Multidimensional solid-state nuclear magnetic resonance spectroscopy of pharmaceuticals and polymers

Crystalline organic materials which have multiple related forms, such as polymorphs, solvates, or isomers, allow structure-property relationships to be investigated. In nedocromil salts and dimethoxybenzoic acid isomers, correlations between conformation and solid-state NMR chemical shifts have been found, and the predictive power of these correlations for determining the structure of crystalline organic materials are discussed in Chapter 3.;It is often impossible to make unambiguous assignments for each resonance in solid-state NMR spectra. Chemical shifts in solids may vary by up to 10 ppm from corresponding solution values and there may be multiple resonances for each carbon due to crystallographically inequivalent sites in the unit cell. Increasing the spinning rate to 28 kHz and the 1H decoupling power to 263 kHz increased the resolution sufficiently for two-dimensional exchange experiments to be used to assign resonances due to crystallographically inequivalent carbons in Chapter 4.;Solution NMR spectroscopy was used to characterize the stereosequence distribution in poly(lactide) (PLA) in Chapter 5. 1H- 13C heteronuclear correlation (HETCOR) NMR experiments were used to assign spectra of PLA. These new assignments do not agree with the previous stereosequence assignments derived from anticipated statistical distributions. We have used both one and two-dimensional NMR experiments on 13C-labeled PLA to assign the NMR spectra.;Solid-state 13C NMR spectroscopy has been used to investigate the physical and morphological properties of PLA synthesized from L-lactide (PLLA) in Chapter 6. Five distinct resonances for the carbonyl and methine carbons of highly crystalline PLLA have been observed, indicating five or more crystallographically inequivalent sites in the crystalline domains of the polymer. Two-dimensional exchange NMR experiments were used to trace connectivity between crystallographically inequivalent sites in PLA. 13C CP/MAS NMR spectroscopy has also been used to study the structure and local environment of stereosequence defect sites in PLA. 13C-enriched L-lactide was used to selectively label the defect sites in PLA. Deconvolution of the peak due to the 13C enriched lactide indicated that these stereosequence defects are located in both the amorphous and crystalline regions of the polymer and that it is possible to quantitate the amount of defect sites in each region.