Accurate Mass Measurements: Identifying “Known Unknowns” using ChemSpider

15 Jun

Over the past few weeks the ChemSpider team has been working hard with James Little from the Eastman Chemical Company. We have been adding new capabilities to support Mass Spectrometry searches. I will detail these capabilities in a later blog post but for now I am pointing to the POSTER that Jim presented at ASMS. It was a real pleasure working with Jim. I met him many years ago when I worked at Eastman Kodak company and before Kodak divested Eastman Chemical (among many other things). Jim gave us great feedback, was exacting in his testing and a gracious collaborator even as we let deadlines slip because of many other distractions.


Accurate Mass Measurements: Identifying “Known Unknowns” using ChemSpider

In very many cases, an unknown to an investigator is actually known in the chemical literature. We refer to these types of compounds as “known unknowns.” ChemSpider is a particular good collection of “known unknowns” for the identification of compounds in commercial products, environmental matrices, etc. However, several modifications were necessary to refine the initial search results sorting with orthogonal filters such as the number of associated patents and references. Previously we described a similar approach using the CAS registry with either SciFinder or STN Express, but ChemSpider is a viable alternative and it is freely accessible to the public.Accurate mass GC-MS and LC-MS measurements were performed on mixtures using, respectively, either Waters GCT or LCT (LockSpray) instrumentation. MassLynx (Waters) elemental software was used to determine molecular formulae which were further refined by i-FIT for ranking to theoretical isotope distributions. Candidate structures were obtained by searching either molecular formulae or monoisotopic molecular weights with ChemSpider. Further data such as EI or MS/MS fragmentation, number of exchangeable protons, or sample history were used to identify the “known unknown.” The ChemSpider database of >25 million chemicals was searched by either molecular formulae or monoisotopic molecular weights to identify “known unknowns.” The latter is an attractive approach since no subjective restrictions on the elements, the range of elements, and the double bond equivalents are required prior the ChemSpider search to limit candidate compounds. Changes were made in the ChemSpider to refine the initial candidate list by number of associated references or patents. This tended to bring more promising candidates to the top of the list. The success of these approaches was evaluated with a group of 90 compounds from literature sources, internet sites, and American Society for Mass Spectrometry Conference presentations. Furthermore, the results were compared to similar methods employed searching the Chemical Abstracts Services databases.


About tony

Antony (Tony) J. Williams received his BSc in 1985 from the University of Liverpool (UK) and PhD in 1988 from the University of London (UK). His PhD research interests were in studying the effects of high pressure on molecular motions within lubricant related systems using Nuclear Magnetic Resonance. He moved to Ottawa, Canada to work for the National Research Council performing fundamental research on the electron paramagnetic resonance of radicals trapped in single crystals. Following his postdoctoral position he became the NMR Facility Manager for Ottawa University. Tony joined the Eastman Kodak Company in Rochester, New York as their NMR Technology Leader. He led the laboratory to develop quality control across multiple spectroscopy labs and helped establish walk-up laboratories providing NMR, LC-MS and other forms of spectroscopy to hundreds of chemists across multiple sites. This included the delivery of spectroscopic data to the desktop, automated processing and his initial interests in computer-assisted structure elucidation (CASE) systems. He also worked with a team to develop the worlds’ first web-based LIMS system, WIMS, capable of allowing chemical structure searching and spectral display. With his developing cheminformatic skills and passion for data management he left corporate America to join a small start-up company working out of Toronto, Canada. He joined ACD/Labs as their NMR Product Manager and various roles, including Chief Science Officer, during his 10 years with the company. His responsibilities included managing over 50 products at one time prior to developing a product management team, managing sales, marketing, technical support and technical services. ACD/Labs was one of Canada’s Fast 50 Tech Companies, and Forbes Fast 500 companies in 2001. His primary passions during his tenure with ACD/Labs was the continued adoption of web-based technologies and developing automated structure verification and elucidation platforms. While at ACD/Labs he suggested the possibility of developing a public resource for chemists attempting to integrate internet available chemical data. He finally pursued this vision with some close friends as a hobby project in the evenings and the result was the ChemSpider database ( Even while running out of a basement on hand built servers the website developed a large community following that eventually culminated in the acquisition of the website by the Royal Society of Chemistry (RSC) based in Cambridge, United Kingdom. Tony joined the organization, together with some of the other ChemSpider team, and became their Vice President of Strategic Development. At RSC he continued to develop cheminformatics tools, specifically ChemSpider, and was the technical lead for the chemistry aspects of the Open PHACTS project (, a project focused on the delivery of open data, open source and open systems to support the pharmaceutical sciences. He was also the technical lead for the UK National Chemical Database Service ( and the RSC lead for the PharmaSea project ( attempting to identify novel natural products from the ocean. He left RSC in 2015 to become a Computational Chemist in the National Center of Computational Toxicology at the Environmental Protection Agency where he is bringing his skills to bear working with a team on the delivery of a new software architecture for the management and delivery of data, algorithms and visualization tools. The “Chemistry Dashboard” was released on April 1st, no fooling, at, and provides access to over 700,000 chemicals, experimental and predicted properties and a developing link network to support the environmental sciences. Tony remains passionate about computer-assisted structure elucidation and verification approaches and continues to publish in this area. He is also passionate about teaching scientists to benefit from the developing array of social networking tools for scientists and is known as the ChemConnector on the networks. Over the years he has had adjunct roles at a number of institutions and presently enjoys working with scientists at both UNC Chapel Hill and NC State University. He is widely published with over 200 papers and book chapters and was the recipient of the Jim Gray Award for eScience in 2012. In 2016 he was awarded the North Carolina ACS Distinguished Speaker Award.

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