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

Abstract

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.

Beyond the paradigm: Combining mass spectrometry and nuclear magnetic resonance for metabolomics

“…MS also boasts higher resolution (∼10 3 -10 4 ) and dynamic range (∼10 3 -10 4 ). Conversely, MS only detects metabolites that readily ionize, as a result of which upwards of 40% of chemical libraries are not observable by MS [37, 38]. Similarly, ion suppression is a well-known problem in MS, which further reduces the detection of ions of interest due to matrix effects [39].…”

The use of fast molecular descriptors and artificial neural networks approach in organochlorine compounds electron ionization mass spectra classification

“…However, several attempts of MS spectra modelling appeared in the literature. Two major approaches can be distinguished, namely, predicting MS spectra features using quantum-chemical computations (Cautereels et al 2016;Ásgeirsson et al 2017;Spackman et al 2018) and 2D structure and topology-based methods (Gray et al 1980;Gasteiger et al 1992;Copeland et al 2012). The latter approach can be regarded as an extension of popular fragmentation rules.…”

“…Noteworthy, in many cases, there are no reference standards and no reference spectra available in the literature. There have been several attempts to use theoretical models for EI-MS spectra analysis (Gray et al 1980;Gasteiger et al 1992;Copeland et al 2012;Ásgeirsson et al 2017;Spackman et al 2018). According to our best knowledge, 1D and 2D descriptor-based models devoted to the organochlorine compounds have never been reported in the literature.…”

NMR Metabolomics Analysis of Parkinson's Disease

“…In contrast, MS depends on compound ionization and volatility. A number of metabolites do not produce a detectable molecular ion [224]. Moreover, the heterogeneity and complexity of the metabolome may lead to additional ion suppression and further diminish the detection of weakly ionizable metabolites.…”