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