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CHIRAL RECOGNITION IN NEUTRAL AND IONIC MOLECULAR COMPLEXES

Ananya Sen, Aude Bouchet, Valeria Lepere, Katia Le Barbu Debus, Anne Zehnacker Rentien

Institut des Sciences Moléculaires d’Orsay ISMO CNRS-Université Paris Sud Orsay-France

International Symposium on Molecular Spectroscopy - 68th Meeting (June 17-21 2013)

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INTRODUCTION

An object that cannot be superimposed on its mirror image is called chiral.

S R

Mirror plane

S(-)-limoneneOrange aroma

R(+)-limoneneTurpentine odour

QUININE : A CINCHONA ALKALOID

1N

H

H

OH

H

N

OMe

3 4

8 9

(-)-Quinine (Qn) (1S,3R,4S,8S,9R)

4’

* *

*

**

3’

Quinuclidine

Amino alcoholLinker.Flexibility.

Quinolinechromophore

• Antimalarial drug • Enantio-selective catalysts (hydrogenation of ketones)• Chiral stationary phase (chromatography)

3

*8

98

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QUININE: A PSEUDOENANTIOMER

(+)Quinidine (Qd)(1S,3R,4S,8R,9S)

N

H

HOH

H

N

MeO

(-)Quinine (Qn) (1S,3R,4S,8S,9R)

N

H

H

OH

H

N

OMe

PSEUDOENANTIOMERS

* *

*

**

**

**

• slightly different packing properties in the crystal.• slightly different efficiency against malaria interpreted in terms of different solubility.

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Protonated Quinine used as a fluorescence standard.(Qf =0.546 for exc=310 nm) h

OH/H 2

HO

H

h

Neutral quinine

n *

Protonated/H-bonded quinine

¹ Addition of water/ protonation no charge transfer. Locally Excited (high Qf) emission restored

*

¹Albert M Brouwer J. Phys. Chem. C 2009, 113, 11790-11795

PHOTOPHYSICS OF QUININE

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Nonpolar solvents Charge Transfer low Qf

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The spectroscopic properties of jet-cooled Quinine in gas phase.

Comparison with Vibrational Circular Dichroism studies of Quinine in solution.

OBJECTIVE

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TECHNIQUES

In the gas phase: Laser ablation and Supersonic Expansion

Resonance Enhanced Multiphoton Ionisation (REMPI)

Laser Induced Fluorescence Spectroscopy (LIF)

IR-UV Double Resonance Spectroscopy

In solution:

Vibrational Circular Dichroism

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CALCULATIONS

1. Global exploration of the potential energy surface.Molecular dynamics

2. Local optimization (B3lyp/6-31G(d,p))

3. Dispersion-corrected DFT calculations.

4. Simulations of vibrational spectrum in vacuum and in solution considering the solvation model (PCM)

Calculations performed by Dr Katia Le Barbu-Debus.

cis--open

Cis OMe

= no H bond

MOST STABLE GEOMETRY IN GAS PHASE

Identical for the two pseudo enantiomers

Open geometry with Quinuclidine N far away from the Quinoline ring.

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QUININE QUINIDINE

B3lyp-6-31G+(d,p)

LASER INDUCED FLUORESCENCE

• Same electronic spectroscopy• Same vibrational pattern AND same resonant emission

characteristic of the * transition of Quinoline (no n* transition)

• low QF

8b₁g

8a₁g

8b₁g 8a₁g5a₁g

EXCITATION EMISSION

QUININEQUINIDINE

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QUININE vs QUINIDINEProbe kept on 0-0

bendChiral linker

bend OMe

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Same (OH)Different (CH)

QUINIDINE: Probe kept on 0-0, +23 cm-1

and +45 cm-1 show no difference.

QUININE: +14 cm-1 and +5 cm-1 are hot bands or higher energy conformers ??

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QUININE vs QUINIDINE

2800 3000 3200 3400 3600 3800 4000

trans--open (8%) cis--closed (9%) cis--open (11%) cis--open (72%)

Rel

ativ

e In

tens

ity

QUININE

Wave number(cm-1)

CALCULATED VIBRATIONAL SPECTRUM

conformer not likelyShift in (OH) not observed experimentally

Trans conformer not likelyCalculated transition energies (TDDFT) does not match withexperimental value.

Hence the bands at +5 and +14 cm-1 are hot bands!

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G=1.24 kcal/molToo high for excitationwithin 20 cm-1.

VIBRATIONAL CIRCULAR DICHROISM

Difference in absorbance of left vs right circular polarized IR light

∆A=AL – AR Enantiomers have opposite spectra Sign and intensity of bands very sensitive to molecular

conformation

Calculated spectra:Contribution of different conformers

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Good mirror-image relation

Presence of higher-energy conformers, more for Quinidine at RT. Mirror-image relation lost for the delocalised modes

Exp

Calc

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1 = aromatic CH in plane bend2 = OCH3 CH bend3 = CH bend on the linker

1 22 3

Quinine

Quinidine

RESULTS OF VCD

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STABLE GEOMETRY IN SOLUTION

cis--open trans--open

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Most abundant conformerSame in gas phase and solution.

QUININE

One additional open conformer populated at room temperature in solution. FOUR in case of Quinidine.

mol/kcal5.1G

The two pseudo-enantiomers of Quinine do fluoresce in gas phase. Pseudo-enantiomers have very similar properties in the gas phase (same structure). Difference between the two are more prominent in solution than in gas phase. Quinidine is more flexible than Quinine in solution.²

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GENERAL CONCLUSION

Role of higher energy conformers in Chiral Recognition.Role of higher energy conformers in Chiral Recognition.

² Sen et. al J. Phys. Chem. A 2012, 116(32), 8334-8344

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ACKNOWLEDGEMENTS

Dr Anne Zehnacker-Rentien

Dr Philippe Bréchignac

Dr Katia Le Barbu-Debus

Dr Valeria Lepère

Dr Debora Scuderi

Dr Aude Bouchet

And the helpful mechanics and electronic workshop team at ISMO.

THANK YOU FOR YOUR ATTENTION

Pellet

Supersonicexpansion

EXCITATION LASER

IONISATION LASER

Carrier gas Ne

Ions detected at the microchannel plates.

System of detection of ions

Axis of jet Axis of detection of ionsAxis of excitation

EXPERIMENTAL SET-UP : REMPI

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Ablation laser