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Med-Chem Labs: What’s Changed?

Traveling today, so not much time for a full-scale post. But I wanted to toss out a question to my fellow medicinal chemists instead. I was talking with some colleagues the other day, including a couple of people who’d been around for a while, and we were discussing what things med-chemists used to spend more time on versus what they do now. It’s a lot easier for people with longer histories, which means the people with longer histories than mine can outdo my stories pretty easily as well. In my own case, running chromatography columns more-or-less by hand used to take up a real percentage of my lab time, virtually all of which has been freed up over the years by automated systems. Running TLC plates (analytical ones) was a constant feature of organic synthesis, now (and for some time) largely wiped out by walkup LC/MS machines.

These are well-known changes. But another hit me the other day: I used to move around a lot more four-liter solvent jugs. Hexane, ethyl acetate, dichloromethane – I’ve pulled a lot of brown glass out of the cabinets under my hood over the years, and poured a lot of solvent out of those jugs into columns, Erlenmeyers, and sep funnels. But the last two buildings I’ve worked in have had solvent distribution plumbing, so all of these (and more) are on tap. If you’d shown such a system to me in graduate school, I’d have watched in disbelief at the thought of such luxury (although the automated chromatography, and especially the disposable pre-packed columns that come with it, would have staggered me even more). But I had barely noticed the passing (for the most part) of solvent jugs from my lab life until a couple of days ago.

So let’s here from people who’ve been at it for all lengths of time – what’s changed for you? Maybe a few more things than you’ve noticed!

 

87 comments on “Med-Chem Labs: What’s Changed?”

  1. Bob Seevers says:

    I used rub-on chemical structures (available from Aldrich) to create the steroids in my thesis. Because I was doing radioiodination, I quickly ran out of Is and had to resort to slicing the legs of of Hs to make up the difference. Now, you can draw anything you want with a variety of programs.

    1. Some idiot says:

      Oh yes, I remember those… they were the upmarket versions when they came out…! I used a large fairly wide plastic stencil with a rotoring pen to draw the structures. I think I still have it somewhere… But that was well over 30 years ago, and well before Chemdraw…

  2. Jb says:

    Flow reactor hydrogenations under very high pressure using prepacked catalyst columns rather than baloons and/or those old school hydrogenators that shake. The H cube is pretty awesome. Just pop in your material, flow it through, and collect the product.

    1. Derek Lowe says:

      Yeah, the Parr hydrogenator has had a long run, but it’s definitely heading over the horizon. Still a lot of them around, though.

      1. Tim says:

        I had to do a hydrogenation in my PhD (only about 4 years ago), and regular balloon as well as using an H-cube didn’t work well, over all the catalysts I had at my disposal. I ended up dusting off an old Parr that was probably not touched for several years, and it ended up being a crucial instrument for me (clean quantitative conversion with palladium on carbon). I tried again later in a “bomb” reactor which was not as good. So there’s still something to say for the old pieces, not sure why that particular instrument worked so well.

  3. John Wayne says:

    1. There are now very few silicon oil baths for heating. The solid (often aluminum) blocks you can get now do a great job, and are much safer and cleaner.

    2. Rotovap pumps are now awesome. I’ve gone from water aspirated rotovaps to the first model Buchi pumps (which were terrible but better than water); now the pumps are so quiet and do such a good job you can both walk away from it and forget that is it running.

    3. The fraction collectors on the new purification systems are fantastic; I had an optical-eye based collector at my first job that was marginally better than collecting by hand. You had to keep some attention on it at all times because it made so many mistakes (always on the fractions you wanted).

    4. Has anybody seen a chromatotron recently? They were great for purifying fairly polar compounds, but have been usurped by walk up prep systems.

    5. Glass syringes. Every had a huge number of sets and had trouble matching the plungers to the bases. Now everybody uses prepackaged sterile syringes for all but the most sensitive and dangerous reagents and reactions.

    6. Washing glassware yourself. Most of us now use disposable vials for reactions; us old timers used to wash everything by hand, sometimes with the use of a base bath, every day.

    I’d like to take a moment to get on a soapbox about IR spectroscopy. People should use it more than they do. You won’t do it every week, but ten minutes at the IR can save a day at the NMR. It has fallen out of our lexicon, which is unfortunate.

    1. AQR says:

      We must be of the same vintage. Probably the biggest improvement for me has been the ease of doing electronic searches of the literature and getting immediate access to the pdfs. I remember the bad old days of pulling those 6 inch thick bound volumes of the Chem Abstract Cumulative Indices and searching for a compound of interest by its chemical name. Substructure searches were impossible.

      1. John Wayne says:

        Ah, printed CA. I remember you well. I was in the stacks for so long one afternoon I totally lost track of time. When I came out of the basement it was dark outside and everybody was gone. Searching through collected volumes one at a time took forever.

    2. Derek Lowe says:

      You’re right about the disposable vials – I do far, far fewer reactions in RB flasks than I used to, since a 20mL vial works just fine. The demise of oil baths has been hastened by safety departments, but I will admit that I never liked the mess. The generation before me swore by them, though, for temperature control, but heathen that I am, I never noticed much difference.

      1. BK says:

        Derek,

        I was working at a CRO about 1-1.5 years ago. A new employee caught an oil bath on fire because they decided to reflux something without a water condenser and without N2. I was astonished. Additionally, that person used to bleach the ENTIRE lab after they did cyanation reactions…. I’m talking floors, walls, and any part of the ceiling he could reach.

    3. Anon says:

      For the first time I’m feeling old. The chromatotron was such an advance over prep TLC that I bought one of the first. Soon every one in the building was using them.

      1. Some idiot says:

        And really fun making the plates, too!!! 🙂 And unlike prep TLC (which is/was awesome for getting very pure samples of small amounts of materials) the plates were reusable… 🙂

    4. Some idiot says:

      I’ll back you up on the IR. I am also guilty here, but I have a fantastic (old) book which is a fantastic reference for subtle variations in IR bands with structure. I bought it at a second-hand book market, and it made my jaw drop seeing what could be done…!

      1. Jeff says:

        Care to name said book? I teach structure determination and would love to know more about these subtle variations in IR. Your comment confirms my feeling that IR is still a wickedly powerful technique but much of the more subtle aspects of it have been lost to ravages of time.

    5. Stan says:

      I spent nearly 2 years at HLR at Nutley (1992-3) and brought back many improvements to my lab expertise. Chromatotron was one of them. I bought one immediately after my return to the Czech Republic. However, it has been resting for years under the hood.

  4. Some Dude says:

    At least you did not have to learn German for the Beilstein.

    1. Derek Lowe says:

      I did have to take a German proficiency exam, which fortunately was pretty weak.
      http://blogs.sciencemag.org/pipeline/archives/2006/10/15/german_anyone

      1. oldnuke says:

        Ugh. Four years of German in middle and high school (after two of Latin), then two more years of German in college (you had to take two years of a foreign language, German or Russian, regardless of your high school courses!).

        The one time I did a translation from Beilstein, I destroyed the window in my fume hood. Thankfully my advisor’s German wasn’t any better than mine — he checked before I ran the synthesis.

        My first do-it-yourself project my freshman year was making spiral glass columns and packing them with silica by hand. Fortunately, I had learned how to do some pretty good glassblowing in my home lab, so my advisor was pretty amazed when I sat down and blew a spiral column on the first try. The bad news is that word got around and people drove me crazy making columns for our F&M gas chromatograph. Then there was the d–n purple ink in the chart recorders…

        1. Nick K says:

          Ah, chart recorders! Thank God they’ve gone. I hated the never-dry ink, which would smudge at the slightest touch.

          Another thing I don’t miss: mass spec recorded on strips of photographic film. One had to count the m/e manually, and, within a few minutes in sunlight, the film was completely fogged.

          1. Kevin says:

            Chart recorders aren’t completely gone. We’ve got one chugging away in our lab. (Hooray for academia and its packrats.) When you just want to know if you’ve got one peak or not….

            The PI bought a couple of boxes full of tractor feed chart paper rolls from eBay a few years ago. He figures that when he runs out of chart paper it will be time to retire.

    2. Some idiot says:

      I did… a reading course in scientific German was part of honours organic chemistry in my day (probably showing my cobwebs a bit…). But we _did_ learn how both Beilstein and CA actually worked… I remember the hours of trying to hunt down a reference…! 🙂

    3. b says:

      On a related note… Google Translate for procedures in German. It does a good enough job to where you can fill in the rest with recognizable chemistry terms and separating compound words.

  5. Mister B. says:

    I am certainly less experienced than many of you ! But I have been through old-fasion labs, in which solvents purification by distillation are still running in every corner.
    Now, more and more have these resin-based columns, that give nicely dried solvent, with much less risks for the users ! These machines are still quite expensive and to me, columns are not very efficient for a long time, but it’s so easy to use !

    I must admit too, that I kept my benzophenone – sodium mixture when I need THF ! (On a small-scale, indeed)

    Note: We’ve been down to 17 ppm water in THF, DMF and acetonitrile, with our in-house drying machine !

  6. Chrispy says:

    One old school thing I miss is recrystallization. There was something so wonderful about scratching on the side of your flask of murky solvent with a spatula and having crystals burst forth.

    1. John Wayne says:

      – I haven’t seen a steam heater in a while. Hoods used to be plumbed with steam, which was pumped into a sort of heating block. The top line was steam, water came out the bottom into your cup sink (also gone), and you put the thing you wanted to heat (often a recrystallization) on the top. You could change the size of the aperture by adding or removing some nested metal rings. Worked great.

      – Pulling pipettes. It has a been a while since I’ve done this.

      – Most of my terrifying stories from grad school have to do with stills, so it is probably good that they are mostly gone. There are times when you do need to use really distilled solvents, so it is good to keep the technique in mind.

      1. Some idiot says:

        We had steam piped around the lab, and virtually everyone had a steam can on their bench. Always entertaining to see someone start one up when the plumbing was the wrong way around… 🙂

    2. Nick K says:

      I can assure you that recrystallization is alive and well in Process Chem and contract synthesis labs. A large-scale recryst is one of the most satisfying and enjoyable jobs in Chemistry.

  7. Uncle Al says:

    What would you do if you could do anything given ease of process? You would do as you were told, for oversight has benefited from like enhancements. “Who borrowed the flask?” No! “Who embezzled laboratory funding?” Add overhead cameras and personal RFID chips, then behold the spreadsheet, PowerPoint deck, and HR-narrated video of your potty trips.

    “The R&D Function.” Harvard Business Review 61(6) 195 (1983). I did not like it then, or now,
    https://strikemag.org/bullshit-jobs/

    http://brightspec.com/
    … OTOH, near all the science fiction analytical equipment is threatened by one sample port requiring no sample prep, no consummables, and no waste can (and no cluster of defatted chicken bones hanging from a string nailed into the ceiling above the HPLC),

  8. Magrinho says:

    A list of things that I am happy to see disappear:
    Steam lines that just spewed hot, dirty water
    Cracked and dirty NaCl plates for an IR machine with a burned out bulb
    Sludge-filled THF still that it was my turn to clean (I once saw flames come up three sink drains simultaneously). But, hey, nothing quenches organometallics quite like water.
    Completely disintegrated caps on vintage SOCl2 and POCl3 bottles.
    Parr shakers that screetched like caged animals for days on end.

    I do miss stretching pipettes and cutting TLC plates – it was often my anxiety release.

    1. Fluorine Chemist says:

      Ah, stretching pipettes and cutting TLC plates – one of my favourite stress busters too! Used to be really good at it! Thanks for reminding me of that!!

  9. Billy says:

    This reminds me of the Google doodle of Har Gobind Khorana from earlier this year. In the lab mouth-pipetting something.

  10. CB says:

    Current advances in catalyst reaction screening has been such a time saver (and precious material saver too). I remember BEFORE Buchwald starting to publish his ligands. Well that was nice to have something else to try, but I remember spending so much time at the lab scale weighing out Palladium acetate etc. and a random ligand in hopes that it will work this time. When those G1 catalysts came around, oh my it was GREAT! Screening still took like 10-20mg per vial, but it saved time over all. Now I can screen 96 conditions with 40mg total.

    Also, electronic notebooks are nice. I do not miss spending time countersigning other people NBs, although it was a good time to see what other people were doing at the moment.

  11. ScientistSailor says:

    On a day-to-day bases working here, by far the biggest in over the last 20 years of my career are automated chromatography of various sorts, UV-vis/ELSD detectors on normal-phase and mass-based collection on RP systems. These allow us to spend much more time on data analysis and PP slides.

    Also outsourcing of intermediates, I spend most of my lab time now on 2-4 step synthesis of final compounds from building blocks made overseas. It’s been a couple of years since I’ve done a reaction on >10 g.

  12. Anon says:

    “what things med-chemists used to spend more time on versus what they do now”.

    Actual work vs meetings?

  13. Metal-bonds says:

    Using metal Dreiding models for hands on molecular modeling used to be very common. When I retired a few years ago, I could find no one interested in my personal set I had used for more than 30 years. BTW, I would consider donating my set if someone has a good use for it.

    1. John Wayne says:

      Are you kidding? I’d love a set of those; the old metal ones are hard to come by these days. I use them at work all the time to show nonchemists the differences between molecules. There is something about holding something in your hand that makes the human brain work. I also like to make the molecules I’m working on to make sure I completely understand their 3D nature.

      Let me know if I sound like a good place for your models to go.

      1. Metal-Bonds says:

        Hello John Wayne,

        Send contact info to omnivore385@gmail.com and we can work out details for transfer. I’m thinking of splitting my collection between you and ChemProf.

      1. 2G says:

        Germany (normally super-sized pieces are available from Aldrich):
        Dreiding models
        NO PRODUCTS AVAILABLE IN YOUR COUNTRY

    2. MTK says:

      Nothing demonstrated ring strain better than those metal Dreiding models.

    3. j says:

      contact these people, they are running an exchange ofndreiding models https://gfp.people.uic.edu/dreiding/dreidingexchange.htm

      1. Metal-Bonds says:

        Several years ago I contacted the Dreiding Model Exchange folks at UIC with a listing of pieces from my collection. At that time I was informed that they had already received so many items that they did not have room for additional donations. Please provide an update if this situation has changed.

  14. ChemProf says:

    Dear Metal-bonds,
    If you are serious about donating your Dreiding models I would happily pay for shipping. I teach organic chemistry (3rd and 4th year, in Canada) and often use plastic molecular models when student come to my office, or circulate them in my small classes. They are much better than anything else available now.

    1. Mister B. says:

      I should arrive in Canada (Québec) in a few month. In the lab, we’ve got several unused Dreiding models I could bring to you if you’re in the area of Montreal / Québec / Sherbrooke !

    2. metalbonds says:

      Hello ChemProf,
      Send contact info to omnivore385@gmail.com and we can work out details.

  15. MTK says:

    Electronic lab notebooks are a big change.

    And as everyone has managed automation in general. Chromatography of course is a big one, but so is NMR. Pop your sample into the holder, enter your experiment, then go back to your office to work up the FID. It really does result in better utilization of a very expensive piece of equipment, since no one processes data at the actual NMR. Although since the cost of NMRs have risen I’m not sure that it has resulted in greater value for the company or department.

    1. John Wayne says:

      Agreed on both counts. I’ve spent a lot of time writing in a notebook, which is now mostly copy/paste. Most people can type faster than they write; ELN is a win in every way.

      NMR is also a big change. Back in my day (insert cranky tone) we had to do everything manually because it was the only way to get good looking spectra. Now, the computer does it much faster and better than you.

      1. a. nonymaus says:

        I’ll have to disagree with you on that. I can write (not neatly, but legibly) faster than I can type, especially one-handed. Further, I am happy to throw out a contaminated Biro, but don’t have the cash to regularly replace keyboards.

  16. was a chemist says:

    Glad to see the chromatotron mentioned–I found it extremely useful, though when the lab decided pre-made rotors were too expensive and we had to start making our own it did make the experience less rewarding.

    I did some prep GC work in on insect defensive compounds in grad school. That was tedious! Did a lot of fraction collection from column chromatography, too. I asked about the likelihood of getting a fraction collector, and one of the students who had been in the group longer told me the boss didn’t think it was cost-effective, as long as he had graduate students.

    And like everyone else, I thought the THF still was a disaster waiting to happen. It seemed like it was refluxing over benzophenone/sodium from the day I arrived in grad school until the day I left.

  17. MoMo says:

    I see fewer using science libraries as todays scientists are content to sit in front of screens and be limited by Scifinder or PubMed searches.

    Gone are the days of spending hours/days among the stacks, knowledge hopping and getting ideas and inspiration from other shelves and fields while hunting paper trails for synthesis.

  18. Steve says:

    Melting Points does anyone still do them? Hours peering down a hot stage microscope waiting for something to happen, only to chat to someone for 1 minute and miss the melting!

    1. Adamantane says:

      Yep, they’re still required. If you’re submitting a manuscript to a journal for publication and you’ve made some new solid compounds, then part of the required characterization information includes melting points.

  19. Wavefunction says:

    Bench chemists using at least some computational tools in real time is something you see more often, and I think it’s going to become even more common. A simple case is a lab I worked in where they were using ROCS to search for compound analogs in real time.

  20. Isolation of Phosphorous-32 labeled phospholipids starting off with “hot calf brains” from the local slaughter house, transporting them across the centre of Oxford in a bucket of ice on a bicycle – pleased I never fell off as not sure how I would have explained such. Then incubation of brain slices with a Chernobyls worth of P-32 on the bench in Erlenmeyer flasks followed by solvent extraction then silica column chromatography using a Chloroform-Methanol gradient in a cold room (no ventilation) with an ancient fraction collector…. believe it may have been previously used to isolate penicillin by the Florey crew. The isolation of various phospholipases from Brewer’s yeast was a little more fun as the yeast was actually obtained from Morrell’s Brewing Co (now defunct) – literally a bucket full (and a wonderful smell)….. got some interesting comments from folks walking past the lab as to what project we might be working on at the time. Those were the days at SWDSOP.

  21. Bruce Hamilton says:

    Loss of chemicals because of safety and environmental concerns. Benzene, Freons, carbon tetrachloride, asbestos ( for Gooch and high temperature ), etc etc.
    IR : from KBr to ATR
    Glassware conical joints that are standardised and thus easy to disassemble ( no grinding or numbering required ).
    Use of Pyrex glassware.
    Use of SPE for separations.
    Chromatography Solvents – From tedious fractional distillation purifications of technical grades to purchased winchesters of specialist and LC-MS grades.
    Normal Phase Chromatography : from glass column ( >40um ), pressurised columns ( 25-40 um ), to radially-compressed HPLC ( prep=25um and analytical 5um), UPLC ( <2um ).
    Reverse Phase Chromatography : TLC to HPLC to UPLC, with repeatable columns and ability to handle 100% water ( for characterisation, and also replacing normal phase and ion-exchange for purification of many products ).
    Silica going from Type A to Type B
    Use of acetonitrile, methanol, and TFA, as chromatography mobile phases.
    Paper Chromatography – died in 1990s.
    Mass Spectrometer detectors that now work unaided for more than a day, with other evaporative detectors such as ELSD and CAD.
    TLC to Iatroscan to HPLC with mass sensistive detectors.
    Rotary Evaporators with long life seals and easy to dismantle, clean and replace seals with repeatable speed and temperature controls.
    Fume hoods almost everywhere.

    1. Annonned says:

      Where do you work? I have been semi-retired for about 8 years and have worked a couple of consulting jobs in the past few years, as recently as April. I did not see the labs you describe, at least not in the northeast US.
      Also, I am sorry, but after 30 years working with a wide variety of mass spectrometers, I still cringe when I see the term “mass spectrometer detectors” not referring things like electron multipliers or micro-channel plates.

      1. Bruce Hamilton says:

        I work in New Zealand.
        Most of the techniques I listed, original to current, are still available on this site. Paper chromatography probably being one exception, because the equipment has been tossed out, and the room repurposed. Sorry for offending your sensibilities about using detector after MS, but I was referring to MS instruments attached to chromatography, rather than standalone instruments.

  22. tom says:

    The comments mainly appear to list techniques that are still in use in New Zealand today.

  23. Fluorine Chemist says:

    Steam Distillation – does any one do it now? I did a couple of isolations with this technique using in-house steam, which was quite good!

    Talking of distillations, does any one do spinning band distillation? I used to separate compounds boiling as less as 7 degrees apart with this technique!

    Activating zinc – stir crude zinc with water and a few drops of conc. HCl till it coagulates. Wash thoroughly with acetone followed by ether and dry under full vacuum. You get beautiful silvery white zinc powder good enough for zinc insertion even in carbon-bromine bonds! Now, I guess people buy it straight off the shelf.

    Solid addition funnels – used to take me half a day to slowly add about 200 g of sodium carbonate.

    Laboratory notebooks – during my 15 year tenure in the US, I must have filled up 1000s of pages. Now, it is all ELN or LIMS.

    1. Design Monkey says:

      Steam Distillation – very rarely, when ancient preparation method calls fot it and it’s justified.

      Generally, if one works in rich pharma – then he just buys and outsources all those small building blocks, that would be amenable to steam distillation. If one is in poor academy, or is the poor sod, who comercially makes those building blocks – then whatever works. If steam, then steam, no big deal, although digging up a classic old times steam overheater might be not so easy anymore.

  24. Anonymous says:

    Working my way down the comments:

    I think when Derek referred to solvents on tap, I think he was referring to Grubbs columns, mentioned in another reply. Or, Derek, do they really pump flammables through the building to your bench or hood?

    Dry-transfer chem structures: Fieser plastic template (or other freebie, from Alfa and others).

    Silicone oil bath: also used high MW PEGs; the residual washes off your flask with water, speeding up clean-up. Also used sand in heating baths in place of pricey Al or alloy granules. “Reagent” sand is pricey; sand from the beach is free.

    Chromatotron: I can no longer find Analtech’s award winning ad videos documenting the anachronistic adventures of Ana L’tech. (Think Steampunk but Knights of the Round Table meet HPLC.)

    Hardcopy Chem Abs: I think a complete set, up to ~1998 or so, would fill several hundred feet of shelf space. But using hardcopy gives you a much better understanding of the database and how incomplete the GUI versions are.

    Reactions in vials: I’ve done reactions in melting point capillaries (learned that from another grad student). Saves material! Nowadays, I even like doing reactions in giant vials = 1 L to 4 L pyrex bottles with GL45 fittings. You can get GL45 threaded teflon adapters to create fancy inert gas set-ups. The flat bottoms sit on the stirrers and are very stable.

    Chromatotron, again: Chromatotron has the same and not better resolution as flash. It’s an acquired taste that I never acquired (despite having access to them).

    Steam baths, etc.: I used to use a Meker burner to vacuum flame dry my glassware (sucked in some huge dimples on my flasks when I overdid it). Some of the electric heat guns can get pretty darn hot and probably melt tubing and start a fire, even w/o an open flame.

    Disintegrated caps on corrosives: and completely blackened or disintegrated labels on a cabinet-full of reagent bottles! In the old days, you’d take your best guess and dispose of each one in a presumed to be safe manner; today, each bottle is an “unknown” that must be disposed of at huge cost by the dispo companies.

    Dreiding models: I still have a set! Beautiful models! Others mentioned “Dreiding Model Exchange” at U Chicago. There were also CPK (Corey – Pauling – Koltun) models. Both Dreiding and CPK were designed to Angstrom-like precision. That is, there were different atom pieces for dozens of bond types: a sigma-C-N amine bond was different from a sigma-C-N amide bond. I think that the NSF funded some of the development of CPK models (1950s-60s) because precision models were desperately needed by researchers (except Watson and Crick who got by with cardboard cutouts). Today, “CPK” or space-filling is an option in molecule viewing software that is even more precise than those expensive plastic CPKs. “Dreiding” models are pretty much viewed as stick figures in software. If you want a “real” model to hold in your hand for research or teaching, you can 3D print a model from crystal structures or computer generated structures. I’ve seen highly accurate rigid 3DP models and jiggly or squishy 3DP models that you can bend and twist – “molecular dynamics” 🙂 – to see what might be going on.

    Open stacks in real libraries (Momo): A great tragedy. Sic transit gloria mundi. When choosing grad schools, I made sure they had to have 24/7 chem library access.

    I don’t think anyone specifically contrasted gravity columns and flash columns yet. I did gravity as an undergrad and flash in grad school and onward. Today, even undergrads go directly to flash. And, of course, automated flash (MPLC) systems.

    I learned to use a lot of instruments when you HAD to learn how to use them: shimming the NMR, calibrating the mass spec, etc. Modern instruments autotune, have greater sensitivity, are a lot faster and better in so many other ways. Although, I just remembered a poorly designed project that didn’t have an assay. When I asked how they were going to measure the products, the answer was “Kjeldahl.” (I’ve never done one. Without modern automation, it’s time consuming, laborious, not very sensitive, not species specific, and very difficult.)

    (Derek asked about what things have sped up, not just what has changed in general. Otherwise, I would mention that, years ago, I accepted a lot of published literature as truthful and reliable. I took literature based advanced classes that showed how reliable a lot of old experiments were (Ingold, Winstein, et alia). Even if an interpretation has changed, the experiments and data have withstood the test of time. After years of reading a lot of literature and being able to correlate it to the real world, what has drastically changed for me is the awareness of the huge amount of garbage lit, false claims, and, to paraphrase Tom Hudlicky, the increasing lack of integrity in modern research.)

    Fluorine Chemist: Stress relief by pulling pipettes (see next paragraph). Spinning band: been there, done that. Sometimes you need to “waste” hours waiting to achieve equilibrium or adjust your reflux ratio (see next P).

    One more comment about speeding things up. To listen to some modern managers’ ideas, it seems that they want to “increase productivity” by making things go faster and faster and non-stop. “Idle hands make work for the devil!” Purchase every reagent, even if they don’t work as well as freshly made. They fail to realize that “down time” (e.g., washing glassware, pulling capillaries, letting a reaction reflux or stir for a couple of hours, sitting in front of the LC waiting for the timer to ding and direct your attention to the fraction collector, etc.) is time to THINK. There is a huge loss of productivity when you just have human automatons setting up more automated reactions to go into more automated analyzers until they drop from fatigue or burn out. I am biased, but I think that chemists, especially, have a lot to think about during those “wasted” hours and minutes staring off into space. I have had some great insights during those idle “wasted” moments. Einstein said, “Everything should be made as simple as possible, but not simpler.” I’ll concede that “Everything should be made as speedy as reasonable, but not speedier.”

    1. Derek Lowe says:

      Both of these were actually pumped solvents from huge tanks. They didn’t go out to the bench or to everyone’s hoods, but rather to a hood of their own off to the side, full of solvent taps.

    2. oldnuke says:

      https://www.youtube.com/watch?v=06gRhDMnPp8

      Adventures of Ana L’Tech – a great Chromatographic Comedy

  25. MTK says:

    I’ve relayed this story before, but…

    when I was a postdoc our LC’s integrator was down and one of the grad students couldn’t measure the d.e. of a reaction. I suggested hooking up the old chart recorder, cutting out the peaks, and weighing them to determine the d.e. He looked at me like I was crazy, but did it anyway. A few days later when the integrator was fixed, he reran the sample and found that the results were within a half-percent. He got a big ol’ laugh out of it.

  26. OldLabRat says:

    Late to the thread; as I see most of the usual suspects already mentioned. IR is missing in action today, which is a real shame for those learning and doing chemistry. I also don’t miss iron magnet NMRs and beam balances for weighing reagents.
    I do notice that wooden hoods and lead topped wooden benches haven’t made the list. The latter were great at giving falling glassware a gentle landing, and a quick tap with a hammer removed the need for cork rings to hold RB flasks.

    1. Derek Lowe says:

      I have to say, I missed out on the lead-bench era, although I did see some (beaten-up) wooden fume hoods in old academic labs earlier in my career.

  27. Mic says:

    What about the change w.r.t. pulling data together to understand an SAR? In my time it went from taped pieces of paper to excel like tools to more sophisticated software. Seems to me it was a huge time saving.

  28. CR says:

    Didn’t see it mentioned, but my lab does not use water condensers for refluxing any more. Too many instances of the tubes coming undone and flooding the lab (even with the metal connectors). We use the findenser on all refluxing reactions.

    1. Derek Lowe says:

      That’s a good one – I think that water condensers are indeed disappearing from the world. TBH, for some years I’ve avoided them anyway, just sticking a larger-than usual glass condenser on top without water flow: the budget Findenser for smaller scale.

  29. lfert says:

    Hanging 1/4″ copper tubing from the 4th floor of the stairway in the Chem Dept to pour the stationary packed bed (prepped separately in the rotovap) into for your GC column, then winding them up and attaching compression fittings to fit into the oven. The good old days.

    1. Barry says:

      If memory serves, the favored mandrel to coil those GC packed columns was a fire extinguisher.

  30. E. M. Unfred says:

    Your comment about solvent distribution systems caught my eye (saw it on reddit). Is this in Cambridge? Because the Boston Fire Department would not let us run even HPLC mobile phase at 1 mL/min between floors.

    Of course we managed to burn down the building anyway:
    http://archive.boston.com/news/local/articles/2005/03/27/blaze_damages_science_lab_spewing_radioactive_agents/

    1. Derek Lowe says:

      Both of these systems were floor-by-floor, to the best of my knowledge, probably for just the reasons you describe. . .

  31. Barry says:

    I’m astonished it took so long for anyone to mention electronic lab notebooks.
    Also first-to-file changed the necessity of signing and counter-signing those notebooks in ink, day by day.

  32. Anonymous says:

    Derek and solvents IN: I have seen some setups with coolant (maybe propylene glycol?) circulating to the hoods from a centralized chiller (operating 24/7, I assume). One open tap or popped hose and you drain your reservoir pretty quick, don’t you? There goes everybody else’s cooling, right? Anybody? I have also seen centralized waste solvent collection via funnel-like cups or cup sinks in the hoods. Pour your waste down the drain and it collects in the drums in the basement. Same deal: I have no idea how it actually works and in which jurisdictions it’s legal. Chemistry reminder: NEVER MIX CHLOROFORM AND ACETONE in the same waste container! With a trace of base or some metals, CHCl3 + CH3COCH3 –> 1,2-addition product EXOTHERMICALLY and it then self-propagates. So many exploding waste cans of the past were probably misattributed to human errors or carelessness while overlooking that too little known chemistry. (Swirl CHCl3 in a flask, decant, swirl acetone and see the smoky vapor form.)

    oldnuke: Thanks for the Ana L’Tech link!

    Chart recorders v integrators: I swear that modern instruments are designed for Big Pharma analytical labs only. In the research lab, you sometimes need to overlap injections or deliberately rezero or reset a recorder (or detector) as your baseline drifts mid-run. That is practically IMPOSSIBLE with new machines which are designed to prevent data tampering for FDA and other legal reasons. When just wanting to optimize a condition or prep out some product we (research lab, not FDA testing lab) do not need all of that. The hardware has often been the same for many years (tubes, valves, gizmos, thingies) but the software is killing me. I can’t get the instruments to do what I want them to do because I can’t just twist a valve when I want to. (This is a change that SLOWS things down in the lab. You have to let an entire injection and re-equilibration run to completion — 30 min? 2 hr? — instead of just getting the peak you want at 5 minutes and injecting an overlapping sample at 10 minutes, and another and another.)

    OldLabRat, permanent magnet NMR. They are making a comeback! I have seen desktop 40 MHz to around 80 MHz machines. I think the 40s are iron magnets and the 80s are neodymium “supermagnets.” Sometimes, all you need is a quick 40 or 60 to know whether a reaction worked. Some are multi-nuclear capable, 2D capable, etc. I think they are for undergrad lab, too. And no lead or wooden hoods or benches in my experiences. I have worked in labs with hoods so bad that is was a throwback to Liebig. The open labs had huge windows for ventilation. Some reactions, it was cautioned, should only be carried out on a day “mit einem lustig Wind.”

    I also switched to air condensers, sometimes throwing in a Vigreux column for an extra 10 cm of heat transfer.

    EM Unfred, fire on Albany St: The old New England Nuclear site (bought by Perkin-Elmer)? I started working with radiolabled materials as an undergrad and attended several seminars by NEN’s (Pres? Res Director?). Japanese guy, published many articles and appeared in their ads. I forget his name.

    That’s a change that might slow down some bio research. Radioactive tracer experiments are sometimes the simplest and easiest to do. However, the use of radioactive materials has been subordinated and replaced by other methods: fluorescent labeling, etc., etc., etc., sometimes not as good and not as pertinent as an isotopic label. I think that radioactive labeling is sometimes the method of last resort or, maybe, the final piece of proof after the non-radioactive methods have proven that it’s worth it.

  33. An IT guy says:

    Glass desiccator jars covered with a mesh of plastic electrical tape on the hope the tape would keep pieces from flying too far if the jar broke.

    Staff walking around the R&D building with plastics bags of bloody animal remains before the animal building was built.

    The best was the building evacuations, 3 in 5 years, due to old chemicals becoming unstable – mostly perchlorates I believe. After the third evacuation the place was shutdown for a day so all the labs could be searched for old and possibly unstable chemicals especially the back of the top shelves.

  34. doc says:

    When Wohler was describing the many marvellous innovations of the new laboratories (in Tubingen?), he mentioned that amongst the surpassingly wondrous features- amongst others, like distilled water and gas for the Bunsen burners- was “beer, on tap”.

    One can only imagine what he would think of solvents on tap.

    (For those of a historic bent, the comment was recorded in John Read’s “Humor and Humanism in Chemistry”)

  35. Sublimation? Anyone use it anymore? Used it all the time. Lovely process.

    4-Phenyl-1,2,4-triazolinedione (bright carmine red crystals)
    4-Methyl… (pinker red)
    4,4’-bis-triazolinediones (1,3-xylyl or (CH2)n linkers): Had to resurrect the oil diffusion pump for these babies, as “normal” (0.1 torr) vacuum wasn’t good enough; needed 1E-6 torr. BRIGHT, hot pink, like some sort of gaudy nail polish.

    And the kicker: Anhydrous FeCl3 … sublimed at atmospheric pressure, if I recall correctly, *in an atmosphere of Cl2*. And the Cl2 got out, and into the hoods, and into my lungs. An experience never forgotten, believe you me. But the crystals… beautiful, glistening greenish black. Exquisite! (Looks a lot like Koelsh’s radical*, but prettier. I still have the sample of Koelsh’s radical I prepared—and after 33 years, it still looks like it was made yesterday.)

    * C. F. Koelsch (1957) “Syntheses with Triarylvinylmagnesium Bromides. a,g-Bisdiphenylene-b-phenylallyl, a Stable Free Radical” J. Amer. Chem. Soc., 79, 4439. Footnote 1 to this paper is of interest and tells its history: “The experimental work in the present paper was done in the Converse Memorial Laboratory of Harvard University in 1931-1932, when the author was a National Research Council fellow. A paper describing the work was submitted to This Journal, June 9, 1932, but it was not accepted for publication. The referee held that the properties of the chief compound, a,g-Bisdiphenylene-b-phenylallyl, could not be those of a radical.

    1. Fluorine Chemist says:

      Ah, sublimation! Thanks for the memories! As a TA, we had the camphor synthesis experiment, which involved subliming camphor on a cold finger. I used to really enjoy that experiment as I just love the smell of camphor and I used to get a huge kick in explaining its DEPT 135 spectrum!

    2. loupgarous says:

      Nice to be a regular reader of a blog where someone says “stable free radical” and no one mentions “Noam Chomsky”.

      Just sayin’

  36. Koelsh’s actual footnote 1 is of historical (think: progress of science, acceptance of new ideas) interest:

    RECEIVED 1 April 10, 1957

    (1) The experimental work in the present paper was done in the Converse Memorial Laboratory of Harvard University in 1931-1932, when the author was a National Research Council fellow. A paper describing the work was submitted to THIS JOURNAL June 9, 1932, but it was not accepted for publication. The referee held that the properties of the chief compound, a,g -bisdiphenylene-b-phenylally could not be those of a radical.

    Recent quantum mechanical calculations by M. M. Kreevoy (to be published in J. Chem. Phys.), however, now indicate that a radical of the structure named would be unusually resonance-stabilized, and that the properties reported for the substance in question would be not at all inconsistent with the structure claimed. A study of the thermodynamics of addition of sodium to the substance [N. B. Keevil, THIS JOURNAL 69, 2104 (1937)] hinted that the compound might be unusually stable as a radical. And finally, recent studies by J. E. Wertz and J. L. Vivo, using electron spin resonance methods (briefly reported in OSR Technical Note 55-203, May 1955, p. 133, and to be published in detail in J . Chem. Phys.) indicate that the substance is highly dissociated, has an unusually narrow line-width, and is very stable. A sample kept in air 23 years [I have Koelsh beat by 10 years!] is unchanged in appearance and shows a high free-radical content.

    Because the structure originally suggested appears to be confirmed, and because many requests for samples and preparational details are being received, it appears desirable to publish the work now. In the interest of historical accuracy, the only important changes in the original paper are the additions of footnotes 5, 6 and 8.

  37. festus says:

    They only came up with that solvent distribution thing at Novartis cause of the fire codes in Cambridge not allowing large amounts of solvent on upper floors.

    Are they still forcing you to pour your waste in non ventilated conditions?
    And they claim to be working towards improving human health, LOL

  38. festus says:

    Note, valid safety complaints to OSHA at Novartis are met with slander, character assassinations and attempts to prevent one from earning a livelihood.

  39. Dane Goff says:

    Speaking of chromatotrons- the best part was having Ian Harrison deliver it in person and show you how to make the plates

  40. Gord says:

    Didn’t anyone mention pressing Na wire into winchesters? Fun… not

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