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Amsterdam-Zuidoost, Netherlands

Gargano A.F.G.,University of Vienna | Gargano A.F.G.,Van t Hoff Institute for Molecular science | Lammerhofer M.,University of Tubingen | Lonn H.,Astrazeneca | And 2 more authors.
Journal of Chromatography A

Mucin glycoproteins belong to a class of high molecular weight, heavy glycosylated, proteins that together with water, salts and lipids constitute mucous secretions. Particular disease states (e.g. obstructive chronic bronchitis and ovarian tumor) are known to modify the composition and the thickness of those barriers. Therefore, it is important to address whether the absorption of potential drug candidates to be administered is influenced by the presence of interaction with this class of proteins. Typically, the methods adopted to characterize drug-protein interaction are dialysis, ultrafiltration and gel filtration. Besides these, bio-affinity chromatographic methods have demonstrated to be valuable tools offering the advantageous characteristics such as simplicity, efficiency, high-throughput capability and robustness. The present contribution reports on the synthesis and analytical characterization of a new chromatographic stationary phase based on covalently immobilized mucin and explores the use of LC-UV affinity zonal chromatography as a tool to screen drugs for their affinity to mucin. A series of different binding chemistries for the covalent linkage of mucin to silica-based supports as well as distinct immobilization protocols (static and dynamic) have been evaluated in order to optimize surface coverage. Resultant stationary phases have been characterized chromatographically by studying the effect of mobile phase and analyte structure on the distribution and retention of test compounds. As conclusive study, we report the evaluation of the retention characteristics of 41 drug-like compounds (having heterogeneous chemical properties) for their interaction with this novel stationary phase. © 2014 Elsevier B.V. Source

Veguillas M.,Manchester Metropolitan University | Sola R.,Manchester Metropolitan University | Fernandez-Ibanez M.A.,Van t Hoff Institute for Molecular science | Macia B.,Manchester Metropolitan University
Tetrahedron Asymmetry

An efficient catalyst for the enantioselective synthesis of chiral methyl carbinols from aldehydes is presented. The system uses methyltriisopropoxytitanium as a nucleophile and a readily available binaphthyl derivative as a chiral ligand. The enantioselective methylation of both aromatic and aliphatic aldehydes proceeds with good yields and high enantioselectivities under mild conditions. © 2016 Elsevier Ltd Source

Lechner W.,Van t Hoff Institute for Molecular science | Dellago C.,University of Vienna | Bolhuis P.G.,Van t Hoff Institute for Molecular science
Journal of Chemical Physics

We study the mechanisms of the homogeneous crystal nucleation from the supercooled liquid to the crystal phase in the Gaussian core model for colloidal suspensions with the aim to find optimal reaction coordinates. We introduce a set of novel collective variables based on the local structure of particles. By applying likelihood maximization of the committor function for the reweighted path ensemble constructed by replica exchange transition interface sampling, we select the optimal reaction coordinates from the set of collective variables. We find that the size of the cloud of prestructured particles surrounding the crystalline nucleus enhances the description of the transition. Further, we show that the rearrangement of the inner core of the nucleus according to Ostwalds step rule is a separate process, independent of the growth of the nucleus. © 2011 American Institute of Physics. Source

Meeuwissen J.,Van t Hoff Institute for Molecular science | Reek J.N.H.,Van t Hoff Institute for Molecular science
Nature Chemistry

Supramolecular catalysis - the assembly of catalyst species by harnessing multiple weak intramolecular interactions - has, until recently, been dominated by enzyme-inspired approaches. Such approaches often attempt to create an enzyme-like 'active site' and have concentrated on reactions similar o those catalysed by enzymes themselves. Here, we discuss the application of supramolecular assembly to the more traditional transition metal catalysis and to small-molecule organocatalysis. The modularity of self-assembled multicomponent catalysts means that a relatively small pool of catalyst components can provide rapid access to a large number of catalysts that can be evaluated for industrially relevant reactions. In addition, we discuss how catalyst-substrate interactions can be tailored to direct substrates along particular reaction paths and selectivities. © 2010 Macmillan Publishers Limited. All rights reserved. Source

Navarro J.R.G.,CNRS Systems and Applications of Information Technologies and Energy Laboratory | Plugge M.,Van t Hoff Institute for Molecular science | Loumaigne M.,University Paris - Sud | Sanchez-Gonzalez A.,University of Pisa | And 4 more authors.
Photochemical and Photobiological Sciences

The binding of disulfides to gold nanoparticles was investigated using fluorescence spectroscopy and a perylene-monoimide dye coupled to a dissymmetric disulfide via a tetraethyleneglycolalkyl chain (PMImSS). Quantum chemical calculations using the polarizable continuum model (PCM) predict a strong quenching of perylene-monoimide fluorescence by gold nanoparticles as a result of efficient excitation energy transfer from the dye to the particle. Such quenching is indeed observed when unfunctionalised gold nanoparticles are added to a solution of PMImSS. The fluorimetric titration curves show behaviour indicative of the existence of an equilibrium between free and bound ligands (association constant 5 × 105 M-1), whereas the affinity of thiols and disulfide for gold surfaces is in general assumed to be much higher. Gold nanoparticles fully functionalised with PMImSS were synthesised and purified. Fluorescence correlation spectroscopy shows the appearance of free PMImSS ligands in dilute (approx. pM) suspensions of these PMImSS-functionalised nanoparticles over a period of several days. © 2010 The Royal Society of Chemistry and Owner Societies. Source

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