Developing CAS Products for Substructure Searching by Chemists. Linda Toler

Transcription

1 Developing CAS Products for Substructure Searching by Chemists Linda Toler

2 Developing CAS Products for Substructure Searching Evolution of the CAS Registry Development of substructure searching for CAS products Future challenges 2

3 Evolution of the CAS Registry 3

4 Names and MFs Evolution of the CAS Registry Fragment Codes and Linear Notations 4

5 Building the CAS Registry Register Number Dyson linear notation Late 1950 s 5

6 Building the CAS Registry Dyson linear notation Registry I Morgan Connection Table

7 Sample of a CAS Connection Table CAS Registry Number: Rank # : Atom : C C C C C C C C C O C C C C C Bond to: Bond is: * -* -* -* =* -* -* =* -* -* -* RC -* RC -* RC -* Mol Form: C14 H20 O o o o 7

8 Building the CAS Registry Dyson linear notation Registry I Morgan Connection Table Covered organic molecules -CAS Registry Number - Normalized ring bonds 8

9 Building the CAS Registry Dyson linear notation Registry I Morgan Connection Table Registry II Covered all compound classes - Standardized stereo descriptors - Normalized tautomer bonds 9

10 Building the CAS Registry Dyson linear notation Registry I Morgan Connection Table Registry II Registry III Streamlined internal handling and display of connection table information 10

11 CAS Registry Handles New Chemistry Superconducting substances of the 1980s registered ranges of element compositions registered non-stochiometric compositions RN REGISTRY CN Barium calcium mercury rhenium oxide (Ba4Ca1.5Hg2Re0.5O8.5) (9CI) (CA INDEX NAME) MF Ba. Ca. Hg. O. Re AF Ba4 Ca1.5 Hg2 O8.5 Re0.5 Component Ratio Component Registry Number ==============+====================+=================== O Ca Ba Re Hg

12 CAS Registry Handles New Chemistry Textual descriptions of stereochemistry became outdated and difficult to use Upgraded connection tables to include stereo parity RN REGISTRY CN Benzeneethanol,.beta.-[(2-furanylmethyl)[(1R)-1-methyl-2- propynyl]amino]-, (.beta.r)- (9CI) (CA INDEX NAME) Absolute stereochemistry. 12

13 CAS Registry Handles New Chemistry Emphasis on biomolecules mushroomed in the 1990 s Macromolecules represented via one letter codes for their basic building blocks RN REGISTRY CN G protein-coupled receptor 35 (mouse fragment) (9CI) (CA INDEX NAME) FS PROTEIN SEQUENCE SQL 93 SEQ 1 AHMVWANLAV FVICFLPLHV VLTVQVSLNL NTCAARDTFS RALSITGKLS 51 DTNCCLDAIC YYYMAREFQE ASKPATSSNT PHKSQDSQIL SLT 13

14 CAS Registry Today World s Largest, Most Diverse Substance Collection "Organic" 45% >32,400,000 records Sequences 43% "Inorganics" 2% Polymers Coordination 3% compounds 5% Alloys 2% 14

15 CAS Registry Today Know for the Quality and Integrity of Its Structural Information <Pictures of CAS Registry staff> 15

16 CAS Registry Today An International Resource for Substance Identification CAS Registry Numbers are used throughout the world to identify substances Databases Handbooks Government regulatory agencies Consumer products 16

17 CAS Registry Today Largest publicly available structure searchable compound collection Biosequences >13.9M Connection Tables >18.3M 17

18 Substructure Searching in the CAS Registry 18

19 Substructure Searching Can Mean Different Things Compounds with structures answers contain specified structural characteristics Alloys and non-stochiometric inorganics answers are compounds of various composition ranges Protein and nucleic acid sequences answers are sequences containing the same string of building-block residues 19

20 Substructure Searching Can Mean Different Things Compounds with structures answers contain specified structural characteristics 20

21 What Should a Good Substructure Search System Offer? Query Input Easy-to-use query input mechanism Flexible query definition options -C; -CH3; R=Me, Et, or n-pr; Ak Retrieval Quick, comprehensive retrieval of all matching compounds Tools for dealing with registration idiosyncracies 21

22 Query Input Methods Evolved Over Time Screens Commands Drawing 22

23 Query Input via Screens => SCREEN 1867 AND AND 745 AND 1033 AND 1139 AND 1142 AND 1707 AND TR DDDDDD 42 AS C-C*C*C-C-O 1199 AA C -1C -1O -2O 745 BS A *2A *1A *1A *1A *1A *1A 23

24 Query Input via Commands => STR :GRAPH R6, 1 C1, 3 C1, 4 C3, 5 C1, 6 C1, 9 C1 :NODE 8 OH, O, AK :BOND ALL S, D :RSP I, CON E1, DIS 2 7 O 1 C 3 OH 8 C C 13 6 Ak C 5 4 C 9 C C O Ak Ak 12 O 14 => STR :GRAPH R6, 1 C1, 3 C1, 4 C3, 5 C1, 6 C1, 9 C1 :NODE 8 OH, O, AK :BOND ALL S, D :RSP I, CON E1, DIS 24

25 Query Input Offline via Drawing 25

26 What Should a Good Substructure Search System Offer? Query Input Easy-to-use query input mechanism Flexible query definition options -C; -CH3; R=-CH3, Et, or n-pr; Ak Retrieval Quick, comprehensive retrieval of all matching compounds Tools for dealing with registration idiosyncracies 26

27 The CAS Substructure Search System Evolved Over Time Development of Prototype SSS system 1960 s Substructure searching via screens 1980 Substructure searching via structure diagrams

28 Substructure Searching Is a Two-step Process Structure Compilation Screen Generation Screen Search Candidate Answers Iterative Search 28

29 The CAS Substructure Search System Evolved Over Time Development of Prototype SSS system Substructure searching via screens Substructure searching via structure diagrams Substructure searching extended to Markush 1960 s Query structure: C Ak???? Markush specification: R= unsaturated alkyl of 1-4 carbon atoms R = methyl, ethyl, or n-propyl 29

30 What Should a Good Substructure Search System Offer? Query Input Easy-to-use query input mechanism Flexible query definition options -C; -CH3; R=-CH3, Et, or n-pr; Ak Retrieval Quick, comprehensive retrieval of all matching compounds Tools for dealing with registration idiosyncracies 30

31 Structural Representations Present Search Challenges Salts 31

32 Structural Representations Present Search Challenges Enol-keto tautomers 32

33 Structural Representations Present Search Challenges Pyrazoles 33

34 CAS Designed Search Tools/Systems to Address Structuring Conventions Query input tools to allow for all relevant structural characteristics Algorithms that handle structural representation conventions 34

35 STN Searchers Have a Variety of Tools To Allow for Different Structural Representations Unspecified bonds Connectivity Answers: 35

36 SciFinder Search Algorithms Handle Many Structure Conventions 36

37 What Should a Good Substructure Search System Offer? Query Input Easy-to-use query input mechanism Flexible query definition options -C; -CH3; R=-CH3, Et, or n-pr; Ak Retrieval Quick, comprehensive retrieval of all matching compounds Tools for dealing with registration idiosyncracies 37

38 What Does the Future Hold? 38

39 Customers Want More! Chemical substance retrieval Similar structures Shape matching Converting information into knowledge Tools for discovering structural relationships Tools for mining the diversity in the CAS Registry for relevant substances 39

40 What Does the Future Hold? "To remain relevant to the work of scientists in the twenty-first century., CAS information technology must keep pace with the evolution of the chemical sciences, including related biological sciences, and remain adaptive enough to accommodate the unexpected and exciting developments that undoubtedly lie ahead." From: Chemical Abstracts Service Information System", Encyclopedia of Computational Chemistry, John Wiley & Sons, November

41 Acknowledgements Weisgerber, D. W. (1977) Chemical Abstracts Chemical Registry System: History, Scope, and Impacts. Journal of the American Society for Information Science 48(4) p Fisanick, W., Amaral, N.J., Metanomski, W.V., Shively, E.R., Soukup, K.M., Stobaugh, R.E. (1998) Chemical Abstracts Information System. Encyclopedia of Computational Chemistry p