title: 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.
authors: School of Chemistry, University of Leeds, Leeds, LS2 9 JT, UK.
authors: Maria L
authors: ML
authors: Pellizzaro
authors: Andrea M
authors: AM
authors: McGhee
authors: Lisa C
authors: LC
authors: Renton
authors: Michael G
authors: MG
authors: Nix
authors: Julie
authors: J
authors: Fisher
authors: W Bruce
authors: WB
authors: Turnbull
authors: Andrew J
authors: AJ
authors: Wilson
mesh_terms: D000577:Amides / Q000737:chemistry; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D000577:Amides; D007093:Imidazoles; D009287:Naphthyridines; D003596:Cytosine; D014508:Urea