Dynamics of Switch-Binding by a Linear Ligand That Transforms to a Macrocycle upon Chelation to a Metal Ion: Synthesis, Kinetics, and Equilibria

Abstract

It is proposed that for chemical processes in which equilibration is too slow to achieve certain goals, switch-binding and switch-release reactions may be used to accelerate complex formation. Whereas photo triggers are well known for switch-releasing, switch binding is first described here for notably slow complex formation reactions between metal ions and macrocyclic ligands. A linear tetradentate ligand, L L/C , was designed with functional groups that will react with each other (primary amine, carbonyl) at its extremities. Upon complexation the metal ion is predicted to cause reaction between these functional groups, producing a macrocyclic ligand that encircles the metal ion. Equilibrium studies were made with the metal ions Cu 2+ , Hg 2+ , Ni 2+ , and Zn 2+ both with the switch-binding ligand, L L/C , and with a ligand, L L , that is very similar except it cannot undergo the switching process. The formation constants were very similar for the two ligands, with the metal ion affinities decreasing in the order Cu 2+ » Ni 2+ ≈ Zn 2+ > Hg 2+ . The kinetics of reaction were studied for formation of the nickel(II) complexes of both ligands. Results gave a first indication that nickel very rapidly chelates to the switch-binding ligand before forming the macrocycle. The nickel(II) reacts with L L/C in a complicated rapid set of processes on the fractional second time scale, followed by a process in the hour time regime. In contrast, under the same conditions, only a single rapid rate process was observed for the reaction of nickel(II) with L L . The specific rate constants for L L are greater than those for L L/C . Detailed analysis, strongly augmented by mass spectrometric studies, proved that the rapid process produces a nickel complex of the linear ligand and that intramolecular ring closure takes place relatively slowly and under the control of the metal ion. This proof of concept for switch binding, using the template effect, completes the model for replacing equilibration for the reversible formation of metal complexes with a switch-binding and release process.