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Possible Oligomers/Polymers of DMT

Migrated topic.
Experiment #2 also done now. But this is now much cooler than the theoretical talks with no experiments, so it is pasted at first position into the first post. So click back to Page 1 to see the full text.

In short:

Radically induced Polymerization seems to produce the SAME reaction pattern regarding positions of DMT to Polymerize and the SAME reaction ratio of non-reacted to reacted bonds.

That makes me think if there is

A) a saturation of reactivity where no more positions are likely to react per molecule (probably disfavored by steric hindrance)

B) a saturation of coupled C-C bonds after which the polymerization degree does not rise any further (probably disfavored by entropy)

N-Oxide formation in both cases was also pretty similar ~ 2,5 %. If these are built into the Polymer or just stick around inbetween we won't know, as we also cant extract them as monomeric molecules with Hexane. As reaction conditions were quite different regarding initiation/catalyzing system and time, this makes chances kind of high that the proposed Polymer structure from Experiment 1 is the one that was mostly retrieved in both cases.

At the end there is also a picture shown which is mapping the reactivity of DMT across the molecule regarding the results of this experiment, at least for Polymerization purposes. Now also posting here:

Reactivity_Pattern.png

In conjugated systems you often share a reactivity across 1,3-positions or 1,5-positions and so on. In this case it is different for the 6-Ring as you can see. Reason is: if you draw the Mesomery that can be induced from the indolic N then if you delocalize the N-electron towards left position you will end up with a negative charge at position #8. If you delocalize the N-electron towards the upper position you will end up with a negative charge at position #11. This former rule seems the be overcome by the fact that the ring of the N is only 5-membered, so in total in DMT position #8 and #11 show the same reactivity pattern, even if the are conjugated in a 1,4-(para)-positioning.

So to conclude, the conditions which created those polymers are not exactly what we expect in an extraction or when vaporizing Spice. But I think it is still rather likely that reactivity patterns which are observed here should also give hints how the DMT molecule would behave in similar conditions and therefore would possibly create Polymers pretty similar or not too different from what I have drawn here.

Here as a summary of everything the proposed "average DMT-Polymer structure" that was retrieved from those experiments:

Polymer_Pattern_Final.png

This structure is only valid if we assume that 1 DMT binds 2 new molecules. Also 3 (or with Position 9 / 10 even more) would be possible, but probably chance for creating these decreases dramatically. Therefore based on these experiments I may carefully assume that DMT Polymerization stops at the shown Hexamer with only minor chances of elongating the Polymer chain at the outermost positions #9 / #10.

As usual with Polymerization, there might be any kind of other isomers / wild combinations possible. But as any reaction will have a certain prefered pathway through minimizing energy barriers and thermodynamically most stable products, there should be at least a set of preferred patterns of Oligomers.
 
Sadly have to revise all both experiments :cry: :cry:

Initial post is therefore corrected and just for sake of information the wrong one then attached above this post.

There was an error:

To get the total count of aromatic signals per 1 molecule it was important to normalize the whole spectrum to 1 signle molecule. Putting the NMe2-Peak to 6 at 2,23 ppm is wrong, because also N-Oxide is evolving and thus "1 molecule" is shared into X DMT and Y DMT-N-Oxide, which make up for a total of 1 molecule. This way the aromatic signals and the indolic NH can be analyzed pretty well.

But I mistook the signal at 2,50 ppm for the N-Oxide :!: :roll: Which is actually DMSO. Instead N-Oxide is at ~ 3,15 ppm, but forgot. Now in both cases N-Oxide is much less. That also means that X for DMT is much higher and pretty close to 6. Now increasing this number it will also increase the aromatic signals + indolic NH integral. It's actually increasing so much, that you now get to an amount which is basically 1 for all single protons :oops: :oops: That would be a perfect indication that NOTHING actually happened. As this is now in accordance with the actual chemical shift, I have to strongly assume that the corrected version is correct ... and therefore no sign of polymerization took place.

Still the link to the old spectrum is given as a side comment, but that probably means no additional insight into possible DMT-Polymer structures.

Comes out quite weird that these *harsh conditions* seemed to make absolute 0 effect. Some decrease of indolic NH, but nothing else so still no information of how it could have reacted. At least this is somehow in accordance with any other result, which also never saw any reasonable evolution of N-Oxide or Polymers. But that makes me again wonder too much why whatever leftover I have in both cases does still not dissolve in boiling Heptane, if it really would be not pure freebase DMT? :shock:
 
Brennendes Wasser said:
Experiment #2 also done now. But this is now much cooler than the theoretical talks with no experiments, so it is pasted at first position into the first post. So click back to Page 1 to see the full text.

In short:

Radically induced Polymerization seems to produce the SAME reaction pattern regarding positions of DMT to Polymerize and the SAME reaction ratio of non-reacted to reacted bonds.

That makes me think if there is

A) a saturation of reactivity where no more positions are likely to react per molecule (probably disfavored by steric hindrance)

B) a saturation of coupled C-C bonds after which the polymerization degree does not rise any further (probably disfavored by entropy)

N-Oxide formation in both cases was also pretty similar ~ 2,5 %. If these are built into the Polymer or just stick around inbetween we won't know, as we also cant extract them as monomeric molecules with Hexane. As reaction conditions were quite different regarding initiation/catalyzing system and time, this makes chances kind of high that the proposed Polymer structure from Experiment 1 is the one that was mostly retrieved in both cases.

At the end there is also a picture shown which is mapping the reactivity of DMT across the molecule regarding the results of this experiment, at least for Polymerization purposes. Now also posting here:

Reactivity_Pattern.png

In conjugated systems you often share a reactivity across 1,3-positions or 1,5-positions and so on. In this case it is different for the 6-Ring as you can see. Reason is: if you draw the Mesomery that can be induced from the indolic N then if you delocalize the N-electron towards left position you will end up with a negative charge at position #8. If you delocalize the N-electron towards the upper position you will end up with a negative charge at position #11. This former rule seems the be overcome by the fact that the ring of the N is only 5-membered, so in total in DMT position #8 and #11 show the same reactivity pattern, even if the are conjugated in a 1,4-(para)-positioning.

So to conclude, the conditions which created those polymers are not exactly what we expect in an extraction or when vaporizing Spice. But I think it is still rather likely that reactivity patterns which are observed here should also give hints how the DMT molecule would behave in similar conditions and therefore would possibly create Polymers pretty similar or not too different from what I have drawn here.

Here as a summary of everything the proposed "average DMT-Polymer structure" that was retrieved from those experiments:

Polymer_Pattern_Final.png

This structure is only valid if we assume that 1 DMT binds 2 new molecules. Also 3 (or with Position 9 / 10 even more) would be possible, but probably chance for creating these decreases dramatically. Therefore based on these experiments I may carefully assume that DMT Polymerization stops at the shown Hexamer with only minor chances of elongating the Polymer chain at the outermost positions #9 / #10.

As usual with Polymerization, there might be any kind of other isomers / wild combinations possible. But as any reaction will have a certain prefered pathway through minimizing energy barriers and thermodynamically most stable products, there should be at least a set of preferred patterns of Oligomers.
Click to expand...

I have to ask...did you smoke it? If yes, what were the effects?

If no, what would you expect the effects to be?
 
I think that thing would never evaporate if you heat it up. Probably just burn. So even if you would have it, it will probably never be administrable, except if you eat it straight away?

Cheers
 
BW's updated NMR interpretation ("it's just DMT") could be seen as indicating that a non-oxidative olig-/polymerisation may have occurred - in which case, thermal depolymerisation is also a thing, c.f. preparation of styrene from polystyrene, or methyl methacrylate from Perspex/Plexiglas, both by thermal depolymerisation.

If at least a significant proportion of the DMT polymer is non-oxidised, we could expect it to be amenable to vaporisation. Careful re-examination of NMR results, for example, should be performed before accepting this hypothesis; are there any other observations which might contradict my suggestion?
 
SpaceTraveller said:
I have to ask...did you smoke it? If yes, what were the effects?

If no, what would you expect the effects to be?
Click to expand...

Sadly you can forget that substance/structure. As I wrote in the post exactly above your question the structure was derived from an error within analyzing that spectra. Marked it now in red so should be clear :)

Reason is: The ructure of a potential oligo/polymer is derived from first understanding how much unreacted DMT is still left in the sample. As I first had this number somehow lower than it actually was, I had a way too high amount for "stuff that should not be DMT". So what information I could get from possible binding modes of DMT-units when polymerizing was used to get that structure, but the numbers were wrong in the first place, so that substance was nothing (probably) that actually was inside of my sample. I just left it there for completion of information, but in the first post it was already reverted directly 1 day later to the original text.

Therefore sadly even though those experiments induced some really harsh conditions for poor DMT and should have given a good push towards certain polymerization pathways, it was found that still nearly everything of the analyzed samples was still unreacted DMT - even though being red and oily.

Sad for finding out any more insights into DMT Polymers, but then on the other hand also a sign that DMT polymerization is truly just happening at a really low rate.




Still regarding that potential substance and its structure:

Not sure if it would have any activity, even if you eat or IM that stuff. Reason is that the indole/tryptamine motive inside of any substance carrying it would most likely be the responsible structure to induce the ligand-receptor-activity.
Now it seems logical that combining many of these motifs to a long chain might have some interesting properties or stronger receptor activation. But most likely a receptor will just have 1 binding site (for a certain motif, it still can have multiple binding sites for other types of ligands). So if you have a chain of many ligands at once, it might be really likely that anyways just 1 or at least a very low count of them anyways can interact with the receptor.

Even worse: very small molecules are probably even more likely to induce receptor interactions, because they are way more mobile let's say and therefore will have an easier time fitting into the binding site. The "ease of fitting into a binding site" thus chance to activate the receptor directly correlates with the activation strength AKA potency of the ligand (not counting competetitive inhibitors here, but of course even they have their own potency scales) and so a bulky oligomeric ligand might actually activate it even worse.
It might get better by attaching DMT molecules with a flexible chain to each other, which serves as connection points, but still keep their mobility (I'm sure this is not the right word, but well the meaning should be clear) as high as possible, like a spacer of DMT-C10H20-DMT or similar.
But in terms of connecting DMT to DMT by an inflexible chain of more DMT I would assume interaction with the binding site might be even more difficoult and therefore weaker.

The true way of increasing a drugs potency on a molecular level would be some rational design based on known structure-activity-relationship. I dont know any real scientific numbers for binding strength, but just based on the total amount needed for a certain effect 5-MeO-DMT and 4-OH-DMT seem stronger than regular DMT. So you might assume that around the 4-5 Position of the Tryptamine ligands in the respective binding site of 5HT receptors there might be other positive (partial-)charges, which make 5-MeO-DMT and 4-OH-DMT "fit even better" into the binding site, thus subjective potency of the drug is felt greater than with regular DMT.

Still current trend in pharmacology is to not go the rational design way and simply make a collection of 1000s variations of a drug and simply check which one of them has the strongest receptor interaction and then use this for further tests, so it is just determined by randomization and called combinatoric design (not sure if also english name). As there seems to be a big advent of those Neuroplasticity drugs, maybe combinatoric design might soon show a Tryptamine framework that will show exceptional fitting into 5HT receptors and then some changes can be made by other people to re-engineer their psychedelic effects (which are deleted upon going from classic tryptamines to neuroplasticity drugs) :twisted: So far Shulgin used kind of a mix of both ways: Creating a library of different variations, but only with a very similar set of changes between all molecules (first try Dimethyl-", then Diethyl-", then Methyl-Isopropyl-", ...). Also it was all performed "by hand" and so you can never go high-throughput. With a true combinatoric design you will have thousands of small random variations and simply by the power of high numbers you will ultimately find one which is exceptionally better. Currently that is a faster way to find a good candidate in drug discovery, but maybe with some current advancement in AI we can get a better understanding of binding sites and their structure-activity-relationships to directly compute the perfect ligand. :roll:
 
I love how DMT is still clinging on to its secrets here :D

Btw the English term is "combinatorial chemistry/design" - the "-isch" suffix can correspond to a variety of English suffixes on account of the language's promiscuity.

I take issue, to some extent, with your interpretation of structure activity relationships although it's clear that you were talking within the context of DMT polymers I'd still like to highlight that LSD is a very good example of a molecule being somewhat larger than DMT and having a significantly higher activity at 5HT receptor sites. Then again, pretty much any indolic psychedelic is going to be bigger than DMT anyhow. You do go on to say how functional groups can enhance receptor affinity, but we should be aware that this is not the only factor at play - some modifications may increase affinity at the expense of activity, case in point being BOL-148, bromo-LSD.

We could speculate, in light of the receptor ligand activities of some of the DMT-oligomer-like alkaloids found, for example, in Psychotria alba that some DMT oligomers might be expected to show activity at NMDA receptor sites or (kappa) opioid sites, which would add other dimensions to their visionary activity. How this might contribute to variability of effects in vivo would be a further level of speculation.

When it comes to predicting "the perfect ligand", I can only presume that the models will be equally effective at predicting activity as they will affinity and I would suggest this would be a fascinating area to look into. You may have heard of the "ultraLSD" - it's a computational chemistry project that has focussed on 5-HT receptors and is said to have obtained interesting results. Hamilton Morris covered it, but I forget the name of the actual professor involved.
 
Good point receptor affinity and potency being 2 different pair of shoes :lol: And yes indeed, LSD is probably bigger than any other conventional tryptamine and way stronger 😁 😁 But regarding the size of DMT / 5-MeO it was more meant like: The smaller molecule simply lacks some groups for that increased activity. But that still also shows that binding pouches might be actually bigger than only for small molecules of low molecular weight.

ultraLSD sounds pretty funny, might be worth a peek into Youtube 8)
 
As someone with no formal chemistry training, I'm out of my element and this is hard to follow. Brennendes, did you smoke the red stuff! Did it kick like 2 angry mules?

Please let me know 😁
 
SpaceTraveller said:
Relevant!!!

https://www.sciencedirect.com/science/article/pii/S0026265X13000544
Click to expand...
Ah, yes - Gaujac et al. 2013 aroused considerable interest here when it was published. Thanks for linking it here, it does contain a lot of useful data. Besides those two main forms in that paper, the pattern gets repeated in other published investigations - except the melting points are practically always different from those reported in Gaujac et al. Does this indicate anything other than melting point being a capricious analytical tool for polymorphic substances?

Considering the variation shown depending on the rate of heating, I'd say this explains a lot. For each of the data points from the other investigations it would be helpful to find out as much detail as possible regarding the equipment and methodology used - information that likely won't be as detailed or precise as the Gaujac paper, if it is even forthcoming at all.
 
SpaceTraveller said:
As someone with no formal chemistry training, I'm out of my element and this is hard to follow. Brennendes, did you smoke the red stuff! Did it kick like 2 angry mules?

Please let me know 😁
Click to expand...

No sadly not :p As I said the formula derived above was a misinterpretation and so the actual molecule probably did not even exist in my sample. Also nothing was consumed - simply analyzed. You wrote red stuff, but I think there are no pictures? But the funny thing is that indeed all those samples looked dark red after treatment.
 
Aaaaah indeed. But that red stuff is not the same.

Here in this experiment more stuff was added, to forcefully (and hopefully) induce a polymerization. But this did not happen - at least not to a noticable threshold.

The other picture only shows DMT that was heated. But also there not much seemed to be happening.

Both are red, but that's just the regular colour of DMT. Either the crystal grid gets broken up, DMT molecules are more mobile and can "glue together" in a process called pi-Stacking.

Here the electrons of the respective molecules come in closer interaction than they would do otherwise, creating something like a bigger Chromophore = scaffold of the molecule, that is responsible for a molecule's colour in our eyes. This means upon "glueing together" molecules might start become coloured, like the now reddish coloured molten spice.

Another theory could be that indeed polymerization happens and very big molecules often tend to also become coloured. Even trace amounts of colourfull impurities sometimes can cause an otherwise 99 % pure white substance to look colourful. No proof for this in the analysis, but as I said even traces can sometimes cause a colour.


So as a summary both samples are reddish stuff and were obtained upon heating, but not the same sample. But the thing from that post also never was vaporized, I have no clue what I did with that ... it's so many years ago already, time flies :roll:
 
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