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To Synthesize or to Buy? That is the question.

And you should too!

Einstein probably synthesized his own compounds. (Flickr user hernandezmariacristina)

Happy summer, everyone!  Sorry for the cheesy title.  Because I’m still an undergrad, I get the chance to take some pretty cool classes that have a little to nothing to do with chemistry.  This can either be a nice break (i.e: Shakespeare, see title) or an unwelcome distraction (…Spanish).  I’m soaking in as much diverse education as I can before I start specializing in my PhD.  This is all besides the point.

Anyway, I wanted to pose a question.  When you’re running a synthesis, an assay, or whatever else it is you do in your lab, and you require a reagent that is expensive and difficult to synthesize, do you spend days synthesizing it yourself, or buy it at ridiculous price from a manufacturer?  From what I can gather, there are two camps.  Tell me if I’m wrong.  PIs/Professors are more likely to encourage grad students to synthesize everything from scratch, and the graduate students vice versa.  Whether their opinion is born from distrust of the manufacturers, a desire to teach you (the student) some more synthesis, or plain sadism is up to debate.  The advantage is that you get to gain some more experience in what is probably a very classic synthesis, helping you gain some ‘lab chops.’  The disadvantage, of course, that that you have to stop watching Futurama to synthesize this molecule that you could just buy.

I’ve recently had an interesting experience.  I had bought a reagent from a manufacturer, expecting to use it as a positive control.  For whatever reason, it wasn’t working.  After around two weeks of frustrated testing, I found that the molar mass of my positive control didn’t match to mass it was supposed to be (by MALDI).  So therefore, we got sent a faulty reagent.  Kind of a bummer, right?

After this debacle, I resolved myself to synthesize it myself, spurning the multimillion dollar industry for my own two hands.  After a week of synthesis and purification, I am a proud owner of a compound which has a molar mass that is too large for the compound I would’ve wanted to synthesize.  I still haven’t run enough tests to see how far I’ve gone wrong, but as of now it seems possible that I’ve somehow messed up, which puts me at a unique crosscroads.

Do I synthesize my positive control again?  It only took me a week, and is much less expensive than buying it from a manufacturer.  Also, I can make gobs at a time (technical term), and I can only buy a small quantity.   On the other hand, I could just buy it again and hope for this best.  Sure, it’s much more expensive, but it’d be so easy!  Plus, I could finish this episode of futurama.

So, my chemist friends, if you were in my place, what would you do?  Synthesize or buy?


How do Elephants Brush Their Teeth? Ask a chemist.

Look!  My hand made a cameo!

Note: Do not use this to brush your teeth.

Outreach is becoming one of the most important aspects of undergraduate, graduate, and professional chemistry. Reaching out to kids at a young age and helping them get in to chemistry is a priority.  This is also one of the main focuses of the ACS’s International Year of Chemistry (IYC) 2011.

I remember in my first chemistry class when my teacher showed us the classic demo where she turned water to wine, then wine to milk, then the milk to beer. To me and my classmates, it seemed like magic.  It was pretty much the coolest thing since, well, the power rangers.  Or the Offspring.  Anyway, we now have a much different perspective.  These chemistry demonstrations utilize relatively simple chemistry to produce really fun and exciting results.  Does that mean that all the magic is gone?  I don’t think so.  A few weeks ago, I had the chance to do some of these demos to a crowded audience of elementary school kids.  Needless to say, I had a blast.  The kids did too.  Over the next couple weeks, I’m going to be profiling a couple of the demos I did, and how to do them for your friends, neighbors, or chemistry classes.  We all know that chemistry is fun:  other people just need some help remembering.

Today, I’m profiling one of my favorites:  The elephant’s toothpaste.  Here’s how it’s done:

What you need:

  1. One (1) Graduated cylinder, as large as you can find it.  Really, the bigger the better.  I used a 2.o L guy I found lying around in my lab,  but I imagine that doing this with a 4 L or 8 L would make some kid’s day.
  2. 150 mL of dish soap.  Really doesn’t matter what kind
  3. 150 mL 30% Hydrogen Peroxide.  This is dangerous – it’s an irritant and will hurt if you get it on you.  Wear gloves, a lab coat, and goggles.
  4. Food coloring (be very generous)
  5. ~5mL of saturated KI.  I do this by putting a lot of KI into a 50mL falcon tube and adding water.  Then I shake until I’ve dissolved all I can, and add 5mL

This is how it’s done:

  • Put the peroxide, soap, and food coloring (again, be generous)
  • Add some KI
  • Watch it happen

This demo is really fun.  Just don’t forget to lay down some newspaper so cleanup is a easier.  Also, a note about safety:  because of the peroxide, don’t be staring down the tube as you pour the KI in.  First, you’ll get burned by peroxide, then you’ll get majorly stained by KI.  Neither of these things will be enjoyable, I promise.  If you’re prepared correctly and introduced the demo in a fun and interesting way, this should go off great and be a highlight of your chemistry show!  Enjoy!

-Sidechain

P.S:  The recipe above is optimized for a 2 L graduated cylinder.  If you want to use bigger or smaller, scale up or down respectively.


What is Chemical Biology? Perhaps it’s Peptidomimetics

Disclaimer: I am not an expert. In fact, this series of blog posts is as informative  to me as it is to you. Probably even more so. My views and the views of people interviewed for this blog do not, in fact, reflect what exactly “chemical biology” is, but only a snapshot.  Please direct any comments or suggestions below!

This doesn't seem like Chemical Biology to me...

No, not THAT kind of mimicry! (Credit to Flickr user christopherasmith58102)

Peptidomimetics is something I think about all the time.  So, I decided it would be a pretty good starting point for this series, especially considering that right now it’s finals week and I barely have enough time to be running a synthesis, much less studying for finals.  But that’s beside the point, because I’m very excited to learn more about peptidomimetics (and who needs to study for finals when you can do research instead, am I right?)!

What is peptidomimetics?   From what I’ve seen, it’s pretty much exactly how it sounds.  The essential goal of the field is to take a peptide of interest, which usually means that it’s bioactive or important in some way physiologically, and synthesize and test organic mimics of it to fulfill a number of different goals.  So if we have bioactive peptides why not just use them as drugs?  Because peptides have some inherent problems to their usage that peptidomimetics seeks to solve:

  1. Protease Resistance/Serum Stability:  One of the main reasons that peptide drugs (mainly mimics of allosteric regulators) have been largely unsuccessful.  When a peptide is taken up by the body, either intravenously or orally, the body has a suite of enzymes (such as proteases and E3-Ubiquitin Ligases) which degrade small peptides and foreign ingested proteins.  While these processes are important in metabolism and immune function, we would rather our peptides not be degraded by the body.  One of the main goals of peptidomimetics is to avoid the body’s natural defense against peptides and to get at biological targets.
  2. Membrane permeability:  Most biological targets are located inside cells.  In order to get your favorite peptide into a cell, you need to cover it with lipophilic groups (or else somehow reduce the charge) to help it squeegee its way (technical term) into the cell.  Small molecules, being generally much smaller, rigid, and lipophilic, rarely have this problem.  Because peptides routinely break Lipinski’s Rule of Five for drug-likeness, special provisions must be taken in synthesis and design.
  3. Conformational Restriction:  Very often, peptides are considered “floppy.”  They require an optimal “active conformation” to bind to or inhibit other enzymes.  Very often, peptidomimetics seeks to modify peptides by constraining them into a more stable and active conformation, thus reducing the entropic cost of a peptide’s action.
A peptido-mimeticist's dream come true

Beta-Peptides and Peptoids have structures that make that protease resistant

So what kind of research do people in peptidomimetics do?  This kind of research is widely diverse but can be divided into a few categories.  Beta peptides are peptides which have the amine group bound to the beta carbon instead of the alpha.  This allows for (a) more membrane permeability and (b) greater protease resistance.  Already, beta-peptides are being researched as antimicrobials, and have been shown to readily form alpha-helices.  Peptides are another kind of amino acid mimic that are widely used.  Instead of having the R group on the alpha carbon, they have it on the amine group.  They’re also called N-substituted glycines.  Again, you see here greater protease resistance because proteases do not recognize these amino acid mimics.  In addition, the lack of amide protons and achirality of the alpha carbon gives rise to greater membrane permeability.  However, the pretty secondary structures you can get with beta-peptides are impossible to achieve with peptoids.  You can read more about beta peptides and peptoids and their antimicrobial potential in this great review from Chemical Biology and Drug Design.  For more reading, you can check out this cool review on incorporating beta-peptides and peptoids into the same chains from ChemBioChem.  Imagine how much trouble that would be without solid phase peptide synthesis.

Credit to the University of Maine MechE website

Gramicidin is a cyclic peptide that forms pores in bacterial cell membranes

Another branch of peptidomimetics involves regular, plain-old amino acids.  Very often, it is possible to restrict the conformation of a peptide to its active conformation by cyclizing it, especially if the active conformation of the peptide includes a loop or turn.    This accomplishes what I was talking about earlier:  paying the entropic barrier up front, and locking a peptide into a smaller series of conformational possibilities.  Cyclic peptides are also more protease-resistant due to a restricted conformation, and are more membrane permeable, because of (a) the smaller size and (b) the elimination of the N and C termini, making the molecule overall more nonpolar.  The European Journal of Organic Chemistry has another good review on peptidomimetics that you can check out at your leisure.

This sounds a whole lot like medicinal chemistry to me, so far.  So why put it into the large umbrella that is Chemical Biology?  I would argue that peptidomimetics belongs in Chemical Biology because (a) peptides are biological molecules, and bioactive molecules are the focus of Chemical Biology and (b) these peptidomimetic molecules can be modeled in vivo and in vitro and (c) the field incorporates aspects of organic chemistry, classic biochemistry, and some cell biology, and this duality of research (to me) characterizes Chemical Biology.

I hope this was as helpful to you as it was to me.  I think peptidomimetics is pretty cool, and wouldn’t mind going into it in grad school.  This review is really small in scope and I encourage you to read the reviews that I’ve linked to.  What would you like to see next Monday?  Right now I’m thinking about Native Chemical Ligation, but I could be persuaded otherwise.  Feel free to post in the comments below!


Fun With Quantum Mechanics: Scanning Tunneling Microscopes

Note:  Check out my new avatar!  Also, Chiral and I are in the process of updating the “about this blog” and blogrolls.

Credit to the Sykes Lab of Tufts University

A research-grade low pressure/temperature STM (top) and a portable laptop-capable STM (bottom)

I know what you’re thinking:  aren’t Scanning Tunneling Microscopes (STMs) hundreds of thousands or millions of dollars?  Who has that lying around, much less in grant money?     Well… almost nobody.

STMs do indeed cost a lot of money, but can tell you a whole lot of stuff about a surface.  They’re so expensive that a simple google search doesn’t yield any results for websites which sell STMs.  Going further, I found that DME-SPM sells a whole range of STMs.  However, the prices aren’t listed (kind of like an expensive restaurant, where you only get the price once the bill comes).  Not really too affordable.

However, if you have the cash, an STM can be a fun thing to have.  After all, who doesn’t want to see things on the atomic level?  One can move hydrogen atoms around under a Pd crystal or Xenon atoms on a metal surface.  This is done using an atomically sharp tip (and the electrons attached).  Using this method, Paul Weiss managed to spell out the PSU Logo on a Pd Crystal.  (He was also part of the team that wrote out the IBM Logo in Xenon atoms).

One of the coolest things about STMs is that you can get a gigantic apparatus which has space for liquid Helium and a super vacuum and can resolve images on a atomic level OR you can get a STM that can fit on your desk, plug into a laptop, and work at STP! Well, I had the chance recently to work with one of these STMs for a Quantum Mechanics lab.

Can you see individual monolayers?  Etch points?  Sections of C10 SAMs?

My very own STM image of SAMs on a Au surface!

My group made the road trip through time and space (well, really just space) to the Sykes lab of Tufts University, where we had the chance to explore the world of atoms.  This was especially fun considering my lab group consisted of myself, an undergrad interested in synthetic chemstry, and another undergrad currently researching inorganic chemistry but going to business school.  If you’ve keeping score, that equals exactly zero people who would be interested in Quantum Mechanics.  Even so, we all had a blast playing with an STM.  Predictably, we didn’t get to use the giant STM that the lab has (which uses liquid He to cool and contains a very, very strong vacuum).  Instead, we had the chance to use a portable STM that hooks right up to a laptop.  Using this setup, we analyzed surface-assembled monolayers (alkanethiols of C8 and C10 length) on a gold surface.  Pictures on the side.

If you were curious, you can get one of these desktop STMs for around $9000 (so told by a friend in the Sykes lab).  It’s on my graduation wish list for sure.  Check back soon for more posts – now that school is winding down, Chiral and I will be on CENtral Science more.  Also tune in next monday for a look at peptidomimetics!


What is Chemical Biology? No… seriously.

Disclaimer: I am not an expert. In fact, this series of blog posts is as informative  to me as it is to you. Probably even more so. My views and the views of people interviewed for this blog do not, in fact, reflect what exactly “chemical biology” is, but only a snapshot.  Please direct any comments or suggestions below!

NOT Chemical Biology

Maybe one day, research like this could be chemical biology

The next several months are pretty big for me.  Soon, I’ll be taking the GRE and deciding where to go for my PhD, but I honestly have no idea where I want to study.  Because of my current research and classes I’ve taken, I know that Chemical Biology is the field for me.  The only issue is, when asked recently by friends, family, and random strangers  what Chemical Biology really is, I’m kind of at a loss.

For me, Chemical Biology means probing biological systems with chemical agents.  Recently, I’ve had a chance to talk to a couple PhD candidates (including our very own  Christine Herman) in Chemical Biology, and they all had varied definitions.  Christine’s and my research could not be more different; she does research in bioassays, and I do a lot of work in peptidomimetics and drug discovery.  Her research is in the analytical department, and mine in the organic.  It surprised me to learn that she classified herself as a chemical biologist as well.  This led me to a couple conclusions:

Chemical Biology is less of a specific field but more of a classification encompassing a wide range of different kinds of research.  Things that would have once been considered organic chemistry (such as what I do), analytical chemistry (what Christine does), or even physical chemistry (see some later posts!) are now under the great big umbrella that is Chemical Biology.  So, what’s a young blogger to do?  Over the next several months, I’m going to examine different areas of research in Chemical Biology, one by one.  I’m planning on getting in touch with some of the leaders in field.  Hopefully, this will be fun for everyone, and help me decide where I want to do my PhD.

Next Monday tune in for a subject near and dear to my heart:  peptidomimetics!  Any suggestions on who to talk to?  Post below!


Yale Student Dies in Chemistry Machine Shop

After standing for some time in the rainy streets of Boston, I finally hailed a cab to the airport. As I tried my best to wring myself out, while not making a mess of the cab, the cabbie chattered away into his bluetooth, and the radio was on some news station, barely audible.

My ears perked up when I heard “…chemistry…”. I leaned a bit closer to the speakers.

“…Yale student died…”

“Hey, can you turn this up!?,” I blurted to the cabbie.
“Huh?,” he replied.
“The radio – can you turn it up?”
“Oh, ok,” he said, turning the radio up as the news report ended.

While we sat, listening to the weather and traffic at an uncomfortably loud volume, I hopped on my space-phone to get the full scoop.

Last night, Yale senior Michele Dufault died in an accident in the Sterling Chemistry Lab. Details are unfortunately spotty, and for now, the only chemistry-related news is that the accident occurred in the machine shop, but word on what exactly happened. The full story can be found at the Yale Daily News, and I’ll post updates here as they’re available.

She was an astronomy and physics major, and by all reports, generally awesome. My deepest sympathy to her family, and the Yale community.
Stay safe out there.


Not at #ACSAnaheim, but still having fun in lab!

Tin foil, it just makes the world go 'round

Hello!

Look at all that heating tape!

I hope you’re all having fun at the ACS conference.  Don’t forget to go to Disneyland, and know that we on the east coast are all thinking fondly of you.  This morning I’m “stuck” in lab doing some exciting assays and studying for a Biological Anthropology exam (which I’m taking for the social science credit, due to the fact that I can’t handle ‘regular’ social science classes).  The week before spring break, I got the chance to do a really fun Quantum lab – examining the fluorescence spectra of Iodine gas.  If you’ve ever done this lab, you know that you have to heat an evacuated chamber up to around 170C – much, much higher than is comfortable.  But you get some pretty cool pictures out of it!  These were taken with a DROID camera, so are not of the best quality.  I hope you can forgive me, blogosphere.


Spring Break musings – chemistry in the old days

Hello all!

Sorry for the sparse updates over the past week and half or so.  It’s been spring break in college land, and for undergrads that means vacation.  I’m currently in the West Palm Beach airport in sunny FL, about to head back to the snow-and-windswept plains of the northeast (where I call my home).  While here, I had the pleasure of visiting with my girlfriend and grandparents and being treated to far too many gigantic meals.  Today at lunch I was eating with my grandmother and her friend, and learned that she was once a high-school chemistry teacher.  She told me all sorts of stories (including one of her in graduate school, when she mouth-pipetted snake venom!), and one of my favorites is below.  Feel free to share your favorites!

Once upon a time, in Illinois, my friend was taking her class (from Minn.) to a science fair.  They were working on irradiated chickens, and kept them and the irradiated eggs in the trunk of the car.  Of course, in order to keep the specimens alive, they needed to open the trunk every once and a while to give the poor guys some air.  In a small town in Illinois, the chickens got loose and my poor friend had to chase these irradiated (maybe radioactive?) chickens through the streets.

Why does this story speak to me?  Well, first, I find it absolutely hilarious – a scientist chasing her specimens through the streets of a small town just would not happen.  (Also, does anybody use chickens as a model system anymore)?  Second, we don’t even have what were called “Becquerel Chemicals” in high schools anymore, much less do radiation experiments on chickens.  It’s just a different day today.  Well anyway, in honor of Friday, spring break, and the good old times, feel free to share your favorite old time chemistry story in the space below – thanks!

-Sidechain


REU Round-Up Part II – An interview!

Hello everyone!

Sorry for the long delay, but here is the long-promised interview with a real-live graduate student!  Amanda is a first-year grad student at a new-england university.  She can tell you all about her experience below.  What is interesting is that even though Amanda did hardcore inorganic chemistry in her REU, she has since gone on to a biochemistry lab, but still would like to apply her interest in metal binding.  So as advice for all of you fledgeling researchers, don’t feel trapped by your interests: an REU can be a great experience to expand your scientific understanding and learn a new field that you can apply to your own.  With that said, here’s Amanda! Continue reading →


An interesting op-ed (semi-unrelated to chemistry)

Hello!

For all of you folks there who are worried about the nuclear situation in Japan and it’s potential impacts for the nuclear power industry, this undergrad from Tufts University put together a really great article.  It really focuses on what we as scientists (or budding scientists) need to do and take responsibility for.  Definitely a good reminder of life outside the fume hood.   This article was originally published in the Tufts Daily, and I think it’s a pretty good read for undergrads and professionals alike. Thanks to Evan Weixel for permission to reprint his work. Enjoy!

-Sidechain

Continue reading →



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