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

3

What are Reaxys and Reaxys Medicinal Chemistry 2015?

A Bibliographic Database >50 million records

(from ~16,000 journal titles plus records from key patent

organisations)

A Substance Database

>99 million substances (total integrated content)

~ 87 million substances (unique)

A Chemical Reaction Database

>39 million single- and multi-step reactions

A Property Database

> 500 million experimental properties

in > 400 fields in > 130 subject areas

Reaxys & RMC 2015

A Bioactivity

Database >29 million experimental

bioactivity data points

A Target

Database 12.700 targets incl.

species information

What is Reaxys 2015?

Reaxys 2015

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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• 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

Supported Structure Editors

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• 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

Java vs Java-free

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• 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 (http://supportcontent.elsevier.com/Support%20Hub/Reaxys/Documents/5915_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

Using Structure Editors

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• 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

Differences between search capabilities and structure

editor features

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

11

Single compound Component compound

Markush compound

Markush Structure

Role

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

Type E.g. alloy, glass/ceramic, mineral, nano etc.

Modification

Macroscopic Type

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

Name

Amount

Compound List

Role

Modification

Macroscopic Type

Structure

Molecular Formula

Name

Accessible through

Structure and MF searching

Accessible through

Structure and MF searching of components

Accessible through

associations to examples

Structure

Searching

Examples

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• 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

Structure Searching Examples

Reaction Similarity

Searching

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• Creating a “Butadiene” for subsequent Diels-Alder

Reaction Similarity Searching

Example: key step in the synthesis of kempanes

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Building a “Reaction Molecule”

1. Assign reaction center, unchanged groups and leaving groups

How does it work?

+

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H

Step 2: Build a “Reaction Molecule” from “transition”

state and make it machine readable

Note: Protons are ignored. Just illustrative

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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)

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

It is fast: this example <2 sec

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Examples in the „Near“ Similarity shell (24 hits)

Thank you for your

attention