Applications of mass spectrometry surface sampling techniques towards natural products research

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Vincent P. Sica (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Nicholas Oberlies

Abstract: Since the pharmaceutical industry has experienced a decline in output over the past decade, natural products research has regained interest. The complexity and molecular diversity seen in nature remains unmatched, even against combinatorial chemistry. However, this re-approach to natural products will look different from our predecessor’s, since advancements in technology provide higher-throughput screening, innovative structure-guided fractionation, and chemical visualization. The recent development of ambient ionization techniques for mass spectrometry can assist in the revival and sustainability of natural products research for drug discovery. The goals of project sought to explore natural products in situ using ambient ionization mass spectrometry in three ways: (1) visualize the chemical ecology, (2) implement higherthroughput screening, and (3) elucidate the chemical entities. Aim 1 was achieved by utilizing desorption electrospray ionization (DESI) and the droplet-liquid microjunction-surface sampling probe (droplet-LMJ-SSP) by performing mass spectrometry imaging and mapping experiments to understand the spatial and temporal distributions of secondary metabolites. This information, which is lost through the traditional extraction protocols, can provide deep insight into the chemical ecology that takes place between organisms. The effects that herbicidal and fungistatic metabolites have on their environment were visualized via mass spectrometry imaging and mapping experiments. Aim 2 was achieved by coupling the droplet-LMJ-SSP with UHPLC–PDA–HRMS/MS, thus regaining the mutually supportive data that is typically lost through ambient ionization, such as UV data, retention time, and chromatographic separation. The pre-existing database of over 300 fungal secondary metabolites was implemented at least six weeks earlier in the drug discovery process by screening fungal cultures directly from the Petri dish. This new methodology sacrificed none of the data that would be lost using other ambient techniques. Aim 3 was achieved by exploring a suite of analytical techniques to characterize secondary metabolites in situ. Techniques such as post-column lithium infused chromatography, HRMS/MS fragmentation patterns, and mass defect filtering were all possible, since the droplet–LMJ–SSP incorporates liquid chromatography and traditional electrospray ionization. The structural class known as acetogenins was used to highlight this ability by differentiating between analogues and isomers, while elucidating their structures in situ.

Additional Information

Language: English
Date: 2016
Ambient Ionization, Fungi, Mass Spectrometry, Natural Products, Secondary Metabolites, Surface Sampling
Environmental chemistry
Natural products $x Research
Mass spectrometry

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