title: Combined experimental and quantum chemical investigation of chiroptical properties of nicotinamide derivatives with and without intramolecular cation-pi interactions.
abstract: The circular dichroism (CD) spectra of neutral and cationic nicotinamide derivatives were experimentally examined in solution and in the solid state to show dramatic differences in the two phases and appreciable dependence on temperature and solvent. The CD spectrum of neutral nicotinamide 1 in solution was reproduced theoretically by averaging the theoretical spectra calculated for all of the extended and folded conformers (s-trans-G(+), s-cis-G(+), s-trans-T, and s-cis-T) weighted by their population. The preference for the folded, over the extended, conformers in less polar solvent was indicated by the calculation and confirmed experimentally by the analysis of specific rotations. Theoretical CD spectrum calculated for the conformer found in the X-ray structural analysis (s-cis-T) well reproduced the experimental CD spectrum measured in the solid state. Introducing cation-pi interactions by N-methylation of 1 to give 1-Me(+) led to dramatic changes in CD spectrum. Nevertheless, the experimental CD spectrum of 1-Me(+) was well reproduced by averaging the theoretical spectra calculated for a pair of most stable conformers (s-cis-G(+) and s-trans-G(+)) of 1-Me(+). The CD spectrum calculated for the s-trans-G(+) conformer, which was found in the X-ray crystallographic analysis, did not agree with the experimental one. The theoretical spectra were better reproduced in general by the more sophisticated RI-CC2 method, but the conventional TD-DFT method also gave acceptable results. This allowed us to successfully calculate the larger derivative 2-Me(+), for which the RI-CC2 method was not practically applicable. These results show that the structure/conformation may vary with the conditions employed (e.g., by altering the solvent or phase) and thus the experimental analysis under the identical condition is essential for a serious structural study. The present study on a series of nicotinamide derivatives 1, 1-Me(+), and 2-Me(+) with and without cation-pi interactions demonstrates that the combination of experimental and theoretical chiroptical methods is capable of providing reliable structural/conformational information in solution phase, which is complementary to the X-ray crystallographic structure in the solid state.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimizu
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mori
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamada
mesh_terms: D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008956:Models, Chemical; D008958:Models, Molecular; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D002412:Cations; D009536:Niacinamide