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The Applicability of Molecular Descriptors for Designing an Electrospray Ionization Mass Spectrometry Compatible Library for Drug Discovery

[ Vol. 15 , Issue. 10 ]


Jennifer C. Copeland, Levi J. Zehr, Ronald L. Cerny and Robert Powers   Pages 806 - 815 ( 10 )


Detecting a small molecular-weight compound by electrospray ionization mass spectrometry (ESI-MS) requires the compound to obtain a charge. Factors such as gas-phase proton affinities and analyte surface activity are correlated with a positive ESI-MS response, but unfortunately it is extremely challenging to predict from a chemical structure alone if a compound is likely to yield an observable molecular-ion peak in an ESI-MS spectrum. Thus, the design of a chemical library for an ESI-MS ligand-affinity screen is particularly daunting. Only 56.9% of the compounds from our FAST-NMR functional library [1] were detectable by ESI-MS. An analysis of ~1,600 molecular descriptors did not identify any correlation with a positive ESI-MS response that cannot be attributed to a skewed population distribution. Unfortunately, our results suggest that molecular descriptors are not a valuable approach for designing a chemical library for an MS-based ligand affinity screen.


Chemical library, drug discovery, electrospray ionization, ligand-affinity screens, mass spectrometer, molecular descriptors.


Department of Chemistry, 722 Hamilton Hall, University of Nebraska-Lincoln, Lincoln, NE 68588- 0304, USA

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