Determination of Torsional Barriers of Itaconic Acid and N-acetylethanolamine using Chirped-pulsed...

Determination of Torsional Barriers of Itaconic Acid and N-acetylethanolamine usingChirped-pulsed FTMW Spectroscopy.

Josiah R. Bailey, Timothy J. McMahon, Ryan G. BirdUniversity of Pittsburgh Johnstown

David PrattUniversity of Vermont

Introduction

Itaconic Acidm.p. 168 °C

N-Acetylethanolamineb.p. 150 °C

Be careful what you wish for!

CP-FTMW Spectrometer

MW Synthesizer

Arbitrary Waveform Generator

Fourier Transform

Free Induction Decay

Chirped Pulse240 MHz

500 MHzDigitizer(10 Gs/s)

Itaconic Acid

• Itaconic acid (methylenesuccinic acid) is an important chemical in the immune system’s response bacteria.

• Recently, it was discovered that white blood cell macrophages release itaconic acid to disrupt the metabolism of bacteria such as salmonella and tuberculosis.1

• How this molecule is utilized by our immune system is greatly dependent on its three-dimensional structure.

1Michelucci, A.; et.al. Proc. Natl. Acad. Sci. USA. 2013, 110, 7820

Itaconic Acid Spectrum10,000 averages~240 MHz chirped pulse50°C

Itaconic Acid Conformations

Conformer 1:0 kJ/mol

Conformer 3:14.5 kJ/mol

Conformer 2:1.7 kJ/mol

m052x/6-311g(d,p)

Itaconic Anhydride

JB95 MP2/ 6-311+G(2d,p)

A (MHz) 3914.62(3) 3901.42B (MHz) 1886.05(2) 1912.60C (MHz) 1282.791(9) 1293.768

ΔI -3.089(4) -3.185

Torsional Splitting

b-typea-type

N-Acetylethanolamine (AEA)

• AEA or (2-hydroxyethyl)acetamide contains both an acetamide and an alcohol functional group

• Amides form the backbone of peptide chains• Additionally, the alcohol group allows for an

intramolecular hydrogen bond• How this molecule folds up on itself dramatically

effects the barrier of the acetamide methyl rotor

10,000 averages~240 MHz chirped pulse40°C

AEA Spectrum

Rotational Constants and BarrierXIAM MP2/6-

311+G(2d,p)A (MHz) 5114.(1) 5103.1701B (MHz) 1726.(1) 1732.8742C (MHz) 1409.4(6) 1403.0590χaa (MHz) 1.55(3)a 1.61b

χbb (MHz) 1.54(5)a 1.66b

χcc (MHz) -3.09(5)a -3.27b

V3 (cm-1) 123.(4) 160c

aFit with A-band using JB95bb3pw91/6-311+g(df,pd)cm052x/6-31+g(d,p)

Structure vs. Barrier

~420 cm-1

24 cm-1 73 cm-1

123 cm-1

Suenram, R. D., et.al.. Journal of Molecular Spectroscopy 2001, 208, 188.

Ohashi, N., et.al., , J. Journal of Molecular Spectroscopy 2004, 227, 28.

Conclusion

• Collected and fit the spectra of itaconic anhydride and n-acetylethanolamine

• Both molecules displayed unexpected torsional splitting

• Compare similar molecules to help understand these motions

Future Work

• Research ways to heat itaconic acid without reacting it

• Study other dicarboxylic acids to see how methyl and methylene groups affects structure and dynamics

• Study more anhydrides of above molecules to further investigate the cause of the torsional splitting in itaconic acid

• Investigate the dynamics and structure of other acetamide to compare with AEA

Acknowledgements

Josiah Bailey

Bird Group at UPJ

Tim McMahon

Dr. David Pratt – University of Vermont