My late wife had multiple carboplatin treatments, then had to change to cisplatin when she became violently allergic to carboplatin. Then she developed an allergy to that as well. We read a lot of literature about the syntheses of the different platins. Cancer sucks. Fascinating vid as always.

@arnavtete7793

11 ай бұрын

sorry for your loss. she rests in peace.

@NickiRusin

11 ай бұрын

sorry for your loss

@BackYardScience2000

11 ай бұрын

Sorry for your loss. Cancer does indeed suck. 😔

@mastershooter64

11 ай бұрын

I can't even imagine losing my SO, cancer really does suck :( I hope you're doing better now

@MachiningandMicrowaves

11 ай бұрын

@@mastershooter64 She had a most extraordinary life and had a big impact on so many other lives. The surgeries and platins gave her an extra four years so she was able to meet her first great-grandchild. Go Chemistry!

I always like when my nitrate ions f*** off 🤣

the little bits of humor sprinkled into your videos is sublime

@vatsalparmar5740

11 ай бұрын

Frfr they make these videos so much more charming

@kinexkid

11 ай бұрын

I love it. He has a similar style to a channel I follow that does videos on runescape called Limpwurt

@129140163

9 ай бұрын

You should hear how rude he is to the poor, unfortunate nitrate ion! 8:11 😂

@Jokke13th

2 ай бұрын

They sublime?!?

@WhileTrueCode

2 ай бұрын

@@Jokke13th LOL good one 😁

I used to work for Johnson Matthey in the US. I personally helped make 100s of kilograms of all the platinum chemo drugs. It is amazing how these materials are made.

Love to see this video. Have been doing my own research on platinum based anti-cancer drugs with azaindoles as ligands. I was not really interested in inorganic and complex-based chemistry, but after learning about these drugs and their potential, I immediately fell in love with the topic.

@hkillorean6254

11 ай бұрын

If you want an interesting research paper related to this: "Molecular Spectroscopy Evidence of 1,3,5-Tris (4- carboxyphenyl)benzene Binding to DNA: Anticancer Potential along with the Comparative Binding Profile of Intercalation via Modeling Studies" authored by Dr. Zargar. Its a very fascinating paper with some interesting implications to its results and the strength of the intercalation bonds.

@SamirHusainy

11 ай бұрын

Inorganic biochemistry is probably one of the most interesting fields. Almost all enzymatic systems in the body use some sort of metal ion to do reactions. The organic stuff is kinda there as a scaffold. I probably would have done it if it weren't for quantitative chemistry.

I was lucky enough to have taken a cell biology course taught buy one of the first persons to scientifically describe how the first chemo therapy agents worked (mustard gas, look up mustard Bari Italy chemo therapy) . The course was really more of a Professor emeritus to relive his glory days, but I felt honored to be able to sit and listen to his stories.

@tsmith3286

10 ай бұрын

Bendamustine

this is the best channel

@XYZ-dz2ox

11 ай бұрын

Nile red , Prussian blue 🙂

@BackYardScience2000

11 ай бұрын

Better than Nile Red any day.

@savromx4230

11 ай бұрын

​@@BackYardScience2000Nile just post like once a year....yea

They "might" not have to purify it more, they have to meet standards that make your setup look like the most off-brand methlab in existence. srsly, chemotherapy drugs are some of the most carefully regulated drugs in both manufacturing and handling.

@loganosmolinski4446

11 ай бұрын

Frfr the purity regs are insaaaane. Which is good given chemotherapy is basically veeery carefully controlled poisoning of your patient and hoping the cancer dies faster than your victim.

@wingl5841

11 ай бұрын

Basic washing and crystallization doesn't get the purity you need. They most likely use column chromatography to purify which is an expensive process

@crabcrab2024

11 ай бұрын

Bullshit. You can achieve pharmacy grade purity in a very simple lab setting as long as you know what you are doing. It won’t be approved though, since what is desired is not only purity, but also consistency, asepticity, specification correctness and longevity of the formulation. Hence multilevel QC and fail safes. And Chemiolis’s lab is definitely much better than 99% of methlabs. The latter aren’t even really labs, rather cookeries.

@Skrillfreak

11 ай бұрын

Parenteral drugs in general have a high cost involved in manufacturing, especially when you consider that the dry powder for you've created isn't necessarily the last step, they generally keep it in fluid form for compounding in order to make it easier to keep sterile, plus the lyophilization step to keep it shelf stable is an extremely expensive portion for sterile fill and finish

@Avery.D99

11 ай бұрын

@@wingl5841 Yes exactly this, the reaction though done accurately will still produce free radicals, uncompleted synthesis byproducts and varying isotopes and positioning/degress of the molecules themselves that all have different degrees of toxicity as well as binding abilities

These chemotherapy drugs are quite literally precious

The platins tend to cause hearing loss, which is bad, but the reason this happens is interesting and worth reading about

@moboshirolf

11 ай бұрын

really? i never heard about that. only of kidney failure and development of allergies

@djalienprime

11 ай бұрын

The reason is that hair follicles are also consists of quick-growing cells so they react to DNA damage rapidly and hair growth stops for a long time until follicle cell-level repair processes complete (few weeks after the chemo drug left the system).

@aduantas

3 ай бұрын

​@@djalienprimehearing, not hair

We produce those Pt-compounds in our company and many other precious metal compounds.

@knockoutfever4

4 ай бұрын

Which company?

@mathieub3953

4 ай бұрын

@@knockoutfever4 won't tell that on social media, sorry. Just Google, there aren't many of them. 😉

Gotta love molecules containing squares!

Makes sense, one day during one of the rounds of chemo I went through, the nurse was stringing up a bag for me and she said, "Here's another $3000 bag for you." I replied, "Can I sell it? I don't want it." A good laugh was had.

As a cancer patient, i approve of this

@BHop999

11 ай бұрын

Stay strong

@allahkilled7billionJEWS

5 ай бұрын

do you have a drug empire?

You cured my need for good chemistry videos. Thank you

Perhaps you could make Trimethylplatinium Iodide next? It is a cube, after all

I am a research chemist whose PhD is about synthesis and study of novel Pt(IV) prodrugs based on Pt(II) drugs. In my research I use almost exclusively cisplatin, but I consider turning to carboplatin as well. Your video is incredibly informative, I think I might use it in my own synthesis of carboplatin.

I don’t think the AgNO3 reaction counts as an oxidation reaction since there’s no redox with the Pt(II). Looks like a salt metathesis!

Crazy you synthesized the chemo drug I was allergic to when I had treatment when I was younger. Great video btw

to be fair a big part of the cost in drug development is to repay investment from the testing process as well as the initial development an research instead of the raw production volume cool video regardless

@insertaverygenericnamehere

11 ай бұрын

✅

I absolutely love the content that you've been producing on this channel! Although my education was in chemical engineering, the way you present the reactions and the steps is quite thorough and I always learn something new from your videos. You're one of my favorite chemistry channels on KZread and I look forward to seeing more content that you create :)

@highbread817

11 ай бұрын

I'm a layman and I think this guy does a fantastic job at showing every step. He shows the equation clearly on screen and explains exactly what chemicals are doing what better than most other KZread chemists (ofc most ppl are there for the 'fun' stuff). Really good content overall

You really know your chemistry, it's impressive. Great vid, Thank you

At 0:03 the one in the lower left hand corner is cisplatin, or cis-diamminedichloroplatinum(II), the first platinum complex to be used as a chemo drug.

QA testing and regulations (GMP) make up most of the cost of medication, so yeah, that is very fair^^ In pharma, you need a quality concept, you need to test all raw materials, all intermediated, all APIs and all finished products. For the latter two you'll also have to do stability studies at different conditions, maybe photostability studies. You have to qualify companies selling you chemicals and materials. You have to repeatedly audit labs doing testing for you. Authorities like the FDA will audit you. All data created needs to be stored for a minimum of 10 years.

@timkurz6086

11 ай бұрын

And that is only the cost for the drug when it got an admisson from the fda. You have to factor in RnD and especially the clinical studies for new drugs aswell! It is really expensive overall!

@GodlikeIridium

11 ай бұрын

@@timkurz6086 True, if you develop a new drug the costs get very high. Whithout being sure to be successful. Sadly the media love to portray the pharma industry as evil.

@johannesgutsmiedl366

11 ай бұрын

@@GodlikeIridium it's entirely reasonable that the drugs are expensive, but any affluent civilized society should have enough compassion to afford the expenses for those who need it rather than leaving them to fend for themselves, that tends to be the real issue with the costs.

6:40 silver nitrate is not an oxidant, it's just used to precipitate halides.

dude this is awesome chem content. keep it coming! also great editing

Sir, you are a good man. Thank you for such a great insight

Man. The quality of your videos is beyond anything I've seen on youtube before.

Such an innovative approach to video content. Thanks. Saw the Cubane video.

I pressed the like button, amid loud guffaws, the moment you said "to make sure the nitrate ion f*cks off" xD Reminded me of a friend who talks like that Top rank content even aside from the humour. You go, dude! ❤ Amazing work.

@129140163

9 ай бұрын

8:11 The first time I heard that, I didn’t see any other comments acknowledging it, so I thought I was imagining it! 😂

@FarhanAmin1994

9 ай бұрын

XD Rewatched that bit and relaughed

Oxalaplatin was a pretty nasty treatment for me (duodenal adenocarcinoma) but worked well in conjunction with other drugs (I started with folfox then switched to a more customized approach). In remission now for 3 years

Keep it up my brother! Relly nice video🙌🏻🤲🏻🌟

In my college chemistry, cisplatin was an example that linked a chemical with a realistic use case with our ligands and isomerism topics.

You are without a doubt, a very skilled chemist. Where did you learn your craft?

During one of the courses of my degree. We briefly covered platinum based drugs. Specifically Cis-Platin. Very fascinating.

love to see you try Welireg !

Amazing job well done how are you

The lone pair on N7 is what coordinates to the platinum. The structure you showed implies there is a CH2 there

My dad got a platinum based drug for his chemotherapy too (I don't remember which exact one) Sadly, when they discovered the cancer he was already in the "we can't save you anymore" phase and the chemo was only used to buy some precious time

There's a few patents that describe a method of electroless platinum plating, using a chemo compound (edit:cisplatin direct precursor: diaminodinitrite platinum), and hydrazine as reducing agent. Apparently the method should be choice for DIY platinized electrodes.

Can you do an arsenic-based chemotherapy drug and do a similar comparison? I remember someone I know actually giving themselves a large enough tolerance to arsenic that they had to use something else, and I've been curious ever since

Well done!!

FYI silver nitrate doesn't oxidise the platinum, it goes from Pt(II) to Pt(II). Silver salts are used in inorganic chemistry as halide extraction reagents due to the entropic driving force from poorly soluble silver halide salts. Also it's "gwanidine" not "goo-arnidine"

Also need to consider the purity grade of the reagents, the cleaness of instalations and working materiel, and the cost of fabrication itself (electric energy, air filtering sys., water instalations, etc) ..... Man..... Good for Europe for having some of the best healthcare systems in the world

I synthesized a lot of pipeline compounds based on cisplatin ! Love to see this video ! Thank you for your sharing of my daily work.

In the US, it is disturbingly common for cancer patients to run out of money trying to afford their treatments (even if they have health insurance). Some have to resort to selling everything they own, including their house. The heads of these pharmaceutical companies ought to be drawn and quartered.

Yeah, agree on the price. I'd say a lot goes to testing and certification.

I have no idea what any of this means but its fun to watch

Video idea:- Extract Thorium

I have a question. If a base that can accept 2 acidic groups (for example piperazine dihydrochloride) can those groups have different acids ? for example react piperazine monochloride with nitric acid to form piperazine monochloride mononitrate. Is this possible or yo will end up with a mixture of 50/50 piperazine dinitrate and piperazine dihydrochloride ? Thanks

I've been wanting to see someone make a chemo drug. Just to show that it can be made in an amature lab setting. Execpt for the last reagent (which you said could be made), all the stuff can be obtained from around town: Platinum from junk cars (catalytic converters), KCl is a salt substitute, sulfuric acid is a drain cleaner, etc. This could be how people beat cancer in a post-apocalyptic world.

We learn about cis-platin in A level chemistry in the UK (on some exam boards)

is the formation of cis-diamine in the ammonia step always prefered or do you get some amount ofthe trans diamine?

yeah, i do research at my uni with ruthenium to make chemo drugs similar to ones with platinum

YOU are awesome my friend. I love your lessons. the questions that I ask below are from a nerd in general but at the same time.... Sure.. it only cost @ $228 for 600mg to manufacture? Can you describe with any scientific reasoning why chemo treatments cost $5,000 or up ? What in it's synthesis would cause such a simple process be turned on its ear? Is it the crystal to liquid measuring at some far off factory? Is it the refrigeration that it may require? (Ie: short shelf life. ) Is it the C-SUITE guys just rolling dice at meetings and making prices?? It's happened before. I know... A ton to injest but i would be interested in your reply. Betwen chemotherapy drug and insulin prices here in the US, im begging to wonder.

What is the deal with the 'diamond' motif in this molecule? I've seen it in at least two other chemo-drugs...is this a specific class of medication? [Don't know enough chemical terms to ask coherent question...be nice!]

I had testicular cancer and took lots of cisplatin. It was the main chemo drug that made me super sick.

@Ori-lp2fm

3 ай бұрын

I’m sorry bruh 😢

5:48 why does the iodine replace the chlorine in this reaction? Is it because of the size of iodine? Or it’s reactivity?

Don’t forget that cost of R&D, clinical trials, regulatory etc. is also included in the price

Those carboxyl groups are sucking the life out of that cylcobutane ring😂

Why does the iodine replace the Cl when adding KI? Wouldn't steric interference be a pretty big factor?

Hmm that seems to be exactly the price in the Netherlands. Also, the manufacturing happens under GMP rules, which involve a lot of paperwork and tests. So indeed it is pretty reasonable.

I'd love to see more chemo related videos, they're fascinating substances, lots of vesicants/nasty cytotoxic compounds. Like mustard gas.

@arnavtete7793

11 ай бұрын

mustard gas? no

@pucky8231

11 ай бұрын

@@arnavtete7793 Oh yeah. You should read up on how it works.

@rey3472

11 ай бұрын

Mechlorethamine HCl.

@pucky8231

11 ай бұрын

@@rey3472 yep and we also incorporate nitrogen mustard into many other structures for different chemo drugs.

@TomM2727

5 ай бұрын

@@rey3472 There's also cyclophosphamide, chlorambucil, uramustine, melphalan, and bendamustine.

A guy at my uni was researching organometallics for anti cancer. I forget what the metal and ligands were lol. I think Pt(ii) with some aromatic compounds

Badass man thank you. Advanced but still in reach 4 most hobbyist

Aahh je bent nederlands zie ik,ik hoorde het aan je stem. Mooie video trouwens

Lance Armstrong recieved chemo for ball cancer with platinum compounds,but refered to it as plutonium.

Can you do precious metal recovery and refining videos especially the platinum group metals i think they would be really popular

Nice, keep going

> recently I learned about them in like 5 separate chemistry courses

What happens to the rest of the platinum? Is it just lost as a side product somewhere? Shouldn't it be possible to recover it?

They are pumping this stuff into my mother atm. Or at least something similar: Cis-Platinum

Make an isonitrile complex next

the fact there is platinum in cancer remedy reminds me of that south park episode when we discover that magic johnson cured his aids by injecting money

I feel like this could have tons of yield loss because there’s so much scraping of solids off the filters

Zofran synthesis when?

I would love to see the same price analysis for the synthesis of Ritalin, Methylphenidate

@drywall897

11 ай бұрын

Actually synthesizing it might not be very legal

This is a fair comparison. Your carboplatin clearly has a small amount of side-products, and the pharmaceutical grade product cannot tolerate this. Those last purification steps are probably the most expensive in terms of net yield.

We currently have shortages of cisplatin and carboplatin

The standard handling precautions used in medicine for these drugs is hilariously extreme in contrast to watching you do this synthesis. Special gloves, doubled up, dedicated special container for waste (anything contacting the chemo) brought in specifically for the procedure, then removed, patients told to flush toilet twice, men sit down so bathroom isn't contaminated with aerosolized chemo-pee...

@rey3472

11 ай бұрын

Repeated exposure of the hospital staff. I am sure being exposed many times per day every week factors.

We need more videos about making medications... In case SHTF?

The coincidence that I just sat in a hospital this week with my ill father, who got one of the platinum chemos, is very scary...

I love it ❤️😍

I was expecting tens of thousands per mg so was happly surprised with reasionable costa

This acid is to hard? It seems that: diethyl malonate C-alkylation with 1,3-dibromopropane and then hydrolysis of ester should do the job. After making cube, square is not fancy enough? mmm? :P XD

@elnombre91

11 ай бұрын

Diethyl malonate + 1,3-dibromopropane doesn't make the cyclobutane, it alkylates once at the alpha position and once at oxygen forming a cyclic, 6-membered enol ether.

@ejkozan

11 ай бұрын

@@elnombre91 well this way you make cyclopropane with dihaloethane, so I expected cyclobutane is not problem. And o alkylation is more common with alkylation of pentadione not malonate ester

@elnombre91

11 ай бұрын

@@ejkozan yeah it's not an obvious one. I wouldn't have known about it if I hadn't demonstrated this to undergrads in organic labs countless times during my PhD.

@durshurrikun150

11 ай бұрын

Actually, the formation of 4 membered rings by enolate alkylation is kynetically disfavoured, 3 and 5 membered rings form much more easily

@durshurrikun150

11 ай бұрын

@@ejkozan If the haloalcane can't attack perpendiculary with respect to the enolate, then alkylation can't occur. You can easily make 3 and 5 membered rings with the enolates of malonic esters, but 4 and 6 membered rings form much more slowly

I had one of them and it’s harsh on the body. 10 hrs a day for 10 weeks.

The nitrate ion fucks off to form KNO3 😂😂

Good work. I normally would not suggest making your own medicine at home, however, it is well known that people that would otherwise be dying of cancer have the right to do almost whatever they want in their last days. Body hackers unite!

@ppunkk

11 ай бұрын

You will absolutely die if you make it and give yourself a shot. Chemo needs a lot of supportive medication to keep your body working while it’s being poisoned with the therapy (and it costs more than the therapy itself).

What happens to the nitrate ion?

3:18 Explosions&Fire has entered the chat.

Don't forget, they also have to get approval from the Government to sell. Even for generic drugs, that is quite expensive...

the algoritm sent me here. great vid. subscribed

You discover this compound or this exist before

I wonder if its possible to extract metallic platinum from cancer patient piss

Awwww 999 only shows up for us when we’re done a war. 🥰🥰🥰 On the element we studied in catalysis for our master thesis. #astrology #synchronicity #indigenous #2Spirit

Oh damn, I've been selling Pt compounds at waaaay too cheap of a price! Time to make chemo drugs for sale on the black market! 🤣🤫😉

@xydegek3121

11 ай бұрын

So we have come to a point where clandestine chemo therapy is offered. That episode from Vice will be epic. LOL

7:16 i dont know that doesnt look like an oxidation, thats a ligand replacing reaction

It became curious, but in this reaction, at the minute 6:20, does the oxidation state of platinum or nitrogen change? ... Or is it an exchange reaction?

@ianc8375

11 ай бұрын

Good question. The oxidation state of the platinum does not change. It's an exchange reaction driven by the high affinity of iodide for the silver (I) ion. Insoluble AgI precipitates out. It remains Pt(II) throughout the reaction.

@user-je3fx6li3w

11 ай бұрын

@@ianc8375 Thank you, I seem to understand. It looks like the resulting substance, including nitrogen, platinum and hydrogen, is essentially an acid.

@tschadschi1010

11 ай бұрын

0:34 isn't an oxidation either...

@user-je3fx6li3w

11 ай бұрын

@@tschadschi1010 Oh, how does it work at the level of physiology - is already too complicated for me ... I just would like to understand where in the reactions of salt, base and acid. These formulas of organometallic compounds are so bizarre and beautiful :) And it is not always clear at first glance which of them is who

I love the black mirror potential of this.

@leonardotrein1440

11 ай бұрын

i don't see the potential

@fahedsires

11 ай бұрын

@@leonardotrein1440 people cook cancer drugs instead of meth and other stuff. As the earth slowly becomes inhabited they’d do whatever to get a hold of a gram, scavenging the streets for what they can’t get a hold of behind glass. It turns out, the writers of our show also need to pull a script.

Have you taken into account that the supplier of the carboplatin manufacturer might not be selling the ingredients at retail price?