It takes a lot of sense, it would get around a lot of the current antibiotic resistant mutations. I guess we started with arsenic, now we’re going back!
@@thricegreat7175 Thiomersal was already used for a long time and is still used. Furthermore, it is actually safe. Next would be a Lead-based medication - now that would be amazing if it wasn’t dangerous.
When I was taught how to do column chromatography, the offical method for packing and "tapping" the column was actually to attach an overhead stirrer next to it, put a piece of soft bent rubber hose onto it and then turn it on so it would smack the column constantly and pack it more efficiently. After initially thinking that the column was gonna break, it was kinda hilarious to me.
@@jogandspBecause there's an optimum rate of elution. Too fast and the mobile and stationary phase can't equilibriate, too slow and diffusion broadens the bands.
Arsenic based compounds were one of the first treatments for syphilis and have seen widespread use until other classes of antibiotics (sulfa drugs and penicillin) were discovered. Early antibiotics were kinda like how small molecule chemotherapy drugs against cancer are nowadays: Significantly toxic to the patient, but not dying due to the underlying disease is still better than the side effects.
Arsenic based compounds are still being used for treating African sleeping sickness, they're using melarsoprol as a second line anti protozoan drug effective against the second stage of Trypanosoma brucei rhodesiense....
Or, coming from a different field, this time psychiatry: First and, to a large extent, second generation anti-psychotics. Actively harms the patient due to neurotoxicity mediated through numerous pathways, inducing a reduction of white matter and general brain volume. It is 100% clear that dopamine, or more specifically, the D2 sub-type receptor, or rather the affinity of a small molecule acting as an antagonist is directly correlated to antipsychotic potency. But then here we have the atypical antipsychotic Clozapine, which doesn't really have much affinity to D2 receptors compared to others, especially first generation phenothiazines come to mind (some if not more than half of them have a comperatively clean binding profile) basically in most cases just targeting the D subtypes along with mAChRs and the Histamine 1 receptor. This is a field I actively do lab work in, and, compared to antibiotics and the inevitable multi-drug resistance if we don't stop prescribing them for every tiny fever or cold is surely threatening, but trust me, neurobiology and psychiatry is a whole different beast.
@@williamkane I was misdiagnosed as Bipolar after a concussion, put on Aripiprazole and Lurasidone, and have had Cariprazine and Olanzapine, Haldol, etc in hospital. These drugs and their after-effects, which lasted for a long time, and the withdrawals from them were legitimately worse than IV methamphetamine withdrawal. Also, they made me _REALLY_ crave anything that made me feel better and I started to do drugs way more than I had done ever before while on them, which resulted in someone getting me into that crap. The restlessness alone was so horrific, and I doubt ADHD and whatever that means for my brain made it better when combined with these. I'd get up, walk around for 5 minutes, then have to sit down, and repeat it 5 minutes later. Otherwise the most horrific anxiety would build up until it felt like I wanted to die. I think getting those antipsychotics is what started my downward spiral overall.
@@samyakjain5377 now is a good time as any to learn to google stuff before you say dumb stuff online. In other words, they're an infectious diseases medical professional.
As a microbiologist, I wet my pants. Don't give a chemist an inoculation loop. I have never seen anyone attempt to spread a bacterial dilution for an antibiogram using an inoculating loop on Mueller-Hinton agar. 🤣🤣🤣 For this you use a Drigalski spatula and you actually isolate a germ before doing an antibiogram. This antibiotic can be very effective on one germ and have no effect at all on another germ. However, if I have a mixture of different germs, I can't judge whether it is effective or not. But this isn't actually a channel for biologists I know. I also wanted to teach some useful knowledge to chemists. No offense to all chemists. 😜😘
Woah this is siiick organic chemistry right there! Btw, I don't think the SO2 reduction of the organoarsenate proceeds via nucleophilic attack of the sulfur on the As=O. This is not a true double bond but rather an ylid, much like P(V) oxides, because there is very poor overlap between the 2p orbitals of Oxygen and the 4d orbitals of Arsenic. Therefore, you would have something that looks more like a positively charged Arsenic and a negatively charged Oxygen, for which the electrophilic position would be As rather than O. The same is true for the SO2, but the orbital overlap is better between S & O. Plus, the Sulfur is more electronegative than As and is therefore more electrophilic. I suspect the As-O(-) attacks at Sulfur, and then the sulfur's electrons can form another S=O bond and push back the electrons of the As-O bond into the arsenic center.
Just don't maintain your erection for 4 hours or longer. If you do, your N2O-producing endothelium will die of hypoxia and your lil' guy will never be the same again. 🥺
Sadly, those surges of joy are often short-lived as those antibiotics frequently are found to be unsafe and have to be withdrawn. See, e.g., gatifloxacin, telithromycin, and others.
You almost got it right at the end. What you should have done. 1. Prepare 2 plates, on one plate you spread out the antibiotic. 2. Make up enough solution of 50/50 water + spit to do both plates at the same time. Treat both plates with the solution the same way.. 3. Incubate as before..
“It’s about the journey, not the destination” - I was lol’ing and cheering this assertion with the unceremonious end to the anti-spicy video. And then to hear it stated her was 🎉💪🤘
Very cool and nicely edited video as always! One question tho: have you considered testing the antimicrobial properties of the reactants? Because if for ex. As2O3 was also antimicrobial, your seemingly positive result would be easily disproven. But I know this vid is about synthesis and not so much about the result.
Would you mind linking the publications you're working from in the future? Or even titles and authors in the video? I'd like to see the purification method with a strange column they talk about.
This was certainly quite an interesting video to watch, reading up on these amonia based antibiotics that are currently in development was also quite an interesting read and hives some hope for antibiotics. based on your accent I am wondering if you are dutch?
Very cool synthesis, and very exciting that we've finally discovered a new small molecule antibiotic class. Hopefully this means it won't be absurdly expensive to purchase and use like the glycopeptides and related drugs... Who am I kidding, it's still going to be ridiculously costly no matter how easy it is to synthesize.
Just got introduced to Sodium Arsenate NaAsO2 in my drinking water treatment adventures. Solid Manganese particles can interfere with DPD colorimeter testing of free/total Chlorine residual. To determine the amount of interference, NaAsO2 is used to destroy the free Chlorine without affecting Manganese or sample color. Potassium Iodide may also be used to destroy other Chlorine compounds and release Hydrogen Iodide HI and Sodium Arsenite NaAsO3, then the treated sample result is subtracted as interference from the un-treated sample result to determine the true Chlorine residual.
adding the MeI to the warm solution not down the condenser was not the best decision, and in my opinion and experience its so volatile that its hard to avoid losses without a closed system above its boiling point
@@skyrailmaxima As=O has more of a dative bond character no? sp3 hybridization on the As -> no conjugated system. Plus idk how well conjugation would actually work between the As 4d and C sp2 orbitals? The enolate is strongly nucleophilic so I dont see why it would go e2
If memory serves, some of the meds I've taken over the years had the "sudden death due to unknown reasons in rare cases" side-effect on the package insert so modern arsenic meds don't sound too-bad. On a slightly-related omega-poison note, I'm curious about the old mercury amalgam fillings I have turning all-shiny after I ate like ten pounds of oranges in a month. If it sounds like a good video idea, would be curious how many cans of tuna's worth of mercury I ingested for each filling alongside those oranges.
Interesting compound, I wonder what its risk profile and pharmaceutically relevant ranges and interactions and side-effects are. ABs are this one class of meds that always mess in a
I'd be careful when drawing mechanisms involving elements that aren't in the second period. It is impossible that the oxygen atom pushes an electronic pair to arsenic to form an oxygen-arsenic double bond as there is no As-O double bond present in arsenates (just as in phosphates and sulfonates). Edit: Great Video btw, it's exciting seeing new antibiotics being developed as the situation is more than dire!
Is this in reference to the initial nucleophilic attack on 1,2-dichloroethane? Presumably the double bond has to form at some point, unless the product structure for that step is wrong, and while the mechanism given might be iffy (?) the electron accounting seems reasonable? End of the day electron arrow pushing is a powerful predictive model for organic chemistry, but it's far from a perfect description of what's going on, so I'm usually a bit more tolerant for stuff like this which seems largely concerned with the synthetic pathway. Perhaps if you were interested in the intricacies of the individual mechanistic steps you would need to be more precise.
@thricegreat7175 impossible as in there is no scientific evidence that hypervalency is real for main group elements, bud. But there is plenty disproving it.
@tomsmith48 Yeah I agree, can be useful if used within its limitations. Every real double bond is susceptible to addition reactions tho, so one has to come up with an explanation as to why no addition reactions take place across the As-O double bond.
@@B_u_L_i hmm, you've definitely got me thinking about the nature of formal double bond X=O type species. Quite interesting. In terms of hypervalency, at least in the very narrow sense of 'do heavier p block elements exceed the octet rule' then you only need to look at the various p-block fluorides to see that hypervalency (in that strict sense) is a real thing. What's more at issue is how best to describe the bonding in heavier p block oxo species. I suppose there's some evidence in the difference in the reactivity of the oxygens of say phosphoric or sulfuric acid (to take a very well known set of molecules). They are H3PO4 and H2SO4 respectively. Of course the position of protonation can change, but any bonding model does have to account for why phosphoric acid has a single non-protonated oxygen, and sulfuric two. In both cases you have two oxygen 'environments'. This combined with the shorter bond lengths on the non-protonated oxygens probably represents the most direct evidence. When combined with VSEPR and the idea that oxygen should want to have a complete octet, then you get a basic theoretical model (which I admit is probably very flawed) for why the non-protonated oxygen in these acids has a double bond character. Again, are these 'real' double bonds....I guess the best evidence would be to do a full MO treatment and see if you see something like a pi cloud MO in a similar fashion to C=C systems. I know what you mean about addition reactions, but I don't think it's a hard and fast rule that a double bond must be able to add over for it to be 'real'. N2 can be added over, but it's a very tough nut to crack. Similarly, many of these heavy p block elements form very strong bonds to oxygen and typically undergo addition-elimination type reactions to preserve that strong bond in the product.
Very interesting. Five years after its discovery it seemingly is still not being used in any clinical trials and the word appears nowhere on the clinicaltrials website. Because it's a naturally occurring compound and the pharma companies can't patent it?
someone doesnt understand pharmaceuticals. a vast majority of the compounds used in pharma research are primarily derived first from naturally occurring sources such as phytocompounds. almost all chemotherapeutic drugs are discovered in this way.
It will always take a long time before a drug can be approved for clinical trials. It has to go lots of animal testing, in vivo and in vitro. At least you can expect it to go clinical trials in about 5 yrs from now....
Ehh... Really the only thing i need to know is that this was isolated from Bhurkholderia, which was the re-classification of Ceapacia bhurkholderia. Using a tool that Bhurkholderia is specifically adapted to opens up a person to infection by Bhurkholderia and other Cepaecia-like infective agents. I suppose second and tertiary infection events might just be me though.
I would suggest that brmination or iodination of beta lactams would be a new clas if enzyme resistant antibiotic like chloro and flouro analogues have been developed before
Interesting and thanks. A penicillin and something like Septra DS? Co-administered? This combo was used to sterilize a person's intestine before and operations, I've heard? Been a while.
Nice synthesis, and marries well with the recent report in Nature Chem (doi: 10.1038/s41557-023-01362-3) on the asymmetric decarboxylation of aminomalonic acids (since I'm guessing specifically the L- version is the bioactive compound, but I haven't read the arsenic paper so...) to produce chiral amino acid products! If you want to do the paper disc test in the future to avoid the "did the plate just go bad" thing, I literally just used a hole punch with some Whatman filter paper when I used to setup undergrad labs. Ideally you want them autoclaved (you could pressure cook them in a glass dish), but you could also probably get away with soaking them in 70% EtOH, letting them air dry, then low-heat oven drying them. Also, while spit works (human mouths are worse than dog mouths), human saliva also contains lysozyme which is antibacterial in its own right. Making some sterile q-tips and swabbing a toilet/water fountain, or plating some melted ice from a fast food ice machine (those things are not cleaned NEARLY as much as they should be, as I found out in my undergrad microbiology lab) are great sources of bacteria. Just be careful if you do the toilet one, BSL-2 human pathogens and all that jazz.
I guess Arsenic Trioxide can be used to treat certain forms of cancer as well. Interesting any Arsenic compounds at all can have medicinal properties. I wonder if any other Arsenic-substituted amino acid analogs have been studied at all.
Dude the first ever synthetic drug contained arsenic, it was called Salvarsan and it cured everything, good old Paul Ehrlich and and his magic bullet, it worked by killing the patient.
Looks chiral to me... 4 ligands no e- pairs so tetrahedral. And then 4 different ligands makes a chiral centre (plus you can't rotate the mirror image to fit the original) id say but don't quote me lol
I think it is chiral, but I suspect the As-OH and =O might be able to inter-convert. Not sure how quick that would be, but my guess is you'd probably struggle to keep it from forming a racemic mixture over a long period, particularly if it's dissolved in a protic solvent.
Glutamate itself and glutamate-like chemical structures are found all around life itself. Some plants have it as a poison. Some bacteria use it as bactericide.
Fun fact. A small amount of arsenic in your diet is good for you. There is a syndrome a little like scurvy that is due to arsenic deficiency. Arsenic deficiency is alo probably the explanation for how oysters got a reputation as an aphrodisiac - because their arsenic content is high and reinvigorates anyone arsenic deficient. (Doesn't work otherwise).
is the first reaction the same mechanism as an Aburzov reaction? never seen it before although arsenic chemistry is not that popular :D BTW have you ever smelled triethyl phosphite?
You need to crank up your volume a good 20%. I have to increase my TV volume by at least 5 points to hear you talking at all at first, then ads come on and deafen everyone in the room. Plz? Also, you're both thorough and capable, and I appreciate all of your videos. You always get a thumbs up from me.
I am 10 seconds into this video, and stunned that enterobacter cloacae is named as such. looking for a name origin turned up only that it comes from an older (and now defunct) name of cloaca cloacae, and that name is as hilarious as it's funny. I can't get any further on the name origin though, does anyone know why we have bacteria named bird ass bird assae?
Saw the dreaded signature of yellow chemistry... something must be horribly wrong in Tom's universe on a day that yellow chemistry is working... someone should do a wellness check on Australia assuming it still exists in our timeline... thoughts and prayers...
If Burkholderia gladioli already makes this, it should be very hard to enslave a large population of Burkholderia, and whip and beat it untill it produces large quantities inside giant steel vats. Still, thankyou again for the chem man.
I don't really know much of anything about arsenic besides that it's horrifically toxic, is this actually safe enough to use as an antibiotic? Or is it purely for sterilizing surfaces?
First of all, i though arsenic was green so i was a bit surprised the solution was yellow. Second of all, im doing my masters in medicinal chemistry and the message of the video pretty much sums up how i feel "fuck biology"
How about the antimicrobial properties of Ketamine and its closely related analogues? I've done a small test with one of them and the results were pretty promising! I'd be really interested in seeing one of the big chemistry TH-camrs try to make a new ketamine related compound with those properties but with less of the psychoactive part!
An organoarsenic compound (Arsphenamine) was one of the first antibiotics, Paul Ehrlich won a Nobel prize for the discovery in 1908. Inorganic arsenic (like the starting material used here) is very toxic though.
Toxicity of chemical compounds depends not only on the atoms in the compound but each compound has its own effects since they react different from each other. H2S, a toxic gas for example reacts very different in the body than for example Methionin, a sulfur containing essential amino acid. I suppose arsenic reacts in a different way in the body than this compound. He did mention that this compound is also toxic to the human enzyme but much more so to the bacterial one and is thereby an effective way of killing bacteria without dealing serious harm to humans
You should get a clip of extractions and ire saying "it's fookin yella", or however his silly Aussie accent would say it, when you have a solution that turns yellow.
@@gluesniffingdude It's charged on one end and non polar on the other, LIPID! untill proven innocent, the acetyl choline resemblance is irrelevant, that is a minor contribution to the effects of the type of compound I am referring to anyway. The concern I expressed refers to the enzyme disrupting property evident and mentioned, (assume it has a more promiscuous spectrum of binding because of its simplicity, charge and shape). Also the compound is evidently an effective biocide and it looks at home when compared to fatty acid amide hydroxylase inhibitors. Which is what is responsible for the rapid and lethal accumulation of signaling and structural lipids in the central nervous system. That is what causes sudden cytotoxicity in neurons with that type of molecule. And given the context of this , really quite good, video, that does not mention any animal toxicity studies, is a concern I would have when risk assessing a synthesis like this. And that's before thinking about toxic metabolites containing arsenic. On the other hand it might induce murine narcosis. Role on the bio nutters publication on Cannabinarsinoids (maybe), who knows given the limited info. Remember negating without evidence leads nowhere.
I think the use of electromagnetic radiation (photons) is under utilized. There must be a unique resonant wavelength and energy for the DNA of any microbe that will only destroy chemical bonds unique to that organism. Similar to a microwave oven.
No, that's sadly not gonna work. The basic structure of DNA is the same for every organism. The differences in base sequences don't really change absorption spectra by an appreciable amount, especially not considering you would need to be able to specifically recognize pretty long sequences. This would also mean be could sequence DNA by just quickly measuring its absorption spectrum, which would be absolutely amazing. Then we wouldn't have to deal with these overpriced next-generation sequencing chips from illumina. Also what do you mean "similar to a microwave oven"? Microwaves don't break any bonds (except indirectly through heat, I guess) and they're certainly not selectively for specific DNA sequences.
@@lunkel8108 I used microwaves just so people could understand the basic principle of targeting molecules with EM radiation. It seems you have superior knowledge on the topic 🙂 I agree that I didn't think deeply about it, but if not DNA, then other things, like cell walls, or other unique biochemical signatures .. ? 🤔 I'll defer to your expertise. We know that molecules are vibrating, and there ought to be some unique frequency to do damage via resonance.
@@chadkline4268 I won't rule it out completely but I'm not very optimistic. Most of life is based on very similar building blocks. But you might be interested to know that we do use light in some interesting medical applications like photodynamic therapies for example. There you introduce a chemical that is harmless by itself but when it absorbs a certain wavelength of light, it messes with the oxygen present in cells to make it far more reactive, which kills the cells. The advantage here is that you can use the light to very precisely direct where that damage happens. These methods are used mainly to treat some skin diseases and certain cancers as far as I'm aware. Another example I find interesting is phototherapy for newborn jaundice. Infants are sometimes a bit yellow because their liver isn't yet fully developed and struggles to get rid of the breakdown product of hemoglobin (bilirubin). Often it resolves itself but in slightly more severe cases the babies are placed under blue light, which causes bilirubin to change its shape and allows the body to get rid of it more easily.
Chemistry like this makes me wonder how the bacteria produces these compounds. I assume they have the advantage of dna/rna to build molecules in pieces but the process is beyond my understanding.
Wait, what hybridization is that? Is that sp³d or something? Nah, that does not make sense… Ah, I guess it has to be a coordinate bond and not literally four electrons between As and that O at the top.
Asbestos is only dangerous when it gets into the air and you breathe it. It could be used safely in a lot of applications but I’d expect that companies are afraid of lawsuits and it’s a bit of an ecological nightmare to mine.
@@chemistryofquestionablequa6252 There are dangers all across the chain from mining, refining, production of the end product, possibility of leaks from the product, and decommissioning. Not worth it in 99% of cases.
I think these new antibiotics will buy us time but what we really need to do is start discovering the bacterial phages that can attack these broad spectrum resistant bacteria. If you want to read about a success story read a book called The perfect predator.
It's totally safe because the arsenic can't possibly break free and build up in the body and if thousands of people start presenting arsinic poisioning symptoms they are wrong it can't possibly be that and is a statistical coincidence.
If you die from a bacterial infection you can at least be glad that you didn't get a minor arsenic poisoning. Skeletor will return next week with more disturbing facts.
![Making Dibenzo[a,e]cyclooctene - an Emerging Ligand?](http://i.ytimg.com/vi/_2FNaCZldE4/mqdefault.jpg)
![Making [1.1.1]Propellane](/img/n.gif)
A comeback of arsenic medication. Didn´t think this would happen. Great prep! 🗿
It takes a lot of sense, it would get around a lot of the current antibiotic resistant mutations. I guess we started with arsenic, now we’re going back!
@@thricegreat7175
Thiomersal was already used for a long time and is still used. Furthermore, it is actually safe.
Next would be a Lead-based medication - now that would be amazing if it wasn’t dangerous.
are you making it? @_@
When I was taught how to do column chromatography, the offical method for packing and "tapping" the column was actually to attach an overhead stirrer next to it, put a piece of soft bent rubber hose onto it and then turn it on so it would smack the column constantly and pack it more efficiently. After initially thinking that the column was gonna break, it was kinda hilarious to me.
@@exoticarcher6625 He should read the Clark Still Rapid Separation Column Chromatography Paper
@@exoticarcher6625flash columns are great but for some reason they don't work for every mixture
@@jogandspBecause there's an optimum rate of elution. Too fast and the mobile and stationary phase can't equilibriate, too slow and diffusion broadens the bands.
@@Paksusuoli95 yea, that's the van Deemter curse
Arsenic based compounds were one of the first treatments for syphilis and have seen widespread use until other classes of antibiotics (sulfa drugs and penicillin) were discovered. Early antibiotics were kinda like how small molecule chemotherapy drugs against cancer are nowadays: Significantly toxic to the patient, but not dying due to the underlying disease is still better than the side effects.
Arsenic based compounds are still being used for treating African sleeping sickness, they're using melarsoprol as a second line anti protozoan drug effective against the second stage of Trypanosoma brucei rhodesiense....
Or, coming from a different field, this time psychiatry: First and, to a large extent, second generation anti-psychotics. Actively harms the patient due to neurotoxicity mediated through numerous pathways, inducing a reduction of white matter and general brain volume. It is 100% clear that dopamine, or more specifically, the D2 sub-type receptor, or rather the affinity of a small molecule acting as an antagonist is directly correlated to antipsychotic potency. But then here we have the atypical antipsychotic Clozapine, which doesn't really have much affinity to D2 receptors compared to others, especially first generation phenothiazines come to mind (some if not more than half of them have a comperatively clean binding profile) basically in most cases just targeting the D subtypes along with mAChRs and the Histamine 1 receptor.
This is a field I actively do lab work in, and, compared to antibiotics and the inevitable multi-drug resistance if we don't stop prescribing them for every tiny fever or cold is surely threatening, but trust me, neurobiology and psychiatry is a whole different beast.
@@williamkane I was misdiagnosed as Bipolar after a concussion, put on Aripiprazole and Lurasidone, and have had Cariprazine and Olanzapine, Haldol, etc in hospital.
These drugs and their after-effects, which lasted for a long time, and the withdrawals from them were legitimately worse than IV methamphetamine withdrawal. Also, they made me _REALLY_ crave anything that made me feel better and I started to do drugs way more than I had done ever before while on them, which resulted in someone getting me into that crap.
The restlessness alone was so horrific, and I doubt ADHD and whatever that means for my brain made it better when combined with these. I'd get up, walk around for 5 minutes, then have to sit down, and repeat it 5 minutes later. Otherwise the most horrific anxiety would build up until it felt like I wanted to die.
I think getting those antipsychotics is what started my downward spiral overall.
@@williamkane To sum it up really - I would rather have atropine & scopolamine injected into my dick than go near an antipsychotic.
@@williamkaneAntibiotic resistance is being blown completely out of proportion and is creating needless hysteria.
As an infectivologist, I appreciate this work and have a lot of hope
Think it can work against late stage Lyme?
c'mon is that really a job?😂
@@ohbeardedone9253 Studies have found it effective against early state Ligma so maybe
@@samyakjain5377 now is a good time as any to learn to google stuff before you say dumb stuff online.
In other words, they're an infectious diseases medical professional.
As a microbiologist, I wet my pants. Don't give a chemist an inoculation loop. I have never seen anyone attempt to spread a bacterial dilution for an antibiogram using an inoculating loop on Mueller-Hinton agar. 🤣🤣🤣 For this you use a Drigalski spatula and you actually isolate a germ before doing an antibiogram. This antibiotic can be very effective on one germ and have no effect at all on another germ. However, if I have a mixture of different germs, I can't judge whether it is effective or not. But this isn't actually a channel for biologists I know. I also wanted to teach some useful knowledge to chemists. No offense to all chemists. 😜😘
Woah this is siiick organic chemistry right there!
Btw, I don't think the SO2 reduction of the organoarsenate proceeds via nucleophilic attack of the sulfur on the As=O. This is not a true double bond but rather an ylid, much like P(V) oxides, because there is very poor overlap between the 2p orbitals of Oxygen and the 4d orbitals of Arsenic. Therefore, you would have something that looks more like a positively charged Arsenic and a negatively charged Oxygen, for which the electrophilic position would be As rather than O.
The same is true for the SO2, but the orbital overlap is better between S & O. Plus, the Sulfur is more electronegative than As and is therefore more electrophilic. I suspect the As-O(-) attacks at Sulfur, and then the sulfur's electrons can form another S=O bond and push back the electrons of the As-O bond into the arsenic center.
Edging to this right now💪
Just don't maintain your erection for 4 hours or longer. If you do, your N2O-producing endothelium will die of hypoxia and your lil' guy will never be the same again. 🥺
you didn't need to write that comment
Whenever I hear of a new antibiotic, I feel a surge of joy. I just hope that people use it responsibly!
They wont
Sadly, those surges of joy are often short-lived as those antibiotics frequently are found to be unsafe and have to be withdrawn. See, e.g., gatifloxacin, telithromycin, and others.
@@affegpus4195 Especially in China
@1:51 Fun fact: Arsenic trioxide is also known as "inheritance powder".
You almost got it right at the end. What you should have done.
1. Prepare 2 plates, on one plate you spread out the antibiotic.
2. Make up enough solution of 50/50 water + spit to do both plates at the same time. Treat both plates with the solution the same way..
3. Incubate as before..
“It’s about the journey, not the destination” - I was lol’ing and cheering this assertion with the unceremonious end to the anti-spicy video. And then to hear it stated her was 🎉💪🤘
Very cool and nicely edited video as always! One question tho: have you considered testing the antimicrobial properties of the reactants? Because if for ex. As2O3 was also antimicrobial, your seemingly positive result would be easily disproven. But I know this vid is about synthesis and not so much about the result.
Again, I'm reminded (like with every video from you) why you are my favorite chemistry youtuber.
Well done, can't wait for more!
Would you mind linking the publications you're working from in the future? Or even titles and authors in the video? I'd like to see the purification method with a strange column they talk about.
I will add them to the description!
I wonder if the antimony derivative shares similar antimicrobial properties
would have been cool if you tested it later in the control plate with the growth, to see if it had an effect on the bacteria
Yess
This was certainly quite an interesting video to watch, reading up on these amonia based antibiotics that are currently in development was also quite an interesting read and hives some hope for antibiotics.
based on your accent I am wondering if you are dutch?
He is Dutch, yes.
Very cool synthesis, and very exciting that we've finally discovered a new small molecule antibiotic class. Hopefully this means it won't be absurdly expensive to purchase and use like the glycopeptides and related drugs... Who am I kidding, it's still going to be ridiculously costly no matter how easy it is to synthesize.
Just got introduced to Sodium Arsenate NaAsO2 in my drinking water treatment adventures. Solid Manganese particles can interfere with DPD colorimeter testing of free/total Chlorine residual. To determine the amount of interference, NaAsO2 is used to destroy the free Chlorine without affecting Manganese or sample color. Potassium Iodide may also be used to destroy other Chlorine compounds and release Hydrogen Iodide HI and Sodium Arsenite NaAsO3, then the treated sample result is subtracted as interference from the un-treated sample result to determine the true Chlorine residual.
Neat! Thanks for posting!
adding the MeI to the warm solution not down the condenser was not the best decision, and in my opinion and experience its so volatile that its hard to avoid losses without a closed system above its boiling point
Tremendous amount of work. Great job
I am shocked that goes Sn2 and not E2 in the Ethanol/huge nucleophile step. It would also have massive hinderance from the arsenate group!
Wouldn’t a double bond with the carbon bonded to an As center be unstable?
@@espanadorada7962 Why would it? If it goes SP2 then you have Pi delocalization through both the AsO group and Carbon, seems highly favorable to me
@@skyrailmaxima As=O has more of a dative bond character no? sp3 hybridization on the As -> no conjugated system. Plus idk how well conjugation would actually work between the As 4d and C sp2 orbitals? The enolate is strongly nucleophilic so I dont see why it would go e2
@@skyrailmaxima Actually, no, the double bond would not be conjugated with the arsonic group.
If memory serves, some of the meds I've taken over the years had the "sudden death due to unknown reasons in rare cases" side-effect on the package insert so modern arsenic meds don't sound too-bad. On a slightly-related omega-poison note, I'm curious about the old mercury amalgam fillings I have turning all-shiny after I ate like ten pounds of oranges in a month. If it sounds like a good video idea, would be curious how many cans of tuna's worth of mercury I ingested for each filling alongside those oranges.
You are a master of chemical videos!!!
Interesting compound, I wonder what its risk profile and pharmaceutically relevant ranges and interactions and side-effects are.
ABs are this one class of meds that always mess in a
I'd be careful when drawing mechanisms involving elements that aren't in the second period. It is impossible that the oxygen atom pushes an electronic pair to arsenic to form an oxygen-arsenic double bond as there is no As-O double bond present in arsenates (just as in phosphates and sulfonates).
Edit: Great Video btw, it's exciting seeing new antibiotics being developed as the situation is more than dire!
Is this in reference to the initial nucleophilic attack on 1,2-dichloroethane? Presumably the double bond has to form at some point, unless the product structure for that step is wrong, and while the mechanism given might be iffy (?) the electron accounting seems reasonable? End of the day electron arrow pushing is a powerful predictive model for organic chemistry, but it's far from a perfect description of what's going on, so I'm usually a bit more tolerant for stuff like this which seems largely concerned with the synthetic pathway. Perhaps if you were interested in the intricacies of the individual mechanistic steps you would need to be more precise.
@thricegreat7175 impossible as in there is no scientific evidence that hypervalency is real for main group elements, bud. But there is plenty disproving it.
@@thricegreat7175 don't be cocky if you don't know shit about chemistry
@tomsmith48 Yeah I agree, can be useful if used within its limitations. Every real double bond is susceptible to addition reactions tho, so one has to come up with an explanation as to why no addition reactions take place across the As-O double bond.
@@B_u_L_i hmm, you've definitely got me thinking about the nature of formal double bond X=O type species. Quite interesting. In terms of hypervalency, at least in the very narrow sense of 'do heavier p block elements exceed the octet rule' then you only need to look at the various p-block fluorides to see that hypervalency (in that strict sense) is a real thing. What's more at issue is how best to describe the bonding in heavier p block oxo species. I suppose there's some evidence in the difference in the reactivity of the oxygens of say phosphoric or sulfuric acid (to take a very well known set of molecules). They are H3PO4 and H2SO4 respectively. Of course the position of protonation can change, but any bonding model does have to account for why phosphoric acid has a single non-protonated oxygen, and sulfuric two. In both cases you have two oxygen 'environments'. This combined with the shorter bond lengths on the non-protonated oxygens probably represents the most direct evidence. When combined with VSEPR and the idea that oxygen should want to have a complete octet, then you get a basic theoretical model (which I admit is probably very flawed) for why the non-protonated oxygen in these acids has a double bond character. Again, are these 'real' double bonds....I guess the best evidence would be to do a full MO treatment and see if you see something like a pi cloud MO in a similar fashion to C=C systems. I know what you mean about addition reactions, but I don't think it's a hard and fast rule that a double bond must be able to add over for it to be 'real'. N2 can be added over, but it's a very tough nut to crack. Similarly, many of these heavy p block elements form very strong bonds to oxygen and typically undergo addition-elimination type reactions to preserve that strong bond in the product.
I was still slightly mad at you for scopping Tom (aussie represent!), but this is amazing. Thanks for sharing!
Very interesting. Five years after its discovery it seemingly is still not being used in any clinical trials and the word appears nowhere on the clinicaltrials website.
Because it's a naturally occurring compound and the pharma companies can't patent it?
May be, unfortunate there are a bunch of effective drugs that aren’t made or marketed because of patent and money problems.
someone doesnt understand pharmaceuticals. a vast majority of the compounds used in pharma research are primarily derived first from naturally occurring sources such as phytocompounds. almost all chemotherapeutic drugs are discovered in this way.
It will always take a long time before a drug can be approved for clinical trials. It has to go lots of animal testing, in vivo and in vitro. At least you can expect it to go clinical trials in about 5 yrs from now....
@@ChimeraX0401 there are no preclinical in vivos either....
Well this is the brightest comment section on TH-cam. Nice to see some good 'ol column chromatography too.
Ehh...
Really the only thing i need to know is that this was isolated from Bhurkholderia, which was the re-classification of Ceapacia bhurkholderia.
Using a tool that Bhurkholderia is specifically adapted to opens up a person to infection by Bhurkholderia and other Cepaecia-like infective agents. I suppose second and tertiary infection events might just be me though.
When the world needed it most, it returned
Incredible synthesis! Would doing a TLC of the final product give any insight about the purity?
Good to have in the arsenyl
I would suggest that brmination or iodination of beta lactams would be a new clas if enzyme resistant antibiotic like chloro and flouro analogues have been developed before
Unfortunately, iodine and bromine generally can go out of the molecule as I- and Br- more easily than chlorine and fluorine...
Interesting and thanks. A penicillin and something like Septra DS? Co-administered? This combo was used to sterilize a person's intestine before and operations, I've heard? Been a while.
Great content here! 7:01 how do i know that the product is in the water layer? I dont get it :D Thanks.
Nice synthesis, and marries well with the recent report in Nature Chem (doi: 10.1038/s41557-023-01362-3) on the asymmetric decarboxylation of aminomalonic acids (since I'm guessing specifically the L- version is the bioactive compound, but I haven't read the arsenic paper so...) to produce chiral amino acid products! If you want to do the paper disc test in the future to avoid the "did the plate just go bad" thing, I literally just used a hole punch with some Whatman filter paper when I used to setup undergrad labs. Ideally you want them autoclaved (you could pressure cook them in a glass dish), but you could also probably get away with soaking them in 70% EtOH, letting them air dry, then low-heat oven drying them. Also, while spit works (human mouths are worse than dog mouths), human saliva also contains lysozyme which is antibacterial in its own right. Making some sterile q-tips and swabbing a toilet/water fountain, or plating some melted ice from a fast food ice machine (those things are not cleaned NEARLY as much as they should be, as I found out in my undergrad microbiology lab) are great sources of bacteria. Just be careful if you do the toilet one, BSL-2 human pathogens and all that jazz.
Arsenic redemption arc
You should follow up with making Salvarsan, the very first antibiotic.
I guess Arsenic Trioxide can be used to treat certain forms of cancer as well.
Interesting any Arsenic compounds at all can have medicinal properties.
I wonder if any other Arsenic-substituted amino acid analogs have been studied at all.
Dude the first ever synthetic drug contained arsenic, it was called Salvarsan and it cured everything, good old Paul Ehrlich and and his magic bullet, it worked by killing the patient.
Arsenic chemistry amazes me. Yeah we need other antibiotics.
I'm somewhat concerned that the arsenic could react out of this. What if it gets oxidized?
Bro drops a synthesis every day
Is the arsenic atom a chiral centre and if so, does the stereochemistry matter or nah? Anyway nice video
Looks chiral to me... 4 ligands no e- pairs so tetrahedral. And then 4 different ligands makes a chiral centre (plus you can't rotate the mirror image to fit the original) id say but don't quote me lol
I think it is chiral, but I suspect the As-OH and =O might be able to inter-convert. Not sure how quick that would be, but my guess is you'd probably struggle to keep it from forming a racemic mixture over a long period, particularly if it's dissolved in a protic solvent.
Is Arthrinoricin found in nature? I vaguely remember a similar compound found in Creosote bush micro /flora
Glutamate itself and glutamate-like chemical structures are found all around life itself. Some plants have it as a poison. Some bacteria use it as bactericide.
Fun fact. A small amount of arsenic in your diet is good for you. There is a syndrome a little like scurvy that is due to arsenic deficiency. Arsenic deficiency is alo probably the explanation for how oysters got a reputation as an aphrodisiac - because their arsenic content is high and reinvigorates anyone arsenic deficient. (Doesn't work otherwise).
is the first reaction the same mechanism as an Aburzov reaction? never seen it before although arsenic chemistry is not that popular :D BTW have you ever smelled triethyl phosphite?
DId you isolate a possible dioxaarsole byproduct in the first step?
remember arsenic?
it's back
Can you make the antibiotic halicin from chemical synthesis?.
You should make an Arsole molecule
Is it possibile using in this reaction a pyrosulfide as reducing agent instead sulfur dioxide?
How are you making your clean up and residue treatment?
Ah yes, good old "succession powder".
What do u use for the SO2 generator? H2SO4 and? Thanks :D
You need to crank up your volume a good 20%. I have to increase my TV volume by at least 5 points to hear you talking at all at first, then ads come on and deafen everyone in the room. Plz?
Also, you're both thorough and capable, and I appreciate all of your videos. You always get a thumbs up from me.
Holy 💩 a slight tweak of that molecule would make a very potent neurotoxin.😮😮😮
Can you please point out which neurotoxin are you talking about
How would that arsenic be a nucleophile if it has so many bonds to oxygen?
Bro u need a rotovap, how long are you just destilling per vid?
I’m so interested in salt and sugar moleculars.
looks like a nightmare of a synthesis to scale up
I am 10 seconds into this video, and stunned that enterobacter cloacae is named as such. looking for a name origin turned up only that it comes from an older (and now defunct) name of cloaca cloacae, and that name is as hilarious as it's funny. I can't get any further on the name origin though, does anyone know why we have bacteria named bird ass bird assae?
The Occam's razor explanation is that it's called that because that's where it was first found.
"bird ass" is unprofessional and inaccurate. We usually prefer "multi-purpose hole".
@@hairymcnipples Sounds like something a bird would say.
@@Gameboygenius Indeed. The origin of Mycobacterium smegmatis is left up to the reader...
Saw the dreaded signature of yellow chemistry... something must be horribly wrong in Tom's universe on a day that yellow chemistry is working... someone should do a wellness check on Australia assuming it still exists in our timeline... thoughts and prayers...
If Burkholderia gladioli already makes this, it should be very hard to enslave a large population of Burkholderia, and whip and beat it untill it produces large quantities inside giant steel vats. Still, thankyou again for the chem man.
I don't really know much of anything about arsenic besides that it's horrifically toxic, is this actually safe enough to use as an antibiotic? Or is it purely for sterilizing surfaces?
Just stop at your fifth word and call it a day.
@@Failure_Is_An_OptionHe asked a legitimate question, Neckbeard.
what a nightmare to make wow thank you taking the time
I have a degree in physics, and “F biology” was our departments rallying cry 🤣
How does KI act as a catalyst?
Afaik iodide ion can help in transfer of electrons, speeding up the reaction
Tf kind of parafilm are you using that leaves residue? Lol
sticky and soft from being in the oven
Why not film the column chromatography? I never see other TH-cam chemists doing it either. It would make great time lapse footage
What is this field that you are studying?
That's chemistry
First of all, i though arsenic was green so i was a bit surprised the solution was yellow.
Second of all, im doing my masters in medicinal chemistry and the message of the video pretty much sums up how i feel "fuck biology"
Plot twist : the contaminants were very toxic that it killed the microorganisms.
How about the antimicrobial properties of Ketamine and its closely related analogues? I've done a small test with one of them and the results were pretty promising! I'd be really interested in seeing one of the big chemistry TH-camrs try to make a new ketamine related compound with those properties but with less of the psychoactive part!
Why is Arsenic being used in an antibiotic compound as a main functional group ingredient
Isn't it supposed to be poisonous to humans?
An organoarsenic compound (Arsphenamine) was one of the first antibiotics, Paul Ehrlich won a Nobel prize for the discovery in 1908. Inorganic arsenic (like the starting material used here) is very toxic though.
Toxicity of chemical compounds depends not only on the atoms in the compound but each compound has its own effects since they react different from each other. H2S, a toxic gas for example reacts very different in the body than for example Methionin, a sulfur containing essential amino acid. I suppose arsenic reacts in a different way in the body than this compound. He did mention that this compound is also toxic to the human enzyme but much more so to the bacterial one and is thereby an effective way of killing bacteria without dealing serious harm to humans
Chlorine is toxin to humans but you probably don't think twice before eating table salt
When you want to make sure the reaction at least gives you cancer if the arsenic doesn't get you
You should get a clip of extractions and ire saying "it's fookin yella", or however his silly Aussie accent would say it, when you have a solution that turns yellow.
Hopefully this and bacteriophages will finally end TB
What type of bacteris would this be active againsts gtam negative or or Mrsa, this looks like toxic shit like chloramphenicol...
but whhy is the arsenic ok?
take a shot every time he says short path vacuum distillation
You should do a video on extracting morphine from poppy seeds
Vice already has a video on it.
bros weeks away from developing the cure to cancer
What other enzymes does it bind to, it looks a lot like a lipid, I'm thinking Sarin.
Wouldn't be a very good antibiotic if it was also AChE inhibitor.
This does not resemble a lipid in the slightest and neither is it functionally analogous to acetylcholine
@@gluesniffingdude It's charged on one end and non polar on the other, LIPID! untill proven innocent, the acetyl choline resemblance is irrelevant, that is a minor contribution to the effects of the type of compound I am referring to anyway. The concern I expressed refers to the enzyme disrupting property evident and mentioned, (assume it has a more promiscuous spectrum of binding because of its simplicity, charge and shape). Also the compound is evidently an effective biocide and it looks at home when compared to fatty acid amide hydroxylase inhibitors. Which is what is responsible for the rapid and lethal accumulation of signaling and structural lipids in the central nervous system. That is what causes sudden cytotoxicity in neurons with that type of molecule. And given the context of this , really quite good, video, that does not mention any animal toxicity studies, is a concern I would have when risk assessing a synthesis like this. And that's before thinking about toxic metabolites containing arsenic.
On the other hand it might induce murine narcosis. Role on the bio nutters publication on Cannabinarsinoids (maybe), who knows given the limited info. Remember negating without evidence leads nowhere.
This can only end well.
I think the use of electromagnetic radiation (photons) is under utilized. There must be a unique resonant wavelength and energy for the DNA of any microbe that will only destroy chemical bonds unique to that organism. Similar to a microwave oven.
No, that's sadly not gonna work. The basic structure of DNA is the same for every organism. The differences in base sequences don't really change absorption spectra by an appreciable amount, especially not considering you would need to be able to specifically recognize pretty long sequences. This would also mean be could sequence DNA by just quickly measuring its absorption spectrum, which would be absolutely amazing. Then we wouldn't have to deal with these overpriced next-generation sequencing chips from illumina.
Also what do you mean "similar to a microwave oven"? Microwaves don't break any bonds (except indirectly through heat, I guess) and they're certainly not selectively for specific DNA sequences.
@@lunkel8108 I used microwaves just so people could understand the basic principle of targeting molecules with EM radiation. It seems you have superior knowledge on the topic 🙂 I agree that I didn't think deeply about it, but if not DNA, then other things, like cell walls, or other unique biochemical signatures .. ? 🤔 I'll defer to your expertise. We know that molecules are vibrating, and there ought to be some unique frequency to do damage via resonance.
@@chadkline4268 I won't rule it out completely but I'm not very optimistic. Most of life is based on very similar building blocks. But you might be interested to know that we do use light in some interesting medical applications like photodynamic therapies for example. There you introduce a chemical that is harmless by itself but when it absorbs a certain wavelength of light, it messes with the oxygen present in cells to make it far more reactive, which kills the cells. The advantage here is that you can use the light to very precisely direct where that damage happens. These methods are used mainly to treat some skin diseases and certain cancers as far as I'm aware.
Another example I find interesting is phototherapy for newborn jaundice. Infants are sometimes a bit yellow because their liver isn't yet fully developed and struggles to get rid of the breakdown product of hemoglobin (bilirubin). Often it resolves itself but in slightly more severe cases the babies are placed under blue light, which causes bilirubin to change its shape and allows the body to get rid of it more easily.
We will leave synthesis of antibiotics in the past and turn to bacteriophages for treatment. Most reliable way and selective way to treat AMR.
Chemistry like this makes me wonder how the bacteria produces these compounds. I assume they have the advantage of dna/rna to build molecules in pieces but the process is beyond my understanding.
Always appreciate chromatography in your chemistry videos!
2:21 did the authors try something like 1-chloro-2-iodoethane? Sure, it costs more, but time is money, man!
Wow i like arsenic
Great!
Wait, what hybridization is that? Is that sp³d or something? Nah, that does not make sense…
Ah, I guess it has to be a coordinate bond and not literally four electrons between As and that O at the top.
new treat for chickens
Next up for 2024/2025: Asbestos comeback?!?
Just put asbestos back in cigarette filters. How bad can it be? Or for the modern nicotine enjoyer, use asbestos instead if cotton in your vape tank.
Asbestos is only dangerous when it gets into the air and you breathe it. It could be used safely in a lot of applications but I’d expect that companies are afraid of lawsuits and it’s a bit of an ecological nightmare to mine.
@@chemistryofquestionablequa6252 There are dangers all across the chain from mining, refining, production of the end product, possibility of leaks from the product, and decommissioning. Not worth it in 99% of cases.
I'm hoping for cadmium yellow to make a return 🙏🙏🙏
It seems logical; arsenic sure as hell can end biota.
Blankly stared at the screen for a moment when you added water to sodium hydroxide. Jeez.
I think these new antibiotics will buy us time but what we really need to do is start discovering the bacterial phages that can attack these broad spectrum resistant bacteria.
If you want to read about a success story read a book called The perfect predator.
Noice!
It's totally safe because the arsenic can't possibly break free and build up in the body and if thousands of people start presenting arsinic poisioning symptoms they are wrong it can't possibly be that and is a statistical coincidence.
its okay to not understand how chemistry works xxx
@@sidesplitter9497 No it isn't.
If you die from a bacterial infection you can at least be glad that you didn't get a minor arsenic poisoning. Skeletor will return next week with more disturbing facts.
Well you'd need a pretty strong reducing agent to get that arsenic reduced to As (0) I suppose. Idk look up arseno-organic chemistry
And hey, chlorine is also extremely toxic - better stop eating that nasty sodium chloride!