Finding the Needle -

Finding the Needle Reaxys® Structure Searching

Dr. Juergen Swienty-Busch

29. October 2015

Agenda • Introduction 

What is Reaxys?

• Structure Searching – Essentials   

Editors Substance Model Search Engine and Editors

• Structure Searching - Examples  

Simple Sophisticated

• Reaction Similarity

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is Reaxys What are Reaxys2015? and Reaxys Medicinal Chemistry 2015?

A Bibliographic Database >50 million records (from ~16,000 journal titles plus records from key patent organisations)

A Bioactivity Database

A Substance Database >99 million substances (total integrated content) ~ 87 million substances (unique)

A Target Database

Reaxys &2015 RMC 2015

>29 million experimental bioactivity data points

A Chemical Reaction Database >39 million single- and multistep reactions

12.700 targets incl. species information

A Property Database > 500 million experimental properties in > 400 fields in > 130 subject areas

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

Seamlessly connecting Bioactivity with Synthesis…

Structure Searching Essentials

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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

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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

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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) •  

Biovia: AccelrysDraw, MDL Draw, ISISDraw PerkinElmer: ChemDraw -



Note: requires installation of a structure editor plugin (http://supportcontent.elsevier.com/Support%20Hub/Reaxys/Documents/5915_PlugIn_ 1_10.zip)

Special note: requires PerkinElmer plugin available through SciStore free of charge: search for “Reaxys”)

InfoChem: ICedit

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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

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E.g. MarvinSketch: predefined generics dialog

Reaxys Help explains the differences and ways to enter structure queries in various editors

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Searching for Structures and Reactions – Chemical Substance Model Single compound Structure Molecular Formula

Component compound Name

Markush compound Markush Structure

Compound List Amount

Name

Role Modification Macroscopic Type

Modification

Role

Macroscopic Type

E.g. dope additive, carrier, layer/film

Modification

Type

E.g. diamond, graphite, rutile, anatase etc.

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

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Structure Searching Examples

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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

Reaction Similarity Searching

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

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

+

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Step 2: Build a “Reaction Molecule” from “transition” state and make it machine readable

H

Note: Protons are ignored. Just illustrative

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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(03070809)|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