Identification of “Known Unknowns” Utilizing Accurate Mass Data and Chemical Abstracts Service Databases

Abstract

In many cases, an unknown to an investigator is actually known in the chemical literature. We refer to these types of compounds as "known unknowns." Chemical Abstracts Service (CAS) Registry is a particularly good source of these substances as it contains over 54 million entries. Accurate mass measurements can be used to query the CAS Registry by either molecular formulae or average molecular weights. Searching the database by the web-based version of SciFinder is the preferred approach when molecular formulae are available. However, if a definitive molecular formula cannot be ascertained, searching the database with STN Express by average molecular weights is a viable alternative. The results from either approach are refined by employing the number of associated references or minimal sample history as orthogonal filters. These approaches were shown to be successful in identifying "known unknowns" noted in LC-MS and even GC-MS analyses in our laboratory. In addition, they were demonstrated in the identification of a variety of compounds of interest to others.

Identification of “Known Unknowns” Utilizing Accurate Mass Data and ChemSpider

“…The experimental detail, including calibrations, typical chromatographic separations, and sample preparations were previously described in detail [1]. Briefly, the accurate mass electrospray LC/MS/UV-Vis (ultraviolet-visible) data were obtained on a LCT time-of-flight mass spectrometer (Waters Corporation, Milford, MA, USA) equipped with a LockSpray secondary ESI probe.…”

“…W e have previously demonstrated [1] that searching the Chemical Abstracts Service (CAS) Registry employing accurate mass mass spectrometry data is a very useful approach for the identification of "known unknowns." We define a "known unknown" as a compound which is unknown to the investigator but is known in the chemical literature, a reference database, or an internet resource.…”

“…There is a particular need for additional approaches for the identification of "known unknowns" found in liquid chromatography/mass spectrometry (LC/MS) analyses because the availability of computer searchable collisioninduced dissociation (CID) mass spectral databases is limited for LC/MS [1] compared with that of electron ionization (EI) mass spectral databases. We have found that searching "spectraless" databases such as the CAS Registry [1] by elemental compositions or molecular weights, then sorting the hit list in descending order by the number of associated references to be very effective in the identification of "known unknowns."…”

“…We have found that searching "spectraless" databases such as the CAS Registry [1] by elemental compositions or molecular weights, then sorting the hit list in descending order by the number of associated references to be very effective in the identification of "known unknowns." The most likely candidates are normally brought to the top of the list where they can be further scrutinized by employing additional data.…”

“…In our current work, the ChemSpider interface was modified [2] such that the initial search results can be sorted by the number of references associated with an entry. The approach was then evaluated with a wide variety of compounds and compared with previous results obtained with the CAS Registry [1].…”