Enantiomer-specific detection of chiral molecules via microwave spectroscopy

• Published in: Nature (London) Vol. 497; no. 7450; pp. 475 - 477
• Main Authors: Patterson, David, Schnell, Melanie, Doyle, John M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.05.2013; Nature Publishing Group
• Subjects: 639/638/11/873; 639/638/440/527; 639/766/930/12; 639/766/930/527; Analytical chemistry; Animal behavior; Chemical reactions; Chemistry; Chirality; Cold; Electric fields; Enantiomers; Exact sciences and technology; Humanities and Social Sciences; letter; Methods; Microwave radiation; Microwave spectroscopy; Microwaves; multidisciplinary; Observations; Radiation (Physics); Science; Spectrometric and optical methods; Spectroscopy; Spectrum analysis; Stereoisomers; United States; Diol; Chiral compound; Experimental study; Cryogenic temperature; Growth from vapor; Microwave spectrometry; Racemic; Analysis method; Chirality; Enantiomeric excess; Qualitative analysis; Measurement method; Propanediol; Organic compounds
• DOI: 10.1038/nature12150
• ISSN: 0028-0836

Microwave spectroscopy is used to map the sign of an electric dipole Rabi frequency — which depends directly on the chirality of the molecule — onto the phase of emitted microwave radiation, thereby determining the chirality of cold gas-phase molecules. Microwave spectroscopy measures chirality Chiral molecules exist as enantiomers that form non-superimposable mirror images, and chirality has a fundamental role in many aspects of chemistry and biology. It is notoriously difficult to detect and quantify chirality because conventional spectroscopic methods exploit weak effects that produce weak signals. Patterson et al . now show that microwave spectroscopy combined with a switched electric field can map the sign of an electric dipole Rabi frequency — a variable that depends directly on the chirality of the molecule — onto the phase of emitted microwave radiation. The effect is then used to determine the chirality of cold gas-phase molecules, illustrated with S and R enantiomers of 1,2-propanediol and their racemic mixture. The method produces large and definitive signatures of chirality, and is both sensitive and species-selective — making it a potentially ideal and unique tool for determining the chirality of multiple species in a mixture. Chirality plays a fundamental part in the activity of biological molecules and broad classes of chemical reactions, but detecting and quantifying it remains challenging 1 . The spectroscopic methods of choice are usually circular dichroism and vibrational circular dichroism, methods that are forbidden in the electric dipole approximation 2 . 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 samples 3 , 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.