1. SEVEN CONFORMERS OF PIPECOLIC ACID IDENTIFIED IN THE GAS PHASE
Grupo de Espectroscopia Molecular, Unidad Asociada CSIC
Laboratorios de Espectroscopia y Bioespectroscopia
Edificio Quifima. Parque Científico
Universidad de Valladolid. SPAIN
EIGTH
SEVEN CONFORMERS OF PIPECOLIC ACID IDENTIFIED IN THE GAS PHASE
CARLOS CABEZAS, ALCIDES SIMAO and JOSE L. ALONSO
International Symposium on Molecular Spectroscopy, June 20  24, 2016
Champaign-Urbana, Illinois, USA

2. Research in our group is devoted to :
*Rotational Spectra of Molecules of Astrophysical Interest
The combination of Lab. Data and Radioastronomy provides a power
capability for the detection and conclusive identification of molecular
species in the ISM
Frequency Domain
Stark Modulation MW: GHz
Millimeter and Submillimeterwave : GHz
*Conformation and Structure of Biomolecules.
Rotational studies of solid biomolecules by FTMW spectroscopy in a
supersonic expansion combined with laser ablation techniques of
vaporization.
Time Domain
MB-FTMW: GHz
LA-MB-FTMW : GHz
LA-MB-FTMW : 4-26 GHz
CP-FTMW: GHz

3. Why Biomolecules in Gas Phase?
STRUCTURE
FUNCTIONALITY
To understand the structure and functionality of biological systems in their native environments (in vivo condensated phases) it is often imperative to first understand these properties for the isolated system in the gas-phase.

4. Why Amino Acids in Gas Phase?
Amino Acids in their natural condensed phases are stabilized as by strong intermolecular interactions as zwitterions which does not occur in the polypetide chain
The structural research of the neutral amino acids should be conducted in gas phase where the they present an unsolvated neutral form HN-CH(R)-COOH which represents the best approximation of an amino acid residue in a polipeptide chain.
Gas phase
Condensed phase
H2N−CH(R)−COOH
Neutral
Zwitterion
H3N−CH(R)−COO
bipolar ionized form + -

5. The 20 Natural Amino Acids

6. Pipecolic Acid Pipecolic Acid Proline
Proline homologue (piperidine ring vs pyrrolidine ring)
Can be produced from L-lysine (natural pathway envolves PIPO)
It can be found in human physiological fluids, fungi and plants
Constituent of various pharmaceutical compounds (ropivacaine, rapamycin...)
Melting point : 280ºC
Pipecolic Acid
Proline

7. Pipecolic Acid Melting point : 280ºC Pipecolic Acid Proline
Proline homologue (piperidine ring vs pyrrolidine ring)
Can be produced from L-lysine (natural pathway envolves PIPO)
It can be found in human physiological fluids, fungi and plants
Constituent of various pharmaceutical compounds (ropivacaine, rapamycin...)
Melting point : 280ºC
Pipecolic Acid
Proline
PCCP, 11,617 (2009)
Angew. Chem. 41, 4673 (2002)

8. Conformational Panorama of Pipecolic Acid: What Can We Expect?
ring configuration
Axial-equatorial
Intramolecular
hydrogen bonding

9. Conformational Panorama of Pipecolic Acid: What Can We Expect?
Conformer
ΔE(cm-1) ΔG A B C
|µa|
|µb|
|µc| Pc
C-a-I
138 20
3247
1094
942
1.1
1.8
0.0
40.55
C-e-I 40 1
2562
1425
1166
0.3
59.24
C-e-I 95
3264
1142
892
0.7
1.2
15.40
C-a-II 49
2544
1447
1154
4.4
1.5
2.2
54.99
C-e-II
181
182
3221
1123
959
5.1
0.6
39.97
C-a-II
336
351
3199
1159
895
14.68
C-e-III
210
102
3252
1144
897
0.8
1.4
16.88
C-a-III
446
330
3248
1084
961
1.9
0.2
47.96
C-e-III
161
118
2536
1445
1177
59.82
dCa-e-I
aCd-e-I
dCa-a-I
dCa-e-III
dCa-a-III
aCd-a-II
dCa-e-II
dCa-a-II
aCd-e-III

10. Experimental Approach
Spectroscopic
Characterization
Vaporization
Gas Phase Isolation
FT-MW
Supersonic Expansion
Laser Ablation LA MB
FTMW + +
LA + MB-FTMW Spectroscopy
LA + CP-FTMW Spectroscopy

11. Experimental: CP-FTMW + Laser Ablation
Vaccum Chamber
Picosecond Laser
FT-MW Spectrometer

12. Experimental: CP-FTMW + Laser Ablation
Jet
Diffusion
pump
Laser

13. Experimental: CP-FTMW + Laser Ablation
Jet
Diffusion
pump

14. Broadband Fourier Transform: Operation
Gas pulse
Jet Ne
Laser pulse
Solid
sample
Rotary
Diffusion
pump
Laser
Nd:YAG laser

15. Broadband Fourier Transform: Operation
CP-FTMW
spectrometer
Gas pulse
Molecular emission Ne
Laser pulse
Chirped MW pulse
Rotary
Diffusion
pump
Detection

16. Broadband Fourier Transform: Operation
CP-FTMW
spectrometer
Gas pulse
Molecular emission Ne
Laser pulse
Chirped MW pulse
Rotary
Diffusion
pump
Detection
Detection
Frequency-domain
Time-domain FT

17. Pipecolic Acid: Observed Conformers
dCa-e-I
aCd-e-I
dCa-a-I
aCd-a-II
dCa-e-II
dCa-a-II
dCa-e-III
dCa-a-III

18. Observation Type III Pipecolic Acid Alanine Type III Type I
< 275 cm-1
~ 450 cm-1

19. Grupo de Espectroscopia Molecular Laboratorios de Espectroscopia
y Bioespectroscopia Edificio Quifima.
Universidad de Valladolid. Spain
Carlos Cabezas
Isabel Peña
Lucie Kolesnikova
Santiago Mata
Elena R. Alonso
Veronica Diez
Jose M. Rodriguez
Marta San Juan
Research Funded by: