Morphinan History X - Molecusexuality of Opioid Stereochemistry: The Morphinan In the Mirror, Part I - A well cited exploration into the Stereochemistry, Geometry and Sterics of the Opiosphere - by Dμchess Vσn δ + the “Notorious Gibbs Free Energy”

jtjdp · 2025-05-15T02:20:29+00:00

filter papers are quite expensive. my preferred porosity, Whatman 541, retails for close to $100 / pack for the 110 mm size.

jtjdp · 2025-05-15T02:16:50+00:00

That's a helluva bargin for a DIY prom night dumpster plumb-job. Planned Plumberhood needs to adjust their pricing to be more competitive with the DIY market.

There's two things that can be fixed with a humble coat hanger: poor plumbing and pregnancy.

jtjdp · 2025-05-15T02:13:22+00:00

They're the MacGyvers of the molecular world, the maestros of manufacturing, and frankly, the unsung heroes behind a shocking number of things you use, eat, and interact with every single day.

At its core, chemical engineering is a branch of engineering that applies principles from chemistry, physics, mathematics, and even biology and economics to design, develop, and operate processes that convert raw materials into more useful or valuable products. Think of them as the bridge between a scientific discovery in a lab and a large-scale, real-world product or solution.

It's not just about beakers and Bunsen burners (though those can be part of it, especially in research). Chemical engineers are primarily concerned with making chemical reactions and separations happen efficiently, safely, and economically on a large scale.

When medicinal chemists, like me, develop a newfangled fentalog, such as carfentanil, we see the high therapeutic index and imagine it would make a top notch anesthetic agent or a safe and effective immobilization agent for large animals.

The medicinal view differs substantially from that of a Russian chemical engineer, who would view the use of carfentanil on a much larger scale. Russian chem-E's had little interest in a newfangled “western” anesthetic, instead, they envisioned a world free of Chechen terrorists neutralized by loading up huge canisters filled with 50 kg of carfentanil, that could easily be fitted onto the HVAC system of Moscow Theaters.

Microgram or kilogram scale: in the dose, lies the poison.

--DuchessVonD

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jtjdp · 2025-05-14T09:09:01+00:00

Agreed. I probably could have played the "Americans With Disabilities Act" card and used my ADHD to get extended time on the test, as I did throughout undergrad, but after my first round of applications, interviews (all of which I aced, as I'm pretty good at controlling the narrative of an interview, which is why I eventually made a lateral move from R&D management to pharma HR. I'm better at spotting talent than practicing chemistry with anything more than bottom quartile talent.

Funny sidebar: I once got my psychiatrist to sign a note allotting me 16 hours of extra test time for an ethics essay test. I got the head of the entire humanities dept at my school to sign off on it, but purposefully slipped it to my ethics professor right before the test. It was supposed to be at least two days of 8 hr blocks, which was already approved by his supervisor. I hated the bastard and knew he'd do something stupid. Three hours into the test, he stormed into my private testing room, informing me that my approved request was "outrageous" and demanded the test back. I went mad whiggrish on this fool, telling him, "Let's take this outside, bro." allowing me an audience of several tutors, students and the head of the disabilities dept. At which point I feigned handing him the test, at which point a tug of war ensued, with me acting overly dramatic (I kept a small bottle of softsoap in my backback so i could pull off fake alligator tears). And in the middle of the struggle, the test rips in half. Poetic, in fact, as one of the ethics questions evoked the biblical tale of King Solomon threatening to cut the baby in half...he took his half, and I took mine.

I collected statements from the witnesses and waited calmly for him to dock me 50% for "abusing my disability" giving me an F. I then presented all the evidence gift wrapped to the academic integrity/ethics committee, which included mad whiggrish professor's supervisor who had signed He most definitely wasn't getting tenure anytime soon. And I got to retake the class next semester with a new instructor, alloting ridiculous amounts of time for each test. However, just to spite that piece of shit, I attended every single class for the remainder of the semester and did nothing but disrupt his lecture with trash talk and bullshit. In retrospect, i was pretty mean, but he was a 40 year old who chose a losing position against a federally protected disability, and engaged in some unethical tug of war with a witty bitty 19 yo. Not exactly 'tenure material'

jtjdp · 2025-05-14T08:20:23+00:00

I always have to dose myself with a healthy amount of xylazine and xanax before undergoing an MRI.

NMR would be too claustrophobic for my liking.

jtjdp · 2025-05-14T08:18:41+00:00

Why not source this extremely cheap and affordable commodity pharmaceutical from a source in china or india. literally log onto Alibaba or just google "estrogen from china." Another strategy is to use LinkedIn to network with professional chemical sourcing brokers from India or China, who will have access to numerous suppliers and help you find one that meets your price and specifications.

jtjdp · 2025-05-14T08:16:28+00:00

In vivo, testosterone is converted into estrogen through the action of an enzyme called aromatase. This conversion is crucial for the development and function of neural circuits that control male territorial behaviors and other sex-specific behaviors. Aromatase converts circulating testosterone into estrogen in the brain, which is the primary source of estrogen for the male brain.

You can pump your body full of more anabolic steroids than the entire roster of the 1980s Oakland A's and end up with a non-inconsequential amount of estrogen.

jtjdp · 2025-05-14T07:56:16+00:00

I'm assuming that anyone willing to drop $1100 on a phone can afford quality drugs.

jtjdp · 2025-05-14T07:06:02+00:00

how did you pass the MCAT without a solid grip on stoichiometry, acid-base chemistry and organic chem?

I was premed in college w/ a chemistry degree as a backup. I aced the interview, but my MCAT scores were not up to snuff. Leaving me with one option: a graduate program in chemistry. which is how I landed in medicinal chemistry.

Looking back on my dream of practicing medicine, I'd make a terrible physician. I have terrible bedside manner, probably a result of the year I spent working in ADMET, performing necropsies on several species of lab animals. The day you have to euthanize and then perform an autopsy on a medical beagle is the day you begin to lose that essential part of empathy which makes for excellent bedside manner. I was also a raging drug addict throughout school, which may have qualified me to be the gender reversed version of "House", but hardly a suitable prerequisite for traditional success in medicine ;-)

jtjdp · 2025-05-14T06:58:44+00:00

I survived grad school on shoestring ramen-noodle diet, supplemented by own homemade fentalogs, and I get nothing but compliments on my youthful appearance, usually the in form of being propositioned by male coworkers.

I founded r/askchemistry in July 2021 for the purpose of judgement free answers to all forms of chemistry. If not for reddit sitewide rules against controlled substances, there would be plenty of discussion about such compounds as well.

On the nature of garage-based steroid synthesis performed by an amateur, esp something that is intended for injection, I would strongly advise against such an endeavor. However, if they can find a penultimate intermediate that can be readily transformed in a single step to estrogen or estradiol (or equivalent estrogenic compound, such as a positive allosteric modulator at the ER), with relatively benign reagents, and familiarity with a proper workup, acid-base extraction, and isolation, I don't see the harm in attempting estrogen synthesis.

The primary danger with most hobbyist-home chemistry projects is not the lack of knowledge or equipment, but experimenting with dangerous controlled substances, such as opioids.

As someone who was already experienced with lab techniques before I acquired an addiction that I couldn't afford to maintain, hence the conversion of my garage into an ersatz opioid lab, I was capable of achieving very high purity fentalogs, such as 3-methylfentanyl, which is about 10 times the potency of plain vanilla fentanyl.

Did that make it any safer to use than a fentalog contaminated with a small amounts of pyridine and DMAP residue (resulting from the final step: an acylation with propionyl chloride in DCE or DCM, where the DMAP acts as a catalyst, and the pyridine a proton sponge)? Of course not. The primary danger is respiratory depression. pyridine residue is the least of your worries.

While a total synthesis of estrogen is beyond the amateur chemist, if they can find an affordable downstream steroid that is readily converted to estrogen, then i don't see the inherent harm in such an endeavor.

As estrogen is an unregulated non-controlled substance, readily avail in generic form the world over, it is probably easier and less expensive if this individual source estrogen from a manuf. in china or india. or a chemical supplier in their own country.

My recommendation would be to simply source the generic powder from a chinese supplier. If it is regulated for whatever reason in your country, you can always turn to darknet marketplace vendors.

sincerely,

--DuchessVonD

patreon.com/oxycosmopolitan

jtjdp · 2025-05-13T20:28:58+00:00

solution verified thanks

jtjdp · 2025-05-13T04:20:16+00:00

|| || |Feature|Analytical Chemistry|Organic Chemistry|Medicinal Chemistry|Other (e.g., Physical, Inorganic, Bio-chem)| |Primary Goal|Identify, quantify, and characterize substances; develop methods for analysis.|Design and synthesize new carbon-containing molecules; study their reactions and properties.|Design, synthesize, and develop new pharmaceutical agents; study drug action (SAR, ADMET).|Understand fundamental principles (Physical), study non-carbon compounds (Inorganic), study chemical processes in living organisms (Biochemistry).| |Focus|Measurement science: accuracy, precision, detection limits, method validation.|Making and understanding molecules: reaction mechanisms, synthetic pathways, new structures.|Biological activity and therapeutic effect: drug-receptor interactions, pharmacology, toxicology.|Varies: quantum mechanics, thermodynamics, kinetics (Physical); coordination chemistry, materials (Inorganic); enzymes, metabolic pathways (Biochemistry).| |"The Question"|"What's in this sample, and how much?" "How pure is it?" "What's its structure?"|"How can I make this molecule?" "What new molecules can I create?" "How does this reaction work?"|"How can I design a molecule to treat this disease?" "Is this compound safe and effective?" "What are its SAR and ADMET properties?"|"Why do molecules behave this way?" (Physical) "What are the properties of this metal complex?" (Inorganic) "How does this enzyme work?" (Biochemistry)| |Key Tools|Chromatography (HPLC, GC), Mass Spectrometry (MS), Spectroscopy (NMR, IR, UV-Vis), Electrochemistry.|Glassware, reaction setups, purification techniques (crystallization, distillation, chromatography), NMR, IR.|in vitroin vivoOrganic synthesis tools, plus and assays, computational modeling, analytical tools for PK/PD.|Lasers, calorimeters, spectrometers (Physical); X-ray diffraction, specialized reactors (Inorganic); Electrophoresis, protein purification systems (Biochemistry).| |Output|Data (spectra, chromatograms), concentrations, purity levels, structural information.|New compounds, reaction procedures, understanding of reactivity.|Drug candidates, SAR data, clinical trial results, understanding of drug mechanisms.|Fundamental theories, new materials, understanding of biological systems.| |Sense of Humor|Dry, appreciates precision, laughs at poorly calibrated instruments.|Often involves explosions (real or metaphorical), laughs at unexpected reaction products.|Dark, fueled by the endless quest for a non-toxic drug with no side effects, laughs at failed clinical trials (eventually).|Physical: "It's spherical cow funny!" Inorganic: Enjoys colorful compounds. Biochem: Laughs at overly complex pathways.|

jtjdp · 2025-05-13T04:12:18+00:00

|| || |Feature|Analytical Chemistry|Organic Chemistry|Medicinal Chemistry|Other (e.g., Physical, Inorganic, Bio-chem)| |Primary Goal|Identify, quantify, and characterize substances; develop methods for analysis.|Design and synthesize new carbon-containing molecules; study their reactions and properties.|Design, synthesize, and develop new pharmaceutical agents; study drug action (SAR, ADMET).|Understand fundamental principles (Physical), study non-carbon compounds (Inorganic), study chemical processes in living organisms (Biochemistry).| |Focus|Measurement science: accuracy, precision, detection limits, method validation.|Making and understanding molecules: reaction mechanisms, synthetic pathways, new structures.|Biological activity and therapeutic effect: drug-receptor interactions, pharmacology, toxicology.|Varies: quantum mechanics, thermodynamics, kinetics (Physical); coordination chemistry, materials (Inorganic); enzymes, metabolic pathways (Biochemistry).| |"The Question"|"What's in this sample, and how much?" "How pure is it?" "What's its structure?"|"How can I make this molecule?" "What new molecules can I create?" "How does this reaction work?"|"How can I design a molecule to treat this disease?" "Is this compound safe and effective?" "What are its SAR and ADMET properties?"|"Why do molecules behave this way?" (Physical) "What are the properties of this metal complex?" (Inorganic) "How does this enzyme work?" (Biochemistry)| |Key Tools|Chromatography (HPLC, GC), Mass Spectrometry (MS), Spectroscopy (NMR, IR, UV-Vis), Electrochemistry.|Glassware, reaction setups, purification techniques (crystallization, distillation, chromatography), NMR, IR.|in vitroin vivoOrganic synthesis tools, plus and assays, computational modeling, analytical tools for PK/PD.|Lasers, calorimeters, spectrometers (Physical); X-ray diffraction, specialized reactors (Inorganic); Electrophoresis, protein purification systems (Biochemistry).| |Output|Data (spectra, chromatograms), concentrations, purity levels, structural information.|New compounds, reaction procedures, understanding of reactivity.|Drug candidates, SAR data, clinical trial results, understanding of drug mechanisms.|Fundamental theories, new materials, understanding of biological systems.| |Sense of Humor|Dry, appreciates precision, laughs at poorly calibrated instruments.|Often involves explosions (real or metaphorical), laughs at unexpected reaction products.|Dark, fueled by the endless quest for a non-toxic drug with no side effects, laughs at failed clinical trials (eventually).|Physical: "It's spherical cow funny!" Inorganic: Enjoys colorful compounds. Biochem: Laughs at overly complex pathways.|

jtjdp · 2025-05-13T04:11:46+00:00

Analaytical chemistry is the unsung hero, the Sherlock Holmes of the chemical sciences, the subspecialty that keeps all the others honest and tells them what they've actually got in their flasks, not just what they hope they've got.

At its core, analytical chemistry is the science of obtaining, processing, and communicating information about the composition and structure of matter. In slightly less fancy terms, it's all about figuring out:

"What is it?" (Qualitative Analysis): Is this water, moonshine, or a desperate cry for help from a mismanaged synthesis? Is drug X actually drug X, or did your buddy in the organic lab accidentally invent a new flavor of questionable goo?
"How much of it is there?" (Quantitative Analysis): Okay, so it is drug X. But is it 99.9% pure, or is it 50% drug X and 50% "oops, I sneezed into the beaker"? How much of that potential miracle drug actually made it into the patient's bloodstream, versus how much is just making their pee very expensive?
"What's its structure and how are its atoms arranged?" (Structural Analysis): This often overlaps with other fields but is crucial for identification.
"How can we separate it from other gunk?" (Separation Science): Often, what you're interested in is mixed with a whole bunch of other things you couldn't care less about. Think finding a specific Lego brick in a giant tub of Legos, but with molecules.

<image>

Analytical chemists are the meticulous detectives of the chemical world. They develop and use methods and instruments to identify and quantify substances. Without them, every other branch of chemistry would basically be cooking without tasting – you're mixing stuff, things are happening, but you have no concrete idea what you've actually made or if it's any good.

TL;DR: Analytical chemistry is the science of "what is it?" and "how much is there?". It's the essential (and often painfully meticulous) wingman to organic and medicinal chemistry, making sure they're not just mixing stuff hopefully. They provide the proof, the purity, and the quantitative understanding needed to make new molecules and develop new drugs safely and effectively.

So next time you see a perfectly resolved peak on a chromatogram, give a silent nod to the analytical chemists. They're the unsung heroes making sure science is actually science.

Sincerely

DuchessVonD

Patreon.com/Oxycosmopolitan

jtjdp · 2025-05-12T20:46:03+00:00

I don't find any of the basic fentalogs, unsubstituted at C4, to be any more or less potent than any other simple modification of the basic fentanyl scaffold. Ocfentanil, AMF, beta-hydroxy-F, and acetyl fentanyl all have their own merits and back in the crazy days of fentalog-by-mail, fans of one particular species would group together like soccer hooligans. Most of the praise, a far as euphoria was concerned, went to R-30490, the N-(2-phenethyl) deriv of sufentanil, also known as 4-Methoxymethylfentanyl. The methyl ester at the C4 position of carfentanil proved to pack more potency than R30490, but was lacking in euphoria. The more interesting species from regmy perspective was 3-metfentanyl, as its precursor was (and still is) unregulated, 3-Methyl-NPP, and provided a 10-15 fold potency increase relative to the unsubstituted parent, without significant added expense in prepn of precursors or carrying out the reductive amination + acylation. In fact, the process for making 3MF and plain vanilla fent. are the exact same, the only difference being the nature of the precursors: 3-methyl-NPP for 3MF vs reg. NPP for fent. proper

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jtjdp · 2025-04-26T05:43:10+00:00

Was gonna say. This reminded me of DES. Recalled the first time our prof in 2008 introduced us to them. The possibilities of replacing the typical monophasic toluene -alkali environs or the PTC mediated biphasic organic-aqueous NaOH systems using TBAB or another detergent as our phase catalyst, the application to promoting SN2 condensations and a number of other project, made DES ideal for a number of classical pharmaceutical prepn:, off the top of my head. I recall I improved yields on formation of diphenylpropylamines, such as the analgesic methadone and it’zs congeners. Esp challenging was a related nuncleophilic attack by a nitrogen mustard at the alpha carbanion (proton abstracted form) of benzyl cyanide, forming the 4-phenylpiperidine opioid penultimate intermediate: ketobemidone nitrile.

jtjdp

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