Dynamic combinatorial chemistry at the phospholipid bilayer interface

Thioester exchange was found to be a suitable reversible reaction to achieve rapid equilibration of dynamic combinatorial libraries at the egg phosphatidyl choline bilayer interface. Competing thioester hydrolysis can be minimised by judicial choice of the structure of the thioesters and the experimental conditions. Comparison of the library compositions in bulk solution with those in the presence of egg PC revealed that the latter show a bias towards the formation of library members rich in membrane-bound building blocks. This leads to a shift away from macrocyclic towards linear library members.The methodology to perform dynamic combinatorial chemistry at the phospholipid bilayer interface has been developed. The spatial confinement of building blocks to the membrane interface can shift the ring-chain equilibrium in favour of chain-like compounds. These results imply that interfaces may be used as a platform to direct systems to the formation of (informational) polymers under conditions where small macrocycles would dominate in the absence of interfacial confinement.Dynamic combinatorial chemistry [1-3] is a growing field in the general area of systems chemistry [4-11] and revolves around equilibrium mixtures of molecules or supramolecules that can exchange the building blocks from which they are constituted. The resulting dynamic combinatorial libraries (DCLs) are inherently responsive to influences that alter the relative thermodynamic stabilities of the library members. For example, addition of a template (a guest molecule or a biomolecule) to a DCL will result in a stabilization of those library members that bind to the template, inducing a shift in the product distribution, ideally in favour of the best binders and at the expense of the other unwanted library members. This responsiveness makes dynamic combinatorial chemistry an important tool for the discovery of new synthetic receptors [12-21] and ligands for biomolecules [22-25]. Moreover, the technique has