Combinatorial chemistry programmes

Two main approaches to combinatorial chemistry are used—parallel synthesis and split synthesis. In parallel synthesis, each compound is prepared independently. Typically, a reactant is first linked to the surface of polymer beads, which are then placed into small wells on a 96-well glass plate. Programmable robotic instruments add different sequences of building blocks to tfie different wells, thereby making 96 different products. When the reaction sequences are complete, the polymer beads are washed and their products are released. 

The development of combinatorial chemistry and high throughput screening programmes has stimulated efforts to find experimental and computational models to estimate and predict drug absorption, distribution, metabolism and elimination based on drug physicochemical properties. 

Since the introduction of combinatorial chemistry techniques, the emphasis has shifted from the design of large diverse libraries towards smaller more focused libraries. Indeed, as the number of protein crystal structures that are available has increased, so too has the interest in using this structural knowledge for combinatorial library design, compound acquisition programmes and virtual screening. This trend is likely to continue in the near future. 

Even with combinatorial chemistry and HTS, lead generation can be extremely laborious because of the vast number of different molecules possible (framework and biofunctional group combinations). To ease this burden, some rational drug design and quantitative structure activity relationships (QSARs) are often introduced to direct the programme and utilise a company s finite screening resource as efficiently as possible. 

Dynamic Chemistry. Supramolecular Materials Programmable, Dynamic, Combinatorial Materials... 

The combination of the features of supramolecular systems - information and programmability, - dynamics and reversibility, - combinatorics and structural diversity, leads towards the emergence of the global concept of ADAPTIVE CHEMISTRY, which lies higher up the axis of complexity. It implies combinatorial assembly, selection and growth under time reversibility. 

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