225th ACS National MeetingMarch 24-27, 2003

Multidimensional NMR of Synthetic Polymers

Peter L. RinaldiDepartment of ChemistryThe University of AkronAkron, Ohio 44325-3601

http://www.chemistry.uakron.edu/magnet/whatsnew.html

Outline

• Introduction/Problems & Practice– Sensitivity

– Experiment times

– Dataset sizes

• Homonuclear 3D NMR

• Heteronuclear Triple Resonance 3D NMR– Alphabet soup experiments in structural biology

– Polymer Applications

• Heteronuclear Double Resonance 3D NMR– Applications with unlabeled materials

– Applications with isotopic labeling

( )tn-1tn

Preparation Acquisition

Preparation Evolution Mixing Acquisition

1D

nD

n-1

t1

Preparation Evolution Mixing Acquisition

2D

1D/2D/3D-NMR Sequences

Sample Considerations in 3D-NMR of Synthetic Polymers

• Occurrence of structural unit• Possibility of labeling• Abundance of heteronucleus• Molecular weight• Structural diversity• Solubility

13C Spectrum ofPoly(isobutylene-b-butadiene)

x100

Tokles et al., Macromolecules, 28, 3944 (1995)

Relative Signal Strength for Polymer Structure Components

1H-12C

1H-13C M

inor

Junc

tion

Bac

kbon

e

012345

Log Intensity

NMR Signal

Component

MinorJunctionBackbone

- increase dynamic range by eliminating unwanted signals prior to acquisition

- time saving by elimination (or reduction) of phase cycling

- reduction of artifacts such as t1-noise

- improve spectral quality

Magnetic Field Gradients in NMR

Tokles et al., Macromolecules, 28, 3944 (1995).Rinaldi et al., Polymer International, 36, 177, (1995).

PE HMBC NMR Spectra at 120oC

ppm22283440

ppm22283440

F2(ppm)0.951.05

F1 (ppm)

101622283440

1.451.55

F2(ppm)0.951.05

101622283440

1.451.55

b

ca

d

1.351.251.15

1.351.251.15

With PFG

Without PFG

W. Liu et al., J. Magn. Resonance, 140, 482 (1999)

NMR Experiment Sizes & Times

4 hours164k x 32 x 32

80 days 16,0004k x 1k x 1k3D

4 hours164k x 1k

300 hours2,00064k x 64k2D

20 sec . 0.2564k1D

Experiment Time

File Size(Mbytes)

Data Size

NMR Experiment Spectral Windows (750 MHz)

1,00010-50%13C

100-1,000Only few resonance

X

16,00050-80%1H3D

20,00050%13C

2,00050-80%1H2D

10,00040,000

FullFull

1H13C

1D

Window (Hz)Window Nucleus

3D Data Processing

• F3– Full window/DSP to filter undesired peaks– Linear prediction & zero filling

• F1 & F2– Extensive folding– Linear prediction 4x collected data– Zero filling 16x collected data

Homonuclear 3D of Polymers

• Characterization of polymer chain conformations by NOESY-2DJ

– P. Mirau et al., Macromolecules, 23, 4482 (1990)

– Ibid.,Polymer Int., 26, 29 (1991)– Ibid, Polymer, 33, (1992)

Homonuclear 3D NMR

• Advantages– Usually 1H/ 1H/ 1H– 100% natural

abundance– Single channel

• instrument• Probe• calibrations

– Simple setup– Formed by

combining 2D experiments

• Disadvantages– Complex spectra– Many correlations– Less facile selective

excitation– Limited dispersion

Homonuclear 3D NMR

Griesinger, Sorensen & Ernst, J. Magn. Resonance, 84, 14 (1989)

Cross-Diagonal Back-Transfer Cross-Diagonal

f1f2

f3

νa

νaνa

νb

νb

νb

νc

νc

νc

X

Diagonal

Back Transfer

Cross Diagonal

Cross Peaks

X

XX

XX

X

ωa

ωb

ωc

B N2

N1

Homonuclear 3D NMR

3D NMR spectra usually viewed as planes through the 3D data matrix.

Cross Diagonal(a-b-b) or (a-a-b)

Diagonal(a-a-a)

Cross Peak(a-b-c)Back Transfer Peak

(a-b-a)

Griesinger, Sorensen & Ernst, J. Magn. Resonance, 84, 14 (1989(

No of Peaks in Homonuclear nDNMR Spectra of an AB System

643D-COSY-COSY

162D-COSY

41D

No PeaksDimensionality

Heteronuclear 3D NMR

• Advantages– Huge dispersion– Simple spectra– Correlation give

unequivocal data– Formed by

combining coherence transfer steps

• Disadvantages– Low sensitivity or– Isotopic labeling– Multiple channel

• instrument• Probe• calibrations

– Complex setup– Large spectral

windows

HXY 3D-NMR Sequence t3

t2t1Y X

H

C

H

C

H

t1

t2τ ττ

g1g2

∆ ∆ ∆∆

X

H1

GZ

τDecouple

ϕ1

ϕ2

ϕ3

ϕ4

ϕ5t3

A C D E F G HB

Y

Saito et al. J. Magn. Resonance, 130, 135 (1998).Saito et al. J. Magn. Resonance, 132, 41 (1998).

Biological 3D-NMR Pulse Sequnces

H

N C

H

C N

H

C

H

C

O O

a H

N C

H

C N

H

C

H

C

O O

b

H

N C

H

C N

H

C

H

C

O O

c H

N C

H

C N

H

C

H

C

O O

d

H

N C

H

C N

H

C

H

C

O O

e

R1 R2

R1 R2

R1 R2

R1 R2

R1 R2

HNCO HNCA

HCACO

HCA(CO)N

15N-TOCSY-HMQC

Clore & Gronenborn, Progress NMR Spectoscopy, 23, 43 (1991).Griesinger et al., J. Magn. Resonance, 84, 14 (1989).

The Power of Conditioning

1H, 19F and 13C 1D-NMR Spectra of PCFE

Li et al., Macromolecules, 30, 520 (1997)

)(Cl FF Cl ClF

mmmm rmmm rrmm rrrm rrrr

mrmm rmrm rrmr

rmmr

mrrm

19F

1H

13C

Relative Signal Strength for Polymer Structure Components in 1H/13C/X Experiments

1H-1

2C

1H-1

3C

1H-1

3C-1

9F

1H-1

3C-X

01234567

Log IntensityJunctionBackbone

DOD = log [ IH / I HCX fragment = 2-3

Cl F FF Cl Cl

( )mr

1H/19F/13C 3D-NMR Spectrum

Li & Rinaldi, Macromolecules, 29, 4808 (1996)Li et al., Macromolecules, 30, 520 (1997)

1H-13C HMQC19F-13C HMQC

3D-HFC 1H-13C HMBC

Strategy for Using 2D-& 3D-NMR to Obtain Resonance Assignments

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3F F F F F

Cl Cl Cl Cl Cl

Relative Signal Strength for Structure Components in 1H/13C/29Si Experiments

DOD = log [ IH / I HCSi fragment = 4-5

SiCH2CH2 CH2CH2Si

Me

Si

CH2

CH2

Me

Me

Si

CH2

CH2

MeSi1H

-12C

1H-1

3C

1H-1

3C-1

9F

1H-1

3C-

29Si

01234567

Log IntensityCoreSurface

1H/13C/29Si 3D-NMR Pulse Sequence

Chai et al. Macromolecules, 30, 1240 (1997)

2J = 5 HzCSi

J = 59 HzCSi

CH2CH

H

CH2 CH

CH2

CH

J = 140 HzCH

+5 +1A B C D E F G H

∆∆H1 ∆∆

φ1 φ5t3

φ φτ ττ τC13

2 4t2 MPF

φ3Si29

t1 MPF

Si

H

Si CH3CH3

H

2

C H

HC

Si CH3

CH3Si

HC

HC

2

H

CH3

C

H

C

H

Si

~~

0 1

Polycarbosilane Second Generation Dendrimer Jcsi

Si

H

CHCH2 CH2CH

H

Si

A B

J = 140HzCH1

J = 59HzCSi1

J = 140HzCH1

J = 7HzCSi2

1H/29Si/13C 3D-NMR Spectrum With 1JcsiGeneration 2 Dendrimer

δ Si = 7.99ppm29

F1 (ppm)-6-226

F3(ppm)0.30.50.70.91.1

d

δ Si = 2.25ppm*29

F1 (ppm)-6-226

F3(ppm)0.30.50.70.91.1

e

F1 (ppm)-6-226

F3(ppm)0.30.50.70.91.1 δ Si = 9.95ppm29

cδ H1

δ C13

F1 (ppm)-12-6-048

F2(ppm)0.20.40.60.81.0

aδ H1

δ Si29

HMQC JHSi=5Hz

b

F2 (ppm)0246810

F3(ppm)0.20.40.60.81.0

δ H1

3D Projection

δ C13

[ 2 ]CH CH2

Me

Si ( 2CH CH iS H )2Si

Me

Me

4

H

JCH=140Hz

JCsi=59Hz

Chai et al. J. Am. Chem. Soc,121, 273 (1999).

1H/29Si/13C 3D-NMR Spectrum With 2JcsiGeneration 2 Dendrimer

[ 2 ]CH CH2

Me

Si ( 2CH CH iS H)2Si

Me

Me

4

HJCH=140Hz

JCsi=7Hz

d

δ S i = 7 . 9 9 p p m2 9

δ S i = 2 . 2 5 p p m2 9

e

δ S i = 9 . 9 5 p p m2 9

c

δ C1 3

δ H1

F 1 ( p p m )F 1 ( p p m )- 6- 226

F 3( p p m )0 . 20 . 40 . 60 . 81 . 0

F 1 ( p p m )- 6- 226

F 3( p p m )0 . 20 . 40 . 60 . 81 . 0

F 1 ( p p m )- 6- 226

F 3( p p m )0 . 20 . 40 . 60 . 81 . 0

Chai et al. J. Am. Chem. Soc,121, 273 (1999).

Poly(1-phenyl-1-silabutane)a

b

c

Saito, Chai, Pi, Tessier & Rinaldi, Macromolecules, 30, 1240 (1996)

1H-1

2C

1H-1

3C

1H-1

3C-1

9F

1H-1

3C-

29Si

01234567

Log IntensityChain EndBackbone

3D-NMR of PPSB

Saito et al., Macromolecules, 30, 1240 (1996)

Silane Curing Agent

(H3CO)3Si Si(OCH3)3(H3CO)3Si

Si(OCH3)3 Si(OCH3)3Si(OCH3)3

Si(OCH3)3

Si(OCH3)3

(H3CO)3Si

Si(OCH3)3

(H3CO)3Si

Si(OCH3)3

1 3 5

2 4 6

IV

IV'

IIII'

II'

V

V'

VI

VI'

III III'

CH2

CH3OH/Catalyst

HSiCl3+

Liu et al. Organometallics, 21, 3250 (2002).

H/C/Si 3D-NMR of SilaneCuring Agent

7

2

8

64

315

(H3CO)3Si

Si(OCH3)3

IV

IV'

26

43

15

(H3CO)3Si Si(OCH3)37 8II

II'

F3(ppm)

0.8

1.0

1.2

1.4

1.6

1.8

2.0

F1 (ppm)

010203040

F3(ppm)

0.8

1.0

1.2

1.4

1.6

1.8

2.0

F1 (ppm)

010203040

F1 (ppm)

10203040

JCSi=96Hz JCSi=13Hz JCSi=5Hz b c

fd e

a

4 4

4 4

2,6 2,6

3,5

3,5

2,6 2,6

3,5

3,5

δ29Si = - 45.57

2

1

δ29Si = - 44.97

Liu et al. Organometallics, 21, 3250 (2002).

Sn-containing Star Branched Polybutadiene

= PBD

Li + Me SnCl4-n n

+

++

Me

Me3Sn Sn

Sn Sn

Me

Me

(CH3-CH2-CH2-CH2)4-Sn50 20 240

Relative Signal Strength for Polymer Structure Components in 1H/13C/119Sn Experiments

1H-1

2C

1H-1

3C

1H-1

3C-1

9F

1H-1

3C-

119S

n

01234567

Log IntensityJunctionBackbone

DOD = log [ IH / I HCX fragment = 6-7

PBDSnBu3

PBDSnBu3

PBDSnBu3 PBDSnBu3

F1 (ppm)

68101214161820

F3(ppm)1.01.21.41.61.82.02.22.4

F1 (ppm)

-21-19-17-15

F2(ppm)1.01.21.41.61.82.02.22.4

F1 (ppm)

5791113151719

F2(ppm)1.01.21.41.61.82.02.22.4

F1 (ppm)

68101214161820

F3(ppm)1.01.21.41.61.82.02.22.4

F1 (ppm)

68101214161820

F3(ppm)1.01.21.41.61.82.02.22.4

F1 (ppm)

68101214161820

F3(ppm)1.01.21.41.61.82.02.22.4

F1 (ppm)

68101214161820

F3(ppm)1.01.21.41.61.82.02.22.4

2D- & 3D- Spectra of Bu3SnPBD

H/C-HMQCH/C-3D-Proj H/Sn-HMQC

δ Sn = -20.4δ Sn = -14.2 δ Sn = -16.3 δ Sn = -17.0

Sn

3

Sn

3

Sn

3

H/C-3D-slicesfromH/C/Sn 3D with 1JCSn

Liu et al. Macromolecules, 33, 2364 (2000)

TPO-Initiated Styrene Polymerization

nArCO

Ph Ph Ph

Ph+ ArC

O

4

PhPh Ph

+ PhPh Ph

CArO

nn ArCO

5

PhPh Phn2 n

PhPh Ph Ph PhPhn

or6

nPhPh Ph

nPhPh Ph

+

7 8Ar = 2,4,6 Me3Ph

Ph2PO

+ Ph

Ph2PO

Ph Ph Ph

n

Ph+ Ph2P

OnPh2P

O

Ph Ph

Ph

1

2

n Ph2PO

nPPh2

O

PhPh Ph

+ PhPh Ph

3

31P-containing Polymer Chain Ends in Polystyrene (PS)

Ph2 P

O Ph

Ph

Phn

Ph2 P

O

PhPh

Phn

Ph2 P

O Ph Ph Phn

1

2 3

ppm323436384042444648505254

ppm242628303234363840

ppm0.51.01.52.02.53.03.5

1H

31P

13C

Meng et al., Macromolecules, 34, 801 (2001)

t3

t2t1P C

H

C

H

C

H

C

H

HCP 3D-NMR Pulse Sequence

t1

t2τ ττ

g1g2

∆ ∆ ∆∆

C13

H1

GZ

P31

τDecoupling

a b

c d e f

g

ϕ1

ϕ2

ϕ3

ϕ4

ϕ5t3

Saito et al., J. Magn. Resonance, Ser. A, 120, 125 (1996).

HCP 3D-NMR Spectra of Polystyrene

δH

36.538.039.5

36.538.039.5

(ppm)δC

36.538.039.5

36.538.039.5

(ppm)

2.32.42.52.62.7

δP (ppm)31.46

31.30

31.15

30.76

P31

ppm30.730.931.131.331.531.7

a

b

c

d

Ph2 P

O Ph

Ph

Phn

Ph2 P

O

PhPh

Phn

Ph2 P

O Ph Ph Phn

1

2 3

Saito et al., J. Magn. Resonance, Ser. A, 120, 125 (1996).

H(CA)P-CC-TOCSY3D-NMR Pulse Sequence

t1 t2/2

τ τ τ

∆ ∆ ∆∆

C13

H1

GZ

P31

τDecoupling

a

f

i

ϕ1

ϕ2

ϕ3

ϕ8

c

b

d

Decoupling

SL

2δ t2/2 + δ

t2/2 + CT CT - t2/2

g1 g2 g3

g4

g h

ϕ5 ϕ6 ϕ7ϕ4

t3

e

P C

H

C

H

C

H

C

H

t1t2 t2t2t2 t2

t3t3t3t3

Saito et al., J. Magn. Resonance, 130, 135 (1998).

HCCH Pulse Sequence

∆ ∆ ∆∆

C13

H1

GZ

MPF7

ϕ1

ϕ2 ϕ3

δ + t1/2 δ

CT CT

g1g3

ϕ5

ϕ4

t3

g2

CT + t1/2 CT - t1/2 t2

P C

H

C

H

C

H

C

H

t1 t2

t3

Prestegard et al. J. Magn. Reson., Ser. B, 101, 126 (1993) Prestegard et al. J. Magn. Reson., Ser. B, 102, 137 (1993)

Saito et al. J. Magn. Reson., Ser. A, 118, 136 (1996)

H1

H2

H3

H4

HCP HCCH HCPCCHHCCH HCCH HCCHHCPCCH HCCHHCPCCH

Saito et al., J. Magn. Resonance A, 120, 125 (1996),J. Magn. Resonance, 132, 41 (1998).

Meng et al., Macromolecules, 34, 801 (2001)

13C Labeled PS Structure From Combined HCP HCCH & H(CA)P-CC-TOCSY

3D-NMR Pulse Sequences

F2 (ppm)27.3027.75

F3(ppm)

1.41.6

1.82.0

2.2

2.42.6

2.83.0

3.23.4

F2 (ppm)-4.4-2.4

F2 (ppm)27.3027.75

F1 (ppm)37.738.7

F2 (ppm)1.42.4

F2 (ppm)27.3027.75

F1 (ppm)37.738.7

F2 (ppm)5.46.4

F2 (ppm)27.3027.75

F1 (ppm)37.738.7

a b c d e f g h i jC1=38.3 C1=38.3 C2=38.2 C2=38.2 C2=38.2 C3=43.4 C3=43.4 C3=43.4 C4=41.7 C4=41.7

Relative Signal Strength for Polymer Structure Components in 1H/13C & 1H/13C/15N Experiments

1H-1

2C

1H-1

3C

1H-1

3C-X

01234567

Log IntensityCoreSurface

DODHCN = log [ IH / I HCX fragment = 6-7Dab-16 Dendrim er

N N

N

N

H N

H N

NH2

NH2

NH2

NH2

NH2

NH2

N

N

N

N

2

2

N H

N

N

N

N

H2N

H2N

H2N

H2N

H2N

H2N N H

N

N

2

2

DODHC = log [ IH / I HC fragment = 4-5

Dab-16 Dendrimer

N

N

H N NH2

NH2

NH2

N

N

2

N

DAB-16 1D-NMR Spectra

ppm1.41.82.22.6

ppm303540455055

3

65

49

8

7

10

11

1H

13C

1

2

Chai et al. Macromolecules, 33, 5395 (2000).

3D-HMQC-TOCSY Slices DAB-16

p p m2 53 03 54 04 55 05 5

2.12

F3(ppm)

1.4

1.6

1.8

2.0

2.2

2.4

2.6

δH

54.15

2.12

52.32

2.12

52.19

2.12

52.13

2.12

52.06

F2 (ppm)δH

2.12

51.74

2.40

40.40

1.32

30.61

1.00

24.89

1.20

24.38

1.46

24.31δC (ppm)

Dab-16 Dendrimer

N

N

H N NH2

NH2

NH2

N

N

2

N

Chai et al. Macromolecules, 33, 5395 (2000).

2.2

F1(ppm)

1.01.21.41.61.82.02.22.42.6

0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 2.2

F3 (ppm)

53.31 51.83 51.75 51.68 51.60 51.29 39.95 30.08 24.49 24.10 23.94

ppm25303540455055

DAB-16 3D NOESY-HSQC in CHCl3

Chai et al. J. Am. Chem. Soc.,123,4670 (2001)

DAB-16 Solvent-Dendrimer Interactions

N N

NN

N N

N

NN

N

N N

NN

NH2

NH2

NH2

NH2

NH2

NH2

NH2

NH2

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

N N

N

N

N N

N

NN

N

N

N

NN

N

N

N

H

N

N

N

NH

N

N

N

H

N

N

N

N

HH

HN

H

H

H

H

H

H

H

H

HH

H

H

H

H

H

H

H

H

NH

H

HH

HH

HH

Extended Chain Conformation Folded Chain Conformation

S S

S

S

SS

S SS

S

S

S S

S

Chai et al. J. Am. Chem. Soc., 123,4670 (2001)

C-centeredB-centered

CCCECCECE

BCC/CCBBCB(2)

ECB/BCE

BBB(3)EBB(2)

EBECBB(2)/BBC(2)

CBCEBC/CBE

EEEEEB

BEB(2)CEECEC

BEC/CEB

E-centered

E = ethylene C = carbon monoxide B = n-butylacrylate

Possible Triads of Poly(EBC)

1D 13C NMR of Labeled Poly(BCE)

200 180 160 140 120 100 80 60 40 20 ppm

Unlabeled

O

13C

OBuO

13CH

OBuO13C

1H

13CAliph

13CC=O

GZ

∆ ∆ ∆ ∆t3

t2

g1g4 g5 g6g2

ττ

Decouple

τ

t1

τ

13C

H

O OBu

C

(2)(4)

(3)

(1)(6)

(5)

(7)

t1

t3

t2

1JCH

1JCC

H2C

(1) (2) (3) (4) (5) (6) (7)

3D Pulse Sequence

Monwar et al., Polymer Preprints, 44, 257 (2003)

Decouple

g3

Truncated 3D of Poly(EB*C)

3940414243444546

F3(ppm)

2.5

2.9

2.5

2.9

174175176 40424446F1 ppm F2 ppm

HMBC HSQC

HCACO HCACO

F2(ppm)

Monwar et al., Polymer Preprints, 44, 257 (2003)

3D Slices HCACO Poly(EB*C)

ppm174175176

F3(ppm)

2.5

2.9

46.5 45.5 40.5 40.5F2 ppm

HSQC

45 40

F1=175.3 F1=174.9 F1=174.7 F1=174.2

Monwar et al., Polymer Preprints, 44, 257 (2003)

ppm173.5174.0174.5175.0175.5176.0176.5

Acknowledgments• Senior• C. Tessier• W. Youngs• H. J. Harwood• W. Mattice• J. Visintainer• R. Hirst• A. Halasa• L. Galya• J. Hansen• L. Wilczek• E. McCord• M. Buback

• Funding• NSF (DMR-9310642, DMR-9617477, DMR-0073346, CHE-

9412387)• Kresge Foundation• Donors to Kresge Challenge Program at University of Akron• Ohio Board of Regents, Research Challenge• University of Akron• Dupont, Dow Corning, Goodyear, Nalorac, Varian

StudentsT. SaitoL. LiO. AssematL. WeixiaM. ChaiH. MengM. MonwarS. OhS. SahooM. ToklesF. WyzgoskiH. T. WangR. MedskerG. OuangC. HelferZ. PiY. NiuD. HensleyV. Litman

StaffV. DudipalaS. StakleffT. WaglerJ. Massey G. S. HatvanyD. G. Ray

http://www.chemistry.uakron.edu/magnet/whatsnew.html