Chirality and Cold Molecules – Enantiomer differentiation, mixture analysis and precision measurements
Since the introduction of broadband rotational spectroscopy by Brooks H. Pate (University of Virginia) in 2006, impressive developments in the area of high-resolution molecular spectroscopy were achieved. In broadband rotational spectroscopy, the molecules are excited by a short microwave chirp, and their response is detected as broadband free-induction decay in the time domain. Subsequently, the molecular response will be Fourier transformed from the time to the frequency domain . With this approach, it is now possible to record large parts of the rotational spectra in a single acquisition, which does not only provide access to larger and more complex molecules and their complexes, but also opens up new directions of double-resonance experiments.
In collaboration with Dave Patterson and John M. Doyle from Harvard University, we recently developed and demonstrated a new method to differentiate between the enantiomers of chiral molecules based on broadband rotational spectroscopy [54, 56, 57]. With this microwave three-wave mixing approach, we can determine the absolute configurations of the enantiomers and determine their enantiomeric excess in mixtures. Our method relies on strong effects and is inherently mixture-compatible – a unique advantage with respect to other established techniques, such as polarimetry and circular dichroism. Chiral mixture analysis is required in nearly all development phases of modern pharmaceutical drugs, from the early search for suitable molecular candidates to optimization and production.
So far, we applied this technique to several chiral molecules containing one or two stereogenic centers . We mainly concentrated on alcohols and terpenes, which are also of relevance for the perfume industry and for studying the relationship between molecular structure and olfaction . In future experiments, we will extend this new analytical tool to the analysis of larger and more complex molecules containing several stereogenic centers and towards biologically and pharmaceutically relevant samples. As an important preliminary study, we could record and analyse the broadband rotational spectrum of ibuprofen, which exhibits several gas-phase conformers under the conditions of a cold molecular jet . Experiments aiming at a chiral analysis of ibuprofen samples are under way.
In the field of cold molecules, we are exploring the potential of using intense and well-tailored microwave fields for manipulating and controlling the motion of polar molecules in the gas phase. We could demonstrate a microwave lens that focuses the molecules and thus keeps them together in transverse direction  and a novel microwave decelerator . Currently, we are working on decelerating the molecules to standstill and to subsequently trap them. Such a microwave trap is in immediate reach and will offer unique possibilities for future experiments on trapped molecules, such as sympathetic cooling (since it has a very open design and an easily adjustable trap depth by simply lowering the microwave input power).
Furthermore, we explore the possibilities of extending microwave manipulation to larger, heavier molecules that are more challenging to be controlled with the existing methods such as Stark deceleration. These slow molecules are important ingredients for performing precision spectroscopy experiments.
Supported by the Deutsche Forschungsgemeinschaft via an individual research grant for three years, entitled “Tailored molecular samples for precision spectroscopy” (SCHN 1280/1-1, 2012-2015), we developed a new apparatus to perform rotational spectroscopy with very high resolution . In this research branch, we combine two of our main research directions (high-resolution spectroscopy and the generation of slow and cold molecules). One ultimate aim is to gain sufficient resolution and stability in the experiment that we will be able to precisely determine the frequency difference of the two enantiomers of chiral molecules due to parity violation. This would be the first experimental detection of this predicted very small effect. The precise knowledge of these differences between the two enantiomers will not only help to answer important questions that relate to the homochirality of life, but it will also allow for important feedback for the theoretical methods employed to predict the effect.
The size of the effect depends largely on the choice of the molecule. In collaboration with Prof. Robert Wolf from the Universität Regensburg (Inorganic Chemistry) we evaluate potential candidate molecules. Strong candidates are heavy metal-organic molecules such as CpRe(CO)(NO)I (Cp: cyclopentadienyl) for which large effects are predicted. Recently, we obtained the broadband rotational spectrum of the related molecule CpRe(CO)(NO)(CH3) . The spectrum is very rich due to nuclear quadrupole coupling and the presence of the two rhenium isotopologues. The analysis of the rhenium nuclear quadrupole coupling shows that relativistic effects have to be considered for their correct description, while the influence of relativistic effects on the rotational constants is not so critical.
Besides that,we expect to observe a variety of interesting phenomena when going well beyond the 1 kHz resolution in microwave spectroscopy, such as unusual spin-rotation coupling, to be observed and understood on our road towards this ambitious goal, so that the way by itself will become very exciting and interesting.