While a diverse set of design strategies have produced various chemical tools for biomolecule labeling in aqueous media, the development of nonaqueous, biomolecule-compatible media for bioconjugation has significantly lagged behind. In this report, we demonstrate that an aprotic ionic liquid serves as a novel reaction solvent for protein bioconjugation without noticeable loss of the biomolecule functions. The ionic liquid bioconjugation approach led to discovery of a novel triphenylphosphine-mediated amine–azide coupling reaction that forges a stable tetrazene linkage on unprotected peptides and proteins. This strategy of using untraditional media would provide untapped opportunities for expanding the scope of chemical approaches for bioconjugation.

Valproic acid is widely used as a mood stabilizer. We report a case of an adult with bipolar disorder taking therapeutic doses of valproic acid, who presented to the emergency department with coma related to hyperammonemia as a complication of valproic acid treatment. Valproic acid was discontinued which resulted in rapid clinical recovery. Valproic acid induced coma was likely related to a urea cycle enzymopathy. Clinicians should consider hyperammonemia in all patients who present with coma and other mental status changes while on valproic acid. In such patients, ammonia level should be obtained in addition to liver function tests.

Metrics & MoreArticle Recommendations * sı Supporting Information F urther study of the phosphine-mediated reactions on biomolecules revealed that the structure of the reaction product is a urea group but not a tetrazene group. One of the key peaks (300 ppm, which was assigned as one of the nitrogen Addition/Correction pubs.acs.org/JACS

Bioconjugation of carbohydrates has advanced the modern chemical biology and medical science research by incorporation of desired functionalities to the oxygen-rich biomolecules. However, the labeling process or selective chemical reaction of carbohydrates have been a challenging task because of their chemical, functional, and structural diversities, and no single chemical modification tool can be universally applicable to all the target substrates in different environments. In this report, we have developed a bioconjugation strategy for labeling of carbohydrate derivatives through a phosphine-mediated three-component coupling reaction in an ionic liquid medium. The multiple characterization methods identified a urea group as the reaction product of the phosphine-mediated coupling through the installation of carbonyl group from carbon dioxide in air and loss of nitrogen gas from the azide group. We have developed purification protocols to facilitate the cleanup and analysis of ionic liquid-based bioconjugation processes, which can be used for a diverse set of carbohydrate derivatives. The phosphine-mediated urea-forming reaction was applied to a variety of amine- and azide-containing carbohydrates such as antibiotics, anti-tumor agent, and polysaccharide with corresponding azide- and amine-based reagent, respectively. The ionic liquid-based bioconjugation was amenable for the chemical modification of the mammalian cell lysate in an azide-dependent manner. Thus, the present report represents not only the advancement of the nonaqueous bioconjugation method for carbohydrate derivatives from the reaction development perspectives, but also their practical utility for creation of carbohydrate conjugates as well as a study tool of the biomolecule through the bioorthogonal chemistry-like reactivity.

This chapter discusses the relationship between co-produced research and community development. In particular, it addresses longstanding debates about whether certain forms of co-produced research (especially participatory action research), are, in fact, indistinguishable from community development. This question is explored with reference to Imagine North East, a co-produced research project based in North East England, which was part of a larger programme of research on civic participation (Imagine – connecting communities through research). The chapter offers a critical analysis of three elements of Imagine North East: an academic-led study of community development from the 1970s to the present; starting with the national Community Development Projects in Benwell and North Shields; a series of community development projects undertaken by local community-based organisations; and the challenges and outcomes of a joint process of reflection and co-inquiry. It considers the role of co-produced research in challenging stigma, celebrating place and developing skills and community networks – all recognisable as community development processes and outcomes. It also discusses the difficult process of bringing together a disparate group of people in a co-inquiry group; the time taken to develop identities as practitioner-researchers; and the skills required to engage in a kind of ‘collaborative reflexivity’ whereby members of the group critically reflected together on the group’s role and dynamics.