Unlocking the Metalation Applications of TMP-powered Fe and Co(II) bis(amides): Synthesis, Structure and Mechanistic Insights.

Typified by LiTMP and TMPMgCl.LiCl, (TMP=2,2,6,6-tetramethylpiperidide), s-block metal amides have found widespread applications in arene deprotonative metalation. On the contrary, transition metal amides lack sufficient basicity to activate these substrates. Breaking new ground in this field, here we present the synthesis and full characterisation of earth-abundant transition metals M(TMP)2 (M=Fe, Co). Uncovering a new reactivity profile towards fluoroarenes, these amide complexes can promote direct M-H exchange processes regioselectively using one or two of their basic amide arms. Remarkably, even when using a perfluorinated substrate, selective C-H metalation occurs leaving C-F bonds intact. Their kinetic basicity can be boosted by LiCl or NBu4Cl additives which enables formation of kinetically activated ate species. Combining spectroscopic and structural studies with DFT calculations, mechanistic insights have been gained on how these low polarity metalation processes take place. M(TMP)2 can also be used to access ferrocene and cobaltocene by direct deprotonation of cyclopentadiene and undergo efficient CO2 insertion of both amide groups under mild reaction conditions.

Diurnal fuel moisture content variations of live and dead Calluna vegetation in a temperate peatland.

The increasing frequency and severity of UK wildfires, attributed in part to the effects of climate change, highlights the critical role of fuel moisture content (FMC) of live and dead vegetation in shaping wildfire behaviour. However, current models used to assess wildfire danger do not perform well in shrub-type fuels such as Calluna vulgaris, requiring in part an improved understanding of fuel moisture dynamics on diurnal and seasonal scales. To this end, 554 samples of upper live Calluna canopy, live Calluna stems, upper dead Calluna canopy, dead Calluna stems, moss, litter and organic layer (top 5 cm of organic material above mineral soil) were sampled hourly between 10:00 and 18:00 on seven days from March-August. Using a novel statistical method for investigating diurnal patterns, we found distinctive diurnal and seasonal trends in FMC for all fuel layers. Notably, significant diurnal patterns were evident in dead Calluna across nearly all sampled months, while diurnal trends in live Calluna canopy were pronounced in March, June, and August, coinciding with the peak occurrence of UK wildfires. In addition, the moisture content of moss and litter was found to fluctuate above and below their relative ignition thresholds throughout the day on some sampling days. These findings underscore the impact of diurnal FMC variations on wildfire danger during early spring and late summer in Calluna dominated peatlands and the need to consider such fluctuations in management and fire suppression strategies.

Lateral Metallation and Redistribution Reactions of Sodium Ferrates Containing Bulky 2,6-Diisopropyl-N-(trimethylsilyl)anilide Ligands.

Alkali-metal ferrates containing amide groups have emerged as regioselective bases capable of promoting Fe-H exchanges of aromatic substrates. Advancing this area of heterobimetallic chemistry, a new series of sodium ferrates is introduced incorporating the bulky arylsilyl amido ligand N(SiMe3 )(Dipp) (Dipp=2,6-iPr2 -C6 H3 ). Influenced by the large steric demands imposed by this amide, transamination of [NaFe(HMDS)3 ] (HMDS=N(SiMe3 )2 ) with an excess of HN(SiMe3 )(Dipp) led to the isolation of heteroleptic [Na(HMDS)2 Fe{N(SiMe3 )Dipp}]∞ (1) resulting from the exchange of just one HMDS group. An alternative co-complexation approach, combining the homometallic metal amides [NaN(SiMe3 )Dipp] and [Fe{N(SiMe3 )Dipp}2 ] induces lateral metallation of one Me arm from the SiMe3 group in the iron amide furnishing tetrameric [NaFe{N(SiCH2 Me2 )Dipp}{N(SiMe3 )Dipp}]4 (2). Reactivity studies support that this deprotonation is driven by the steric incompatibility of the single metal amides rather than the basic capability of the sodium reagent. Displaying synergistic reactivity, heteroleptic sodium ferrate 1 can selectively promote ferration of pentafluorobenzene using one of its HMDS arms to give heterotrileptic [Na{N(SiMe3 )Dipp}(HMDS)Fe(C6 F5 )]∞ (4). Attempts to deprotonate less activated pyridine led to the isolation of NaHMDS and heteroleptic Fe(II) amide [(py)Fe{N(SiMe3 )Dipp}(HMDS)] (5), resulting from an alternative redistribution process which is favoured by the Lewis donor ability of this substrate.

Facilitating the Ferration of Aromatic Substrates through Intramolecular Sodium Mediation.

Exploiting cooperative effects between Na and FeII centres present in tris(amide) ferrate complexes has led to the chemoselective ferration of pentafluorobenzene, benzene, toluene, anisole, and pyridine being realised at room temperature. The importance of this bimetallic partnership is demonstrated by neither the relevant sodium amide (NaHMDS or NaTMP) nor the FeII amide Fe(HMDS)2 efficiently metallating these substrates under the conditions of this study. By combining NMR studies with the isolation of key intermediates and DFT calculations, we offer a possible mechanism for how these reactions take place, uncovering a surprising reaction pathway in which the metals cooperate in a synchronised manner. Although the isolated products are formally the result of Fe-H exchange, theoretical calculations indicate that the aromatic substrates undergo Na-H exchange followed by fast intramolecular transmetallation to Fe, thus stabilizing the newly generated aryl fragment.

Lithium-mediated Ferration of Fluoroarenes.

While fluoroaryl fragments are ubiquitous in many pharmaceuticals, the deprotonation of fluoroarenes using organolithium bases constitutes an important challenge in polar organometallic chemistry. This has been widely attributed to the low stability of the in situ generated aryl lithium intermediates that even at -78 °C can undergo unwanted side reactions. Herein, pairing lithium amide LiHMDS (HMDS = N{SiMe3}2) with FeII(HMDS)2 enables the selective deprotonation at room temperature of pentafluorobenzene and 1,3,5-trifluorobenzene via the mixed-metal base [(dioxane)LiFe(HMDS)3] (1) (dioxane = 1,4-dioxane). Structural elucidation of the organometallic intermediates [(dioxane)Li(HMDS)2Fe(ArF)] (ArF = C6F5, 2; 1,3,5-F3-C6H2, 3) prior electrophilic interception demonstrates that these deprotonations are actually ferrations, with Fe occupying the position previously filled by a hydrogen atom. Notwithstanding, the presence of lithium is essential for the reactions to take place as Fe II (HMDS)2 on its own is completely inert towards the metallation of these substrates. Interestingly 2 and 3 are thermally stable and they do not undergo benzyne formation via LiF elimination.

Boosting Conjugate Addition to Nitroolefins Using Lithium Tetraorganozincates: Synthetic Strategies and Structural Insights.

We report the first transition metal catalyst- and ligand-free conjugate addition of lithium tetraorganozincates (R4 ZnLi2 ) to nitroolefins. Displaying enhanced nucleophilicity combined with unique chemoselectivity and functional group tolerance, homoleptic aliphatic and aromatic R4 ZnLi2 provide access to valuable nitroalkanes in up to 98 % yield under mild conditions (0 °C) and short reaction time (30 min). This is particularly remarkable when employing ß-nitroacrylates and ß-nitroenones, where despite the presence of other electrophilic groups, selective 1,4 addition to the C=C is preferred. Structural and spectroscopic studies confirmed the formation of tetraorganozincate species in solution, the nature of which has been a long debated issue, and allowed to unveil the key role played by donor additives on the aggregation and structure of these reagents. Thus, while chelating N,N,N',N'-tetramethylethylenediamine (TMEDA) and (R,R)-N,N,N',N'-tetramethyl-1,2-diaminocyclohexane (TMCDA) favour the formation of contacted-ion pair zincates, macrocyclic Lewis donor 12-crown-4 triggers an immediate disproportionation process of Et4 ZnLi2 into equimolar amounts of solvent-separated Et3 ZnLi and EtLi.

Utilising Sodium-Mediated Ferration for Regioselective Functionalisation of Fluoroarenes via C-H and C-F Bond Activations.

Pairing iron bis(amide) Fe(HMDS)2 with Na(HMDS) to form new sodium ferrate base [(dioxane)0.5 ⋅NaFe(HMDS)3 ] (1) enables regioselective mono and di-ferration (via direct Fe-H exchange) of a wide range of fluoroaromatic substrates under mild reaction conditions. Trapping of several ferrated intermediates has provided key insight into how synchronised Na/Fe cooperation operates in these transformations. Furthermore, using excess 1 at 80 °C switches on a remarkable cascade process inducing the collective twofold C-H/threefold C-F bond activations, where each C-H bond is transformed to a C-Fe bond whereas each C-F bond is transformed into a C-N bond.

Synthetic, structural and magnetic implications of introducing 2,2'-dipyridylamide to sodium-ferrate complexes.

Using a transamination approach to access novel Fe(ii) complexes, this study presents the synthesis, X-ray crystallographic and magnetic characterisation of a series of new iron complexes containing the multifunctional 2,2-dipyridylamide (DPA) ligand using iron bis(amide) [{Fe(HMDS)2}2] and sodium ferrate [{NaFe(HMDS)3}∞] (1) as precursors (HMDS = 1,1,1,3,3,3-hexamethyldisilazide). Reactions of DPA(H) with 1 show exceptionally good stoichiometric control, allowing access to heteroleptic [(THF)2·NaFe(DPA)(HMDS)2] (3) and homoleptic [{THF·NaFe(DPA)3}∞] (4) by using 1 and 3 equivalents of DPA(H), respectively. Linking this methodology and co-complexation, which is a more widely used approach to prepare heterobimetallic complexes, 3 can also be prepared by combining NaHMDS with heteroleptic [{Fe(DPA)(HMDS)}2] (2). In turn, 2 has been also synthesised and structurally defined by reacting [{Fe(HMDS)2}2] with two equivalents of DPA(H). Structural studies demonstrate the coordination flexibility of the N-bridged bis(heterocycle) ligand DPA, with 2 and 3 exhibiting discrete monomeric motifs, whereas 4 displays a much more intricate supramolecular structure, with one of its DPA ligands coordinating in an anti/anti fashion (as opposed to 2 and 3 where DPA shows a syn/syn conformation), which facilitates propagation of the structure via its central amido N. Magnetic studies confirmed the high-spin electron configuration of the iron(ii) centres in all three compounds and revealed the existence of weak ferromagnetic interactions in dinuclear compound 2 (J = 1.01 cm-1).

Accessing sodium ferrate complexes containing neutral and anionic N-heterocyclic carbene ligands: structural, synthetic, and magnetic insights.

This study reports the synthesis and single-crystal X-ray crystallographic, NMR spectroscopic, and magnetic characterization of a series of sodium ferrates using bis(amide) Fe(HMDS)2 as a precursor (HMDS = 1,1,1,3,3,3-hexamethyldisilazide). Reaction with sodium reagents NaHMDS and NaCH2SiMe3 in hexane afforded donor-solvent-free sodium ferrates [{NaFe(HMDS)3}∞] (1) and [{NaFe(HMDS)2(CH2SiMe3)}∞] (2), respectively, which exhibit contacted ion pair structures, giving rise to new polymeric chain arrangements made up of a combination of inter- and intramolecular Na···Me(HMDS) electrostatic interactions. Addition of the unsaturated NHC IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) to 1 and 2 caused deaggregation of their polymeric structures to form discrete NHC-stabilized solvent-separated ion pairs [Na(IPr)2](+)[Fe(HMDS)3](-) (3) and [(THF)3·NaIPr](+)[Fe(HMDS)2CH2SiMe3](-) (4), where in both cases, the NHC ligand coordinates preferentially to Na. In contrast, when IPr is sequentially reacted with the single-metal reagents NaCH2SiMe3 and Fe(HMDS)2, the novel heteroleptic ferrate (THF)3Na[:C{[N(2,6-(i)Pr2C6H3)]2CHCFe(HMDS)2}] (5) is obtained. This contains an anionic NHC ligand acting as an unsymmetrical bridge between the two metals, coordinating through its abnormal C4 position to Fe and its normal C2 position to Na. The formation of 5 can be described as an indirect ferration process where IPr is first metalated at the C4 position by the polar sodium alkyl reagent, which in turn undergoes transmetalation to the more electronegative Fe(HMDS)2 fragment. Treatment of 5 with 1 molar equiv of methyl triflate (MeOTf) led to the isolation and structural elucidation of the neutral abnormal NHC (aNHC) tricoordinate iron complex [CH3C{[N(2,6-iPr2C6H3)]2CHCFe(HMDS)2}] (6) with the subsequent elimination of NaOTf, disclosing the selectivity of complex 5 to react with this electrophile via its C2 position, leaving its Fe-C4 and Fe-N bonds intact. The magnetic susceptibility properties of compounds 1-6 have been examined. This study revealed a drastic change of magnetic susceptibility in replacing a pure σ donor from an idealized trigonal coordination environment by an NHC π donating character.

Vessel motion thresholds for maintaining physical and cognitive performance: a study of naval personnel at sea.

Methods and results are reported from a study of ships companies' exposure to low-frequency motions on three vessels of the Royal Navy. The aim of the study was to investigate relationships between deck accelerations and the incidence of problems such as difficulties with physical tasks, cognitive activities, motion sickness, and work effort. Ship motions were recorded continuously during sea patrols of 10-14 days. The data collected from the three vessels comprised 105 days of ship motions over 12 patrols, with 779 associated daily diaries from 78 participants. Problems most strongly associated with vessel motions were related to the difficulties with physical tasks. Some cognitive aspects of task performance and motion sickness were associated with vertical acceleration magnitudes, but the correlations were less strong than with physical tasks. Practitioner Summary: Little is known about the severity of ship motions that degrade physical and mental performance. The paper offers preliminary estimates of the motion threshold values below which the performance will not be degraded by motion.

A population study of nocturia in Singapore.

OBJECTIVE: To estimate the prevalence of nocturia in the multiracial Asian population of Singapore, using the new International Continence Society standardized definition of one or more voids per night, and to assess its associations, bothersomeness and impact on sleep. SUBJECTS AND METHODS: A door-to-door interview questionnaire survey was conducted amongst a randomly selected sample of 3000 individuals (response rate 78.2%). Nocturia and its associated problems were evaluated using questions from the International Prostate Symptom Score (IPSS), and concurrently, sociodemographic and health variables were recorded. RESULTS: Data from 1134 women (aged 20-95 years) and 1139 men (aged 20-92 years) were analysed; the overall prevalence of nocturia (one or more voids/night) was 55.5%, with an increasing proportion in older groups (P < 0.01). Women had nocturia significantly (P = 0.015) more often than men (58% vs 53%), and it was positively associated with poor health, with the highest odds ratios (95% confidence interval) for diabetes mellitus of 2.0 (1.3-3.1), for renal disease of 6.4 (2.3-18.2), and for strokes of 3.1 (1.1-9.2). In both men and women, the median IPSS in patients with nocturia was significantly higher than that in patients without nocturia (P < 0.001). For individuals waking once a night, only 9.5% considered nocturia a problem and 13.5% complained of sleep disturbances; these values increased to 36% and 40% for individuals waking up twice or more /night. CONCLUSION: Nocturia is a common condition amongst Singaporean adults, especially in the elderly; it has strong associations with poor health and other lower urinary tract symptoms. The degree of nocturia determines whether patients are likely to be bothered by it or have sleep disturbance, which will influence their help-seeking behaviour.

Adrenal leiomyosarcoma: a case report and literature review.

Leiomyosarcoma of the adrenal gland is a very rare tumour. We report a case of this rare tumour and review the previous case reports. The patient, a 68-year-old woman, presented with a 1-week history of right loin pain and fever associated with loss of weight and appetite. Computerised tomography and ultrasound scans showed the presence of a right adrenal gland tumour, which was subsequently surgically removed. Histological examination of the 12.5-cm tumour revealed a leiomyosarcoma of the adrenal gland. The patient was alive and well with no evidence of recurrent disease 1 year later.

Evaluating the motions of a semi-submersible platform with respect to human response.

The motions of a semi-submersible drilling platform have been evaluated so as to predict the effects on the comfort and activities of the crew. The horizontal motions at the drill floor exceeded the 'average threshold of perception' defined in International Standard 6897 (ISO 6897, 1984) by more than a factor of two; they were about half of the limit for the worst 10 min in five years for 'fixed offshore structures where work of a somewhat critical nature is carried out'. Other standards predict that the vertical motion would cause vomiting due to motion sickness in less than 5% of unadapted adults within the first 8h of exposure. The calculated probability of 'motion-induced interruptions' (loss-of-balance events) caused by deck motion was negligible. Notwithstanding the above conclusions, it is considered that current standards are insufficient to predict the effects of the motions of ships and floating platforms on the activities of the crew.

Human factors consideration in clinical applications of virtual reality.

Virtual reality environments have many potential applications in medicine, including surgical training, tele-operated robotic surgery, assessment and rehabilitation of behavioural and neurological disorders and diagnosis, therapy and rehabilitation of physical disabilities. Although there is much potential for the use of immersive virtual reality environments in clinical applications, there are problems which could limit their ultimate usability. Some users have experienced side-effects during and after exposure to virtual reality environments. The symptoms include ocular problems, disorientation and balance disturbances, and nausea. Susceptibility to side-effects can be affected by age, ethnicity, experience, gender and physical fitness, as well as the characteristics of the display, the virtual environment and the tasks. The characteristics of the virtual reality system have also been shown to affect the ability of users to perform tasks in a virtual environment. Many of these effects can be attributed to delays between the sampling of head and limb positions and the presentation of an appropriate image on the display. The introduction of patients to virtual reality environments, for assessment, therapy or rehabilitation, raises particular safety and ethical issues. Patients exposed to virtual reality environments for assessment and rehabilitation may have disabilities which increase their susceptibility to certain side-effects. Special precautions therefore need to be taken to ensure the safety and effectiveness of such virtual reality applications. These precautions include minimisation of possible side-effects at the design stage. Factors are identified which are likely to affect the incidence of side-effects during and after exposures, and which need to be understood in order to minimise undesirable consequences. There is also a need for the establishment of protocols for monitoring and controlling exposures of patients to virtual reality environments. Issues are identified which need to be included in such protocols.

Virtual reality environments for psycho-neuro-physiological assessment and rehabilitation.

Virtual Reality Environments for Psychoneurophysiological Assessment and Rehabilitation-is an European Community funded project (Telematics for health-HC 1053 http:/(/)www.etho.be/ht_projects/vrepar/) whose aim is: to develop a PC based virtual reality system (PC-VRS) for the medical market that can be marketed at a price which is accessible to its possible end-users (hospitals, universities and research centres) and which would have the modular, connectability and interoperability characteristics that the existing systems lack; to develop three hardware/software modules for the application of the PC VRS in psychoneurophysiological assessment and rehabilitation. The chosen development areas are eating disorders (bulimia, anorexia and obesity), movement disorders (Parkinson's disease and torsion dystonia) and stroke disorders (unilateral neglect and hemiparesis). This paper presents the rationale of the different approaches and the methodology used.

Sinusoidal and random whole-body vibration: comparative effects on visual performance.

An experimental comparison of the effect of whole-body sinusoidal and one-third octave-band random vibration on the performance of a display reading task is described. The findings indicate that one-third octave-band random vibration has significantly less effect on performance. Subsequent measurements of rotational head motion demonstrated that this finding may be due to differences in the velocity probability density distributions produced by the different motions. Subjects also performed the visual task during exposure to several broad-band random motions. Predicted error values were obtained by averaging the frequency weighted time histories of these motions. It was found that both R.M.S. and R.M.Q. averaging procedures applied to the broad-band frequency weighted time histories gave accurate error predictions when compared with the measured error scores. Practical implications of the experimental findings and recommendations for future research are discussed.