Solvent effects on chemical shielding: CSGT-DFT studies using the polarizable continuum model

Density functional theory (DFT) combined with the polarizable continuum model (PCM) and continuous set of gauge transformations (CSGT) method is applied to calculate solvent effects on chemical shielding of the nitrogen atoms in 1,2,4,5-tetrazine, 1-methyl-1,2,3,4-tetrazole, 1-methyl-1,2,3,5-tetrazole, and N,N-dimethyl-acetamidine. Theoretical results show that solvent-induced variations in shielding are due in large part to the perturbation of the solvent on the electronic wave function of the solute (direct effect) and not on the relaxation of solute geometry under the influence of the solvent (indirect effect). Geometry optimization of the solute was found to be more important in PCM shielding calculations than in the supermolecule approach. Solvent effects on the chemical shielding of the backbone amide nitrogen and carbonyl carbon, as well as alpha and beta carbons, of omega-conotoxin GVIA were also investigated. Experimental shifts were measured using two-dimensional NMR spectroscopy. Peptide fragments with experimental geometry were used to calculate carbon and nitrogen shielding. A hybrid distance geometry-simulated annealing protocol was used to determine the solution structure of omega-conotoxin GVIA based on NMR data.