1. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy V. Alvin Shubert a, David Schmitz a, Chris Medcraft a, Anna Krin a, David Patterson b, John M. Doyle b, and Melanie Schnell a a Max-Planck Research Group “Structure and Dynamics of Cold and Controlled Molecules” Max-Planck-Institut für Struktur und Dynamik der Materie Hamburg, Germany b Department of Physics Harvard University Cambridge, MA, USA

2. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Introduction Chiral Molecules “Homochirality of life“ Differing chemical properties Enantiomeric excess (ee) determination in mixtures remains challenging Three-wave mixing 1,2 Unambiguous differentiation of enantiomers in mixtures of chiral molecules Signal amplitude proportional to ee Absolute configuration from phase and aid of quantum chemical calculations S-carvoneR-carvone 1.D. Patterson, M. Schnell, J.M. Doyle, Nature. 497, 475 (2013) 2.D. Patterson, J.M. Doyle, Phys. Rev. Lett. 111, 023008 (2013) 1 http://www.rowland.harvard.edu/rjf/fischer/background.php

3. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Broadband Microwave Spectrscopy 1. Generation of a microwave pulse and excitation of a molecular ensemble. 2. Molecules are excited, creating a macroscopic polarization that starts to decay after the pulse(s). 3. Recording of the Free Induction Decay (FID). Provides phase sensitive detection of rotational transitions. 2

4. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Broadband Spectrum of 4-carvomenthenol 3

5. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Broadband Spectrum of 4-carvomenthenol 4 Conformer A Conformer B Conformer C

6. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Recording horn Broadcast horn Ground electrode RF electrode Three-wave Mixing Experiment 5

7. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Broadband Spectrum of 4-carvomenthenol 6

8. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy 165.19 MHz (Twist) 5624.49 MHz (listen) 5459.31 MHz (Drive) Three-wave mixing cycle 7

9. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Results 8

10. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Conformation C Conformation B Coadded MW pulses Coadded RF pulses 3-Wave-Mixing Results 9 Simultaneous excitation and measurement of 2 chiral molecules

11. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Broadband Spectrum of Menthone 10 Drive Listen 2R,5S-(+)-menthone

12. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy 3-Wave-Mixing Results Menthone, listen at 3713.18 MHzCarvone, listen at 5098.12 MHz 11 Mixture of (-)-menthone and S-(+)-carvone Mixture of (+)-menthone and R-(-)-carvone Simultaneous excitation and measurement of 2 chiral molecules S-(+)-carvone R-(-)-carvone 2R,5S-(+)-menthone2S,5R-(-)-menthone

13. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy 3-Wave-Mixing Results Menthone, listen at 3713.18 MHzCarvone, listen at 5098.12 MHz 12 Mixture of (-)-menthone and S-(+)-carvone Mixture of (+)-menthone and R-(-)-carvone Simultaneous excitation and measurement of 2 chiral molecules

14. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy 3-Wave-Mixing Results Menthone, listen at 3713.18 MHzCarvone, listen at 5098.12 MHz 13 Mixture of (-)-menthone and S-(+)-carvone Mixture of (+)-menthone and R-(-)-carvone Simultaneous excitation and measurement of 2 chiral molecules

15. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Enantiomeric Excess 14 Signal amplitude proportional to ee: b can change between experiments Need internal reference Menthone mixture of isomers ee 1:1 mixture of carvone and menthone Use carvone signal intensity as internal reference ee = 0.63 ±.24 (-)-menthone Carvomenthenol Use signal from carvomenthenol drive with RF off as internal reference

16. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Enantiomeric Excess 15 Use drive intensity with RF off as internal reference

17. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Enantiomeric Excess 16 Use drive intensity with RF off as internal reference: Still need a measurement of known ee. Assume ~2:1 ratio for carvomenthenol from Aldrich is correct for (-) sample ee(-) = 0.33 ± 0.07 (ϕ(C) listen = 0.8 radians) ee(+) = 0.30 ± 0.06 (ϕ(C) listen = -2.5 radians) Mixture Prepared ee(-) = 0.049 ± 0.08 (excess (-)) Measured ee = 0.058 ± 0.018 (ϕ(C) listen = 1.4 radians)

18. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Absolute Configuration 17 With aid of quantum chemical calculations, should be possible to determine absolute configuration. Phases of excitation pulses – also different paths to interaction region introduces a phase shift. tRtR Delay between FID start and FID recording introduces an additional shift in the observed phase.

19. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Absolute Configuration 18 tRtR

20. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Conclusion and Outlook Multiple chiral species can be detected simultaneously  species-specific resonances Very similar species Species with opposite optical rotation Phase of signal identifies the enantiomer Absolute configuration Better characterize observed signal and excitation radiation paths More complex mixtures and chiral molecules Larger molecules – more conformations, complex spectra Real world mixtures – e.g. tea tree oil 19

21. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy Acknowledgements Melanie Schnell Simon Merz David Schmitz Thomas Betz Sabrina Zinn Chris Medcraft Jack Graneek Max Planck Research Group “Structure and Dynamics of Cold and Controlled Molecules” Funding: 20 Anna Krin