Aspirin Tablets Help Unravel Basic Physics

[hazelm]

Physics is not in my range of comprehension of the universe.  Silly statement, I know, but I can't help but ask "why aspirin?"  Are they telling us something about aspirin?  Or did aspirin just happen to be the "tool" they used to study motions of electrons and atomic nuclei - what I think they are calling "soft mode frequency"? 

 

https://www.sciencedaily.com/releases/2017/09/170907120341.htm

 

"Aspirin in form of small crystallites provides new insight into delicate motion of electrons and atomic nuclei."  (Science Daily)

 

My comment:  Aspirin is getting credit among the laity as a cure for almost everything.  And scientists are indeed finding new benefits of aspirin every once in a while.  Now aspirin has entered the science labs to provide a study source in physics?

 

I hope we have a physicist here to tell me if my imagination is going overboard.

[exchemist]

Physics is not in my range of comprehension of the universe.  Silly statement, I know, but I can't help but ask "why aspirin?"  Are they telling us something about aspirin?  Or did aspirin just happen to be the "tool" they used to study motions of electrons and atomic nuclei - what I think they are calling "soft mode frequency"? 

 

https://www.sciencedaily.com/releases/2017/09/170907120341.htm

 

"Aspirin in form of small crystallites provides new insight into delicate motion of electrons and atomic nuclei."  (Science Daily)

 

My comment:  Aspirin is getting credit among the laity as a cure for almost everything.  And scientists are indeed finding new benefits of aspirin every once in a while.  Now aspirin has entered the science labs to provide a study source in physics?

 

I hope we have a physicist here to tell me if my imagination is going overboard.

Speaking as a chemist - this is really chemistry, or chemical physics - I can sort of see what they are doing. I think :).

 

It looks to me an interesting example of the breakdown of something called the Born-Oppenheimer approximation:

 https://en.wikipedia.org/wiki/Born–Oppenheimer_approximation. According to this, the motion of atomic nuclei of molecules, such as is involved in molecular vibrations and rotations, can be treated as separate from the motion of the electrons in the chemical bonds. In fact a lot of quantum chemistry proceeds from the assumption that this is true - and it generally seems to be, though there are some well-established exceptions in chemistry.  

 

What they seem to have done is find an intriguing example of coupling between the "pi" electrons of the benzene ring and the partial rotation of the methyl group on the end of the acetyl side chain, when aspirin is in solid crystals, in which there are motions of the whole lattice rather than just individual molecules in solution. So evidently in this case the approximation breaks down. 

 

I find it a bit strange they don't mention the B-O approximation, as to me this is the interesting thing. But perhaps they deal with such cases all the time and it doesn't faze them. 

 

As to your question, there is nothing special here about aspirin, except that it has a molecule with a delocalised "aromatic"  pi electron system and a hindered methyl group. There is no suggestion that this phenomenon has any effect on the medical properties of aspirin, as it only applies to the crystalline solid, not the dissolved form in which is it absorbed in the body.

 

But I tell you what: there is some damned good stuff on that Max Born Institute site, if you are a physical chemist, and quite accessibly written too.  Thanks for the link. 

Edited September 9, 2017 by exchemist

[hazelm]

Speaking as a chemist - this is really chemistry, or chemical physics - I can sort of see what they are doing. I think :).

 

It looks to me an interesting example of the breakdown of something called the Born-Oppenheimer approximation:

 https://en.wikipedia.org/wiki/Born–Oppenheimer_approximation. According to this, the motion of atomic nuclei of molecules, such as is involved in molecular vibrations and rotations, can be treated as separate from the motion of the electrons in the chemical bonds. In fact a lot of quantum chemistry proceeds from the assumption that this is true - and it generally seems to be, though there are some well-established exceptions in chemistry.  

 

What they seem to have done is find an intriguing example of coupling between the "pi" electrons of the benzene ring and the partial rotation of the methyl group on the end of the acetyl side chain, when aspirin is in solid crystals, in which there are motions of the whole lattice rather than just individual molecules in solution. So evidently in this case the approximation breaks down. 

 

I find it a bit strange they don't mention the B-O approximation, as to me this is the interesting thing. But perhaps they deal with such cases all the time and it doesn't faze them. 

 

As to your question, there is nothing special here about aspirin, except that it has a molecule with a delocalised "aromatic"  pi electron system and a hindered methyl group. There is no suggestion that this phenomenon has any effect on the medical properties of aspirin, as it only applies to the crystalline solid, not the dissolved form in which is it absorbed in the body.

 

But I tell you what: there is some damned good stuff on that Max Born Institute site, if you are a physical chemist, and quite accessibly written too.  Thanks for the link. 

I am glad someone gets some good out of it.  It is beyond me.  But, as I said, physics is beyond my comprehension and I never studied chemistry.  Enjoy the web site while I re-read your post a few times.  I take it that aspirin just happened to lend itself to their research.  And as common as it is, perhaps cheap to buy.  Thanks much. 

[Buffy]

My comment:  Aspirin is getting credit among the laity as a cure for almost everything.  And scientists are indeed finding new benefits of aspirin every once in a while.  Now aspirin has entered the science labs to provide a study source in physics?

 

Aspirin gets its reputation as a miracle cure because it's dang near the closest to one that anyone has ever discovered: headaches, muscle aches, fever reducer, blood clots, stroke, heart attack, cramps, heck it does everything for most of what commonly ails you.

 

Now it'll bore a mighty hole in your stomach if you take too much of it (I'm a poster child for that), but it's easier on your liver and kidneys than most of it's "replacements" like ibuprofen, naproxen and Acetaminophen, but those don't all do what aspirin can.

 

Drug companies hate it because it proves that their patent medicines aren't necessarily the best solution for people (e.g. don't take Claritin when Benadryl will do).

 

 

The miracle is this: the more we share the more we have, :phones:

Buffy

[hazelm]

 

Aspirin gets its reputation as a miracle cure because it, dang near the closest to one that anyone has ever discovered: headaches, muscle aches, fever reducer, blood clots, stroke, heart attack, cramps, heck it does everything for most of what commonly ails you.

 

Now it'll bore a mighty hole in your stomach if you take too much of it (I'm a poster child for that), but it's easier on your liver and kidneys than most of it's "replacements" like ibuprofen, naproxen and Acetaminophen, but those don't all do what aspirin can.

 

Drug companies hate it because it proves that their patent medicines aren't necessarily the best solution for people (e.g. don't take Claritin when Benadryl will do).

 

 

The miracle is this: the more we share the more we have, :phones:

Buffy

 

All very true, Buffy.  And Benedryl isn't the best for older people as a cousin of mine found out the hard way.  My motto is the less medicine you take, the healthier you'll be.  And, yes, aspirin has become a "miracle medicine".  Just don't overdo.  The article grabbed my attention because here it was being used for something entirely different.  Always something new.

[hazelm]

exchemist, a question that I am sure you can answer.  Does this research with aspirin relate in any way to the electron beam?  I was reading this in a search for definition of the electron beam:  https://www.britannica.com/science/electron-beam  Somehow I felt there was a connection.

 

There is also another article that I read which spoke of electrons  being forced into atomic atoms.  That's another one that seems connected.  I'd have to go back and find it.  But both seem to be what the researchers in the aspirin report are doing.  Perhaps including the electron accelerator that can melt to materials together by adding heat.   Always, we see the free electrons joining (or rejoining) the ion-charged atoms.

 

 There is more but this is enough for now.  Perhaps I am seeing connections that are not there.  Am I off-base here?  Thank you for a yes or no.

[exchemist]

exchemist, a question that I am sure you can answer.  Does this research with aspirin relate in any way to the electron beam?  I was reading this in a search for definition of the electron beam:  https://www.britannica.com/science/electron-beam  Somehow I felt there was a connection.

 

There is also another article that I read which spoke of electrons  being forced into atomic atoms.  That's another one that seems connected.  I'd have to go back and find it.  But both seem to be what the researchers in the aspirin report are doing.  Perhaps including the electron accelerator that can melt to materials together by adding heat.   Always, we see the free electrons joining (or rejoining) the ion-charged atoms.

 

 There is more but this is enough for now.  Perhaps I am seeing connections that are not there.  Am I off-base here?  Thank you for a yes or no.

Yes you are off target here. They are not shooting anything except electromagnetic radiation at the molecules in this research. They are not bombarding them with electrons. 

 

All that is happening is that the radiation is absorbed by the molecules in certain modes of oscillation that are excited by the frequencies of radiation they have chosen. One mode of oscillation is this hindered rotation of one bit of the molecule. Another mode is the motion of pi electrons within the molecule. But they are not adding any extra electrons or anything.

 

To be honest this is quite advanced chemical physics. You would need an explanation of how molecules absorb radiation, i.e. molecular spectroscopy, to really make sense of this paper - plus maybe a bit of solid state physics (phonons etc) for good measure. I sort of understand it qualitatively, I think, but I had to rack my brains a bit to make it out. (My degree was over 40 years ago.) 

 

I'm impressed that you look up things like this for fun, though. 

Edited September 10, 2017 by exchemist

[hazelm]

All right. I should not have said "free" electrons.  Anyway, thanks.  What is needed is more than eighth grade general science - the wheel, the lever, etc.  Science was not considered a necessary field of study way back then.  In a way, that is good.  It leaves me something to have fun with now.  :-)   Thank you. 

[exchemist]

All right. I should not have said "free" electrons.  Anyway, thanks.  What is needed is more than eighth grade general science - the wheel, the lever, etc.  Science was not considered a necessary field of study way back then.  In a way, that is good.  It leaves me something to have fun with now.  :-)   Thank you. 

Let me know if you want to have a go at molecular spectroscopy one day. But it's a longish haul..... 

[hazelm]

Thank you.  I'll hold that thought. 

[OceanBreeze]

Speaking as a chemist - this is really chemistry, or chemical physics - I can sort of see what they are doing. I think :).

 

It looks to me an interesting example of the breakdown of something called the Born-Oppenheimer approximation:

 https://en.wikipedia.org/wiki/Born–Oppenheimer_approximation. According to this, the motion of atomic nuclei of molecules, such as is involved in molecular vibrations and rotations, can be treated as separate from the motion of the electrons in the chemical bonds. In fact a lot of quantum chemistry proceeds from the assumption that this is true - and it generally seems to be, though there are some well-established exceptions in chemistry.  

 

What they seem to have done is find an intriguing example of coupling between the "pi" electrons of the benzene ring and the partial rotation of the methyl group on the end of the acetyl side chain, when aspirin is in solid crystals, in which there are motions of the whole lattice rather than just individual molecules in solution. So evidently in this case the approximation breaks down. 

 

I find it a bit strange they don't mention the B-O approximation, as to me this is the interesting thing. But perhaps they deal with such cases all the time and it doesn't faze them. 

 

As to your question, there is nothing special here about aspirin, except that it has a molecule with a delocalised "aromatic"  pi electron system and a hindered methyl group. There is no suggestion that this phenomenon has any effect on the medical properties of aspirin, as it only applies to the crystalline solid, not the dissolved form in which is it absorbed in the body.

 

But I tell you what: there is some damned good stuff on that Max Born Institute site, if you are a physical chemist, and quite accessibly written too.  Thanks for the link. 

 

 

Interesting.

 

I do wonder about the bolded part, though.

 

Why is it that a majority of solid drugs are made to be crystals?

 

For example, both paracetamol and  aspirin are manufactured with a crystallized structure.

 

Does the crystal structure have something to do with drug uptake?

[exchemist]

Interesting.

 

I do wonder about the bolded part, though.

 

Why is it that a majority of solid drugs are made to be crystals?

 

For example, both paracetamol and  aspirin are manufactured with a crystallized structure.

 

Does the crystal structure have something to do with drug uptake?

Presumably because these are drugs that are solid at room temperature and therefore in the pure form they will almost inevitably be crystalline. 

[OceanBreeze]

Presumably because these are drugs that are solid at room temperature and therefore in the pure form they will almost inevitably be crystalline. 

 

I don't understand why they couldn't just as easily be amorphous solids at room temperature?

 

Why would they inevitably be crystalline?

[exchemist]

I don't understand why they couldn't just as easily be amorphous solids at room temperature?

 

Why would they inevitably be crystalline?

Because amorphous phase materials would generally be prepared by cooling from molten, e.g. glass. If you carry out reactions in solution, generally you get a crystalline end product, because you usually get the solid out by precipitation or evaporation, both of which encourage crystals to form. Also, allowing crystals to form ensures purity, since you don't get many inclusions of impurities in a crystalline structure.  Further reading here: http://homepage.smc.edu/gallogly_ethan/files/Aspirin%20Synthesis.pdf

[OceanBreeze]

Because amorphous phase materials would generally be prepared by cooling from molten, e.g. glass. If you carry out reactions in solution, generally you get a crystalline end product, because you usually get the solid out by precipitation or evaporation, both of which encourage crystals to form. Also, allowing crystals to form ensures purity, since you don't get many inclusions of impurities in a crystalline structure.  Further reading here: http://homepage.smc.edu/gallogly_ethan/files/Aspirin%20Synthesis.pdf

 

I see. Thank you for the explanation, it makes sense now.

 

I was intrigued about the question of why aspirin was used in these studies, when they could have chosen from many other crystalline substances. I suspected, and still do suspect that there must be some underlying connection to the medical end of things, although the paper makes no reference at all in that direction.

 

I did find another source, not related to the specific experiment mentioned in this thread, but seems to be generally related to this method of investigation, namely vibrational molecular-electronic cross coupling. It seems there may be some link to the “in vivo absorption properties” but nothing definitely spelled out at least that I can understand.

 

Investigations concerning the effects volumetric expansion of these API crystals on their structural and energetic properties are crucial for industrial tableting purposes which are related to practical aspects such as tablets’ degradation and changes related to in vivo absorption properties. The main purpose of this study is to investigate the influence of the volumetric expansion of crystals on inter and intra-molecular structures, cohesion, and vibrational properties. These motivations are linked to practical and economic aspects concerning the potential interest that the approach proposed in this work can attract at development, manufacturing, and medical levels.

 

 

But I think that is as far as my curiosity is going to take me.

[exchemist]

I see. Thank you for the explanation, it makes sense now.

 

I was intrigued about the question of why aspirin was used in these studies, when they could have chosen from many other crystalline substances. I suspected, and still do suspect that there must be some underlying connection to the medical end of things, although the paper makes no reference at all in that direction.

 

I did find another source, not related to the specific experiment mentioned in this thread, but seems to be generally related to this method of investigation, namely vibrational molecular-electronic cross coupling. It seems there may be some link to the “in vivo absorption properties” but nothing definitely spelled out at least that I can understand.

 

 

But I think that is as far as my curiosity is going to take me.

Yes, as I read it, the authors make the case for better modelling of crystalline forms of drugs, since different polymorphs (i.e different crystal structures) can sometime form and these may differ in stability or specific volume (influencing degradation rates, splitting packaging etc) and may have different rates of dissolution, hence rates of absorption and so on.

 

However I could not see, in the extract I was able to read, any reference to vibrational - electronic coupling, and thus could not see any suggestion that such coupling might have a physiological effect once the drug is dissolved in the bloodstream. As I said in my previous post, I would not expect this. If you think about it, in solution the modes of vibration and electronic excitation will be different: the hindered rotation will become a full rotation, the H-bonding will become transient instead of permanent, and so forth.  

[hazelm]

Yes, as I read it, the authors make the case for better modelling of crystalline forms of drugs, since different polymorphs (i.e different crystal structures) can sometime form and these may differ in stability or specific volume (influencing degradation rates, splitting packaging etc) and may have different rates of dissolution, hence rates of absorption and so on.

 

However I could not see, in the extract I was able to read, any reference to vibrational - electronic coupling, and thus could not see any suggestion that such coupling might have a physiological effect once the drug is dissolved in the bloodstream. As I said in my previous post, I would not expect this. If you think about it, in solution the modes of vibration and electronic excitation will be different: the hindered rotation will become a full rotation, the H-bonding will become transient instead of permanent, and so forth.  

"Different crystal structures and different rates of dissolution and absorption..."  I once read that if  a pill does not dissolve (being tested in water) within thirty seconds it is not going to dissolve fast enough to be of full benefit once swallowed.  So, rate of dissolving may be based on structure?

 

"the modes of vibration and electronic excitation will be different" - I'm going out on  a limb here but does the vibration and excitation aid in absorption?  Perhaps speed up dissolution?