Browse
Submit Data
Databases
API
Help
Login

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multidimensional Correlations in Asymmetric Catalysis through Parameterization of Uncatalyzed Transition States.

ABSTRACT: The study of the oxidative amination of tetrahydroisoquinolines under chiral-anion phase-transfer (CAPT) catalysis by multidimensional correlation analysis (MCA) is revisited. The parameterization of the transition states (TSs) for the uncatalyzed reaction, the introduction of conformational descriptors, and the use of computed interaction energies and distances as parameters allowed access to a considerably simplified mathematical correlation of substrate and catalyst structure to enantioselectivity. The equation obtained is suggestive of key interactions occurring at the TS. Specifically, the CAPT catalyst is proposed to coordinate the intermediate iminium cation by P=O???H-O hydrogen-bonding and N???H-C electrostatic interactions. The conformational freedom of the benzyl substituent of the substrate was also found to be important in providing an efficient mode of molecular recognition.

SUBMITTER: Orlandi M

PROVIDER: S-EPMC5658244 | BioStudies | 2017-01-01T00:00:00Z

REPOSITORIES: biostudies

ACCESS DATA

Json Xml

Similar Datasets

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates.

Project description:Nucleophilic trapping of iminium salts generated via oxidative functionalisation of tertiary amines is well established with stabilised carbon nucleophiles. The few reports of organometallic additions have limited scope of substrate and organometallic nucleophile. We report a novel, one-pot methodology that functionalises N-substituted tetrahydroisoquinolines by visible light-assisted photooxidation, followed by trapping of the resultant iminium ions with organometallic nucleophiles. This affords 1,2-disubstituted tetrahydroisoquinolines in moderate to excellent yields.

1000-01-01 | S-EPMC4273301 | BioStudies

Uncatalyzed Oxidative C-H Amination of 9,10-Dihydro-9-Heteroanthracenes: A Mechanistic Study.

Project description:A new method for the one-step C-H amination of xanthene and thioxanthene with sulfonamides is reported, without the need for any metal catalyst. A benzoquinone was employed as a hydride (or two-electron and one-proton) acceptor. Moreover, a previously unknown and uncatalyzed reaction between iminoiodanes and xanthene, thioxanthene and dihydroacridines (9,10-dihydro-9-heteroanthracenes or dihydroheteroanthracenes) is disclosed. The reactions proceed through hydride transfer from the heteroarene substrate to the iminoiodane or benzoquinone, followed by conjugate addition of the sulfonamide to the oxidized heteroaromatic compounds. These findings may have important mechanistic implications for metal-catalyzed C-H amination processes involving nitrene transfer from iminoiodanes to dihydroheteroanthracenes. Due to the weak C-H bond, xanthene is an often-employed substrate in mechanistic studies of C-H amination reactions, which are generally proposed to proceed via metal-catalyzed nitrene insertion, especially for reactions involving nitrene or imido complexes that are less reactive (i.e., less strongly oxidizing). However, these substrates clearly undergo non-catalyzed (proton-coupled) redox coupling with amines, thus providing alternative pathways to the widely assumed metal-catalyzed pathways.

2019-01-01 | S-EPMC6563809 | BioStudies

Functionally diverse nucleophilic trapping of iminium intermediates generated utilizing visible light.

Project description:Our previous studies into visible-light-mediated aza-Henry reactions demonstrated that molecular oxygen played a vital role in catalyst turnover as well as the production of base to facilitate the nucleophilic addition of nitroalkanes. Herein, improved conditions for the generation of iminium ions from tetrahydroisoquinolines that allow for versatile nucleophilic trapping are reported. The new conditions provide access to a diverse range of functionality under mild, anaerobic reaction conditions as well as mechanistic insights into the photoredox cycle.

2012-01-01 | S-EPMC3253246 | BioStudies

Differential quantum tunneling contributions in nitroalkane oxidase catalyzed and the uncatalyzed proton transfer reaction.

Project description:The proton transfer reaction between the substrate nitroethane and Asp-402 catalyzed by nitroalkane oxidase and the uncatalyzed process in water have been investigated using a path-integral free-energy perturbation method. Although the dominating effect in rate acceleration by the enzyme is the lowering of the quasiclassical free energy barrier, nuclear quantum effects also contribute to catalysis in nitroalkane oxidase. In particular, the overall nuclear quantum effects have greater contributions to lowering the classical barrier in the enzyme, and there is a larger difference in quantum effects between proton and deuteron transfer for the enzymatic reaction than that in water. Both experiment and computation show that primary KIEs are enhanced in the enzyme, and the computed Swain-Schaad exponent for the enzymatic reaction is exacerbated relative to that in the absence of the enzyme. In addition, the computed tunneling transmission coefficient is approximately three times greater for the enzyme reaction than the uncatalyzed reaction, and the origin of the difference may be attributed to a narrowing effect in the effective potentials for tunneling in the enzyme than that in aqueous solution.

2009-01-01 | S-EPMC2791643 | BioStudies

Mechanistic studies of uncatalyzed and ruthenium(III)-catalyzed oxidation of the antibiotic drug chloramphenicol by hexacyanoferrate(III) in aqueous alkaline medium: a comparative kinetic study.

Project description:The kinetics of oxidation of the antibiotic drug chloramphenicol (CHP) by hexacyanoferrate(III) (HCF) has been investigated spectrophotometrically both in the absence and presence of ruthenium(III) catalyst in aqueous alkaline medium at 25 °C and at constant ionic strength of 1.10 mol dm(-3). The stoichiometry is identical in both cases, i.e. [CHP]/[HCF] = 1:2. The oxidation products were identified by TLC and spectral studies such as GC-MS, IR, and (1)H NMR. In both catalyzed and uncatalyzed reactions, the order with respect to the concentration of HCF is unity, whereas the order with respect to the concentration of CHP and the concentration of OH(-) is less than unity over the concentration range studied. The order with respect to the concentration of Ru(III) is unity. The reaction in the presence of Ru(III) is approximately tenfold faster than the uncatalyzed reaction. The active species of oxidant and catalyst are [Fe(CN)6](3-) and [Ru(H2O)5(OH)](2+), respectively. On the basis of experimental results suitable mechanisms are proposed. The reaction constants involved in the different steps of the reaction mechanisms were calculated for both cases. The catalytic constant was also calculated for the catalyzed reaction at different temperatures. The activation parameters with respect to the slow step of the mechanism and thermodynamic quantities are also determined.

1000-01-01 | S-EPMC4494844 | BioStudies

Asymmetric cooperative catalysis of strong Bronsted acid-promoted reactions using chiral ureas.

Project description:Cationic organic intermediates participate in a wide variety of useful synthetic transformations, but their high reactivity can render selectivity in competing pathways difficult to control. Here, we describe a strategy for inducing enantioselectivity in reactions of protio-iminium ions, wherein a chiral catalyst interacts with the highly reactive intermediate through a network of noncovalent interactions. This interaction leads to an attenuation of the reactivity of the iminium ion and allows high enantioselectivity in cycloadditions with electron-rich alkenes (the Povarov reaction). A detailed experimental and computational analysis of this catalyst system has revealed the precise nature of the catalyst-substrate interactions and the likely basis for enantioinduction.

2010-01-01 | S-EPMC2993568 | BioStudies

Mechanistic Parameterization of the Kinomic Signal in Peptide Arrays.

Project description:Kinases play a role in every cellular process involved in tumorigenesis ranging from proliferation, migration, and protein synthesis to DNA repair. While genetic sequencing has identified most kinases in the human genome, it does not describe the 'kinome' at the level of activity of kinases against their substrate targets. An attempt to address that limitation and give researchers a more direct view of cellular kinase activity is found in the PamGene PamChip® system, which records and compares the phosphorylation of 144 tyrosine or serine/threonine peptides as they are phosphorylated by cellular kinases. Accordingly, the kinetics of this time dependent kinomic signal needs to be well understood in order to transduce a parameter set into an accurate and meaningful mathematical model. Here we report the analysis and mathematical modeling of kinomic time series, which achieves a more accurate description of the accumulation of phosphorylated product than the current model, which assumes first order enzyme-substrate kinetics. Reproducibility of the proposed solution was of particular attention. Specifically, the non-linear parameterization procedure is delivered as a public open source web application where kinomic time series can be accurately decomposed into the model's two parameter values measuring phosphorylation rate and capacity. The ability to deliver model parameterization entirely as a client side web application is an important result on its own given increasing scientific preoccupation with reproducibility. There is also no need for a potentially transitory and opaque server-side component maintained by the authors, nor of exchanging potentially sensitive data as part of the model parameterization process since the code is transferred to the browser client where it can be inspected and executed.

2016-01-01 | S-EPMC5010871 | BioStudies

Strong Bronsted acid promoted asymmetric hydrogenation of isoquinolines and quinolines catalyzed by a Rh-thiourea chiral phosphine complex <i>via</i> anion binding.

Project description:Rhodium catalyzed asymmetric hydrogenation of both isoquinolines and quinolines provides a new method to synthesize chiral tetrahydroisoquinolines and tetrahydroquinolines. By introducing strong Brønsted acid HCl, anion binding between the substrate and the ligand was established to achieve high reactivity and high enantioselectivity (up to 99% conversion and 99% ee). An NMR study suggests an anion binding between the catalyst and the substrate. Deuterium labeling experiments reveal a plausible reaction pathway.

2016-01-01 | S-EPMC6005156 | BioStudies

Mechanism of amido-thiourea catalyzed enantioselective imine hydrocyanation: transition state stabilization via multiple non-covalent interactions.

Project description:An experimental and computational investigation of amido-thiourea promoted imine hydrocyanation has revealed a new and unexpected mechanism of catalysis. Rather than direct activation of the imine by the thiourea, as had been proposed previously in related systems, the data are consistent with a mechanism involving catalyst-promoted proton transfer from hydrogen isocyanide to imine to generate diastereomeric iminium/cyanide ion pairs that are bound to catalyst through multiple noncovalent interactions; these ion pairs collapse to form the enantiomeric alpha-aminonitrile products. This mechanistic proposal is supported by the observation of a statistically significant correlation between experimental and calculated enantioselectivities induced by eight different catalysts (P << 0.01). The computed models reveal a basis for enantioselectivity that involves multiple stabilizing and destabilizing interactions between substrate and catalyst, including thiourea-cyanide and amide-iminium interactions.

2009-01-01 | S-EPMC2783581 | BioStudies

'Arm-based' parameterization for network meta-analysis.

Project description:We present an alternative to the contrast-based parameterization used in a number of publications for network meta-analysis. This alternative "arm-based" parameterization offers a number of advantages: it allows for a "long" normalized data structure that remains constant regardless of the number of comparators; it can be used to directly incorporate individual patient data into the analysis; the incorporation of multi-arm trials is straightforward and avoids the need to generate a multivariate distribution describing treatment effects; there is a direct mapping between the parameterization and the analysis script in languages such as WinBUGS and finally, the arm-based parameterization allows simple extension to treatment-specific random treatment effect variances. We validated the parameterization using a published smoking cessation dataset. Network meta-analysis using arm- and contrast-based parameterizations produced comparable results (with means and standard deviations being within +/- 0.01) for both fixed and random effects models. We recommend that analysts consider using arm-based parameterization when carrying out network meta-analyses.?© 2015 The Authors Research Synthesis Methods Published by John Wiley & Sons Ltd.

2016-01-01 | S-EPMC5063191 | BioStudies

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data