Imperial College London

Henry Rzepa

Valence shell electron pair repulsion theory is a simple way of rationalising the shapes of many compounds in which a main group element is surrounded by ligands. ClF

 3

is a good illustration of this theory.

VSEPR Theory:   A closer look at chlorine trifluoride, ClF3.

Chemistry as the inspiration for art! The inspiration was the previous post. As for whether its art, you decide for yourself.

And now for something completely different: The art of molecular sculpture.

The Wikipedia page on hypervalent compounds reveals that the concept is almost as old as that of normally valent compounds.

Hypervalency: Is it real?

Lactide is a small molecule made from lactic acid, which is itself available in large quantities by harvesting plants rather than drilling for oil. Lactide can be turned into polymers with remarkable properties, which in turn degrade down easily back to lactic acid. A perfect bio-renewable material!

Bio-renewable green polymers:  Stereoinduction in poly(lactic acid)

Chemists now use the term “curly arrows” as a language to describe the electronic rearrangements that occur when a (predominately organic) molecule transforms to another – the so called chemical reaction. It is also used to infer,

 via

valence bond or resonance theory, what the mechanistic implications of that reaction are.

The 100th Anniversary year of Curly Arrows.

A comment made on the previous post on the topic of hexa-coordinate carbon cited an article entitled “

 Observation of hypervalent CLi
 
 6
 
 by Knudsen-effusion mass spectrometry

”[cite]10.1038/355432a0[/cite] by Kudo as a amongst the earliest of evidence that such species can exist (in the gas phase). It was a spectacular vindication of the earlier theoretical

Is  CLi6 hypervalent?

Another post inspired by a comment on an earlier one; I had been discussing compounds of the type I.I

 n

(n=4,6) as possible candidates for hypervalency.

Hypervalent or not? A fluxional triselenide.

In the previous two posts, a strategy for tuning the nature of the CS bond in the molecule HO-S≡C-H was developed, based largely on the lone pair of electrons identified on the carbon atom. By replacing the HO group by one with greater σ-electron withdrawing propensity, the stereo-electronic effect between the O-S bond and the carbon lone pair was enhanced, and in the process, the SC bond was strengthened.

The nature of the C≡S triple bond: part 3.

A previous post was triggered by Peter alerting me that interactive electronic supporting information (

 IESI

) we had submitted to a journal in 2005[cite]10.1021/ic0519988[/cite] appeared to be strangely missing from the article landing page. This set me off recollecting our journey, which had started around 1998, and to explore what the current state of these ancient

 IESI

s were in 2022.

Four stages in the evolution of interactive ESI as part of articles in chemistry journals.

Thus famously wrote Woodward and Hoffmann (WH) in their classic monograph about the conservation of orbital symmetry in pericyclic reactions.

Violations. There are none!

I occasionally spot an old blog that emerges, if only briefly, as “trending”. In this instance, only the second blog I ever wrote here, way back in 2009 as a follow up to this article.[cite]10.1021/ed084p1535[/cite] With something of that age, its always worth revisiting to see if any aspect needs updating or expanding, given the uptick in interest.

Trimerous pericyclic reactions.

Continuing an exploration of the mechanism of this reaction, an alternative new mechanism was suggested in 1989 (having been first submitted to the journal ten years earlier!).[cite]10.1002/jhet.5570260518[/cite] Here the key intermediate proposed is a thiirenium cation (labelled

 8

in the article) and labelled

 Int3

below.

The Willgerodt-Kindler Reaction: mechanistic reality check 2.

One of the most fascinating and important articles dealing with curly arrows I have seen is that by Klein and Knizia on the topic of C-H bond activations using an iron catalyst.[cite]10.1002/anie.201805511[/cite] These are so-called high spin systems with unpaired electrons and the mechanism of C-H activation involves both double headed (two electron) and fish-hook (single electron) movement.

Curly arrows in the 21st Century. Proton-coupled electron transfers.

My momentum of describing early attempts to use optical rotation to correlate absolute configuration of small molecules such as glyceraldehyde and lactic acid with their optical rotations has carried me to

 L-Malic acid

(below labelled as (

 S

)-Malic acid). The measured optical rotatory dispersion curve at low wavelengths is shown below (dashed line for Malic acid, solid line for Lactic acid). A sign inversion

L-Malic acid: An exercise in conformational analysis impacting upon optical rotatory dispersion (ORD).

In 2012, I wrote a story of the first ever reaction curly arrows, attributed to Robert Robinson in 1924. At the time there was a great rivalry between him and another UK chemist, Christopher Ingold, with the latter also asserting his claim for their use.

Early “curly” (reaction) arrows. Those of Ingold in 1926.

This editorial from Nature[cite]10.1038/d41586-023-01612-x[/cite] is a timely reminder of the importance of data.

“For chemists, the AI revolution has yet to happen”.

Chloroform, often in the deuterated form CDCl

 3

, is a very common solvent for NMR and other types of spectroscopy. Quantum mechanics is increasingly used to calculate such spectra to aid assignment and the solvent is here normally simulated as a continuum rather than by explicit inclusion of one or more chloroform molecules. But what are the features of the hydrogen bonds that form from chloroform to other acceptors?

Hydrogen bonding to chloroform.

In the previous post, I discussed the structure of the free base form of tetrodotoxin, often represented as originally suggested by Woodward[cite]10.1351/pac196409010049[/cite] below in an ionic form:    Quantum calculations suggested that this form was higher in energy than neutral forms devoid of the zwitterionic charge separation in a relatively non polar solvent such as chloroform. For this, a so-called continuum solvation model was used.

The Structure of Tetrodotoxin as a free base – with a better solvation model.

This is another in the occasional series of “what a neat molecule”. In this case, more of a “what a neat idea”. The s-triazine below, when coordinated to eg ZnI

 2

, forms what is called a metal-organic-framework, or MOF.

X-ray analysis and absolute configuration determination using porous complexes.

Its a bit like a jigsaw puzzle in reverse, finding out to disassemble a chemical reaction into the pieces it is made from, and learning the rules that such reaction jigsaws follow. The following takes about 45-50 minutes to follow through with a group of students.

Secrets of a university tutor: dissection of a reaction mechanism.

In 2016, the world heard that gravitational waves had been detected and now a third instance is reported.

 ‡

Given that the data associated with these detections are perhaps amongst the most important instances in recent times, I thought I might take a peek at how it was managed. The original report in 2016[cite]10.1103/PhysRevLett.116.061102[/cite] cited (Ref 116) data as DOI: 10.7935/K5MW2F23.

FAIR Research data: Gravitational waves as an example from the astrophysics community.

We tend to think of simple hydrocarbons as relatively inert and un-interesting molecules. However, a recent article[cite]10.1002/anie.201202894[/cite], which was in fact highlighted by Steve Bachrach on his blog , asks what “

 The Last Globally Stable Extended Alkane

” might be. In other words, at what stage does a straight-chain hydrocarbon fold back upon itself, and no significant population of the linear form remain?

The strangely attractive conformation of C17H36.

Nowadays, data supporting most publications relating to the synthesis of organic compounds is more likely than not to be found in associated

 “supporting information

“ rather than the (often page limited) article itself. For example, this article[cite]10.1021/jacs.6b13229[/cite] has an SI which is paginated at 907;

Supporting information: chemical graveyard or invaluable resource for chemical structures.

Birch reduction of benzene itself results in 1,4-cyclohexadiene rather than the more stable (conjugated) 1,3-cyclohexadiene. Why is this?

The mechanism of the Birch reduction. Part 3: reduction of benzene

Years ago, I was travelling from Cambridge to London on a train. I found myself sitting next to a chemist, and (as chemists do), he scribbled the following on a piece of paper. When I got to work the next day Vera (my student) was unleashed on the problem, and our thoughts were published[cite]10.1039/C39920001323[/cite]. That was then. This is now.

More joining up of pieces. Stereocontrol in the ring opening of cyclopropenes.

Text books (is this a misnomer, much like “papers” are in journals?) in a higher-educational chemistry environment, I feel, are at a cross-roads. What happens next? Faced with the ever-increasing costs of course texts, the department where I teach introduced a book-bundle about five years ago. The bundle included all the recommended texts for an appreciable discount over individual purchase.

&#8220;Text&#8221; Books in a  (higher) education environment.

In the preceding post, I described a fascinating experiment and calculation by Bogle and Singleton, in which the trajectory distribution of molecules emerging from a

 single

transition state was used to rationalise the formation of two isomeric products

 2

and

 3.

In the present post, I explore possible consequences of including a sodium cation (X=Na

 +

below) in the

Dynamic effects in nucleophilic substitution at trigonal carbon (with Na+).

The Baldwin rules for ring closure follow the earlier ones by Bürgi and Dunitz in stating the preferred angles of nucleophilic (and electrophilic) attack in bond forming reactions, and are as famous for the interest in their exceptions as for their adherence. Both sets of rules fundamentally explore the geometry of the transition states involved in the reaction, as reflected in the activation free energies.

Transition state models for Baldwin&#8217;s rules of ring closure.

WATOC 2020 was just held in 2022 in Vancouver Canada, over one week. With many lectures held in parallel, it is not possible for one person to cover anything like the topics presented, so this is a personal view of some of those talks that I attended. As happens with many such events, common themes gradually emerge and here I highlight just two that struck me as important for the future of computational chemistry.

 Dispersion

.

Personal Impressions from WATOC 2020 – Dispersion and non Born-Oppenheimer models.

The properties of electrons are studied by both chemists and physicists. At the boundaries of these two disciplines, sometimes interesting differences in interpretation emerge. One of the most controversial is that due to Bader (for a recent review, see DOI: 10.1021/jp102748b) a physicist who brought the mathematical rigor of electronic topology to bear upon molecules.

Are close H&#8230;H contacts bonds?

Organic chemistry has some no-go areas, where few molecules dare venture. One of them is described by a concept known as anti-aromaticity. Whereas aromatic molecules are favoured species, their anti-equivalent is avoided. I previously illustrated this (Hückel rule) with cyclopropenium anion.

Some fun with no-go areas of chemistry: cyclobutadiene.

The mechanism of ester hydrolysis is a staple of examination questions in organic chemistry. To get a good grade, one might have to reproduce something like the below. Here, I subject that answer to a reality check.

A sideways look at the mechanism of ester hydrolysis.

I mentioned in the last post that one can try to predict the outcome of electrophilic aromatic substitution by approximating the properties of the transition state from those of either the reactant or the (presumed Wheland) intermediate by invoking Hammond’s postulate[cite]10.1021/ja01607a027[/cite]. A third option is readily available nowadays; calculate the transition state directly. Here are the results of exploring this third variation.

Kinetic vs Thermodynamic control. Subversive thoughts for electrophilic substitution of Indole.

One frequently has to confront the question: will a hydrogen bond form between a suitable donor (lone pair or π) and an acceptor? One of the factors to be taken into consideration for hydrogen bonds which are part of a cycle is the ring size. Here I explore one way of quantifying the effect for the series below, n=1-5 (4-8 membered rings).      I will use the NBO approach.

Hydrogen bond strength as a function of ring size.

Cavities promote reactions, and they can also trap the products of reactions. Such (supramolecular) chemistry is used to provide models for how enzymes work, but it also allows

 un-natural

reactions to be undertaken.

Reactions in supramolecular cavities &#8211; trapping a cyclobutadiene: ! or ?

In the previous two posts, I noted the recent suggestion of how a stable frozen S

 N

2 transition state might be made. This is characterised by a central carbon with five coordinated ligands.

It&#8217;s penta-coordinate carbon Spock- but not as we know it!

The iconic diagram below represents a cornerstone of organic chemistry.

Longer is stronger.

Every introductory course or text on aromatic electrophilic substitution contains an explanation along the lines of the resonance diagram shown below. With an

 o

/

 p

directing group such as NH

 2

, it is argued that negative charge accumulates in those positions as a result of the resonance structures shown. MEP for PhNH2. Click for 3D.The opposite occurs for electron withdrawing groups.

Aromatic electrophilic substitution: a different way of predicting regiospecificity

Following on from my re-investigation of close hydrogen bonding contacts to the π-face of alkenes, here now is an updated scan for H-bonds to alkynes. The search query (dataDOI: 10.14469/hpc/2478) is similar to the previous one: QA is any of N,O,F,Cl. X is any atom, including metals and non-metals.

π-Facial hydrogen bonds to alkynes (revisited): how close can an acidic hydrogen approach?

There is much focus at the moment on how to ensure experimental replicability in

 e.g.

the molecular sciences. An important aspect of that is having access to

 FAIR

data; data which is findable, accessible, inter-operable and re-usable. One of the “gold standards” in chemistry is the data associated with crystal structures.

Accessing (raw) chemical data: a peek into the CIF format.

Singleton and co-workers have produced some wonderful work showing how dynamic effects and not just transition states can control the outcome of reactions. Steve Bachrach’s blog contains many examples, including this recent one. This shows that tolyl thiolate (X=Na) reacts with the dichlorobutenone to give two substitution products in a 81:19 ratio.

Dynamic effects in nucleophilic substitution at trigonal carbon.

Ten years are a long time when it comes to (recent) technologies. The first post on this blog was on the topic of how to present chemistry with three intact dimensions.

Ten years on: Jmol and WordPress.

Previously, I looked at autocatalytic mechanisms where the carboxyl group of an oxetane-carboxylic acid could catalyse its transformation to a lactone, finding that a chain of two such groups were required to achieve the result. Here I look at an alternative mode where the oxetane-carboxylate itself acts as the transfer chain, via a H-bonded dimer shown below.

Unexpected Isomerization of Oxetane-Carboxylic Acids – an alternative autocatalytic mechanism evaluated.

The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post. The lowest energies of the four diastereomers

 A-D

, each in two conformations (

 1/2

) were calculated at the ωB97D/6-311G(d,p)/SCRF=ethanol level, and are shown here relative to

 A1

(kcal/mol) as free energies.

Updating a worked problem in conformational analysis. Part 2: an answer.

C&amp;EN has again run a vote for the 2017 Molecules of the year. Here I take a look not just at these molecules, but at how FAIR (Findable, Accessible, Interoperable and Reusable) the data associated with these molecules actually is.  I went about finding out as follows: The article DOI for all seven candidates was linked to the C&amp;EN site.

How FAIR are the data associated with the 2017 Molecules-of-the-Year?

A bond index (BI) approximately measures the totals of the bond orders at any given atom in a molecule. Here I ponder what the maximum values might be for elements with filled valence shells.

What are the highest bond indices for main group and transition group elements?

A little while ago I pondered allotropic bromine, or Br(Br)

 3

. But this is a far wackier report[cite]10.1126/science.aao7293[/cite] of

 a molecule of light.

The preparation and detection of dimer and trimer bound photon states is pure physics; probably considered by the physicists themselves as NOT chemistry. It is certainly true, as a chemist,  that I understood only a little of the article.

Is  (hν)3 an allotrope of light?

Fascination with nano-objects, molecules which resemble every day devices, is increasing. Thus the world’s smallest car has just been built[cite]10.1038/nature10587[/cite]. The mechanics of such a device can often be understood in terms of chemical concepts taught to most students. So I thought I would have a go at this one!

Driving the smallest car ever made: a chemical perspective.

Kinetic isotope effects have become something of a lost art when it comes to exploring reaction mechanisms. But in their heyday they were absolutely critical for establishing the mechanism of the benzidine rearrangement[cite]10.1021/ja00373a028[/cite]. This classic mechanism proceeds

 via


 bis

protonation of diphenyl hydrazine, but what happens next was the crux.

The  Benzidine rearrangement. Computed kinetic isotope effects.

This week the ACS announced its intention to establish a “

 ChemRxiv preprint server to promote early research sharing

”. This was first tried quite a few years ago, following the example of especially the physicists. As I recollect the experiment lasted about a year, attracted few submissions and even fewer of high quality.

Chemistry preprint servers (revisited).

The interface between physics, chemistry (and materials science) can be a fascinating one. Here I show a carbon nanotorus, devised by physicists[cite]10.1103/PhysRevLett.88.217206[/cite] a few years ago. It is a theoretical species, and was predicted to have a

 colossal paramagnetic moment

. Carbon nanotorus.

Metallic carbon nanotori

As the title hints, I have been here before. The S

 N

1 solvolysis mechanism of t-butyl chloride was central to the flourishing of physical organic chemistry from the 1920s onwards, and it appears early on in most introductory lecture courses and text books. There we teach that it is a two-stage mechanism.

The SN1 Mechanism for a third time. Exploration of the intrinsic reaction coordinate.

The title of this post paraphrases E. J. Corey’s article in 1997 (DOI: 10.1016/S0040-4039(96)02248-4) which probed the origins of conformation restriction in aldehydes. The proposal was of (then) unusual hydrogen bonding between the O=C-H…F-B groups. Here I explore whether the NCI (non-covalent-interaction) method can be used to cast light on this famous example of how unusual interactions might mediate selectivity in organic reactions.

Conformational restriction involving formyl CH&#8230;F hydrogen bonds.

Nitrogen tri-iodide, or more accurately the complex between it and ammonia ranks amongst the oldest known molecules (1812). I became familiar with it around the age of 12-13, in an era long gone when boys (and very possibly girls too) were allowed to make such substances in their parent’s back gardens

 ‡

and in fact in the school science laboratory,

 †

an experiment which earned me a personal request to visit the head teacher.

Halogen bonds 3: “Nitrogen tri-iodide”

If you search

 e.g.

Scifinder for N,O-diphenyl hydroxylamine (RN 24928-98-1) there is just one literature citation, to a 1962 patent. Nothing else;

Why is N,O-diphenyl hydroxylamine (PhNHOPh) unknown?

The

 1

H NMR spectrum of an aromatic molecule such as benzene is iconic; one learns that the unusual chemical shift of the protons (~δ 7-8 ppm) is due to their deshielding by a

 diatropic

ring current resulting from the circulation of six aromatic π-electrons following the Hückel 4n+2 rule.

The NMR spectra of methano[10]annulene and its dianion. The diatropic/paratropic inversion.

Zosurabalbin[cite]10.1038/s41586-023-06873-0[/cite],[cite]10.1093/ofid/ofad500.1754[/cite], is receiving a great deal of attention as a new class of antibiotic which can target infections for which current treatment options are inadequate.

Macrocyclic peptide antibiotics – now Zosurabalpin – then  antibacterial  agents based on cyclic D,L-α-peptide architectures.

The Science education unit at the ACS publication C&amp;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.

Molecules of the year: 2023

In discussing ferrocene in the previous post, I mentioned Irving Langmuir’s 1921 postulate that filled valence shells in what he called

 complete

molecules would have magic numbers of 2, 8, 18 or 32 electrons (deriving from the sum of terms in 2[1+3+5+7]). The first two dominate organic chemistry of course, whilst the third is illustrated by the transition series, ferrocene being an example of such.

Beryllocene and Uranocene: The 8, 18 and 32-electron rules.

The preceeding blog entries contain stories about chemical behaviour. If you have clicked on the diagrams, you may even have gotten a Jmol view of the relevant molecules popping up. But if you are truly curious, you may even have the urge to acquire the relevant 3D information about the molecule, and play with it yourself.

On the importance of  Digital repositories in Chemistry

The previous post contained an exploration of the anomeric effect as it occurs at an atom centre X for which the effect is manifest in crystal structures.

A periodic table for anomeric centres, this time with quantified interactions.

In this earlier post, I noted some aspects of the calculated structures of both Z- and B-DNA duplexes. These calculations involved optimising the positions of around 250-254 atoms, for d(CGCG)

 2

and d(ATAT)

 2,

an undertaking which has taken about two months of computer time!

The thermodynamic energies of left and right handed DNA.

The number of repositories which accept research data across a wide spectrum of disciplines is on the up. Here I report the results of conducting an experiment in which chemical modelling data was deposited in six such repositories and comparing the richness of the metadata describing the essential properties of the six depositions. The repositories are as follows:

 Figshare

as a repository dates from 2012.

A comparison of descriptive metadata across different data repositories.

The science journal is generally acknowledged as first appearing around 1665 with the Philosophical Transactions of the Royal Society in London and (simultaneously) the French Academy of Sciences in Paris. By the turn of the millennium, around 10,000 science and medical journals were estimated to exist.

(Hyper)activating the chemistry  journal.

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.

A trip down memory lane: An online departmental connection map from 1989.

In this previous blog post I wrote about one way in which we have enhanced the journal article. Associated with that enhancement, and also sprinkled liberally throughout this blog, are links to a Digital Repository (if you want to read all about it, see DOI: 10.1021/ci7004737). It is a fairly specific repository for chemistry, with about 5000 entries.

A Digital chemical repository &#8211; is it being used?

More inspiration from tutorials. In a lecture on organic aromaticity, the 4n+2/4n Hückel rule was introduced (in fact, neither rule appears to have actually been coined in this form by Hückel himself!). The simplest examples are respectively the cyclopropenyl cation and anion. The former has 2 π-electrons exhibiting cyclic delocalisation, and the 4n+2 (n=0) rule predicts aromaticity.

(anti)aromaticity avoided: a tutorial example

Back in the early 1990s, we first discovered the delights of searching crystal structures for unusual bonding features.[cite]10.1039/P29940000703[/cite] One of the first cases was a search for hydrogen bonds formed to the π-faces of alkenes and alkynes. In those days the CSD database of crystal structures was a lot smaller (&lt;80,000 structures; it’s now ten times larger) and the search software less powerful.

π-Facial hydrogen bonds to alkenes (revisited): how close can an acidic hydrogen approach?

The electrophilic substitution of indoles is a staple of any course on organic chemistry.

Understanding the electrophilic aromatic substitution of indole.

A

 scalemic

molecule is the term used by Eliel to describe any non-racemic chiral compound.

Scalemic molecules: a cheminformatics challenge!

Libraries (and librarians) are evolving rapidly. Thus a week or so ago one of our dynamic librarians here, approached some PhD students and academics to ask them how they used “

 Web 2.0

” (thanks Jenny!). The result was edited (thanks John!) and uploaded, where you can see it below (embedded in this post, I might add, using HTML5). No doubt there is more of this genre to come.

Blogs, Twitter, Wikis and other on-line tools: the movie!

The hydration of an alkene by an acid is one of those fundamental reactions, taught early on in most chemistry courses. What can quantum mechanics teach us about the mechanism of the reaction? The hydration of ethene by a hydronium cation.

Anatomy of a simple reaction: the hydration of an alkene.

I have mentioned Lewis a number of times in these posts; his suggestion of the shared electron covalent bond still underpins much chemical thinking.

Computational &#8220;reality checks&#8221; for mechanistic speculations.

In the previous post, the molecule F3S-C≡SF3 was found to exhibit a valence bond isomerism, one of the S-C bonds being single, the other triple, and with a large barrier (~31 kcal/mol, ν 284i cm-1) to interconversion of the two valence-bond forms.

In the previous post, the molecule F

 3

S-C≡SF

 3

was found to exhibit a valence bond isomerism, one of the S-C bonds being single, the other triple, and with a large barrier (~31 kcal/mol, ν 284

 i

cm

 -1

) to interconversion of the two valence-bond forms. So an interesting extension of this phenomenon is shown below: A cyclic form of the SCS Motif.

Contriving aromaticity from S≡C Triple bonds

Clar islands are found not so much in an ocean, but in a type of molecule known as polycyclic aromatic hydrocarbons (PAH). One member of this class, graphene, is attracting a lot of attention recently as a potential material for use in computer chips.

Clar islands in a π Cloud

The annual “molecule of the year” results for 2021 are now available … and the winner is

 Infinitene

.[cite]10.33774/chemrxiv-2021-pcwcc[/cite],[cite]10.1021/jacs.1c10807[/cite] This is a benzocirculene in the form of a figure eight loop (the infinity symbol), a shape which is also called a

 lemniscate

[cite]10.1021/jo801022b[/cite] after the mathematical (2D) function due to Bernoulli.

Molecule of the year 2021: Infinitene.

In my previous post I speculated why

 bis

(trifluoromethyl) ketone tends to fully form a hydrate when dissolved in water, but acetone does not. Here I turn to asking why formaldehyde is also 80% converted to methanediol in water? Could it be that again, the diol is somehow preferentially stabilised compared to the carbonyl precursor and if so, why? Methanediol. The lowest energy geometry is shown above.

Spotting the unexpected. The hydration of formaldehyde.

My very first post on this blog, in 2008, was to describe how Jmol could be used to illustrate chemical themes by adding 3D models to posts. Many of my subsequent efforts have indeed invoked Jmol. I thought I might review progress since then, with a particular focus on using the new generations of mobile device that have subsequently emerged.

Mobile-friendly solutions for viewing (WordPress) Blogs with embedded  3D molecular coordinates.

Following on from our first mechanistic reality check, we now need to verify how product

 A

might arise in the mechanism shown below, starting from

 B

. This pathway backtracks the original one in reversing the final arrow of that process (shown in red in previous post and in magenta here for the arrow in reverse), to go uphill in energy to reach the secondary (unstabilised) carbocation.

Secrets of a university tutor. An exercise in mechanistic logic: second dénouement.

Previously, I looked at models of how ammonia could be protonated by water to form ammonium hydroxide.

Ways to encourage water to protonate an amine: superbasing.

In the previous post,  it was noted that  Möbius annulenes are intrinsically chiral, and should therefore in principle be capable of resolution into enantiomers. The synthesis of such an annulene by  Herges and co-workers was a racemic one; no attempt was reported at any resolution into such enantiomers.  Here theory can help, since calculating the  optical rotation [α]D  is nowadays a relatively reliable process for rigid molecules.

The Chirality of Lemniscular Octaphyrins

I do not play poker,‡ and so I had to look up a 5-4-3-2-1(A), which Wikipedia informs me is a 5-high straight flush, also apparently known as a steel wheel. In previous posts  I have suggested acids which can be ionised by (probably) 5, 4, 3 or  1 discrete water molecules in the gas phase;

I do not play poker,

 ‡

and so I had to look up a 5-4-3-

 2

-1(A), which Wikipedia informs me is a

 5-high straight flush

, also apparently known as a

 steel wheel

. In previous posts  I have suggested acids which can be ionised by (probably) 5, 4, 3 or  1 discrete water molecules in the gas phase;

A 5-high straight flush of water-ionised acids?

The reaction described in the previous post (below) is an unusual example of nucleophilic attack at an sp

 2

-carbon centre, reportedly resulting in inversion of configuration[cite]10.1021/ja00765a062[/cite]. One can break it down to a sequence of up to eight individual steps, which makes teaching it far easier. But how real is that sequence?

Secrets of a university tutor. An exercise in mechanistic logic: first dénouement.

I started this story by looking at octet expansion and hypervalence in non-polar hypercoordinate species such as S(-CH

 3

)

 6

, then moved on to S(=CH

 2

)

 3

. Finally now its the turn of S(≡CH)

 2

.

 ‡

As the triple bonds imply, this seems to represent twelve shared valence electrons surround the sulfur, six from S itself and three from each carbon.

Octet expansion and hypervalence in dimethylidyne-λ6-sulfane.

Both the cyclopropenium cation and the cyclopentadienide anion are well-known 4n+2-type aromatic ions, but could the two together form an ion-pair? A search of the Cambridge structure database reveals 52 instances of the cyclopropenium cation with a variety of counter-anions, 77 cyclopentadienide anions with a variety of counter-cations and one (SOWMOG, private communication to CSD) where the two sub-structures are common.

Cyclopropenium cyclopentadienide: a strangely neutral ion-pair?

Michael Dewar[cite]10.1016/S0040-4039(01)82765-9[/cite] famously implicated a so-called π-complex in the benzidine rearrangement, back in the days when quantum mechanical calculations could not yet provide a quantitatively accurate reality check. Because this π-complex actually remains a relatively unusual species to encounter in day-to-day chemistry, I thought I would try to show in a simple way how it forms.

The π-complex in the benzidine rearrangement: a molecular orbital analysis.

When Watson and Crick (WC) constructed their famous 3D model for DNA, they had to decide whether to make the double helix left or right handed.

A comparison of left and right handed DNA double-helix models.

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.

Improving the Science blog – The Rogue Scholar service.

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.

The Pinacol rearrangement.

In the mid to late 1990s as the Web developed, it was becoming more obvious that one area it would revolutionise was of scholarly journal publishing. Since the days of the very first scientific journals in the 1650s, the medium had been firmly rooted in paper. Even printed colour only became common (and affordable) from the 1980s. An opportunity to move away from these restrictions was provided by the Web.

Internet Archeology:  reviving a 2001 article published in the Internet Journal of Chemistry.

The recent release of the DataCite Data Citation corpus, which has the stated aim of providing “a trusted central aggregate of all data citations to further our understanding of data usage and advance meaningful data metrics” made me want to investigate what the current state of citing data in the area of chemistry might be. Chemistry is known to be a “data rich” science (as most of the physical sciences are) and  here on this very blog I

Data Citation – a snapshot of the chemical landscape.

The story of Monastral is not about a character in the Magic flute, but is a classic of chemical serendipity, collaboration between industry and university, theoretical influence, and of much else.

Monastral: the colour of blue

Understanding why and how proteins fold continues to be a

 grand challenge

in science. I have described how Wrinch in 1936 made a bold proposal for the mechanism, which however flew in the face of much of then known chemistry.

Why are α-helices in proteins mostly right handed?

In the late 1980s, as I recollected here[cite]10.59350/g4j62-4xk50[/cite] the equipment needed for real time molecular visualisation as it became known as was still expensive, requiring custom systems such as Evans and Sutherland PS390 workstations.

3D Molecular model visualisation: 3 Million atoms +

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.

Molecules of the year 2023 – part 2.  A FAIR data comment on a Strontium Metallocene.

Respiratory pigments are metalloproteins that transport O

 2

, the best known being the bright red/crimson coloured hemoglobin in human blood. The colour derives from Fe

 2+

at the core of a tetraporphyrin ring. But less well known is

 blue blood

, and here the colour derives from an oxyhemocyanin unit based on Cu

 1+

(the de-oxy form is colourless) rather than iron.

Blue blood.

One of the important aspects of chemical reaction mechanisms is the order in which things happen. More specifically, the order in which bonds make or break when there are more than two involved in undertaking a reaction.

One vs two bond rotation – An example using Acyl amides

I am completing my survey of the vote for molecule of the year candidates, which this year seems focused on chemical records of one type or another. The first article[cite]10.1002/chem.201601916[/cite] reports striving towards creating a molecule covering a complete column of the period table.

Molecules of the year? Pnictogen chains and 16 coordinate Cs.

Some time ago in 2010, I showed a chemical problem I used to set during university entrance interviews. It was all about pattern recognition and how one can develop a hypothesis based on this. In that instance, it involved recognising that a cyclic molecule which appeared to have the cyclohexatriene benzene-aromatic pattern

 1

was in fact a trimer of carbon dioxide.

Henry Rzepa's Blog

Harnessing FAIR data: A suggested useful persistent identifier (PID) for quantum chemical calculations.