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OPSIN Taming the jungle of IUPAC

chemical nomenclature

Daniel Lowe, Peter Murray-Rust, Robert C Glen 8th September 2013

Indianapolis, ACS

4-[(19S,21R,26R,27S)-19,21-dihydroxy-27-methoxy-26-

methylnonacosyl]phenyl 3,6-di-O-methyl-α-D-glucopyranosyl-(1→4)-2,3-di-O-

methyl-α-L-rhamnopyranosyl-(1→2)-3-O-methyl-α-L-rhamnopyranoside

2

ol

What is chemical name to structure? (2S)- but 2- Amino 1- -

Stereochemistry locant substituent locant alk unsaturation suffix

an

NH2• 1

2

3

4

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• Identify documents by their chemical structures

• Assist with structure viewing

• Identify incorrect chemical names

• Extract reagent structures hence allowing reactions to be reconstructed from text

Uses of chemical name to structure

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Parsing

• Over 4000 discrete morphemes form the program’s vocabulary

(a morpheme is the smallest section of a word with meaning)

• These are grouped into 140 classes e.g.

• unsaturator (‘ene’)

• aminoAcidEndsInIne (‘tyros’)

• simpleSubstituent (‘amino’)

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Word Rule Example acetal Propanal dimethyl acetal additionCompound Carbon tetrachloride acidHalideOrPseudoHalide Cyanic chloride amide Nitrous amide anhydride Acetic anhydride biochemicalEster Adenosine 5'-triphosphate carbonylDerivative Propanone oxime divalentFunctionalGroup Diethyl ether ester Ethyl ethanoate functionalClassEster Acetic acid ethyl ester functionGroupAsGroup Cyanide glycol Ethylene glycol glycolEther Ethylene glycol monomethyl ether hydrazide Phosphoric hydrazide monovalentFunctionalGroup Ethyl alcohol multiEster Ethyl propyl methylphosphonate oxide Thiophene 1,1-dioxide polymer Poly(ethylene) simple Ethylbenzene substituent Chloro

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Supported chain nomenclature

Alkanes Heteroatom hydrides Heterogeneous heteroatom hydrides

dodectetractkiliane pentaphosphane disilazane

Trivial acids

butyric acid

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Supported ring nomenclature Monocyclic spiro

dispiro[4.2.4.2]tetradecane

Hantzsch-Widman

1,3,5-triazine

furo[3,2-b]thieno[2,3-e]pyridine 2,2':6',2''-terpyridyl

Fused ring Ring assembly

Von Baeyer

tricyclo[2.2.1.12,5]octane

Polycyclic spiro

spiro[piperidine-4,9'-xanthene]

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Structural assembly nomenclature Conjunctive nomenclature

benzeneethanol

Substitutive nomenclature

2,4,6-trinitrotoluene

Additive nomenclature

methylsulfonyl

Multiplicative nomenclature

4,4'-methylenedioxydibenzoic acid

Functional class nomenclature

ethyl alcohol

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Structural modifications

Heteroatom replacement

1-thia-4-aza-2,6-disilacyclohexane

Unsaturation

hexa-1,3-dien-5-yne

Hydro, dehydro, indicated hydrogen and added hydrogen

2,7-dihydro-1H-azepine

Functional replacement Suffixes including

infixed suffixes

methanedithioic acid 1-chloro-2,4-

diimidotricarbonic acid

Lambda convention

2λ6-trisulfane

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Bridges and stereochemistry Bridges

4a,8a-propanoquinoline

E/Z stereochemistry

(Z)-2-chloro-but-2-ene

Relative cis/trans stereochemistry

trans-2,6-dimethyl-2,6-dihydronaphthalene

R/S stereochemistry

(1R,3S)-3-amino-3-methylcyclohexanol

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Miscellaneous nomenclature

1,3-xylene

Groups with indeterminately positioned structural features

Charge and oxidation numbers

methylmercury(1+) or methylmercury(II)

“per-nomenclature”

2-deoxy-ᴅ-ribose

Subtractive nomenclature

perhydroanthracene

perchlorobenzene

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Polymer nomenclature

poly[(benzo[1,2-d:4,5-d']bis[1,3]thiazole-2,6-diyl)-1,4-phenyleneoxy-1,3-phenylene(1,3,5,7-tetraoxo- 1,2,3,5,6,7-hexahydrobenzo[1,2-c:4,5-c']dipyrrole-2,6-diyl)-1,3-phenyleneoxy-1,4-phenylene]

Structure-based polymer nomenclature

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Domain specific nomenclature

Steroid nomenclature

17β-Hydroxy-8α,9β,10α-androst-4-en-3-one

ʟ-leucinamide

Amino acid

cyclo(ᴅ-alanyl-ʟ-phenylalanyl) ʟ-arginyl-O-phosphono-ʟ-seryl-ʟ-alanyl-ʟ-proline

Oligopeptide Cyclic peptide

guanylyl(3'-5')uridine 3'-monophosphate

Nucleotide nomenclature

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Carbohydrate nomenclature (acyclic)

ᴅ-gluco-hexose or ᴅ-glucose (preferred)

ʟ-ribo-ᴅ-manno-nonose

• Carbohydrates are defined using configurational prefixes that each specify the stereochemistry for between 1 and 4 stereocentres

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Carbohydrate derivatives

• These carbohydrate chains can then be algorithmically modified by suffixes

ᴅ-glucose

ᴅ-glucitol

ᴅ-glucaric acid

ᴅ-gluconic acid

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Carbohydrate nomenclature (cyclic)

α-ᴅ-glucopyranose

2,7-anhydro-D-glycero-β-D-galacto-oct-2- ulopyranosonic acid

ᴅ-glucose

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Carbohydrate nomenclature (oligosaccharides)

β-ᴅ-Fructofuranosyl α-ᴅ-glucopyranoside β-ᴅ-glucopyranosyl-(1→3)-β-ᴅ-glucopyranosyl-(1→3)-ᴅ-glucopyranose

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Fused ring nomenclature

• All fused ring nomenclature is processed algorithmically e.g. even benzofuran is constructed from benzene and furan rather than being a trivial name

• For example:

benzo[b]cycloocta[jk]fluorene

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6 6 6

5

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Fused ring nomenclature (numbering)

• Transform to an idealised grid aligned along the longest row of rings

• Apply quadrant rules e.g. favour most rings in upper right quadrant

8 6

6 6 5 6 6 6 5 8

8 6 6 5 6 6 6 6 5 8

6 6 5 6 8 6 6 5 8 6

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Fused ring nomenclature (numbering)

• Atoms numbered in ascending order from upper rightmost ring

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6 6 5 8 Peripheral numbering rules used to

choose grid layout that gives the

best numbering

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Beyond IUPAC: CAS index name un-inversion

CAS Index Name IUPAC name

benzene, ethyl- ethylbenzene

Disulfide, bis(2-chloroethyl) Bis(2-chloroethyl) disulfide

Benzoic acid, 4,4’-methylenebis[2-chloro- 4,4'-Methylenebis[2-chlorobenzoic acid]

Phosphoric acid, ethyl dimethyl ester ethyl dimethyl phosphate

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Beyond IUPAC: Correcting missing spaces

tert-butylacetate tert-butyl acetate

tert-butyl-4-vinylperbenzoate

No locant and perbenzoate has more

than one non-degenerate hydrogen

diethylcarbonate

Has no substitutable hydrogen

Ethylacetate

non-ester would be butanoate or butyrate!

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Performance on machine-generated names

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

ACD/Name 12.02Names

ChemBioDraw13Names

Lexichem 2.1 Names Marvin 6.0.2 Names

No Result

Constitutional Discrepancy

Stereochemical Discrepancy

Correctly Interpreted

30,000 structures randomly selected from PubChem

used as input to machine-generate names

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Performance on unique names from US patent headings

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What’s not supported

• Parsing of generic chemical names

• E.g. 2- or 3- alkylsubstitutedbenzofurans

• Advanced inorganic nomenclature e.g. coordinate bonding

• Some natural product nomenclature

• Advanced stereochemistry e.g. pseudo asymmetric stereo centers, axial stereochemistry etc.

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Usage Batch conversion on the

command line

RESTful web service

(opsin.ch.cam.ac.uk)

NameToStructure nts = NameToStructure.getInstance(); String chemicalName = "acetonitrile"; String smiles = nts.parseToSmiles(chemicalName);

Java API

java -jar opsin-1.5.0-jar-with-dependencies.jar -osmi input.txt output.smi

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Who is using OPSIN? Commercial software

Cinfony

(interface to

Python)

Many text mining efforts

Workflows Web services

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Conclusions

• OPSIN combines high recall, precision and speed of execution

• Recent improvements have significantly improved coverage of biochemical nomenclature

Visit opsin.ch.cam.ac.uk to try it out and download!

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OPSIN: Taming the jungle of IUPAC chemical nomenclature

daniel@nextmovesoftware.com

For more information see:

Chemical Name to Structure: OPSIN, an Open Source Solution

J. Chem. Inf. Model., 2011, 51 (3), pp 739–753

Extraction of chemical structures and reactions from the literature (https://www.repository.cam.ac.uk/handle/1810/244727)

Acknowledgements

Albina Asadulina

Rich Apodaca

Peter Corbett

Roger Sayle

Funding