Incorrect InChI being generated for chemical structure

[amalik01]

I submitted this structure:

The correct InChI/InChIKEY for the structure is:

InChI=1S/C32H40O18/c33-10-20-22(38)24(40)26(42)29(48-20)47-16-6-7-17(19(37)9-16)18(36)8-3-14-1-4-15(5-2-14)46-30-27(25(41)23(39)21(11-34)49-30)50-31-28(43)32(44,12-35)13-45-31/h1-9,20-31,33-35,37-44H,10-13H2/b8-3+/t20-,21-,22-,23-,24+,25+,26-,27-,28+,29-,30-,31+,32-/m1/s1

FYJCXNYYSACEJK-MRYIOYKESA-N

IUPAC InChI generator is giving the following InChI/InChIKEY:

InChI=1S/C32H40O18/c33-10-20-22(38)24(40)26(42)29(48-20)47-16-6-7-17(19(37)9-16)18(36)8-3-14-1-4-15(5-2-14)46-30-27(25(41)23(39)21(11-34)49-30)50-31-28(43)32(44,12-35)13-45-31/h1-9,20-31,33-35,37-44H,10-13H2/b8-3+/t20-,21-,22-,23-,24+,25+,26-,27-,28?,29-,30-,31?,32-/m1/s1

FYJCXNYYSACEJK-AIPIIJKESA-N

It seems that its ignoring two of the stereocenters. The above InChI actually belongs to this structure:

Can this issue be fixed?

[amalik01]

ACD/Labs02192612293D

50 54 0 0 1 0 0 0 0 0 1 V2000
24.0369 -13.6770 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
26.4036 -13.5533 0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
22.8846 -17.0018 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
27.7807 -10.7482 0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
24.3394 -10.7994 0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
26.3404 -15.0074 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
21.7330 -15.0066 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
26.3399 -17.6674 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
27.3410 -9.2221 0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
9.0627 -17.0004 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
25.1877 -19.6621 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
6.7590 -19.6601 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
9.0627 -20.9901 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
11.3664 -17.0001 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
11.3664 -19.6600 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
5.6073 -17.6651 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
13.6696 -20.9902 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
15.9729 -20.9905 -0.0001 O 0 0 0 0 0 0 0 0 0 0 0 0
24.0367 -15.0070 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
26.6289 -11.4129 0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
25.3279 -11.6894 0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
25.1886 -13.0120 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
25.1884 -15.6721 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
25.1882 -17.0024 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
22.8848 -15.6720 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
24.0363 -17.6671 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
27.2938 -12.5648 0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
26.3524 -10.1123 0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
24.0359 -18.9970 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
7.9110 -18.9951 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
9.0627 -19.6601 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
7.9110 -17.6654 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
10.2144 -18.9951 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
10.2144 -17.6654 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
20.5811 -15.6713 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
6.7590 -17.0001 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
20.5809 -17.0013 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
19.4293 -15.0062 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
12.5181 -17.6651 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
19.4289 -17.6662 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
18.2774 -15.6709 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
18.2773 -17.0012 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
12.5179 -18.9951 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
13.6700 -17.0004 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
17.1255 -17.6658 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
13.6699 -19.6602 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
14.8216 -18.9954 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
14.8218 -17.6654 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
17.1251 -18.9958 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
15.9732 -19.6605 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0
19 1 1 6 0 0 0
22 1 1 1 0 0 0
2 22 1 0 0 0 0
2 27 1 0 0 0 0
3 25 1 0 0 0 0
3 26 1 0 0 0 0
20 4 1 6 0 0 0
21 5 1 6 0 0 0
23 6 1 1 0 0 0
25 7 1 1 0 0 0
7 35 1 0 0 0 0
24 8 1 6 0 0 0
9 28 1 0 0 0 0
10 32 1 0 0 0 0
10 34 1 0 0 0 0
11 29 1 0 0 0 0
30 12 1 6 0 0 0
31 13 1 1 0 0 0
34 14 1 1 0 0 0
14 39 1 0 0 0 0
33 15 1 6 0 0 0
16 36 1 0 0 0 0
17 46 1 0 0 0 0
18 50 2 0 0 0 0
19 23 1 0 0 0 0
19 25 1 0 0 0 0
20 21 1 0 0 0 0
20 27 1 0 0 0 0
20 28 1 0 0 0 0
21 22 1 0 0 0 0
23 24 1 0 0 0 0
24 26 1 0 0 0 0
26 29 1 1 0 0 0
30 31 1 0 0 0 0
30 32 1 0 0 0 0
31 33 1 0 0 0 0
32 36 1 1 0 0 0
33 34 1 0 0 0 0
35 37 2 0 0 0 0
35 38 1 0 0 0 0
37 40 1 0 0 0 0
38 41 2 0 0 0 0
39 43 2 0 0 0 0
39 44 1 0 0 0 0
40 42 2 0 0 0 0
41 42 1 0 0 0 0
42 45 1 0 0 0 0
43 46 1 0 0 0 0
44 48 2 0 0 0 0
45 49 2 0 0 0 0
46 47 2 0 0 0 0
47 48 1 0 0 0 0
47 50 1 0 0 0 0
49 50 1 0 0 0 0
M END

[nbehrnd]

@amalik01 Note the syntax of the .mol file currently shared is invalidated by your copy as plain text. For instance the white space prior to the comment line about the creator/date of creation, and the one in the line just prior to the atomic coordinates are both missing.

As an easy fix: 1) retract your copy of the content of the .mol file, 2) return to your molecule editor to save the structure in an identifiable file (e.g., structure.mol), 3) append a .txt to the file name (-> structure.mol.txt), then 4) attach the file to the original post via the paper clip icon (bottom left hand corner) of the original post.

The first InChI/InChi key were generated by ACD Sketch (I presume) -- which version? By "IUPAC InChI generator" about the second pair of InChI / InChi key, do you refer to the demo page, or one of the reference executables on the releases page (version 1.07.5 was published earlier this week)?

[amalik01]

You should be able to download the MOL file directly from ChEBI: https://www.ebi.ac.uk/chebi/CHEBI:140096

Yes, the first InChI/InChIKEY is from ACD/ChemSketch (2019.1.1). I added the MOL file in the demo page and it gave a different InChI to ACD ChemSketch.

We are also using RDKit (https://www.rdkit.org/docs/source/rdkit.Chem.rdinchi.html) in ChEBI to generate the InChI and it gives the same InChI as the demo version so the issue is not only affecting the web demo version.

[djb-rwth]

HI @amalik01,
The only thing I can confirm at the moment is that InChI v.1.07.5 and InChI v.1.06 both give the same output:

InChI=1S/C32H40O18/c33-10-20-22(38)24(40)26(42)29(48-20)47-16-6-7-17(19(37)9-16)18(36)8-3-14-1-4-15(5-2-14)46-30-27(25(41)23(39)21(11-34)49-30)50-31-28(43)32(44,12-35)13-45-31/h1-9,20-31,33-35,37-44H,10-13H2/b8-3+/t20-,21-,22-,23-,24+,25+,26-,27-,28?,29-,30-,31?,32-/m1/s1
InChIKey=FYJCXNYYSACEJK-AIPIIJKESA-N

However, the following warning is displayed:

Warning (Ambiguous stereo: center(s)) structure #1.

Very curious to know how the "correct" InChI string/key is generated in ACD/ChemSketch.

[nbehrnd]

@amalik01 There is something odd.

• The .mol file by https://www.ebi.ac.uk/chebi/CHEBI:140096, read by the InChI demo site's editor assigns an InChI key FYJCXNYYSACEJK-AIPIIJKESA-N (standard parameters of InChI 1.07.5). Here I can replicate your finding.

However,

• If this .mol file is read by ACD ChemSketch (ACD/Labs 2024.2.3 (File Version C45E41, Build 142855, 23 Jan 2025), the InChI key assigned is FYJCXNYYSACEJK-MRYIOYKESA-N
• If this .mol file is read by Biovia Draw (version MDL.Draw.Editor 25.1.0.2318 of 2025), the InChI key assigned is FYJCXNYYSACEJK-MRYIOYKESA-N
• If the .mol file is read by OpenBabel (Windows executable, version Open Babel 3.1.1 -- May 16 2020 -- 11:57:55) there is a warning

obabel CHEBI_140096.mol -oinchikey
==============================
*** Open Babel Warning  in InChI code
  #1 :Ambiguous stereo: center(s)
FYJCXNYYSACEJK-AIPIIJKESA-N
1 molecule converted

By an elder discussion (openbabel/openbabel#2849), OpenBabel currently uses at maximum InChI 1.07.4 (an update to InChI 1.07.5 is in preparation, see openbabel/openbabel#2857). The commercial editiors (ChemDraw, ChemSketch, ISIS/BioviaDraw, ChemDoodle) are not "this open" to report about their inner working.

Returning to https://www.ebi.ac.uk/chebi/CHEBI:140096, I notice the web site reports as InChI key FYJCXNYYSACEJK-AIPIIJKESA-N. However, the site equally reports a SMILES string, i.e. O=C(/C=C/c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O[C@@H]2OC[C@](O)(CO)[C@H]2O)cc1)c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1O. For one, this let me to submit this to Openbabel, i.e.

obabel -:"O=C(/C=C/c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O[C@@H]2OC[C@](O)(CO)[C@H]2O)cc1)c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1O" -oinchikey
FYJCXNYYSACEJK-MRYIOYKESA-N
1 molecule converted

For two, I returned to the molecule editor on InChI's demo page; because Ctrl + O equally allows to load a SMILES string from the clip bord / temporary memory. With O=C(/C=C/c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O[C@@H]2OC[C@](O)(CO)[C@H]2O)cc1)c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1O from your database's web site in hand to paste, and a subsequent "Open as New Project", InChI 1.07.5 with default parameters yields an InChI key of FYJCXNYYSACEJK-MRYIOYKESA-N.

Since both the .mol file by the database, as well as the ACD ChemSketch .mol pasted by you are in the .mol V2000 syntax, below is the .mol from InChI's test site in the elder v2000 syntax.

ketcher.mol.txt

[amalik01]

Thanks for the update.

[fbaensch-beilstein]

Thank you for bringing this interesting problem to our attention, @amalik01. Thank you for looking into it, @nbehrnd.

To avoid any editing issues when using the WebDemo, it is best to use a .mol file in the "Convert Molfile to InChI" tab.

The .mol file in the second comment was likely exported from ChemSketch (see the attached file; thanks to @djb-rwth). It is a permuted version of the ChEBI file.
Both files result in different InChIs/InChIKeys:

• ChEBI: FYJCXNYYSACEJK-MRYIOYKESA-N
• ChemSketch: FYJCXNYYSACEJK-AIPIIJKESA-N.

Using the ChemSketch mol file in the "Draw structure and convert to InChI" tab of the WebDemo with the "Layout" or the "Clean up" function will result in the correct InChIKey: FYJCXNYYSACEJK-MRYIOYKESA-N.

ghi_199_ChemSketch.mol.txt