Dienstag, 25. August 2009

A rose by any other name...

...would smell as sweet. But I have recently wondered why. Maybe the question has to do with my almost neurotic sense of smell. I used to know who walked down the hallway at work just by smelling the perfume trace they left behind, much to the annoyance of my office coleague who was getting a bit paranoid about this sensitivity. In any case, during the writing of my thesis, as a sign of avoiding behaviour I assume the question popped into my head. Ok, stuff smells, but why? What is the structural relationship which makes cabbage smell different than peaches? I shamefully admit that for a person who wanted to work in perfume research it was a bit late to ask this question, but whatever kept me from writing about plasma reactors was a good excuse. I was familiar with the usual story which said that small, hydrophobic and volatile molecules bind to the receptors in the nose and then the neurons take it from there. Now I was curious why do similar molecules (let’s say two alcohols, the well known ethanol and it’s cousin propylalcohol, who just has an extra methyl group) smell different.

The two major theories describing the structure-odor relationship are the odotope theory and the vibrational theory. The first one assumes that the different parts of smelly compounds (odotopes) can be bind to the receptors. More graphically , if we imagine the odor molecule as a small dog, some receptors will pull it’s tail, some will accomodate the belly and some the fluffy ears. By putting all the signals together we can label the obtained sum as „dog“. Seems easy, right?

However, there seem to be some issues with this theory. Good experimental chemists can detect class of substances by their smell. I remember one of my former supervisors telling me that he can smell tert-buthyl groups. But tBu is a relatively voluminous group and hence one could imagine it is selectively detected. If we take for example thiols – all thiols stink and regardless what accompanies the SH-group. But then again, thiols and alcohols are quite similar, Turin argues and hence they should smell the same. The oxygen atom is however smaller than the sulphur one so an alcohol and it’s corresponding thiol will not have exactly the same shape; a slight difference, but a difference however. And we all know how picky nature is about „small“ differences.
Another issue taked with this theory is that if one „burries“ the smelling group between more voluminous groups (and thus the molecule cannot bind its smelly head in the receptor) it should not smell. However 2,4 and 2,6 disubstituted phenols smell the same. But phenols again are not the best example of „hidden“ odotopes.
Finally, if one exchanges an atom in the molecule for an isotope (like hydrogen for deuterium), the resulting molecules should differ only in molecular vibrations, but not in shape or binding ability.

The second theory put forward to counteract the above objections is a bit more complicated and it suggests that the receptors behave like a vibrational spectroscope. More explicitly, if we imagine a Y shape receptor with an arm of the Y more poor in electrons than the other arm, then electron conduction from one side to the other can occur if the receptor catches a molecule able to vibrate at exactly this energy difference. All this talk about spectra can be a bit scary, but as a comfort, other two of our senses (vision and hearing) also heavily relay on spectral aquisition and interpretation.This type of nose-spectrometer would have quite poor resolution, and hence a large number of receptors would be needed to do the job (which by the way, we have; about 1000 genes code their expression).

However this mechanism does not explain why some enantiomers – molecules with the same composition and structure but containing an assymetric atom around which the substituents arange in different ways- smell completely different (the carvone pairs with spearmint and caraway smells respectively, limonene with mint and citrus and citronellol with citrus and rose are just a few examples).

And finally there is the problem of odorless molecules which both theories cannot explain. If we assume that the shape of different molecular parts matter, it would mean that larger molecules, with more „paws“ or „ears“ has more chances to conect to a receptor and should be smelly. But most odorless molecules are particularly the big ones. If we accept the vibration theory it would mean that all molecules binding to receptors should smell (because all molecules vibrate).

The vibration theory was put to the test by a group at Rockefeller University in 2004. Human subjects failed to differentiate acetophenone and it’s deuterated counterpart. This lead them to dismiss „an universal theory based on one man’s sense of smell“. It is worthy to mention at this point that this man’s sense of smell did benefit a successfull company working in the field of synthetic odorant rational design and earned him the surname of „The Emperor of Smell“ (mental note to self to read the book).

In 2007 another group took a look at this problem and their conclusion is a bit more inbetween, namely that besides size and shape other features (like, say, vibration) could also plays a role in olfaction.

So to sum up, as much as I enjoy the idea of being a high tech analytical facility with indirect tunelling happening every time I sniff my favourite perfumes, I cannot completely disagree with the odotope theory. I will try to follow-up on this issue and check the work of people who like to reconciliate the two and admit that size and chemical detection do not mutually exclude.

Montag, 10. August 2009

Silver jewelry..for the viruses


Autumn is drawing close - at least here, where I live -, and with it come increased concerns about a possible swine-flu pandemia. Some people choose to wash their hands more often, the more cautious will go and buy masks and some of them, according to this morning’s news on my local radio station, are stocking up on colloidal-s
ilver sprays. That would be sprays containing really small tiny particles of metallic silver. I am not advertising so no hyperlink.

As a former „nanotech-gal“ I am delighted that a nanoengineered product is experiencing market-success. The question is, however, weather nano-silver is the ultimate weapon to fight the flu pandemic or will it just make the viral surroundings look shiny and disco-like?.

The health benefits of silver are known since the times of ancient civilisations (hence the greeks used silver beverage recipients). In some sources you might also find an interesting hypothesis on the wide spreading of silverware use – apparently this was due to the empirical observations that rich families, who afforded these objects, were less prone to sickness and infections. Historians have probably a better view of this, so I will focus on the scientific aspect of the question.

The antibacterial properties of silver ions, mainly from silver nitrate solutions, started to be investigated after WW2 and, short after, a number of products hit the market . For example, a good review on their applications in the treatment of burns can be found here. (1) In the year of grace 2008 however, people still investigate the mechanism trough which these ions manage to effectively kill bacteria, without having nasty systemic side effects and inducing no resistance. The widest spread theory is that the said silver ions, by their chemical name Ag+ , mess up with the thiol group of respiratory enzymes, making the latest' functioning impossible and thus leading to bacterial death (figure 1). Other paths involve the agglomeration of silver ions in the bacterial vacuoles and cell walls – obviously bacteria don’t appreciate this, they experience change in morphology (both membrane and cytoplasmic contents) and they die. Finally, silver could speed up oxidative degradation and also lead to bacterial death.

Figure 1. An artist' view of a bacterium with nanoparticles stuffed up its ahem, nose

Similar mechanisms are also proposed for the action of silver nanoparticles, and some groups go to great lenghts to demonstrate this. The nanoparticles are however a lot more effective, since one can achieve an important antibacterial effects using concentrations in the nanomolar range. This is easy to understand if we think what a huge increase in surface (and hence virtual silver concentration) can be achieved by colloidal dispersion. Interesting enough this works very well for gram-negative bacteria and far from it for the gram-positive type. The major difference between the two is the thickness of the an intermediate layer in the cell wall. Gram negative ones have a thinner layer. An easy hypothesis would be to assume that this leads to an easier penetration of the Ag nanoparticles. Oh, well, more work for nano-bio PhD students.

So, now that we know bacteria hate silver - and more or less why, or better said how -, what’s the deal with viruses?

Well, here it gets tricky. There have been some sudies regarding the interaction of silver nanoparticles with viruses (some recent ones are reviewed in the introduction of this paper ) and it seems to be all about the scale. Nanoparticles cannot penetrate virus capsids for many reasons, a simple one being a size problem. Nanoparticles and viruses happily share the same tens-of-nanometer dimension. For comparisons bacterias have a couple of microns, so they can eat a lot of particles. Second, viruses don’t have respiratory enzymes which can be messed by silver. At most they could be degraded through a silver-catalysed oxidation process, but usually they are tough little buggers. However, suitably functionalised nanoparticles can bind to viruses, block the groups that they use to attach to cells and thus making them „die“ by solitude, or at least keeping them busy until the next good handwash. I should have mentioned before probably that viruses need a host to do their nasty stuff - like reproduction. So no home, no reproduction, no flu or HIV or Hepatitis.

I couldn’t find any other sources (credible sources that is, not blogs selling colloidal generators :)) proposing a different, universal mechanism through which silver nanoparticles would destroy all types of viruses. For all we know it could also be that the nanoparticles mess up with the cells so bad, that not even viruses have the desire to reproduce inside anymore.

One could therefore conclude that there are a lot of colloidal-generator-sellers out there that profit of the lay men ignorance concerning the differences between viruses and bacterias (aren't they all small evil things that we don’t see ?) and that buying silver-based products for swine-flu profilaxis is just a waste of money. There is a consolation prize however. A very real problem lies in the susceptibility to bacterial infections while having the flu, because the immune system has other priorities. And it is usually these infections which are difficult to treat and can become life threatening – as it is the case for complicated pneumonias. So a good dose of nanosilver could come in handy to prevent these last ones.

This being said, I will just resume myself to washing my hands regularly and not kissing strangers :).

(1) Unfortunately most scientific journals are not open-access (yet). The abstract should however be available in some cases.

Donnerstag, 6. August 2009

The first post (1)

Good evening everyone,

Since a while a number of people ask me to write about science. Not because I some sort of hot-shot in the field, but because apparently they like my crazy explanations about more-or-less-chemistry-related stuff and they would enjoy to see them exposed somewhere. I myself toyed with the idea for a while; I hope this time I will find the energy (and patience) to make it happen.

Thank you for your kind attention,
A.


(1)I read A LOT of blogs and I always like to look at the first post, in the hope to some sort of "motivation statement" of the author. In a dissapointingly large number of cases the first post it's just "Test" :( (2)
(2) Since recently I am a proud Mac Owner. Where ARE the square brackets?