1. 1 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 - 68 th Meeting (June 17-21 2013)

2. 2 INTRODUCTION An object that cannot be superimposed on its mirror image is called chiral. SR Mirror plane S(-)-limonene Orange aroma R(+)-limonene Turpentine odour

3. QUININE : A CINCHONA ALKALOID 1 3 4 8 9 (-)-Quinine (Qn) (1S,3R,4S,8S,9R) 4’ * * * * * 3’ Quinuclidine Amino alcohol Linker.Flexibility. Quinoline chromophore Antimalarial drug Enantio-selective catalysts (hydrogenation of ketones) Chiral stationary phase (chromatography) 3

4. * 8 9 8 9 QUININE: A PSEUDOENANTIOMER (+)Quinidine (Qd)(1S,3R,4S,8R,9S) (-)Quinine (Qn) (1S,3R,4S,8S,9R) PSEUDOENANTIOMERS * * * * * * * * * slightly different packing properties in the crystal. slightly different efficiency against malaria interpreted in terms of different solubility. 4

5. Protonated Quinine used as a fluorescence standard. (Q f =0.546 for exc =310 nm) h H O H h Neutral quinine n  *n  * Protonated/H-bonded quinine ¹ Addition of water/ protonation  no charge transfer.  Locally Excited (high Q f ) emission restored   *  * ¹ Albert M Brouwer J. Phys. Chem. C 2009, 113, 11790-11795 PHOTOPHYSICS OF QUININE 5 Nonpolar solvents  Charge Transfer  low Q f

6. 6 The spectroscopic properties of jet-cooled Quinine in gas phase. Comparison with Vibrational Circular Dichroism studies of Quinine in solution. OBJECTIVE

7. 7 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

8. 8 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.

9. 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. 9 QUININEQUINIDINE B3lyp-6-31G+(d,p)

10. LASER INDUCED FLUORESCENCE Same electronic spectroscopy Same vibrational pattern AND same resonant emission characteristic of the  * transition of Quinoline (no n  * transition) low Q F 8b₁g8b₁g 8a ₁ g 8b₁g8b₁g 5a ₁ g EXCITATIONEMISSION QUININE QUINIDINE 10

11. QUININE vs QUINIDINE Probe kept on 0-0 bend Chiral linker bend OMe 11 Same (OH) Different (CH) QUINIDINE: Probe kept on 0-0, +23 cm -1 and +45 cm -1 show no difference.

12. QUININE: +14 cm -1 and +5 cm -1 are hot bands or higher energy conformers ?? 12 QUININE vs QUINIDINE

13. CALCULATED VIBRATIONAL SPECTRUM  conformer not likely Shift in (OH) not observed experimentally Trans conformer not likely Calculated transition energies (TDDFT) does not match with experimental value. Hence the bands at +5 and +14 cm -1 are hot bands! 13  G=1.24 kcal/mol Too high for excitation within 20 cm -1.

14. VIBRATIONAL CIRCULAR DICHROISM  Difference in absorbance of left vs right circular polarized IR light  ∆A=A L – A R  Enantiomers have opposite spectra  Sign and intensity of bands very sensitive to molecular conformation Calculated spectra: Contribution of different conformers 14

15. Good mirror-image relation Presence of higher-energy conformers, more for Quinidine at RT. Mirror-image relation lost for the delocalised modes Exp Calc 1 1 = aromatic CH in plane bend 2 = OCH 3 CH bend 3 = CH bend on the linker 1 2 2 3 Quinine Quinidine RESULTS OF VCD 15

16. STABLE GEOMETRY IN SOLUTION cis-  -open trans-  -open 16 Most abundant conformer Same in gas phase and solution. QUININE One additional open conformer populated at room temperature in solution. FOUR in case of Quinidine.

17.  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 17 GENERAL CONCLUSION Role of higher energy conformers in Chiral Recognition. ² Sen et. al J. Phys. Chem. A 2012, 116(32), 8334-8344

18. 18 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

19. Pellet Supersonic expansion 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 ions Axis of excitation EXPERIMENTAL SET-UP : REMPI 19 Ablation laser