lewis acidic BH3 unit to the Al-H bond. That said, we find that (unlike the analogous gallium systems) no catalytic turnover can be achieved in the reduction of CO2 by boranes mediated by these aluminium hydrides.

Development and implementation of a decision pathway for general practitioners for the management or referral of suspected allergy.

Many patients with suspected allergy are referred to specialist care inappropriately. We aimed to develop and implement an online decision pathway to aid General Practitioners' (GPs) management decisions in suspected allergy. Our study involved 1487 GPs, 3 referral management centres, 5 GP system suppliers, 4 primary care trusts, and 1 specialist allergy clinic. The pathway was implemented by 3/5 GP system suppliers, published to Map of Medicine and on a specialist clinic website. In the first year, the pathway ranked in the top 10/160 local care maps accessed via Map of Medicine and was viewed 900 times. Only 96 GPs registered to use the clinic website. Only 110 (7%) GPs responded to the feedback request, of which 13/110 (12%) had used the pathway; nearly all thought it useful. It was used by referral management centres as explanation of rejected referrals. Alternative approaches to embed its use are required. Significance for public healthOne in three people in the UK are affected by allergies during their lifetime. Early diagnosis and appropriate management can improve quality of life and reduce emergency hospitalisation. However, referring patients to secondary care is costly in terms of time and resources. We developed a pathway algorithm to support General Practitioners' (GPs) allergy management and referral decisions to ensure that all referrals to specialist clinics were appropriate. The study illustrates a real world implementation with lessons for those seeking to improve the primary-secondary care interface, implementing pathways in various formats. In the UK, Map of Medicine seems to be the most used software. We demonstrated the difficulty of reaching GPs to encourage adoption of online decision support and suggest new ways forward by expanding care pathways into more detailed protocols for use directly by patients.

The Clinical Decision Unit has a role to play in the management of acute undifferentiated abdominal pain.

INTRODUCTION AND AIMS: Patients with undifferentiated acute abdominal pain (AAP) frequently present to the Emergency Department (ED). The most common diagnosis is the nonspecific abdominal pain although missed occult surgical pathology in the haemodynamically stable patient with equivocal symptoms and signs is a potential source of morbidity. The objectives of this study were two-fold. Firstly, to ascertain the accuracy of ED clinicians in the diagnosis of AAP, and to delineate if there was a population of patients who would normally require admission to hospital that would be suitable to be managed on a Clinical Decision Unit (CDU) protocol. Secondly, to prospectively evaluate such a strategy by way of a pilot study. METHODS: An initial retrospective cohort study of consecutive patients presenting to the ED with undifferentiated AAP were analysed. Data were extracted on admission, length of stay and the correlation between initial ED clinical diagnosis and final discharge diagnosis. Following this, a protocol was developed within our institution for the management of patients with stable AAP on a CDU pathway. This was then formally evaluated over a period of 25 months as part of a quality improvement exercise. RESULTS: A total of 501 patients were analysed of whom 48% were admitted from the ED. The initial ED diagnosis was correct in 57% of patients, and 28% of admitted patients were discharged within 48 h with no specific intervention. During the period of the pilot study, 189 patients were entered on to the AAP CDU pathway, of which 85% were safely discharged directly from the CDU and 67% within 24 h. Of the 28 patients admitted only four required an operation. Use of the protocol in this population resulted in the initial ED assessment being correct in 69% of cases. CONCLUSION: The management of stable AAP within the ED environment on a well-defined CDU pathway is feasible and can facilitate safe, efficient and effective care with early discharge and an increase in the accuracy of the final diagnosis.

The effect of beta-blockers on bone metabolism as potential drugs under investigation for osteoporosis and fracture healing.

BACKGROUND: beta-Adrenergic receptor antagonists (beta-blockers) have a well-recognised antihypertensive action that is mediated through a reduction in cardiac output and in the release of renin from the kidneys and inhibition of the action of endogenous catecholamines on beta-adrenergic receptors. This class of drugs has been shown to reduce the incidence of cardiovascular disease. Recent evidence suggests that beta-blockers may also have an effect on bone structure, metabolism and fracture healing. OBJECTIVE: This paper reviews in vitro and in vivo data that suggest beta-blockers have primarily an anabolic effect on bone metabolism. RESULTS: The sympathetic nervous system has a catabolic effect on bone, and in vitro studies have shown that adrenergic agonists stimulate bone resorption. The beta-blocker propranolol has been shown to increase bone formation in ovariectomised female rats. Also, recent observational clinical studies provide evidence to show that beta-blockers are associated with reduction in fracture risk in both men and women. CONCLUSION: Although there are some controversial studies, most research concludes that beta-blockers show promise in the treatment of osteoporosis and fracture healing.