The Art of Structure Elucidation of Small Molecules Using Mass Spectrometry

Course Description:
Mass spectrometry is an indispensable tool for structure elucidation of small molecules. In many instances, tandem mass spectrum is all that analyst has to identify an unknown molecule. Therefore, being able to identify an unknown compound from mass spectrometric data is a valuable skill that any user of mass spectrometry should develop.

The overall motto of the course is “from spectrum to structure”. The course will provide step-by-step instruction on how to extract maximum information from mass spectrometric data to arrive at a reasonable structure. Participants will learn how to determine elemental composition, interpret tandem mass spectra, use spectral and compound databases and describe confidence level in compound identification. The emphasis of the course is on manual (“pencil and paper”) interpretation of data, though recently developed computational tools will also be briefly discussed. Approaches described in class will be illustrated by working through selected problems from the recent CASMI contests and The Lockdown Mass Spec Challenge. Drawing on the experience from these contests students will learn how to avoid most common mistakes in structure ID and obtain a solid grasp on the power and limitations of mass spectrometry for structure ID. The course will deal exclusively with data obtained from soft ionization methods; EI spectra will not be discussed. The practice problems will mostly deal with low molecular mass compounds (❮400Da) so that students can build their skills from the ground up. Though naturally occurring compounds will be featured prominently, examples of synthetic molecules will also be presented. After the course, the participants will be given a take-home problem set that can be used to further practice the methods learned in class. So, bring some paper and a pencil and let’s solve some spectra!

Target Audience:
Students and professionals working in the fields that require compound identification using mass spectrometry. Although the course leans towards identification of natural products, the approaches discussed in the class are applicable to other fields such as environmental or forensic sciences. Basic knowledge of mass spectrometry is expected.

Learning Objectives:
At the end of the course, students will be able to:
1. Confidently determine elemental composition from MS data
2. Propose a reasonable structure from tandem mass spectral data
3. Understand origins of major fragment ions in tandem mass spectra
4. Assign confidence in the structure proposal and understand limitations of MS for structure elucidation

Dejan Nikolic is a Research Associate Professor in the Department of Pharmaceutical Sciences, College of Pharmacy, UIC. His research interests include structure elucidation of natural products using mass spectrometry, determination of ADME properties of plant ingredients and development of new assays for drug discovery from plant sources. For the past several years he has been actively involved in the Critical Assessment of Small Molecules Identification (CASMI) initiative aimed at unbiased assessment of different approaches used in structure elucidation by mass spectrometry. He has authored and co-authored more than 100 publications and trained numerous undergraduate and graduate students both through classroom and hands-on training.