Dynamic combinatorial chemistry

By modern definition, dynamic combinatorial chemistry is generally considered to be a method of facilitating the generation of new chemical species by the reversible linkage of simple building blocks, under thermodynamic control.

[7] Although this approach was arguably utilised in the work of Fischer[8] and Werner[9] as early as the 19th century, their respective studies of carbohydrate and coordination chemistry were restricted to rudimentary speculation, requiring the rationale of modern thermodynamics.

[10][11] It was not until supramolecular chemistry revealed early concepts of molecular recognition, complementarity and self-organisation that chemists could begin to employ strategies for the rational design and synthesis of macromolecular targets.

[4] Their work combined thermodynamic templation in tandem with combinatorial chemistry, to generate an ensemble complex porphyrin and imine macrocycles using a modest selection of simple building blocks.

Sanders then developed this early manifestation of dynamic combinatorial chemistry as a strategy for organic synthesis; the first example being the thermodynamically-controlled macrolactonisation of oligocholates to assemble cyclic steroid-derived macrocycles capable of interconversion via component exchange.

[4] However, their subsequent investigations identified that both the disulfide and hydrazone covalent bonds exhibit effective component exchange processes and so present a reliable means of generating dynamic combinatorial libraries capable of thermodynamic templation.

[22] The development of protein-directed DCC has not been straightforward because the reversible reactions employed must occur in aqueous solution at biological pH and temperature, and the components of the DCL must be compatible with proteins.