Department of Chemistry
Indian Institute of Technology Delhi

From chiral crystals to the absolute configuration of molecules: Is it an easy way?

Prof. Jordi Benet-Buchholz
X-ray Diffraction Unit, Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans,
Tarragona, Spain

Date: August 11th 2017 (Friday)
Time: 4 PM
Venue: Committee Room, Chemistry Department, 6th Floor

The determination of the absolute configuration of enantiopure chiral organic molecules like active pharmaceutical ingredients (APIs) and natural products is a key issue for research groups and companies working in the field of life sciences. Active chiral compounds can show different properties since the biological environment where they act is usually chiral as well. Since the 1960s, were the teratogen effects of R-thalidomide were known, the concern over the stereoselectivity of drug action has drawn a great deal of interest.1
For the determination of the absolute configuration direct methods such as X-ray diffraction analysis, circular dichroism, Raman optical activity, optical rotation measurements and the indirect methods for relative configuration assignment based on NMR spectroscopy and enzymatic transformations can be used.2 Conditioned by the availability of single crystals, the direct method based on X-ray diffraction analysis, is probably the most reliable.
The determination of the absolute configuration through the single crystal X-ray diffraction is based on the anomalous scattering effects produced by the different atoms contained in the structure and is only effective if the differences between Friedel-related reflections collected from a single crystal are large enough to be detected. Absolute configuration determination was traditionally based on single crystal X-ray structure determination performed using CuKa radiation and compounds containing atoms heavier than Si. The anomalous scattering effects, especially using MoKa radiation, are much weaker in organic molecules containing only “light atoms”. This weak inversion distinguishing power is the main problem for the determination of the absolute configuration of most APIs and natural products.
Aim of the presentation is to give an overview on methodologies how to determine the absolute configuration of chiral molecules and finally present an own new experimental validated approach to determine the absolute structure of APIs and natural products.3

  1. Mc Bride W.G., Lancet ii, (1961) 1358.
  2. Allenmark S., Gawronski J., Chirality 20 (2008) 606.
  3. Escudero-Adán E.C.*, J. Benet-Buchholz J.*, Ballester P.; Acta Cryst. (2014) B70, 660-668.

All are cordially invited to attend.
Convener (Seminars)