As many estimable colleagues have noted, guanine's weird. It's not that soluble, which isn't too much of a problem when it's a part of your very soluble DNA, but from an origin-of-life perspective, that's a hassle. Envisioning a primordial-soup scenario with guanine is tricky, because of this low solubility. Further complicating the problem is guanine's prodigous tendency to associate with itself: Monomers of G will do this, forming gels in solution (which exhibit repeating units of the above structure). We knew about guanine's propensity to self-associate before we even had cracked the…

Pfizer's Lipitor is the highest-grossing drug out there right now. This single molecule sells over $10B/year. As discussed in the allopurinol entry, this is another example of a small molecule enzyme inhibitor. The class to which it belongs, the statins, works on one key step of the steroid biosynthesis cycle. They do a good job lowering LDL cholesterol, but aren't so great at raising HDL cholesterol. That's one reason drug companies have been after a different class of anticholesterol drug. Another reason for Pfizer to be worried is that in just a few years, Lipitor goes off patent. One…

Polonium-210 is a radioisotope that's gotten lots and lots of press in the last few weeks because of its purported role in the death of Alexander Litvinenko. Polonium is an alpha emitter - that is, in the process of decay, it gives off energetic helium nuclei. They're massive, so they are stopped by a small amount of shielding (paper is the thing everyone cites as blocking it). Outside your body, it is not nearly as dangerous, since even your skin will stop it. Inside your body, their short range is your loss - the dose from an alpha emitter will be concentrated near the emitter, allowing its…

Cyclopropane is another markedly strained ring (the smallest simple ring geometrically possible, really): It used to find some use as an anaesthetic. Strained rings being strained rings, however, it had a nasty habit of exploding. One movie made good use of this phenomenon (without commenting on it at all, there were just labels on the tanks!), where the villain used it as a weapon. No idea if the conditions were realistic, but at least the authors get some creativity points. Some have invoked the colorfully named banana bond theory to explain bonding in cyclopropanes.

Squaric acid is an unusually strong acid for an organic acid: It's also unique because of its strained ring. In general, five- and six-membered rings dominate in chemistry - hence the endless parade of hexagons. Higher rings are tolerated but not-so-favored. Lower rings are possible, but, again, unfavored, because one tends to find atoms' electrons in clouds that don't overlap so well in this configuration. Along with some other moderately strong organic acids (such as the ubiquitous "alpha-hydroxy acids"), it's attracted some attention for (prescription) dermatological use.

As a followup to the entry earlier today, here is a drug that is used in the treatment of gout: allopurinol. In vivo, purines are metabolized by the enzyme xanthine oxidase to hypoxanthine and xanthine, which are converted to uric acid: Allopurinol is a hypoxanthine mimic, which is oxidized by xanthine oxidase to alloxanthine, which is very tightly bound to xanthine oxidase. Tie up xanthine oxidase, purines don't get metabolized to hypoxanthine and xanthine, and you don't end up with much uric acid. Where do all the purines go? It turns out that catabolism isn't all your body can do with…

Happy Thanksgiving week to the American readers! In celebration, let's talk gout! Uric acid is the final product of purine (the bases that comprise exactly half of your DNA) catabolism in humans. Normally, you urinate it out with no problems. Below are guanine and adenine (the two purines that are found the vast majority of the time in vivo) and their metabolite, uric acid: However, it's rather insoluble, so if you've got too much hanging around, problems arise. It can deposit in various parts of the body, notably (in most first attacks) in the big toe. Gout is as puzzling as the rest of…

With a MotD Thanksgiving-themed double-header, which will probably be the last posts for the rest of the holiday week over here.

Inhalants are ubiquitous illegal drugs of abuse and a public health problem worldwide. Most lipophilic solvents have some kind of neurotoxicity (some gas anaesthetics, in fact, work based mainly on their lipophilicity, and are only special because of lower toxicity). Unavoidably, we find these in glue and, memorably, spray paint. As far as I know, in the States, you have to be 18 just about anywhere to buy spray paint (because of graffiti, as well as inhalant abuse) and solvent-based glues (because of inhalant abuse). One thing you'll probably cover if you ever take a business ethics class is…

Brazilian reader Luis Brudna has begun translating some MotD entries into Portuguese. Feel free to have a look if you're not reading this in your first language!

The urea entry ended up with a discussion in the comments I encourage you to read about early organic chemists, one of whom was Kolbe, who first prepared acetic acid (an indisputably organic and biologically relevant molecule) from inorganic compounds. He worked with Wohler (mentioned in the urea entry) as well as Robert Bunsen (of burner fame). From the ACS bulletin above: In the course of work on chlorinated ethanes Kolbe effected the first complete synthesis of an organic compound, acetic acid, from inorganic precursors. His carbon source was carbon disulfide, chlorination of which gave…

Normally, iodine just makes one bond, as you'd expect from a halogen. Some compounds, though, force it into lively higher oxidation states (hopefully without the tendency to explode, as some highly oxidized iodine reagents worryingly exhibit). There is a whole field of "hypervalent iodine" chemistry. A major use is to get something that is a good oxidizing agent, soluble in organic solvent, and milder than the time-honored usual suspects: things like permanganate or dichromate, which work a treat, but often too well, chewing your stuff up a bit more than you'd like. I (V) reagents tend to be…

Urea gets a bad name. By the name, you'd expect it to stink. It doesn't. It finds use in biology as a denaturant, in farming as a fertilizer, in polymer science, and the odd cameo in cosmetic products. It also was among the very first organic molecules to be prepared from inorganic starting materials (see comments). Friedrich Woehler's synthesis of it is today regarded by many as the antecedent to modern organic chemistry.

Para-dichlorobenzene is the principal molecule found in mothballs. We used to use naphthalene, but these days, we've switched. I suspect neither may be particularly healthy, and I suspect that you wouldn't have much luck getting such a product on the market these days, but mothballs have been around for ages.

I know a lot of people don't have access to these journals, so I try and avoid links to walled content, but there's a review article on fenestranes and planar carbon in Chemical Reviews some might enjoy. Check out "Carbon Flatland: Planar Tetracoordinate Carbon and Fenestranes." Check out the Fenestrane/Windowpane entry again if you like. Have a good weekend.

Saccharin, like so many sweeteners, was discovered by accident. From the Wikipedia article: Saccharin's sweetness was accidentally discovered by Ira Remsen, a professor at Johns Hopkins University, and Constantin Fahlberg, a research fellow working in Remsen's lab. In 1879, while working with coal tar derivatives (toluene), Remsen discovered saccharin's sweetness at dinner after not thoroughly washing his hands, as did Fahlberg during lunch. Remsen and Fahlberg jointly published their discovery in 1880 (Fahlberg, C.; Remsen, I. Ãber die Oxydation des Orthotoluolsulfamids. Chem. Ber. 1879, 12…

Another drug that can claim diphenhydramine as an ancestor is fexofenadine, sold as Allegra: Diphenhydramine for comparison: Fexofenadine is a member of a later generation of antihistamines. Diphenhydramine worked fine as an antihistamine (still does - you can still get the stuff OTC as Benadryl), but one big problem was the pronounced drowsiness associated with taking it. Newer antihistamines such as fexofenadine manage to exert most of their effect outside the CNS. Fexofenadine is actually quite an old drug. Once upon a time, you may have taken a drug called Seldane (a very early non-…

Last night I mentioned that diphenhydramine is a somewhat promiscuous molecule, binding to a number of disparate receptors. One of its effects is some inhibition of serotonin reuptake. As you've probably read in countless pop science articles by now, this is one mechanism of action for antidepressants. Take a look at diphenhydramine again: And Fluoxetine/Prozac: Note the similarity in structure to diphenhydramine. Also note the trifluoromethyl group (-CF3). You don't really see organofluorine compounds in Nature (it's so reactive it's been caught up in rocks and ores for ages), but they are…

Diphenhydramine is one of the earliest antihistamines: Being a first generation antihistamine, it has all the associated problems such as drowsiness and dry mouth. These are some of the least specific small molecule therapeutics you could hope for, which gives rise to many of the side effects. Interestingly, it has some effect on serotonin reuptake, which led to some drugs for depression with similar structure.