26 No. 6
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Bonded by Stereobonds
by Hubert Maehr
We all agree that a molecular diagram representative of a chiral compound should comprise all elements pertaining to the stereochemical information and we abet the current efforts by IUPAC in its attempt to design a corresponding graphical solution. It certainly is an arduous task to consider or accommodate the myriad of opinions and suggestions that the task group (project headed by William G. Town, # 2003-045-3-800; Jul-Aug 2004 CI, p. 23) ) is confronted with and to finally arrive at a proposal that chemists will embrace and actually use. Some of these opinions that were recently voiced demand a reply.
I concur with the summary of the present state of affairs succinctly presented by Kaupp and Naimi-Jamal (Jan-Feb 2004 CI, p. 15) and their proposal for a targeted use of the common stereobonds to bring lucidity to the chemical literature. Solid and hashed wedge bonds should indicate absolute configuration, and “thick and hatched” bonds could represent racemates. It is difficult to imagine a simpler solution to the current problem and I would also like to point out that it is precisely this bond allocation that was proposed by us almost 20 years ago (J. Chem. Edu. 1985, 62, 114–120) and recently reiterated in detail (J. Chem. Inf. Comput. Sci., 2002, 42, 894–902).
Flack points out (Jul-Aug 2004 CI, p. 21) that molecular structure should be able to distinguish three disparate cases, namely enantiopure compounds of known absolute configuration, enantiopure compounds of unknown absolute configuration, and racemates. He also correctly observed that Kaupp and Naimi-Jamal’s suggestions for molecular diagrams address only two of these categories and do not produce graphical representations of enantiopure compounds of unknown absolute configuration. Again, I would like to emphasize that our proposals contained in the above-mentioned papers, address all three scenarios. We also presented examples of pragmatic significance such as single-diagram representations of manifold independent relative configurations as are often encountered, especially during structure elucidation of natural products (e.g., palitoxin). In brief, for every verbal stereochemical nuance, we offered a single pictorial counterpart whose basic elements are summarized below.
The letter of M. Oki (Jul-Aug 2004 CI, p. 22) also deserves a rebuttal. He is concerned that “thick and hatched” bonds do not provide stereochemical information. Let me paraphrase a section of our above-mentioned publication. Clearly, a line, thick or slender, hatched or solid, obviously lacks differentiation of its termini. Such a line indeed appears inherently incapable of serving as a stereobond. Thick, hatched, or broken lines, however, are used as bonds in the context of a longstanding but tacit convention. Accordingly, the stereogenic unit to which the line-type bond symbol is attached is considered to lie in the picture plane so that the bold line reveals its ligand in front of that plane, whereas the hashed symbol is intended to show that the ligand is behind it. This convention elevates line symbols to fully functional stereobonds.
The comment by McNaught (Jan-Feb 2004 CI, p. 16) also elicits a comment. He is concerned that the proposal of targeted redeployment of established stereobonds as descriptors of detailed stereochemical information would be difficult, as the reader would have no means of recognizing that a convention was being used. This apprehension, in our opinion, is unfounded. Imagine, for a moment, that our proposed convention would be in effect. Those readers who are incognizant of the convention would be at exactly the same level of understanding as all of us are presently accustomed. We now look at a structural diagram and wonder what the visible, chiral connotations really mean. More often than not, we have to consult the accompanying text to ascertain the chiral meaning of the diagram or, given a synthetic scheme, we arrive at the stereochemical information after studying the starting materials and reagents used. But those readers who are familiar with the convention would benefit from an unprecedented level of unequivocal information contained in a single molecular diagram. And the ratio of the acquainted versus unacquainted would surely increase exponentially as a function of time. Those who did not know the convention would certainly not receive wrong information. It would only protract the shadow of ambiguity.
Allocating the six commonly used stereobonds, shown above, as determinants of complete, graphic stereochemical descriptions appears very appealing to many of us. The comments by Kaupp and Naimai-Jamal are representative of this conviction.
I doubt that there will ever be a perfect solution. When I asked Kurt Mislow, a paragon of stereochemistry, about his opinion of our proposal, he nodded thoughtfully and said: “I guess this is about as good as we can do. What a shame we can not color-code.”
Hubert Maehr <hubert.maehr@ROCHE.COM> is at Roche Research Center, Hoffmann-La Roche Inc., in Nutley, New Jersey, USA.
last modified 10 November 2004.
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