RInChI. International Chemical Identifier for Chemical Reactions (RInChI) Guenter Grethe, Jonathan Goodman, Chad Allen

Transcription

1 International Chemical Identifier for Chemical Reactions () Guenter Grethe, Jonathan Goodman, Chad Allen 248 th ACS National Meeting) August 10 14, 2014, San Francisco, CA

2 Working Group and Requirements The IUPAC Division VIII Subcommittee and the InChI Trust are working on widening the applicability of the InChI identifier by creating several projects to facilitate the extension ne of the projects is the development of an International Chemical Identifier for Reactions () to describe chemical reactions in a unique machine-readable character string based on the InChI algorithm suitable for data storage and indexing A working group was established in 2010 to define the requirements. The working group decided to initially concentrate on organic reactions and include only the basic structural elements of a reaction: reactants, products, reagents, solvents and catalysts. Analogous to InChI, the format should be a hierarchical, layered description of a reaction with different levels. Requirements: The program had to be able to generate a from a Rxnfile (actual or embedded in an RDfile) and regenerate a Rxnfile file from a. It should be able to handle multistep reactions. For testing purposes, a website with a small database (ca.3000 rxns) had to be created to generate and manipulate s. Furthermore, a program to generate Keys (compression of full string or of individual InChIKeys) had to be developed. Based on these requirements, a prototype was developed by Jonathan Goodman s group in Cambridge and completed in 2012

3 Format Three groups of molecules are described in the identifier, one group for each side of the arrow and one group of molecules which are above, below or on both sides of the arrow Each group is described as a list of InChIs which are sorted within a group Groups representing starting materials and products are sorted using the unix sort command. Valid s do not require all three groups to be present. Groups are separated by triple slashes; molecule InChIs within a group are separated by double slashes. Example: =0.02.1S/C8122/c (3-1)9-5-7(8)10-8/h6-7,1-52/t6-,7+,8- /m1/s1///c8143/c (6,7)10/h6-7,9-10,1-52/t6-,7+,8+/m1/s1//c8143/c (6,7)10/h6-7,9-10,1-52/t6-,7-,8+/m1/s1/d+ = label A B C = InChI of A = InChI of B = InChI of C + = directional label (d+ = left to right; d- = right to left; d= = equilibrium reaction 248 th ACS

4 Keys Long Keys (composite of individual InChIKeys) In long Keys all molecules in the reaction are encoded as separate InChIKeys and grouped similarly to the grouping of InChIs in s Keys consist of sequences of blocks of letters separated by hyphens First block (3 letters) = 1. letter is version identifier, next 2 letters identify the constituents InChIKeys Second block = hashed representation of any additional reaction layers taken as a whole Following blocks = groups of InChIKeys in same order as molecules in original Groups are separated by double hyphen Version A: + Version B: + ashed representation of additional reaction layers including directionality (F, B, E, U) 248 th ACS

5 Keys Short Keys Fixed-length hashed representation of s, produced from itself Version A: Groups of structures from are encoded as simple entities Disregarding layered character Version B: Separating directionality ashing constituent InChIs to preserve layered character Separating InChIs into 3 major parts (formula, connectivity, hydrogen, charge) and 4 minor parts (stereochemistry etc.)

6 Tools Website

7 website at Cambridge University th ACS

8 Generation of from RxnFile Skcfile + Rxnfile 248 th ACS

9 Re-generation of RxnFile/reaction from + Generated from Rxnfile 248 th ACS

10 1. 3, NaC 3, C 2 Cl C 5 5 N, C 2 Cl 2 =0.02.1S/C10163/c ( 3,12)6-9(7)13-8(2)11/h4-5,7,9,12,62,1-33/t7-,9+,10-/m0/s1//C463/c1-3(5)7-4(2)6/h1-23//C4/c1-2/h2,13//C4/c1-2/h2,13///C12186/c1-7-10(16-8(2)14)5-12(4,6-13)18-11(7)17-9(3)15/h6-7,10-11,52,1-43/t7-,10-,11+,12-/m1/s1//C13207/c1-8(12(17)18-5)11(19-9(2)15)6-13(4,7-14)20-10(3)16/h7-8,11,62,1-53/t8-,11-,13-/m1/s1///C55N/c /h1-5//C2Cl2/c2-1-3/h12//C23.Na/c2-1(3)4;/h(2,2,3,4);/q;+1/p-1//3/c1-3-2/d+

11 Generation of Multistep 1 C 3 2 C + + N 2 Et 3 N DMF C 3 N Generate individual s Copy into application box Enter in correct sequential order Calculate overall 2 3 N C 3 N E. Si 2 benzene LiAl 4, TF Pd-C, CN 4, Me N N =0.02.1S/C1925N3/c (22)19( (19)21) /h3-5,9-10,14,2,6-8,11-13,152,13/b20-14+///C34/c /h2-3,12//C79N/c /h1-5,6,82//C9143/c (11) (7)10/h7,2-62,13/d- =0.02.1S/C1721N2/c (15) (16(17)20) /h1-3,7-8,4-6,9-132///C1925N3/c (22)19( (19)21) /h3-5,9-10,14,2,6-8,11-13,152,13/b20-14+/d- =0.02.1S/C1019N/c (9) /h9,11-12,1-82/t9-,10- /m0/s1///c1721n2/c (15) (16(17)20) /h1-3,7-8,4-6,9-132/d-

12 Web application for the generation of overall reaction s verall =0.02.1S/C1019N/c (9) /h9,11-12,1-82/t9-,10- /m0/s1///c34/c /h2-3,12//c79n/c /h1-5,6,82//c9143/c (11) (7)10/h7,2-62,13//c1721n2/c (15) (16(17)20) /h1-3,7-8,4-6,9-132/d- N 2 verall reaction C 3 2 C + + N

13 Analytical Tools for Databases Ring analysis Stereochemical analysis

14 Searching for reaction partners in databases

15 utline of software package structure

16 Acknowledgements project developers - Jonathan Goodman and Chad Allen Working group - Colin Batchelor, Jonathan Goodman, Guenter Grethe, ans Kraut, Sandy Lawson, enry Matuszczyk, Martin Schmidt, Keith Taylor InChI Trust - Alan McNaught, Steve eller Financial support - IUPAC Division VIII Subcommittee (Working Group) Royal Society of Chemistry (Programming work) Reaction test set Elsevier, FIZ Chemie, InfoChem (1000 rxns each)