Spontaneous Hydrolyses in Sulfobetaine Micelles. Dependence of Micellar Charge Effects Upon Mechanism

Rate constants of spontaneous hydrolyses in zwitterionic micelles of N-hexadecyl-N,N-dimethyl-3-ammonio-propanesulfonate (SB3-16) are compared with those in cationic (n-C16H33NMe3X, X = Cl, Br, OMes; CTAC1, CTABr, CTAOMes) and anionic (n-C12H25OSO3Na, SDS) micelles. Substrates are methyl benzenesulfonate, 2-adamantyl and pinacolyl 4-nitrobenzenesulfonate, 4-bromo- and 4-nitrobenzoyl chloride, phenyl and 4-nitrophenyl chloroformate and bis(4-nitrophenyl) carbonate. Hydrolyses are micellar inhibited, except for the nitro substituted acid chlorides. Reactions with extensive bond-breaking in the transition state (SN1 hydrolyses) are faster in SDS than in cationic and sulfobetaine micelles, but the other hydrolyses, which involve significant bond-making, are slower in SDS. Rate constants are similar in cationic and sulfobetaine micelles. These micellar charge effects are ascribed to interactions of the polar transition states with the asymetrically charged interfacial region which complement effects of the lower polarities of micelles relative to water

Structural identification of mouse fecal metabolites of theaflavin 3,3′-digallate using liquid chromatography tandem mass spectrometry

Black tea consumption has been associated with many health benefits including the prevention of cancer and heart disease. Theaflavins are the major bioactive polyphenols present in black tea. Unfortunately, limited information is available on their biotransformation. In the present study, we investigated the metabolic fate of theaflavin 3,3′-digallate (TFDG), one of the most abundant and bioactive theaflavins, in mouse fecal samples using liquid chromatography/electrospray ionization tandem mass spectrometry by analyzing the MSn (n = 1–3) spectra. Four metabolites theaflavin, theaflavin 3-gallate, theaflavin 3′-gallate, and gallic acid were identified as the major mouse fecal metabolites of TFDG. Glucuronidated and sulfated, instead of methylated metabolites of theaflavin 3-gallate, theaflavin 3′-gallate, and TFDG were detected and identified as the minor mouse fecal metabolites of TFDG. Our results indicate that TFDG can be degraded in mice. Further studies on the formation of those metabolites in TFDG-treated mice in germ-free conditions are warranted. To our knowledge, this is the first report on the biotransformation of TFDG in mice

The Microbiota Is Essential for the Generation of Black Tea Theaflavins-Derived Metabolites

BackgroundTheaflavins including theaflavin (TF), theaflavin-3-gallate (TF3G), theaflavin-3′-gallate (TF3′G), and theaflavin-3,3′-digallate (TFDG), are the most important bioactive polyphenols in black tea. Because of their poor systemic bioavailability, it is still unclear how these compounds can exert their biological functions. The objective of this study is to identify the microbial metabolites of theaflavins in mice and in humans.Methods and FindingsIn the present study, we gavaged specific pathogen free (SPF) mice and germ free (GF) mice with 200 mg/kg TFDG and identified TF, TF3G, TF3′G, and gallic acid as the major fecal metabolites of TFDG in SPF mice. These metabolites were absent in TFDG- gavaged GF mice. The microbial bioconversion of TFDG, TF3G, and TF3′G was also investigated in vitro using fecal slurries collected from three healthy human subjects. Our results indicate that TFDG is metabolized to TF, TF3G, TF3′G, gallic acid, and pyrogallol by human microbiota. Moreover, both TF3G and TF3′G are metabolized to TF, gallic acid, and pyrogallol by human microbiota. Importantly, we observed interindividual differences on the metabolism rate of gallic acid to pyrogallol among the three human subjects. In addition, we demonstrated that Lactobacillus plantarum 299v and Bacillus subtilis have the capacity to metabolize TFDG.ConclusionsThe microbiota is important for the metabolism of theaflavins in both mice and humans. The in vivo functional impact of microbiota-generated theaflavins-derived metabolites is worthwhile of further study

Bananas as an Energy Source during Exercise: A Metabolomics Approach

This study compared the acute effect of ingesting bananas (BAN) versus a 6% carbohydrate drink (CHO) on 75-km cycling performance and post-exercise inflammation, oxidative stress, and innate immune function using traditional and metabolomics-based profiling. Trained cyclists (N = 14) completed two 75-km cycling time trials (randomized, crossover) while ingesting BAN or CHO (0.2 g/kg carbohydrate every 15 min). Pre-, post-, and 1-h-post-exercise blood samples were analyzed for glucose, granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity, nine cytokines, F2-isoprostanes, ferric reducing ability of plasma (FRAP), and metabolic profiles using gas chromatography-mass spectrometry. Blood glucose levels and performance did not differ between BAN and CHO (2.41±0.22, 2.36±0.19 h, P = 0.258). F2-isoprostanes, FRAP, IL-10, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG increased with exercise, with no trial differences except for higher levels during BAN for IL-10, IL-8, and FRAP (interaction effects, P = 0.003, 0.004, and 0.012). Of 103 metabolites detected, 56 had exercise time effects, and only one (dopamine) had a pattern of change that differed between BAN and CHO. Plots from the PLS-DA model visualized a distinct separation in global metabolic scores between time points [R2Y(cum) = 0.869, Q2(cum) = 0.766]. Of the top 15 metabolites, five were related to liver glutathione production, eight to carbohydrate, lipid, and amino acid metabolism, and two were tricarboxylic acid cycle intermediates. BAN and CHO ingestion during 75-km cycling resulted in similar performance, blood glucose, inflammation, oxidative stress, and innate immune levels. Aside from higher dopamine in BAN, shifts in metabolites following BAN and CHO 75-km cycling time trials indicated a similar pattern of heightened production of glutathione and utilization of fuel substrates in several pathways

Oxidation of Thioanisole by Peroxomolybdate in Assemblies of Cetylpyridinium Chloride and Methyltri-n-octylammonium Chloride

Methyltri-n-octylammonium chloride (Aliquat 336) is sparingly soluble in water but is readily soluble with a 2-fold excess of micellized cetylpyridinium chloride (CPyCl), and the mixtures show breaks in plots of surface tension or electrolytic conductance against concentration indicative of a critical micelle concentration slightly lower than that of CPyCl. Micellization markedly increases 35Cl and 14N NMR line widths of CPyCl, but addition of NaCl reduces the 35Cl line width and addition of Aliquat increases it. Mixing Aliquat and CPyCl has little effect on their 14N line widths. Ion pairing in alcohol mixtures also increases 35Cl line widths. In water these mixed assemblies behave similarly to micelles of CPyCl as regards effects on rates and equilibria of interconversion of tri- and tetraperoxomolybdate ions, and oxidation of thioanisole by the latter, although it is slightly slower than in micelles of CPyCl. Despite differences in the hydrophobic regions, and relationships between amphiphilic structures and morphologies of association colloids, assemblies of CPyCl and Aliquat behave very much like CPyCl micelles in their physical properties and effects upon reactivity. Geometrical optimization indicates that Aliquat can adopt conformations that allow intercalation with CPyCl micelles

Carbohydrate intake attenuates post-exercise plasma levels of cytochrome P450-generated oxylipins.

INTRODUCTION:Oxylipins are bioactive oxidation products derived from n-6 and n-3 polyunsaturated fatty acids (PUFAs) in the linoleic acid and α-linolenic desaturation pathways. PURPOSE:This study determined if carbohydrate intake during prolonged and intensive cycling countered post-exercise increases in n-6 and n-3 PUFA-derived oxylipins. METHODS:The research design utilized a randomized, crossover, counterbalanced approach with cyclists (N = 20, overnight fasted state, 7:00 am start) who engaged in four 75-km time trials while ingesting two types of bananas (Cavendish, Mini-yellow), a 6% sugar beverage, and water only. Carbohydrate intake was set at 0.2 g/kg every 15 minutes, and blood samples were collected pre-exercise and 0 h-, 0.75 h-,1.5 h-, 3 h-, 4.5 h-, 21 h-, 45 h-post-exercise. Oxylipins were measured with a targeted liquid chromatography-multiple reaction monitoring mass spectrometric method. RESULTS:Significant time effects and substantial fold-increases (immediately post-exercise/pre-exercise) were measured for plasma levels of arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 43 of 45 oxylipins. Significant interaction effects (4 trials x 8 time points) were found for plasma ARA (P<0.001) and DHA (P<0.001), but not EPA (P = 0.255), with higher post-exercise values found in the water trial compared to the carbohydrate trials. Significant interaction effects were also measured for 12 of 45 oxylipins. The data supported a strong exercise-induced increase in plasma levels of these oxylipins during the water trial, with carbohydrate ingestion (both bananas types and the sugar beverage) attenuating oxylipin increases, especially those (9 of 12) generated from the cytochrome P-450 (CYP) enzyme system. These trials differences were especially apparent within the first three hours of recovery from the 75-km cycling bout. CONCLUSIONS:Prolonged and intensive exercise evoked a transient but robust increase in plasma levels of oxylipins, with a significant attenuation effect linked to acute carbohydrate ingestion for 28% of these, especially those generated through the CYP enzyme system. TRIAL REGISTRATION:ClinicalTrials.gov, U.S. National Institutes of Health, NCT02994628