Henry Rzepa's blog

I will approach this example of a molecule-of-the-year candidate – in fact the eventual winner in the reader poll – from the point of view of data. Its a metallocene arranged in the form of a ring comprising 18 sub-units.[1] Big enough to deserve a 3D model rather than the static images you almost invariably get in journals (and C&EN). So how does one go to the journal and acquire the coordinates for such a model?

Well, nowadays most reputable journals include a “data availability” statement, which in this case is indicated using a URL-style identifier for supporting information. This means by the way that this identifier may not be persistent, since the path to the document in the string https://static-content.springer.com/esm/art%3A10.1038%2Fs41586-023-06192-4/MediaObjects/41586_2023_6192_MOESM1_ESM.pdf may change in the future according to the publishers production workflows. The Acrobat file contains the required coordinates, of which I give a small sample here:

18‐ring
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1386
Energy = ‐29312.63737385 dispersion contribution = ‐2.415738946
C 5.1700172 1.6243489 ‐11.0779621
C 5.6857216 1.5855492 ‐12.4187559
C 6.0496599 0.6048512 ‐13.3969079
C 6.1219344 ‐0.8254711 ‐13.5066237

I selected the molecule coordinates within the PDF, pasted into a text editor and then spent a few minutes removing the resulting extraneous blank lines due to the page breaks present in the PDF document (a paginated document format is NOT a good vehicle for data!). I then added further lines (topped and tailed it) to eg make it viewable using a molecular editor such as Gaussview, only to get the following error.

A bit of research leads to eg the following page: The difference between a dash and a minus sign. There you find four different glyphs any of which could look like a minus sign – there could in fact be more. Next, using the following resource: https://www.fontspace.com/unicode/analyzer#e=4oCQ  tells us that the “-” found in the supporting information is in fact a “hyphen“. Typed from a keyboard as a “-” one learns this is a “hyphen-minus“. There is also “−” which emerges as a “Minus sign“, whilst a “–” emerges as an “EN Dash“. Confused yet? Well, it all does rather depend on whether the creator of the molecular viewing program you are about to use has included all these variations in their program code. In this case clearly not, since a hyphen is not recognised. Once you get to this stage, around 30 minutes of occasional head scratching have elapsed, and you further have figured out how to do a global find and replace of a hyphen by a minus using your preferred software.

What does all this have to do with FAIR? This means Findable, Accessible, Interoperable and Reusable. And those actions have to be possible not only by a human but by an autonomous and probably unsupervised system gathering data for machine learning or artificial intelligence. The Finding was facilitated by the “data availability” statement using the article DOI (a fully persistent identifier), but probably only a human could actually cope with the diversity of presentations for data found across multiple publishers (thus, to be technical, the access location of supporting data is rarely if ever actually declared in the metadata record associated with the DOI, which is what a machine would need to access the data). The Access in this case means resolving the URL above, but only if it does not change in the future! But the next bit, the Interoperability, is more of a challenge. Like myself, many a human might also take 30 minutes, or indeed just give up, in coping with the challenge of recognising that a hyphen is not a minus! So although we are grateful for that “data availability” statement, I dream of the day when that will in fact become a “FAIR data availability” statement!^‡ Not many signs of that happening yet. I guess the AI-algorithms will in fact get smarter faster than people for coping with such issues.

Anyway, you now have a 3D model of the 18-metallocene as this year’s selected molecule of the year! Click on the image above to load it.

^‡For example, the data for this post is available at a FAIR repository, with the persistent DOI identifier: https://doi.org/10.14469/hpc/13536. This contains the optimised coordinates using the PM7 method. These are very little different from the coordinates from the article, which were obtained using the PBE0/Def2-TZVP method, a remarkable calculation given it uses 21618 basis functions!

References

1. L. Münzfeld, S. Gillhuber, A. Hauser, S. Lebedkin, P. Hädinger, N.D. Knöfel, C. Zovko, M.T. Gamer, F. Weigend, M.M. Kappes, and P.W. Roesky, "Synthesis and properties of cyclic sandwich compounds", Nature, vol. 620, pp. 92-96, 2023. https://doi.org/10.1038/s41586-023-06192-4

The Science education unit at the ACS publication C&EN publishes its list of molecules of the year (as selected by the editors and voted upon by the readers) in December. Here are some observations about three of this year’s batch.

1. Diberyllocene[1] with its unusual Be-Be bond has already beeen covered on this blog.[2], where I commented that lithioborocene should be possible to make as well.
   
2. The second in the list is the synthesis of the chiral triaryloxonium ion[3] HICBUU(Crystal DOI: 10.5517/ccdc.csd.cc2cjynj). Curiously, this combines the features of two of our recent publications (with Chris Braddock)[4],[5]. The first of these speculated upon a mechanism involving an intermediate (and as it happens chiral) oxonium ion and its subsequent rapid fragmentation by nucleophilic attack. This meant it was never isolated, unlike the one reported this year.[3] The second article of ours involved another class of chiral natural product called polysiphenols and their enantiomerisation by a process called atropisomerism via a two stage process. This as it happens is also the feature reported for the the chiral triaryloxonium ion.

   

   The atropisomerism involves restricted (high energy) rotation about an axis shown as a dotted red line, accompanied at a separate stage with rotation about the C-C single bond shown in blue. The polysiphenols showed similar two-stage atropisomerism.

   I show an intrinsic reaction coordinate calculation of this process below, being respectively the energy response and the dihedral angle responses about the 16-17 bond (blue) and the axis 2-18 (dashed red) and ending with an animation of the process.

   
   
   
   

   Note how the C-C rotation is much lower in energy than the about the red axis. It is also interesting to observe that pyramidal inversion at the chiral oxygen centre via a trigonal planar unit only happens at an IRC value of ~+30, well after both transition states have passed!

3. The third topic is represented by the crystal structure NITRUH (Crystal DOI: 10.5517/ccdc.csd.cc2fcr2n),[6]. This is announced at the C&EN page as “carbene breaks octet rule”, in having only four valence electrons at the central carbon atom. The structure is certainly unique, the motif shown below having only one entry in the crystal structure database. Leaving aside the observation that a true carbene also breaks the octet rule with its nominal six valence electrons, how could this arise? Well, shown below are six canonical forms of this species (the original article shows four) of which species 1a is the one referred to as having only four valence electrons at the central atom, whilst 1b is that favoured in the article.

   

   What does a calculation reveal (ωB97XD/Def2-TZVPP; DOI for data 10.14469/hpc/13532)? The Wiberg bond index calculated for the central carbon atom is 3.8328, which corresponds to 7.67 electrons. Far from four! The Wiberg bond orders along the chain are 1.54, 1.14, 1.83, 1.83, 1.12, 1.58 (the species is calculated as not quite symmetrical as an isolated molecule) which is a close match to structure 1e (not shown in the article). Dare I suggest that the tag line for this entry in the C&EN article is a good example of copywriters hyperbole, something designed to catch the interest and attention of the reader? Well, it certainly succeeded, but I venture to suggest that although the molecule is indeed interesting and unique, it does NOT break the octet rule. A good discussion point perhaps for a chemistry tutorial?

References

1. J.T. Boronski, A.E. Crumpton, L.L. Wales, and S. Aldridge, "Diberyllocene, a stable compound of Be(I) with a Be–Be bond", Science, vol. 380, pp. 1147-1149, 2023. https://doi.org/10.1126/science.adh4419
2. H. Rzepa, "Diberyllocene — and Lithioborocene?", 2023. https://doi.org/10.59350/v1cma-xjk91
3. O. Smith, M.V. Popescu, M.J. Hindson, R.S. Paton, J.W. Burton, and M.D. Smith, "Control of stereogenic oxygen in a helically chiral oxonium ion", Nature, vol. 615, pp. 430-435, 2023. https://doi.org/10.1038/s41586-023-05719-z
4. J. Clarke, K.J. Bonney, M. Yaqoob, S. Solanki, H.S. Rzepa, A.J.P. White, D.S. Millan, and D.C. Braddock, "Epimeric Face-Selective Oxidations and Diastereodivergent Transannular Oxonium Ion Formation Fragmentations: Computational Modeling and Total Syntheses of 12-Epoxyobtusallene IV, 12-Epoxyobtusallene II, Obtusallene X, Marilzabicycloallene C, and Marilzabicycloallene D", The Journal of Organic Chemistry, vol. 81, pp. 9539-9552, 2016. https://doi.org/10.1021/acs.joc.6b02008
5. D.C. Braddock, A. Duran-Corbera, M. Nilforoushan, Z. Yang, T. He, G. Santhakumar, K.A. Bahou, H.S. Rzepa, R. Woscholski, and A.J.P. White, "(±)-Polysiphenol and Other Analogues via Symmetrical Intermolecular Dimerizations: A Synthetic, Spectroscopic, Structural, and Computational Study", Journal of Natural Products, vol. 85, pp. 2650-2655, 2022. https://doi.org/10.1021/acs.jnatprod.2c00749
6. Y.K. Loh, M. Melaimi, M. Gembicky, D. Munz, and G. Bertrand, "A crystalline doubly oxidized carbene", Nature, vol. 623, pp. 66-70, 2023. https://doi.org/10.1038/s41586-023-06539-x

Around 1996, journals started publishing what became known as “ESI” or electronic supporting information, alongside the articles themselves, as a mechanism for exposing the data associated with the research being reported and exploiting some of the new opportunities offered by the World Wide Web. From the outset, such ESI was expressed as a paginated Acrobat file, with the Web being merely a convenient document delivery mechanism. Such ESI would eventually reach more than 1000 such pages in length in some chemistry articles. The richer opportunities of Web interactivity were far less exploited. I have written about various aspects of this throughout this blog[1],[2],[3], together with one early compendium of our own data examples.[4] Here I update that compendium starting from 2005 to the current 2023 and add further information, being the current state of curation of some of these early examples. Curation became necessary because many of the earlier examples were no longer functional due to changes in the way journals expose these data objects or indeed changes at the data repository end of things over this 18 year period.

^aTo inspect the metadata associated with any article, use eg https://api.crossref.org/works/10.1002/anie.202006283/transform/application/vnd.crossref.unixsd+xml
and check how eg the data citation is expressed there.

The future seems likely to be influenced by the increasing requests from publishers for data to be made available in so-called FAIR-form, via an appropriate citation using a data DOI. The other feature on the horizon is the introduction of tools such as “Finding Aids“, where an automated script is able to automatically identify relationships between various data objects and the molecular content expressed within them and to generate a tool which exploits these relationships by adding further layers of navigation and especially of Findability to the data objects. I hope to show such an example here shortly – watch this space.

References

1. H. Rzepa, "Four stages in the evolution of interactive ESI as part of articles in chemistry journals.", 2022. https://doi.org/10.59350/qypm4-qfv97
2. H. Rzepa, "Web page decay and Journals: How an interactive "ESI" from 2006 was rescued.", 2022. https://doi.org/10.59350/cqesx-a0e83
3. H. Rzepa, "Curating a nine year old journal FAIR data table.", 2017. https://doi.org/10.59350/z9g5j-r2p69
4. H. Rzepa, "(Hyper)activating the chemistry journal.", 2009. https://doi.org/10.59350/wczky-8sf79

In 2023, we very much take for granted that everyone and pretty much everything is online. But it was not always so and when I came across an old plan indicating how the chemistry department at Imperial College was connected in 1989, I was struck by how much has happened in the 34 years since. Nowadays all the infrastructures needed are effectively “built in” to the building when it is constructed and few are even aware of them. But in 1989 that was not at all true.

To introduce the plan I discovered, I will first try to very briefly summarise the evolution of computing and IT infrastructures in a typical university and its departments.

1. I will commence around 1960, when most universities started supporting computer “mainframes”. For Imperial college, this was an IBM machine and to access its resources, one had to physically go to the punch room allocated for the purpose. I remind that this is only around 16 years after the Colossus machine started operating in Bletchley park.
2. By around 1974, although visiting the “card reader” and the “line printer” was still the best way to access the (single) mainframe, a few select users had access to a “teletypewriter” in their own department. In that year I had started my PhD and I spend quite a lot of time in one such room writing programs and running them, all at the speed of 300 baud. The mainframe was now a CDC 6400 and the terminal was connected to it by a wire running through the heating tunnels.
3. By around 1977, the teletypewriter was augmented with a graphics terminal ( Tektronix 4014) which could be used for generating plots, phototypesetting etc. It now operated at 9600 baud, using two line boosters to achieve this effect.
4. By about 1981, there were 3-4 terminals in the department, with the number increasing rapidly. They now could be used to access resources around the world. I remember the impact that access to STN International (connecting to Chemical abstracts, called SciFinder nowadays) using such a terminal had on most of the researchers. If the queue was too long, you instead went to the library, where they had also installed such a terminal. One terminal was devoted to word processing, using a simple command line editor, where I wrote my scientific articles. Joy! To support these terminals, we had installed devices called PADs (packet assemblers/disassemblers) running at 19600 baud and supporting the X25 protocol.
5. By 1986, the department had already gone through one generation of graphical interface computers (Corvus Concept computers with their own network) which supported early word processing and we were starting to support IBM PCs connected to the PADs by serial lines and the newly released Mac Computers. The latter had their own network (Appletalk) and because these machines were so popular (due to Chemdraw), we started to install an extensive Appletalk network, connected to a core Webster Multigate, which was itself routed to the main College resources using thick wire ethernet. Attached to the Appletalk was our first laser printer! I well remember going to an Apple FTP site and periodically downloading the latest version of their operating system onto a floppy disk so that we could update our Macs and stop them crashing quite so much.
6. And so we reach 1989, and the complex networking shown there.“

All this was done within the department, since the central computing resources (the “computing centre”) in 1989 were still focused on the use of mainframes, but starting to devolve into networked workstations (mostly Silicon graphics) by 1991. It would be another decade or so before they full morphed into an IT division and left mainframes behind. By now, networks had become firmly part of the core of their operations.

7. But before this, but not shown on this map, chemistry installed in 1999 about 40 WiFi base stations so that people could start to access online resources without the “wires” shown in the above diagram. Mostly in those days Mac computers.
8. And with WiFi and then cellular support, came the phones of course.
9. I will finish by saying that the current generations of PCs and Macs (which had replaced the workstations) are still “wired” into the department infrastructures, now at speeds of 1 Gbit!

In 2023 a new phenomenon has emerged – software tunnels to allow secure access into the departmental network. We use a product called ZScaler (replacing VPN), and it depends intimately on having a phone to authenticate access. Without that phone and its own 5G access, it is difficult to do anything nowadays.

Quite a lot of change over 34 years!

I am a member of the  Royal Society of  Chemistry’s Historical group. Amongst other activities, it publishes two editions of a newsletter each year for its members. A new theme was recently launched asking for contributions on the topic of  “two influential books” and shortly to appear in the winter 2023 edition will be the following recollections by myself (reprinted here with permission).

Two influential books

1. Practical Organic Chemistry by A. J. Mee, J. M. Dent and Sons, 1959 (”Mee”)
2. Modern Inorganic Chemistry by G. D. Parks and J. W. Mellor, Longmans, 1946 (”Mellor”)

My connection with both these books goes back to around 1962 and is set in a particular context. Being an only child, I played extensively with my two cousins who lived nearby. Their mother had a science degree and was in fact the owner of the inorganic text. When my aunt decided to emigrate to Canada in that year along with my cousins, she left her textbooks with my parents, perhaps in the very prescient anticipation that I would discover and read them. They were stored deep inside in the cupboard under the stairs. I was forever crawling into small spaces – a habit that had often caused consternation to my parents even at the age of three – and it was there I discovered the Mellor one day. It is not the kind of book that a twelve-year-old would normally start reading, but my parents had noted that I was missing my cousins and had decided to purchase a chemistry set for me as some form of distraction. There was something of a disconnect of course between all the fascinating compounds described in the Mellor text, and the relatively small range of chemicals in the boxset. The disconnect was made worse since I was particularly fascinated by the explosive and dangerous compounds described in the Mellor. Chlorine heptoxide (p 507) is just one example that attracted me particularly, including its explosive nature. Nitrogen tri-iodide (p 401) is of course far more famous and therein lie several more stories.[1]
Mellor is scattered with diagrams of the apparatus used to prepare the compounds described, but I have no idea why as a 12-year-old I found all this so fascinating! Indeed I read about almost any oxide avidly- especially if it was coloured. So, after a few days, and with all the chemicals in the set exhausted, I needed to find replacements.

I have no recollection about how I located A. N. Beck and Sons in Stoke Newington (no Google in those days of course), but they were a regular high street pharmacist who happened to have a basement where they would sell often exotic chemicals to 12-year-old boys and girls. None of this bears thinking about nowadays of course! Stoke Newington was a lengthy bus ride away from where we lived in southeast London, but I happily ventured on my own on the 72 bus and started returning not only with a new batch of chemicals but also the glassware needed to perform ”proper” experiments. Imagine my delight when I got a water pump and was able to do reduced pressure distillations. All this in a small (unventilated) annex to the kitchen in the house, the use of which my parents just about tolerated. At least until the day that I mixed ethanol with a mixture of sulfuric and nitric acids and sprayed a rather nice Jackson Pollock brown pattern onto the kitchen ceiling. My punishment for doing this was learning how to repaint the ceiling – I have been none too fond of painting ceilings ever since. I was now able to explore a few more of the compounds mentioned in the Mellor text, which I continued to absorb avidly. But soon I realised that there was much more to chemistry than described in Mellor.

A. N. Beck and Sons not only sold chemicals but also had a few books for purchase and that is how one day I went home clutching A. J. Mee’s text on practical organic chemistry. That contained 297 experiments, many of which could be conducted in my new home laboratory. I started that book with dyes, which magically transform entirely colourless compounds into startingly bright reds and yellows and less often blues and greens. Indeed, at age 17 when I was starting my university course applications, I even applied to the colour chemistry course at Leeds. It is my regret that during this period, I never attempted the synthesis of mauveine, a compound that has a very local flavour since the site of the factory that its discoverer Perkin built to manufacture it is just down the road from where we now live.[2] After several years, I had ticked around half of the experiments in Mee and saved not a few of the final products in sealed glass specimen tubes. Dinitrogen tetroxide is a memorable sample from that period, since it is not easy to seal a compound that boils at 22 C.

I should mention one interesting characteristic of the experiments described in Mee – the propensity to use large quantities of compounds. A typical experiment could use up to 10-50 g of material. As someone with a limited budget (approximately half of which was now being spent on attending football matches), I soon realised that a ten-fold reduction in quantities did not lessen the enjoyment of the preparation. Nowadays in some taught laboratories, the quantities are often measured in mg! The preparation of benzidine was an exception, involving 2g of this highly carcinogenic species and which I followed Mee to the letter. I still have nightmares about my experiments with this species and the quantity of it I produced – the Mee text does not mention the toxicity.

Just to balance things out, I should mention that I also (tried to) read a theoretical chemistry text by J. W. Linnet^‡ which contained no home experiments to perform but probably sowed the seeds for my subsequent career years later.

By the time I started my university course in 1968, I was able to shut down my home laboratory (much to the relief of both parents) and continued in a somewhat safer university laboratory. Perhaps unsurprisingly, given the six years or so of practical experience I already had, I was delighted to win a prize for practical chemistry in my final year. By this stage of course, the standard inorganic texts were books by Cotton and Wilkinson and Vogel’s practical organic chemistry – both in a very different style from my two selections above. I continued making molecules for my three years of PhD during the period 1971-74 – mainly sterically hindered indoles and indolinones – and it was these final syntheses that set me on my subsequent career of modelling reactions using quantum mechanics – a story told elsewhere.[3] But without doubt, both the Mellor and the Mee books played a crucial role in directing me along this long and winding path.

In 2014, some fifty years after reading my two highlighted books, I decided to find out if anyone else had similar experiences and I posted about them on my blog.[4] To my delight 52 responses have been received to date and perhaps this newsletter article might encourage a few more? It turns out I was not alone. I even got one response from Hillary Beck Grant, whose father Kingsley Beck was the son of Albert Neve Beck. She vividly remembers the smell in the basement where two women did all the bottling, packing and dispatching. Sounds very similar to my own kitchen annex!

^‡J. W. Linnett, The Electronic Structure of Molecules: A New Approach. 1964, Methuen.

References

1. H. Rzepa, "Halogen bonds 3: "Nitrogen tri-iodide"", 2014. https://doi.org/10.59350/d4xrw-f1j66
2. H. Rzepa, "William Henry Perkin: The site of the factory and the grave.", 2013. https://doi.org/10.59350/j80na-mgz43
3. H.S. Rzepa, "The Long and Winding Road towards FAIR Data as an Integral Component of the Computational Modelling and Dissemination of Chemistry", Israel Journal of Chemistry, vol. 62, 2021. https://doi.org/10.1002/ijch.202100034
4. H. Rzepa, "Chemistry in the early 1960s: a reminiscence.", 2014. https://doi.org/10.59350/hjf0v-c0z37

Some 13 years ago, I speculated about the longevity of the type of science communication then (and still now) represented by Blogs. I noted one new project called ArchivePress that was looking into providing solutions equivalent to what scientific journals have done for some 350 years of science communication. The link to ArchivePress no longer works, but details of the project can still be found here. Since then the technology and infrastructure has moved on, with a new backbone provided by the use of persistent identifiers (PIDs) in the form of DOIs. The PID ecosystem is now extensive and so a revival of the concept has recently been launched called The Rogue Scholar. Here I take a look at some of is features and illustrate these with application to this blog.

To quote its aims “The Rogue Scholar improves your science blog in important ways, including full-text search, long-term archiving, DOIs and metadata”. Lets take these four ways and compare them with how scientific journals function.

1. Full text search. The traditional journal is full-text indexed by its publisher, but of course there are many science publishers out there and they focus on indexing only their own journals. There are an estimated 30,000+ science journals, covered by commercial abstracting agencies such as SciFinder. A search engine that aggregates full text searches across (most?) journals is Google of course. Type a full text search string, enclosing it in quotes to get a literal search of the entire string,^‡ and you are quite likely to find the journal article. Try this for yourself and report back if it does not work. If you try scholar.google.com instead, it will not work (even using the Advanced search/Exact phrase constraint). Try then some text from a blog^† and again with scholar.google.com it will not work but with Google it does (I have not tried other search engines).
   • • Now try eg the blog search using RogueScholar and you get the successful result shown below.
       
     • Full “advanced mode” searching is of course second nature to chemists, who apply a variety of fielded or constrained searches are part of their regular routine (including eg chemical substructure searching), but you often need specialist abstracting and indexing agencies such as Scifinder for this. But RogueScholar will offer constrained searches I understand at some stage, based on “metadata” and so I will take this topic next.
2. MetaData and DOIs. When a journal article is published, part of the process is to gather metadata about the article and submit it to a metadata aggregating agency such as CrossRef. In exchange, the latter offer a DOI which functions as a unique and persistent identifier for that article. The metadata terms can be used in a constrained search with CrossRef, and with DataCite for FAIR data. RogueScholar does exactly the same, it gathers metadata from a registered blog post, including ORCID identifiers associated with the post, registers it and enables searching. Try e.g. 0000-0003-3315-3524 as a search term and see what you get. This also works for DOIs (try 10.59350/65c45-3ew97 as a search term). So here too, we can see parity emerging with conventional journal publishing.
3. The final component is long-term archiving. Again journals have been doing this for a long time (on paper) and in the last 30 years or so in digital form. Blogs have until now lacked this and here again RogueScholar is promising such long term archiving in its next iteration.
   • This actually raises one interesting, albeit difficult, aspect of blogs – one however that may in fact be somewhat unique to this particular blog. The topic of my very first post here back in 2008 was how interactive 3D molecular models could be included in the post itself to help the reader explore the chemical points I was trying to make. Back then I regarded it as something that could not be so easily done as part of journal articles[1] (although you do see it nowadays), but that feature certainly presents a challenge to long term archival! I do not see a solution for this one on the horizon.

Rogue Scholar is still a very young service, and no doubt will evolve rapidly from this point, so I may revisit in say six months time to see how it has come along. Meanwhile, try it out and see what you think. And because science blogs can now be assigned a DOI on the same level as journal articles, they too can join the so-called universe of “Knowledge or PID graphs“[2].

^‡ For example “In 2022, bicyclo[3.1.1]heptanes were proposed to mimic the fragment of meta-substituted benzenes in biologically active compounds”
^† “The schematic representation of a chemical reaction mechanism is often drawn using a palette of arrows connecting or annotating the various molecular structures involved. These can be selected from a chemical arrows palette, taken for this purpose from the commonly used structure drawing program Chemdraw.”

This post has DOI: 10.59350/8m2d8-47b52

References

1. D. James, B.J. Whitaker, C. Hildyard, H.S. Rzepa, O. Casher, J.M. Goodman, D. Riddick, and P. Murray‐Rust, "The case for content integrity in electronic chemistry journals: The CLIC project", New Review of Information Networking, vol. 1, pp. 61-69, 1995. https://doi.org/10.1080/13614579509516846
2. H. Cousijn, R. Braukmann, M. Fenner, C. Ferguson, R. van Horik, R. Lammey, A. Meadows, and S. Lambert, "Connected Research: The Potential of the PID Graph", Patterns, vol. 2, pp. 100180, 2021. https://doi.org/10.1016/j.patter.2020.100180

I have variously talked about persistent identifiers on this blog. These largely take the form of DOIs (Digital object identifiers), and here they relate to either journal articles or datasets associated with either the article or the blog post or both. Other disciplines, particularly the earth sciences, have long used persistent identifiers (PIDs) to identify physical objects rather than digital ones. One of my ambitions is to assign such identifiers to a small but highly historical collection of physical objects in my possession, as described at this post. As a prelude to this project, here I describe some ways of searching for physical objects that have been assigned a PID. Thanks Rorie for providing these! 

1. Here is a general search for physical objects with associated metadata describing them as registered with DataCite. https://commons.datacite.org/doi.org?query=types.resourceTypeGeneral:PhysicalObject (11,269,090 items)
2. The search can be slightly constrained to find only identifiers that originate from the earlier IGSN ID (International generic sample number) see here for details and https://www.igsn.org/about/ for the organisation set up) using the syntax query=client.client_type:igsnCatalog types.resourceTypeGeneral:PhysicalObject (9,642,030 items)

The exciting prospect is that in due time, such searches could be constrained by adding specifically chemical properties, most obviously eg an InChI identifier. At the moment, it is unlikely any existing samples have even been registered with such a term.

3. Thus combining two queries would give the following:
   query=client.client_type:igsnCatalog types.resourceTypeGeneral:PhysicalObject+AND+subjects.subjectScheme:inchikey+AND+subjects.subject:*
4. Removing the PhysicalObject constrain gives a different response:
   query=(subjects.subjectScheme:inchikey+AND+subjects.subject:*+OR+subjects.subjectScheme:inchi+AND+subjects.subject:*)

 When this becomes possible, (see project above!), it would enable for example journal articles (or the FAIR data associated with them) to reference information about a physical sample associated with eg the preparation of a molecule new to science.

Sometimes, the properties of a molecule are predicted long before it is synthesised. One such is diberyllocene. I first encountered a related molecule, beryllocene itself, many moons ago.[1] This was unusual because unlike the original metallocenes, the metal atom was not symmetrically disposed between the two cyclopentadienyl faces. Now diberyllocene is finally reported in which replacing one Be by Be-Be induces (according to calculation, D₂) symmetry[2]. I will not repeat the excellent analysis of the wavefunction reported in this article, but confine myself to showing two molecular orbitals which examplify its bonding.

Highest occupied molecular orbital
Lowest occupied π-molecular orbital

The HOMO (FAIR data 10.14469/hpc/12702) essentially shows a Be-Be single bond, originating formally from the central Be₂²⁺ dication, balanced by the two cyclopentadienyl anion ligands. Click on the images to see this orbital in  3D.

Oddly, an excited state of Be₂ on its own actually carries a Be=Be double bond, a property again predicted a long time ago by theory. The most stable π-MO in diberyllocene originates in the six electron aromatic cyclopentadienyl rings. By acquiring a share of six electrons from one Cp ring, and a share of the two electrons from the Be-Be bond, each Be atom achieves the octet of electrons known by generations of students. This is the sort of molecule that could be taught in schools at an early stage to illustrate the octet rule. And its good to know that simple new molecules illustrating this are still being discovered by chemists.

Since this started with experimental realisation of a predicted molecule, can I suggest as a new prediction, lithioborocene, in which a B and an Li replace two Be atoms? Individually, lithiocenes, boracenes and Li-B bonds are known from crystal structures. So its not a way out prediction to combine these observations. Any friendly synthetic chemist up for the challenge?

This post has DOI: 10.14469/hpc/12704

References

1. M.J.S. Dewar, and H.S. Rzepa, "Ground states of molecules. 45. MNDO results for molecules containing beryllium", Journal of the American Chemical Society, vol. 100, pp. 777-784, 1978. https://doi.org/10.1021/ja00471a020
2. J.T. Boronski, A.E. Crumpton, L.L. Wales, and S. Aldridge, "Diberyllocene, a stable compound of Be(I) with a Be–Be bond", Science, vol. 380, pp. 1147-1149, 2023. https://doi.org/10.1126/science.adh4419

This is a venerable organic reaction, which curiously I have not previously covered here. First described in 1859, its nature was only properly elucidated in 1873. It is a member of a class of reaction I have previously named “solvolytically assisted pericyclic”, or “perisolvolytic“. Here I explore some of the subtle stereoelectronic effects observed for this apparently simple reaction.

It applies to a class of molecule known as 1,2-diols. Protonation is quickly followed by migration of a (in this example) methyl group, followed by deprotonation of the carbonyl group formed by this process. There are two mechanistic stages, the first being the departure of the now protonated “ol” unit, and the second the migration of the methyl. In most text books and of course Wikipedia, these are shown as very distinct steps. But they could also occur in one concerted step, albeit probably asynchronously.

A B3LYP+GD3+BJ/Def2-TZVPP/SCRF=ethanol calculation provides mechanistic detail (FAIR Data 10.14469/hpc/1769)

1. To start with, we note the H-bond formed between O22-H21. Between IRC = -10 and -6, this lengthens from 1.625Å to 1.843Å, destabilising the protonated alcohol group.
2. Between IRC -6 to -1, the C1-O19 bond breaks, from a starting length of 1.556Å to ~2.787Å.
3. When IRC 0.0 is reached (the transition state), the C11 methyl starts to migrate across, a process mostly complete by IRC +2. 
4. The final stage is formation of a weak interaction between C2 and O19 to reach IRC 7.
5. Several more minor effects can also be discerned. Firstly methyl C3 rotates, to set up a better hyperconjugative interaction with the temporary carbocation forming at C1. This rotamer forms the first of several “hidden intermediates” in the reaction, intermediates which almost form before being consumed, at IRC -6.5 (see the plot above labelled RMS gradient form, for the minimum in the function at this IRC value).
6. Another hidden intermediate appears at IRC -2, being the transient carbocation, as shown in stepwise versions of this mechanism, such as the Wikipedia page. But its not real, merely hidden! As it approaches, methyl C7 rotates to maximise the hyperconjugative interactions.
7. At IRC ~+3, methyl C15 rotates to again maximise hyperconjugation with the newly formed C=O bond.

Ca we quantify some of these effects? This can be done by computing localised orbitals (NBOs) and pairwise interactions between a donor NBO (a bond or a lone pair) and an acceptor NBO (an antibonding orbital). 

1. The E(2) interaction between donor bond C2-C11 and acceptor C1-O19 is 3.3 kcal/mol (above the noise, but not especially strong). It corresponds to an antiperiplanar alignment of the C2-C11 σ orbital and the C1-O19 σ^* orbitals and results in the breaking of bond C2-C11 (and reformation as C1-C11). 
2. The E(2) value between donor lone pair O22 and acceptor C2-C11 σ^* is 6.9 kcal/mol and corresponds to antiperiplanar alignment of these two orbitals, resulting in formation of the C=O carbonyl π-bond, whilst simultaneously increasing the antibonding character of the C-C bond to encourage it to break.

Models of these two interactions can be seen below. Click on the image to load them. The colour blue overlaps positively with the colour purple, and red with orange.

By the time the transition state is reached, these two interactions have evolved to the following:

So this venerable reaction has some nice subtle stereoelectronic behaviour. Those methyl rotations have been skipped over here, but a deeper look into them might also be worthwhile. There is much more to this reaction, but I will leave this analysis here.

This post has DOI https://doi.org/10.14469/hpc/12684