Pages

Tuesday, September 06, 2011

How should we draw that sulfur anyway?

I yesterday asked about the existence of a particular sulfur compound. Reference to it has not been found so far (a patent was by Chris in the comments yesterday), but only shows a related compound), but thanx to those who looked into it! Nina asked a colleague (organic chemist) who told us the compound could exist, and pointed out that the sulfur in fact has a lone pair (much like the sulfoxide) which people often do not draw. Elsewhere, David reported inconsistency between stereochemistry of the sulfur compound between PubChem and ChemSpider, which prompted Antony noted that both structures give the same InChI nevertheless.

Now, recall the lengthy write up by Brecher on correctly drawing stereochemistry (which I discussed before). I have not checked what it says about sulfurs. Also recall the discussion last week about how sensitive the InChI code is to small angle changes with stereochemistry perception (ping of there is online coverage; cannot find it right now).

Let's zoom in on this sulfur:

A clear tetrahedral stereochemistry is suggest, but is wrong. We must include the lone pair too. It's stuff like this why I care so much about hydridization hints in the CDK. The CDK does report the lone pair on the sulfur, but lists a sp3d2 hybridization, which seems wrong to me. Should that not be sp3d instead, or so?

Now, importantly, is the sulfur still chiral in the true coordination? I think it would be. The InChI library has its own opinion, causing it to give the same InChI even if the input files show a different stereochemistry.

So, my question yesterday is very much about this sulfur. That's why we need experimental data on existing compounds with such a sulfur. The compound I posted yesterday just happened to be one of the lighter compounds I found in PubChem.

The search continues...

4 comments:

  1. Just to clarify, there isn't a actually a difference between the PubChem and ChemSpider records - both records have the same InChI. The actual issue is the representation of the structure in PubChem (and the way that this is processed). The PubChem record displays a mixture of 2D and 3D representation. This never ends well! ;-) Wedged bonds can only be properly interpreted in the context of a plane defined by the rest of the molecule - which is impossible if you have a 3D representation.

    ReplyDelete
  2. The mentioned blog post about how sensitive the InChI to small angle changes can be found here: http://blog.mcule.com/2011/08/same-or-different-molecules-what-do-you.html

    ReplyDelete
  3. Dave, Ferenc, thanx for the details!

    ReplyDelete
  4. experimental data about chiral lambda 4 sulfanyl derivatives could be found here DOI: 10.1021/jo052539r
    the main problem is imho, that stereo centers with a coordination sphere other than 4 are not easy to handle / draw properly (and of course, lone pairs count).
    it is (mainly) a problem of inorganic chemistry. therefore inchi does not handle these cases properly.
    iupac also treats higher order stereochemistry poorly.

    ReplyDelete