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Trump Tantrum

Dear Reader,

I have become aware that Donald Trump (not the most level headed of men) has thrown a tantrum during a meeting with members of the press. Now I am sure that many of the readers of this blog will have spotted some time ago that Donald is not “of sound mind and sober habit“. By the way I can not claim to have coined this wonderful phrase, it is a phrase from the UK law on firearms and explosives.

Section 25 of the 1968 Firearms Act states

It is an offence for a person to sell or transfer any firearm or ammunition to, or to repair, prove or test any firearm or ammunition for, another person whom he knows or has reasonable cause for believing to be drunk or of unsound mind.

While for real poetic text see Section 30 which relates to revoking a firearms certificate. This is the legal basis in the UK for taking guns away from someone who is licensed but has either gone mad, turned into a drunk, is no longer physically able to comply with the terms of the license, appears to have turned bad or has some other new (or previously undetected which has now come to light) character flaw. This reads

The certificate may be revoked if the chief officer of police has reason to believe—

(a)that the holder is of intemperate habits or unsound mind or is otherwise unfitted to be entrusted with a firearm; or

(b)that the holder can no longer be permitted to have the firearm or ammunition to which the certificate relates in his possession without danger to the public safety or to the peace.

I would apply the same test when considering the question of is a person a fit person to have a license for explosives, a license for explosives can cover a range of things. It includes firework factorys, firework dealers, coal mine operators and a range of other things which might not at first to the public look like explosives work. It is interesting that more explosives tend to be used for peaceful tasks such as mining than are used in acts of war.

In the case of both Donald Trump and Boris Johnson I would feel quite reasonable in writing both men fall within the subset of people who are of intemperate habits or unsound mind or are otherwise unfitted to be entrusted with a country.

One of my objections to both men is the fact they are either recklessly or deliberately communicating false facts to the outside world and that it appears that both men have a conflict of interests. But OK now on with the chemistry, now one of the possible drugs for the treatment of the new virus is a antimalarial drug which dates back to the 1940s. It is chloroquine. This is a drug which is being considered and trialed for the treatment of the virus but it is not clear that the drug is effective. It is also a drug which can have some serious side effects, so I do not think we can argue a case that people should take chloroquine on the off chance that it protects against the new virus.

If the medical trials produce evidence that it is effective, then it might be possible to make an evidence based choice to start to use the drug for the treatment of the virus. But if we consider the chemistry of the compound. It has amine groups and a benzopyridine (Quinoline) system in it. Here is a 2D drawing of the freebase form of the molecule.

chloroqui

Now we have three nitrogen atoms, we need to consider which of the nitrogen atoms will have the greatest amount of electron density. I first used molecular mechanics to work out what shape the floppy group attached to the nitrogen which is bonded to the ring will have. The nitrogen bonded to the ring has one hydrogen atom attached and a rigid group (the quinoline) attached and also a flexible group made up of carbons bonded with single bonds to each other.

picture of the antimal drug

The calculated structure of the drug

According to the extended Huckel calculations done by Chem 3D, the nitrogens have the following partial charges on them. The most right nitrogen which has three carbons attached has a charge of -0.138, the nitrogen bearing two carbons and a hydrogen atom has a charge of +0.247 and the last nitrogen (the quinoline nitrogen) has a charge of -0.379. we need to ask why the nitrogens have such different charges on them.

The best thing for us to do is to consider the resonance in the aromatic ring, there are four resonance forms in which we only have two charges and the left hand aromatic ring is left aromatic. Thus these are the likely to be be to lowest four resonance forms in terms of energy. Here they are.

important res forms of chloroquin

The four lowest energy resonance forms of the aromatic system

We should understand that all the resonance forms exist at the same time, and that reality is a combination of all the possible resonance forms. The combination is not one where each form has an equal contribution, instead those resonance forms with lower energies will make a greater contribution than those with higher energies. Because of the bottom left one we should understand quickly how electron density is withdrawn from one of the amine groups is then transferred to the “pyridine” nitrogen.

We can draw some more resonance forms which have higher energies, it is interesting to note that the nitrogen in the ring will increase the positive charge character on the atom bearing the chlorine atom. This is due to withdrawal of electron density by resonance. Here are these slightly higher energy resonance forms. It is also important to keep in mind that the resonance effects also withdraw electron density from the chlorine atom.

medium energy res forms of chloroquin

The medium energy resonance forms of the drug’s aromatic ring system.

The charge predicted by the computational software on the chlorine atom was 0.036 while the carbon atom bearing it is predicted to have a charge of 0.166. If we compare this with chlorobenzene which are shown below. Then it appears that the computational software did not predict that the nitrogen in the aromatic ring would increase the positive charge of the chlorine or the carbon bearing it.

charges on the non hydrogen atoms of chlorobenzeneThe charges on the non hydrogen atoms of chlorobenzene

But back to the drug, when we look at the crystallography of the drug then we find that it is dominated by salts. There is one form which has the spacegroup P21/c which is listed at GEXXAI which is a bis dihydrogen phosphate. There is also another form with a spacegroup of P21/c (HOJLOI) and another one which is P21/a (CLQUON). These three different structures have the following cells.

Name A b c a b γ V Z
  Å Å Å Degrees Degrees Degrees Å3  
                 
GEXXAI 9.835 16.865 15.786 90 105.75 90 2520.118 4
CLQUON 15.741 16.865 9.815 90 105.58 90 2509.868 4
HOJLOI 12.544 9.484 20.700 90 93.97 90 2456.766 4

I do think that the cell for GEXXAI does look very similar to CLQUON,

HOJLOI is reported in a paper A Solid-State Dehydration Process Associated with a Significant Change in the Topology of Dihydrogen Phosphate Chains, Established from Powder X-ray Diffraction, by David Albesa-Jové, Zhigang Pan,Kenneth D. M. Harris and  Hidehiro Uekusa in Cryst.Growth Des. , 2008, volume 8, page 3641. This paper is the paper with work done using powder diffraction methods.

The other two are of more interest CLQUON is from a 1970 paper by H.S.Preston and J.M.Stewart, J. Chem. Soc. D., 1970, page 1142. This is a strucutre which has been redetermined by some other workers (G.Macetti, L.Loconte, S.Rizzato, C.Gatti, L.Lo Presti, Cryst.Growth Des. 2016). I will have to ask a crystallographer the difference between P21/a and P21/c. I do not want to stick my neck out and write something which I later discover is wrong.

One of the books which was instrumental in my development as a radioactivity worker was “Lessons Learnt from Accidents in Industrial Radiography“, it is a book all about radiological safety mainly considering what can go wrong with sealed source work and also how it should be done correctly. One of the bits of advice in the book which is aimed at the radiographic worker is on page 39. Here it crisply states in the 11th commandment to radiographers that they should refuse work which they are either not trained or equipped for.

In todays world where everyone wants their 15 minutes of fame on the internet, it is still important that before we comment on a matter we should equip ourselves with some knowledge of the thing and try to come up with a reasoned view of the matter rather than a knee jerk reaction.

The some of the other commandments to the radiographer are good general life lessons, but we will leave that for another day.

Go on, Have your say !

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