Conformation-directing effects of a single intramolecular amide-amide hydrogen bond: variable-temperature NMR and IR studies on a homologous diamide series

Abstract

We have studied intramolecular hydrogen bonding in a homologous series of diamides (compounds 1-6) in methylene chloride, 9: 1 carbon tetrachloride/benzene, and acetonitrile. By correlating variable-temperature 'H NMR and 1R measurements, we have shown that the temperature dependence of the amide proton NMR chemical shift (Ab/AT) can provide qualitative (and in some cases quantitative) information on the thermodynamic relationship between the intramolecularly hydrogen bonded and non-hydrogen-bonded states of flexible molecules. Among the hydrogen-bonded ring sizes represented in the diamide series, the intramolecular interaction is particularly enthalpically favorable in the nine-membered hydrogen-bonded ring (compound 4). Variable-temperature IR and NMR data indicate that the internally hydrogen bonded state of diamide 4 is 1.4-1.6 kcal/mol more favorable enthalpically than the non-hydrogen-bonded state, in methylene chloride solution; the non-hydrogen-bonded state is 6.8-8.3 eu more favorable entropically in this solvent. In contrast, there appear to be much smaller enthalpy differences between the internally hydrogen bonded and non-hydrogen-bonded states of diamides 2 and 3. Our findings are important methodologically because the temperature dependences of amide proton chemical shifts are commonly used to elucidate peptide conformation in solution. Our results show that previous "rules" for the interpretation of such data are incomplete. In non-hydrogen-bonding solvents, small amide proton Ab/AT values have been taken to mean that the proton is either entirely free of hydrogen bonding or completely locked in an intramolecular hydrogen bond over the temperature range studied. We demonstrate that an amide proton can be equilibrating between intramolecularly hydrogen bonded and non-hydrogen-bonded states and still manifest a small chemical shift temperature dependence (implying that the hydrogen-bonded and non-hydrogen-bonded states are of similar enthalpy).

Intramolecular hydrogen bonding of (+)-biotin and biotin derivatives in organic solvents

“…Non-hydrogen bonded amide protons generally show a small temperature dependence, < 3 ppb/K. 10,11 In order to confirm the degree of intramolecular hydrogen bonding of biotin and its derivatives (1-9), the temperature dependence was determined at 1 mM in CDCl 3 and shown in Table 1 (2 % DMSO-d 6 and 98% CDCl 3 for biotin).…”

Salicylaldehyde Hydrazones: Buttressing of Outer-Sphere Hydrogen-Bonding and Copper Extraction Properties

“…As temperature is increased the larger shift of the hydrazone signal to high field compared to that of the phenol is consistent with the former forming inter-and the latter intra-molecular hydrogen bonds. [57][58][59][60][61] The preference for the phenolic proton to form an intramolecular hydrogen bond to the imino nitrogen accords with solid state structures (see Figure 4). An exception is the 3-nitrosubstituted ligands where the nitro-group competes effectively for the phenolic proton to give structures such as those shown in Figure 6 (see also computational results below).…”

Purification and characterization of hydrosoluble components from the sap of Chinese lacquer tree Rhus vernicifera

“…3) and of the two polysaccharides, GP1 and GP2 (Fig. 4) the wide peak at about 3418 cm −1 for all of the spectra is assigned to the stretching vibration of O-H and/or non-hydrogen-bonded N-H [29]. The peaks at about 1648, 1540, and 1310 cm −1 can be attributed to the amido groups, and the strong peaks of 1648 and 1540 cm −1 (only for L1 and L2) were amide I (stretching vibration of C O and deformation vibration of -NH) and II (stretching vibration of C-N-H) bands respectively [30,31].…”