A number of carboxylic acids are used as cosmetics. Familiar to many readers will be glycolic acid. It’s used in over-the-counter “cosmeceuticals” to improve skin tone. Also used in professional “chemical peels” is trichloroacetic acid. These acids are all closely related to the familiar acetic acid, but they have “electronegative” substituents.

In the aqueous systems we’re talking about, the strength of an acid is related to its tendency to liberate protons. An acid’s tendency to dissociate into protons is related to the thermodynamic stability of its “conjugate base” - the acid, minus a proton. These electronegative substituents withdraw some electron density from the negative charge on the conjugate base, giving a more potent acid. Read the rest of this entry »

Here’s one many will have heard of - creatine. Most people know it as a bodybuilding supplement; it is used to add lean mass (from working out harder, and it’s contended, some intracellular water retention), as well as allow harder anaerobic workouts before failure. It’s the latter we’re interested in.

Creatine actually occurs endogenously, and it is synthesized by the liver. An enzyme called creatine kinase exists in the body to move a phosphate from ATP to creatine, making N-phosphocreatine and ADP. This reaction is not very thermodynamically favorable - you will only make 1 molecule of phosphocreatine for every 1000 molecules of ATP or so. This is good, because your body needs the ATP for other things (you’ve probably heard of ATP as the “universal energy currency” of the body) as well. Phosphorylation of creatine only happens when your body has a large excess of ATP.

The reverse reaction takes place too, and, as you might guess, phosphocreatine still would prefer to transfer its phosphate to ADP, regenerating ATP. It’s favored in the low-ATP regime - such as during the last repetition of a weightlifting set. This latter reaction is shown below:

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This one is a much larger molecule than we usually do, but it’s easy to forget that enzymes (and all proteins) are really just very large molecules. Taq polymerase is a DNA polymerase (DNA-copying enzyme) from the microorganism thermus aquaticus, a bacterium that lives in very hot water. Read the rest of this entry »

Hydrogen peroxide seems boring at first blush- after all, you can get it in those little brown bottles at the drugstore, and they don’t do much but fizz - and then, only when

you pour it on a cut (more on that later). H₂O₂ has a structure a lot like water - H-O-O-H instead of H-O-H. That O-O bond is the peroxide bond, and it’s what’s responsible for H₂O₂’s oxidizing power.

The drugstore H₂O₂, you’ve probably noticed, is only a 3% solution (and it can still burn your skin a little bit). Even in a lab, the highest concentration I can easily get is 30%. These bottles are vented, since peroxide tends to decompose to water plus oxygen. This is the bubbling reaction you obersrve when you pour it on a cut. This is due to the action of the enzyme catalase, which exists to do just this. Like many enzymes, catalase is present at an unusually high concentration in liver. Chop some liver up finely and pour some peroxide on it (3% from the store will do) and you’ll see what I mean. Certain other metal compounds will work, notably silver and manganese dioxide.

The 30% peroxide we get in the lab comes with dire warnings not to spill it on paper or anything combustible (because it would ostensibly start a fire). I believe it, but it’s never happened to me. Peroxide actually gets dangerous in the 70%+ range. It will happily propel a rocket. It’s really amazing how a 25-fold or so increase in concentration can make something act like a completely different substance.

Just about anyone who’s ever been in a GNC knows melatonin by now. People know it best as a sleep aid. However, it is responsible for a diverse range of biological processes, and you might be surprised to know that it is a sufficiently ancient compound that it seems to be found in quite a wide range of species.

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This drug is one that really has had a profound effect on the medical landscape, but you don’t hear much about it in popular culture. Naloxone, commercial name Narcan, is an opioid antagonist. An antagonist is a drug that binds to a receptor, without activating it. Contrast an agonist, which binds a receptor and activates it. Opioid agonists are drugs like heroin, morphine, codeine, etc. Read the rest of this entry »

PABA, or para-aminobenzoic acid, was used as a sunscreen some time ago. Most sunscreens are simply organic molecules that aren’t too soluble in water (so they don’t wash away) that absorb UV light (and convert it into heat). There are other kinds, like zinc oxide creams, that just provide an opaque/reflective layer. PABA, however, is of the first type.

It is also a biosynthetic precursor to folic acid in many bacteria. This is a profoundly essential nutrient, especially for rapidly dividing cells. This applies to pregnant women (hence the inclusion of extra folate in prenatal vitamins) and most bacteria, which tend to be pretty busy dividing. Since people don’t depend on the PABA-Folate conversion system (because we don’t have it), PABA has been used as a drug target for antibiotics. These are the ancient sulfa drugs, which predate even penicillin. Here is the structure of PABA:

Today, PABA is not in sunscreens because of allergy and carcinogenicity concerns (close analogues are safe and included, though). Sulfa drugs have also fallen by the wayside, largely because of allergy and poor efficacy compared to the modern stuff.

Interestingly, furosemide (Lasix) contains a sulfa-drug like structure, but works on a completely different pathway (it’s a diuretic).

See you tomorrow!

In the comments, yesterday, we started talking about other retinoids a bit. We were talking about naturally occuring ones and close pharmaceutical analogues. I was racking my brain today trying to come up with one that didn’t follow the terpenoid/long chain of alternating double bonds pattern. I know of one that a friend targets for his research, but I can never remember the structure. Then I remembered another: adapalene!

Not very like retinoic acid (a vitamin A-related compound):

It is a topical acne drug. Many of the acne drugs, such as Accutane (isotretinoin) and Retin-A (tretinoin, just retinoic acid, above) target Vitamin A (really retinoic acid) receptors.

My favorite part about adapalene is that it has an adamantyl group:

Adamantane is named from Latin, from Greek, from adamas (”diamond,” or “invincible” depending whom you ask). This is because the 3-d structure of that ugly thing is actually very much like diamond. This has led into a bunch of research on diamondoids and molecular diamonds, which are kind of neat. Here, it is just a bulky alkyl group.

I think it’s 4-day weekend time. See you later.

I’ve mentioned this in the past as one of the canonical bitter compounds. It was originally extracted from the bark of the cinchona tree. It has been found useful in the treatment of malaria. The scope of malaria’s effects is both broad and amazing. According to a citation in Wikipedia, malaria infects 350-500M individuals annually - for reference, this is roughly 6-8% of the world! The vast majority of infections are in African children.

Antimalarial drugs, then, are a godsend. One of the most famous natural products ever, quinine was extracted from cinchona for years, and finally synthesized by Bob Woodward in 1944. The pharmaceutical and chemical industry would look incredibly different today if this man had never existed. You can see a picture of him at Dylan’s Tenderblog. He is the one on the right, smoking the cigarette next to the flask of the toxic and/or flammable chemicals. Amazingly, RB Woodward’s total synthesis of quinine takes up only one page in a journal. It would be slightly longer today. With more pictures. Here’s a picture:

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Here is one with which many readers will be acquainted first hand: nicotine. Named after Jean Nicot, tobacco booster extraordinaire, nicotine is an alkaloid that occurs in the whole nightshade family, of which tobacco is a member. Typically people will give the structure on the left, below.

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