Stable Three-Center Hydrogen Bonding in a Partially Rigidified Structure

Abstract

The three-center hydrogen bond in diaryl amide 1 was examined by IR and 1H NMR spectroscopy, X-ray crystallography, and ab initio calculations. By comparing 1 with its structural isomers 2, 3 and 4, and with its conformational isomers 1a-c, it was found that the two two-center components of the three-center interaction reinforce each other, that is, the enhanced stability of the three-center hydrogen bond is a result of positive cooperativity between the two components. Substituents not involved in hydrogen bonding have little effect on the strength of the two- and three-center hydrogen bonds. To our knowledge, this is the first three-center hydrogen-bonding system that has been shown to exhibit positive cooperativity. Ab initio calculations of the geometries, vibrational modes, and 1H NMR chemical shifts also support the experimental findings. These results have provided a new insight into the three-center intramolecular hydrogen bonding in a partially rigidified structure and have provided a reliable motif for designing stably folded structures.

Creating nanocavities of tunable sizes: Hollow helices

“…Our results indicated that the three-center hydrogen-bonding system, consisting of the S(5) and S(6) type (21) hydrogen-bonded rings, was particularly stable in the solid state and in solution (19,20). It persisted in chloroform, the highly polar dimethyl sulfoxide (DMSO), and even in water (unpublished data), and this structure was confirmed by NMR, IR, and x-ray crystallographic studies on short oligomers.…”

“…Our previous studies have demonstrated that short oligomers with m-backbones adopt a well-defined crescent conformation (12,19,20). Our results indicated that the three-center hydrogen-bonding system, consisting of the S(5) and S(6) type (21) hydrogen-bonded rings, was particularly stable in the solid state and in solution (19,20).…”

“…Strong nuclear Overhauser enhancements (NOEs) exist between each of their amide NH signals and the protons of the methyl, or ␣͞␤-methylene of the two substituents on the S(5) and S(6) type hydrogen-bonded rings (see supporting information). These NOEs, which are typical for these three-center hydrogen bonds (12,19,20), suggest that the backbones of both 2a and 3 are rigidified and adopt crescent conformations. An obvious and significant difference is observed when comparing the NOESY spectra of 2a and 3: while an obvious NOE between the end methyl protons and the aromatic Hb1, and a weaker contact between the end methyl H atoms and the amide Hb, can be detected for 2a (Fig.…”

“…The amide NH signals of both 6 and 7 appeared at downfield positions, between 10.1 ppm and 10.7 ppm, a range typical for amide protons involved in this type of three-center hydrogen bond (19,20). In particular, 5 of the 7 amide NH signals of 15-mer 6 appeared as well-resolved single peaks, whereas 6 of the 10 amide NH signals of 21-mer 7 were well resolved.…”

Thermodynamic characterization of three centered hydrogen bond using o-aromatic amides, oxalamates and bis-oxalamides as model compounds

“…In fact there is a controversy about the energetic superiority of THB over regular or two centered HB. There are some studies that provide experimental evidence in favor, [11][12][13] however some experimental 14,15 and theoretical studies, 3 using flexible molecules as a model, provide contrary evidence.…”