Plenary Lecture:
“Mass Spectrometry Based Metabolomics to Identify Bioactive Components of Natural Product Mixtures”
Professor Nadja Cech, UNC Greensboro, Department of Chemistry and Biochemistry
The expansion of small molecule mass spectrometry into the –omics realm over the past decade has been both exciting and confounding. Orbitrap and Q-ToF mass spectrometers have enabled an unprecedented number of mass spectrometrists to access high resolving power data for complex mixtures. The challenge we now face is how to extract meaning from these datasets. The Cech laboratory works to address this problem as it relates to the field of natural products. In particular, we focus on two research areas related to this goal, (1) the application of biochemometrics to identify biologically active components from complex natural product mixtures, and (2) the use of mass spectrometry to extract mechanistic information when screening natural product mixtures. In this talk, specific examples will be presented of how these approaches are being used to identify small molecules that can serve as leads for the development of anti-infective therapeutics.
Student Lecture:
Matthew Campbell, Laboratory of Professor Gary Glish, UNC Chapel Hill, Department of Chemistry
Differential ion mobility spectrometry (DIMS) is a useful method for analysis of complex mixtures prior to mass spectrometric analysis because of its capability to separate mixture components and increase signal-to-noise and signal-to-background ratios on millisecond timescales. However, adding a DIMS device to the front end of an analysis can also alter the subsequent mass spectrometric analysis in several ways. One example is that adding a DIMS device can reduce the sensitivity of an analysis. This is due to ions becoming neutralized at the electrodes of the DIMS device, ion diffusion to the walls of the DIMS device, or inefficient transfer of ions from the DIMS device through the aperture of the mass spectrometer. This problem of transferring ions can be partially corrected by modifying the front end of the inlet capillary leading to the vacuum of the mass spectrometer. A bore drilled into the ion-sampling end of a commercial capillary creates a conical flare while the other end of the capillary remains unchanged. These flared capillaries allow for a greater number of ions from the DIMS device to be sampled relative to the precursor capillary. Another way a DIMS device can alter analysis is by removing charges from multiply charged ions. The average charge state observed in a mass spectrum of several proteins decreases when a DIMS device is used compared to the spectrum observed without the device. The average charge state further decreases as the length of the planar electrodes in the DIMS device increases, giving some insight into the mechanism for the charge stripping. Finally, the motion of the ions induced by the high electric field increases ion interaction with the carrier gas. This has been shown to induce fragmentation of ions as well as aid in desolvation when less volatile solvents are used.