An N-Fluorinated Imide for Practical Catalytic Imidations.

Catalytic imidation using NFSI as the nitrogen source has become an emerging tool for oxidative carbon-nitrogen bond formation. However, the less than ideal benzenesulfonimide moiety is incorporated into products, severely detracting its synthetic value. As a solution to this challenge, we report herein the development of a novel N-fluorinated imide, N-fluoro-N-(fluorosulfonyl)carbamate (NFC), by which the attached imide moiety acts as a modular synthetic handle for one-step derivatization to amines, sulfonamides, and sulfamides. Furthermore, this study revealed the superior reactivity of NFC as showcased in a copper-catalyzed imidation of benzene derivatives and imidocyanation of aliphatic alkenes, overcoming the limitation of NFSI-mediated reactions.

Roles of Lys191 and Lys179 in regulating thermodynamic binding forces of ligands to determine their binding affinity for human histamine H1 receptors.

Docking simulations based on the crystal structure of human histamine H1 receptors have predicted crucial roles of Lys1915.39 and Lys179ECL2, which exist at the entrance of the ligand-binding pocket, in increasing the H1-receptor selectivity for carboxylated second-generation antihistamines via electrostatic interaction. In this study, we evaluated the roles of Lys1915.39 and Lys179ECL2 in regulating the thermodynamic binding forces of non-carboxylated and carboxylated antihistamines that determine their binding affinity for human H1 receptors. The binding enthalpy and entropy of the 3 sets of non-carboxylated and corresponding carboxylated antihistamines (doxepin and olopatadine, desloratadine and loratadine, and terfenadine and fexofenadine, respectively) were estimated using the van't Hoff equation with the dissociation constants obtained from the displacement curves of the non-carboxylated and carboxylated antihistamines against the binding of [3H]mepyramine to the membrane preparations of Chinese hamster ovary cells expressing human H1 receptors at various temperatures, ranging from 4 °C to 37 °C. We found that the affinity for carboxylated antihistamines was lower than that for the corresponding non-carboxylated compounds due to lower enthalpy-dependent electrostatic binding forces and/or entropy-dependent hydrophobic binding forces. Mutations of Lys1915.39 and/or Lys179ECL2 to alanine mostly increased the binding affinity for antihistamines due to a variety of changes in both enthalpy- and entropy-dependent binding forces. These results suggest that Lys1915.39 and Lys179ECL2 may not contribute to selectively increasing the binding affinity for carboxylated antihistamines via electrostatic interaction, but that they can negatively modulate the binding affinity for non-carboxylated and carboxylated antihistamines non-selectively by affecting their electrostatic as well as hydrophobic binding forces.

Association between dietary fibre:carbohydrate intake ratio and insulin resistance in Japanese adults without type 2 diabetes.

An easily understandable index that measures the quality of carbohydrate may aid people in adopting dietary habits that improve their glucose tolerance. We aimed to evaluate the relationship between a ratio of dietary fibre to carbohydrate intakes (fibre:carbohydrate ratio (F:C-R)) and glucose tolerance cross-sectionally and longitudinally. Subjects were 190 Japanese men and women without type 2 diabetes (mean age 55·4 years) who participated in a 5-month diet and exercise programme. We compared baseline anthropometric, dietary and metabolic profiles between those with higher F:C-R and those with lower ratios. Multivariable regression analyses were performed to examine the associations between the F:C-R and homoeostasis model of assessment for insulin resistance (HOMA-IR) and HbA1c at baseline and between changes in the F:C-R and changes in HOMA-IR and HbA1c over the 5-month period. At baseline, the higher F:C-R group had significantly lower body weight, lean body mass, fasting insulin level and HOMA-IR as compared with the lower F:C-R group. The two groups had similar intakes of carbohydrate and fat, whereas protein intake was greater in the high F:C-R group. Baseline F:C-R was not significantly associated with HOMA-IR or HbA1c at the beginning of the study in multivariable models. Increases in the ratio during the 5-month programme was associated with reductions in HbA1c (P<0·001). These findings highlight the potential utility of the F:C-R in strategies aimed at type 2 diabetes prevention.

Identification and characterization of a novel N-acyl-homoserine lactonase gene in Sphingomonas ursincola isolated from industrial cooling water systems.

Biofilm formation by bacteria is one of the main causes of fouling in industrial cooling water systems. In many gram-negative bacteria, biofilm formation is regulated by N-acyl-homoserine lactone (AHL)-mediated quorum sensing. In this study, we isolated three AHL-degrading bacteria from cooling water systems and identified them as Sphingomonas ursincola. The draft genome sequence of S. ursincola A1 revealed the presence of an AHL-degrading gene homolog, designated qsdS. The qsdS region was also amplified by PCR from the genomes of the other two S. ursincola strains, SF1 and SF8. Escherichia coli DH5α harboring a QsdS-expressing plasmid showed high degradative activity against AHLs with short and 3-oxo-substituted acyl chains. High-performance liquid chromatography analysis revealed that QsdS is an AHL lactonase, an enzyme that catalyzes AHL ring opening. Furthermore, heterologous expression of QsdS in Pseudomonas aeruginosa PAO1 resulted in degradation of endogenous AHLs and interfered with the quorum-sensing-regulated phenotype.