Gas Phase Drug Discovery: Physicochemical Property Measurements with Differential Mobility Spectrometry

W. Scott Hopkins, Chemistry Department, University of Waterloo

Abstract: 

In vitro measurements of physicochemical properties such as pKa and cell permeability routinely serve as a key step in a drug’s overall development pathway. However, these measurements can be time-consuming, labor-intensive, and low-resolution. Recently, in partnership with researchers SCIEX and Pfizer, we have begun developing a physicochemical properties measurement technique which employs differential mobility spectrometry (DMS). DMS is an analytical technique that can separate isomers, conformers, and even tautomers based upon their different microsolvation propensities in a gas-phase environment. By using DMS to assess the interaction strengths between drug molecules and solvent vapor, we have identified correlations between drug microsolvation and several condensed phase drug properties. Our measurements, which can be conducted in seconds using only nanograms of sample, and supporting electronic structure calculations provide insight regarding the subtle effects of geometric and electronic structure on in vitro drug properties. Our most recent results suggest that this DMS-based technique can potentially be used as a new, high-throughput tool in rational drug design.

In this seminar, I will discuss our most recent results and provide a perspective for future directions in this research.

To know more about Prof. Hopkins' group, see his web site.

Cette conférence est présentée par le RQMP Versant Nord du Département de physique de l'Université de Montréal et de Génie physique de la Polytechnique.