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Polymorphic properties of DMT Options
 
Loveall
#41 Posted : 3/7/2022 10:24:17 AM

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Thank you so much Mindlusion for the info 🙏

The other day I was pouring a warm-to-room temp cloudy DMT naphtha solution out of a jar and it became clear after pouring. Was it because I mechanically disrupted the xtal seeds? Is it important to not disrupt them or letting them re-form before colling further?

Thanks again 🙏
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Mindlusion
#42 Posted : 3/9/2022 10:30:55 PM

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Loveall wrote:
Thank you so much Mindlusion for the info 🙏

The other day I was pouring a warm-to-room temp cloudy DMT naphtha solution out of a jar and it became clear after pouring. Was it because I mechanically disrupted the xtal seeds? Is it important to not disrupt them or letting them re-form before colling further?

Thanks again 🙏


It sounds to me like yes, you probably have redissolved them. I wouldn't be too concerned though because it sounds like it was still very early in the crystallization process, so if everything redissolved, it will just start again and get back to where it was very quickly, so it won't affect the final outcome. Typically I do all my transfers while it is still warm or close to room temp, but once it is in the crystallization flask I try not to touch it at all until waiting 12-18 hours unless to transfer it to the fridge or freezer.
Expect nothing, Receive everything.
"Experiment and extrapolation is the only means the organic chemists (humans) currrently have - in contrast to "God" (and possibly R. B. Woodward). "
He alone sees truly who sees the Absolute the same in every creature...seeing the same Absolute everywhere, he does not harm himself or others. - The Bhagavad Gita
"The most beautiful thing we can experience, is the mysterious. The source of all true art and science."
 
Ruffles
#43 Posted : 3/12/2022 11:56:22 PM
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Loveall wrote:
I'm leaning towards forgoing handling freebase altogether and simply moving towards a salt soluble in PG (like DMT citrate).


Can you please elaborate on that?

Is salt-DMT vapeable??? If so, which salt would be better???

This has been in my mind since ever! Never had the guts to try it myself but just about to...


To the point of this discussion... if the polymorphs exist as such, I wonder what would their pharmacokinetics would be.

Will digestion monomerize the polymorphs before absorption? Do we have specific enzymes for that (tryptophan polymorphs as storage)? Will oligomers have distinct absorption rates through all tissues? Do polymorphs or oligomers invade synapses? Do they interact with receptors? How would they modulate the effects?

Wonderful subject this one.
 
Mindlusion
#44 Posted : 3/13/2022 8:24:36 PM

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Ruffles wrote:
Loveall wrote:
I'm leaning towards forgoing handling freebase altogether and simply moving towards a salt soluble in PG (like DMT citrate).


Can you please elaborate on that?

Is salt-DMT vapeable??? If so, which salt would be better???

This has been in my mind since ever! Never had the guts to try it myself but just about to...


To the point of this discussion... if the polymorphs exist as such, I wonder what would their pharmacokinetics would be.

Will digestion monomerize the polymorphs before absorption? Do we have specific enzymes for that (tryptophan polymorphs as storage)? Will oligomers have distinct absorption rates through all tissues? Do polymorphs or oligomers invade synapses? Do they interact with receptors? How would they modulate the effects?

Wonderful subject this one.



There is no monomerization, there is no difference in absorption because there is no difference in properties. Once DMT is in the solution phase, or virtually any other phase (gas, and liquid) the DMT molecules assume their regular free rotation and the molecules become absolutely indistinguishable. The purpose of my previous post was to highlight this fact by looking at DMT 1H NMR, and comparing it with a molecule that does exhibit different chemical environments in the solution phase, although I admit it was not really fully fleshed out. Polymorphism is very common among organic compounds, because organic molecules have a high degree of complexity, so a low degree of symmetry (lots of possible bond rotations and conformations, and ways to pack inside a solid crystal). Chocolate (cocoa butter) has something like 6 unique polymorphs, with specific ones being ideal (give you a chocolate that is solid at room temperature and has a good texture when you bite into it).

The point is, that has been missed, is that these interactions are only relevant in the solid phase or in the liquid-to-solid phase transition. It is only when the molecules are tightly packed, like in a solid or a liquid, and the temperature is low enough (to solidify), that the bond rotation becomes significantly hindered enough so that different chemical environments arise, and those differences express themselves with different chemical properties, like melting point, color, and in their spectrograph. Just like it doesn't make any sense to inquire about a chemical compound's density when it's in the gas phase, or a metals malleability and tensile strength while it's in a liquid phase, it doesn't make any sense to inquire about a polymorphs properties beyond the solid phase. You're not alone in this misinterpretation in this thread as well as other threads describing something similar, and referring to it as an "oligomerization" or "polymerization" (which, for added confusion, should really be referring to the formation of covalent bonds, not the non-covalent interactions being discussed here) which led to a lot of chasing ghosts and theorizing based on the incorrect interpretation of the phenomenon and misunderstanding of the diving forces at work. For the same reasons, it doesn't make sense to talk about pi-stacking interactions taking place in solution, to cause aggregation of molecules in the solution phase (especially aqueous solution) which is taking the interactions out of their actual context.

The crux of what we are discussing here, the phase properties of matter, and it is an extremely deep question in of itself, and not very intuitive at the most fundamental level. It should start with asking questions like "why are gasses compressible and why are liquids incompressible?" the phases of matter are not elementary properties of the individual atoms or molecules, but instead are emergent properties out of how matter is interacting with itself. The important thing to remember then, the environment dictates what forces will determine the behavior of the system. For example, the weak intermolecular forces that bind molecules together in a solid, are not at all relevant they are dissolved in solution. Or often we will talk about how powerful water hydrogen bonding is, so much that it can stay liquid up to 100C at 1atm, except above that temperature, even though it possesses this powerful property, water suddenly doesn't seem so special, because its hydrogen bonding is no longer relevant in the gas-phase.

You can even sort of think of it like a government, or the properties of people as a whole compared to their fundamental properties as individuals. The force of government will not dictate the properties of any one individual person, but it will supress some properties it doesn't wish to see, and encourage others, and that can change the properties/behavior of the system of a whole. When that regime changes, the behavior of the system changes, not because anything new has been injected into it, but what properties of the individuals that were already there underlying it, and it will change dramatically until it reaches a new equilibrium, which is an energy intensive process. This is like a phase-transition. Perhaps a better example, is when you transition from dreaming consciousness to waking consciousness, or after taking a good dose of a psychedelic. Your consciousness is undergoing a phase transition, because the boundary forces that are governing your current state of consciousness has changed, and different properties can emerge.

Another, even more primordial example, is even in the fundamental forces underlying the universe itself. We know of one clear example where the entire universe underwent a phase transition, during the rapid cooling and expansion the electroweak regime transitioned into the current regime, where before, you had a single electroweak force, to now you have the electromagnetic and weak nuclear forces. This completely blew my mind when I first conceptualized it in this way. And it points to, and leads you to wonder what forces and what phenomena are really truly fundamental. In the same way that if you have liquid water and rapidly reduce the pressure, the hydrogen bonding isn't enough to keep the water together as a liquid and it transitions into a gas where that hydrogen bonding 'force' no longer exists. The electroweak force no longer exists in our universe as a driving interaction (but it still exists!), but at one point it was as real as electromagnetism today, and these conditions can be recreated in a particle accelerator.
Expect nothing, Receive everything.
"Experiment and extrapolation is the only means the organic chemists (humans) currrently have - in contrast to "God" (and possibly R. B. Woodward). "
He alone sees truly who sees the Absolute the same in every creature...seeing the same Absolute everywhere, he does not harm himself or others. - The Bhagavad Gita
"The most beautiful thing we can experience, is the mysterious. The source of all true art and science."
 
benzyme
#45 Posted : 3/13/2022 9:08:42 PM

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The polymorphic properties of dmt can be traced to its origin in nature as the ubiquitous amino acid, tryptophan. The partial rotatability of its (tryptophan's) alpha and beta carbons is what permits its participation in protein-folding. Obviously, chirality is lost upon decarboxylation. And of course, as a salt, the orientation of the molecule is 'locked', so to speak.
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Loveall
#46 Posted : 3/13/2022 10:28:22 PM

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Ruffles wrote:
Loveall wrote:
I'm leaning towards forgoing handling freebase altogether and simply moving towards a salt soluble in PG (like DMT citrate).


Can you please elaborate on that?

Is salt-DMT vapeable??? If so, which salt would be better???

This has been in my mind since ever! Never had the guts to try it myself but just about to...


To the point of this discussion... if the polymorphs exist as such, I wonder what would their pharmacokinetics would be.

Will digestion monomerize the polymorphs before absorption? Do we have specific enzymes for that (tryptophan polymorphs as storage)? Will oligomers have distinct absorption rates through all tissues? Do polymorphs or oligomers invade synapses? Do they interact with receptors? How would they modulate the effects?

Wonderful subject this one.


DMT-salt is "vapable" in PG, but that is a misnomer. What can be done is aerosolize the salt in an e-juice and the tiny dropplets carry the salt, same as the very popular nicotine salts have been doing for the past few years in the "vaping" world.

IDK about the "best salt". I think we would prefer one that is stable at the "vaping" temp of ~200C (citrate is not, but fumaric and acetic should be) and is also soluble in PG at least at the 20% level. There is a discussion here.
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Ruffles
#47 Posted : 3/19/2022 11:04:58 PM
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Quote:
referring to it as an "oligomerization" or "polymerization" (which, for added confusion, should really be referring to the formation of covalent bonds, not the non-covalent interactions being discussed here) which led to a lot of chasing ghosts and theorizing based on the incorrect interpretation of the phenomenon and misunderstanding of the diving forces at work.


Yes, understood your point more clearly now. Thank you mindlusion for the deep and beautiful observations on the phase properties of matter and the connection to DMT.

Also, thank you loveall for the point and the link to a thread about vaping (aerosolizing) magic salts.

Much love to you!
 
Mindlusion
#48 Posted : 3/20/2022 4:26:57 PM

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Ruffles wrote:
Quote:
referring to it as an "oligomerization" or "polymerization" (which, for added confusion, should really be referring to the formation of covalent bonds, not the non-covalent interactions being discussed here) which led to a lot of chasing ghosts and theorizing based on the incorrect interpretation of the phenomenon and misunderstanding of the diving forces at work.


Yes, understood your point more clearly now. Thank you mindlusion for the deep and beautiful observations on the phase properties of matter and the connection to DMT.

Also, thank you loveall for the point and the link to a thread about vaping (aerosolizing) magic salts.

Much love to you!


No problem, I should clarify because it was asked:

Quote:
To the point of this discussion... if the polymorphs exist as such, I wonder what would their pharmacokinetics would be.

Will digestion monomerize the polymorphs before absorption?
Do we have specific enzymes for that (tryptophan polymorphs as storage)? Will oligomers have distinct absorption rates through all tissues? Do polymorphs or oligomers invade synapses? Do they interact with receptors? How would they modulate the effects?


The first two questions are actually legitimate questions when it comes to polymorphs, drug pharmacokinetics. Just not DMT, in this case, and I wanted to clarify that by stating clearly what a polymorph actually is.

But, polymorphs can indeed affect a drugs pharmacokinetics. For instance, if you had a drug with a polymorph that had a lower solubility, or a formulation that took a lot more time to dissolve in acidic water, it will definitely affect the drugs oral bioavailability. This is certainly the case with large peptide drugs, which can have many polymorphs by their nature, and being not easily ionized or solubilized in water, depending on the peptide. Small, easily ionized molecules like DMT don't fit into this category, because of how easily they can be solubilized and ionized.
Expect nothing, Receive everything.
"Experiment and extrapolation is the only means the organic chemists (humans) currrently have - in contrast to "God" (and possibly R. B. Woodward). "
He alone sees truly who sees the Absolute the same in every creature...seeing the same Absolute everywhere, he does not harm himself or others. - The Bhagavad Gita
"The most beautiful thing we can experience, is the mysterious. The source of all true art and science."
 
downwardsfromzero
#49 Posted : 3/20/2022 7:06:07 PM

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The second the highlighted sentence, "Will digestion monomerize the polymorphs before absorption?", appears to betray a misunderstanding. 'Polymorph' is not synonymous with 'polymer'.

While ML explained this quite exhaustively the first time around, it seems worthwhile to highlight this point explicitly and in isolation. The words do look and sound fairly similar Smile




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― Jacques Bergier, quoting Fulcanelli
 
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