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Enantiomer-specific detection of chiral molecules via microwave spectroscopy


Chirality plays a fundamental part in the activity of biological molecules and broad classes of chemical reactions, but detecting and quantifying it remains challenging1. The spectroscopic methods of choice are usually circular dichroism and vibrational circular dichroism, methods that are forbidden in the electric dipole approximation2. The resultant weak effects produce weak signals, and thus require high sample densities. In contrast, nonlinear techniques probing electric-dipole-allowed effects have been used for sensitive chiral analyses of liquid samples3,4,5,6,7. Here we extend this class of approaches by carrying out nonlinear resonant phase-sensitive microwave spectroscopy of gas phase samples in the presence of an adiabatically switched non-resonant orthogonal electric field; we use this technique to map the enantiomer-dependent sign of an electric dipole Rabi frequency onto the phase of emitted microwave radiation. We outline theoretically how this results in a sensitive and species-selective method for determining the chirality of cold gas-phase molecules, and implement it experimentally to distinguish between the S and R enantiomers of 1,2-propanediol and their racemic mixture. This technique produces a large and definitive signature of chirality, and has the potential to determine the chirality of multiple species in a mixture.

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Figure 1: The two enantiomers of chiral 1,2-propanediol.
Figure 2: 1,2-propanediol as a rigid rotor.
Figure 3: A cryogenic buffer gas Fourier transform microwave spectrometer that provides enantiomer-specific detection.
Figure 4: Enantiomer-dependent microwave radiation.


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We thank D. DeMille, A. Vutha and C. Connolly for discussions, and D. DeMille and C. Connolly for contributions to the final manuscript.

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D.P. had the idea for this work, built the apparatus and produced the theoretical simulations. J.M.D. and D.P. developed experimental approaches and designed the apparatus. D.P. and M.S. performed the measurements. All authors wrote the manuscript.

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Correspondence to David Patterson.

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Competing interests

D.P. and J.M.D. declare a financial interest: patents related to this research have been filed by Harvard University. The university’s policy is to share financial rewards from the exploitation of patents with the inventors. M.S. declares no competing financial interests.

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Patterson, D., Schnell, M. & Doyle, J. Enantiomer-specific detection of chiral molecules via microwave spectroscopy. Nature 497, 475–477 (2013).

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