Dynamic Structure of Organic Compounds in Solution According to NMR Data and Quantum Chemical Calculations: III. Noradrenaline

Parameters of restricted internal rotation about the C–C bond of the O–C–C–N fragment in the neutral and protonated forms of noradrenaline in D 2 O, CD 3 OD, and DMSO- d 6 were estimated by quantum molecular dynamics and NMR methods. The one-dimensional internal rotation potentials were calculated in the MP2/aug-cc-pVTZ approximation. The multiplet structure of the 1 H NMR spectra of neutral and protonated noradrenaline in the given solvent series was resolved, and signals of diastereotopic methylene protons pro- S and pro- R were assigned. The conformational dependences of the proton coupling constants were calculated at the FPT-DFT 6-311++G(2 df ,2 p ) level of theory. The relative contributions of different rotamers were evaluated by solving a series of inverse vibrational problems in terms of the large-amplitude vibration model to achieve the best agreement between the calculated and experimental coupling constants. The neutral form of noradrenaline was shown to prefer conformation g + , while conformer g − was found to be the minor one. Protonation of noradrenaline molecule essentially stabilizes conformer g − . In all cases, the contribution of conformer t with transoid orientation of the oxygen and nitrogen atoms did not exceed 1%. The obtained data can be useful for the construction of a quantitative model for noradrenaline binding to receptors at the molecular level.