Comparison of multi-standard and TMS-standard calculated NMR shifts for coniferyl alcohol Heath D. Watts, Mohamed N.A. Mohamed, James D. Kubicki 7 April.

Comparison of multi-standard and TMS-standard calculated

NMR shifts for coniferyl alcohol

Heath D. Watts, Mohamed N.A. Mohamed, James D. Kubicki

7 April 2011

www.lbl.gov/Publications/YOS/Feb/

Goal – Build a reasonably accurate modelof lignin testable against spectroscopic data

1 2

3

45

6

a

b

g

Me

Carbon d13C (ppm)1 130.22 109.93 148.44 147.15 115.76 120.6a 130.4b 128.0g 63.4

Me 56.1http://ars.usda.gov/Services/docs.htm?docid=10491

Experimental 13-C NMR data for coniferyl alcohol in acetoneMonomer provides less convoluted spectrum, but has ambiguous shifts

Can computational chemistry methods reproduce the observed NMR chemical

shifts for coniferyl alcohol?

NMR Theory: Chemical shielding B3LYP/6-311+G(2d,p);

NMR standard: TMS

Energy minimization method: Structure B3LYP/6-311++G(d,p)

d13C = sTMS - ssampleSi

Inorganic character

Cheeseman et al. Journal of Chemical Physics. 1996, 104(14), 5497.

40 60 80 100 120 140 16040

60

80

100

120

140

160

13Cexp (ppm)

13C

calc

(ppm

)

B3LYP/6-311+G(2d,p)Slope: 1.01 y-intercept (ppm): 7.41r2=0.975Mean-unsigned error (MUE) (ppm): 8.1Root mean-squared error (RMSE) (ppm): 9.4 ppmMax Error (ME) (ppm): 21.4

MG5

http://ars.usda.gov/Services/docs.htm?docid=10491

(Watts, 2011)

1:1 line

Is there a conformational isomer effect?

MG1 MG2 MG3

MG4 MG5 MG6

12

34

5

6

ab

g

Me

NMR Theory: B3LYP/6-311+G(2d,p);

NMR standard: TMS

NMR Theory: HF/6-311+G(2d,p); NMR standard: TMS

NMR Theory: mPW1PW91/6-31G(d); NMR standard: benzene sp2 C;

CH3OH sp3 C

d13C = sM-S – ssample + exp,ref

d13C = sTMS - ssample

Multi-standard

TMS, single standard

Organic standards

Cheeseman et al. Journal of Chemical Physics. 1996, 104(14), 5497.

Sarotti & Pellegrinet; Journal of Organic Chemistry. 2009, 74, 7254.

40 60 80 100 120 140 16040

60

80

100

120

140

160

13Cexp (ppm)

13C

calc

(ppm

)

Watts et al. Journal of Physical Chem-istry B. 2011, 115(9), 1958.

MG3

mPW1PW91/6-31G(d)Slope: 1.00y-intercept (ppm): -0.42r2=0.994MUE (ppm): 2.2RMSE (ppm): 2.4 ppmMax Error (ppm): 3.7

NMR Theory: B3LYP/6-311+G(2d,p);

NMR standard: TMS

NMR Theory: HF/6-311+G(2d,p); NMR standard: TMS

NMR Theory: mPW1PW91/6-31G(d); NMR standard: benzene sp2 C;

CH3OH sp3 C

Reviewer comments:…the authors conclude that the MG3 should be the “experimentally observable conformer”. In the case of flexible compounds, the generally accepted protocol is to calculate the Boltzmann-averaged shielding constants, which gives a more “realistic” result, because it takes into account the effect of all significantly populated conformations. In addition, the authors did not mention the relative energies of the different conformers.

The Gibbs free energy of solution (G°soln) was calculated by:

G°soln = G°IEFPCM + G°TCDG

G°IEFPCM total free energy in solution with all non-electrostatic terms from the polarized continuum calculation (solvents were acetone, DMSO, & CHCl3)G°TCDG thermal correction to Gibbs free energy from the gas-phase frequency calculation

The relative G°soln for each model was determined by setting the model with the lowest G°soln to 0 kJ/mol

(Foresman, 1996; www.gaussian.com/g_whitepap/thermo.htm)

Coniferyl alcohol model

Relative DG°soln

(kJ/mol; acetone)MG1 10.2MG2 0.7MG3 4.4MG4 10.9MG5 0.0MG6 4.0

N

N Cδ

/RT)ºΔG exp(

/RT)ºΔG exp( C δC δ

N

1i

iXi

13

N

1i

N

1i

i

iXi

13X

13

Boltzmann-weighted NMR chemical shifts to account for contribution of each conformer based the energy distribution

13CX Boltzmann averaged chemical shift of atom X13CXi Chemical shift of atom X in conformer i

(Barone, 2002)

Probability

MG1 MG2 MG3 MG4 MG5 MG6Relative DG°soln Acetone (kJ/mol) Sum 10.2 0.7 4.4 10.9 0.0 4.0

[Ni/N] acetone 1.00 0.01 0.35 0.08 0.01 0.46 0.09

Carbon ExperimentalWeighted

shifts MG1 MG2 MG3* MG4 MG5 MG6

1 130.2 128.0 128.7 127.8 128.2 128.8 128.0 128.4

2 109.9 111.1 120.1 106.5 107.4 126.8 114.1 115.2

3 148.4 145.2 145.9 145.4 146.4 145.1 144.7 145.5

4 147.1 145.3 150.2 145.5 145.7 149.7 144.9 144.8

5 115.7 115.0 116.7 114.4 115.3 117.6 115.2 116.2

6 120.6 121.0 127.8 125.1 124.2 121.1 118.1 117.0

a 130.4 133.4 132.9 133.4 133.4 132.9 133.4 133.5

b 128.0 125.9 126.4 125.5 125.3 126.5 126.3 126.1g 63.4 65.2 65.2 65.1 65.1 65.3 65.3 65.3

OMe 56.1 53.4 57.2 53.4 53.1 57.0 53.4 53.1

40 60 80 100 120 140 16040

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100

120

140

160

13Cexp (ppm)

Bol

tzm

ann-

wei

ghte

d 1

3Cca

lc

(ppm

)

Boltzmann-weighted mPW1PW91/6-31G(d)Slope: 1.00y-intercept (ppm): 0.06r2: 0.996MUE (ppm): 2.1RMSE (ppm): 2.1Max Error (ppm): 3.2

Watts et al. Journal of Physical Chem-istry B. 2011, 115(9), 1958.

MG3 onlymPW1PW91/6-31G(d)Slope: 1.00y-intercept (ppm): -0.42r2=0.994MUE (ppm): 2.2RMSE (ppm): 2.4 ppmMax Error (ppm): 3.7

Conclusion: coniferyl alcohol• For d13C NMR calculations on coniferyl alcohol– Performance of multi-standard method >> TMS-

standard method• Linear correlation• Statistical errors

• Multiple, Boltzmann-weighted conformers better predict chemical shifts than did comparison of a particular conformer with data

AcknowledgmentsUSDA National Needs Graduate Fellowship Competitive Grant 2007-38420-17782 from the National Institute of Food and Agriculture to H.D. Watts through Nicole Brown.

Instrumentation funded by the National Science Foundation through grant OCI-0821527.

JDK, MNAM, and HDW acknowledge support of the U.S. Department of Energy grant for the Energy Frontier Research Center in Lignocellulose Structure and Formation (CLSF) from the Office of Science, Office of Basic Energy Sciences under Award Number DE-SC0001090.

HDW acknowledges support from Shell Geosciences Energy Research Facilities Award

MNAM was supported by the USDA grant “Improved Sustainable Cellulosic Materials Assembled Using Engineered Molecular Linkers” through Jeff Catchmark.

Computational support was provided by the Research Computing & Cyberinfrastucture group at the Pennsylvania State University.

Discussions with Ming Tien, Brett Diehl, Nicole Brown and other members of the Center for Nanocellulosics and CLSF are also acknowledged.

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