Draw better structures, Dr. Yudin

A first year undergraduate student once came to see me during an office hour and posed a question involving thiophene. Some aromatic substitution, I think. He drew a molecule on the board. Those of you who teach organic chemistry might know the feeling… I looked at the structure and almost got upset by how unappealing it looked. For instance, the C-S-C angle was ridiculously close to 90 degrees. Of course, it takes time to know how to draw things well in chemistry and we all have been there. So I tried to encourage my visitor by saying: “You might want to take into account some geometrical considerations when you draw 5-membered rings. Your structure is somewhat unrealistic – where is the 120 degree C-S-C angle?”. Unbeknownst to him, the student was correct and should have jabbed me by saying: “Why don’t you learn your inorganic chemistry and know your bond lengths!”.

Indeed, the other day I was looking through some protein/inhibitor complexes in the pdb (Protein Data Bank). At some point, I said to myself: “Hmmm. Furan and thiophene are distinctly different!”. I checked other structures and indeed – sulfur’s d-orbitals, long C-S bonds, and associated geometrical preferences make their presence felt. Here is an expanded view that shows the two furan and thiophene fragments I looked at:

ImagePerhaps I need to know the chemistry of main group elements a bit better when I draw them in my structures. I think that from now I might make it a point to draw an angle that is close to 90 degrees in my thiophene structures. Will I actually do it? Who knows, probably not. But I do think that our tools of rendering molecules are adequate, yet not perfect. A lot of important features are “lost in translation”, so to speak.

2 thoughts on “Draw better structures, Dr. Yudin

  1. in medicinal chemistry, it is well known that furan is very different from thiophene: Thiophene is best approximated by benzene, with one important exception – there is a net positive charge on thiophene sulfur (the same goes for a thiazole sulfur) so if there is a carbonyl substituent in the 2-position placed one or two bonds away, the electrostatics will lock the bond rotation so that the carbonyl is in plane with the thiophene ring and the CO points towards the S, forming “O – S bond” But when you replace thiophene in such a molecule with furan, apart from having a smaller ring, the preferred conformer now will have carbonyl oxygen pointing away from furan O

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