Systems chemistry: using thermodynamically controlled networks to assess molecular similarity

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The assessment of molecular similarity is a key step in the drug discovery process that has thus far relied almost exclusively on computational approaches. We now report an experimental method for similarity assessment based on dynamic combinatorial chemistry. Results In order to assess molecular similarity directly in solution, a dynamic molecular network was used in a two-step process. First, a clustering analysis was employed to determine the network’s innate discriminatory ability. A classification algorithm was then trained to enable the classification of unknowns. The dynamic molecular network used in this work was able to identify thin amines and ammonium ions in a set of 25 different, closely related molecules. After training, it was also able to classify unknown molecules based on the presence or absence of an ethylamine group. Conclusions This is the first step in the development of molecular networks capable of predicting bioactivity based on an assessment of molecular similarity. </jats:sec

Chain-reaction anion exchange between metal-organic cages

Differential binding affinities for a set of anions were observed between larger (1) and smaller (2) tetrahedral metal-organic capsules in solution. A chemical network could thus be designed wherein the addition of hexafluorophosphate could cause perchlorate to shift from capsule 2 to capsule 1 and triflimide to be ejected from capsule 1 into solution

Five Discrete Multinuclear Metal-Organic Assemblies from One Ligand: Deciphering the Effects of Different Templates

A rigid organic ligand, formed through the <i>subcomponent self-assembly</i> of <i>p</i>-toluidine and 6,6′-diformyl-3,3′-bipyridine, was employed in a systematic investigation into the synergistic and competing effects of metal and anion templation. A range of discrete and polymeric metal-organic complexes were formed, many of which represent structure types that have not previously been observed and whose formation would not be predicted on taking into account solely geometric considerations. These complex structures, capable of binding multiple guests within individual binding pockets, were characterized by NMR, ESI-MS, and single-crystal X-ray diffraction. The factors that stabilize individual complexes and lead to the formation of one over another are discussed

Facile synthesis of a peptidic Au(i)-metalloamphiphile and its self-assembly into luminescent micelles in water

We report a short synthetic route for the preparation of a peptidic Au(i)-metalloamphiphile which, in buffered environments of physiological ionic strength, self-assembles into luminescent micellar nanostructures of 14 nm in diameter

Chain-Reaction Anion Exchange between Metal–Organic Cages

Differential binding affinities for a set of anions were observed between larger (<b>1</b>) and smaller (<b>2</b>) tetrahedral metal–organic capsules in solution. A chemical network could thus be designed wherein the addition of hexafluorophosphate could cause perchlorate to shift from capsule <b>2</b> to capsule <b>1</b> and triflimide to be ejected from capsule <b>1</b> into solution

Chain-Reaction Anion Exchange between Metal–Organic Cages

Differential binding affinities for a set of anions were observed between larger (<b>1</b>) and smaller (<b>2</b>) tetrahedral metal–organic capsules in solution. A chemical network could thus be designed wherein the addition of hexafluorophosphate could cause perchlorate to shift from capsule <b>2</b> to capsule <b>1</b> and triflimide to be ejected from capsule <b>1</b> into solution

Anion-induced reconstitution of a self-assembling system to express a chloride-binding Co(10)L(15) pentagonal prism

Biochemical systems are adaptable, capable of reconstitution at all levels to achieve the functions associated with life. Synthetic chemical systems are more limited in their ability to reorganize to achieve new functions; they can reconfigure to bind an added substrate (template effect) or one binding event may modulate a receptor's affinity for a second substrate (allosteric effect). Here we describe a synthetic chemical system that is capable of structural reconstitution on receipt of one anionic signal (perchlorate) to create a tight binding pocket for another anion (chloride). The complex, barrel-like structure of the chloride receptor is templated by five perchlorate anions. This second-order templation phenomenon allows chemical networks to be envisaged that express more complex responses to chemical signals than is currently feasible