Applications of artificial intelligence for chemical inference. VIII. Approach to the computer interpretation of the high resolution mass spectra of complex molecules. Structure elucidation of estrogenic steroids

Smith, Dennis H.; Buchanan, Bruce G.; Engelmore, Robert S.; Duffield, A. M.; Yeo, Adrian N. H.; Feigenbaum, Edward A.; Lederberg, Joshua; Djerassi, Carl

doi:10.1021/ja00772a005

Cited by 45 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The radical pyridinium ion at m/z 79 is of relatively low abundance. The ions at m/z 146, 172, 185 and 213 all appear to arise from E1, and all are also prominent in the EI spectrum of E1 [41]. Their formation has been discussed in detail in earlier reports [38][39][40][41].…”

Section: Lc-esi-ms/ms Of the Ps Derivatives Of E1 Ee2 Eq And Eqnmentioning

confidence: 88%

“…The ions at m/z 146, 172, 185 and 213 all appear to arise from E1, and all are also prominent in the EI spectrum of E1 [41]. Their formation has been discussed in detail in earlier reports [38][39][40][41]. The product ion spectrum of the PS derivative of EE2 shows a significant peak at m/z 374, assigned to [M+H−SO 2 ] + , while the radical EE2 cation at m/z 296 and the radical pyridinium ion at m/z 79 are of relatively low intensity (Fig.…”

Section: Lc-esi-ms/ms Of the Ps Derivatives Of E1 Ee2 Eq And Eqnmentioning

confidence: 99%

“…Based on extensive studies of the EI mass spectra of underivzatized estrogens and estrogen analogs [38][39][40][41], several fragmentation pathways were proposed by these previous authors, leading to the structural assignments for prominent ions depicted in Scheme 3. The peak at m/ z 254, one that is prominent in the MS 3 spectrum of the PS derivative of E2 but is of very low intensity in the EI spectrum of E2, is most likely formed by the loss of H 2 O from the C-17 hydroxyl group, a process that may be more favorable in CID rather than in EI-induced fragmentation.…”

Section: Lc-es-ms 3 Of the Ps Derivative Of E2mentioning

confidence: 99%

See 2 more Smart Citations

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Spink

2008

Analytical Biochemistry

View full text Add to dashboard Cite

Sulfonyl chlorides substituted with functional groups having high proton affinity can serve as derivatization reagents to enhance the sensitivity for steroidal estrogens in liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The most commonly used reagent for derivatization of estrogens for LC-ESI-MS/MS is dansyl chloride. In this study, we compared dansyl chloride, 1,2-dimethylimidazole-4-sulfonyl (DMIS) chloride, pyridine-3-sulfonyl (PS) chloride, and 4-(1H-pyrazol-1-yl)benzenesulfonyl (PBS) chloride for derivatization of 17β-estradiol (E2) prior to LC-ESI-MS/MS. The product ion spectra of the dansyl and DMIS derivatives were dominated by ions representing derivatization reagent moieties. In contrast, the product ion spectrum of the PS derivative of E2 and, to a lesser extent, the PBS derivative, showed analytespecific fragment ions. Derivatization with PS chloride was therefore chosen for further investigation. The product ion spectrum of the PS derivative of E2 showed intense ions at m/z 272, assigned to the radical E2 cation, and at m/z 350, attributed to the loss of SO 2 from the [M+H] + ion. Third-stage mass spectrometry of the PS derivative of E2 with isolation and collisional activation of the m/z 272 ion resulted in steroid C and D ring cleavages analogous to those observed in electron ionization mass spectrometry. The product ion spectra of the PS derivatives of estrone, 17α-ethinylestradiol, equilin, and equilenin showed similar estrogen-specific ions. Using derivatization with PS chloride, we developed an LC-ESI-MS/MS method with multiple reaction monitoring of primary and confirmatory precursor-to-product ion transitions for the determination of E2 in serum.

show abstract

Section: Lc-esi-ms/ms Of the Ps Derivatives Of E1 Ee2 Eq And Eqnmentioning

confidence: 88%

Section: Lc-esi-ms/ms Of the Ps Derivatives Of E1 Ee2 Eq And Eqnmentioning

confidence: 99%

Section: Lc-es-ms 3 Of the Ps Derivative Of E2mentioning

confidence: 99%

See 1 more Smart Citation

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Spink

2008

Analytical Biochemistry

View full text Add to dashboard Cite

show abstract

“…By the mid 1960’s the field had some surprising success and interest in the programming methods expanded. Edward Feigenbaum, Bruce Buchanan, Joshua Lederberg, and Carl Djerassi teamed up to develop an approach to use AI to interpret mass spectra of small molecules [26]. A goal was to use a heuristic approach to interpret mass spectra in much the same way a human would, and this idea was encoded in a software program called Dendral .…”

mentioning

confidence: 99%

Pivotal Role of Computers and Software in Mass Spectrometry – SEQUEST and 20 Years of Tandem MS Database Searching

Yates

2015

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Advances in computer technology and software have driven developments in mass spectrometry over the last 50 years. Computers and software have been impactful in three areas: the automation of difficult calculations to aid interpretation, the collection of data and control of instruments, and data interpretation. As the power of computers has grown so too has the utility and impact on mass spectrometers and their capabilities. This has been particularly evident in the use of tandem mass spectrometry data to search protein and nucleotide sequence databases to identify peptide and protein sequences. This capability has driven the development of many new approaches to study biological systems including the use of “bottom-up shotgun proteomics” to directly analyze protein mixtures.

show abstract

“…A number of earlier programs, such as the Heuristic DENDRAL program [7] and the PLANNER program [8], did incorporate simple 'Inference' or 'Planning' functions that could infer structural constraints from mass spectra, However, the approaches employed in those programs were limited in their versatility and in their applicability, especially by the close coupling of the spectruminterpretation process and structure-generation procedure. The lack of a clear boundary between data-dependent interpretive procedures and structure-generating functions makes it particularly difficult to extend such programs to handle new classes of compounds.…”

mentioning

confidence: 99%

Computer Assisted Structural Interpretation of Mass Spectral Data

Gray

Buchs

Smith

et al. 1981

Helvetica Chimica Acta

Self Cite

View full text Add to dashboard Cite

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

show abstract

Applications of artificial intelligence for chemical inference. VIII. Approach to the computer interpretation of the high resolution mass spectra of complex molecules. Structure elucidation of estrogenic steroids

Cited by 45 publications

References 0 publications

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Pivotal Role of Computers and Software in Mass Spectrometry – SEQUEST and 20 Years of Tandem MS Database Searching

Computer Assisted Structural Interpretation of Mass Spectral Data

Contact Info

Product

Resources

About