Tag Archives: chemicals

Chemistry: Not quite so elementary

Harold Urey, father of isotopic chemistry. Image from Wikipedia.

Chemistry, like many of the sciences, is laden with a horribly confusing vocabulary that persists for merely historical reasons. For example, atoms are not indivisible even though atom comes from an ancient Greek word atomos meaning “indivisible”. “Free” energy is not free, at least not as most speakers of modern English would understand the word.

And so it is with the chemical “elements”: they aren’t elementary. Take carbon for example. This supposedly elementary substance can be chemically separated into (at least) two types, each with a different reactivity. I’m talking, of course, about isotopes. The heavier type of carbon is carbon-13 or 13C for short, and is made of atoms that have six protons and seven neutrons in its nucleus. The lighter, more prevalent type is carbon-12 (12C), with the same number of protons, but only six neutrons instead of seven. Admittedly, the differences in chemical reactivity of 13C and 12C is very slight — entirely negligible for most practical purposes. So in a sense, calling “carbon” an “element” is only a slightly misleading, but there are certainly times when the difference can be very important.

Don’t just take my word for it. Poul Anderson explained the same thing in, well, slightly different terms back in 1989:

Unclefts with the same tale of firstbits but unlike tales of neitherbits are called samesteads. Thus, everyday sourstuff has eight neitherbits with its eight firstbits, but there are also kinds with five, six, seven, nine, ten, and eleven neitherbits. A samestead is known by the tale of both kernel motes, so that we have sourstuff-13, sourstuff-14, and so on, with sourstuff-16 being by far the most found. Having the same number of bernstonebits, the samesteads of a firststuff behave almost alike minglingly. They do show some unlikenesses, outstandingly among the heavier ones, and these can be worked to sunder samesteads from each other.

One other crazy thing about isotopes (or samesteads if you prefer). Not all neutrons have the same mass. The 13C atom’s mass 13.0034 daltons (Da), and the 12C atom’s is 12.0000 Da (by definition). Since those atoms differ only by a neutron, it would seem that a neutron in a carbon atom has a mass of 13.0034 – 12.0000 = 1.0034 Da. But hydrogen also has two isotopes: 2H with one neutron and one proton, and 1H with no neutrons at all, only a single proton. But a 2H atom’s mass is 2.0141 Da, and a 1H atom’s is 1.0078 Da. If you do the same subtraction, you’ll find that the mass of neutron in a 2H atom is 1.0063 Da. Those numbers are close but they are NOT the same. A neutron in a hydrogen atom is about 0.3% heavier than a carbon atom’s neutron.

The reason for the difference has to do with Einstein’s famous mass-energy relationship and the strong nuclear force and…well, let’s make it a subject for another time. For now, let’s end by saying that these seemingly slight differences in neutron mass from atoms of one element to another — called the mass defect — can be detected in modern mass spectrometers. And what of it, you say? Well, I’m glad you asked: that will be the subject of some upcoming posts. (Here’s a taste.)

Raman spectroscopy is awesome and you should too

Sir C.V. Raman, the namesake of Raman spectroscopy. Image from Wikipedia.

Raman spectroscopy is awesome. But these days it is rapidly getting more awesome. Here are a just a few new reasons to love Raman spectroscopy:

  1. It measures the metabolism of single living bacterial cells (in conjunction with stable isotopes).
  2. In mere seconds, it quantifies essentially all the various gases in 27 nanoliters of human breath.
  3. It does video-speed label-free chemical imaging on microscopic scales.
  4. It tracks in real-time the yields and titers of chemical and bichemical reactions, even at small scales.

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The Insider goes to the #ChemMovieCarnival

Biologists have been moving on in to chemists’ territory for a while now. So I hope no-one minds too much that I’m choosing to celebrate a biochemist of the silver screen as part of my late entry to SeeArrOh’s Chemistry Movie Carnival.

The biochemist is Jeffrey Wigand (Russel Crowe). The movie is the Insider. Dr. Wigand, who has a Ph.D. biochemistry and endocrinology, is the eponymous title character. He was a former medical scientist and executive who went to work in the tobacco industry as a VP of Research. After a few years, he’s so frustrated by his company’s conscious disregard for the health of their customers, that he quits and turns whistleblower, testifying in 1996 in both court and on 60 Minutes about the misdeeds of his former employer.

Dr. Wigand’s testimony is high drama as well as interesting chemistry. I could go on and on about this movie, but its better just to watch. Here are two clips:

Clip 1: The 60 Minutes interview – Nicotine is a drug:

Clip 2: Legal testimony. Coumarin is the straw that broke the camel’s back.

What makes the chemistry in The Insider so cool? It’s a few different things:

  • The biochemist in the story is both (a) the good guy and (b) the main character. We see the ups and downs of his life as he goes through with his decision to blow the whistle, and the toll that this professional decision takes on his family life. We’re way beyond the hackneyed “man-in-a-labcoat spews jargon for a scene or two” trope here.
  • The main character is an inspiration and a role model for scientists everywhere. What if Bengü Sezen was your labmate and you somehow knew she was playing fast-and-loose with the data? Or if Annie Dukhan was your co-worker, and you knew she played fast-and-loose with, well, everything? Would it be the right thing to stand up and say so? What price would you be willing to pay for speaking out?
  • It’s a true story*! Jeffrey Wigand is a real person, who really has a Ph.D., and he did actually blow the whistle against big tobacco. (* I should say “based on” a true story: the movie exaggerates some details — for example, tobacco companies probably did not make any threats or trespasses against Dr. Wigand.)
  • There’s only one lab scene in The Insider, in the very beginning. In it, people are eating cake. In the lab!  Not even this movie can get all the details right.

No movie I’ve seen has a more impactful portrayal of a professional scientist than this one. I hope if I’m ever thrust into a situation like Dr. Wigand’s — that if I come to know of chemical crimes or misdeeds, and no one else is saying anything — then, even if the stakes aren’t as high, even if it’s not a problem on the national scale — then I hope that I can have the courage to speak out and tell the world (or just the person down the hall) what I know. Thank you Dr. Wigand for a being great example and thanks to Russel Crowe for a great portrayal of a fine character.

Defending Chemical & Engineering News

Over at In the Pipeline, the commenters waged a fierce attack on the American Chemical Society’s trade magazine for chemistry, Chemical & Engineering News. They were responding to In the Pipeline blogger Derek Lowe, who’d been invited to join the editorial board of Chemical & Engineering news, and who was asking for feedback on what his readers felt about the magazine.

Commenters had a lot of negative things to say about C&E News, and about the ACS more generally. I was shocked to see that so many commenters held such strong anti-immigration views. Their argument seemed to be that C&EN’s articles on the employment outlook for chemists were too rosy. They felt that H1B visa-holders were taking jobs from qualified American chemists. Some of them also felt that the ACS in general was intentionally trying to attract cheap foreign labor and drive down the wages of American chemists.

These views seem a bit far fetched to me, as I’ve noted. I was glad to see Derek Lowe address these arguments in a later post.

I have to say here, as I did in the comments to some of the posts at In the Pipeline, that I’m a fan of C&EN. I love skimming the digests of recent research. And I did start off my grad school admissions essay by saying that it was through reading C&EN that I realized that a career in the biotechnology was what I wanted. C&EN comes every week. It has research highlights, business-oriented articles, and often in-depth discussions of regulatory and policy issues facing the chemical industry. Plus did I mention their “Facts and Figures Of The Chemical Industry” articles? The other trade magazines I’ve read at one time or another — mainly ASM News, Chemical Engineering Progress, but also Genome Technology and Physics Today, don’t attempt nearly as much breadth.

In my view this breadth makes for interesting reading. It’s probably also a reflection of the breadth of interests among members of the ACS, which is after all the world’s largest scientific society. I am glad to know that my ACS dues go in part towards producing C&EN. The magazine isn’t perfect — for one, I’d like to see a bit more writing contributed by active chemical researchers — but I think it is remarkably good, both in absolute terms and in comparison to other technical trade magazines.

Good job, C&EN. You’re a good magazine.

Molecule of note: 3-formyltyrosine

I wish I had a nickel every time I hear that the “metabolome” — the collection of all of the small molecules which exist as intermediaries in the biochemical machinery of living cells — consists of only a few hundred metabolites.  “The number of known metabolites present in many organisms (e.g., yeast) is 10- to 100-fold fewer than the number of genes or proteins,” said one paper, which later went on to say that the yeast metabolome was around 600 metabolites.  Another says that the erstwhile laboratory favorite, the bacterium Escherichia coli, has “694 metabolites present in the in silico metabolome.”

The key words are “known” and “in silico”.  Of course if you limit yourself to what you know about, or limit yourself to “in silico” databases of metabolites that other people know about, you won’t find anything new.  But that doesn’t mean that we know what all of the metabolites are!

Leah C. Blasiak and Jon Clardy provide an excellent counterexample to the idea that we have a handle on the chemical diversity of microbes in a recent paper in the Journal of the American Chemical Society, which details their discovery of 3-formyltyrosine and related metabolites in a marine bacterium.  Drs. Blasiak and Clardy went searching through genomic databases for genes that seemed to encode proteins similar to a newly discovered class of rather funky enzymes, the “ATP-grasp-type ligases”. They found an interesting set of genes from Pseudoalteromonas tunicata, a seabound bacterium which is often found on the surface of seaweed, floating debris, and intervetebrates. They moved those genes to E. coli cells, and then looked in cellular extracts for blips in their mass spectra that did not show up in E. coli cells. They found a few, and after extensive chemical characterization of those blips, they were ready to announce to the world that 3-formyltyrosine was a biologically produced metabolite.

It wasn’t in anyone’s database and hasn’t yet appeared in an in silico metabolome yet, to my knowledge, despite it having been in the Pseudoalteromonas tunicata metabolome for hundreds (at least) of years. How many more metabolites like 3-formyltyrosine are there waiting to be discovered? My money says, “more than a lot of people think.”

The Chemistry Nobel Prizes

Nearly all the chemist-bloggers I read felt that the chemistry nobel prizes should go to chemists, and that the work of Ramakrishnan, Steitz, and Yonath on the X-ray crystallography of the ribosome is more biology than chemistry.

I suppose that in a sense they have a point. Ribosomes come from cells, and cells are, traditionally at least, the province of biologist, not chemists.  Still, I can’t help but feel the attitude that only “real” chemists deserve the chemistry Nobel is somewhat provincial and narrow-minded.

For example, ribosomes have become a great tool for chemical synthesis (Here’s one example). Ribosomes catalyze the template-directed, sequence-specific polymerization of an increasingly diverse set of monomers. And these polymeric products, the proteins, are themselves amazingly diverse of course. Catalysts, drugs, poisons, you name it.

Maybe you have to squint a little harder than normal to make ribosomes look like chemistry, but it doesn’t seem like too tough a task to me. Then again, I’m not a chemist.

UPDATE: kylefinchsigmate reflects over the fascinating history of the Nobel and biochemistry.

UPDATE 2: I fixed some syntax problems in the first two paragraphs.

A, C, G, and T – For some people, four letters are not enough.

Ever since the time of Phoebus Levene, we’ve known that DNA has contained 4 bases – G, C, A, and T. Erwin Chargraff showed that the number of Gs in DNA were equal to the Cs, and the As were equal to the Ts. Then some guys you have definitely heard of solved the structure of DNA and it all made sense: our genes were written in a four-letter alphabet, with Gs bonded to Cs and As to Ts in a scheme now called “Watson-Crick base pairing”.

Today, we’ve gotten good at reading and writing in this alphabet. We can solve crimes, produce drugs, retrace the steps of human evolution, and even solve complex computational problems by reading and writing As, Gs, Cs, and Ts.

But for some people, four letters are not enough. For many years, several research groups have been working on adding new letters to the language of DNA. For example, Eric Kool and his co-workers have made size-expanded DNA. By this they mean, what happens if you drop in another benzene ring to adenine?

One example of a new letter in the DNA alphabet.

One example of a new letter in the DNA alphabet.

Floyd Romesberg and his co-workers have been coming up with additional DNA letters for as long as just about anyone else. One exemplary finding: Watson-Crick base pairing is not even necessary for the creation of new DNA letters. Instead, purely hydrophobic forces can bind oligonucleotides together, as in the artificial base pair d5SICS and dMMO2.

Two new letters for DNA

Two more new letters for the DNA alphabet, d5SICS and dMMO2

Floyd Romesberg, Eric Kool, and many other workers are getting close to engineering new letters for DNA that can be read and written using existing DNA processing tools. That is, some recently reported synthetic nucleotide base pairs can be replicated by DNA polymerases with high fidelity and good catalytic specificity. The As, Gs, Cs, and Ts of DNA will have to make room for new letters.

Soothly we live in mighty years!