University of Ottawa NMR Facility Blog: March 2015

Tuesday, March 31, 2015

Cross Polarization Based Mixture Resolution in Solids

One of the most common techniques used to collect solid-state NMR data for spin I = ½ nuclides is a combination of cross polarization (CP) and magic angle spinning (MAS). CPMAS provides high sensitivity from the CP and high chemical shift resolution from the MAS. Furthermore, the scan repetition rate depends on the shorter relaxation time of the protons rather than the longer relaxation time of the spin I = ½ nuclide therefore, more scans can be collected per unit time. It must be remembered however, that the success of the CP technique depends on the dipolar coupling interaction between proximate protons and the nucleus being observed. In the absence of dipolar coupled protons, CP signals are not observed. For this reason, it is sometimes necessary to use a conventional one-pulse method (Bloch decay) which can be used to observe the spin I = ½ nuclide, albeit with lower sensitivity, whether protons are present or not. When a sample consists of a mixture with some protonated components and some components without protons, then it may be advantageous to collect both a CPMAS and a Block decay spectrum. When both methods are used, the data can be used to resolve the spectrum of the mixture into subspectra; the protonated components in one spectrum and those components without protons in another. An example of this is shown with the ¹³C NMR data for a common antacid tablet in the figure below.

The two most abundant carbon containing components of an antacid tablet are calcium carbonate and sucrose. Spectrum (a) is the CPMAS spectrum. It consists only of the resonances of sucrose (color coded in yellow) since calcium carbonate (color coded in pink) contains no protons. Spectrum (b) is the Bloch decay spectrum with high power proton decoupling. It consists of both the resonances of sucrose and calcium carbonate. Spectrum (c) is a linear combination of (a) and (b) and represents, primarily, the spectrum of calcium carbonate. Another interesting example of CP based mixture analysis is given here using Christmas shortbread cookies as an example.

Thursday, March 26, 2015

Mixture Resolution in ¹³C CPMAS NMR

The recycle delay necessary to get the highest signal-to-noise ratio in a multi-scan ¹³C CP MAS NMR spectrum depends on the relaxation properties of the protons in the sample. The protons in pure solid samples normally belong to a single homogeneous dipolar coupled network. As a result, all of the protons in the coupled network have a common T₁ relaxation time. One would expect the same behavior for a mixture of compounds only if the components were mixed at the molecular level. If the compounds are not mixed at the molecular level, the sample consists of domains of pure materials, each of which has a common proton T₁. If the proton T₁'s of the domains are significantly different, then one has a means of discriminating between the domains and hence the compounds of the mixture with ¹³C CPMAS NMR data. The figure below illustrates this principle for a tablet of vitamin C ground into a powder. The vitamin C tablet consists primarily of ascorbic acid for which the structure is shown in the figure. The other major solid organic additives are hypromellose (hydroxypropyl methylcellulose), stearic acid (n-C₁₇H₃₅COOH), magnesium stearate and carnauba wax (a complex mixture of C₂₆ to C₃₀ acids, esters and alcohols). When the tablet is ground up, the powder consists of ascorbic acid domains, stearic acid domains, magnesium stearate domains and carnauba wax domains.

¹³C CPMAS NMR spectra were acquired with a 30 second and a 2 second recycle delay and are shown in (a) and (b), respectively. One can see that relative intensity of the components in the mixture depends on the recycle delay. The proton T₁ of the ascorbic acid is obviously longer than that of the other components of the mixture. The spectra in (c) - (e) are linear combinations of (a) and (b). The linear combination in spectrum (c) was created such that the ascorbic acid resonances were nulled. The resulting spectrum is that of only the organic additives. The hypromellose resonances are in the 50 ppm to 110 ppm range. The aliphatic resonances of the stearic acid, magnesium stearate and carnauba wax overlap in the 10 ppm to 50 ppm range and appear to have similar proton T₁'s. The linear combination in spectrum (d) was created such that the aliphatic stearic and wax resonances were nulled. The resulting spectrum is that of ascorbic acid and the inverted spectrum of the hypromellose. The linear combination in spectrum (e) was created such that the hypromellose resonances were nulled. The resulting spectrum is that of the ascorbic acid with the stearic acid, magnesium stearate and carnauba wax additives. This combination allows observation of the ascorbic acid with no overlapping resonances from the additives.

Wednesday, March 25, 2015

¹³C NMR of Vitamin C - Solids vs. Liquids NMR

In ¹³C[¹H] NMR spectra of liquids, one observes a single resonance for each symmetrically nonequivalent carbon atom. The same is true of the ¹³C CPMAS spectra of solids. The difference is that the molecular symmetry is the determining factor in liquids NMR whereas the crystallographic symmetry is the determining factor in solids NMR. As a result, solids NMR can give different spectra for different solid polymorphs and multiple resonances due to multiple nonequivalent molecules in the asymmetric unit of the crystal structure. The figure below compares the solids ¹³C CPMAS and liquids ¹³C[¹H] NMR spectra of a vitamin C (ascorbic acid) tablet.

The structure is provided in the figure and the assignment for all of the carbon atoms is color coded. In the liquids spectrum, one observes resonances for each carbon in the molecule. In the ¹³C CPMAS spectrum, one observes that three of the six ¹³C resonances are doubled. This doubling is consistent with there being two nonequivalent ascorbic acid molecules in the asymmetric unit of the crystal. Presumably, the other three resonance are doubled as well but there is insufficient resolution in the spectrum for this observation. The broad features in the spectrum are due to additives in the vitamin C tablet which include, hypromellose, stearic acid and carnauba wax.