Conformational Behavior and Magnetic Properties of a Nitroxide Amino Acid Derivative in Vacuo and in Aqueous Solution

Abstract

The conformational behavior and magnetic properties of the R-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 R -tetrasubstituted residues points out the difference between cyclic and open-chain substituents. The nitrogen isotropic hyperfine coupling constants (A N ) 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 A N values of extended TOAC conformers are significantly lower because of the constrained nearly planar structure of the piperidine ring.

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

“…A quantum mechanical study of TOAC in vacuo and in aqueous solution showed that the nitroxyl group in an equatorial position is more stable than in the axial position (D'Amore et al 2003). In addition, the crystallographic characterization of some TOAC derivatives showed the piperidine ring in an approximate chair conformation, with the α-amino group in the axial position and the α-carboxyl group in the equatorial position (Flippen-Anderson et al 1996; Crisma et al 2005).…”

Complete structural and magnetic characterization of biological radicals in solution by an integrated quantum mechanical approach: Glycyl radical as a case study

“…While some gradient corrected approximations ͑GGA͒ provide reasonable numerical values for hfc's, 12 several studies have shown that a particular approach to DFT, the so-called hybrid Hartree-Fock/Kohn-Sham ͑HF/KS͒ model, 16 introduces further significant improvements. [17][18][19][20] As a matter of fact, the calculation of hfcs is now a standard feature of many quana͒ Author to whom correspondence should be addressed. Electronic mail: baronev@unina.it tum chemical packages and can be easily and routinely performed.…”

Selected hydroxycoumarins as antioxidants in cells: physicochemical and reactive oxygen species scavenging studies

“…Geometry optimizations for each selected conformer were then performed by means of density functional theory (DFT) at the B3LYP/6-31G(d) level as implemented in the GAUSSIAN 03 package, because it is well known that computational models based on DFT are particularly suitable for the analysis of magnetic properties for open-shell species. [62][63][64][65][66] Energetics was further studied in aqueous solution via polarizable continuum model (PCM) using single-point energy calculations at the B3LYP/6-31G+(d,p) level. [67] A scaling factor of 0.9806 was used for the zero-point vibrational energy (ZPE) correction for the B3LYP geometries.…”