Chemiolis - 2023-12-15
In this video I am making and self-testing the molecule Capsazepine (albeit crude), a molecule that blocks access to the receptor activated by the spicy-molecule capsaicin, thus removing its ability to cause you the spicy feeling. There is no known literature on its use on humans, it is used to study the TRPV1 ion-channel (spicy/heat receptor) but only in biology or biochemistry. For the azepine: https://onlinelibrary.wiley.com/doi/10.1002/anie.201302530 For the isothiocyanate I used a general procedure from: https://scihub.se/https://doi.org/10.1021/jm00125a019 For the final coupling: https://sci-hub.se/https://doi.org/10.1021/jm00039a006 Check out @LabCoatz_Science who notified me of this molecule. Don't conduct any chemical reactions without proper and professional safety analysis and risk management. Measures taken can be invisible, not filmed, not properly visible on camera or misjudged by the viewer due to setup or video construction. Always conduct own appropriate measures regardless of video setup.
I was wondering when someone would finally get around to this synthesis! I actually managed to get a hold of some Capsazepine a couple years ago and my experience was similar. For me it reduced the spicyness, but only for about a half an hour, and didn't reduce it any more than perhaps drinking a glass of milk.
Been breeding Ghost Peppers for 14 years, milk and bread are placebo. The real trick is honey.
Is it possible that it's like capsaicin and needs to be in a salt form to be effective? Or was it already prepared injestion? (When i say salt form, something that will disolve in water as pire capscaicin doesn't have a strong effect until it dissolves slowly).
@@nunyabisnass1141 I was told, alcohol latches onto the capsaicin even better. Taking a shot of tequila and swirling it around in your mouth after eating something spicy would flush it out. it WILL HURT a lot more than the spice, but it's for a shorter period, because the capsaicing is flushed away and doesn't dislodges from the receptors
@@iWhacko i have no idea, I know that it's more soluble in alcohol, but that's as far as my knowledge goes.
Did you take it before or after you ate the spicy food?
So... It prevents the burn going in... But that's only half the battle, sir.
Please elaborate in detail.
@@ryanjohnson4565🍑🔥🧯
I assume it would also affect nerves elsewhere if you swallowed it...
@@TheHuntermj I suppose that depends on the dosage, and how well it survives stomach acid and enzymes... The mouth is a far less harsh environment, chemically, than the rest of the digestive tract.
Just need to also make suppositories...
Actually, suppositories may be the superior product. Many times the pleasure in consumption was overshadowed by fear of the outcome.
That's an impressive multi-step synthesis for "amateur" chemistry!
It also serves as a neat demonstration of the "general synthesis loop" of organic chemistry: dissolve in solvent -> reaction -> workup -> distill off the solvent -> repeat
Well, amateur doesn’t really denote a lack of skill, but rather an independent chemist who works outside of a laboratory/company. It is, however, a very impressive reaction route.
@@chessgaming9942I think you've passed "amateur" in chemistry when you can look at a molecular chain and go "yeah, that'll explode if exposed to oxygen."
@@chessgaming9942Amateur= lover of the subject, ie motivated by love rather than money.
Theres another anti spicy compound.
Your capsazepine just blocks heat, but there's another one that functionally reverses the action of the trpv1 receptor, it's called
"Iodoresiniferatoxin".
If you consume it, it makes you feel cold.
Im guessing here i could be wrong but i believe menthol is different, and works on a cold sensing receptor, but iodoresiniferatoxin actually latches onto a generally heat sensing receptor with an action functionally the opposite of capsaicin.
I hope you enjoy reading about it!
You might be able to tell me, is iodoresiniferatoxin just copying menthol and they all just work on the same receptor, OR if it really is different and iodoresiniferatoxin is unique, pretty much in the same league as capsazepine with your one in this vid blocking the receptor, and iodoresiniferatoxin acting as an antagonist at the same receptor.
Great video btw, thanks!
IRTX and capsazepine are both antagonists of TRPV1 which means they block activation of the receptor. You might be talking about inverse agonism, but I don’t think IRTX is an inverse agonist of TRPV1 and I also don’t think inverse agonism if TRPV1 would give a cooling effect. Like you said, menthol acts via a different receptor to produce to cooling sensation.
What makes IRTX so interesting is that the non-halogenated RTX is an extremely potent agonist of TRPV1 (1000 times stronger than capsaicin), and adding that single iodine completely eliminates the molecule’s ability to activate the receptor
@@pente12 yeah it is interesting isn't it.
Just like in the most crude visual sense, estrogen and testosterone are vaguely similar looking molecules.
And you can take a very potent traditional opioid, oxymorphone, and just at a single allyl group to the nitrogen and suddenly you have a potent antagonist naloxone.
@thomasrussell4674 Yup, pharmacology is wicked cool. There are also opioid agonists and antagonists that covalently bind to opioid receptors, so they basically work for days until the receptors themselves are broken down. They’ve done a lot of pharmacological research into different opioidergic compounds, so that entire class of drugs is very intriguing to learn about.
@@Sniperboy5551 yes you're exactly right and the only covalent bonding example I know is oxymorphone itself.
I'd like to know if fentanyl or etorphine is capable of this additional form of receptor bonding. It's funny the way some old fashioned super strong opioids like levorphanol and oxycodone were actually quite long acting, while some modern high potency synthetics are ultra short acting.
Interestingly the covalent bonding rapidly accelerates the formation of tolerance, because nearly all opioids cause beta arrestin recruitment and lead to receptor internalisation, but normally this requires repeated and frequent dosing to trigger the cell/the body (which seeks homeostasis and reacts to continual over activation of an opioid receptor as unusual and something to be stopped) to effectively put the overstimulated receptor out of commission. Actually homeostasis works in at least 3 ways to counteract ongoing opioid intake, 1. Plasma antibodies to bind and inactivate an exogenous opioid before it gets to a receptor, 2. Internalisation 3. Eventual upregulation of substance P to maintain pain perception and gut motility and 4. Something to do with expectation, I can't remember the exact mechanism but there's a weird counterintuitive nocebo effect which can be blocked with proglumide, but only if the person was expecting a drug dose, basically the body tries to prepare itself if the person is in a state of anticipation and it secretes a type of neurokinin, but proglumide can block it.
Only 2 opioids I know don't cause beta arrestin recruitment. 1 is a strange, non-nitrogenous relative of salvinorin but it's not a mu agonist, I think it might be delta. 2 was a big pharma designer opioid called oliceridine which was designed not to, supposedly to be less addictive....But it didn't make it through multistage clinical trials.
There's another fascinating old drug
Sorry it was meant to say levorphanol and oxymorphone , but it all ends up the same because of cyp2d6
Man, you didnt really just eat a chemical in a long multi-step synthesis without even doing a column after the last step?!?😂😂
He isn't scared of the byproducts, he IS the byproduct.
It's a very small amount, but still... it's always a risk.
"it's more convenient to purify it later"
purification later: wash it with some water and into the mouth it go
The problem with home chemistry labs. No money for test equipment. Some things just take a University.
@@guygordon2780 apparently not this thing, though, since he got it done
I run Wittig reactions all the time and you don’t realize how much work you’ve just saved me! I swear I’ve looked everywhere to find validated methods for removal of PPh3O and I’ve never heard of this paper! The different salts for different solvent systems chart is so helpful!
I was surprised at an Indian restaurant where they served no alcohol but did have mango nectar as an aperitif/beverage. While eating some of the mixed crisps only one item in the mix was SPICY — I grabbed my mango nectar and took a drink — to my surprise, the heat was stopped. I’m thinking that papain might have been the actor in this pleasant discovery(?)
"And here we add the brother to a literal chemical warfare weapon, but don't worry this one smells like meat. Now its time to taste..."
I found a little on this chemical. While capsaicin stimulates the TRPV1 receptor responsible for sensing heat and pain, capsazepine blocks and hinders the function of this receptor. While it sounds all well and good that it can limit the pain from spicy foods and potentially offer some burn relief, strictly uncontrolled doses can be too effective by tricking the body into not realising its warm and cause your body temp to rise, possibly to dangerous levels.
So dont just go on thinking you found a cheat code foe next uears chili cookoff, or stock your first aid kit with it.
Yo, next, hot weight loss supplement!? Causing you to burn fat and overheat and hopefully not die???
@@jbdawinna9910 it could def have some useful medical applications assuming there's no other adverse reactions. But yeah, a controlled dose could in theory stimulate metabolism, though you might feel cold while it does so.
Cool
I can't remember the name but at university I got to try a compound (tasting awful) that inhibits the ability to taste sweetness. After trying it, I got as many sweets as possible. Cookies: dense concrete. Honey: Salty paste.
I tried to look it up and I can't find the name of the molecule. If you're up to another experiment, I would love to see you synthetize it and then get to try all sweets you got at hand. That was a funny experiment!
Sounds like some kind of gymnemic acid. It is derived from a plant known in Hindi as gurmar which means sugar destroyer.
Try chewing up ibuprofen pills. You'll get a similar effect
@@trippyvortexit's the opposite. people use it to lose weight, especially those with diabetes, as it makes it less desirable to eat the sweets.
beetus
@@trippyvortexyou either have pica or misread the comment 😅
0:12 Now if that wasn't funny enough, here are two words that'll make this even funnier: He's Dutch
I can’t begin to imagine the work you put in on this. Great job brother!
Hey it’s the other chemistry guy
Awesome step but step verbal explanation of each reaction and their intermediates, trying to get into curb and this really helps
My favourite part was watching 25 minutes of chemistry for the final result...
"It tastes a bit foul"
Well worth the watch, and well worth how ever many weeks of work you went through to make a foul chemical.
Non-chemists when he says he washed it with water: The f*ck you did.
Pack your column by running several column lengths of solvent prior to adding sand. Tighter packed columns give better separation as well!
After 16 million chemical steps and washings, and distillations etc etc etc, you are one ballzy dude to actually consume this end product! No way I would do this.
There's definitely not greater problems to find solutions for than this. Best and brightest.
Thank you very much! You are now my favorite chemistry YouTuber. I know it took you a week to make this.
Once I have eaten ginger caramel and then spicy chocolate. It was definitely less spicier than this chocolate alone, and I have tested this multiple times. Now I am wandering that maybe some molecule in ginger candy had similar effect.
Ginger contains gingerol, which is chemical that also activates trpv1 like how capsaicin does. I assume it would either activate the receptor weaker than capsaicin and compete with the capsaicin trying to bind with the receptor, or it might desensitise the receptor making the action of capsaicin weaker.
@@cafeinozooh interesting
How'd the Pd/C filtration go? I had to do that a lot after hydrogenations. one time I got absent minded and keep the vacuum running well past the absence of solvent, forgetting about the pyrophoric properties. Filter paper burst into flames lmao
Ah, we've all done stupid shit in a lab lol. I once rinsed out a Buchner funnel with water, forgetting that it had been used to filter out sodium hydride. The pyrotechnic display was not appreciated.
somebody let this man know you can just drink milk
Home chemistry labs, one of the only places where you make human drug testing, while also making a counter to police warfare.
My guy is crazy for tasting that end product without cleaning it up more. I could never
Ah yes this should be any the travel kit of anyone going to Thailand.
This could very well be a commercial product!
I'm sure it would have it's place, i.e. I love spicy food, but after some genetic-related surgeries, anything more than a pinch of pepper will destroy my guts and leave the exit hole like The Eye of Sauron.
I think this does the opposite: makes you not taste the spicyness, but it’d still destroy your guts and third eye
@@kaleoscreations The worst of both worlds.
Although not as serious as yours. My gut also can't tolerate too much capsaicin.
My tongue/mouth are enjoying capsaicin. The heavier the dose the better. But i will have to go to the toilet multiple times when i got too much of it
As an Indonesian who can't stand spicy foods, this would be my helper whenever I had to eat in public.
Indonesians are notorious for obsession with spicy foods, but not me. At least sour drinks help neutralize the pain a bit everytime.
I love this video! :D Personally I like the pain from eating spicy food. Y'know, the huge endorphin rush from the pain. lol
Eating my favourite combination of spicy compounds as I watch this.
Just feels proper.
Your channel page says that you're based in the Netherlands, so I assume English is not your native language. However, your grammar is much better than the grammar of most native speakers post-commentary videos I have seen. It's not a thing I like to complain about, but it is such a breath of fresh air not to hear people constantly going back and forth between past tense and present tense in the same sentence. So thank you for that, and well done.
Man this synthesis is long and tedious, but somehow its cool to experience it, that freaking decantation flask was the most common aside from ethyl acetate, both were probably the most used throught the video, congrats btw :D
Love the synthesis, but uhh...realtalk, if you want to resolve the burning when you eat something spicy, just eat the spicy thing and wash it down with a sip of whole milk. the milkfats almost immediately cancel the 'spicy'. The more you do that, the higher your tolerance to the heat gets, until you no longer need the milk at all.
This was my own youthful experience. Now, 4 decades later, about 6-18 hours after my spicy meal my family members stand in the hall outside my locked bathroom door asking why I keep yelling, “Come on ice cream!”
@@STEAMerBear I had that for a few months, but in time, both ends grew accustomed to spice and now it isn't even a thing. Just flavor really.
@@thricegreat7175 Very much the truth. Try it for yourself. throw some cayenne pepper powder on your tongue then take a swig of whole milk. Burn disappears. Repeat but with water, burn just gets worse.
Yeah, I'm a HEAVY milk drinker and can 100% confirm this is not true. If does help, like other fats, but nah, it's a far, far cry from "cancelling the spicy."
@@TravisTerrell I'm gonna listen to my own tastebuds over a rando on a youtube comment section 🤷 and my tastebuds confirm it to be right on the money.
Watching this as I drink spicy coffee, another gorgeous viewing experience!
Gotta love the probabilities of seeing this as I upload a video on capsaicin extraction 😅
Guys, I need advice.
I‘m in my 3rd year of Bachelor in Chemistry. I‘m currently struggling with my motivation, I‘m exhausted from all the stress, the hours of lab work, the days of writing reports, the hours of commuting etc. It feels like it caught all up to me, the lack of a balanced life in the past years. As an introvert it‘s really tiring. Grades were always good, did not struggle too much because of the grades, it‘s just the amount of work. And right now I don‘t have any motivation left, I honestly think chemistry sucks. I remember first year, full of motivation and then it slowly decreased.
Do you guys have any advice or similar stories?
"We saw NileRed have multiple failed attempts at the synthesis of benzaldehyde... likely due to some small mistakes that ended up ruining the whole experiment; which is quite typical for chemistry, and there is some art in finding and fixing them which often requires advanced knowledge of chemistry, ACQUIRED THROUGH MANY YEARS OF SUFFERING" - Chemiolis
Focus on how rewarding it will be to be able to do things the majority of humans can't even comprehend! And when you apply for a job, you'll get way more money if you search for "material manufacturing" instead of "chemistry or lab work" Like 100k+ manufacturing coatings for anything from lubricating gears to coating spaceships for NASA or SpaceX
Talk to the university’s welfare department. It’s what it’s there for and they may be able to help. They are used to burnout and should have procedures in place. Don’t be put off and nag them until you get a result.
Just at the end of my 1st semester, 2nd year of studying chemistry of materials and chemical engineering. Am not that far as you, obviously, but have little to no motivation to do anything. I think the only motivation I have is that I like learning chemistry (while also hating it, insane, right? xd). I just look at some people and want to do the work they do and to do that I need to finish at least the Bc. But I would literally trade the ability to make PCHEM disappear instead of world peace, ngl.
Life is a marathon, it will be OK bro 🫡
Everything worth doing is difficult. The coolest shit has tough moments, otherwise - everyone would be doing it.
If you are continuously over- burdened, burnout is imminent. Think how could you lessen the load - can you share the work differently? Move somewhere closer or change hours you have to be physically present at the lab so the commute is taking less time? Could you talk with department to swap some hours?
Perhaps the shorter days and lessening amount of daylight is affecting your mood. Think of how you can incorporate daylight exposure - a short,brisk walk a day helped my mood and energy levels tremendously. You can always use this time to listen to lectures or audio notes, but I think it's more valuable to unwind.
Have you thought about utilising some AI tools to lessen the workload? It's not a sin to use AI to redact lab notes, or rephrase papers or notes but I've heard it can cut out some of the tedious aspects of work.
Remember, the uni department is there for you - contact them if you are struggling. Asking for help is an important skill.
Remember that the boring parts are a part of a test and as all troubles - are temporary.
Don't make same mistake I did and run yourself so far into ground with pointless perfectionism that there's no way out but to give up.
When I did a Wittig reaction I was able to eliminate phosphine oxyde by column, it depends on the polarity.
Although my products were less polar than the oxyde
Seeing octopuslady’s platform get some love has made my day
It might be quicker to just learn to like spicy foods 😂
take part in hot ones and use this.
now to test it against pepperX and see which is stronger
Been wating for someone to try synthesizing this!
This guy actually went mad-scientist enough to actually try it. Cool
Huh, cool! I have often wondered if there was a compound that blocks Capsaicin receptors. Neat! Yeah, wet chem, and organic at that, is just a slog. That's why I went computational. XD Good video.
It would solve another problem as well if you were to use it as a rectal application. Protection for the day after.
ClO2 seems to completely neutralize capsaicin. I was getting to a point where I could no longer handle going up on the reapers added to tacos, until I accidentally discovered ClO2's neutralizing effect. It neutralizes the heat in the mouth but most importantly(for me) the stomach and beyond.
what an insane amount of steps! i guess it would be easier to just make a new variety of chili that doesn't produce capsicin...
Few comments: For the LiAL4 quench, a fieser style work up is much safter and uses readily available chemicals.
"In the Fieser work-up, following reduction with n grams of LAH, careful successive dropwise
addition of n mL of water, n mL of 15% NaOH solution, and 3n mL of water provides a
granular inorganic precipitate that is easy to rinse and filter. For moisture-sensitive
substrates, ethyl acetate can be added to consume any excess LAH and the reduction
product, ethanol, is unlikely to interfere with product isolation"
For the column i'd apply air pressure above your column if possible, it will help pack the column. Move 1-2 column volumes through and then load the column and it will be nice and packed.
Weird Explorer is like, I didn't bother with all those steps, I just got heatless peppers. 😂
11:48 poor stirbar holding on for dear life
In the reduction with pd/c why does the carbonyl not reduce as well? I assumed that pd/c reduction was powerful enough to do so
Turns out, regular hydrogenation with Pd/C is not effective for carbonyl compounds
@Chemiolis - 2023-12-15
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@cezarcatalin1406 - 2023-12-16
There is a much simpler chemical that selectively blocks TRPV1.
en.wikipedia.org/wiki/AMG-9810
You could make this really really easily.
It also probably tastes better since it has a more neutral pH and it doesn’t trigger noxious chemical receptors.
@highlander723 - 2023-12-21
tasting your own chemical product...... That's either really stupid or fucking savage!
@Zane.Wellnitz - 2023-12-31
Getting rid of the burn and the taste is no help. The spice is still going to do the damage, also you are still going to feel the burn on its way out😱💥💩
@YoKnow - 2024-01-13
I believe I am the man your looking to prove this. Perhaps I can prove you right!