1. Advanced Structure Searching in Reaxys using Marvin JS
Jim Rinker, Reaxys Accounts Development Manager, Elsevier
Chemaxon User Group Meeting – 4/12/18

2. A summary of today’s presentation
Overview
A summary of today’s presentation
Over the past 10 years the amount of chemical reactions and substances in databases such as Reaxys and SciFinder have grown exponentially. The challenge for chemical information tools has shifted from having enough representation in the chemistry space to refining and filtering structure and reaction searches to find the exact substances or reactions one is seeking. This presentation will highlight the advanced structure and reaction search features that Marvin JS provides to allow the searcher to perform more complex structure searches in the Reaxys environment. Examples searches and resulting hit sets will be presented.

3. What is Reaxys? Find Organize Segregate
Reaxys allows researchers to search for chemistry related information via four broad categories
Reactions, substances, properties, suppliers
Substances, bioactivities, animal models, ADME, toxicology
Reaction searching
Substance Searching
Document Searching
Bioactivity Searching
Find
Organize
Segregate

4. Brief Reaxys Overview
General overview of Reaxys features and functionality
Batch structure search
Advanced search
Basic search
Reaxys advanced algorithm recognizes concepts, interprets what information is being sought, and returns result set choices for the searcher
Interprets a search as either a structure or reaction search and returns result set choices for the searcher

5. How Reaxys interprets a structure search
Brief Reaxys Overview
How Reaxys interprets a structure search

6. How Reaxys interprets a text based topic search
Brief Reaxys Overview
How Reaxys interprets a text based topic search

7. Advanced search capabilities are realized via the query builder
Brief Reaxys Overview
Advanced search capabilities are realized via the query builder
One can build complex queries from all available Reaxys search fields
One can use Boolean operators to combine fields in a number of ways
One can search for and display information based on type
In addition to individual fields, Reaxys has a number of pre-built forms intended to aid the searcher in finding complex datasets
The history allows one to combine hit sets together using Boolean operators

8. Marvin JS is embedded into the Reaxys search environment
Brief Reaxys Overview
Marvin JS is embedded into the Reaxys search environment
Marvin JS is embedded into the Reaxys environment
In addition to Marvin, Reaxys provides a number of search features to include or exclude broad substance categories

9. Search Examples

10. Frustrations in structure searching
How to find ONLY the reactions you want!
Selective Oxidation
Search gives too many erroneous results
Example of desired transformation

11. Frustrations in searching
Marvin JS provides the necessary features to find ONLY the reactions you wanted!
Lock substitution
Define topology
Filter for specific reagents
Further refinements can be made by using the filters in the Reaxys environment
1131 RXN’s vs in original search
A review of all available features in Marvin JS will be presented later!

12. Moving from a general to a specific search
An example of knowing how to employ specific search strategies
7252 Reactions
Position variation, ring expansion,
R groups, atom lists, Reaxys generics
Atom Mapping
Fischer Indole
434 Reactions
One can expand from a specific transformation to general methodology by defining a reaction center with no SM
808 Reactions
61 Reactions
One can exclude specific transformations by blocking where the ring system is being formed

13. Moving from a general to a specific search
The final result set provides a diverse set of indole ring formations methodologies

14. Moving from a general to a specific search
Knowing how and when to use multiple advanced features in Marvin JS
Further refinement of any result set can be done by using filters provided in the Reaxys environment

15. Expanding on methodologies
One can define a reaction center to expand on multiple methods for making a specific ring system
Multistep via hydrazine (Fischer Indole)
Palladium catalyzed cyclization
Search for exact same product without constraint of hydrazines as starting material (54 reactions vs. 11 with hydrazine as starting material)
Rearrangement

16. Fragment based reaction searching
Find selective transformations using a fragment search

17. Combining marvin and Reaxys features
Some complex searches require the combined features of Marvin and Reaxys
Find all heterocyclic variations of highlighted ring while excluding phenyl rings. Substructure search will return both heterocycles and phenyl ring systems
One can use the query builder in Reaxys to search for multiple structures and exclude hit sets leaving only heterocycles

18. Combining marvin and Reaxys features
Some complex searches require the combined features of Marvin and Reaxys
Current search returns too many similar heterocycles

19. Combining marvin and Reaxys features
Some complex searches require the combined features of Marvin and Reaxys
One can use the group function to exclude multiple structure types from the intended hit set

20. Combining marvin and Reaxys features
Some complex searches require the combined features of Marvin and Reaxys

21. Marvin js overview

22. Marvin Sketch – A robust structure drawing tool
Name to Structure
Select Tool
Common Templates
Reaxys Generics
Add Explicit hydrogens
Bond Types
Atom Lists
Determine Stereochemistry
Generic Atoms
Clean Structure
Repeating Units
R-Group Selector
R-Group Attachment
Reaction Arrow/Atom Mapping

23. Marvin Sketch – A robust structure drawing tool
Set or lock substitution

24. Marvin Sketch – A robust structure drawing tool
Click on atom or bond, it will highlight in
green as shown, right click
Click on atom or bond properties
to find further options

25. In summary - in marvin JS in reaxys you can……..
Interesting and advanced searches for reaction and structure searching in Reaxys
•Do a fragment based substructure or reaction search using two or more fragments
•Search for a “product only” by defining the reaction center
•Define atom lists, atom “not” lists, generic groups, and R groups
•Lock substitution on an atom by using substitution count
•Lock a ring to prevent additional ring systems
•Find a specific isotope (ex.C13, H3)
•Define a bond as being either in a ring or chain
•Create a position variation bond at multiple positions in a molecule
•Define a variable ring size or chain length
•Define and search for stereospecific and/or regiospecific molecules
•Find tautomer's of a substance where a tautomer is possible
•Include or exclude salts, mixtures, isotopes, or radicals
•Use the query builder to combine structure or reaction searches
•Use filters in the results to refine substance or reaction searches
•Use “find similar” to expand on a reaction of interest in the results set
Thank You! (for your time and attention)

26. For a copy of this presentation please email Jim rinker: j
For a copy of this presentation please Jim rinker:

27. Additional search examples

28. Using a similarity search to find reactions
Within a reaction hit set one can expand on a particular reaction of interest using “find similar”

29. Using a similarity search to find reactions
Reaxys performs a similarity search that incrementally widens the scope of the search

30. Using a similarity search to find reactions
One can see by using “wide” that one finds a general reaction for this specific transformation

31. Using a similarity search to find reactions
Expanding to “widest” can lead to major modifications in the methodology and serendipitous chemistry

32. Using a similarity search to find reactions
Not only do we now see expansion on diversity but new ring systems using similar methodology

33. Using the import function for batch query
One can do a batch structure search using the import function for an SD or smiles file
Batch structure search

34. Using the import function for batch query
Smiles strings provide a robust mechanism to search for fragments

35. Using the import function for batch query
One can view the execution details to review the hits for each individual search

36. Using the import function for batch query
One can save the search to use as a filter file for future searches

37. Using the import function for batch query
One can search for monomers and subtract unwanted molecules from the filter file

38. Using the import function for batch query
One can search for monomers and subtract unwanted molecules from the filter file
Indoles
Reactive fragments

39. Using the import function for batch query
One can then use the filters to find only products available for purchase

40. Using the import function for batch query
Further refinements can be made by identifying more unwanted functionality

41. aDvanced use of the r-group function
The R-group function can be used to create complex searches

42. aDvanced use of the r-group function
The R-group function can be used to create complex searches
HAR
Aryl
HAR
Aryl
Vs.

43. Marvin JS allows you to create quite complex Markush like searches

44. Marvin JS allows you to create quite complex Markush like searches

45. Markush like searches
There are certain limitations in searching with generics
This query won’t run! A generic can only have one attachment point!