in vivo chemistry

Now we can’t drink tea!

If you’re a man and you live in Scotland do not drink tea. According to a BBC report  >7 cups a day give you a >50% greater chance of developing prostrate cancer than “normal” tea drinkers. This was the result of a  study over 37 years involving 6000 volunteers aged between 21 & 75 years of age. I’m surprised they didn’t choose whisky and/or beer (they have probably been checked at some point in distant past). This is in direct contrast to a National Cancer Institute report which suggests the opposite, at least for green tea.

What’s next I wonder, coffee is already on the black list, as well as fatty foods smoking, no doubt sex will also rear it’s ugly head in the list of cancer producing agents, water is also dangerous, fish swim in it and you can drown as well.

Wiki tells us the exact opposite to the results reported by the Glasgow study. Tea is actually beneficial for you in all sorts of ways.

So what’s in tea that makes it so harmful or so good for you? Well there is theanine and caffeine, making up about 3% of its dry weight up to 90mg per cup, depending upon the tea. Theanine moves across the blood brain barrier (quite distant from the prostrate) and has a synergistic effect with caffeine, high doses even providing a neuroprotective effect. Caffeine is a stimulant and the author of the Wiki page suggests that it may even have moderately protective effect against certain cancers.


There are also things like theobromine (or should it be teaobromine) and theophylline. So those compounds are  probably not the cause of this higher prostrate cancer risk.

What else?

Up to 30% of the dry weight of tea are the catechins. These look like a possible candidates! Some present in green tea are shown below.


Just look at all those nasty phenols, they may even have antioxidant properties, but as carcinogens, well,  I think they are not very high on the list.

The tea plant apparently has the capacity to absorb lots of the pollutants we pump out every day, e.g. fluoride and aluminum, the latter  can be present up to 30,000ppm by dry weight! Exactly what the form of the fluoride and aluminum is I don’t know, presumably sodium fluoride, perhaps someone can enlighten me as to the aluminum source.

So everyone, what shall we drink now? How about red wine, with all that reservatrol it must be good for you perhaps the chances of developing cancers will be reduced. It’s like everything we do (apart from working and paying tax), taken in moderation it is very enjoyable, but taken in excess, well I guess we have all suffered a hangover at some time.

Enjoy your tea breaks.


Glucose Fuel Cell for Medical Implants

Professor Rahul Sarpeshkar and colleagues at MIT have created an implantable fuel cell which relies on glucose as its fuel. The device could potentially be used as a power source for the computers needed to decode brain signals and manipulate prosthetic or perhaps paralyzed limbs. The article was published in PLos ONE.

There are many layers of cool in this story. Implantable glucose fuel cells have been invented before – back in the 70s – but contained enzyme-based anodes which degraded over time and needed to be replaced. Because of this, implants like pacemakers rely on lithium ion batteries – which also drain over time, but have a much longer lifespan. This design utilizes a platinum anode to oxidize glucose ultimately to gluconic acid, liberating 2 electrons. The cathode is a matrix of single-walled carbon nanotubes which reduce dissolved oxygen to water.

What strikes me as the coolest part of this story, the fuel cell is fabricated on a silicon chip and would be placed in the cerebralspinal fluid next to the brain. Platinum is already known for being fairly biocompatable, but placing the chip in the cerebrospinal fluid is beneficial as there are very few white blood cells in the CSF to trigger an immune response and potential rejection. The CSF contains roughly the same concentration of glucose as plasma, and is not predicted to consume enough glucose fuel so as to impair brain function.

via DOI:10.1371/journal.pone.0038436

To avoid short circuiting the fuel cell, the platinum anode is enclosed in a ring of the carbon nanotube cathode. The cathode sequesters the dissolved oxygen for the reduction reaction, creating a concentration gradient across the cathode such that dissolved oxygen does not penetrate past the cathode. The nanotubes do not oxidize glucose, but are permeable to glucose, so the glucose passes through the cathode unreacted. The cathode is separated from the anode by a strip of nafion, a biocompatable perfluorniated polymer similar to teflon, but with branched sulfonate groups throughout. The sulfonate groups allow protons to flow through the nafion from the anode to the cathode, and nafion is permeable to glucose as well. The anode is at the center and can be as large as 2.5cm x 2.5cm.

The oxidation reaction at the anode is considerably less efficient than other implantable glucose fuel cells, but the biocompatability and long lifespan of the fuel cell makes this a really nice step forward in the treatment of paralysis and spinal cord injuries.

#ToxicCarnival: Nitroglycerin

Tonight, we make soap.

Matt over at Sciencegeist is organizing this blog carnival in an effort to reclaim the word chemical from the hands of ignorant people who blindly assume anything with ‘chemicals’ in it must be evil. This is not a moment too soon.  I’m not exactly sure how the pendulum of public opinion swung from products being advertised as ‘Better living through chemistry’ to products being advertised as ‘chemical free’ (whatever that means). Soaps and other skin care/beauty products are certainly in the cross-hairs of the ‘chemical free’ crowd, but that’s not what I’m talking about today.

As the tallow renders, you skim off the layer of glycerin. If you were to add nitric acid, you got nitroglycerin.  If you were to add sodium nitrate and a dash of sawdust, you’d have dynamite. 

Read more ›

Nexium’s Dirty Little Secret

This is Prilosec OTC (omeprazole, also marketed as losec, antra, gastroloc, and a number of other names in other countries):

This is Nexium (esomeprazole, also marketed as sompraz, zoleri, lucen, etc):

Did you note the difference?  I’ll give you a second to look again.

Omeprazole was brought to market by (what is now) AstraZenica in 1989.  It is used in treatment of gastroesophageal reflux desease (GERD, commonly known as acid reflux).  It is a proton pump inhibitor which works by blocking the production of gastric acid by parietal cells.  It was a blockbuster drug.  In the year 2000 alone, omeprazole made $6.26 billion.  But in 2001, omeprazole’s patent was set to expire.  AstraZenica needed something to fill their pipeline, so they looked at their data for omeprazole.

Omeprazole is an example of a little-known class of chiral molecules where the stereogenic atom is not carbon.  We  typically think of stereocenters with carbon as the central atom.  But this is an example of a stereogenic sulfur atom (in case you’re wondering where the fourth ‘thing’ bonded to sulfur is, it is a pair of electrons.  See the explanation of chiral sulfoxides for more information.  Ellman’s chiral auxiliary is a good example of chiral sulfoxides in use).  Omeprazole is a racemic mixture: an equal mixture of (R) and (S) enantiomers.

In looking at their data on omeprazole, they noticed that the (S) enantiomer was more potent than the (R) enantiomer (according to this website, 4 times more potent).  So in 2001, AstraZenica prepared and won FDA approval for enantiomerically pure (S) omeprazole, which they called… esomeprazole.  Very creative.

So in 2001 when omeprazole lost patent protection, esomeprazole came to market.  In theory, you should be able to take a smaller dose of esomeprazole to achieve the same efficacy of omeprazole.  Indeed, the top suggested dose of omeprazole is 80 mg, and the top suggested dose of esomeprazole is 40 mg.  The only difference between the two drugs is the optical purity.  Omeprazole is a racemic mixture, and esomeprazole is optically pure (S) enantiomer.

So while I’m no health care professional (and my opinions should not be taken as such), it seems to me that if you’re taking prescription esomeprazole, you should ask your doctor if a higher dose of omeprazole (which would be cheaper if you get the generic version) would work just as well.

What’s also interesting to me (which I did not know until I was reading up for this post), is that omeprazole and esomeprazole are technically prodrugs: the ingested compound is not actually the active molecule.  Under acidic conditions (like in gastric acid), omeprazole is converted to a tetracyclic cation which is then covalently bound to ATPase:

Note that the tetracycle is achiral – it has no stereocenters, sulfur or otherwise.  So whether you take the chiral esomeprazole or the racemic omeprazole, both are converted to the same achiral tetracycle.  Again something to note if you’re taking the optically pure version of the drug.

Also, another interesting piece of trivia:  omeprazole competitively inhibits the CYP2C19 and CYP2C9 enzymes.  Other drugs – like warfarin and diazepam (valium) depend on these enzymes for metabolism.  As a result of the competitive inhibition, these drugs cannot fully metabolize.  The effective concentrations of these drugs is increased.  People taking warfarin or diazepam should be warned if they are planning on taking omeprazole.

So now you know: omeprazole and esomeprazole are effectively the same drug.  I’m not sure why one would take prescription esomeprazole when omeprazole is available (over the counter in most places).  I understand omeprazole sometimes has more side effects than esomeprazole in some patients, so if that’s the case, so I get taking the drug which minimizes side effects.  Make sure you also read this interesting article written in 2002 about the history of omeprazole.

By October 18, 2010 19 comments in vivo chemistry