Double-level "orthogonal" dynamic combinatorial libraries on transition metal template

Dynamic combinatorial libraries are mixtures of compounds that exist in a d ynamic equilibrium and can be driven to compositional self adaptation via s elective binding of a specific assembly of certain components to a molecula r target. We present here an extension of this initial concept to dynamic l ibraries that consists of two levels, the first formed by the coordination of terpyridine-based ligands to the transition metal template, and the seco nd, by the imine formation with the aldehyde substituents on the terpyridin e moieties. Dialdehyde 7 has been synthesized, converted into a variety of ligands, oxime ethers L-11-L-33 and acyl hydrazones L-44-L-77, and subseque ntly into corresponding cobalt complexes. A typical complex, Co(L-22)(2)(2) is shown to engage in rapid exchange with a competing ligand L-11 and wit h another complex, Co(L-22)(2)(2+) in 30% acetonitrile/water at pH 7.0 and 25 degreesC. The exchange in the corresponding Co(III) complexes is shown t o be much slower. Imine exchange in the acyl hydrazone complexes (L-44-L-77 ) is strongly controlled by pH and temperature. The two types of exchange, ligand and imine, can thus be used as independent equilibrium processes con trolled by different types of external intervention, i.e., via oxidation/re duction of the metal template and/or change in the pH/temperature of the me dium. The resulting double-level dynamic libraries are therefore named orth ogonal, in similarity with the orthogonal protecting groups in organic synt hesis. Sample libraries of this type have been synthesized and showed the c omplete expected set of components in electrospray ionization MS.