Streptomyces - Genus of plenty (of drugs)

Okay. Actinomycetes are a group (phyla, actually) of Gram-positive bacteria that like hanging out in soil and water (as decomposers of organic materials) and plants and animals (some are pathogenic, while others do the whole symbiotic thing). The Actinomycetes get their name from the fact that some of them form branching filaments that look kind of like the branching hyphae (collectively referred to as a mycelium) formed by fungi. In an effort to lessen confusion, Actinomycetes are now commonly referred to as Actinobacteria.

Actinobacteria are neat because they tend to produce cool secondary metabolites, many of which have been successfully isolated and turned into useful drugs and other organic chemicals. In particular, an appreciable number of Actinobacteria produce antibiotics, which they use to compete with fungi and other bacteria for resources (and because they are totally badass). The genus Streptomyces (not to be confused with Streptococcus!) is a particularly fruitful source of these compounds, a number of which have been developed as antifungals, antibiotics (antibacterials), and chemotherapeutic (anticancer) drugs. Sit tight, here we go with the lists.

Streptomyces-derived antifungals tend to be macrolide polyenes (large ring structure with lots of conjugated carbon-carbon double bonds), and include such illustrious members as: nystatin (the first Actinobacteria-sourced human antifungal, made by S. noursei), amphotericin B (made by S. nodosus, originally isolated from a sample of Venezuelan soil), and natamycin (made by S. natalensis, insert not-a-mycin joke here).

There are a friggin’ tonne of Streptomyces-derived antibiotics used specifically as antibacterial agents. To begin with, a good number of the aminoglycosides (a class of antibiotics that possess cyclohexyl rings substituted with amine groups and linked together by glycosidic bonds) are the work of this genus. These include: streptomycin (S. griseus), neomycin (S. fradiae), and kanamycin (S. kanamyceticus).

Other antibacterial antibiotics of note include: erythromycin (a macrolide that often subs for penicillin when people be allergic to it, made by S. erythraea), tetracycline (a longstanding acne drug that makes you light-sensitive, made by S. rimosus), chloramphenicol (cheap, effective, but can cause aplastic anemia, made by S. venezuelae), vancomycin (a relatively ginormous glycopeptide that can turn people red, made by S. orientalis), and thienamycin (made by S. cattleya, modified by us to make imipenem, the first carbapenem beta-lactam antibiotic). Whew!

Here is where it gets really cool. A number of the antibiotics produced by Streptomyces have proven to be too toxic for use as antibiotics in humans, but because of their toxicity towards cells (specifically dividing cells) they have been reinvented as chemotherapy drugs. We’re talking drugs like: actinomycin-D (the original), bleomycin (glycopeptide made by S. verticullus), mitomycin (aziridine made by S. lavendulae), and plicamycin (made by S. plicatus). Plus we have the anthracyclines daunorubicin and doxorubicin (S. peucetius), and migrastatin (macrolide, under investigation, made by S. platensis).

Whoo-wee! As you may have noticed, drugs isolated from species of Streptomyces tend to have the suffix -mycin, although there are lots of exceptions. And that's that.

- Birnbaum J, Kahan FM, Kropp H, MacDonald JS (1985). Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin. Am. J. Med. 78 (6A): 3-21.
- http://en.wikipedia.org/wiki/Actinobacteria
- http://en.wikipedia.org/wiki/Streptomyces


Osmium tetroxide - Oxidizer...of death!

Osmium (Os) is one of those elements situated smack dab in the middle of the periodic table and thus destined to be ignored by pretty much everyone. Let's show it a little love, shall we? A couple of choice facts about osmium: it is a member of the platinum family of transition metals, is incredibly dense (22.61 g/cm3 - gold is only 19.3 g/cm3 and lead a measly 11.34 g/cm3), has a very high melting point (3033 ºC - iron melts at 1538 ºC), and gets its name from the Greek osme (meaning odour). To explain that last bit, when solid osmium is heated above 100 C, it readily reacts with oxygen in the air to form osmium tetroxide, which apparently stinks like ozone or chlorine (i.e. very acrid). This reaction occurs slowly at room temperature with powdered osmium.

Osmium tetroxide is a wonderful combination of highly volatile (evaporates quite readily) and highly toxic. Solids generally don't appreciably sublime (convert directly into a gas) at room temperature, but osmium tetroxide is special. Its high toxicity is the result of it being: (A) an extremely powerful oxidizing agent, meaning that it loves to react with (and so damage) living tissues, and (B) relatively small and water soluble, such that it easily penetrates skin and mucous membranes.

Exposure to even low concentrations of osmium tetroxide vapour can cause severe irritation of the skin, eyes, and respiratory tract. This can mean fun things like dermatitis and ulceration, blindness (it can stain the cornea of the eye), and pulmonary edema. Chronic exposure to the vapour can lead to the accumulation of osmium in the liver and kidney with damage to these organs.

The whole oxidizing living tissues things makes osmium tetroxide useful to researchers as a means of fixing biological samples in place, since the oxidation of macromolecules such as lipids leads to their atoms becoming cross-linked. It is also used by researchers to stain biological things in order to image them using transmission electron microscopy. Osmium nuclei are nice and dense, and so are good at scattering electrons.

- Makarovsky I, Markel G, Hoffman A, Schein O, Finkelstien A, Brosh-Nissimov T, Tashma Z, Dushnitsky T, Eisenkraft A. Osmium tetroxide: a new kind of weapon. Isr Med Assoc J. 2007 Oct;9(10):750-2. Review.
- Smith IC, Carson BL, Ferguson TL. Osmium: an appraisal of environmental exposure. Environ Health Perspect. 1974 Aug;8:201-13.


Cyclopropane - The little ring that can knock you out cold

Like it's acyclic cousin, cyclopropane is a colourless gas with a notable smell and taste that is both inflammable and potentially explosive and typically stored in metal cylinders as a liquid under pressure.

Cyclopropane is the simplest possible cyclic hydrocarbon, consisting of just three carbon atoms bonded together at 60 degree angles to one another, plus a bunch of hydrogen atoms. Since carbon bonds are normally (and ideally) positioned at a 109.5 degree angle to one another, the bonds in cyclopropane are weakened by angle strain, making the gas more reactive than any other cyclic or acyclic alkane. Molecules of cyclopropane really like to break down to form linear acyclic compounds, and this decomposition can be explosive. Such an explosion can be even more powerful if the gas is mixed with oxygen. Sufficient volumes of pure liquified cyclopropane will self-detonate. The liquid has to be shipped in containers filled with metal or glass wool to improve its stability in order to prevent explosions.

Cyclopropane was first investigated as a potential anaesthetic agent in the early 1930s. Doctors liked it because unlike the other anaesthetic gases/vapours available at the time, it was non-irritating to the respiratory tract, did not significantly depress respiration, heart function or blood pressure, was highly potent (meaning that it could be diluted way down with oxygen), was not appreciably metabolized in the body, and possessed a relatively wide margin of safety between therapeutic and toxic concentrations.

The propensity for cyclopropane to burn/explode and occasionally produce arrhythmias, particularly ventricular tachycardia, led to it being replaced by halothane and it's brethren in the 1950s and 60s (in the Western world).

- Goodman and Gillman
- http://en.wikipedia.org/wiki/Cyclopropane