Solid-State NMR Studies On The Reaction Mechanism Of Hetcrogeneous Catalysis And On The Polymorphy Of Pharmacetical Compounds

With the discovery of innovative cross-polarization method and magic-angle-spinning technique (CP/MAS), the solid-state NMR (SSNMR) technique has been widely used in the field of chemistry, structural biology, materials science, industrial catalysis, food and drug sciences, etc. Solid-state NMR parameters, such as isotropic and anisotropic chemical shifts are very sensitive to electronic environment of the nuclear spins. Therefore, solid-state NMR techniques are particularly suitable for monitoring of reaction products in heterogeneous catalysis, determination of structure in crystalline solid, and observation of host-guest chemistry.Based on our previous in situ stopped-flow magic-angle-spinning NMR studies of surface alkoxy species, we investigated the reactivity of surface ethoxy species (SES) on acidic molecular sieve catalysts using high-resolution solid-state NMR. It has been shown that the SES is an active intermediate in the interconversion and degradation of C2species (ethylene, ethanol, diethyl ether). By controlling the concentration of acid sites of acidic zeolites, for the first time we observed the interconversion between SES and ethylene. Combined with the DFT calculations,13C-scrambling mechanism of SES mediated by π-complex of ethylene with a transient carbenium ion was revealed. The reactivity and relative stability of SES was further investigated by its reaction with a variety of probe molecules. Among them, the unique reactivities of SES at the low and high temperatures were compared using water and hydrogen chloride as probe molecules. In-depth understanding of the reactivity of SES on acidic zeolite catalysis, is not only of great significance in the field of basic science research, but also of practical importance for design and optimization of industrial processes.A number of solid-state NMR techniques, such as CP/MAS of13C,15N,19F and solid-state two-dimensional methods (SUPER, FIREMAT,13C-1H and13C-19F HETCOR) have been applied to explore the solid structure of three polymorphs of atorvastatin calcium (ATC). For the first time, we demonstrated that there are two atorvastatins in an asymmetric unit of three polymorphs of ATC and their major structure difference is along the aliphatic carbon chain. A complete solid-state NMR chemical shift assignment of13C,15N, and19F of ATC, an important active pharmaceutical ingredient (API) of the best-selling drug (LipitorTM), was determined. In addition to isotropic chemical shifts, the13C chemical shift tensors of resolvable resonances (C6-C12, C25, and C33-C35) of Form I of atorvastatin calcium (ATC-I) have also been measured and the results were analyzed to provide critical structural information. Without recourse to an X-ray crystal structure for this solid, we proposed a local structure of ATC-I that is consistent with solid-state NMR data and DFT calculations.