Conformational behavior and magnetic properties of a nitroxide amino acid derivative in vacuo and in aqueous solution

The conformational behavior and magnetic properties of the -acetylamino, N'-methylamide derivative of TOAC (4-amino-2,2,6.6-tetramethylpiperidine-1-oxyl-4-carboxylic acid) have been investigated in vacuo and in aqueous solution by an integrated computational approach including density functional, post-Hartree-Fock, and continuum solvent models. According to our computations, piperidine rings with an equatorial placement of the nitroxide moiety are more stable by about 1 kcal/mol than their axial counterparts both in vacuo and in aqueous solution. With respect to natural residues, TOAC shows a marked preference for helical conformers, which is further enhanced by polar solvents. A comparison with other C-tetrasubstituted residues points out the difference between cyclic and open-chain substituents. The nitrogen isotropic hyperfine coupling constants (AN) of folded TOAC conformers are similar to those of other nitroxides involving six-membered rings and are well reproduced by a composite QM/QM/PCM model. The AN values of extended TOAC conformers are significantly lower because of the constrained nearly planar structure of the piperidine ring.