42 research outputs found
Selectivity control in Pt-catalyzed cinnamaldehyde hydrogenation
Chemoselectivity is a cornerstone of catalysis, permitting the targeted modification of specific functional groups within complex starting materials. Here we elucidate key structural and electronic factors controlling the liquid phase hydrogenation of cinnamaldehyde and related benzylic aldehydes over Pt nanoparticles. Mechanistic insight from kinetic mapping reveals cinnamaldehyde hydrogenation is structure-insensitive over metallic platinum, proceeding with a common Turnover Frequency independent of precursor, particle size or support architecture. In contrast, selectivity to the desired cinnamyl alcohol product is highly structure sensitive, with large nanoparticles and high hydrogen pressures favoring C=O over C=C hydrogenation, attributed to molecular surface crowding and suppression of sterically-demanding adsorption modes. In situ vibrational spectroscopies highlight the role of support polarity in enhancing C=O hydrogenation (through cinnamaldehyde reorientation), a general phenomenon extending to alkyl-substituted benzaldehydes. Tuning nanoparticle size and support polarity affords a flexible means to control the chemoselective hydrogenation of aromatic aldehydes
Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating the metabolic characteristics and gene expression of in vitro differentiated myotubes established from well characterized PCOS subjects.Using radiotracer techniques, RT-PCR and enzyme kinetic analysis we examined myotubes established from PCOS subjects with or without pioglitazone treatment, versus healthy control subjects who had been extensively metabolically characterized in vivo. Results. Myotubes established from PCOS and matched control subjects comprehensively expressed all insulin-sensitive biomarkers; glucose uptake and oxidation, glycogen synthesis and lipid uptake. There were no significant differences between groups either at baseline or during acute insulin stimulation, although in vivo skeletal muscle was insulin resistant. In particular, we found no evidence for defects in insulin-stimulated glycogen synthase activity between groups. Myotubes established from PCOS patients with or without pioglitazone treatment also showed no significant differences between groups, neither at baseline nor during acute insulin stimulation, although in vivo pioglitazone treatment significantly improved insulin sensitivity. Consistently, the myotube cultures failed to show differences in mRNA levels of genes previously demonstrated to differ in PCOS patients with or without pioglitazone treatment (PLEK, SLC22A16, and TTBK).These results suggest that the mechanisms governing insulin resistance in skeletal muscle of PCOS patients in vivo are not primary, but rather adaptive.ClinicalTrials.gov NCT00145340
State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)
PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy
Selective Hydrogenation of Polyunsaturated Fatty Acids Using Alkanethiol Self-Assembled Monolayer-Coated Pd/Al<sub>2</sub>O<sub>3</sub> Catalysts
Pd/Al<sub>2</sub>O<sub>3</sub> catalysts
coated with various thiolate
self-assembled monolayers (SAMs) were used to direct the partial hydrogenation
of 18-carbon polyunsaturated fatty acids, yielding a product stream
enriched in monounsaturated fatty acids (with low saturated fatty
acid content), a favorable result for increasing the oxidative stability
of biodiesel. The uncoated Pd/Al<sub>2</sub>O<sub>3</sub> catalyst
quickly saturated all fatty acid reactants under hydrogenation conditions,
but the addition of alkanethiol SAMs markedly increased the reaction
selectivity to the monounsaturated product oleic acid to a level of
80–90%, even at conversions >70%. This effect, which is
attributed
to steric effects between the SAMs and reactants, was consistent with
the relative consumption rates of linoleic and oleic acid using alkanethiol-coated
and uncoated Pd/Al<sub>2</sub>O<sub>3</sub> catalysts. With an uncoated
Pd/Al<sub>2</sub>O<sub>3</sub> catalyst, each fatty acid, regardless
of its degree of saturation had a reaction rate of ∼0.2 mol
reactant consumed per mole of surface palladium per second. Using
alkanethiol-coated Pd/Al<sub>2</sub>O<sub>3</sub> catalysts, the activity
was reduced by a factor of 4 for polyunsaturated reactants and by
a factor of 100 for the monounsaturated reactants. In contrast to
the hydrophobic alkanethiol modifiers, hydrophilic thioglycerol SAM
modifiers were found to strongly inhibit reaction kinetics
Control of Metal Catalyst Selectivity through Specific Noncovalent Molecular Interactions
The
specificity of chemical reactions conducted over solid catalysts
can potentially be improved by utilizing noncovalent interactions
to direct reactant binding geometry. Here we apply thiolate self-assembled
monolayers (SAMs) with an appropriate structure to Pt/Al<sub>2</sub>O<sub>3</sub> catalysts to selectively orient the reactant molecule
cinnamaldehyde in a configuration associated with hydrogenation to
the desired product cinnamyl alcohol. While nonspecific effects on
the surface active site were shown to generally enhance selectivity,
specific aromatic stacking interactions between the phenyl ring of
cinnamaldehyde and phenylated SAMs allowed tuning of reaction selectivity
without compromising the rate of desired product formation. Infrared
spectroscopy showed that increased selectivity was a result of favorable
orientation of the reactant on the catalyst surface. In contrast,
hydrogenation of an unsaturated aldehyde without a phenyl ring showed
a nontunable improvement in selectivity, indicating that thiol SAMs
can improve reaction selectivity through a combination of nonspecific
surface effects and ligand-specific near-surface effects