This document discusses extending the International Chemical Identifier (InChI) to represent more complex chemicals. It provides examples of InChI and explains its current limitations in representing mixtures, polymers, organometallics, and other complex substances. Efforts underway by IUPAC to expand InChI capabilities to reactions, polymers/mixtures, and Markush structures are summarized. Challenges in representing complex real-world substances in databases and approaches taken by organizations like FDA and OpenPHACTS are also reviewed.

1. How can the International Chemical
Identifier (InChI) be extended to non-
trivial chemicals?
of the pillars of a
V. Tkachenko, A.J. Williams,
Y. Borodina, F. Switzer, T. Peryea, L. Callahan
ACS Philly August 2012

2. What is InChI

3. InChI Examples
CH3CH2OH
InChI=1S/C2H6O/c1-2-3/h3H,2H2,1H3
ethanol
InChI=1S/C6H8O6/c7-1-2(8)5-
L-ascorbic acid 3(9)4(10)6(11)12-5/h2,5,7-8,10-
11H,1H2/t2-,5+/m0/s1

4. InChI Structure

5. InChIKey
 The condensed, 27 character standard InChIKey is a hashed version of the full standard InChI (using the
SHA-256 algorithm)
 Designed to allow for easy web searches of chemical compounds
 InChIKeys consist of
 14 characters resulting from a hash of the connectivity information of the InChI
 followed by 9 characters resulting from a hash of the remaining layers of the InChI
 followed by a single character indication the version of InChI used
 followed by single checksum character
 InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2-5,10-
11,13,16,19-20H,6-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1
 BQJCRHHNABKAKU-KBQPJGBKSA-N
 Unlike InChI, InChIKey  CT only by lookup

6. Proliferation of InChI

7. Search by InChI

8. ChemSpider Google Search
http://www.chemspider.com/google/

9. What’s the catch?
 InChI has limitations
 InChI is ideal for
 Simple
 Static
 Well-defined graphs
 Real chemical substances can only be
approximated by such graphs

10. Limitations
 Non-trivial stereo (e.g. axial, planar)
 Non-trivial tautomers (e.g. ring-chain)
 Mixtures – full stereo is rarely known
 Polymers
 Markush structures
 Organometalics
 Inorganics
 Materials
 Reactions
 Etc

11. Chemical data complexity

12. Work in progress
 InChI Extensions: Under the guidance of IUPAC, several sub-teams are now
working on expanding InChI to new areas of chemical representation:
 Reaction InChI (RInChI): the reaction working group has completed its
recommendations, and work is ready to begin.
 Polymers/Mixtures: The polymers/mixtures working group also has
submitted its recommendations, and work to incorporate the new
representations should begin once version 1.04 is released.
 Markush: This project is the most complex undertaken to date. The initial
recommendations have been submitted, but financing of the work still
needs to be sorted out.
 But what do we do NOW???

13. Data
Validation
Standardization
Filtering
Componentization
Deposition Process
Deduplication
Mapping
data
Non-
redundant

14. ChemSpider Data Model

15. Organometallics

16. Mixtures or unknown stereo

17. Accelrys Enhanced Stereo

18. MOL V3000

19. Enhanced stereo and InChI…
 Unfortunately not supported
 Is it important?
 Now real-world examples…

20. FDA Substance Registration System

21. Stoichiometric and non-stoichiometric mixtures
Moiety 1:
Substance:
Moiety 2:

22. Substance: Moiety 1:
Moiety 2:
Moiety 3:
Moiety 4:

23. Substance: Moiety 1:
Moiety 2:
(undefined)

24. Moiety 1:
Substance:
(A)
Moiety 2:
(B)

25. D-glucose

26. SRS standardization approach
 Substance description
 Standardization module
 Moieties generator
 Normalization
 InChI[Key] generator
 Hash function f(InChIKeys, moieties)
 Unique ID
 Standard description

27. SRS TBD
 Markush
 Polymers
 Proteins
 Inorganics
 Materials

28. OpenPHACTS
 Open PHACTS is an Innovative Medicines Initiative
(IMI) – 3 years project
 To reduce the barriers to drug discovery in industry,
academia and for small businesses
 To build an open platform, integrating chemistry and
biology data from public domain resources
 Semantic web platform
 Open Standards, Open Data and Open Source

31. OpenPHACTS specifics
 Active/inactive ingredient
 Parent/child
 Sample/substance
 Misreferences (!!!)

32. ChemSpider Reactions

34. ChemSpider Reaction Challenges
 Deduplication
 Identification
 Deposition

35. Conclusions
 InChI is The Identifier
 InChI has its limitations
 InChI is work in progress
 InChI deficiencies can be hot-fixed

36. Acknowledgements
 RSC Cheminformatics group
 FDA SRS group
 OpenPHACTS consortium
 Software: InChI, GGA Software

37. Thank you
Email: tkachenkov@rsc.org
Blog: www.chemspider.com/blog
SLIDES:
http://www.slideshare.net/valerytkachenko16