Wednesday, 23 May 2012

When Mol files go wrong III

Let's play spot the difference. Are the following structures the same? (Mol files from CHEMBL186139 and CHEMBL1180158.)
But if they're the same, then how come there are two distinct entries for this in the database? Well guess what - they don't have the same InChI:
InChI=1S/C30H36N4/c1-2-10-20-32-28-18-24-34(30-16-8-6-14-26(28)30)22-12-4-3-11-21-33-23-17-27(31-19-9-1)25-13-5-7-15-29(25)33/h5-8,13-18,23-24H,1-4,9-12,19-22H2/p+2/b31-27+,32-28?
InChI=1S/C30H36N4/c1-2-10-20-32-28-18-24-34(30-16-8-6-14-26(28)30)22-12-4-3-11-21-33-23-17-27(31-19-9-1)25-13-5-7-15-29(25)33/h5-8,13-18,23-24H,1-4,9-12,19-22H2/p+2/b31-27-,32-28+
The nitrogen attached to the ring is treated as a C=N once the two protons are added to neutralise the charge. The InChI code then considers the stereochemistry across that double bond to be defined in one case (177.2°) but undefined in the other (179.1°). Here are the pictures from winchi (click to enlarge):
I'm not quite sure where the problem is. Is the InChI correct to make the distinction? Any thoughts?

4 comments:

Patrik Rydberg said...

2 degrees is not much. By what method has those two degrees been determined?
I suspect that this is simply a difference in how input geometry has been determined, and not an actual difference. Thus, I think the Inchis should be the same.

baoilleach said...

I measured the angle in Avogadro.

I'll probably post this to the InChI mailing list and see if I get a response...

Patrik Rydberg said...

I was rather thinking how the original structure was determined. Is it an X-ray structure, or a computationally determined structure? And what is the resolution of the X-ray structure if it is one? The two degree deviation might be within experimental error.

baoilleach said...

The underlying data are from 2D mol files. The original structure was determined using a mouse. :-)