The Reversible Dimerization of Chiral Ureidopyrimidinones. Chiroptical Signaling via the Formation and Disruption of Quadruple Hydrogen Bonding Arrays

In solution, 2-ureido-4[1H]-pyrimidinones show a strong propensity to dimerize via a well-defined quadruple donor-donor-acceptor-acceptor hydrogen bonding array. For derivatives that have been modified with chiral functional groups, intermolecular associations of this kind are accompanied by conformational and structural perturbations that, acting together, serve to significantly alter measured optical rotation values. Thus, changes in solvent composition, solution pH, along with other environmental “inputs” that either disrupt or encourage hydrogen bonding interactions, can be effectively harnessed to reversibly modulate the chiroptical output signals generated by these simple derivatives. In this regard, the chiral ureidopyrimidinone analogues described herein can be viewed as a new class of molecules that exhibit stimuli-responsive or adaptive chiroptical behavior.