University of Ottawa NMR Facility Web Site

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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 CPMAS 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. 

Wednesday, March 4, 2015

BLOG Index



University of Ottawa NMR Facility BLOG INDEX
March 2015

               H20 vs D2O
1D selective HOESY
               1H-19F
               1H-31P
               for exchanging roramers
1D TOCSY measurements
               as a function of mixing time
               for mixture analysis
1H NMR with X nucleus decoupling
               1H[11B]
               1H[13C]
               1H[19F]
               1H[27Al]
               1H[31P]
2D correlation spectroscopy (COSY)
               11B COSY
               COSY 90 vs COSY 45
               double quantum filtered
               ECOSY for measurement of coupling constants
               magnitude vs phase sensitive
               vs TOCSY
               and NOE (1)
               and NOE (2)
               better data – more scans or more slices?
               data apodization
               phasing (video tutorial)
2D NOESY measurements
               19F NOESY
               and exchange (1)
               and exchange (2)
               choice of mixing time
               effect of viscosity
               phasing
               phasing (video tutorial)
               small vs large molecules
               HSQC - TOCSY
               TOCSY vs COSY
2H NMR of liquids
               chemical shift referencing in
               on Bruker AVANCE spectrometers
               backward linear prediction to correct for
               pulse sequence to minimize
ASCII file generation
               in TOPSPIN (1)
               in TOPSPIN (2)
Background signals
               11B
               23Na
               from dirty NMR probe
Background suppression
               11B in liquids
               11B in solids
Baseline correction
               improving
               in 2D NMR spectra
               in solids MAS spectra of quadrupolar nuclides
Benchtop NMR
               (1)
               (2)
Chemical exchange agents for spectral simplification
               D2O shake
               trifluorocaetic acid
Chemical shift referencing
               1H in aqueous solution
               external
               in 2H NMR
Chemical shift tensors
               and MAS sideband manifolds (1)
               and MAS sideband manifolds (2)
               from static CP spectra
               measurement from static solids spectra
Chemical shifts
               concentration dependent
               temperature dependent
Concentration gradients
               effect on spectral quality (1)
               effect on spectral quality (2)
Coupling
               13C – 14N
               13C-14N-31P
               13C – 19F
               13C – 2H (1)
               13C - 2H (2)
               13C – 2H (3)
               13C - 59Co
               signs of coupling constants vis ECOSY
               virtual
               CPMAS of household dust
               effect of contact time
               effect of MAS spinning speed
               importance of Hartman-Hahn match
               in relation to MAS and high power decoupling
               measurement of 13C 90 degree pulses with
               measurement of relaxation times with
               optimizing 1H decoupling in
               ramped contact pulses
               sensitivity improvement from
               to distinguish solid polymorphs
               vs Bloch decay
               with FSLG HETCOR
               as an assignment tool
               effect of spinning speed
               with long dephasing delays (1)
               with long dephasing delays (2)
Decoupler pulse calibration
               in liquids
               in solids
Decoupling
               1H and 31P decoupling
               1H decoupling and 13C signal-to-noise ratio
               1H decoupling and 31P signal-to-noise ratio
               11B decoupling
               13C decoupling
               19F decoupling
               2H decoupling
               27Al decoupling
               31P decoupling
               high power 1H decoupling in solids
               homonuclear decoupling
               modes of heteronuclear decoupling in liquids
DEPT
               and quaternary alkyne carbon sites
               APT vs DEPT 135
               effect of 1H tuning on
               missing signals in
               of “acetone-d6”
               of “perdeuterated “ solvents
               vs DEPTQ
               with 29Si
DEPTQ
               vs DEPT
Diffusion and DOSY
               diffusion in CPMG measurements
               DOSY
Dynamic processes studied by 1D NMR
               exchange studied by saturation transfer
               exchanging rotamers
               the NMR time scale
Echoes
               CPMG
               Fourier transform of
               gradient spin echoes and selective excitation
               simple spin echo
               to remove 11B background in solids
               tutorial video
               tutorial video
Floor vibrations
               effect on NMR spectra
Food and drink
               candy cane
               coffee
               fruit cake
               popcorn
               rum and eggnog
               shortbread cookies
Free induction decay
               effects of truncation
HMBC experiments
               HMQC responses in HMBC spectra
               measuring  19F – 13C coupling in 1H - 13C HMBC
               missing signals in              
               Nyquist fold-backs in
HMQC, HSQC and edited HSQC experiments
               1H – 11B
               19F – 13C
               31P -109Ag
               31P – 13C
               doubled signals / poor decoupling
               HMQC vs HSQC
               HSQC - TOCSY
               HSQC vs edited HSQC
               isotope effects in 19F – 13C HMQC
               removing t1 noise in
               Bloch-Siegert shifts
               broadband 1H decoupled 1H spectra
iPad / iPhone apps
               Bruker Almanac
               educational
Isotope effects
               acetone
               chloroform
               complexed solvents
               ethane
               in 19F – 13C HMQC
               methylene chloride
               “perdeuterated” solvents
               triphenyl phosphate
               water    
               erroneous
Linear prediction
               backward
               backward LP to correct for receiver overload
               forward
               forward LP for 2D data
Lock
               consequence of locking on the wrong solvent
               how high should the lock signal be?
               paramagnetic samples
               spectra acquired with a sweeping field
               spectral distortion from weak lock signal
               Varian
               1H MAS
               and available rf field
               effect on Hartman-Hahn match
               field dependence of chemical shift resolution
               how fast to spin
               how much sample
               increasing signal-to-noise ration in
               setting the magic angle (1)
               setting the magic angle (2)
               solution vs MAS spectra
               rotor crashes
Magnet
               accessing a used magnet
               measurement of field drift
               quench
Magnet cryogen fills and spectral quality
               helium fills
               helium one-way valve oscillation
               nitrogen fills
               nitrogen pressure in the magnet
Magnetic resonance imaging (MRI)
               gradient calibration / 1D MRI
               MRI photocopier
               Nyquist fold-backs in MRI images
               slice selection
               why MRI scanners are loud
NMR of more than one isotope
               23Na and 51V
NOE’s and decoupling
               negative NOE’s and decoupling
               positive NOE’s and decoupling
               and digital filtering
               and mode of data acquisition
               in HMBC data
               in MRI
Paramagnetism
               13C spectra of paramagnetic compounds
               determination of paramagnetic susceptibility
               paramagnetic shifts
               the effect of paramagnetic oxygen
               first order phase errors
               phasing a 1D spectrum (video tutorial)
               phasing a 2D spectrum (video tutorial)
Probes
               broadband vs inverse broadband
               coil geometry
               solids
               why so expensive
               effect of 1H tuning on 13C spectra
               effect of cable length
               effect of sample spinning
               effect on 90 degree pulse
               probe electronics
               problems with salty samples
               effect of probe tuning
               fast determination
               for shaped pulses              
               for spin I = n/2 quadrupolar nuclei in solids
               expressed in dB Bruker vs Varian
               expressed in Hz  
               pulses
Pulsed field gradients
               calibration
               dephasing ability
               gradient spin echoes
               recovery times
               distortions in QCPMG spectra
               for solid state 2H NMR
Quadrature spikes
               how to remove
               finding lost 13C signals
Receiver gain
               and signal-to-noise ratio
               distortion from mis-setting
Relaxation
               effect of paramagnetic oxygen
               faster relaxation time measurements in solids
               T1 anisotropy in solids
               T1 measurement
               T1r
               T2 CPMG filter to enhance sharp lines
               T2 measurements and diffusion
               T2 vs T2*
               by using benzene as a solvent
Sample limitation
               making the best of
Scans
               and signal-to-noise ratio
               broadband 180 degree pulses
               calibration
               excitation profiles (1)
               excitation profiles (2)
               for selective excitation
Shimming
               effect of concentration gradients
               effect of sample depth
               effect of sample mixing
               effect of sample volume
               line shapes resulting from bad shimming
               without a lock signal
               1H spin pairs
Solid state 2H NMR spectroscopy
               echoes and Fourier transforms
               increasing signal-to-noise ratio
               measuring spectral parameters
               QCPMG
               T1 anisotropy
               to determine molecular motions
               90 degree pulse calibration
               baseline correction
               field dependence
               Fourier transform of a single rotational echo
               satellite transitions
Solvent effects
               improving resolution
Solvent suppression
               absolute water suppression
               double presaturation
               presaturation
               watergate
               watergate vs presaturation
Spin simulations
               butane
               ethane
               isopropyl groups
               quadrupolar line shapes in solids (QUEST)
               virtual coupling
t1 noise removal in 2D spectra
               heteronuclear (tutorial video)        
               homonuclear (tutorial video)
Triple resonance experiments
               13C [2H][1H]
               13C [31P][1H]
               31P -13C HMQC with 1H decoupling
Variable temperature measurements
               temperature calibration (1)
               temperature calibration (2)
               temperature dependent chemical shifts
               temperature gradients
               variable temperature to improve resolution
Video tutorials
               1D spectrum phasing
               2D spectrum phasing
               exponential line broadening
               EZ NMR
               removing t1 noise from homonuclear 2D spectra
               and throwing away noise