4D creatures watching this are like "I don't get it, they're the same thing, you can flip it"

As a physicist, this stuff is fascinating to me because, yes! Parity symmetry is conserved in almost every interaction in the universe (the _only_ interaction we know of that breaks this rule is the weak force aka nuclear beta decay), so if you want a chiral object you need to _start_ with a chiral object but how do you even get that chiral object in the first place? We don't know! Some process spontaneously broke that symmetry while first building the structure of life and we have no clue what it was.

The cute dog is a vital collaborator in this video and he should be credited

5:56 "Enanti-" comes from the greek έναντι, which means opposite and the suffix "-mer" from μέρος (meros) which means part. So the one part of two opposites

10/10 vids its unfortunate u guys dont have more viewers, these vids genuinely make me interested in chemistry as someone who prefers physics

If I slap you with my left hand, it won't help with Parkinson's. If I slap you with my right hand, it won't help with Parkinson's either but it will hurt more. I'll take my chemistry degree now please. In all seriousness, great vid -- thanks for making the effort to make something so interesting so accessible. I genuinely didn't "get" chirality before.

Many minerals form crystal structures which are chiral, and these are able to selectively crystallize with one chirality (without twinning) given the right conditions. Though the formation of the initial seed crystal seems like it would still be a random chirality. For example, quartz crystals are chiral, as they contain helical arrangements of silicate units. (Not that chiral quartz crystals were involved in the origin of life) One theory for abiogenesis is that clay minerals could catalyze some reactions that build up sequences of amino acids or RNA. Even though the clays involved aren't chiral (usually, defects are a different story), they can show preferences for catalyzing the reaction between two molecules of the same chirality over opposite chiralities, and different reaction rates for the two enantiomers. It has something to do with the stability of the complex of the monomers with the clay catalyst, though I don't know the details of how it ends up being asymmetric.

Nucleic acids are chiral. When they first showed up, you would have had a racemic mixture dissolved in seawater, but the first molecule of DNA/RNA to be part of a living organism would have had to have one chirality or the other, which then would have helped set the chirality for everything else in biological systems.

Wonder about this. Talking to a drug researcher about how formulations of the same drug can be tolerated better/more effective, he made mention of enantiomers as well as additives that don't have to be disclosed as part of the formula (and all the minor modifications you can make to a molecule to qualify for new patents). It was all this subterfuge to differentiate from generics.

It's almost like biochemistry's version of all those physicists saying "hey! Where did all the antimatter go?"

Thank you for this very easy to understand explanation of a very complicated subject.

Conspiracy theorist stoner voice: “I see the chiral vectors, maaan!”

"skip ahead to the next section" uh... there are no chapter markings

I'm glad you brought up the point that regulatory groups consider different handed molecules to be distinct. "Celexa's patent expiring? Let's make Lexapro!"

This is one of the coolest/most informative videos Reactions has made in a while, good shit

Another interesting pair of enantiomers: Dextromethamphetamine (as well as a racemic mix) is meth. Levomethamphetamine is the decongestant in Vicks VapoInhaler.

This is great. I've been trying to explain to my mum for the past year why her Dexibuprofen is more expensive than regular Ibuprofen, and she has not understood it at all. Perhaps you can get the message through better than I could.

There's a Goosebumps book where a magic mirror swaps the viewer with their evil reflection. When I got older and learned about the chirality of glucose, I wonder how long the reflection doppelgänger could've survived on our side of the mirror.

There actually IS a way to recrystalize certain substances in order to get an enantiomeric excess! And that includes certain amino acids -- theorized as one of the mechanisms that created the initial enantiomeric excesses that led to the chiral biochemistry we know today. Certain chiral molecules can be made to crystalize in a homoselective way, i.e. when the lattice energy of a chiral crystal is much lower than that for a racemic one, a racemic solution will naturally form distinct segregated crystal grains for each enantiomer as it crystalizes. For some theoretical substance that forms especially large crystal grains in this way, it might be enough to then sort the grains mechanically in an optical sorter (under polarized light), and recycle the rejected chirality by re-dissolving, re-racemizing, and re-recrystalizing them with the next batch. For others, you might need to crush the crystalized mass and mechanically separate out just a few grains under a polarized microscope, then use those grains as seed crystals to lower the energy barrier to then get _only_ the matching enantiomer in a racemic solution to crystalize out onto their substrate. Perfect homoselective recrystalization usually only happens under specific conditions -- the concentration of the desired enantiomer is large enough, the non-desired small enough -- but with the right solvent mix, temperature, etc, you can often get that to at least include a few-percent margin around 50/50 racemic -- and then, by continuously re-racemizing an fractionally-depleted 49/51 solution back to 50/50 in a continuous-flow process, you can get near 100% conversion from an initial racemic crude mixture into the desired enantiomer. And, with a bit more complexity, this can also be made to work for materials that won't form exclusively homoselective crystals from any racemic solution, if you can still manage to get your seed crystals to grow at least a bit while other smaller crystals also form, so you can then separate these crystals from the bulk with a mesh sieve or optical sorter and use them again until they're large enough to be crush into more seed crystals.

thalidomide is a very interesting example of "which part of the racemic mixture is dangerous?"

I enjoy the visual presentation in this video. Pretty quick subscription gained :)

this yt channel is simply amazing

Super cool video, love ur energy. Will show to my kids

Just got this notification. I had my final chemistry exam earlier today. Great timing.

This was really fascinating, thanks George and team! I really liked showing the molecular models right next to each other. I usually see that illustrated when talking about chirality but showing it in 3D like that made it far easier to grasp.

This is good shit and no bullshit keep up the good work.

Yeah that was really interesting. Didn't know the history

In principle, you could do the same thing with circularly polarized UV light. As a bonus, you don't need chiral molecules to create circularly polarized light, you just need a linear polarizer and a quarter wave plate. (Those are optically anisotropic, but have no "handedness". The "handedness" comes from the relative orientation of the polarizer and the quarter wave plate.)

Actually chiral molecules often crystallize differently. First ever parting of two enantiomers was done by hand, sorting the crystals of the stuff into two piles.

Great video

I heard a story that sugar is chiral in it's calorie content, but not it's taste. D-Sugar being what nature makes and L-sugar being a 0 calorie sweetener that is physically and chemically the same.

Is this title a dated John Green reference or a timeless Hindu mythology reference?

Sooo... The answer is yes? It's turtles all the way down? Enantiomers come from enantiomers come from enantiomers ... Ad infinitum? But we know that can't be true because life has a beginning

there’s actually a paper on astronomy(?!?!) by a Furkan Ozturk that explores magnetite-induced chirality from the ocean floor that might’ve broken homochirality and basically created life, crazy stuff

Interesting! I guess that's why I take Levothyroxine, a synthetic form of a thyroid hormone I need to live, and not Dextrothyroxine, a cholesterol-lowering drug discontinued for causing heart problems.

It is useful to note that there are some stereospecific processes that can separate enantiomeric mixtures of specific compounds. Most famous of these is Tartaric acid, the compound responsible for the discovery of chirality in the first place. When crystallized, synthetic Tartaric acid (in the form of Sodium Ammonium Tartaric Acid) will appear in 2 different crystals that are mirror images of one another; these can be manually (though very laboriously) separated under a microscope. A particularly dedicated chemist could feasible use this to create a whole host of compounds of a specific chirality.

love your voice and the video.

Love the foray into biochemistry and chirality there. Could also be that we just landed on that chirality.

L-DOPA?! House MD reference.

Same for S-ALA (S-alpha-lipoic acid) and R-ALA (R-alpha-lipoic acid) S-ALA or just ALA sold for cheap but practically is useless while R-ALA is extremely expensive. Sometimes it sold in 50% - 50% S-ALA and R-ALA and it seems that not only S-ALA useless but it also inhibits R-ALA therapeutic effect.

Fun fact, it's not turtles all the way down! We have seen parity symmetry (chirality in chemistry) violations with reactions involving weak force interactions. The discovery of this was also followed by a Nobel prize!

Very informative, as always, George. But please slow down in future for the hearing, visually and comprehension impaired. Keep up the great work 👍.

In physics we have CP violation, also it is so hard to find supersymmetry particle, it seems universe are indeed asymmetrical

Nice

Regarding your hammer analogy: I'm not Jewish but I've *heard* there is some old story in the Jewish scriptures about how one of the first thnigs God gave to blacksmiths was the first pair of tongs. This is because tongs are so integral to blacksmithing that nobody could imagine making a pair without having a pair to use in the smithing process.

The thing I had been pronouncing wrong was racemic not enantiomer.

Great video. 1) what is your mirror set doing in your microwave? 2)they sell racimic vitamin E - dl-(alpha) tocopherol, and some amino acids. Why is this OK?

For synthesis of chiral molecules without chiral feedstock, could circularly polarized light be used to create a slight bias towards production of one enantiomer, and then the bias be amplified chemically?

Can you think of a organic molecule that is mostly an electron cloud, and not a defined shape, but once the O- or OH- comes along, it shapes itself to a defined rigid shapes, which defines the chiral image (which side of a mirror) that amino acids and proteins build onto it? The bottom of the turtle...

You know, there is a way for enantiomers to separate naturally. If a racemic mixture crystallizes, it will often produce separate crystals of the different enantiomers. This process does not require a turtle beneath it. If one of those crystals somehow gets separated and later redissolves... Hey presto, you have separated enantiomers under primordial conditions.

So there is a good chance that if we find Alien life they might use different mirrored molecules and we would not be able eat alien plants and alien meat, even though the alien life also was carbon based lifeforms.🤔 If it is "Turtles All the Way Down" but only mirrors would alien life still look like life as we know it, just mirrored, or would it "look" completely different?

6:35 you need to first react the racemic mixture with thionyl chloride and then bring in the alkoxide

Why are both the molecules at 0:55, the same? If you mirror image it and flip the bonds, they are the same isomer.

As i practicing organic chemist, i can tell you beyond a doubt that his fly is unzipped.

I don't see why "wasting" 2/3rds or even more is that big an issue for drugs. Probably 99% of the cost of drug production is the R&D (and 99% of the price is inflated, but that's beside the point). The point is that the actual mass production is relatively cheap compared to the price of the product. If production costs you 4 or even 10x as much, as long as there isn't a cheaper competing method that's still perfectly commercially viable. Besides, I'm sure someone somewhere will find some use for the byproducts. It would be a problem if they were effectively toxic waste that had to be stored indefinitely, but worst-case they can be broken down into more basic components (for example; burned)

Wow, when I started watching this video, I had no idea how amazing it is gonna be! Currently reading "How life works" by Philip Ball. He advocates strongly against information-theory view of the life. I like his argument, but at the same time, the idea that it is all an unbroken chain of chemical reactions dating back billions of years - is in some weird way elegant and enticing, almost purporseful.

Chirality is not only at the molecular level. The right hand rule demonstrates that this is a feature of this SIDE of the temporal manifold. This is why there are no atoms made of antiprotons and positrons on this SIDE of the temporal manifold. Time is a compactified dimension one single Planck second in size. This is why there are limits of lambda and event horizon. Limit theorem. This is why there is conservation. We are closed in the present moment. This evolves a hyperplane of the present using Kuramoto synchrony. Matter on one side and antimatter on the other.

I wish you'd call out the subgroup that aren't CNOH. Ph? MeO? Ac? Good ol' protective actinide groups, is best way.

So a random fluctuation in the original racemic mixture of amino acids (?) caused a slight excess of one enantiomer, which grew exponentially by some kind of auto-catalysis and totally wiped out the other (family of) enantiomers. Do I understand this correctly?

The question of interest to me is why did life on Earth end up using levo amino acids instead of dextro? Was it equally probable, or is there some faint quantum effect that gently nudges the probability towards R(-) or what we call levo or left handed enantiomers?

What about Tartaric acid? It naturally occurs as a racemate but when it crystallizes the enantiomers separate and form unique crystal shapes that are enantiopure and can be visually separated. This is how Louis Pasteur discovered chirality.

The answer must be polarised light right?

Is there a meaningful difference between S/R and L/D? How do you know when to use which?

Shouldn't the next turtle be below the last one?

Wonderful! Now explain what it is that we don't understand about those first "turtles". Thanks for another great lesson.

Hi i understand amphetamine's dextro and levo thing but methylphenidate confusing me

The first hammer wasn’t made, it was found

Not sure if they're mirror images, the blue thing has a completely different bond angle.

0:45 These molecules are not mirror images.

Can someone explain to me what turtles specifically have to do with any of this?

Maybe there actually wasn't a first single enantiomer but there was a racemic mixture of early life (likely mutually incompatible) until the group of life with a particular enantiomer wiped out the competition?

Should be called "The dope on the DOPAs"

The bottom turtle is autocatalyzing.

Hammers Stones 🪨 And Magnetism 🧲 Here are the answers to the questions in the video

im pretty sure i don't understand the turtle analogy

To answer your hammer question: A rock.

Well, what's Dopabean's story then?

I came across this video recently ehich claimed the mustery of natures enantioselectivity is solved. Basically they say that it was due to the iron sand/ particles present in the ocean and rivers durign early formation of earth which caused the enantioselectivity. There was also a paper published but i am not sure how true it is though.

I just don't understand why it was ever allowed for racemic mixtures to be considered the same drug. What was the reasoning for this?

So basically we're trying to figure out how to do what nature solved millions of years ago

Neither molecule was pointing toward me. They were pointing toward the bottom and top of my screen... Instructions unclear, synthesized racemic meth

Leopold Horner never got the Nobel Price...

the turtles wanted you to know - it's turtles all the way up...

- How was the first hammer made? A ROCK. How do you make an enantiomer if you need an enantiomer to make it? You use one that's easy to make or one that's already readily-available. - I'm surprised you didn't mention thalidomide; that was a hard-learned lesson on enantiomers, more notorious than D-DOPA.

OMG did the L-DOPA just prove God. Just kidding but also not kidding ;)

My guess is the weak force is the driving force of chirality in our nature, just like how the weak force breaks the parity symmetry.

What a poor explanation

I pronounce the 't' in enantiomer same as the 't' in lotion. Sh

So annoying