Trehalose enhances mitochondria deficits in human NPC1 mutant fibroblasts but disrupts mouse Purkinje cell dendritic growth ex vivo.

Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol accumulation that leads to early neurodegeneration in Niemann-Pick type C (NPC) disease. Mitochondria pathology and deficits in NPC1 deficient cells are associated with impaired lysosomal proteolysis and metabolic signaling. It is thought that activation of the transcription factor TFEB, an inducer of lysosome biogenesis, restores lysosomal-autophagy activity in lysosomal storage disorders. Here, we investigated the effect of trehalose, a TFEB activator, in the mitochondria pathology of NPC1 mutant fibroblasts in vitro and in mouse developmental Purkinje cells ex vivo. We found that in NPC1 mutant fibroblasts, serum starvation or/and trehalose treatment, both activators of TFEB, reversed mitochondria fragmentation to a more tubular mitochondrion. Trehalose treatment also decreased the accumulation of Filipin+ cholesterol in NPC1 mutant fibroblasts. However, trehalose treatment in cerebellar organotypic slices (COSCs) from wild-type and Npc1nmf164 mice caused mitochondria fragmentation and lack of dendritic growth and degeneration in developmental Purkinje cells. Our data suggest, that although trehalose successfully restores mitochondria length and decreases cholesterol accumulation in NPC1 mutant fibroblasts, in COSCs, Purkinje cells mitochondria and dendritic growth are negatively affected possibly through the overactivation of the TFEB-lysosomal-autophagy pathway.

Reducing LGBTQ+ adolescent mental health inequalities: a realist review of school-based interventions.

BACKGROUND: LGBTQ+ young people have elevated rates of poor mental health in comparison to their cisgender heterosexual peers. School environment is a key risk factor and consistently associated with negative mental health outcomes for LGBTQ+ adolescents. AIMS: To examine how, why, for whom and in what context school-based interventions prevent or reduce mental health problems in LGBTQ+ adolescents. METHODS: A realist review methodology was utilised and focused on all types of school-based interventions and study designs. A Youth Advisory Group were part of the research team. Multiple search strategies were used to locate relevant evidence. Studies were subject to inclusion criteria and quality appraisal, and included studies were synthesised to produce a programme theory. Seventeen studies were included in the review. RESULTS: Eight intervention components were necessary to address LGBTQ+ pupils mental health: affirmative visual displays; external signposting to LGBTQ+ support; stand-alone input; school-based LGBTQ support groups; curriculum-based delivery; staff training; inclusion policies; trusted adult. Few school-based interventions for this population group were identified. CONCLUSIONS: The programme theory indicates that "to work" school-based interventions must have a "whole-school" approach that addresses specifically the dominant cis-heteronormative school environment and hence the marginalisation, silence, and victimisation that LGBTQ+ pupils can experience.

'The Addiction Was Making Things Harder for My Mental Health': A Qualitative Exploration of the Views of Adults and Adolescents Accessing a Substance Misuse Treatment Service.

The relationship between substance use and mental health is complex, and both constitute a global public health burden. In the UK, the estimated annual financial costs of alcohol-related harm and illicit drug use are GBP 21.5 billion and GBP 10.7 billion, respectively. This issue is magnified in the North East of England, where treatment access is low and a large proportion of individuals experience socioeconomic deprivation. The present study aimed to explore the experiences of adults and adolescents accessing a substance misuse treatment service in the North East, in order to inform policy makers, commissioners, and providers of substance misuse treatment and prevention. Semi-structured qualitative interviews were conducted with an opportunistic sample of n = 15 adult participants (aged 18 years and over) and n = 10 adolescent participants (aged between 13 and 17 years). Interviews were audio-recorded, transcribed, anonymised, and analysed thematically. Five key themes were identified: (1) initiation of substance use, (2) early life experiences, (3) the bi-directional relationship of mental health and substance use, (4) cessation of substance use, and (5) accessing treatment. Future preventative interventions should focus on providing support to individuals who have been exposed to adverse childhood experiences, with treatment provision for individuals experiencing co-occurring mental health and substance use issues taking a more holistic approach.

Understanding How School-Based Interventions Can Tackle LGBTQ+ Youth Mental Health Inequality: A Realist Approach.

Globally, research indicates that LGBTQ+ young people have elevated rates of poor mental health in comparison with their cisgender heterosexual peers. The school environment is a major risk factor and is consistently associated with negative mental health outcomes for LGBTQ+ young people. The aim of this UK study was to develop a programme theory that explained how, why, for whom, and in what context school-based interventions prevent or reduce mental health problems in LGBTQ+ young people, through participation with key stakeholders. Online realist interviews were conducted in the UK with (1) LGBTQ+ young people aged between 13-18 years attending secondary schools (N = 10); (2) intervention practitioners (N = 9); and (3) school staff (N = 3). A realist retroductive data analysis strategy was employed to identify causal pathways across different interventions that improved mental health outcomes. The programme theory we produced explains how school-based interventions that directly tackle dominant cisgender and heterosexual norms can improve LGBTQ+ pupils' mental health. We found that context factors such as a 'whole-school approach' and 'collaborative leadership' were crucial to the delivery of successful interventions. Our theory posits three causal pathways that might improve mental health: (1) interventions that promote LGBTQ+ visibility and facilitate usualising, school belonging, and recognition; (2) interventions for talking and support that develop safety and coping; and (3) interventions that address institutional school culture (staff training and inclusion polices) that foster school belonging, empowerment, recognition, and safety. Our theoretical model suggests that providing a school environment that affirms and usualises LGBTQ+ identities and promotes school safety and belonging can improve mental health outcomes for LGBTQ+ pupils.

Substance Use, Health, and Adverse Life Events amongst Amphetamine-Type Stimulant Users in North East England: A Cross-Sectional Study.

Amphetamine-type stimulants (ATS) are the second most commonly used class of illicit drugs globally, yet there is limited understanding of which factors contribute to different pathways of ATS use. We sought to compare current, former, and exposed non-ATS users' substance use, mental/physical health, and adverse life experiences. A cross-sectional survey, using computer-assisted personal interview software, was conducted between June 2018 and March 2019 in North East England. Quota-based sampling was used to recruit 389 individuals (aged 18 to 68; 52.6% male): 137 current ATS users; 174 former users; and 78 exposed non-users. Standardized screening questionnaires captured current/prior substance use. Participants self-reported diagnoses of selected physical and mental health disorders and specific adverse life experiences. Analysis used descriptive statistics and comparative tests (including chi-square, Kruskal-Wallis and Mann-Whitney U). Early exposure to illicit substances, challenging mental health, and certain adverse life experiences (such as growing up in statutory care) were more common in individuals currently using ATS compared to those who had never used or stopped using stimulants. Multi-level interventions are needed that address the mental health, social, and economic needs of people with dependent drug use. These could include targeted efforts to support children growing up under care, integrated mental health and substance use support, and joined-up substance use interventions reflective of wider structural factors.

Topological Design of Highly Anisotropic Aligned Hole Transporting Molecular Bottlebrushes for Solution-Processed OLEDs.

Polyvinyl polymers bearing pendant hole transport functionalities have been extensively explored for solution-processed hole transport layer (HTL) technologies, yet there are only rare examples of high anisotropic packing of the HT moieties of these polymers into substrate-parallel orientations within HTL films. For small molecules, substrate-parallel alignment of HT moieties is a well-established approach to improve overall device performance. To address the longstanding challenge of extension from vapor-deposited small molecules to solution-processable polymer systems, a fundamental chemistry tactic is reported here, involving the positioning of HT side chains within macromolecular frameworks by the construction of HT polymers having bottlebrush topologies. Applying state-of-the-art polymer synthetic techniques, various functional subunits, including triphenylamine (TPA) for hole transport and adhesion to the substrate, and perfluoro alkyl-substituted benzyloxy styrene for migration to the air interface, were organized with exquisite control over the composition and placement throughout the bottlebrush topology. Upon assembling the HT bottlebrush (HTB) polymers into monolayered HTL films on various substrates through spin-casting and thermal annealing, the backbones of HTBs were vertically aligned while the grafts with pendant TPAs were extended parallel to the substrate. The overall design realized high TPA π-stacking along the out-of-plane direction of the substrate in the HTLs, which doubled the efficiency of organic light-emitting diodes compared with linear poly(vinyl triphenylamine)s.

School culture and student mental health: a qualitative study in UK secondary schools.

BACKGROUND: There is consistency of evidence on the link between school culture and student health. A positive school culture has been associated with positive child and youth development, effective risk prevention and health promotion efforts, with extensive evidence for the impact on student mental health. Interventions which focus on socio-cultural elements of school life, and which involve students actively in the process, are increasingly understood to be important for student mental health promotion. This qualitative study was undertaken in three UK secondary schools prior to the implementation of a participative action research study bringing students and staff together to identify changes to school culture that might impact student mental health. The aim was to identify how school culture is conceptualised by students, parents and staff in three UK secondary schools. A secondary aim was to explore which components of school culture were perceived to be most important for student mental health. METHODS: Across three schools, 27 staff and seven parents participated in in-depth interviews, and 28 students participated in four focus groups. The Framework Method of thematic analysis was applied. RESULTS: Respondents identified elements of school culture that aligned into four dimensions; structure and context, organisational and academic, community, and safety and support. There was strong evidence of the interdependence of the four dimensions in shaping the culture of a school. CONCLUSIONS: School staff who seek to shape and improve school culture as a means of promoting student mental health may have better results if this interdependence is acknowledged, and improvements are addressed across all four dimensions.

What is the impact of structural and cultural factors and interventions within educational settings on promoting positive mental health and preventing poor mental health: a systematic review.

Mental health (MH) difficulties are on the increase among children and young people (CYP). Evidence has shown that educational settings contain both risk and protective factors for MH. This review investigated which structural and cultural factors and interventions within educational settings promote positive MH and prevent poor MH in 4-18 year olds. Searches were conducted in PsychINFO, Embase, ERIC, ASSIA and British Education Index, and reference lists from key studies and relevant systematic reviews were hand-searched. Intervention, cohort, and qualitative studies were included. Of the 62 included papers, 36 examined cultural factors (30 social/relational and six value-related) while 12 studies examined structural factors (eight organisational and four physical) and 14 studies examined multiple factors. There was strong evidence for the impact of positive classroom management techniques, access to physical activity, and peer mentoring on student MH. Studies examining the impact of positive school culture, teacher training in MH and parent involvement in school MH activities also found predominantly positive results for student MH, albeit the evidence was of lower quality or from a low number of studies. Few studies explicitly examined the impact of interventions on MH inequalities; those that did indicated limited if any reduction to inequalities. A very small number of studies suggested that interventions targeting those at risk of poor MH due to socioeconomic factors could successfully improve wellbeing and reduce depression, anxiety and behavioural problems. Studies exploring the effect of management and leadership strategies within schools, policies, and aspects of the physical environment other than green space were scarce or absent in the literature. This review highlights the need to consider the ways in which educational settings are organised, the culture that is created and the physical space in order to improve the MH of CYP.

A qualitative exploration of 14 to 17-year old adolescents' views of early and preventative mental health support in schools.

BACKGROUND: Preventative interventions may be effective in reducing and preventing symptoms of mental ill health in children and young people. However, there is a paucity of research in this area that explores the views of young people. This paper reports on a qualitative study to inform the future development of attractive and appropriate early and preventative school-based mental health interventions. METHODS: Semi-structured interviews were conducted with a purposive sample of 12 young people aged 14-17 in North East England. Interviews were audio-recorded, transcribed, anonymised and analysed following a thematic approach. RESULTS: Four key themes were identified, relevant to those providing, designing and commissioning early and preventative mental health interventions in schools: 'mental health literacy', 'risk factors for wellbeing decline', 'experience of school-based support' and 'recommendations for future support'. CONCLUSIONS: Young people have varying levels of mental health literacy, but are able to identify academic stress, bullying and the transition from primary to secondary school as leading causes of worry. Young people want more regular and in-depth mental health education, tailored levels of support in school and improved training for teachers.

'The Drugs Did For Me What I Couldn't Do For Myself': A Qualitative Exploration of the Relationship Between Mental Health and Amphetamine-Type Stimulant (ATS) Use.

Substance use and mental ill health constitute a major public health burden, and a key global policy priority is to reduce illicit and other harmful substance use. Amphetamine-type stimulants (ATS) are the second most used class of illicit drugs and a range of mental health issues have been documented amongst users. This paper explores the relationship between mental health and ATS use, through a thematic analysis of qualitative interviews with n = 18 current and former ATS users in England. The findings are presented by trajectory point of; (1) Initiation of ATS use; (2) continued and increased ATS use and (3) decreased and remitted ATS use. This work helps to develop understanding around the complex and bi-directional relationship between ATS use and mental health. Many ATS users lead chaotic lives and engage in multiple risk behaviours, however there is a need to better understand and conceptualise the dynamic interaction between different individual, social, environment and cultural factors that determine individuals' mental health and substance use. There is no 'one size fits all' approach to prevention and treatment, and these findings highlight the need for more joined-up, tailored and holistic approaches to intervention development.

Using Behavioural Insights to Improve the Uptake of Services for Drug and Alcohol Misuse.

In the U.K., 270,705 adults were in contact with drug and alcohol treatment services between April 2019 and March 2020. Within the same time period, 118,995 individuals exited the treatment system, and just over a third (36%) left treatment without completing it. The latter includes individuals declining further treatment and unsuccessful transfers between services. The aim of this study was to explore the factors that affect drug and alcohol treatment uptake within a drug and alcohol service in North East England. A mixed-methods approach was adopted. The exploration of factors affecting treatment uptake was captured through a behavioural insights survey and 1:1 in-depth qualitative interviews with service users within one council area within the North East of England. There were 53 survey participants, and a further 15 participants took part in qualitative interviews. We triangulated data sources to report consistencies and discrepancies in the data. Findings show that treatment services aiming to reduce missed appointments and increase retention rates need to implement several strategies. Consistently distributing appointment cards, using text message reminders, displaying a timetable presenting all treatment options, and displaying information in a format to ensure it is accessible to individuals with lower health literacy and reducing wait times for appointments will all improve appointment attendance.

Exploring pathways into and out of amphetamine type stimulant use at critical turning points: a qualitative interview study.

Amphetamine Type Stimulants (ATS) are increasingly used drugs globally. There is limited evidence about what shapes ATS use at critical turning points located within drug using pathways. Using turning point theory, as part of a life course approach, the ATTUNE study aimed to understand which social, economic and individual factors shape pathways into and out of ATS use. Qualitative, semi-structured interviews (n = 70) were undertaken with individuals who had used ATS, or had been exposed to them at least once. Our findings show that turning points for initiation were linked to pleasure, curiosity, boredom and declining mental health; increased use was linked to positive effects experienced at initiation and multiple life-stressors, leading to more intense use. Decreased use was prompted by pivotal events and sustained through continued wellbeing, day-to-day structure, and non-using social networks. We argue that the heterogeneity of these individuals challenges stereotypes of stimulant use allied to nightclubs and 'hedonism'. Further, at critical turning points for recovery, the use of services for problematic ATS consumption was low because users prioritised their alcohol or opioid use when seeking help. There is a need to develop service provision, training, and better outreach to individuals who need support at critical turning points.

Health and social care providers' perspectives of older people's drinking: A systematic review and thematic synthesis of qualitative studies.

BACKGROUND: alcohol may increase risks to late-life health, due to its impact on conditions or medication. Older adults must weigh up the potential risks of drinking against perceived benefits associated with positive roles of alcohol in their social lives. Health and social care workers are in a key position to support older people's decisions about their alcohol use. OBJECTIVE: to systematically review and synthesise qualitative studies exploring health and social care providers' views and experiences of older people's drinking and its management in care services. METHOD: a pre-specified search strategy was applied to five electronic databases from inception to June 2018. Grey literature, relevant journals, references and citations of included articles were searched. Two independent reviewers sifted and quality-appraised articles. Included study findings were analysed through thematic synthesis. RESULTS: 18 unique studies were included. Four themes explained findings: uncertainty about drinking as a legitimate concern in care provision for older people; the impact of preconceptions on work with older adults; sensitivity surrounding alcohol use in later life; and negotiating responsibility for older adults' alcohol use. Discipline- and country-specific patterns are highlighted. CONCLUSIONS: reservations about addressing alcohol could mean that service providers do not intervene with older adults. Judgements of whether older care recipients' drinking warrants intervention are complex. Providers will need support and training to recognise and provide appropriate intervention for drinking amongst older care recipients.

Using life course charts to assess and compare trajectories of amphetamine type stimulant consumption in different user groups: a cross-sectional study.

BACKGROUND: Amphetamine-type stimulants (ATS) are the second most commonly used illicit drugs in Europe and globally. However, there is limited understanding of what shapes patterns of ATS use over the life course. The ATTUNE project "Understanding Pathways to Stimulant Use: a mixed methods examination of the individual, social and cultural factors shaping illicit stimulant use across Europe" aims to fill this gap. Here we report initial findings from the life course chart exercise conducted as part of qualitative interviews with ATS users and nonusers. METHODS: Two hundred seventy-nine in-depth qualitative interviews were conducted with five ATS user groups (current and former dependent users;current and former frequent users;non-frequent users) and one group of exposed non-ATS users in five European countries (Germany, UK, Poland, Netherlands and Czech Republic). As part of the interviews, we used life course charts to capture key life events and substance use histories. Life events were categorised as either positive, neutral or negative, and associated data were analysed systematically to identify differences between user groups. We applied statistical analysis of variance (ANOVA) and analysis of covariance (ANCOVA) to test for group differences. RESULTS: Out of 3547 life events documented, 1523 life events were categorised as neutral, 1005 life events as positive and 1019 life events as negative. Current and formerly dependent ATS users showed more negative life events for the entire life course after age adjustment. Although some group differences could be attributed to the individuals' life course prior to first ATS use, most negative life events were associated with periods of ATS usage. A detailed analysis of the specific life domains reveals that dominantly, the social environment was affected by negative life events. CONCLUSIONS: For non-dependent, frequent and non-frequent ATS users, negative life events from the period of ATS use do not become obvious in our analysed data. Besides preventing a pathway into ATS dependency, the aim of an intervention should be to reduce the harm by for example drug testing which offers also the opportunity for interventions to prevent developing a substance use dependency. For the group of dependent ATS users, our study suggests holistic, tailored interventions and specialist treatment services are needed, as a single, simple intervention is unlikely to cover all the life domains affected.

Drinking in later life: a systematic review and thematic synthesis of qualitative studies exploring older people's perceptions and experiences.

Background: alcohol presents risks to the health of older adults at levels that may have been 'safer' earlier in life. Moderate drinking is associated with some health benefits, and can play a positive role in older people's social lives. To support healthy ageing, we must understand older people's views with regards to their drinking. This study aims to synthesise qualitative evidence exploring the perceptions and experiences of alcohol use by adults aged 50 years and over. Methods: a pre-specified search strategy was applied to Medline, PsychINFO, Scopus, Applied Social Sciences Index and Abstracts and Cumulative Index to Nursing and Allied Health Literature databases from starting dates. Grey literature, relevant journals, references and citations of included articles were searched. Two independent reviewers sifted articles and assessed study quality. Principles of thematic analysis were applied to synthesise the findings from included studies. Results: of 2,056 unique articles identified, 25 articles met inclusion criteria. Four themes explained study findings: routines and rituals of older people's drinking; self-image as a responsible drinker; perceptions of alcohol and the ageing body; and older people's access to alcohol. Differences between gender, countries and social patterns are highlighted. Conclusions: older people perceive themselves as controlled and responsible drinkers. They may not recognise risks associated with alcohol, but appreciate its role in sustaining social and leisure activities important to health and well-being in later life. These are important considerations for intervention development. Drinking is routinised across the life course and may be difficult to change in retirement.

Which individual, social and environmental influences shape key phases in the amphetamine type stimulant use trajectory? A systematic narrative review and thematic synthesis of the qualitative literature.

BACKGROUND AND AIMS: There is limited evidence on what shapes amphetamine-type stimulant (ATS) use trajectories. This systematic narrative review and qualitative synthesis aimed to identify individual, social and environmental influences shaping key phases in the ATS use trajectory: initiation, continuation, increase/relapse and decrease/abstinence. METHODS: MEDLINE, PsycINFO, EMBASE, and PROQUEST (social science premium collection) were searched from 2000 to 2018. Studies of any qualitative design were eligible for inclusion. Extracted data were analysed according to four key phases within drug pathways, and then cross-analysed for individual, social and environmental influences. RESULTS: Forty-four papers based on 39 unique studies were included, reporting the views of 1879 ATS users. Participants were aged 14-58 years, from varied socio-economic and demographic groups, and located in North America, Europe, Australasia and South East Asia. Reasons for initiation included: to boost performance at work and in sexual relationships, promote a sense of social 'belonging' and help manage stress. Similar reasons motivated continued use, combined with the challenge of managing withdrawal effects in long-term users. Increased tolerance and/or experiencing a critical life event contributed to an increase in use. Reasons for decrease focused on: increased awareness of the negative health impacts of long-term use, disconnecting from social networks or relationships and financial instability. CONCLUSIONS: Amphetamine-type stimulant users are a highly diverse population, and their drug use careers are shaped by a complex dynamic of individual, social and environmental factors. Tailored, joined-up interventions are needed to address users' overlapping economic, health and social care needs in order to support long-term abstinence.

Degradation of Hole Transport Materials via Exciton-Driven Cyclization.

Organic light-emitting diode (OLED) displays have been an active and intense area of research for well over a decade and have now reached commercial success for displays from cell phones to large format televisions. A more thorough understanding of the many different potential degradation modes which cause OLED device failure will be necessary to develop the next generation of OLED materials, improve device lifetime, and to ultimately improve the cost vs performance ratio. Each of the different organic layers in an OLED device can be susceptible to unique decomposition pathways, however stability toward excitons is critical for emissive layer (EML) materials as well as any layer near the recombination zone. This study will specifically focus on degradation modes within the hole transport layer (HTL) with the goal being to identify the general decomposition paths occurring in an operating device and use this information to design new derivatives which can block these pathways. Through post-mortem analyses of several aged OLED devices, an apparently common intramolecular cyclization pathway has been identified that was not previously reported for arylamine-containing HTL materials and that operates parallel to but faster than the previously described fragmentation pathways.

Tetrahalide complexes of the [U(NR)2]2+ ion: synthesis, theory, and chlorine K-edge X-ray absorption spectroscopy.

Synthetic routes to salts containing uranium bis-imido tetrahalide anions [U(NR)(2)X(4)](2-) (X = Cl(-), Br(-)) and non-coordinating NEt(4)(+) and PPh(4)(+) countercations are reported. In general, these compounds can be prepared from U(NR)(2)I(2)(THF)(x) (x = 2 and R = (t)Bu, Ph; x = 3 and R = Me) upon addition of excess halide. In addition to providing stable coordination complexes with Cl(-), the [U(NMe)(2)](2+) cation also reacts with Br(-) to form stable [NEt(4)](2)[U(NMe)(2)Br(4)] complexes. These materials were used as a platform to compare electronic structure and bonding in [U(NR)(2)](2+) with [UO(2)](2+). Specifically, Cl K-edge X-ray absorption spectroscopy (XAS) and both ground-state and time-dependent hybrid density functional theory (DFT and TDDFT) were used to probe U-Cl bonding interactions in [PPh(4)](2)[U(N(t)Bu)(2)Cl(4)] and [PPh(4)](2)[UO(2)Cl(4)]. The DFT and XAS results show the total amount of Cl 3p character mixed with the U 5f orbitals was roughly 7-10% per U-Cl bond for both compounds, which shows that moving from oxo to imido has little effect on orbital mixing between the U 5f and equatorial Cl 3p orbitals. The results are presented in the context of recent Cl K-edge XAS and DFT studies on other hexavalent uranium chloride systems with fewer oxo or imido ligands.

Phototriggered DNA phosphoramidate ligation in a tandem 5'-amine deprotection/3'-imidazole activated phosphate coupling reaction.

We report the preparation and use of an N-methyl picolinium carbamate protecting group for applications in a phototriggered nonenzymatic DNA phosphoramidate ligation reaction. Selective 5'-amino protection of a modified 13-mer oligonucleotide is achieved in aqueous solution by reaction with an N-methyl-4-picolinium carbonyl imidazole triflate protecting group precursor. Deprotection is carried out by photoinduced electron transfer from Ru(bpy)(3)(2+) using visible light photolysis and ascorbic acid as a sacrificial electron donor. Phototriggered 5'- amino oligonucleotide deprotection is used to initiate a nonenzymatic ligation of the 13-mer to an imidazole activated 3'-phospho-hairpin template to generate a ligated product with a phosphoramidate linkage. We demonstrate that this methodology offers a simple way to exert control over reaction initiation and rates in nonenzymatic DNA ligation for potential applications in the study of model protocellular systems and prebiotic nucleic acid synthesis.

A direct route to bis(imido)uranium(V) halides via metathesis of uranium tetrachloride.

Metathesis reactions between uranium tetrachloride and lithium 2,6-diisopropylphenylamide in the presence of 4,4'-dialkyl-2,2'-bipyridyl (R(2)bpy; R = Me, (t)Bu) or triphenylphosphine oxide (tppo) appear to generate bis(imido)uranium(IV) in situ. These extremely reactive complexes abstract chloride from dichloromethane to generate U(NDipp)(2)Cl(R(2)bpy)(2) or U(NDipp)(2)Cl(tppo)(3) (Dipp = 2,6-(i)Pr(2)C(6)H(3)). The preparation of the bromide and iodide analogues U(NDipp)(2)X(R(2)bpy)(2) was achieved by addition of CH(2)X(2) (X = Br, I) to the uranium(IV) solutions. The uranium(V) halides were characterized by X-ray crystallography and found to exhibit linear N-U-N units and short U-N bonds. Electrochemical measurements were made on the chloride bipyridine species, which reacts readily with iodine or ferrocenium to generate bis(imido)uranium(VI) cations.