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Temozolomide Is Explosive
- microtherion 5y agoSomewhat surprisingly, this was NOT filed under "Stuff I Won't Work With"
- _Microft 5y agoIf you had told me that the article was by Derek Lowe and that there are a number of nitrogen atoms involved, I would have indeed (wrongly) guessed that it were Things I Won’t Work With, that the compound had been created by the Klapötke group at Munich University and that it would go boom ;) Well, not quite. This time at least.
- wolfgang42 5y agoSounds like it got off on a technicality: > I have personally worked with compounds that are this hazardous, but at least I knew up front that they were!
- fabian2k 5y agoThe stuff in that series is generally much more dangerous or unusual in handling than this one.
- ufmace 5y agoIt sounds like this stuff is only mildly dangerous and easy to keep safe with if you know what you're doing. Considering that it's been used as a chemotherapy drug for years, it'd be surprising if it wasn't. Most of the "Stuff I Won't Work With" is fantastically dangerous even when you know exactly what you're dealing with and take all of the right precautions.
- ashtonkem 5y agoIt seems like the hazardous bit is more the fact that this stuff is extremely toxic.
- andreareina 5y agoHe's a drug discovery chemist so explosiveness notwithstanding it's right up his alley.
- ashtonkem 5y agoHe’s a research pharmaceutical chemist, this particular compound more likely to end up under the category of “things I will have to work with”.
- mnw21cam 5y agoThere's quite a stark difference between "it might go bang if you abuse it" and Chlorine Trifluoride (sand won't save you this time) https://blogs.sciencemag.org/pipeline/archives/2008/02/26/sand_wont_save_you_this_time https://blogs.sciencemag.org/pipeline/archives/2008/02/26/sa...
- azinman2 5y agoChemotherapy is basically cave man medicine. That a therapeutic drug is explosive only adds to that sentiment. The idea that we'll basically poison you just up to a point that's nearly fatal in order to kill the cancer is such a terrible way to treat someone. Now I'm not saying don't ever do it -- unfortunately that's where we're at in 2021. It's just kind of unbelievable that cancer remains so elusive that we're still using medical treatments that started from mustard gas usage during world wars, when we're so advanced technologically in so many other ways. Interestingly, cancers for children are largely successfully treated. I was at a fancy conference a few years ago where some cancer researchers were socializing over wine, and I asked them why that was versus adults. They said the difference was that parents are willing to do almost anything (aka enroll their kids in experimental treatments) to cure their kids, but adults aren't quite so willing for themselves. Thus the rate of experimentation was just so much higher for children to the point where it's often curable. Perhaps one day we'll be able to simulate the body well enough to the point where we can brute force treatments computationally to fix this gap.
- fabian2k 5y agoMany of the modern treatments are much more targeted, any antibody-based treatment is by nature extremely specific. But then you also have the problem that cancer isn't a single, unified disease, so a very targeted approach doesn't work for every cancer.
- vibrio 5y agoI agree with your wine-drinking physicians on clinical trial participation, and your question on how to improve broader participation. I also believe that there are fundamental difference in cancers that arrive in a young person versus cancers that have slowly evolved in the patients bodies, perhaps over a decade or more-the latter are likely much more stubborn.
- robbiep 5y agoThe cancers that are treated successfully in children are the blood borne ones (mostly leukemias) and generally because they’re easier to wipe out and replace the marrow with. Some Childhood brain tumours are also very successfully treated, and most other adult cancers children don’t get. Sarcomas still kill people left right and centre though. The truth is that we’re already peeking out of the dark ages of chemotherapy. Immunothérapies have revolutionised the field and new stuff coming online is incredible. When I started medical school 11 years ago the 5 year survival of metastatic melanoma was close to 0%. It’s now close to the population average (well, not really, but it’s greater than 50%). Records are being smashed
- dylan604 5y ago"What they found was rapid onset of decomposition at 170 degrees" So this seems to be more about people in a lab situation rather than it being so unstable it reacting sitting in someone's hot car. Suspecting it to react at 212 and finding it reacting at 170 could ruin a lab tech's day to be sure. Those are the jobs that sound fun "for the science" lets see what happens when...
- munificent 5y agoI think you're overlooking the most important scenario: mass production of it in a factory setting.
- ISL 5y agoAnd just handling/storage. Things that are flammable or explosive have more-stringent requirements. A familiar example: one should take much greater care when storing rubbing alcohol (or Bacardi 151 or vodka) than wine. One will magnify a house-fire. The other will help to douse a flame.
- laurent92 5y agoAt every people’s house, I see a cupboard with the chemicals. WD-40, 90° alcohol, acetone, white spirit, all in the same IKEA (=plywood) cupboard (although it would be hard to protect children if they were each in a different cupboard too). I wonder how many fires start from the chemicals cupboard. We know that a lot of artists had their rag pile spontaneously heating up then catching fire…
- throwawayboise 5y agoThose things are fine in their separate containers. They will not spontaneously combust. If the containers are leaking, or fire starts elsewhere, yeah they could become fuel. But really no more than any other hydrocarbons in your house (e.g. wood, plastic, cloth, upholstrey and foam cushions, etc.)
- meepmorp 5y agoIs it all that surprising though, considering how much nitrogen is stuffed into that molecule?
- rbanffy 5y agoJust by looking at it I get the impression every part of the molecule has a deep hatred for every other part.
- lmilcin 5y agoI mean, seriously, just look at the molecule. All those nitrogen atoms lying there restless to each go their own separate way:) I would be surprised if it wasn't.
- throwaway0a5e 5y agoAt a bare minimum it'd probably be a damn good oxidizer at which point you're 80% of the way to a good explosive.
- deleted 5y ago[deleted]
- mabbo 5y agoAs someone who dropped chemistry in grade 11- what makes Nitrogen so exciting like that? So many common explosive compounds seem to have it.
- Thorondor 5y agoWhen nitrogen compounds combust, they tend to produce nitrogen gas (N2). Since nitrogen molecules contain a very strong nitrogen-nitrogen triple bond, a lot of energy is released when they form.
- G3rn0ti 5y agoNitrogen-Nitrogen bonds inside larger molecules are never quite stable because 1) nitrogen “wants” to form stable di-nitrogen (N2) molecules containing a very stable triple bond (an exothermic reaction) and 2) the result of such decompositions is nitrogen gas increasing the amount of entropy released (due to more molecules being created). Reactions are driven both by the amount of heat released (enthalpy) and the amount of “disorder” created (entropy). Explosive reactions tend to be the ones where both factors add to the driving force.
- morpheuskafka 5y agoDoes the same apply to oxygen? Since it also likes to be in a diatomic form.
- ashtonkem 5y agoKind of surprising nobody thought to check until now. Even as a non chemist (albeit a regular reader of Derek Lowe), I look at that and say “boy is that a lot of nitrogens, I wonder if they’re itching to become an expanding cloud of hot nitrogen gas and broken lab equipment”.
- languagehacker 5y agoReminds me of how DNP, a chemical used for creating explosives, has been used as a weight-loss drug. It's surprisingly effective, but overdosing on it will result in a long, hot, agonizing death.
- southeastern 5y agoDNP was banned after causing a lot of deaths. Still a fascinating drug, I don't remember exactly how it worked but it disrupted respiration so that less ATP was produced from electrons while their energy instead was 'spent' increasing heat
- bserge 5y agoSo has Clenbuterol (pure stimulant), Sibutramine (an ADHD medication way before its time, marketed as a weight loss drug by some idiot marketers), and many others. Really should stop banning drugs because a few morons overdosed on them. I mean, no one has banned stairs yet. They tried to ban alcohol, but the conviction turned out paper thin. I guess it is easier to ban something that only benefits a sad small minority. Bonus evil points when the rich can get the drug regardless.
- G3rn0ti 5y agoThe fundamental reason why 2,4-Dinitrophenol (DNP) burns fat is surprisingly complicated. Basically, it intoxicates mitochondria in your cells being their power houses. These organelles create ATP, a universal metabolic energy carrier, by maintaining a proton gradient across its membrane. By means of chemical osmosis this gradient is what drives the ATP synthase enzyme under normal conditions. Now, DNP is capable of shuttling protons along the gradient and short-circuits this process catalyzing the conversion of fatty acids into worthless heat. Interestingly, babies use a controlled variant of this mechanism to help maintain their body temperature thanks to their brown fat tissue. It makes babies look cute and keep warm. :)
- jcims 5y agoThis is an animation and cursory explanation of ATP synthesis, with suitably dramatic music: https://www.youtube.com/watch?v=OT5AXGS1aL8 https://www.youtube.com/watch?v=OT5AXGS1aL8 This animation and associated narration is much more detailed, but a bit slow for something you haven't vetted your interest in yet :) https://www.youtube.com/watch?v=kXpzp4RDGJI https://www.youtube.com/watch?v=kXpzp4RDGJI
- mcguire 5y ago"You could say that TMZ is a prodrug for a prodrug for methyldiazonium, which is never going to be a drug that can just be administered by itself. ... temozolimide is genotoxic and tetratogenic, so it has to be handled carefully, but honestly, anything that generates a small diazonium compound so readily is going to be similarly hazardous. ... Indeed, drop-hammer tests showed that these TMZ samples decompose suddenly with smoke on impact." So, uh, what are the explosive decomposition products?
- wydfre 5y agoWell, the government is working on ways to deal with cancer[0]. [0]: https://www.irishtimes.com/news/voices-told-woman-she-had-brain-tumour-1.138853 https://www.irishtimes.com/news/voices-told-woman-she-had-br...
- olliej 5y agoI mean in fairness we still use nitroglycerine for some heart ailments, so chemo - a field filled with horrific chemicals - having an explosive shouldn't be too surprising.
- wolfgang42 5y agoThe surprising part is that it’s been around since the 1970s and someone has only just gotten around to discovering this.
- userbinator 5y agoIts dosage as a drug is in the milligrams range, and in that form it will be combined with many times more inert filler material, so I suspect it could simply be because a sufficiently large amount of it has never been subjected to enough energy to produce an actual explosion. The discovery is the opposite of nitroglycerin, whose explosive properties (and the production of massive amounts) were discovered before its medicinal ones.
- gpvos 5y agoFor those who don't know yet, Derek Lowe's series "Things I won't work with" is very fun to read, and also educational. https://blogs.sciencemag.org/pipeline/archives/category/things-i-wont-work-with https://blogs.sciencemag.org/pipeline/archives/category/thin...
- mech422 5y agoDerek's stuff is awesome in general... "Things.." is really funny, but I find his columns about the inner workings of pharma companies to be really interesting as well.
- dvirsky 5y agoThat would have been a perfect device plot for Breaking Bad.
- rbanffy 5y agoEither that of it’d be an origin story for a superhero who can trigger explosions.
- tyingq 5y agoMaybe helpful to note that the phrase "Class 1 Explosive" isn't denoting a certain type, or power of "Explosive". "Class 1" in Hazmat is all explosives. Class 2 is Gases. Class 3 is Flammable or Combustible liquid, and so on.
- code_duck 5y agoSo a liquor cabinet is full of Class 3 explosives.
- Arrath 5y agoFair point. The sub-classification gets into those weeds. For example: 1.1 being "mass explosion hazard", typically high-explosives. 1.4 being "fire or projection hazard", typically consumer fireworks, small arms ammunition. 1.5 is "may mass explode in fire", things like AN fertilizer (Beirut; West, Texas), many industrial blasting agents.
- rob74 5y agoWhere would flour fit in in this classification? I assume it's less explosive than fertilizer, but flour dust suspended in air can also explode...
- Arrath 5y agoWell now, that is an interesting question. According to some research, combustible dust is not an explicit category under the GHS (United Nations Globally Harmonized System of Classification and Labeling of Chemicals), let alone a sub-division of Class 1. I pulled up some Safety Data Sheets[1] for various flours and Combustible Dust is listed under "Hazards Not Otherwise Classified" in section 2, Hazard Identification. Likewise, section 5 (Fire-Fighting Measures) mentions the explosion hazard posed by dispersed dust. Per Chapter 2.1[2] of the GHS, the definitions of explosives is: "...a solid or liquid substance (or mixture of substances) which is in itself capable by chemical reaction of producing gas at such a temperature and pressure and at such a speed as to cause damage to the surroundings..." Which led me down a rabbit hole to see why Combustible Dust is listed as "Not Otherwise Classified", going through amendments to the CFR and some papers on working groups looking to add Combustible Dust to the GHS. Of note, page 16 of this[3] presentation. >"Argentina Intervention > Concern over the definition of "combustible dust" produced by flours, grains and cereals because of the trade implications that such an inclusion could produce > Dust originated from flours, grains and cereals should not be classified as "hazardous chemical substances" > Reasoning: >> Flours, grain and cereal dust are not a chemical substance >> Dust originated from flour, grain and cereal have no intrinsic explosive property >> Dust is not a dangerous substance in itself > Requested explicit exclusion from definition" Luckily saner minds prevailed, and we ended up with GHS Annex 11 which is why Combustible Dust is listed on the SDS I linked. But hey there we see, once again, economic interests trying to muddy up the waters when it comes to safety. But that is a whole different (and rant-y) tangent I could go off on, and I should probably get back to work. [1]http://s3.amazonaws.com/media.agricharts.com/sites/1846/Flour/SDS%20All%20Purpose%20Wheat%20Flour%20CO-EHS-1512-03.pdf http://s3.amazonaws.com/media.agricharts.com/sites/1846/Flou... [2]https://unece.org/DAM/trans/danger/publi/ghs/ghs_rev03/English/02e_part2.pdf https://unece.org/DAM/trans/danger/publi/ghs/ghs_rev03/Engli... [3]https://schc.memberclicks.net/assets/meetings/fall_2017/lantry-miller_powerpoint.pdf https://schc.memberclicks.net/assets/meetings/fall_2017/lant...
- thewakalix 5y ago> tetratogenic That’s like a teratogen, but four times as bad!
- gus_massa 5y agoYep, it looks like a typo. Perhaps you can add a comment there or send an email (it's available under his photo).
- tyingq 5y agoFound the safety sheet for TMZ: https://www.merck.com/docs/product/safety-data-sheets/hh-sds/Temozolomide%20Formulation_HH_MX_EN.pdf https://www.merck.com/docs/product/safety-data-sheets/hh-sds... Nothing about explosions other than dust explosion warnings, but this one is kind of amusing: "H351 Suspected of causing cancer"
- cowboysauce 5y agoA lot of chemotherapy agents works by causing DNA damage and are therefore carcinogenic themselves.
- cratermoon 5y agoAs one comment there notes, just looking at all the Ns lined up ought to cause concern, at least for anyone that has read this authors "things I won't work with" series.
- aazaa 5y agoThe chemical structure is the clue to the explosive potential. The N-N-N triad is a strange beast that shows up in a lot of explosive materials. They're explosive for similar reasons that ammonia nitrate is explosive. https://www.newscientist.com/article/dn23399-texas-disaster-what-links-fertilisers-and-explosions/ https://www.newscientist.com/article/dn23399-texas-disaster-... Think of energy as a vertical scale increasing upward. Including a nitrogen triad (like in the drug) pushes the entire molecule up on the energy scale. It's like riding the elevator to the 42nd floor. In contrast, the N-N triple bond (i.e., atmospheric nitrogen) is way down at the ground floor. This is one reason that despite nitrogen being the most abundant gas in the earth's atmosphere, it requires large amounts of energy to process into fertilizers and other materials. CO2 and H2O also sit near ground level. So there's a large energy difference between the drug and the combustion products N2, CO2, and H2O. All it takes to release all of that stored energy is a trigger. For example, if someone were to push you off the top of the building, you would spontaneously release the stored energy. Hopefully you'd be equipped with an air braking device to dissipate it gradually, but if not - well, that energy will be released into your body and the pavement all at once.
- jsbdk 5y ago>The chemical structure is the clue to the explosive potential. The N-N-N triad is a strange beast that shows up in a lot of explosive materials. This makes me wonder - what properties of a substance can you infer from its structure without ever testing the substance itself?
- rcxdude 5y agoA chemist can usually make an educated guess on most of them based on similarity to other substances, but it's hard to be very accurate and there's still a lot of potential for surprises.
- aazaa 5y agoThere are many. A simple example is solubility. Molecules with amines generally are soluble in acid. Molecules with carboxylic acid groups are usually soluble in base. Molecules with flexible hydrocarbon chains tend to be soluble in oils. Molecules with lots of polar groups tend to be soluble in water. Large, rigid molecules are rarely soluble in anything. Trained chemists can do this sort of thing with specialized properties (such as metabolic stability, brain penetrating ability, and oral bioavailability) as well, although success depends on specifics.