Complexation-induced unfolding of heterocyclic ureas. Simple foldamers equilibrate with multiply hydrogen-bonded sheetlike structures.
The synthesis and conformational studies of heterocyclic ureas (amides) 1-7 and their concentration-dependent unfolding to form multiply hydrogen-bonded complexes are described. Ureas 1 and 7 were prepared by reacting 2-aminopyridine and aminonaphthyridine 25, respectively, with triphosgene and 4-(dimethylamino)pyridine (DMAP). Amine 25, in turn, was synthesized by a Knorr condensation of 2,6-diaminopyridine and 4,6-nonanedione. Heterocyclic ureas 3, 4, and 16 were prepared by treating their corresponding amino precursors with butylisocyanate, whereas bisureido naphthyridines 6 and 17 were prepared by heating 2,7-diamino-1,8-naphthyridine (13) with butylisocyanate and 3,4,5-tridodecyloxyphenyl isocyanate, respectively. The hydrogen-bonding modules 2 and 5 were synthesized by reacting 13 and 2-amino-1,8-naphthyridine with valeric anhydride. X-ray crystallographic analyses were performed on ureas 1, 3, 16, and 17, indicating that these ureas are intramolecularly hydrogen-bonded in the solid state. Moreover, detailed 1H NMR solution studies of 1, 3, 4, 6, and 7 indicate that similar folded structures form in chloroform. In addition, naphthyridinylureas 3 and 7 unfold and dimerize by forming four hydrogen bonds at high concentrations, and ureas 1 and 4 unfold in the presence of their hydrogen-bonding complements, amides 2 and 5, to form complexes with three and four hydrogen bonds, respectively. Likewise, the mixing of 6 and 7 results in a mutual unfolding and formation of a robust, sheetlike, sextuply hydrogen-bonded complex. The hydrogen-bonding modules described are useful building blocks for self-assembly, and the unfolding process represents a very primitive mimicry of the helix-to-sheet transition shown by peptides and potentially shown by the hypothetical naphthyridinylurea 8.
Corbin
P S
PS
Department of Chemistry, 600 South Mathews Avenue, University of Illinois, Urbana, Illinois 61801, USA.
Zimmerman
S C
SC
Thiessen
P A
PA
Hawryluk
N A
NA
Murray
T J
TJ
D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D009287:Naphthyridines; D011725:Pyridines; D014508:Urea