Click Chemistry in Action: The Chemistry Behind the 2022 Nobel Prize

[@AkashS97]

I am a PhD student and doing Anti cancer drug discovery and targeted drug delivery. We frequently use click chemistry to couple linker-drug with antibody. I think Click chemistry has ease the process of drug discovery by more than 50%. Super easy and quick to make a triazole ring.

[@inspiringmuslim]

Wow...that's interesting. U r doing in India or abroad??

[@AkashS97]

@@inspiringmuslim At an Israeli university

[@inspiringmuslim]

@@AkashS97 Wow..that's amazing. I m currently an 11th grader in India interested in cancer research I m a pcmb student preparing for neet...can u just guide me a bit u know like how it all goes...like I m solely interested in research and I m interested in applying to IISC or universities abroad...plz guide me a bit brother

[@inspiringmuslim]

@@AkashS97 Thank you so much for your valuable suggestion and yeah kvpy has been abolished from this year its through neet rank under 5000 one can get into IISC. Best of luck for ur future endeavors 👍🏻

[@markhays170]

I was shadowing in a lab that does anti cancer drug design with click chemistry too recently! This lab was doing it by releasing carbon monoxide at target cells, do you also work with CO-releasing molecules/drugs or is it something else?

[@kaezaklimber3391]

DUUUDE, replicating nobel chemistry is THE GOATEST idea. Beautiful !!!

[@Jeremy.Bearemy]

Goatest??? 🤮

[@selfactualizer2099]

you do realize anyone can repeat scientific projects right? it was published my guy.

[@stefangadshijew1682]

Click chemistry being convenient to replicate is kind of the point, isn't it? :D

[@SodiumInteresting]

@@Jeremy.Bearemy greatest of all timeest I guess 🤷

[@dipankarbanerjee1130]

Nowadays, Dictionary is frequently getting new costumes

[@That_Chemist]

6:36 this is how you know you are a real chemist now - this is exactly the type of trick you would see from a clever peer in a research lab

[@user-mp4bc9qp2x]

triturating? we teach this method of purification to undergrads. you must be lucky if youre making molecules that are soluble in most things.

[@Acute.]

My two favorite KZbin chemists ❤

[@stefangadshijew1682]

@@user-mp4bc9qp2x I think the point is that he made an observation and used it to choose a purification method that he knew would work and would be convenient. If I was his peer, I would beg him to shake his sep funnel more vigorously and use a slightly bigger stir bar, but hey, if it works, it works. :D

[@HaIsKuL]

Which part? Removing the impurity with 5% ethyl acetate and hexate or the vacuum filtration?

[@mnxs]

​@@HaIsKuLthe former

[@patricksweetman3285]

Click chemistry can run in living cells. It well deserves it's Nobel Prize.

[@myronwilde491]

As a practicing chemist I have 2 tips that will save you much pain and time. 1) Brine washes. Any time you do an organic/aqueous extraction and your product is in the organic layer, wash it with brine before any drying step. I've made very polar substances that will go into water, but they don't go into brine. So it doesn't hurt yield (unless you spill) and it seriously cuts down the amount of drying reagent and time required to achieve a dry organic layer. 2) Buy an aquarium air pump. Spending a day doing column chromatography for such simple reactions is just pain. You can speed most columns up (not advisable with DCM/MeOH, but great for all other solvent systems) by doing it under pressure. Even a cheap fish pump is designed to maintain a steady, sometimes variable, low pressure without over-pressurizing. It will accelerate chromatography substantially for not many dollars.

[@brannigandupreez2083]

Flash column chromatography is the way to go, man. Ever heard of countercurrent chromatography?

[@bromisovalum8417]

Definitely, a final brine wash also pre-dries your organic layer to a certain degree. Also helps if emulsion formation at the separation layer is an issue. Regarding flash chromatography, I've seen it done in those big kitchen syringes.

[@humr2346]

one advise for column chromatography: Use sorption of crude product on small amount (5x mass of crude product) on silica gel. Disolve the product, add silica and evaporate. Than just pour it on the top of silica slope in column. This way you avoid diffusion at the begining of chromatography and problems like you had.

[@brannigandupreez2083]

This seems a good point.

[@jakob_212]

Celite as a carrier also works very well, gets nice and dry so is easy to get into the coloum

[@visiblur]

One of the recipients was my Ochem professor. He was so excited about this, even before winning. The party we threw for him at UCPH was amazing. Great professor

[@slimp4644]

Nice video and showcase of click chemistry! When I run a column, I always load my sample with the tiniest amount of DCM or Acetone to avoid having it crash out of the solution, otherwise nice job!

[@andrewg.carvill4596]

5:30 I was a working chemist 30 years ago, before changing career completely (Catholic parish priest!). Happening on your expertly made video brought back to me the fascination of working the "classical" methods of synthesis and purification, and the sense of achievement experienced in upping yields. I'm wondering whether the low solubility of the product could be used to advantage in looking for recrystallization procedures from solvent or solvent mixtures in which the product is much less soluble than the impurities. Might this be worth a try (in place of the column) at this stage ?

[@habboUdviseren]

Watch the discussion between Mohammed Hijab and Jordan Peterson, then the discussion with Jordan and Hamza Yusuf

[@stefangadshijew1682]

I think it definitely should be possible to find a good crystallization strategy, the products and educts are different enough. It actually pains me a bit to see chromatography being a used in a process that is advertised as being easy and convenient. No criticism to the maker of the video intended, just the principal of the thing. I'm working in organic process development, using chromatography automatically kills a process in our price range. I'd rather use harsh conditions and poor yield, but be able to separate the product on scale. Finding a good crystallization strategy is so satisfying, recently brought a process up from 50 % yield to 65 % yield, purity after synthesis of 99,98 % instead of 98,00 %, just by slight adjustment to the crystallization conditions. It takes a lot of work to develop in the lab, but the pay off is huge.

[@alexreidzero1357]

@@habboUdviseren ?

[@chandrakantasarkar7556]

Are you really a chemist.can u answer one of my questions do we get to study mechanisms of inorganic reactions in higher studies chemistry.i was not really intrested in chemistry till 10th standard but when mechanisms of organic reaction came in class 11th and 12th it fascinates me.but when I start to read inorganic I feel the same when I was in class 10th.so I was asking do wet get to study mechanisms of inorganic reactions in higher studies???? Pls answer🙏🙏🙏🙏

[@stefangadshijew1682]

@@chandrakantasarkar7556 Hey there :) Mechanisms make sense if you look at the movement of charge and atom groups in molecules, so you will find them a lot in organic and metal-organic chemistry. Inorganic chemistry is often better described by other models, but those get just as interesting. Inorganic chemistry gets more interesting in university, I don't know how far you will go with that in High School. Hope you have fun in class. :)

[@angelarredondo1016]

I use click chemistry to couple PEG to MOF drug carriers, where the azide of a organic modulator bound to the MOF reacts with a terminal alkyne on PEG. Really cool and easy stuff that you can monitor with FT-IR

[@swapnilpradhan9543]

This is by far the best video I ever watched on KZbin, thank you very much for your explanation. Best explanation of organic chemistry work.

[@fcsolis]

Great! I remember all the endless column chromatography I had to perform in graduate school. So much work for so little yield. Thanks.

[@IronTeddyBear]

You and me both.

[@kaischapen3552]

Yaeh, me too. Especially nasty during summertime, when the heat and the vapour really make you dizzy :-)

[@paulmatamane3397]

Absolutely remarkable, Nobel prize well deserved on this one

[@I_XuMuK_I]

If you have an access to enough tlc plates you can try finding your own eluent for the column using other solvents. Maybe using acetone seeing it's good at dissolving the product.

[@IanHaltom]

Yep. Have always done preliminary tlc before running any column. Saves time, prevents wasting solvent, and of course you then know what you're looking for when you check all of your eluted fractions on tlc (using the same solvent system)

[@kel000001]

Acetone is definitely not what you should use, it will dissolve the silica and come out with your product. Dry loading is what you should do.

[@quantrox8191]

Don't even need to have a lot of plates. Cut the plate very small, use a very fine spotter and if done with care will be enough to see if the separation is enough or not for given solvent polarity. And definitely, doing tlc before the column is a really good idea if there is no information which eluent should be used

[@I_XuMuK_I]

@@kel000001 If using a lot of acetone - sure. But if it is used as a component in not so polar mixture everything should be fine. It is in the same selectivity class as ethyl acetate so it should give somewhat similar results.

[@nitrgnlab9400]

​@@kel000001 still it is easier to separate the product from silica than running liters of eluent. Dry loading is not the best choice if the product and the impurities have similar rf

[@bencetoth9491]

Advice for column chromatography: Layer number 1: cotton wool Layer number 2: sea sand for flat surface Layer number 3: slurry of silica gel Layer number 4: pack the silica gel Layer number 5: sea sand (flat surface is required for good separation) Layer number 6: add the dilluted crude product with glass pasteur pipette (easy to clean) and use circular motion with your hands to evenly distribute the diluted crude product (gently add the diluted crude product to do not mess up the evenly distributed sea sand surface) Layer number 6 alternative: you can use celite as the carrier (flat surface is required for good separation) Layer number 7: another sea sand layer (flat surface is required for good separation) Gently add the eluent mixture to the column and have fun.

[@giovannipelissero1886]

Morten Meldal is my MSc professor, great teacher and very very knowledgeable in synthesis. He came up with the "hand rule" that takes advantage of the fact that our hands are chiral, let me tell you it's sooo useful! You can go from a very complex conformation and spatial disposition of the reagents and rewrite the structure while keeping all the chiral centers correct. It saves so much time and mental energy. The hand rule alone could be enough for a nobel prize 😂

[@brannigandupreez2083]

This is one of the best videos of practical organic chemistry I probably ever saw. Click chemistry is cool.

[@gradboften]

in circumstances where your crude material does not completely dissolve in your eluant, it often helps to load your material onto celite or silica, by taking a solution of your crude (in e.g. acetone), forming a suspension with the celite powder, and then removing all solvent under vacuum (with or without heating). You can then add the resulting free-flowing powdered solid directly atop the bed of sand at the top of your column

[@lablulz2483]

Cool vid! My understanding is that part of click chemistry's appeal, is that it tends to avoid the more fidgetty workup procedures like chromatography. Maybe simple recrystallization of the reaction extract residue would work?

[@Chemiolis]

I have seen an easier purification method when they simply used an expensive Cu(I) catalyst, but for what I did I only saw them doing column so I just followed that. Maybe there is a better way to do this, but I don’t have the time to experiment on it.

[@jimparsons6803]

Nifty and thanks. Heard about this approach. As a chemist that has dabbled in polymers, this sounds sort of familiar, as the stated objective often is to make molecules (usually up to about 5k or so monomers) of repeating monomers. Well done, altogether.

[@swastikbiswas8293]

I loved the trick of washing the isolated compound laden with coloured impurities with insoluble solvents... had it been me I would have did another column chromatography again!

[@carelessanonymous6570]

I got to meet Dr. Sharpless today. He gave a lecture at my university talking about his work developing treatments for tuberculosis using Sulfur flouride exchange.

[@666ksmith2]

Love your channel, keep up the great work 👍🏼 👏

[@kkgt6591]

There are so many chemicals and steps involved. How were these chemicals produced before the click reaction was invented? Also there was so much heating involved and not at room temperature.

[@emma_rose1075]

3:36 i would have loved to see a bit of a dive into the mechanism but maybe thats just me :P (maybe its more obvious to practicing chemists), but i just wasnt sure which molecule attacks because they both have strong electron density... although on second thought the azide probably stabilizes its charge with the opposite charge right next to it using resonance, making it less likely to attack... either way, its an awesome reaction and i can easily see its usefulness (especially from all the comments from other chemists) :) great vid!

[@nomcopterlabs]

Super cool reproduction! What do you use to protect your vacuum pump from the solvent vapors? Or is it a water aspirator?

[@Chemiolis]

My regular pump is a diaphragm pump, teflon internals, so it can handle pretty much anything going through it. For high vacuum applications I use a rotary vane pump, but then I use a cold trap.

[@nitrgnlab9400]

@@Chemiolis don't be so sure, even teflon coated diaphragms swell and die after 2-3 years. Personal experience

[@bromisovalum8417]

For such work I've used a refrigerator compressor as cheap vacuum source. They're very cheap, free even (dumpster diving, recycling plants...), they pull a similar vacuum to a water aspirator (50-60 mmHg, I've seen some as low as 30 mmHg) although the flow rate isn't stellar (just takes some more time to reach peak vacuum). And they can take a surprising amount of abuse. Solvent vapors, acid fumes... sometimes for years. When it dies, you can always get another one. Oh and you can even run lengthy vacuum distillations with it, just put a fan on the pump for cooling and it will run for 12+ hours.

[@IronTeddyBear]

This is a really cool reaction, and I appreciate all the detail you took creating this video. I wonder how easy it is to release the tosyl group to add other substituents to the triazole ring. Also, this looks like there is a bit of Diels-Alder effect causing this "snapping into place" that's aiding the facility of this reaction. Pure chemistry doesn't get a lot of love these days from the Nobel committee.

[@spiderdude2099]

I use this technique in my lab all the time. We've engineering a protein with a non canonical amino acid with an azide allowing it to be coupled to an alkyne linker

[@joshg.6536]

Nice Video Mate and very interesting!

[@daikucoffee5316]

RIP vacuum pump

[@ChemistryProfessor_unStoned]

Great video! Very informative 👏

[@maskedmarvyl4774]

The number of steps involved in this is dizzying. Where they all Really necessary to obtain this product? Given the length of time involved, and the number of chemical processes to obtain this final product, I'm missing the advantage that "click" chemistry is supposed to provide.

[@asensniper]

You should try loading your crude with a solvent you know is going to dissolve your crude (i.e. DCM/Et2O) with a minimal amount. Then flush your column with 100% hexanes (DCM/Et2O) gets taken away, only until then you can start flashing with your desired eluent

[@ejkozan]

i think here better way would be dissolving mix in DCM and evaporating it with siica gel to coat it, then pouring dry silica onto column and eluting everything

[@asensniper]

@@ejkozan that is a great alternative, however dry loading isnt alwais ideal since some product will.alwais adsorb permanently on silica and never elute. I alwais found my yields to be lower when dryloading vs when I dont, but it has its applications!

[@EthnobotanikFAQ]

@@asensniper that’s why you should use Celite

[@ejkozan]

I agree, it depends on separation. As for celite, i found it can decrease flow a lot. I prefer to use coarsest silica i can get, for graffiti separation or even bigger particle one

[@nervonabliss]

@@ejkozan Have you ever tried a 80/20 mix of celite to silica to improve flow?

[@胡若昉]

That's pretty cool. Could I transmit this video to a Chinese video website (bilibili) with a translation attached?

[@guisimoso5]

Awesome as always!!!!!!

[@emlakes]

Barry Sharpless has already won the Nobel Prize for the same subject, I believe. Can anyone explain the differences between the two prizes?

[@xanshriekal]

The workup and purifications required for any sort of synthetic chemistry are why I'm a computational chemist.

[@bromisovalum8417]

practice makes perfect

[@microwave1119]

I think on a technicality this is a “copper-catalysed azine-alkyne coupling” rather than a click?

[@frankmercer7009]

Very good video. I did my graduate work on organic azide chemistry. I liked you video presentation very much.

[@ph1ss1ks93]

Hearing the words column chromatography gives me PTSD from my silica layer cracking 5 TIMES IN A ROW. But as a Chem major I love watching these videos

[@stevestarcke]

Great video. I love chemistry but if this is "click" i would hate to perform "normal"

[@jacob9673]

Wait why? This ran pretty smoothly. (outside of the slow column)

[@FR-kb1fc]

thank you for this video. It is great. My intuition would have led me to fear that there would be an explosion along the way to form N2, especially in (or near) the solid phase. Is that an irrational fear?

[@brettmoore3194]

Could you show a non enzematic way to make 1 andostenediol or 2 andostendiol? Im really looming for the process of changing its locality🎉

[@defaultname992]

I was hoping you would just mix two things and get the new product. I think there is another Nobel prize waiting for someone who would actually make this process much simpler.

[@RuthMorsosa]

The click reaction starts at 2:44 and ends at 3:46, before he was making the reactants and after he was purifying the product

[@LiborTinka]

Could this be used in the preparation of BOP or PyBOP (peptide coupling) reagent?

[@That_Chemist]

the synthesis of BOP/PyBOP/HATU is a really good idea for a video

[@littlehills]

well would be nice if u explained how it would be used and the imprecations of it

[@IronTeddyBear]

Lots of pharmaceuticals have triazole rings.

[@Tarquin2718]

But what can you use the created compound for? And is this the best way to make it?

[@ArjanD78]

Mooi man! Dit ga ik zeker in mijn les in 6V gebruiken. Top!

[@dopa_explainz0080]

i want to make Methamphetamine through click chemistry, please help me synthesize it!

[@crabcrab2024]

Yeah! I can already see that in the news: “DEA found out that Nobel prize winning chemistry CAN be used to synthesize METH!!! The agency calls for immediate BAN of click chemistry in ALL of the US!”

[@a3mia3mi82]

I was going through some comments and understand one thing that lot of non chemical or less chemical background folks are here watching video. For non chemists, the name is actually missing that they thought click chemistry is like a Lego pieces snapped together, they raised concern about why to many chemicals and heating involved etc. if you know the actual process chemistry, then we understand the simplicity of this click chemistry and again in my opinion, it can be named differently.

[@wissen5410]

Sorry but my Prof says ist was Noting new and from what i read it was the active Youse in biological Sythems what was Winning the Price Not the Reaktion ist Self

[@Chemiolis]

Both the inventors of the reaction and the inventor of the modification for biological systems won the prize. It has been in use for many years now, so yes it is not new, but that is not a requirement for the prize.

[@richardwiersma]

Deutsch bitte

[@anonymizationoverload9831]

@@paradiseexpress3639 "Sorry but my Prof says it was nothing new and from what I read it was the active use in biological systems that was winning the prize not the reaction itself" So basically, from what OP read, the thing that got the prize was the use in biological systems and not the reaction itself + the prof said it wasn't a new reaction, even though as Chemiolis said both the original reaction inventors AND the one that discovered the bio-applicable modification got it :)

[@nitrgnlab9400]

@@Chemiolis except Valery Fokin who actually developed this reaction

[@bikrampaul6650]

How much amount (equivalent) of catalyst you have used?

[@elvedin65]

How to you determine the amount of silica gel you need for the column?

[@Chemiolis]

Depending on how good the separation is on TLC, you multiply the amount of g of product you want to purify by 20 for very easy separation. If the separation is very difficult then 100x. Anything else somewhere inbetween.

[@VideoMakesMeHappy]

Subscribed!

[@arsenehanger7456]

I thought you have to use a reagent like TBTA to protect the Cu(I) catalyst for a complete reaction. Otherwise it would disproportionate to Cu(0) and Cu(II) which means your catalyst is not active anymore. Thumbs up if you agree😅

[@orca_ah]

Hey, but we still need so many solvents, etc. I think then it's not a very green reaction? Or there was a reaction before for this product which was not green at all even worse than this one

[@AndreZoiaum]

we did that reaction to produce a 5 membered ring. I remember it was a slave drive and it made me change to plasma chemistry lol

[@C134B]

how about the tetrazole producing ugi 4CR?

[@benzen3179]

what kind of vacuum pump do you have? I mean the model

[@CartwAalbiel]

I really regret not choosing chemistry in university, would have really liked to do this as a career. Anyway, fun to watch!

[@brannigandupreez2083]

Can still be done. You're never too old to do so.

[@CartwAalbiel]

@@brannigandupreez2083 Thank you for your kind comment. I know you're right on principle, but things are a lot harder and more complicated when you're older. Still, maybe I can keep that in mind as a goal...

[@selfactualizer2099]

everyone has more than one thing they want to do. society just doesnt really let us since the world is so competitive.

[@frysebox1]

It's all fun and games until things like 5:10 happen and you spend hours upon hours in the lab trying to unfuck the situation, with 10% yield and a dubious NMR spectra to show for all of it

[@chrisX1722]

Did I miss the explanation of the mechanism?

[@mani-rn1xh]

What is low radiation EMT magnetic oil?

[@e_gorrr]

Cool video!) Remeber how I made some tetrazoles from sodium azide and nitrilles)

[@MCDainter]

Nice video ❤️

[@ahmedaldoori6221]

Dude you are amazing

[@ugarit5]

I think butanone would be a better solvent,being more stable- amazing vid btw

[@ibrahim-sj2cr]

would it be a problem that butanone doesnt mix as well (obviously) or high BP (80 degrees) ?

[@robina6645]

Why is acetone added to the reaction mixture? Acetone is know for reacting with itself and forming tautomers right?

[@Chemiolis]

The aqueous acetone is just the solvent

[@sudiXP]

Well done.

[@cspicer77]

Do you do this in a home lab?

[@riturajsinghpanwar6470]

Thanks

[@mmmhorsesteaks]

One of the postdocs during my master's once ran a click reaction in Jack Daniels on a bet. Got something like 99% yield ^^ Didn't drink the JD after tho.

[@nitrgnlab9400]

I remember Phil Baran showed one of his reactions which proceeded smoothly in different types of beverage (including JD) at one of his conference presentations

[@johnl7524]

Why u didn't use rotavaper?

[@Chemiolis]

If I had one :)

[@RoastCDuck]

Click chem sounds like combining 2 lego pieces without glue. Sadly it dosn't work that way.

[@felixbums6240]

Man thats why i hate column chromatography

[@tongbunsing]

What’s the advantage of this molecule?

[@kkkkk3212]

Perfect opponent of nile red😂💕💕

[@akramraza8361]

Why dont you use cu+1 directly, ?

[@Chemiolis]

Many Cu(I) salts are air sensitive, there are some organic ones that are very good for this but they are very expensive.

[@californium-2526]

Nobel Prize chemistry. I like this.

[@Simonjose7258]

Can you make LSD like that?

[@experimental_chemistry]

7:28 "still very simple"... 🤭

[@thedude7319]

Jonge, wat een efficiëntie

[@kenopyowo]

Quantum Entanglement in Action: The Physics Behind the 2022 Nobel Prize

[@yourlocalscribe948]

Instructions unclear ended up making crack in my basement.

[@intheshell35ify]

Voodoo and witchcraft (I'll stick to v=i*r and a oscope) but very cool tools.

[@loganmichaels6853]

dawg what just happened

[@scienceandmind3065]

The idea is worth the Nobel price but the way it "clicks" is far inferior to biochemical bond breaking/formation.

[@ryhol5417]

I effing love this.l concept. First time

[@davidvaca6593]

Where is that accent from?

[@hnz4339]

Is this organic chemistry?

[@fmdj]

I wish I could understand the significance of this but... not there yet :) Cool video though, I presume :)

[@anujith9697]

Man that was fun

[@robinhidam2868]

Molecular formula of chocolate?

[@OmerFlame]

This dude has sodium azide?! Damn, you're scaring me more than Nigel

[@crabcrab2024]

NaN3 is actually nothing special, man. You should not be scared at all.

[@Iwill_beback]

Jee students: ye azide wagera se to mai warm up me deal karta hu

[@hinz1]

Doesn't deserve nobel price, if it requires column chromatography ;-D

[@DoINeedAHandle]

4:15 looks so much like projectile vomiting

[@Friholio]

Gotta get this guy some air pressure for his columns!

[@NoahGooder]

i feel like i am watching a nilered video

[@jordan4786]

no... but you did a good 42 brother

[@UnitSe7en]

Simple!