1. Academic Validation
  2. Chirality: a key parameter in chemical probes

Chirality: a key parameter in chemical probes

  • RSC Chem Biol. 2023 Aug 8;4(10):716-721. doi: 10.1039/d3cb00082f.
Andrew McGown 1 2 Jordan Nafie 3 Mohammed Otayfah 1 Storm Hassell-Hart 1 Graham J Tizzard 4 Simon J Coles 4 Rebecca Banks 5 Graham P Marsh 5 Hannah J Maple 5 George E Kostakis 1 Ilaria Proietti Silvestri 6 Paul Colbon 6 John Spencer 1 2
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Life Sciences, University of Sussex Falmer BN1 9QJ UK [email protected] [email protected].
  • 2 Sussex Drug Discovery Centre, Department of Chemistry, School of Life Sciences, University of Sussex Falmer BN1 9QJ UK.
  • 3 Biotools, Inc., 17546 Beeline Highway Jupiter Florida 33458 USA.
  • 4 National Crystallography Service, School of Chemistry, University of Southampton Southampton SO17 1BJ UK.
  • 5 Bio-Techne (Tocris), The Watkins Building, Atlantic Road Avonmouth Bristol BS11 9QD UK [email protected].
  • 6 Liverpool ChiroChem Ltd, The Heath Business & Technical Park Runcorn Cheshire WA7 4QX UK.
Abstract

Many small molecule bioactive and marketed drugs are chiral. They are often synthesised from commercially available chiral building blocks. However, chirality is sometimes incorrectly assigned by manufacturers with consequences for the end user ranging from: experimental irreproducibility, wasted time on synthesising the wrong product and reanalysis, to the added cost of purchasing the precursor and resynthesis of the correct stereoisomer. Further on, this could lead to loss of reputation, loss of funding, to safety and ethical concerns due to potential in vivo administration of the wrong form of a drug. It is our firm belief that more stringent control of chirality be provided by the supplier and, if needed, requested by the end user, to minimise the potential issues mentioned above. Certification of chirality would bring much needed confidence in chemical structure assignment and could be provided by a variety of techniques, from polarimetry, chiral HPLC, using known chiral standards, vibrational circular dichroism, and x-ray crystallography. A few case studies of our brushes with wrong chirality assignment are shown as well as some examples of what we believe to be good practice.

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