ABSTRACT
Thiol-reactive Michael acceptors are commonly used for the formation of chemically cross-linked hydrogels. In this paper, we address the drawbacks of many Michael acceptors by introducing pyridazinediones as new cross-linking agents. Through the use of pyridazinediones and their mono- or dibrominated analogues, we show that the mechanical strength, swelling ratio, and rate of gelation can all be controlled in a pH-sensitive manner. Moreover, we demonstrate that the degradation of pyridazinedione-gels can be induced by the addition of thiols, thus providing a route to responsive or dynamic gels, and that monobromo-pyridazinedione gels are able to support the proliferation of human cells. We anticipate that our results will provide a valuable and complementary addition to the existing toolkit of cross-linking agents, allowing researchers to tune and rationally design the properties of biomedical hydrogels.
Subject(s)
Hydrogels , Sulfhydryl Compounds , Humans , Hydrogels/chemistry , Sulfhydryl Compounds/chemistry , Cross-Linking Reagents/chemistryABSTRACT
Protein N-termini provide uniquely reactive motifs for single site protein modification. Though a number of reactions have been developed to target this site, the selectivity, generality, and stability of the conjugates formed has not been studied. We have therefore undertaken a comprehensive comparative study of the most promising methods for N-terminal protein modification, and find that there is no 'one size fits all' approach, necessitating reagent screening for a particular protein or application. Moreover, we observed limited stability in all cases, leading to a need for continued innovation and development in the bioconjugation field.
ABSTRACT
The regio- and stereoselective addition of C(1)-ammonium enolates - generated in situ from aryl esters and the isothiourea catalyst (R)-BTM - to pyridinium salts bearing an electron withdrawing substituent in the 3-position allows the synthesis of a range of enantioenriched 1,4-dihydropyridines. This represents the first organocatalytic approach to pyridine dearomatisation using pronucleophiles at the carboxylic acid oxidation level. Optimisation studies revealed a significant solvent dependency upon product enantioselectivity, with only toluene providing significant asymmetric induction. Using DABCO as a base also proved beneficial for product enantioselectivity, while investigations into the nature of the counterion showed that co-ordinating bromide or chloride substrates led to higher product er than the corresponding tetrafluoroborate or hexafluorophosphate. The scope and limitations of this process are developed, with enantioselective addition to 3-cyano- or 3-sulfonylpyridinium salts giving the corresponding 1,4-dihydropyridines (15 examples, up to 95 : 5 dr and 98 : 2 er).
ABSTRACT
BACKGROUND: This review describes the programmatic features of entry-level master's programs in nursing in the United States that result in a generalist degree for individuals with a baccalaureate degree in another field. The number of entry-level Master of Science in Nursing programs has grown over the past decade, increasing the importance of understanding the features, similarities, and differences among these programs. METHOD: Using a custom report of accredited schools of nursing with entry-level master's programs from the American Association of Colleges of Nursing and the Accreditation Commission for Education in Nursing's website, we conducted a program review to describe the programs' features. RESULTS: There is substantial variation in nomenclature, length, credits, and clinical hours among entry-level master's programs. CONCLUSION: The difference in these programs may create confusion among potential students of the programs and employees of the graduates. Investigations are needed on the relationship between programmatic features and outcomes. [J Nurs Educ. 2019;58(9):525-529.].
