Instrumental advancements in vibrational optical activity

Chirality is an important concept in chemistry, which is also encountered in our everyday life. It refers to objects not being superimposable on their mirror image, with a classic example being our own hands, which are built identically but rotated. Similar configurations can be found in the biochemical world, leading to the emergence of pairs of mirror image compounds, called enantiomers. Since the human body is preferentially made up of one enantiomeric form, chirality has significant implications for the development of medicinal drugs in both a beneficial but also in a possible dramatic way. A prominent example case is the chiral drug Thalidomide (or contergan) which was marketed as a sleeping pill specifically to pregnant women in the 1950s. Tragically, one of its enantiomers, after processing by the body, lead to the emergence of malformities in the developing babies. The worlds regulatory agencies learned from this scandal, leading to the inclusion of chiral analytics in modern pharmaceutical processes. One of those chiral analytics is Raman optical activity (ROA), which analyses the light scattered by the tested molecules when illuminated by a high-power, commonly green, laser. The scattered light is modulated to collect the difference in intensity for left and right-handed circularly polarized light. Unfortunately, this difference is very small, in the order of 1 in 10000, necessitating long measurement times of up to several days. One option of increasing this signal is if the sample is not only scattering the incident laser, but also partly absorbing it, boosting the intensity of the scattering. However, only a limited number of molecules exhibit the necessary behaviour for this so-called resonance effect when measured with commercial systems. The proposed project aims to help improve ROA by innovations in instrumental design. By switching to an ultraviolet laser source, the measurements will profit from signal enhancement due to the shorter wavelengths used. In addition, most chemical compounds absorb in this spectral area, allowing for the described process of resonant signal enhancement to be used for even greater effect and on a broad scale. As part of the project, the instrument will be used to study proteins, which constitute important samples in a pharmaceutical context. They can be used directly as medicinal drugs, but also the interaction of endogenous proteins with novel chemical compounds can be studied in greater detail with the new instrument. Coupled with the theoretical groundwork provided by our cooperation partners, the new instrument will provide an impetus for further developments of ROA and open up more possibilities for collaborative research.