Drawing sp³ Stereocenters

The graphical depiction of sp³ stereocenters is not standardized, despite some efforts from e.g. the IUPAC1 to provide guidelines. Apparently the subject is a minefield even for authoritive organizations! In the section dealing with the graphical representation of 3-D structures2 we can read "Structural diagrams which depict stereochemistry must be prepared with extra care to ensure there is no ambiguity" closely followed by "Strict rules for drawing stereochemistry are not possible". One of the recommendations2 is "Hydrogen atoms attached at stereochemically designated positions should not be omitted". Yet in practice the hydrogen is often assumed implicitly and the stereocharacter (wedge or dash) is put on one of the other bonds to the stereocenter, without introducing ambiguity. See, for instance, the first drawing below, which depicts (2R,3R)-butane-1,2-diol. The drawing is followed by three equivalent ones. Convince yourself that all four drawings depict one and the same molecule.

The two drawings below depict (2R,3S)-butane-1,2-diol, a stereoisomer of the previous molecule.

       

Now compare the last drawings of each of these stereoisomeric compounds. They differ only in the angles between the bonds around the right-hand stereocenter. Let's make the angle between the two plain (non-wedge) bonds 180°, like this:

           

Which of the two stereoisomeric compounds is depicted here? Logic dictates that at a certain value for the angle between the two plain bonds the interpretation must "flip" from one configuration to the other. The IUPAC guidelines2 are silent here, as they recommend drawing hydrogen atoms. The molfile format3, a widespread file format for chemical structures, considers this depiction ambiguous4. In practice this means that the interpretation by chemical software depends on whether the angle between the plain bonds is slightly more or slightly less than 180°. In other words, the critical "flip" angle is 180°.

What about human perception of the drawing? Most chemists would probably interpret it as to mean the first molecule, (2R,3R)-butane-1,2-diol, although quite a few will be confused. Such interpretation is very much in the eye of the beholder. Nevertheless, stereocenter depictions of this type are not uncommon, regarding the following drawing of (−)-sparteine on the left:

   

The intended molecule is drawn on the right, but note that chemical software considers these two molecules as equivalent only if the angle between the plain bonds is slightly more than 180° for both stereocenters!

References and Notes:

  1. IUPAC - Basic Terminology of Stereochemistry. [http://www.chem.qmul.ac.uk/iupac/stereo/]
  2. IUPAC - Graphic Representation of Three-Dimensional Structures. [http://www.chem.qmul.ac.uk/iupac/stereo/intro.html#gra]
  3. Dalby A, Nourse JG, Hounshell WD, Gushurst AKI, Grier DL, Leland BA, Laufer J: Description of Several Chemical Structure File Formats Used by Computer Programs Developed at Molecular Design Limited.  J. Chem. Inf. Comput. Sci. 1992, 32: 244-255.
  4. This can be verified by using ISIS or other database software that interpret molfiles.