Imperial College London

Henry Rzepa

I wrote in an [earlier
post](http://www.ch.imperial.ac.uk/rzepa/blog/?p=3802){target="_blank"
rel="noopener noreferrer"} how Pauling's Nobel prize-winning suggestion
in February 1951 of a (left-handed) α-helical structure for
proteins\[cite\]10.1073/pnas.37.4.205\[/cite\] was based on the wrong
absolute configuration of the amino acids (hence his helix should really
have been the right-handed enantiomer). This was most famously
established a few months later by
Bijvoet's\[cite\]10.1038/168271a0\[/cite\] definitive crystallographic
determination of the absolute configuration of rubidium tartrate,
published on August 18th, 1951 (there is no received date, but a
preliminary communication of this result was made in April 1950). Well,
a colleague (thanks Chris!) just wandered into my office and he drew my
attention to an article by John
Kirkwood\[cite\]10.1063/1.1700491\[/cite\] published in April 1952, but
received July 20, 1951,^‡^ carrying the assertion "*The Fischer
convention is confirmed as a structurally correct representation of
absolute configuration*", and based on the two compounds 2,3-epoxybutane
and 1,2-dichloropropane. Neither Bijvoet nor Kirkwood seem aware of the
other's work, which was based on crystallography for the first, and
quantum computation for the second. Over the years, the first result has
become the more famous, perhaps because Bijvoet's result was mentioned
early on by [Watson and
Crick](http://www.ch.imperial.ac.uk/rzepa/blog/?p=3235){target="_blank"
rel="noopener noreferrer"} in their own very famous 1953 publication of
the helical structure of DNA. They do not mention Kirkwood's result. Had
they not been familiar
with Bijvoet's\[cite\]10.1038/168271a0\[/cite\] result, their helix too
might have turned out a left-handed one!

I record all this because I was today asked to provide an abstract for
an [NSCCS Themed
Workshop](http://www.nsccs.ac.uk/SOC2012.php){target="_blank"
rel="noopener noreferrer"} shortly to be held at Imperial College on the
uses of the Gaussian computational chemistry program in synthetic
chemistry. One of the themes will be chiroptical spectroscopy. Gaussian
of course deploys much of the theory developed by Kirkwood in the 1950s
to make exactly the same sort of predictions that Kirkwood himself used
to verify the Fischer convention in 1951. Whilst the majority of modern
determinations of absolute configuration are still based on Bijvoet's
method,\[cite\]10.1038/168271a0\[/cite\] catching rapidly up are those
based on chiroptical calculations. Perhaps in 2012 they are trusted more
than they were in the 1950s? At any rate, such calculations are nowadays
very much part of a modern undergraduate laboratory experience (slightly
less so still in research laboratories I fear).

Here is another coincidence. Both Pauling and Kirkwood worked in the
same department (Institute of Technology, Pasadena, California). One can
only speculate on whether Kirkwood might have wandered into Pauling's
office in late 1951 to alert him that the protein helix should be right
rather than left-handed (oh to have been a fly on
Pauling's [blackboard](http://osulibrary.orst.edu/specialcollections/images/facilities-lpoffice2-large.jpg){target="_blank"
rel="noopener noreferrer"}). So alerted, would Pauling have foreseen
that eventually such determinations would be routinely made using the
very quantum mechanics that he had popularised?

------------------------------------------------------------------------

^‡^He first proposed a method of calculating absolute configurations as
early as 1937\[cite\]10.1063/1.1750060\[/cite\], applying this
to *d*-butan-2-ol as he noted it (also known as (+)-butan-2-ol),
assigning an (2*R*)-configuration.\[cite\]10.1021/ja803119p\[/cite\] It
took a further 15 years for him to apply his method to Fischer's
configuration!

::: {.wp_orcid_field}
[https://orcid.org/0000-0002-8635-8390](https://orcid.org/0000-0002-8635-8390){target="_blank"
rel="author"}
:::


I wrote in an earlier post how Pauling’s Nobel prize-winning suggestion in February 1951 of a (left-handed) α-helical structure for proteins[cite]10.1073/pnas.37.4.205[/cite] was based on the wrong absolute configuration of the amino acids (hence his helix should really have been the right-handed enantiomer). This was most famously established a few months later by Bijvoet’s[cite]10.1038/168271a0[/cite] definitive crystallographic

Postagens de Rogue Scholar

Confirming the Fischer convention as a structurally correct representation of absolute configuration.