Finding the Needle - Reaxys Structure Searching

Transcription

1 Finding the Needle - Reaxys Structure Searching Dr. Juergen Swienty-Busch 29. October 2015

2 Agenda Introduction What is Reaxys? Structure Searching Essentials Editors Substance Model Search Engine and Editors Structure Searching - Examples Simple Sophisticated Reaction Similarity

3 3 What are is Reaxys 2015? and Reaxys Medicinal Chemistry 2015? A Bioactivity Database >29 million experimental bioactivity data points A Bibliographic Database >50 million records (from ~16,000 journal titles plus records from key patent organisations) A Chemical Reaction Database >39 million single- and multistep reactions Reaxys & 2015 RMC 2015 A Substance Database >99 million substances (total integrated content) ~ 87 million substances (unique) A Property Database > 500 million experimental properties in > 400 fields in > 130 subject areas A Target Database targets incl. species information

4 And it can answer interesting questions like no other solution Reaxys in combination with Reaxys Medicinal Chemistry

5 Seamlessly connecting Bioactivity with Synthesis

6 Structure Searching Essentials

7 7 Supported Structure Editors Elsevier doesn t develop structure editors, but partners with vendors of most commonly used editors: Biovia: AccelrysDraw, MDL Draw, ISISDraw PerkinElmer: ChemDraw ChemAxon: MarvinSketch, MarvinJS Dotmatics: elemental EPAM: Ketcher InfoChem: ICedit

8 8 Java vs Java-free Google and FireFox announced to cease support for Java applets. What are the consequences? Java-based editors and links to stand alone editors will not work on affected browser versions anymore Solution: please switch to Java-free editors This will make Reaxys independent of Java (and its updates) All important search features are available in those editors They are continuously developed: we are in contact with vendors and your voice counts

9 9 Using Structure Editors Java-free Editors: available in Structure querylet or My Settings ChemAxon Marvin JS Dotmatics Elemental GGA Ketcher Java-based Editors: available in Structure querylet or My Settings ChemAxon MarvinSketch Stand-alone editors: available through My Settings (after user registration) Note: requires installation of a structure editor plugin ( 1_10.zip) Biovia: AccelrysDraw, MDL Draw, ISISDraw PerkinElmer: ChemDraw - Special note: requires PerkinElmer plugin available through SciStore free of charge: search for Reaxys ) InfoChem: ICedit

10 10 Differences between search capabilities and structure editor features While Elsevier doesn t develop structure editors, it has developed one of the best and fastest structure and reaction search engines CrossFire, the power house behind Reaxys This engine is optimized for the Reaxys substance model Editors are typically used not only for searching but also for publishing - Query features are often hidden in menus - Reaxys search features have to be translated or incorporated in customized versions - E.g. MarvinSketch: predefined generics dialog Reaxys Help explains the differences and ways to enter structure queries in various editors

11 11 Searching for Structures and Reactions Chemical Substance Model Single compound Structure Molecular Formula Name Name Component compound Compound List Amount Role Markush compound Markush Structure Modification Macroscopic Type Modification Macroscopic Type Role E.g. dope additive, carrier, layer/film Modification E.g. diamond, graphite, rutile, anatase etc. Type E.g. alloy, glass/ceramic, mineral, nano etc. Accessible through Structure and MF searching Accessible through Structure and MF searching of components Accessible through associations to examples 11

12 Structure Searching Examples

13 13 Structure Searching Examples The Structure Querylet and how to use/customize Reaxys search themes Simple Structure Queries Functions available outside editors As drawn, Family, Substructure, Similarity Stereochemistry Sophisticated Structure Queries Functions available inside editors Substitution counts R-Groups Predefined Generics Link nodes Position-variation bond Reaction searching: Atom mapping and more

14 Reaction Similarity Searching

15 15 Reaction Similarity Searching Example: key step in the synthesis of kempanes Creating a Butadiene for subsequent Diels-Alder

16 16 How does it work? Building a Reaction Molecule 1. Assign reaction center, unchanged groups and leaving groups +

17 17 Step 2: Build a Reaction Molecule from transition state and make it machine readable H Note: Protons are ignored. Just illustrative

18 18 Step 3: Build a searchable string and apply it to database content Similarity Searching Subsets and supersets of the TransForm string represent different spheres around reaction center Reaction centers only: highest level of generalization (widest) (RX.TRANS='0/88F62(0205) 80FB1( ) 40F61() 0CF41(05) 07F42(06) 01E*') Step by Step inclusion of further shells of atoms working out from the reaction center. With each shell included, the sets become more focused on the query reaction (and therefore smaller) It is fast: this example <2 sec

19 Examples in the Near Similarity shell (24 hits) 19

20 Thank you for your attention