NMR Applications for Polymer Characterisation Dr. Bernd W.K. Diehl Spectral Service
Cologne, Germany
EDQM Strasbourg, June 2007, (C) Spectral Service
1
Principles
NMR Chemival Shift instead of Retention Time.
Test item should be soluble in deuterated solvent.
Target molecule must be soluble.
NMR signals show molar response.
Qualitative and quantitative analysis is possible.
One characteristical signal without interference is needed.
Temperature dependent analysis (RT up to 80 C).
Drugs or/and formulation aids can be analysed even in complex mixtures.
EDQM Strasbourg, June 2007, (C) Spectral Service
2
Targets
Polydimethylsiloxane
Polysaccharides
Polyether
Polyester
Poly- and Oligopeptides
Polyvinylcompounds
EDQM Strasbourg, June 2007, (C) Spectral Service
3
Polydimethylsiloxane
CH3 H3C O H3C Si O
TMS terminated
OH terminated
Cyclic/modified
H3C
O H3C CH3 O
Si
Si CH3 O
Si CH3 Si O CH3 CH3
CH3 CH3 CH3 O O Si Si Si CH3
CH3
CH3
x
O
Si CH3 H3C Si O H3C CH3 Si
OH
CH3
CH3 H3C
0.6
0.5
0.4
0.3
EDQM Strasbourg, June 2007, (C) Spectral Service
0.2
0.1
0.0
Si
CH3 CH3
-0.1 4
Polydimethylsiloxane FTIR CH3 CH3 CH3 O O O Si Si Si CH3
CH3
CH3 1H
NMR
S i 2 9S i 2 9
EDQM Strasbourg, June 2007, (C) Spectral Service
x
5
Polydimethylsiloxane Comparison of FT/IR and NMR results 2
y = 0,0113x R 2 = 0,9981
1,8
IR-Absorption
1,6 1,4
1,2 1 0,8 0,6 0,4 0,2 0 0
20
40
60
80
NMR Integral
EDQM Strasbourg, June 2007, (C) Spectral Service
140
160
180 6
Polydimethylsiloxane
* = 29Si Satellites + = 13C Satellites
OH terminated *
1H
NMR
*
n-3 n-2
-O-Si(CH3)2-OH
n-1 Tetramethylsilan +
+
0.25
0.20
0.15
0.10
(ppm) -0.00
EDQM Strasbourg, June 2007, (C) Spectral Service
-0.05
-0.10
-0.15 7
1 Polydimethylsiloxane
* * TMS terminated
Tetramethylsilan 2
* = 29Si Satellites
1 = TMS terminal 1H
2 = Si(CH3)2-O-TMS
NMR
-Si(CH3)2-OH
0.14
0.10
0.06
(ppm)
EDQM Strasbourg, June 2007, (C) Spectral Service
-0.02
-0.06
-0.1 8
Polydimethylsiloxane 1
TMS terminated
Tetramethylsilan
2
1 = TMS terminal
0.14
0.10
40.0
117.2
59.5
Integral
2 = Si(CH3)2-O-TMS
0.06
(ppm)
EDQM Strasbourg, June 2007, (C) Spectral Service
-0.02
-0.06
-0.1 9
Polysaccharides
Modified Starches
Aloverose
Heparine
Chondroitin Sulphate
EDQM Strasbourg, June 2007, (C) Spectral Service
10
Polysaccharides
Modified Starches (HES) at 80 C
1H
NMR
9.0
8.0
7.0
6.0
5.0
EDQM Strasbourg, June 2007, (C) Spectral Service
(ppm)
3.0
2.0
1.0
0.0 11
Polysaccharides
Modified Starches (HES) at 80 C
5.4
9.29
85.6 5.8
5.11
NMR
Integral
1H
5.0
4.6 (ppm) 4.2
EDQM Strasbourg, June 2007, (C) Spectral Service
3.8
3.4 12
Polysaccharides
Acetate
H2O
Aloverose (100.000 – 1.000.000 D)
OH
R1
OAc
H
H OAc O
O HO
1H
AcO O
H
O OH H
H OAc O
O HO
H OH H
HO O
O
H
R2
O
H H
H H
OAc
NMR
9
H
H H
H H H
H
H OH
Polymannose
8
7
6
5 (ppm)4
EDQM Strasbourg, June 2007, (C) Spectral Service
Ethanol
3
2
1
0 13
Polysaccharides
Malic Acid Succinic Acid
Aloverose
Aloverose
1H
Pyruvat
Acetic Acid
NMR
Fumaric Acid Glucose
Lactic Acid
Formic Acid
EDQM Strasbourg, June 2007, (C) Spectral Service
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Polysaccharides
heparin of bovine mucosa
Heparine
1H
NMR
heparin of porcine mucosa
Fingerprint identification of animal souces - Cow - Pig
EDQM Strasbourg, June 2007, (C) Spectral Service
15
Polysaccharides Bovine
4.76
4.68
4.60
4.52
4.44
4.36
Chondroitin Sulphate 1H
Porcine Fingerprint identification of animal souces - Cow - Pig - Chicken - Shark
4.76
4.68
EDQM Strasbourg, June 2007, (C) Spectral Service
4.60
(ppm)
4.44
NMR
4.36 16
Polyether
PEG based
PPG based
Copolymers
EDQM Strasbourg, June 2007, (C) Spectral Service
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Polyether
PEG
d
a
O
HO b
b
74
d
OH
O d n
a
a
72
70
9.85
65.60
76
O
b
c
9.64
78
c
O
d
NMR
Integral
13C
c
d
68
66 (ppm) 62
EDQM Strasbourg, June 2007, (C) Spectral Service
60
58
56
54
52 18
Polyether
CH3
PPG
O
HO
O
CH3
75
O
CH3 OH
O
CH3
NMR
60
55
66.0
13C
10.0
121.4
Integral
CH3
70
65
50
45 (ppm) 35
EDQM Strasbourg, June 2007, (C) Spectral Service
30
25
20
15 19
Polyether
a
PEG based
b
c
d
OH
H19C9
O
O e n-1
1H
e
NMR c d
a b
9
8
7
6
5 (ppm)4
EDQM Strasbourg, June 2007, (C) Spectral Service
193.7
350.0
19.95
20.00
20.15
Integral
OH
3
2
1
0 20
Polyether
PEG
PPG
Copolymers
Terminal CH2-OH of PPG
Terminal CH2-OH of PEG 13C
NMR
85
83
81
79
77
75
73
71 (ppm) 67
EDQM Strasbourg, June 2007, (C) Spectral Service
65
63
61
59 21
57
Polyester
Polylactid/glycolid copolymers
Tacticity
EDQM Strasbourg, June 2007, (C) Spectral Service
22
Polyester
Tacticity
EDQM Strasbourg, June 2007, (C) Spectral Service
23
Poly- and Oligopeptides 8 p-Cl-PHE 6 7 Cl 5 4 O 2
1 NH 2 3
O
3
6'
O 5' 1 NH 2 1
2 1 NH 5 O 4 6
Acetat 11 12 Anth-ALA 10
3
4
13 Py-ALA 5 7 8 9
7 O NH2 8' p-Urea-PHE NH 8 6 iPr-LYS NH 6 5 5 7 SER 4 4 OH 6' 4 PRO 5 3 3 3 O O 5' 3 2 2 2 1 NH 2 N 2 1 NH 2 1 3 1 NH 1 NH NH ALA-NH LEU 8 1 5' 3 2 3 O O O 1 NH2 5 6' 7 O NH 4 4 7 5' O 5 6 N NH 6 1 p-Amino-PHE NH O O 2 5 3 NH 4 Hydroorotic O
EDQM Strasbourg, June 2007, (C) Spectral Service
24
Poly- and Oligopeptides
11.6 1H
10.0
NMR
8.8
7.2
5.6
(ppm)
EDQM Strasbourg, June 2007, (C) Spectral Service
3.6
2.0
0.4 25
Poly- and Oligopeptides
p-Amino-PHE Hydroorotic ALA-NH2
13C
free Acetate
NMR
175
174
173
p-Urea-PHE p-Cl-PHE Anth-ALA Py-ALA PRO iPr-LYS LEU SER
Acetate
172 (ppm) 171
169
EDQM Strasbourg, June 2007, (C) Spectral Service
170 26
Polyvinylcompounds Luviskol K120 O
N
O
O CH3
VP
n
m
VA
Luviskol VA 64
4.4
4.0
3.6
3.2
2.8
(ppm) 2.0
EDQM Strasbourg, June 2007, (C) Spectral Service
1.6
1.2
0.8
0.4 27
0.0
Polyvinylcompounds
4.4
4.0
3.6
3.2
2.8 (ppm)
EDQM Strasbourg, June 2007, (C) Spectral Service
2.0
1.6
1.2
0.8
0.4 28
0.0
Polyvinylcompounds Solvent Residue < 100 ppm
PK-Levo 1H
NMR 1.5
Benserazid = 10.5 %
1.3
1.1
int. Std.
200.00
9.6
8.8
173.91
Integral
PVP = 9 %
8.0
7.2
6.4
5.6
4.8 (ppm)
EDQM Strasbourg, June 2007, (C) Spectral Service
3.2
2.4
1.6
0.8 29
0.0
Conclusion
EDQM Strasbourg, June 2007, (C) Spectral Service
30
Thank you for your patience
EDQM Strasbourg, June 2007, (C) Spectral Service
31
