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).

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The development of strategies for modulating the conformation (and thereby the function) of a polypeptide chain is a fundamental challenge in the emerging field of protein design.1 Many natural proteins are regulated by posttranslational modification of amino acid residue side chains, processes that are often enzymatically facilitated and reversible.1 2 We report the use of a chemically

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Rheology and small-angle neutron scattering are used to probe the structure of nonionic surfactant mixtures in water. Small amounts of a C 14 diol ͑Surfynol ® 104͒ cause enormous structural and rheological changes when added to aqueous solutions of an ethylene oxide-propylene oxide-ethylene oxide triblock copolymer ͑Pluronic ® P105͒. The C 14 diol is only soluble up to 0.1 wt % in pure water, but can be added in large quantities to aqueous solutions of the copolymer. The hydrophobic diol incorporates into the existing copolymer micelles and causes a cascade of changes in the micelle structure, with resultant changes in rheology. Particularly striking is the spherical to worm-like micelle transition, where the viscosity changes by a factor of more than 10 4 .