Imperial College London

Henry Rzepa

The title here is taken from a presentation made by Ian Bruno from CCDC
at the [recent conference on Open
Science](http://www.beilstein-institut.de/en/symposia/open-science). It
also addresses the [theme
here](http://www.ch.imperial.ac.uk/rzepa/blog/?p=18257) of the issues
that might arise in assigning identifiers for any given molecule.

The structure was represented as
shown\[cite\]10.3998/ark.5550190.0009.503\[/cite\] by the original
authors, in which the bonding from S to Sn is indicated with both solid
lines (a bond) and dotted lines (an
"interaction").![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/149.jpg){.aligncenter
.size-full .wp-image-18387 decoding="async" width="450"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/149.jpg 654w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/149-279x300.jpg 279w"
sizes="(max-width: 654px) 100vw, 654px"}

Why would this matter? Well, to enable any entry in the Cambridge
structure database as findable (the F of FAIR) it has to be given a
unique identifier. There are in general three such identifiers assigned
by the CCDC:

1.  The **Refcode**, in this case XONHIS. These six or seven letter
    codes are historically the oldest, and started off at least with an
    attempt if possible to assign some semantic inference from the name,
    even if only occasionally. 
2.  The **CCDC deposition number**, in this case 650011. This is the
    number that an author will receive immediately upon deposition, and
    you often find these identifiers quoted in supporting information
    files
3.  The **DOI** (digital object identifier), in this
    case [10.5517/ccptd3z](https://dx.doi.org/10.5517/ccptd3z), which
    can be used to view the structure even if access to the full CSD is
    not available to the user. In that sense, the DOI is the FAIRest of
    the first three of these identifiers.
4.  However, CCDC reported that they are considering adding a 4th very
    common identifier, based on the **InChI** (International chemical
    identifier), which comes as a full string and with the structure of
    the molecule at least in part inferrable from it, together with  a
    shortened (almost) unique string which has the advantage of being
    "Googlable". Both are helpfully FAIR.

It is this 4th identifier that is at issue here. InChIs are derived from
atom connection tables; you need to define all bonds present in the
molecule. And it is here that the dotted "bond"/"interaction" above
becomes a problem. This is the representation shown in the CSD database,
which reveals that all the Sn...S interactions are classified as
"bonds", along with some creative(!) representations of the C...S
bonds.![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/148.jpg){.aligncenter
.size-full .wp-image-18388 decoding="async" width="450"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/148.jpg 624w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/148-300x200.jpg 300w"
sizes="(max-width: 624px) 100vw, 624px"}

So the InChI will very much depend on whether all the Sn...S contacts
are termed as bonds or as interactions. To help clarify that, it is
useful to show the typical range of lengths of such contacts. Below is a
simple search for all Sn and S systems where the pair are either close
in space (\< 3.5Å) or have a bond specified between the two atoms.

![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/Sn-S-non-1024x756.jpg){.aligncenter
.size-large .wp-image-18390 loading="lazy" decoding="async" width="450"
height="332"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/Sn-S-non-1024x756.jpg 1024w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/Sn-S-non-300x221.jpg 300w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/Sn-S-non-768x567.jpg 768w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/Sn-S-non.jpg 1926w"
sizes="(max-width: 450px) 100vw, 450px"}

The main cluster occurs at \~2.5Å, but there is some evidence of a
second peak at about 3.0Å. The third distribution up to 3.5Å is probably
a continuum of very weak dispersion interaction, which most molecules
exhibit. The values for XONHIS are 2.521 and 2.996Å, which match the two
clusters above.

So perhaps a quantum calculation can shed some light
(DOI: [10.14469/hpc/2593](https://doi.org/10.14469/hpc/2593))? The
values on the right are the optimised bond lengths which are pretty
similar to the crystal structure. On the left are the calculated Wiberg
bond orders (B3LYP+D3BJ/Def2-TZVPP/chloroform calculation). These reveal
both "bonds" have an order less than 1. The value of \~0.6 is probably
not contentious, but it does graphically show that when a compound is
indexed as having a "single bond" between two atoms, the quantitative
bond order may be substantially less. What however would one make of a
bond order of 0.214? Should it be classified as a bond, albeit a much
weaker one than normal? Or should it instead simply be a rather strong
"interaction" which is not classified as a bond? And perhaps one should
have in mind the question "how sensitive is this result to the quantum
mechanical procedure
used?"![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/146.jpg){.aligncenter
.size-full .wp-image-18393 decoding="async" width="450"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/146.jpg 902w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/146-273x300.jpg 273w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/146-768x844.jpg 768w"
sizes="(max-width: 902px) 100vw, 902px"}

Why does this distinction matter? Well, the InChI algorithm is based on
simple connectivity; are two atoms connected by a bond or not? There are
no nuances here. At the moment, this decision can be made by an
algorithm based on the distance between any atom pair (whether computed
or measured), but more often I suspect it derives from a "molfile" which
is often derived from a human-drawn representation using a structure
drawing program. It does rather boil down to the individual preferences
of the human drawing the molecule. Due in part to such uncertainties, it
was estimated that only 22% of structures in the CSD can be used to
generate a reliable InChI. Hydrogen bonds are almost always classified
as non-bonds, which means their presence is rarely systematically
flagged during the indexing of the structures. Organometallics often
pose some of the greatest representational problems (there are many
others).

I will end by observing another class of structure that I deal with,
"reaction transition states". As you might imagine these forms are full
of pairs of atoms with ambiguous bond lengths and hence connectivity. We
currently have no truly reliable method for assigning useful identifiers
to them. So lots of challenges for the future then!

 

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The title here is taken from a presentation made by Ian Bruno from CCDC at the recent conference on Open Science. It also addresses the theme here of the issues that might arise in assigning identifiers for any given molecule.

Messaggi di Rogue Scholar

Challenges in reliably representing the chemistry of crystal structures.