Near-Quantitative Formation of Imines in Water with Allosteric Control

We demonstrate the near-quantitative formation of an imine bond in water under physiologically relevant conditions using a stoichiometric ratio of aldehyde and amine. To overcome the low hydrolytic stability of imines in water, a complementary metal coordination bond between the amine and aldehyde monomers is introduced to enhance the thermodynamic stability of the imine. Imine bond formation is substrate-selective, tolerates the presence of a variety of functional groups, and produces imines that are stable in a broad pH range. We also show that the presence of a second metal-ion complex in the building blocks provides a regulatory handle to 'switch on' imine-bond formation using ATP as an external allosteric effector.