Computer Assisted Structural Interpretation of Mass Spectral Data

Abstract

SummaryAn interactive system of programs has been developed to assist in structure elucidation based on mass spectral data. The program relies on algorithms for generating all the structural isomers that constitute alternative explanations of the observed data and it associates relative plausibility values with the different isomers. The structure assembly part of the program allows for the use of overlapping substructural components, such as substructures inferred from the appearance of particular ion patterns in the spectrum of an unknown compound. Mass spectrum interpretation procedures used with this structure assembly process could exploit any form of spectrum-substructure correlation scheme. In this work, the emphasis has been on the use of detailed and class specific spectrum-substructure correlations. Applications of the program are illustrated by means of an example analysis of the mass spectra of a variety of marine sterols.Introduction. -We have recently described computer programs that can exploit structure-spectrum relationships to determine which of a set of plausible candidate structures provides the best rationalization of an observed mass spectrum [ 2 ] [3]. Though of general utility, these programs are limited by the prerequisite of a set of candidate structures. They can be most appropriately applied to problems where spectral and chemical evidence provide sufficient structural constraints for an isomer generating program [4] to produce a reasonably limited number of plausible candidates. Other applications are to cases where the unknown is related to a known structure and where plausible candidates can be generated by a program applying, for example, biosynthetic reactions 151.There remains considerable scope for the development of an approach in which mass spectral data provide substructural constraints for a structure generating

Computational mass spectrometry for small molecules

“…Molecular isomer generators such as MOLGEN [170,172], SMOG [173], and Assemble [174] have helped with the structural elucidation of unknowns for many years [175,176]. Recently, the open source software OMG was introduced [177].…”

New kids on the block: novel informatics methods for natural product discovery

“…Note that Kangas et al 19 do not claim these predictions to be "true" fragmentation rules, different from, say, the rules learned during the DEN-DRAL project, see for example. 9 ISIS predicts fragmentation spectra by simulating the behavior of ions in a linear ion trap using a kinetic Monte Carlo (KMC) simulation. First, the model linear ion trap is lled with replicates of the same ion with internal energies stochastically sampled from an ionization model.…”

Mass spectrometry

“…This approach permitted identification of six previously unknown metabolites. The high-resolution mass spectra were of considerable value in establishing respective fragmentation pathways which led, in turn, to information on the skeletal sites of metabolic attack (07).…”

“…Djerassi's group continues to make a major contribution to this area and recently they have applied their knowledge of fragmentation pathways of various steroid classes to a computerized investigation of marine sterols (07,OS). In this computer-aided approach to structure elucidation, plausible candidate structures are proposed (taking biosynthetic considerations into account) and then the major fragmentation pathways of these compounds are predicted and compared with spectra of the unknowns.…”