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1.
Molecules ; 24(16)2019 Aug 20.
Article in English | MEDLINE | ID: mdl-31434280

ABSTRACT

The synthesis and surface self-assembly behavior of two types of metal-porphyrin dimers is described. The first dimer type consists of two porphyrins linked via a rigid conjugated spacer, and the second type has an alkyne linker, which allows rotation of the porphyrin moieties with respect to each other. The conjugated dimers were equipped with two copper or two manganese centers, while the flexible dimers allowed a modular built-up that also made the incorporation of two different metal centers possible. The self-assembly of the new porphyrin dimers at a solid-liquid interface was investigated at the single-molecule scale using scanning tunneling microscopy (STM). All dimers formed monolayers, of which the stability and the internal degree of ordering of the molecules depended on the metal centers in the porphyrins. While in all monolayers the dimers were oriented coplanar with respect to the underlying surface ('face-on'), the flexible dimer containing a manganese and a copper center could be induced, via the application of a voltage pulse in the STM setup, to self-assemble into monolayers in which the porphyrin dimers adopted a non-common perpendicular ('edge-on') geometry with respect to the surface.


Subject(s)
Porphyrins/chemistry , Copper/chemistry , Dimerization , Manganese/chemistry , Microscopy, Scanning Tunneling , Porphyrins/chemical synthesis , Single Molecule Imaging/methods
2.
Nat Chem Biol ; 12(7): 559-66, 2016 07.
Article in English | MEDLINE | ID: mdl-27239787

ABSTRACT

Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action on the basis of behavioral profiles alone. Although zebrafish (Danio rerio) behavior has been used to rapidly identify neuroactive compounds, it is not clear what types of behavioral assays would be necessary to identify multitarget compounds such as antipsychotics. Here we developed a battery of behavioral assays in larval zebrafish to determine whether behavioral profiles can provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated zebrafish could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multitarget mechanisms of action.


Subject(s)
Antipsychotic Agents/analysis , Antipsychotic Agents/pharmacology , Behavior, Animal/drug effects , Zebrafish , Animals , Antipsychotic Agents/chemistry , Larva/drug effects , Mice , Molecular Structure , Zebrafish/growth & development
3.
Chem Commun (Camb) ; 50(55): 7291-4, 2014 Jul 14.
Article in English | MEDLINE | ID: mdl-24871585

ABSTRACT

STM reveals that self-assembled bilayers of covalently linked Cu-Mn porphyrin dimers can dynamically rearrange at a solid/liquid interface by rapid exchange of molecules between the bilayer and the supernatant, or via a slower two-dimensional translation of the whole top layer.


Subject(s)
Porphyrins/chemistry , Dimerization , Microscopy, Electron, Scanning Transmission
4.
Macromol Biosci ; 10(5): 475-80, 2010 May 14.
Article in English | MEDLINE | ID: mdl-20336699

ABSTRACT

Biodegradable PLLA capsules with a narrow size distribution were prepared using a microfluidics platform. With this technique, an oil-in-water emulsion was produced in which the polymer, a hydrophobic non-volatile non-solvent and a hydrophobic model drug were dissolved in the organic phase. The polymer precipitated at the droplet interface, yielding a drug deliverable microcapsule of which the release of this model drug was investigated. These capsules with an organic phase in the core were also used to prepare hollow particles by conveniently removing the core phase by lyophilization. Optimal conditions for the preparation of biodegradable capsules were found with respect to the flow rate of the continuous phase and the molecular weight of the PLLA polymer. This approach of preparing biodegradable capsules is of potential interest for the field of drug delivery.


Subject(s)
Capsules/chemical synthesis , Drug Delivery Systems , Lactic Acid/chemistry , Microfluidics/methods , Polymers/chemistry , Alkanes/analysis , Emulsions/chemistry , Polyesters
5.
Macromol Biosci ; 8(11): 991-1005, 2008 Nov 10.
Article in English | MEDLINE | ID: mdl-18655033

ABSTRACT

For decades scientists have been working on closed systems for transportation, catalysis and protection, which are inspired by natural cells. Only recently polymer based systems have emerged for these systems, since they are more robust, give protection from the environment and give a more stable membrane. Various methods have been developed to prepare polymer based capsules. They can be made by self-assembly, templating, in situ polymerization or precipitation. Their application has been explored in various areas e.g. drug delivery, diagnostics, sensors and nano reactors. Considering the output in this field has substantially grown, more developments can be expected from this latter application.


Subject(s)
Biomimetic Materials/chemistry , Capsules/chemistry , Nanotechnology/methods , Polymers , Cell Compartmentation
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