dewey h. barich, ph.d. director of solid-state nmr ... · applications of solid-state nmr dewey h....
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Applications of Solid-state NMR
Dewey H. Barich, Ph.D.Director of Solid-State NMR Facility
Molecular Structures [email protected]
Outline Overview of Solid State NMR Spectroscopy (SSNMR) Advantages and Disadvantages Contribution Examples:
Environment characterization Physical form characterization Molecular conformation Reactive intermediates in catalysis
Summary
Solid-State NMR Spectroscopy
Analysis of Solids and Semi-solids Organics (Fine Chemicals, Pharmaceutics) Catalysts, Reactive Intermediates Mixtures (e.g., Pharmaceutical Formulations) Biomass (Plant Stalk, Leaves) Soils, Sediments Energy Materials (Coal, Shale, Battery Materials) Polymers, Proteins Membranes, Tissues, Gels
Solid-State NMR Spectroscopy
More information available from solids
Orientation-dependent interactions Dipolar Couplings Chemical Shift Anisotropy
Spectra more complicated Line broadening from multiple phenomena
Overview Research Areas Species Characterization
Chemical Shift Fingerprint
Material Characterization Crystalline polymorphs Crystalline vs. amorphous Influence of environment on spectra Analyzing mixture components
Molecular Structure Conformation Arrangement, degree of disorder
Advantages of Solid-State NMR Non-destructive
Non-invasive
Selective Nucleus specific (13C, 15N, 31P, 19F, etc) Mixture components
Quantitative
Disadvantages of SSNMR Expertise required to utilize properly
Insensitive (Analyses can be long)
Expensive
Automation is challenging
Common NMR Experiments
Solution 13C ObserveExcite the 13C nucleus,Decouple protons during acquisition
1H
13C
Decoupling
Common Solids ExperimentsCross Polarization (CP)
Excite the 1H nuclei,Transfer Magnetization to X nuclei (e.g., 13C)Decouple protons during acquisition
1H
13C
Decoupling
90y
CP advantages: For 13C, get 4x signal enhancementRepetition rate driven by 1H not 13C
CP
TCH Growth Followed by T1 Relaxation
500 ms
100 ms
40 ms
25 ms
5 ms
10 ms
16 ms
NMR Chemical Shifts
Result of electronic environment
Can distinguish functional groups Carboxylic acids, aromatics, aliphatics, etc.
11
22
33
iso
(iso is observed in solution)
In solids, can observe anisotropic chemical shift (x, y, z directions)
Magic Angle Spinning (MAS)
7 mm8 kHz
4 mm15 kHz
2.5 mm30 kHz
Magic Angle Spinning (MAS)
20406080100120140160
11
22
33
iso
Static SSNMR
MAS SSNMR
13C FIREMAT of Kanamycin A
0255075100125150
105.3102.7
92.976.575.974.272.271.570.269.366.862.254.853.649.843.736.5
CHCH
CHCHCHCHCHCHCHCHCH
NCHNCH
CH2
NCH2CH2
NCH
O
O
OH
OH
NH2
OHH
NH2NH2
OH
O
O
NH2
H
OH
OH
OH
13C CP/MAS TOSS SSNMR of3-Methylglutaric Acid (MGA)
O O
OHHOCOOH
CH3
CH2
CH
Crystalline Systems
SSNMR and X-Ray Diffraction (XRD) are complementary techniques:
XRD: long range order
SSNMR: short range order
Crystalline Systems
Unit cell: smallest repeatable unitnecessary to construct a crystallattice via translation
Asymmetric unit: smallest volumethat can be replicated to produce aunit cell (rotations or reflectionsrequired)
Crystalline Systems
Translation only fails to form unit cell:
Asymmetric units are magnetically equivalent
Contents of an asymmetric unit are magnetically inequivalent
SSNMR of Crystalline Systems
12
34
4a4b
8a 8b
5
6
78
4a, 4b, 8a, 8b
2, 3, 6, 7
1, 4, 5, 8
Barich, D. H. et al., J. Phys. Chem. A 2000, 104 (35), 8290–8295
Representation of Biphenylene Crystal
P
D
8b'1'
2'
3'4'
4a'
1 2
344a
56
7
88a
8b
4b
DD
D P
P
Barich, D. H. et al., J. Phys. Chem. A 2000, 104 (35), 8290–8295
13C FIREMAT of Ambuic Acid
050100150200250300
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
ppm from TMS
ppm from TMS
Ambuic Acid
O
O O
COOH
O
H H
H11C5
s-cis
O
O O
COOH
O
H H
H11C5
s-trans
Typically s-trans conformations are more stable; however, comparison of
the computed and experimental shifts for C8, C9, C11, and C12 finds the
s-cis to be the best fit at > 85 % confidence.
Bulk crystalline1H T1 = 243 s
Tablets1H T1 = 79 s
Spray-dried1H T1 = 4.1 s
120 100 80 40ppm
Lyophilized1H T1 = 3.8 s
60
O
OH
OH
H
HO
HH
HO
H
OH
O
OH
OH
H
HH
OHH
HO
H
Distinguishing Physical Forms:Crystalline vs. Amorphous Lactose
Quantitation of Mixtures:Neotame Monohydrate
Offerdahl, T. J. et al., J. Pharm. Sci. 2005, 94 (12), 2591–605
13C Solid-State NMR Spectra of Neotame Forms A and G
Form G
Form A
200 100 0150 50 ppm
135.
6 pp
m13
8.6
ppm
Offerdahl, T. J. et al., J. Pharm. Sci. 2005, 94 (12), 2591–605
13C SSNMR Spectrum of a 50/50 Mixture of Neotame Forms A and G
Offerdahl, T. J. et al., J. Pharm. Sci. 2005, 94 (12), 2591–605
13C SSNMR of a 50/50 Mixture ofAmorphous Neotame and Form G
120125135145 130140
83
100
Offerdahl, T. J. et al., J. Pharm. Sci. 2005, 94 (12), 2591–605
13C SSNMR of Oil Shales
Miknis, F. P.; Smith, J. W. Org. Geochem. 1984, 5, 193–201
15N SSNMR of Crosslinked Polymer
13C SSNMR of Soils
Courtesy, Prof. Sharon Billings
29Si CP/MASCharacterization of Catalysts
Courtesy, A. Ramanathan and B. Subramaniam
Q2 Q3 Q4
Material (Q3+Q2)/Q4 Q3/Q4Zr-200 5.3 4.0Zr-100 5.5 4.2Zr-40 4.1 3.2Zr-20 3.1 2.4Zr-20 Silylated 1.9 1.5
29Si CP/MASCharacterization of Catalysts
Courtesy, A. Ramanathan and B. Subramaniam
Material (Q3+Q2)/Q4 Q3/Q4Ce-100 6.1 4.6Ce-50 6.8 5.2Ce-25 5.5 4.2Ce-10 5.5 4.2SiK5 6.5 5.0
Q2 Q3 Q4
ppm200 150 100 50 0
50 15 1045 40 35 30 25 20ppm
Line Width as a Probe of Bulk Environment:13C SSNMR of Ibuprofen
37 3935
31 3233
Barich, D. H.; et al., J. Pharm. Sci. 2006, 95 (7), 1586–1594
50 45 40 35 30 25 20 15 10ppm
13C Solid-State NMR Spectra of Ibuprofen Preparations
51 52 4945
47 48
47 47 44 4142 43
38 38 35 31 32 33
37 39 35 3131 33
Ibuprofen Recrystallized from Acetonitrile
Cryoground Ibuprofen
Manually Ground Ibuprofen
Bulk Ibuprofen
Barich, D. H.; et al., J. Pharm. Sci. 2006, 95 (7), 1586–1594
SEM and PXRD of Ibuprofen Preparations
Cryoground IbuprofenBulk Ibuprofen
NMR Line Width = 42.2 HzNMR Line Width = 31.5 Hz
Crystallized From Acetonitrile
NMR Line Width = 47.0 Hz
30 m
5 10 20 30 4015 25 35 45 5 10 20 30 4015 25 35 45
Degrees 2 Degrees 2Degrees 2
30 m 30 m
5 10 20 30 4015 25 35 45
≈
Summary
Solid State NMR is a powerful technique for analyzing abroad range of materials and phenomena Species identification
Catalyst composition
Reactive intermediates
Physical form identification and quantitation
Influence on bulk environment
Acknowledgements Researchers
Jacob Davis Dr. Eric Gorman Dr. Joe LubachDr. Tom Offerdahl Dr. Loren Schieber Jon SalsburyDr. Patrick Goguen Dr. Teng Xu Dr. Weiguo SongDr. Mark Zell Prof. Jim Harper Prof. Eric MunsonProf. Sharon Billings Dr. Jianwei Li Dr. Anita OrendtDr. A. Ramanathan Prof. B. Subramaniam
FundingPhRMA Foundation NutrasweetUniversity of Kansas PfizerNSF CHE0840515 National Institutes of Health
Nuclei Accessible at Facility H He
Li Be B C N O F Ne
Na Mg Al Si P S Cl Ar
K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr
Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe
Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn
Fr Ra Ac Rf Db Sg Bh Hs Mt
Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb Lu
Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No Lr
Accessibility at Facility: Yes Maybe
Types of Materials Studied at theKU SSNMR Facility
Soil Biomass Battery Materials Catalysts Organometallic
Pharmaceutics Biological Inorganic Polymers
Quantitation of Mixtures
Ideally, peak area is proportional to the number of nuclei
Challenge: Cross polarization spectra are rarely quantitative Peak area depends on cross polarization rates and
relaxation rates (TCH and T1)
At short-to-optimum contact times (CT), cross polarization rates (TCH) increase the signal intensity. At longer CT, signal decays by proton T1 relaxation