This is a presentation given to a group of students at the UNC Eshelman School of Pharmacy. As chemists many of us want to resource information that is high quality, accurate and addresses our query. With the increasing proliferation of online chemistry resources it is very common for us to turn to these resources to source data. However, are resources such as Wikipedia, PubChem and the plethora of databases delivering information for metabolism, medicinal chemistry and synthetic chemistry trustworthy? Which of these resources, if any, should be treated as authorities? What is the most integrated approach to resource chemistry related data online? What approaches can be taken to validate the data that is available and how can individual scientists participate in helping to improve the content and quality of chemistry related data on the web. Antony Williams is ChemSpiderman. He started the ChemSpider database (www.chemspider.com) as a hobby to deliver a free platform for the community to source chemistry related data. Within three years the system was acquired by the Royal Society of Chemistry and now serves up close to 25 million chemical structures linked to over 400 data sources across the internet and offers individual scientists the opportunity to host and share their data with the community and to participate in data curation and annotation. Tony will share his experiences of building this chemistry database with a focus on data validation and curation and sourcing high quality data. During the presentation he will discuss ways to check chemical structure representations before submission to public systems for searching and provide an overview of chemical identifiers such as SMILES strings and the International Chemical Identifier (InChI) allows for the interlinking of resources. Attendees can expect to leave the session with a deeper understanding of utilizing the internet to resource chemistry related data.

1. Chemicals, Chemical Identifiers and
Navigating Through Databases
Antony Williams
UNC Chapel Hill, October 2010

2. 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

3. What is the Structure of Vitamin K?

4. MeSH
 A lipid cofactor that is required for normal blood
clotting. Several forms of vitamin K have been
identified: VITAMIN K 1 (phytomenadione) derived
from plants, VITAMIN K 2 (menaquinone) from
bacteria, and synthetic naphthoquinone provitamins,
VITAMIN K 3 (menadione). Vitamin K 3 provitamins,
after being alkylated in vivo, exhibit the
antifibrinolytic activity of vitamin K. Green leafy
vegetables, liver, cheese, butter, and egg yolk are
good sources of vitamin K

5. What is the Structure of Vitamin K1?

6. Wikipedia

7. What is the Structure of Vitamin K1?

8. CAS’s Common Chemistry

9. PubChem

11. “2-methyl-3-(3,7,11,15-tetramethylhexadec-2-
enyl)naphthalene-1,4-dione”
 Variants of systematic names on PubChem
 2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7S,11R)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7R,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7S,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E)-3,7,11,15-tetramethyl
 2-methyl-3-(3,7,11,15-tetramethyl
 2-methyl-3-[(E)-3,7,11,15-tetramethyl

12. Bioassay Data are Associated…

14. Lack of Stereochemistry

15. ChEBI – Manual Curation

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

20. 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

21. 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

22. 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

23. Stereo

24. Tautomers

25. 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

26. The InChI Identifier

27. 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

28. Multiple Layers

29. Tautomers – “Mobile H Perception”

30. Double Bond Orientation

31. Stereo

32. Checking for Stereochemistry

33. Checking for Stereochemistry
Use your drawing package!

34. Checking for Stereochemistry

35. Checking for Stereochemistry

36. Checking for Stereochemistry

37. InChIStrings Hash to InChIKeys

39. PubChem InChIKeys
 MBWXNTAXLNYFJB-NKFFZRIASA-N
 MBWXNTAXLNYFJB-LKUDQCMESA-N
 MBWXNTAXLNYFJB-UHFFFAOYSA-N
 MBWXNTAXLNYFJB-FAKCLFGASA-N
 MBWXNTAXLNYFJB-NIHVXYICSA-N (O-18 label)
 MBWXNTAXLNYFJB-ODDKJFTJSA-N
 MBWXNTAXLNYFJB-KSVLJPARSA-N
 MBWXNTAXLNYFJB-UDCSOKOMSA-N
 MBWXNTAXLNYFJB-JHBCSKSVSA-N
 MBWXNTAXLNYFJB-JXAKDHTRSA-N

40. PubChem InChIKeys
 MBWXNTAXLNYFJB-NKFFZRIASA-N
 MBWXNTAXLNYFJB-LKUDQCMESA-N
 MBWXNTAXLNYFJB-UHFFFAOYSA-N
 MBWXNTAXLNYFJB-FAKCLFGASA-N
 MBWXNTAXLNYFJB-NIHVXYICSA-N (O-18 label)
 MBWXNTAXLNYFJB-ODDKJFTJSA-N
 MBWXNTAXLNYFJB-KSVLJPARSA-N
 MBWXNTAXLNYFJB-UDCSOKOMSA-N
 MBWXNTAXLNYFJB-JHBCSKSVSA-N
 MBWXNTAXLNYFJB-JXAKDHTRSA-N

41. Databases and Standardization

42. Databases and Standardization

43. 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

44. Vancomycin

45. Vancomycin
Search Molecular
SKELETON
Search Full Molecule

46. Full Skeleton Search: 104 Hits

47. Full Molecule Search: 4 Hits

48. 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

49. Linked Data on the Web
Taken from: Rafael Sidis’ Blog

50. www.chemspider.com

51. Search for a Chemical…by name

52. Available Information…
 Linked to vendors, safety data, toxicity, metabolism

53. How do we build it?
 25 million chemicals from 400 data sources
 We deal in Molfiles or SDF files – including
coordinates
 We do rudimentary filtering – valence checking,
charge imbalance – prior to deposition
 We have our own “business logic” to standardize
 We use InChI to “aggregate tautomers” to one
record
 We link out to external sites where possible using
their IDs

54. Inherited Errors
 We have inherited errors from every database…
all public compound databases, including ours,
have errors
 “Incorrect” structures – assertions, timelines etc
 “Incorrect” names associated with structures
 Properties
 Links
 Publications
 ENORMOUS CHALLENGE

55. Compounds and Identifiers

56. Be careful searching by Name!
 Determining the correct structure by name
searching is difficult online! Good, not perfect
 Wikipedia
 ChEBI/ChEMBL
 ChemIDPlus
 ChemSpider
 Be VERY careful with MOST databases

57. 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!

58. Online Curation
 Online databases generally do NOT allow
curation or annotation
 If you find errors they stay there!
 ChemSpider is unique…immediate curation
 ChemSpider live demo following this lecture
 Searching
 Deposition and Curation
 ChemSpider SyntheticPages

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