Racemization of mixtures and it's relationship with drug absorption.

[Frankster]

racemization is a conversion, by heat or by chemical reaction, of an optically active compound into a racemic (optically inactive) form. Half of the optically active substance becomes its mirror image (enantiomer) referred as racemic mixtures (i.e. contain equal amount of (+) and (−) forms). If the racemization results in a mixture where the D & L enantiomers are present in equal quantities, the resulting sample is described as a racemate. Racemization can proceed through a number of different mechanisms, and it has particular significance in pharmacology as different enantiomers may have different pharmaceutical effects.

Of note, the L form of amino acids and the D form of sugars (primarily glucose) are usually the biologically reactive form.

(S)-Alanine (left) and (R)-alanine (right) in zwitterionic form at neutral pH

The stereoselective nature of most biochemical reactions meant that different enantiomers of a chemical may have different properties and effects on a person. Many psychotropic drugs show differing activity or efficacy between isomers, e.g. amphetamine is often dispensed as racemic salts while the more active dextroamphetamine is reserved for refractory cases or more severe indications; another example is methadone, of which one isomer has activity as an opioid agonist and the other as an NMDA antagonist.


Racemization of drugs can occur in vivo. Thalidomide as the (R) enantiomer is effective against morning sickness, while the (S) enantiomer is teratogenic, causing birth defects. The configurational stability of a drug is therefore an area of interest in pharmaceutical research. The production and analysis of enantiomers in the pharmaceutical industry is studied in the field of chiral organic synthesis.

 

[tobh]

this is a hell of a read, yet I feel only barely scratches the surface in terms of what's actually going on. At personal risk I'll go into some experiences I've had with extraction and ingestion of various compounds.

I've had MDMA that in reagent tests out with a near volatily in terms of the reaction that occurs for Mercks and Ehrlichs tests. The visual impression is white, flaky, damn near snowflake cocaine quality. Trust the insuffalation experience is worse than methamphetamine. Takes a particular type to insuffulate such a substance. The same source of this MDMA also provides MDA, and it's of equal quality however I've noticed it's more "wet" in structure. We even discussed how the crystaline structure behaves between the two compounds. One clumps, wants to stick together, while the other is free -- it doesn't seem to bond or be so hygroscopic, or so "oily." Only way I can describe it.

What I'm getting at is if produced in a lab setting what do those compounds fall under? Would MDMA be considered racemized and a more primitive form, similar to that of amphetamine vs d-amphetamine?

This carries further into personal experiments with DMT extraction. NN-DMT, 5meo-DMT, DMT fumerate.. What I'm getting at is what resources can one observe to definitively say, either through synthesis or more simple extraction, these resulting compounds fall into this particular category. We're talking organic molecules here, so this shit can be incredibly toxic or have unexpected side effects (Thalidomide is a prime example) and I think it's important knowing how to distinguish the entiomers is valuable.

Full disclosure -- I took AP chemistry in high school almost 20 years ago. I'm not an organic chemist nor an aspiring clandestine chemist. Genuinely curious how is the deliniation defined and how can one recognize these properties based off of chemical signatures.

 

[Frankster]

Well in the specific case of MDMA; addition of (energy) heat source will cause the racemization into it's two enantiomer S-MDMA and R-MDMA.

MDMA is a chiral and has been almost exclusively administered as a racemate. The two enantiomers have different kinetics. The disposition of MDMA may also be stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. The area under the blood plasma concentration versus time curve was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after 40mg. Half-life of (R)-MDMA is much longer than that of the (S)-enantiomer (5.8 vs 3.6 hours). MDMA excretion and metabolism have nonlinear kinetics; Half-lives would be even higher at typical doses ie. 100mg or more.

So my main point here is that heat energy breaks chemical bonds; and it changes the kinetics in many respects. (in many organic molecules)

Now lets look at the Brønsted–Lowry acid–base theory; which is a chemical compound formed when an acid donates a proton (H+) to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a hydrogen ion. On the other hand, a conjugate base is what is left over after an acid has donated a proton during a chemical reaction. Hence, a conjugate base is a species formed by the removal of a proton from an acid, as in the reverse reaction it is able to gain a hydrogen ion. Because some acids are capable of releasing multiple protons, the conjugate base of an acid may itself be acidic.

Free base (freebase, free-base) is the conjugate base (deprotonated) form of an amine, as opposed to its conjugate acid (protonated) form. The amine is often an alkaloid, such as nicotine, cocaine, morphine, and ephedrine, or derivatives thereof. Freebasing is a more efficient method of self-administering alkaloids via the smoking route. Whereas if your insufflation would be far better served in it's cocaine hydrochloride form. Which is done by adding energy (heat) The formulation as follows; (purity denotes both proper molar mass weights and pure feedstock)

when using sodium bicarbonate is
Coc-H+Cl− + NaHCO3 → Coc + H2O + CO2 + NaCl

With ammonium bicarbonate:
Coc-H+Cl− + NH4HCO3 → Coc + NH4Cl + CO2 + H2O

With ammonium carbonate:
2(Coc-H+Cl−) + (NH4)2CO3 → 2 Coc + 2 NH4Cl + CO2 + H2O

Whereas in cocaine four pairs of enantiomers are theoretically possible, only one (commonly termed l-cocaine) occurs naturally. Cocaine is structurally related to atropine (hyoscamine) and hyoscine (scopolamine), substances with quite different pharmacological properties. So there's lot of rules basically.

​

 

[Frankster]

So in synoptics of what I'm suggesting here is this;

fluctuations (cycling) daily temperature helps the plants in many respects; when it's brought up to that 75f or so zone; and then dropped back down to an acceptable "cool"... (ie. 60's ish) It really helps build that process along; in a very pure and unadulterated way. Whereas allowing the plants to cycle higher than necessary is often bad; very bad; because it's breaking down molecules; or even converting them into something undesirable.... Watching and monitoring heat sources are so very important.

Not only for the plant itself; but for the things that we are even feeding to the plants. #disclamer; keep in mind this comes with a caveat; cause when were generally talking about no-organic molecules, just the opposite is often true. Heat becomes a net benefit. (ie. eggshells as a source of calcium).

Lots of rules; but there's a method to the madness.

 

[tobh]

So in synoptics of what I'm suggesting here is this;

fluctuations (cycling) daily temperature helps the plants in many respects; when it's brought up to that 75f or so zone; and then dropped back down to an acceptable "cool"... (ie. 60's ish) It really helps build that process along; in a very pure and unadulterated way. Whereas allowing the plants to cycle higher than necessary is often bad; very bad; because it's breaking down molecules; or even converting them into something undesirable.... Watching and monitoring heat sources are so very important.

Not only for the plant itself; but for the things that we are even feeding to the plants. #disclamer; keep in mind this comes with a caveat; cause when were generally talking about no-organic molecules, just the opposite is often true. Heat becomes a net benefit. (ie. eggshells as a source of calcium).

Lots of rules; but there's a method to the madness.

this is a fantastic point to consider. especially late in flower where volatile terpenes are more likely to, well, do what volatile compounds do and become aerosol. Or even further, post harvest when it comes to the decarboxylation process for making infusions, the structure of the active substances is a consequence of adding heat. However, I'm not sure if decarboxylation fits into racemization. Or does it? Decarboxylation is its own process and racemization might very well be part of that process, or is the fundamental abstract process and decarboxylation is the consequence of racemization?

 

[Dirtbag]

Quite the post. Reminds me of this.

 

[Ponky]

Hmmmmm. Maybe I don't rent you guys my shop....

 

[tobh]

Quite the post. Reminds me of this.

hahaha shit man. starts with typical corporate speak then goes off the deepend real quick. pretty sure i applied for a job with rockwell software when i was starting out. iirc they were one of the targets of the Stuxnet malware as well.

 

[Frankster]

this is a fantastic point to consider. especially late in flower where volatile terpenes are more likely to, well, do what volatile compounds do and become aerosol. Or even further, post harvest when it comes to the decarboxylation process for making infusions, the structure of the active substances is a consequence of adding heat. However, I'm not sure if decarboxylation fits into racemization. Or does it? Decarboxylation is its own process and racemization might very well be part of that process, or is the fundamental abstract process and decarboxylation is the consequence of racemization?

Similar; but removes the carboxyl group, ie. removal of a carbon atom from a carbon chain. RCO2H → RH + CO2

Whereas Racemization rates are dependent on the molecule and conditions such as pH and temperature. Racemization can proceed through a number of different mechanisms. It can also be flipped back again. It's a rotational change in the angle of a molecule, (at a specific juncture) not a removal of any component.

In the case of decarboxylation; an enzyme is needed to put the carbon back in it's position again. Enzymes that catalyze decarboxylation's are called decarboxylases or, the more formal term, carboxy-lyases. The reverse process, which is the first chemical step in photosynthesis, is called carboxylation, the addition of CO2 to a compound.

 

[Dirtbag]

hahaha shit man. starts with typical corporate speak then goes off the deepend real quick. pretty sure i applied for a job with rockwell software when i was starting out. iirc they were one of the targets of the Stuxnet malware as well.

Haha nah man that whole video is fake nonsense.
Technobabble.

Turbo encabulator - Wikipedia

en.m.wikipedia.org

 

[Frankster]

Quite the post. Reminds me of this.

You got it bro. Basically how I look at it also.

Figuring out what's happening with the construction of cannabis is like taking 100 different (10,000 piece puzzles) throwing them on the floor; and sorting though pieces that look similar to one another. Then sorting them into piles, then start sorting each pile one at a time... It's an enormous task; and lots of luck involved.

Discoveries are usually observed at random; or by mistake; but if you understand a little of the process a little; you can start patching it slowly together.

 

[Frankster]

Haha nah man that whole video is fake nonsense.
Technobabble.

Turbo encabulator - Wikipedia

en.m.wikipedia.org

I suppose I could take the same approach many do here and simply purchase some pre-made formulations from a corporate fertilization company that's already done the work for them. Everything I've covered here might seem like nonsense to some; but it's certainly not fake.

Very much real; using bio-chemical principles in formulating all of my approaches to growing cannabis for a few years now. Your well aware of that; nothing's changed. My regime includes some of the purest; highly refined; organic medical grade supplements available. Many of the key ones on the right there are actually human neurotransmitters.... The plants thrive on them. I believe it's possibly evolving them in some respects.

The molecular charge of elements matter. For instance; calcium hydroxide vs calcium carbonate. Very similar; but availability (reaction) rates are massively different. Carbonate form has to be "charged" somehow. Cannabis cannot uptake calcium in some of it's inert form unless energy potential is stored within them. (often under bacterial or fungal action) Having a fundamental grasp of that information; can be advantageous. Simply put; what you feed a plant matters; it's purity matters; it's charged state matters. It can be done blindly (in big hunks as 99% of everyone else does) or by assembling little pieces together. I prefer doing it the latter way; because of the tight control it offers...

Calcium carbonate CaCO3

The actual active form of Calcium as hydroxide Ca(OH)2 which drives the flowering stage.

 

[Frankster]

hahaha shit man. starts with typical corporate speak then goes off the deepend real quick. pretty sure i applied for a job with rockwell software when i was starting out. iirc they were one of the targets of the Stuxnet malware as well.

Thus is the world. It's complexity; and our inability to make any sense out of it; So we poke fun; and/or deride.

Yet everyone here on the web (and the world at large) is a virtual slave to this sort of nonsense. Because our very lives revolve around things we cannot possibly control; nor understand. Or do anything about. We go to the markets; pick out our processed foods; (or have it prepared for us) Onto the gas station; but not a clue on how anything works; or what it's doing to mother earth.

Mankind is in a sad state of self-denial and utter delusion. Nobody wants to give up their gravy train; for independence. (I certainly don't)
Why innovate; when all the problems of mankind have already been solved for us.

 

[Dirtbag]

I suppose I could take the same approach many do here and simply purchase some pre-made formulations from a corporate fertilization company that's already done the work for them. Everything I've covered here might seem like nonsense to some; but it's certainly not fake.

Very much real; using bio-chemical principles in formulating all of my approaches to growing cannabis for a few years now. Your well aware of that; nothing's changed. My regime includes some of the purest; highly refined; organic medical grade supplements available. Many of the key ones on the right there are actually human neurotransmitters.... The plants thrive on them. I believe it's possibly evolving them in some respects.

View attachment 1204869


The molecular charge of elements matter. For instance; calcium hydroxide vs calcium carbonate. Very similar; but availability (reaction) rates are massively different. Carbonate form has to be "charged" somehow. Cannabis cannot uptake calcium in some of it's inert form unless energy potential is stored within them. (often under bacterial or fungal action) Having a fundamental grasp of that information; can be advantageous. Simply put; what you feed a plant matters; it's purity matters; it's charged state matters. It can be done blindly (in big hunks as 99% of everyone else does) or by assembling little pieces together. I prefer doing it the latter way; because of the tight control it offers...

Calcium carbonate CaCO3

View attachment 1204879

The actual active form of Calcium as hydroxide Ca(OH)2 which drives the flowering stage.

View attachment 1204880
View attachment 1204884

Oh I know what you were talking about is real stuff. It just went over my head so fast I felt like I was reading about the turboencabulator.

 

[Frankster]

Oh I know what you were talking about is real stuff. It just went over my head so fast I felt like I was reading about the turboencabulator.

Thanks for clarifying Dirtbag. I know I go off the reservation sometimes; but there's usually a point to be made somewhere. It might be a subtle one; but more than anything It's just turning wheels in my head.

The whole Racemization spiel is just about clarifying that it's more than simply ingredients. Energy and pH play a major role; and what can happen if those get out of line can be quite concerning. It can convert a generally healthy substance into a harmful toxic one.

 

[tobh]

Whereas Racemization rates are dependent on the molecule and conditions such as pH and temperature. Racemization can proceed through a number of different mechanisms. It can also be flipped back again. It's a rotational change in the angle of a molecule, (at a specific juncture) not a removal of any component.

This is the explanation I needed to understand what racemization is. I've very limited organic chem knowledge. Took a course when I was in college but that's been over a decade ago and what I learned then simply isn't relevant to working at a fintech company as a software engineer now. Appreciate you dropping this kind of knowledge. It's a lot to grok, and like you said, to most it sounds like bullshit but these are basic rules of how molecules interact with each other. Knowing that racemization isn't actually relevant to decarboxylation (with this quoted explanation being the key detail) now it makes sense. I guess I was confused as to what exactly was happening, and thought maybe the removal of that carboxyl group was, in a way, racemization.

Moving a molecular branch is not equal to REmoving a molecular branch.

In a sense, decarboxylation is related to combustion in a way, then correct?

EDIT: or more so, combustion is decarboxylation in a much more volatile fashion

 

[Frankster]

Moving a molecular branch is not equal to REmoving a molecular branch.
In a sense, decarboxylation is related to combustion in a way, then correct?

EDIT: or more so, combustion is decarboxylation in a much more volatile fashion

Yes, moving the position along it's axis... Here's GABA for instance... It's in all cells everywhere.

Racemic gamma vinyl-GABA (R,S-GVG) blocks methamphetamine-triggered reinstatement of conditioned place preference

Preventing relapse poses a significant challenge to the successful management of methamphetamine (METH) dependence. Although no effective medication currently exists for its treatment, racemic gamma vinyl-GABA (R,S-GVG, vigabatrin) shows enormous potential ...

www.ncbi.nlm.nih.gov

As for decarboxylation; is a chemical (heat) reaction that actually cleaves off a portion; in this case. * removes a carboxyl group and releases carbon dioxide. ie. removal of a carbon from it's chain.

Everything living is made from these types of carbon chains. every single living cell on the planet... Mostly; carbon, hydrogen, oxygen and nitrogen in that order.

Think of life like a massive recycle facility; the more stuff that's created; the bigger the pile of stuff (us) that's constantly in circulation.... Then more and more is eventually leached out of rocks, and the physical elemental world around us; get fed into that recycle pit. (ie. C02 spewed from volcanos; ect.) That's why our oceans are filled with water; and our planet has an atmosphere; cause accumulated life; over time; put it there..... They turned that C02 into something different... took the carbon; and gave back hydrogen... life arranged it so.

The most common oxidation state of carbon in inorganic compounds is +4, while +2 is found in carbon monoxide and transition metal carbonyl complexes.
Electron configuration; [He] 2s22p2

Whereas hydrogen is atomic number 1. Hydrogen is the lightest element. With three isotopes: hydrogen, deuterium, and tritium. At standard conditions hydrogen is a gas of diatomic molecules having the formula H2; it's electron config is 1s1. It's also the most abundant element comprising 75% of the known universe.

There a good match for each other chemically speaking. That's why we have so much water on this earth. Buffers create that fundamental (math) language that makes life possible. It's much like the language of music in some sense; the elements being pitch, beat or pulse, tempo, rhythm, melody, harmony; and life being the song. ie. the expression of it all.