This is a short presentation given to chemistry students at Drexel University as a remote presentation. This was for the class of Jean-Claude Bradley.

1. ChemSpider and Traveling the Internet
via Chemical Structures
Antony Williams
Drexel University, November 2012

2. Compounds and Identifiers

3. Chemistry on the Internet
 Where do you source chemistry information?
 What can you trust online?
 How can you recognize potential issues?
 Cross-referencing and curating data

4. Molfiles (http://en.wikipedia.org/wiki/Chemical_table_file)

5. Molfiles
 10 9 0 0 1 0 0 0 0 0 1 V2000
 31.2937 -9.0366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
 26.6526 -9.0366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
 31.2937 -7.7066 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
 30.1161 -9.6877 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
 25.5096 -9.6877 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
 28.9731 -9.0366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
 27.8163 -9.7016 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
 26.6664 -7.7066 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
 32.4367 -9.6877 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
 30.1161 -11.0177 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
 3 1 2 0 0 0 0
 4 1 1 0 0 0 0
 9 1 1 0 0 0 0
 7 2 1 0 0 0 0
 5 2 2 0 0 0 0
 8 2 1 0 0 0 0
 6 4 1 0 0 0 0
 4 10 1 6 0 0 0
 7 6 1 0 0 0 0
 M END

6. Molfiles
 Molfiles are the primary exchange format between
structure drawing packages
 Can be different between different drawing packages
 Most commonly carry X,Y coordinates for layout
 Can support polymers, organometallics, etc.
 Can carry 3D coordinates

7. SMILES (http://en.wikipedia.org/wiki/SMILES)
 SMILES is a common format
 Can support polymers,
organometallics, etc.
 Does NOT carry X,Y or Z
coordinates for layout so
requires layout algorithms –
can be problematic!
 Generally different between
drawing packages

8. Stereo

9. Tautomers

10. SMILES
 ACD/Labs
 CC(C)CCC[C@@H](C)CCC[C@@H]
(C)CCCC(C)=CCC2=C(C)C(=O)c1ccccc1C2=O
 OpenEye
 CC1=C(C(=O)c2ccccc2C1=O)C/C=C(C)/CCC[C
@H](C)CCC[C@H](C)CCCC(C)C
 ChEMBL
 CC(C)CCC[C@@H](C)CCC[C@@H]
(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C

11. The InChI Identifier

12. InChI
 SINGLE code base managed by IUPAC –
integrated into drawing packages. No variability
as with SMILES
 InChI Strings can be reversed to structures –
same problem as with SMILES – no layout
 Well adopted by the community (databases,
publishers, blogs, Wikipedia) – good for searching
the internet

13. The InChI Standard

14. Tautomers – “Mobile H Perception”

15. Double Bond Orientation

16. Stereo

17. Checking for Stereochemistry

18. Checking for Stereochemistry
Use your drawing package!

19. Checking for Stereochemistry

20. Checking for Stereochemistry

21. Checking for Stereochemistry

22. InChIKeys
Search the Web by Structure

23. InChIs

24. Databases and Standardization

25. Databases and Standardization

26. InChI
 No support for polymers, organometallics
 Many option settings can lead to variability and
make integration across databases difficult –
FixedH option especially problematic
 “Slight” chance of collisions of InChIKeys
 VERY USEFUL FOR INTEGRATING THE WEB

27. Vancomycin

28. Vancomycin
Search Molecular Search Full Molecule
SKELETON

29. Full Skeleton Search: 104 Hits

30. Full Molecule Search: 4 Hits

31. Where is chemistry online?
 Encyclopedic articles (Wikipedia)
 Chemical vendor databases
 Metabolic pathway databases
 Property databases
 Patents with chemical structures
 Drug Discovery data
 Scientific publications
 Compound aggregators
 Blogs/Wikis and Open Notebook Science

32. www.chemspider.com

33. How do we build it?
 We deal in Molfiles or SDF files – with coordinates
 Valence checking, charge imbalance
 We have our own “business logic” to standardize
 InChI to “aggregate tautomers” to one record
 We link out to external sites using their IDs

34. Searches: The INTERNET
All ChemSpider and Internet searches are “simply algorithms”
but synonym searching is based on an assertion

35. Validated Names for Searching…

36. Validating structures
 Check for “full stereo” and use stereo descriptors
especially for checking!
 Check for quality of associated data sources
 Check against reference literature when available
– but it can be wrong
 Question EVERYTHING!

37. Contributing to The Quality of Data
What is the Structure of Vitamin K?

38. Contributing to The Quality of Data
What is the Structure of Vitamin K?
A lipid cofactor that is required for normal blood
clotting. Several forms of vitamin K have been
identified: VITAMIN K1 (phytomenadione)
derived from plants, VITAMIN K2
(menaquinone) from bacteria & synthetic
naphthoquinone provitamins, VITAMIN K3
(menadione).

39. What is the Structure of Vitamin K1?

40. CAS’s Common Chemistry

41. Wikipedia

42. Wolfram Alpha

43. DailyMed

45. ALL Different, ALL “Domoic Acids”

46. Thank you
Email: williamsa@rsc.org
Twitter: ChemConnector
Blog: www.chemspider.com/blog
Personal Blog: www.chemconnector.com
SLIDES: www.slideshare.net/AntonyWilliams