Isosceles Orthogonal Triples in Linear 2-Normed Spaces

A triple (x, y, z) in a linear 2-normed space (X, ‖.,.‖) is called an isosceles orthogonal triple, denoted |(x, y, z), if |(.,.,.) is said to be homogeneous if |(x, y, z) implies |(ax, y, z) for all real a and it is additive if |(x₁, y, z) and |(x₂, y, z) imply that |(x₁ + x₂, y, z). In addition to developing some basic properties of |(.,.,.), this paper shows that under the assumption of strict convexity, every subspace of X of dimension ≤ 3 contains an isosceles orthogonal triple. Further, if (X, ‖.,.‖) is strictly convex and |(…,.) is either homogeneous or additive, then (X, ‖.,.‖) is a 2-inner product space.     

A rhodium‐catalyzed route for oxidative coupling and cyclization of 2‐aminobenzyl alcohol with ketones leading to quinolines

2‐Aminobenzyl alcohol undergoes oxidative cyclization with aryl(alkyl), alkyl(alkyl) and cyclic ketones in dioxane at 80° in the presence of a catalytic amount of RhCl(PPh₃)₃ along with KOH to afford the corresponding quinolines in good yields. The catalytic pathway seems to be proceeded via a sequence involving initial oxidation of 2‐aminobenzyl alcohol to 2‐aminobenzaldehyde by a rhodium catalyst, cross aldol reaction between 2‐aminobenzaldehyde and ketones, and cyclodehydration.     

Missing-link macrocycles: hybrid heterocalixarene analogues formed from several different building blocks

The synthesis and structural characterization of hybrid heterocalix[4]arene analogues containing pyrrole, benzene, methoxy-substituted benzene, and pyridine subunits is described. Macrocycles 1 and 2, examples of calix[2]benzene[2]pyrrole and calix[1]benzene[3]pyrrole systems, respectively, are synthesized by the condensation of pyrrole and an appropriate phenylbis(carbinol). Macrocycles 3 and 7, examples of calix[2]benzene[1]pyridine[1]pyrrole and calix[1]pyridine[3]pyrrole, respectively, are synthesized by the use of a carbene-based pyrrole-to-pyridine ring-expansion procedure. Single-crystal X-ray analysis reveals that compounds 1a, 1b, and 2b adopt 1,3-alternate conformations in the solid state, whereas compounds 3 and 7 display structures that are best described as "flattened partial cones" in terms of their conformation. (Series a refers to pure benzene-derived systems, whereas series b indicates macrocycles containing 5-methoxyphenyl subunits). In the solid state, the methoxy-functionalized macrocycles 1b and 2b, and the chloropyridine-containing macrocycle 7 exist as dimers. In the case of 1a and 7, these compounds interact with neutral solvent in the solid state. The conformations of the macrocycles in solution were explored by temperature-dependent proton NMR and NOESY spectral analysis. At 188 K, macrocycles 1a and 2a adopt flattened 1,3-alternate conformations, whereas macrocycles 3 and 7 exist in the form of flattened partial-cone conformations. Standard proton NMR titration analyses were carried out in the case of macrocycles 1a and 2a, and reveal that at least the second of these systems is capable of binding fluoride and chloride anions in CD(2)Cl(2) solution at room temperature (K(a)=571 and 17M(-1) in the case of 2a and F(-) and Cl(-), respectively).     

Hydrogen-bonding effects in calix

The synthesis and spectroscopic characterization of self-assembling calix[4]arene based capsules 1a.1a and 1b.1b are described. These compounds feature four urea substituents at the upper rims and four secondary amide fragments at the lower rims that can participate in inter- and intramolecular hydrogen bonding in apolar solution. Communication between the calixarene rims in 1a, b influences the self-assembled cavity's size and shape. Specifically. dimerization results in a perfect cone conformation of the calixarene skeleton in 1a, b and stabilizes a seam of intramolecular amide C=O...H-N hydrogen bonds at the lower rim. This seam is cycloenantiomeric, with either clockwise or counterclockwise arrangements of the head-to-tail amides. Complexation of Na+-cation breaks hydrogen bonds at the lower rim but maintains the capsular assembly. Encapsulation properties of 1a.1a and 1b.1b were studied in nonpolar solvents and their binary mixtures as well as through heterodimerization experiments. The presence of amide groups at the lower rim causes notable differences in the capsule's binding affinities when compared to the corresponding tetraester capsules 1c.1c and 1d.1d. In the monomeric state calixarenes 1a, b are in a pinched cone conformation. The solid state X-ray crystallographic studies with monomeric 1a reveal only two intramolecular C=O...H-N hydrogen bonds between the adjacent amides at the lower rim, and an extensive network of intermolecular hydrogen bonds between urea groups at the upper rim.     

A new synthesis of 1,2,3,5‐tetrahydroimidazo[2,3‐b]‐[1,3]benzodiazocines

A new synthesis of 6‐carbomethoxy‐1,2,3,5‐tetrahydroirnidazo[2,3‐b][1,3]benzodiazocines 13 by the intramolecular cycloaddition reaction of methyl 2‐(1‐aziridinylmethyl)‐3‐(2‐ureidophenyl)propenoates 10 under Appel's dehydration conditions is described. The latter were readily obtained from 2‐nitrobenzalde‐hyde with methyl acrylate through the Baylis‐Hillman reaction.     

Hepatoprotective Effects of Ixeris chinensis on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice: An Integrated Gut Microbiota and Metabolomic Analysis

Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1β, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.     

Human Serum Amyloid a Impaired Structural Stability of High-Density Lipoproteins (HDL) and Apolipoprotein (Apo) A-I and Exacerbated Glycation Susceptibility of ApoA-I and HDL

Human serum amyloid A (SAA) is an exchangeable apolipoprotein (apo) in high-density lipoprotein (HDL) that influences HDL quality and functionality, particularly in the acute phase of inflammation. On the other hand, the structural and functional correlations of HDL containing SAA and apoA-I have not been reported. The current study was designed to compare the change in HDL quality with increasing SAA content in the lipid-free and lipid-bound states in reconstituted HDL (rHDL). The expressed recombinant human SAA1 (13 kDa) was purified to at least 98% and characterized in the lipid-free and lipid-bound states with apoA-I. The dimyristoyl phosphatidylcholine (DMPC) binding ability of apoA-I was impaired severely by the addition of SAA, while SAA alone could not bind with DMPC. The recombinant human SAA1 was incorporated into the rHDL (molar ratio 95:5:1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC): cholesterol: apoA-I) with various apoA-I:SAA molar ratios from 1:0 to 1:0.5, 1:1 and 1:2. With increasing SAA1 content, the rHDL particle size was reduced from 98 Å to 93 Å, and the α-helicity of apoA-I:SAA was decreased from 73% to 40% for (1:0) and (1:2), respectively. The wavelength maximum fluorescence (WMF) of tryptophan in rHDL was red-shifted from 339 nm to 345 nm for (1:0) and (1:2) of apoA-I:SAA, respectively, indicating that the addition of SAA to rHDL destabilized the secondary structure of apoA-I. Upon denaturation by urea treatment from 0 M to 8 M, SAA showed only a 3 nm red-shift in WMF, while apoA-I showed a 16 nm red-shift in WMF, indicating that SAA is resistant to denaturation and apoA-I had higher conformational flexibility than SAA. The glycation reaction of apoA-I in the presence of fructose was accelerated up to 1.8-fold by adding SAA in a dose-dependent manner than that of apoA-I alone. In conclusion, the incorporation of SAA in rHDL impaired the structural stability of apoA-I and exacerbated glycation of HDL and apoA-I.     

Development of a Quantitative Method for Detection of Multiclass Veterinary Drugs in Feed Using Modified QuPPe Extraction and LC–MS/MS

A method was developed for the rapid and quantitative analysis of 30 veterinary drugs belonging to 17 classes (amphenicols (1), anthelmintics (1), cephalosporins (4), coccidiostats (1), lincosamides (1), macrolide (1), nitroimidazole (1), penicillins (3), phenylhydrazines (1), polypeptides (1), pyrethrins (1), quinolones (5), sulfonamides (3), tetracycline (3), neuroleptic agents (1), triazene trypanocidal agents (1), other. (1)) in feeds. The proposed method with a modified Quick Polar Pesticides (QuPPe) sample preparation was validated for the determination of 30 veterinary drugs in feed samples by liquid chromatography triple-quadrupole mass spectrometry (LC–MS/MS). The sample was extracted with methanol containing 1% acetic acid and purified by dispersive solid-phase extraction (d-SPE) with C18. Good linearity (r² ≥ 0.98) was observed, and the LOQ values ranged from 10 to 200 µg/kg. Average recoveries ranged from 70.8 to 118.4%, and the relative standard deviation was ≤ 18.7%. This validated method was used in the determination of 30 veterinary drugs in 142 feed samples obtained from South Korea. The results show that lincomycin was present in only one of the tested feed samples, although it was detected at a value lower than the LOQ. In conclusion, this multi-residue method can be used for screening through the detection and quantitation of residual multiclass veterinary drugs in feed samples.