Solvent Effects on the Conformational Preferences of 2,6-Pyridylcarboxamide Foldamers.

The marked influence of organic solvents and water on the conformational preferences of a chiral, soluble 2,6-pyridylcarboxamide foldamer has been established in an array of seventeen distinct solvents/solvent mixtures. Circular dichroism (CD) spectroscopy has been used to determine the conformational behavior of the soluble PEGylated foldamer as a function of the solvent for aromatic solvents (benzene, toluene and pyridine), chlorinated solvents (chloroform, dichloromethane and tetrachloroethane), polar aprotic solvents (tetrahydrofuran, acetone, acetonitrile, nitromethane, dimethylformamide and dimethylsulfoxide) and polar protic solvents (methanol, methanol/water mixtures). In aromatic and chlorinated solvents, the foldamer displays pronounced CD signals indicating the adoption of a stable helical conformation in these environments. Notably, even in the presence of polar protic solvents containing high levels of water (of up to 35% water in methanol mixtures), a helical conformation is still adopted by the foldamer, albeit with a less well-defined helical conformation than for other less competitive solvents. These investigations provide crucial insights into the conformational preferences of this foldamer class in a wide range of organic solvents and water mixtures. It is anticipated that this solvent study will prove to be highly important for aiding the future design and operation of functional foldamers, including water compatible systems, in diverse environments.