Conformer-independent ureidoimidazole motifs--tools to probe conformational and tautomeric effects on the molecular recognition of triply hydrogen-bonded heterodimers.

ABSTRACT

Linear arrays of hydrogen bonds are useful for the reversible assembly of "stimuli-responsive" supramolecular materials. There is thus an ongoing requirement for easy-to-synthesise motifs that are capable of presenting hydrogen-bonding functionality in a predictable manner, such that high-affinity and high-fidelity recognition occurs. The design of linear arrays is made challenging as a consequence of their ability to adopt multiple conformational and tautomeric configurations; with each additional hydrogen-bonding heteroatom added to an array, the available tautomeric and conformational space increases and it can be difficult to anticipate where unproductive conformers/tautomers will arise. This paper describes a detailed study on the complementary ureidoimidazole donor-donor-acceptor (DDA) array (1) and amidoisocytosine donor-acceptor-acceptor (DAA) array (2). A specific feature of 1 is that two degenerate, intramolecular hydrogen-bonded conformations are postulated, both of which present a DDA array that is complementary to appropriate DAA partners. 1D and 2D (1)H NMR spectroscopy, isothermal titration calorimetry, and ab initio structure calculations confirm 1 interacts with 2 (K(a) ≈ 33,000 M(-1) in CDCl(3)) in a conformer-independent fashion driven by enthalpy. Comparison of the binding behaviour of 1 with hexylamidocytosine (4) and amidonaphthyridine (5) provides insight on the role that intramolecular hydrogen-bonding plays in mediating affinity towards DAA partners.