Bringing biocatalytic deuteration into the toolbox of asymmetric isotopic labelling techniques.

Enzymes dependent on nicotinamide cofactors are important components of the expanding range of asymmetric synthetic techniques. New challenges in asymmetric catalysis are arising in the field of deuterium labelling, where compounds bearing deuterium (2H) atoms at chiral centres are becoming increasingly desirable targets for pharmaceutical and analytical chemists. However, utilisation of NADH-dependent enzymes for 2H-labelling is not straightforward, owing to difficulties in supplying a suitably isotopically-labelled cofactor ([4-2H]-NADH). Here we report on a strategy that combines a clean reductant (H2) with a cheap source of 2H-atoms (2H2O) to generate and recycle [4-2H]-NADH. By coupling [4-2H]-NADH-recycling to an array of C=O, C=N, and C=C bond reductases, we demonstrate asymmetric deuteration across a range of organic molecules under ambient conditions with near-perfect chemo-, stereo- and isotopic selectivity. We demonstrate the synthetic utility of the system by applying it in the isolation of the heavy drug (1S,3'R)-[2',2',3'-2H3]-solifenacin fumarate on a preparative scale.

Generating single metalloprotein crystals in well-defined redox states: electrochemical control combined with infrared imaging of a NiFe hydrogenase crystal.

We describe an approach to generating and verifying well-defined redox states in metalloprotein single crystals by combining electrochemical control with synchrotron infrared microspectroscopic imaging. For NiFe hydrogenase 1 from Escherichia coli we demonstrate fully reversible and uniform electrochemical reduction from the oxidised inactive to the fully reduced state, and temporally resolve steps during this reduction.

Copper(II)-mediated thermolysis of alginates: a model kinetic study on the influence of metal ions in the thermochemical processing of macroalgae.

Thermochemical processing methods such as pyrolysis are of growing interest as a means of converting biomass into fuels and commodity chemicals in a sustainable manner. Macroalgae, or seaweed, represent a novel class of feedstock for pyrolysis that, owing to the nature of the environments in which they grow coupled with their biochemistry, naturally possess high metal contents. Although the impact of metals upon the pyrolysis of terrestrial biomass is well documented, their influence on the thermochemical conversion of marine-derived feeds is largely unknown. Furthermore, these effects are inherently difficult to study, owing to the heterogeneous character of natural seaweed samples. The work described in this paper uses copper(II) alginate, together with alginic acid and sodium alginate as model compounds for exploring the effects of metals upon macroalgae thermolysis. A thermogravimetric analysis-Fourier transform infrared spectroscopic study revealed that, unusually, Cu(2+) ions promote the onset of pyrolysis in the alginate polymer, with copper(II) alginate initiating rapid devolatilization at 143°C, 14°C lower than alginic acid and 61°C below the equivalent point for sodium alginate. Moreover, this effect was mirrored in a sample of wild Laminaria digitata that had been doped with Cu(2+) ions prior to pyrolysis, thus validating the use of alginates as model compounds with which to study the thermolysis of macroalgae. These observations indicate the varying impact of different metal species on thermochemical behaviour of seaweeds and offer an insight into the pyrolysis of brown macroalgae used in phytoremediation of metal-containing waste streams.

Dental therapy in the United Kingdom: part 4. Teamwork--is it working for dental therapists?

OBJECTIVES: To determine whether practising dental therapists, including dually qualified hygienist/therapists, considered themselves to be part of the clinical team and whether clinical work referred to them met with their expectations. METHODS: A postal survey enquired about work experiences of UK dental therapists, as previously described earlier in the series. RESULTS: While they certainly considered themselves to be part of the clinical team, the majority of respondents did not feel 'fully utilised'. Seventy percent of respondents felt that the dentist had more patients that could be referred and 55% thought that they could do more extensive work. There was concern that dentists lacked awareness of therapists' clinical potential, although some respondents highlighted very positive experiences in practice. CONCLUSIONS: Dental therapists feel that they are part of the clinical team but consider that their skills are not fully utilised in many cases. There is scope for raising awareness among dentists regarding the therapists' clinical potential as well as sharing ideas for good working practice both within individual clinical settings and between different practices.

Dental therapy in the United Kingdom: part 3. Financial aspects of current working practices.

OBJECTIVES: To enquire into current remuneration arrangements among UK dental therapists and to explore the nature of any financially related concerns. METHODS: Part of the postal survey of therapists described in the previous paper in this series. RESULTS: The majority of therapists (63%) often work in multiple locations and therefore may be in receipt of more than one type of payment mechanism. Two thirds of therapists are paid an hourly rate in at least one of the locations where they work; just over half are paid a fixed monthly amount and one third are self-employed. Nine percent of respondents were receiving performance-related pay, using goal setting, incentives and bonuses. A number of financially-related concerns were identified. CONCLUSION: Diverse payment systems were reported. Some aspects could present important implications for future recruitment and retention.

Dental therapy in the United Kingdom: part 2. A survey of reported working practices.

OBJECTIVES: To conduct a survey of current working practices of UK dental therapists following the changes in permitted duties, allowed clinical settings and the introduction of the new dental contract in England and Wales. METHODS: A piloted postal questionnaire was circulated in 2006 to all General Dental Council (GDC) registered therapists and those on the hygienists register possessing a dental therapy qualification. Two subsequent mailings were used to boost the response rate. RESULTS: There was an 80.6% response rate (n = 587). Ninety-eight percent of respondents were female. Average time since qualification was 17 years. Eighty percent (n = 470) of respondents were currently working as a dental therapist, 53% part-time. Of the 470, half were engaged entirely in general dental practice (GDP), one third in the salaried dental services (SDS), while others worked across different settings. Only 39% claimed to spend most of their time treating children. Recently qualified therapists more often worked in GDP (p <0.001). Overall, a wide range of clinical duties were performed, although there was concern about maintaining skills across all the competencies since qualification, while emphasis on hygiene work was a limiting factor for some. On the basis of the continued professional development (CPD) activities described over one year, only half would have met the GDC CPD requirements from August 2008 for dental care professionals (DCPs). CONCLUSIONS: More than half of therapists now work in GDP, compared with none six years previously. Many undertake a full range of duties. However, there was concern that some dentists use them for hygiene skills rather than across the whole range of their competencies, risking deskilling, while others reported their inability to gain employment as a therapist.

Dental therapy in the United Kingdom: part 1. Developments in therapists' training and role.

The number of students entering training for dental therapy has been increasing rapidly over the last few years. In practice, the scope of their work has increased, both in terms of permitted duties and their range of clinical settings. The possibilities for dental practitioners to work with therapists is therefore increasing, so it is important for them to be clear about therapists' potential capacity to provide added value to the dental team. This paper, which is the first of four covering aspects of dental therapy in the UK, traces the history of dental therapy together with the development of therapists' training opportunities and emerging competencies, up to the present. The subsequent three papers will describe aspects of a survey of dental therapists undertaken in late 2006.