Imperial College London

Henry Rzepa

This molecule is not leaving me in peace. It and I first met in 1990 (DO: 10.1039/C39910000765), when we spotted the two unusual π-facial bonds formed when it forms a loose dimer.

Déjà vu: Pirkle for a third time!

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.

For those of us who were around in 1985, an important chemical IT innovation occurred. We could acquire a computer which could be used to draw chemical structures in one application, and via a mysterious and mostly invisible entity called the

 clipboard

, paste it into a word processor (it was called a Macintosh). Perchance even print the result on a laserprinter.

Data-round-tripping: moving chemical data around.

The rather presumptious title assumes the laws and fundamental constants of physics are the same everywhere (they may not be). With this constraint (and without yet defining what is meant by strongest), consider the three molecules: Property  (CCSD/aug-cc-pVTZ) N≡N (H-N≡N)

 +

(H-N≡N-H)

 2+

NN length, Å 1.0967 1.0915 1.0795 NN stretch, cm

 -1

2418.8 2356.4

The strongest bond in the universe!

The title of this post merges those of the two previous ones. The tunable C-Cl bond brought about in the molecule tris(amino)chloromethane by anomeric effects will be probed using the Laplacian of the electronic density.

Tunable bonds looked at in a different way

So ingrained is the habit to think of a bond as a simple straight line connecting two atoms, that we rarely ask ourselves if they are bent, and if so, by how much (and indeed, does it matter?). Well Hursthouse, Malik, and Sales, as long ago as 1978, asked just such a question about the unlikeliest of bonds, a quadruple Cr-Cr bond, found in the compound

 di-μ-trimethylsilylmethyl-bis-[(tri-methylphosphine)

Blisteringly bent (quadruple) bonds

In a time when large (molecules) are considered beautiful (or the corollary that beauty must be big), it is good to reflect that small molecules may teach us something as well. Take ethane. Is there anything left which has not been said about it already? Well, consider the reaction below, in which two hydrogen atoms mutually hop from one carbon to the other. The dyotropic reaction of ethane.

Less is more: the dyotropic rearrangement of ethane

Janus was the mythological Roman god depicted as having two heads facing opposite directions, looking simultaneously into the past and the future. Some of the most ancient (

 i.e.

19th century) known reactions can be considered part of a chemical mythology; perhaps it is time for a Janus-like look into their future. Reaction of the diazonium cation with cyanide.

Janus mechanisms (the past and the future): Reactions of the diazonium cation.

Curly arrows are something most students of chemistry meet fairly early on. They rapidly become hard-wired into the chemists brain. They are also uncontroversial! Or are they? Consider the following very simple scheme. Curly arrow pushing  It represents protonation of an alkene by an acid.

Secrets of a university tutor: (curly) arrow pushing

Some molecules, when you first see them, just intrigue. So it was with carbobenzene, the synthesis of a derivative of which was recently achieved by Remi Chauvin and co-workers (DOI: 10.1002/chem.200601193). Two additional carbon atoms have been inserted into each of the six C-C bonds in benzene. Carbobenzene  The structure shows two resonance forms, which remind one of Kekulé and of course benzene itself.

Carbobenzene: benzene with a difference

Climbers scale Mt. Everest,

 because its there

, and chemists have their own version of this. Ever since G. N. Lewis introduced the concept of the electron-pair bond in 1916, the idea of a bond as having a formal bond-order has been seen as a useful way of thinking about molecules. The initial menagerie of single, double and triple formal bond orders (with a few half sizes) was extended in the 1960s to four, and in 2005 to five.

Quintuple bonds

After around 40 posts here, I decided to take a look at the whole effort and ask some questions. For example Should (scientific) blogs be used to report new science, or merely opinion on existing science (see this blog also)? If the former, should they be abstracted in the manner of regular articles (e.g. by CAS etc). Unlike e.g. a journal, a blog is often (and certainly in this case) the effort of an individual.

How long will a blog last?  ArchivePress

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.

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 &#8211; An example using Acyl amides

Nature has produced most natural molecules as chiral objects, which means the molecule can come in two enantiomeric forms, each being the mirror image of the other. When a natural product is synthesised in a laboratory, a chiral synthesis means just one form is made, and then is compared with the natural product to see if it matches.

Determining absolute configuration: Cylindricine.

Previously, I explored the unusual structure of a molecule with a hydrogen bonded interaction between a phenol and a pyridine. The crystal structure name was RAKQOJ and it had been reported as having almost symmetrical N…H…O hydrogen bonds. This feature had been determined using neutron diffraction crystallography, which is thought very reliable at determining proton positions.

3-Methyl-5-phenylpyrazole: a crystallographic enigma?

Normally, aromaticity is qualitatively assessed using an electron counting rule for cyclic conjugated rings. The best known is the Hückel 4n+2 rule (n=0,1, etc) for inferring diatropic aromatic ring currents in singlet-state π-conjugated cyclic molecules

 ‡

and a counter 4n rule which infers an antiaromatic paratropic ring current for the system.

A four-atom molecule exhibiting simultaneous compliance with Hückel 4n+2 and Baird 4n selection rules for ring aromaticity.

In the previous post, I showed some of the diverse “non-classical”interactions between Biotin and a protein where it binds very strongly. Here I take a look at two of these interactions to discover how common they are in small molecule structures.

Protein-Biotin complexes. Crystal structure mining.

The homologous hydrocarbon series R

 4

C is known for R=Me as neopentane and for R=Et as 3,3-diethylpentane.

Tetra-isopropylmethane and tetra-t-butylmethane.

A reaction can be thought of as molecular dancers performing moves. A choreographer is needed to organise the performance into the ballet that is a reaction mechanism. Here I explore another facet of the Michael addition of a nucleophile to a conjugated carbonyl compound.

Choreographing a chemical ballet: a story of the mechanism of 1,4-Michael addition.

All of the molecules in this year’s C&amp;EN list are fascinating in their very different ways. Here I take a look at the twisty tetracene (dodecaphenyltetracene) which is indeed very very twisty.[cite]10.1002/anie.201812418[/cite]    Click on image to view 3D model  Unfortunately, the authors point that the twisty-ness does not lead to a stable helical configuration at room temperatures and so separate enantiomers cannot be isolated.

Molecules of the year – 2019: twisty tetracene.

The Royal Society of Chemistry historical group (of which I am a member) organises two or three one day meetings a year. Yesterday the October meeting covered (amongst other themes) the fascinating history of madder and its approximately synthetic equivalent alizarin. Here I add a little to the talk given by Alan Dronsfield on the synthesis of alizarin and the impact this had on the entire industry.

The history of  Alizarin (and madder).

FAIR data

is increasingly accepted as a description of what research data should aspire to; **F**indable, **A**ccessible, **I**nter-operable and

 R

e-usable, with Context added by rich metadata (and also that it should be Open). But there are two sides to data, one of which is the raw data emerging from say an instrument or software simulations and the other in which some kind of model is applied to produce semi-

FAIR data ⇌ Raw data.

The triennial conference is this year located in Munich. With 1500 participants and six parallel sessions, this report can give only a flavour of proceedings. Edward Valeev talked about the scaling problem in coupled cluster theories, the so-called gold standard for computing the energy and properties of small molecules.

WATOC 2017 report.

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.

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?

Pursuing the topic of halogen bonds, the system DABCO (a tertiary dibase) and iodine form an intriguing complex. Here I explore some unusual features of the structure HEKZOO[cite]10.5517/CCYJN03[/cite] as published in 2012[cite]10.1021/cg300669t[/cite] and ask whether the bonding between the donor (N) and the acceptor (I-I) really is best described as a “non-covalent-interaction” (NCI) or not.

Halogen bonds 2: The DABCO-Iodine structure.

I have written earlier about the Amsterdam Manifesto. That arose out of a conference on the theme of “

 beyond the PDF

”, with one simple question at its heart:

 what can be done to liberate data from containers it was not designed to be in

? The latest meeting on this topic will happen in January 2015 as FORCE2015. The format is suitably modern, starting with a Hackathon, and then two days of talks, posters and demos.

Data discoverability

I was reminded of this article by Michelle Francl[cite]10.1038/nchem.1733[/cite], where she poses the question “What anchor values would most benefit students as they seek to hone their chemical intuition?” She gives as common examples: room temperature is 298.17K (actually 300K, but perhaps her climate is warmer than that of the UK!), the length of a carbon-carbon single bond, the atomic masses of the more common elements.

Anchoring chemistry.

Following the discussion here of Kekulé’s suggestion of what we now call a vibrational mode (and which in fact now bears his name), I thought I might apply the concept to a recent molecule known as [2.2]paracyclophane.

Kekulé’s vibration: A modern example of its use.

As my previous post hints, I am performing my annual spring-clean of lecture notes on pericyclic reactions. Such reactions, and their stereochemistry, are described by a set of

 
 selection rules
 

. I am always on the lookout for a simple example which can most concisely summarise these rules. The (hypothetical) one shown below I think nicely achieves this, and raises some interesting issues in the process.

A simple pericyclic reaction encapsulating the four thermal selection rules.

Not long ago, I described a cyclic carbene in which elevating the carbene lone pair into a π-system transformed it from a formally 4n-antiaromatic π-cycle into a 4n+2 aromatic π-cycle. From an entirely different area of chemistry, another example of this behaviour emerges; Schreiner’s[cite]10.1039/C2SC21555A[/cite] trapping and reactions of t-butyl-hydroxycarbene, as described on Steve Bachrach’s blog.

Avoided (pericyclic) anti-aromaticity: Reactions of t-butyl-hydroxycarbene.

In the two-publisher model I proposed a post or so back, I showed an example of how

 data

can be incorporated (transcluded) into the story narrative of a scientific article, with both that story and the data each having their own independently citable reference (using a doi for the citation). Here I take it a step further, by publishing a functional procedure in a digital repository[cite]10.6084/m9.figshare.811862[/cite] and

Publishing a procedure with a doi.

In 1993-1994, when the Web (synonymous in most minds now with the Internet) was still young, the pace of progress was so rapid that some wag worked out that one “

 web-year

” was like a dog-year, worth about 7 years of normal human time. So in this respect, 1994 is now some 133 web-years ago. Long enough for an archaeological excavation.

Internet Archaeology: Blasts from the past.

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.

My last comment as appended to the previous post promised to analyse two so-called extended porphyrins for their topological descriptors. I start with the Cãlugãreanu/Fuller theorem

Linking numbers, and twist and writhe components for two extended porphyrins.

A simple correlation between a ring size and the hydrogen bonding as quantified by the O(Lp)/H-O σ* NBO interaction in that ring, indicated a 7- or 8-membered ring was preferred over smaller ones. Here is the same study, but this time using the π-electrons of an alkene as the electron donor. n  E(2), kcal/mol  O…H length, Å

π-hydrogen bonds as a function of ring size.

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.

When methyl manganese pentacarbonyl is treated with carbon monoxide in

 e.g.

di-n-butyl ether, acetyl manganese pentacarbonyl is formed. This classic experiment conducted by Cotton (of quadruple bond fame) and Calderazzo in 1962[cite]10.1021/ic50001a008[/cite] dates from an era when chemists conducted extensive kinetic analyses to back up any mechanistic speculations. Their suggested transition state is outlined below.

Mechanisms of carbon monoxide insertion reactions: A reality check on carbonylation of methyl manganese pentacarbonyl

A month or so ago at a workshop I was attending, a speaker included in his introductory slide a QR (Quick Response) Code. It is a feature of most digital eco-systems that there is probably already “an app for it”. So I thought I would jump on the band wagon by coding an InChI string. Here it is below:    QRCode for an InChI string. Point your smart device at it, and see the InChI appear!

QR codes and InChI strings.

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.

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

Violations. There are none!

My previous post introduced the interesting guts of taxol. Two different isomers can exist, and these are called atropisomers; one has the carbonyl group pointing up, the other down. The barrier to their interconversion in this case is generated by a rotation about the two single bonds connecting the carbonyl group to the rest of the molecule.

Atropisomerism in Taxol. An apparently simple bond rotation?

I have mentioned Lewis a number of times in these posts; his suggestion of the shared electron covalent bond still underpins much chemical thinking. Take for example mechanistic speculations on the course of a reaction, a very common indulgence in almost all articles reporting such, and largely based on informed * arrow pushing*. This process is bound to follow the rules of reasonable Lewis structures for any putative intermediates.

Computational “reality checks” for mechanistic speculations.

This is a spin-off from the table I constructed here for further chemical examples of the classical/non-classical norbornyl cation conundrum. One possible entry would include the transition state for inversion of methane

 via

a square planar geometry as compared with

 e.g.

NiH

 4

for which the square planar motif is its minimum.

How does methane invert (its configuration)?

Science is about making connections. And these can often be made between the most unlikely concepts. Thus in the posts I have made about

 pentavalent carbon

, one can identify a series of conceptual connections.

It’s Hexa-coordinate carbon Spock – but not as we know it!

One of the many clever things that clever people can do with the Web is harvest it, aggregate it, classify it etc. Its not just Google that does this sort of thing! Egon Willighagen is one of those clever people. He runs the Chemical blogspace which does all sorts of amazing things with blogs.

The Fragile Web

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 – trapping a cyclobutadiene: ! or ?

This story starts with an organic chemistry tutorial, when a student asked for clarification of the  Finkelstein reaction. This is a simple S

 N

2 type displacement of an alkyl chloride or bromide, using sodium iodide in acetone solution, and resulting in an alkyl iodide. What was the driving force for this reaction he asked?

The mystery of the  Finkelstein reaction

Unusual bonds are always intriguing, and the Xe-Xe bond is no exception.

Extreme chemical intimacy: the Xe2@C60 ion-pair.

The two previous posts have explored one of the oldest bonding rules (pre-dating quantum mechanics), which postulated that filled valence shells in atoms forming molecules follow the magic numbers 2, 8, 18 and 32. Of the 59,025,533 molecules documented at the instant I write this post, only one example is claimed for the 32-electron class.

Nobelocene: a (hypothetical) 32-electron shell molecule?

Thalidomide is a chiral molecule, which was sold in the 1960s as a sedative in its (S,R)-racemic form. The tragedy was that the (S)-isomer was tetragenic, and only the (R) enantiomer acts as a sedative. What was not appreciated at the time is that interconversion of the (S)- and (R) forms takes place quite quickly in aqueous media.

Thalidomide. The role of water in the mechanism of its aqueous racemisation.

Chemistry can be very focussed nowadays. This especially applies to target-driven synthesis, where the objective is to make a specified molecule, in perhaps as an original manner as possible. A welcome, but not always essential aspect of such syntheses is the discovery of new chemistry.

Spotting the unexpected: Anomeric effects

In my blogroll, I link to Tim Gowers’ blog. He is a very eminent mathematician, and so it is interesting to see what motivates him to write a blog about mathematics. This latest post goes a large way to explaining why. He starts by speculating about the features of some piece of research that might render it conventionally unpublishable, highlighting two reasons; (1) it is not original and (2) it does not lead anywhere conclusive.

Is there a difference between a scientific blog and scientific journal?

C

 2

(dicarbon) is certainly interesting from a theoretical point of view. Whether or not it can be described as having a

 quadruple bond

has induced much passionate discussion[cite]10.1038/nchem.1263[/cite],[cite]10.1002/anie.201208206[/cite],[cite]10.1002/anie.201301485[/cite],[cite]10.1002/anie.201302350[/cite]. Its occurrence in space and in flames is also well-known.

Is dicarbon (C2) a molecule of chemical interest?

In an earlier post, I discussed[cite]10.59350/dfkt5-k2b20[/cite] a phenomenon known as the “anomeric effect” exhibited by tetrahedral carbon compounds with four C-O bonds. Each oxygen itself bears two bonds and has two lone pairs, and either of these can align with one of three other C-O bonds to generate an anomeric effect. Here I change the central carbon to a boron to explore what happens, as indeed  I promised earlier.

Detecting anomeric effects in tetrahedral boron bearing four oxygen substituents.

The phenomenon of

 bond stretch isomerism

, two isomers of a compound differing predominantly in just one bond length, is one of those chemical concepts that wax and occasionally wane.[cite]10.1016/S1631-0748(02)01380-2[/cite] Here I explore such isomerism for the elements Ge, Sn and Pb. In one earlier post, I noted a form of bond stretch isomerism that can arise from a Jahn-Teller distortion ending in two different geometries

Bond stretch isomerism. Did this idea first surface 100 years ago?

I recently followed this bloggers trail; link1 → link2 to arrive at this delightful short commentary on atom-atom bonds in crystals[cite]10.1107/S2052252515002006[/cite] by Jack Dunitz. Here he discusses that age-old question (to chemists), what is a bond? Even almost 100 years after Gilbert Lewis’ famous analysis,[cite]10.1021/ja02261a002[/cite] we continue to ponder this question.

Intermolecular atom-atom bonds in crystals? The O…O case.

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.

I previously blogged about anomeric effects involving π electrons as donors, and my post on the conformation of 1,2-difluorethane turned out one of the most popular.

The gauche effect: seeking evidence by a survey of crystal structures.

This is the third and final study deriving from my Ph.D.[cite]10.1039/P29750001822[/cite]. The first two topics dealt with the mechanism of heteroaromatic electrophilic attack using either a diazonium cation or a proton as electrophile, followed by either proton abstraction or carbon dioxide loss from the resulting Wheland intermediate.

I’ve started so I’ll finish. The ionisation mechanism and kinetic isotope effects for 1,3-dimethylindolin-2 one

We have been experimenting with full-colour 3D printing of molecular objects. I thought I might here share some of our observations. Firstly, I list the software used: Crystal structures as sources of ball&amp;stick models (

 e.g.

the CCDC database). Gaussian style cube files for sources of wavefunctions.

Full-colour 3D printing of molecular models and orbitals (wavefunctions).

Amides with an H-N group are a component of the peptide linkage (O=C-NH). Here I ask what the conformation (it could also be called a configuration) about the C-N bond is. A search of the following type can be defined:    The dihedral shown is for H-N-C=O (but this is equivalent to the C-C-N-C dihedral, which is also often called the dihedral angle associated with the peptide group). I have also added a distance, from a C-H to the

The conformational preference of s-cis amides.

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.

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.

The mechanism of forming an oxime from nucleophilic addition of a hydroxylamine to a ketone is taught early on in most courses of organic chemistry. Here I subject the first step of this reaction to form a tetrahedral intermediate to quantum mechanical scrutiny. The first decision is to decide which atom of the hydroxylamine acts as the nucleophile. Reaction

 1

shows the oxygen and reaction

 2

the nitrogen.

Oxime formation from hydroxylamine and ketone: a (computational) reality check on stage one of the mechanism.

According to Guggemos, Slavicek and Kresin, about 5-6![cite]10.1103/PhysRevLett.114.043401[/cite]. This is one of those simple ideas, which is probably quite tough to do experimentally. It involved blasting water vapour through a pinhole, adding HCl and measuring the dipole-moment induced deflection by an electric field.

How many water molecules does it take to ionise HCl?

Click on diagram to see model. The reaction above is ostensibly a very simple pericyclic ring opening of a cyclopropyl carbocation to an allyl cation, preceeded by a preparatory step involving SN-1 solvolysis. As a 2-electron thermal process, the second step proceeds with disrotation of the terminii. Can this stereochemistry be illustrated with a computed model for the transition state for this process?

Pericyclic assistance for SN-1 solvolysis

You might have noticed if you have read any of my posts here is that many of them have been accompanied since 2006 by supporting calculations, normally based on density functional theory (DFT) and these calculations are accompanied by a persistent identifier pointer

 ‡

to a data repository publication.

HPC Access and Metadata Portal (CHAMP).

Following from much discussion over the last decade about the nature of C

 2

, a diatomic molecule which some have suggested sustains a quadruple bond between the two carbon atoms, new ideas are now appearing for molecules in which such a bond may also exist between carbon and a transition metal atom.

Two new reality-based suggestions for molecules with a metal M⩸C quadruple bond.

The previous post was about an insecticide and made a point that the persistence of both insecticides and herbicides is an important aspect of their environmental properties. Water hydrolysis will degrade them, a typical residency time being in the order of a few days. I noted in passing a dioxepin-based herbicide[cite]10.1039/P29890001265[/cite] which contains a ketal motif and which in water can hydrolise to a ketone and alcohol.

A computational mechanism for the aqueous hydrolysis of a ketal to a ketone and alcohol.

My previous three posts set out my take on three principle categories of pericyclic reaction. Here I tell a prequel to the understanding of these reactions. In 1965, Woodward and Hoffmann[cite]10.1021/ja01080a054[/cite] in their theoretical analysis (submitted Nov 30, 1964) for which the Nobel prize (to Hoffmann only of the pair, Woodward having died) was later awarded.

So near and yet so far. The story of the electrocyclic ring opening of a cyclohexadiene.

The folks at DataCite have announced a new research object discovery service which aims to give users a “

 comprehensive overview of connections between entities in the research landscape”

. The portal https://commons.datacite.org acts as the entry point for three basic types of persistent identifiers (PIDs); Research works, using the DOI (digital object identifier) as a PID.

Exploiting the power of persistent identifiers (PIDs) for locating all kinds of research object.

Sometimes the originators of seminal theories in chemistry write a personal and anecdotal account of their work. Niels Bohr[cite]10.1007/BF01326955[/cite] was one such and four decades later Robert Woodward wrote “

 The conservation of orbital symmetry

” (Chem. Soc. Special Publications (Aromaticity),

 1967

,

 21

, 217-249;

Woodward’s symmetry considerations applied to electrocyclic reactions.

A

 PID

or persistent identifier has been in common use in scientific publishing for around 20 years now. It was introduced as a

 DOI

(Digital Object Identifier), and the digital object in this case was the journal article. From 2000 onwards, DOIs started appearing for most journal articles, journals having obtained them from a registration agency, CrossRef.

The Persistent Identifier ecosystem expands &#8211; to instruments!

In this series of posts on optical rotations, I firstly noted Kirkwood’s 1937 attempt to correlate the optical rotation of butan-2-ol with its absolute configuration.

What effect do explicit solvent molecules have on calculated optical rotation: D-(“+”)-Glyceraldehyde.

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?

I have discussed the vibration in benzene known as the Kekulé mode in other posts, the first of which was all of ten years ago.

Cyclo[18]carbon: The Kekulé vibration calculated and hence a mystery!

William Henry Perkin is a local chemical hero of mine. The factory where he founded the British (nay, the World) fine organic chemicals industry is in Greenford, just up the road from where we live. The factory used to be close to the Black Horse pub (see below) on the banks of the grand union canal.

William Henry Perkin: The site of the factory and the grave.

It was about a year ago that I came across a profusion of colour in my local Park. Although colour in fact was the topic that sparked my interest in chemistry many years ago (the fantastic reds produced by diazocoupling reactions), I had never really tracked down the origin of colours in many flowers. It is of course a vast field.

Why do flowers such as roses, peonies, dahlias, delphiniums (etc), exhibit so many shades of colours?

I don’t normally write about the pharmaceutical industry, but I was intrigued by several posts by Derek Lowe (who does cover this area) on the topic of creating new drugs by deuterating existing ones. Thus he covered the first deuterated drug receiving FDA approval last year, having first reviewed the concept back in 2009. So when someone introduced me to

 sila-haloperidol

, I checked to see if Derek had written about it.

Silicon drug analogues.

In the previous post, I referred to a recently published review on hypervalency[cite]10.1039/C5SC02076J[/cite] which introduced a very simple way (the valence electron equivalent γ) of quantifying the effect. Diazomethane was cited as one example of a small molecule exhibiting hypervalency (on nitrogen) by this measure.

Can any hypervalence in diazomethanes be amplified?

Little did I imagine, when I discovered the original example of using curly arrows to express mechanism, that the molecule described there might be rather too anarchic to use in my introductory tutorials on organic chemistry. Why? It simply breaks the (it has to be said to some extent informal) rules!

The first curly arrows…lead to this?

For around 16 years, Floyd Romesberg’s group has been exploring un-natural alternatives (UBPs) to the Watson-Crick base pairs (C-G and A-T) that form part of the genetic code in DNA.

A form of life that can stably store genetic information using a six-letter, three-base-pair alphabet?

A few years back, I took a look at the valence-shell electron pair repulsion approach to the geometry of chlorine trifluoride, ClF

 3

using so-called ELF basins to locate centroids for both the covalent F-Cl bond electrons and the chlorine lone-pair electrons.

VSEPR Theory: Octet-busting or not with trimethyl chlorine, ClMe3.

This is a corollary to the previous post

 ‡

exploring how many molecules are needed to ionise HCl. Here I am asking how many water molecules are required to form the ionic ammonium hydroxide from ammonia and water.

How many water molecules does it take to form ammonium hydroxide from ammonia and water?

As the Internet and its Web-components age, so early pages start to decay as technology moves on. A few posts ago, I talked about the maintenance of a relatively simple page first hosted some 21 years ago. In my notes on the curation, I wrote the phrase “

 Less successful was the attempt to include buttons which could be used to annotate the structures with highlights.

Curating a nine year old journal FAIR data table.

Research data (and its management) is rapidly emerging as a focal point for the development of research dissemination practices.

The challenges in curating research data: one case study.

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.

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.

Halogen bonds are less familiar cousins to hydrogen bonds. They are defined as

 non-covalent interactions

(NCI) between a halogen atom (

 X

, acting as a Lewis acid, in accepting electrons) and a Lewis base

 D

donating electrons;

 D….X-A


 vs


 D…H-A

. They are superficially surprising, since both D and X look like electron rich species.

Halogen bonds: Part 1.

In answering tutorial problems, students often need skills in deciding how much time to spend on explaining what does

 not

happen, as well as what does. Here I explore alternatives to the mechanism outlined in the previous post to see what computation has to say about what does (or might) not happen.

A tutorial problem in stereoelectronic control. A Grob alternative to the Tiffeneau-Demjanov rearrangement?

In the previous posts, I explored reactions which can be flipped between two potential (stereochemical) outcomes. This triggered a memory from Alex, who pointed out this article from 1999[cite]10.1070/MC1999v009n02ABEH000995[/cite] in which the nitrosonium cation as an electrophile can have two outcomes

 A

or

 B

when interacting with the electron-rich 2,3-dimethyl-2-butene.

Computationally directed synthesis:  2,3-dimethyl-2-butene + NO(+).

I have just noticed unexpected links between two old posts, one about benzene, one about diphenyl magnesium and a link to August Kekulé.

 †

Click for 3D The post about benzene dealt with the apparently simple issue of why all the C-C bonds are of equal length. The answer, in brief is purely because of the σ-electrons. If the π-electrons had their way, benzene would have three short and three long C-C bonds.

More (blog) connections spotted. Something new about diphenyl magnesium?

A feature of a blog which is quite different from a journal article is how rapidly a topic might evolve. Thus I started a few days ago with the theme of dicarbon (C

 2

), identifying a metal carbide that showed C

 2

as a ligand, but which also entrapped a single carbon in hexa-coordinated mode.

Hexacoordinate hydrogen.

The concept of a shared electron bond and its property of an order is almost 100 years old in modern form, when G. N. Lewis suggested a model for single and double bonds that involved sharing either 2 or 4 electrons between a pair of atoms[cite]10.1021/ja02261a002[/cite]. We tend to think of such (even electron) bonds in terms of their formal bond order (an integer), recognising that the actual bond order (however defined) may not fulfil this

A (very) short history of shared-electron bonds.

My two previous explorations of aromatic substitutions have involved an electrophile (NO

 +

or Li

 +

). Time now to look at a nucleophile, representing

 nucleophilic aromatic substitution

. The mechanism of this is thought to pass through an intermediate analogous to the Wheland for an electrophile, this time known as the Meisenheimer complex[cite]10.1002/jlac.19023230205[/cite]. I ask the same question as before;

Concerted vs stepwise (Meisenheimer) mechanisms for aromatic nucleophilic substitution.

The (hopefully tongue-in-cheek) title

 Mindless chemistry

was given to an article reporting[cite]10.1021/jp057107z[/cite] an automated stochastic search procedure for locating all possible minima with a given composition using high-level quantum mechanical calculations. “Many new structures, often with nonintuitive geometries, were found”. Well, another approach is to follow unexpected hunches.

Mindless chemistry or creative science?

The following is a short question in a problem sheet associated with introductory organic chemistry.

Multiple personalities of  Magnesium.

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.

Henry Rzepa's Blog

Aromatic electrophilic substitution: a different way of predicting regiospecificity

A lab in a backpack

On the importance of Digital repositories in Chemistry

The SN-1 Reaction live!

Pericyclic assistance for SN-1 solvolysis

A Disrotatory 4n+2 electron anti-aromatic Möbius transition state for a thermal electrocyclic reaction.

Jmol and WordPress: Loading 3D molecular models, molecular isosurfaces and molecular vibrations into a blog

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