Chemistry World Podcast - May 2009

00:12- Introduction 

01:57-- Tackling malaria by reinvigorating current drugs     

05:44-- Gel detectors spot cancer biomarkers 

09:01-- Harry McArdle discusses functional foods that could improve health     

15:03 -- Force-sensitive catalysts could help damaged polymers self-heal  

18:08-- Chemical coatings that behave like cartilage 

21:36-- John Turner describes efforts towards the artificial leaf 

27:37 -- How did today's oxygen-rich atmosphere arise? 

29:50-- Don't ignore earthquake chemistry 

33:33-- The chemical conundrum - what is the chemical name of the most active member of the auxin family of plant hormones, responsible for promoting plant growth? 

(Promo)

Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.

(End Promo)

(00:12 -- Introduction)

Interviewer - Chris Smith

Hello! This is May 2009 edition of the Chemistry World podcast with James Mitchell Crow, Phil Broadwith and Bibiana Campos-Seijo.   In this month's show, how chemists are breathing new life into old drugs.

Interviewee - Phillip Broadwith 

What they have done is taken a molecule, which has its own antimalarial activity and combined that with some activity, which will reverse the resistance of the malaria parasite to drugs such as chloroquine and quinine.

Interviewer - Chris Smith

A clever way to combat antimalarial resistance, there'll be more on that story in just a moment. Also how micronutrient research looks at to make us whole a lot healthier.

Interviewee - Harry McArdle 

And it may be you may be able to get things that really do make a difference for arthritis or do make a difference for osteoporosis, things like that, you may be able to do that nutritionally.   And with proper research and with proper science, it may be possible to make those advances and if you did manage to do that then you could end up in a situation where people would remain healthy for much longer than they do at the moment.

Interviewer - Chris Smith

Indeed, you are what you eat, as they say. And also on sunlight to split water the way, how chemists are copying the water splitting process that goes on in leaves.

Interviewee - John Turner 

Well we are trying to use the energy and sunlight to split water into hydrogen and oxygen and we do that by taking semiconductor materials and instead of putting them in a solar panel, we put them in water and shine light on them and interestingly enough sunlight has enough energy in it to split water to hydrogen and water.

Interviewer - Chris Smith

John Turner, who will be explaining how he is doing that later in the show.   Hello, I'm Chris Smith and this is the Chemistry World podcast.

(Promo)

The Chemistry World podcast is brought to you by the Royal Society of Chemistry. Look us up online at chemistryworld dot org.

(End Promo)

(01:57 -- Tackling malaria by reinvigorating current drugs)

Interviewer - Chris Smith

Every year there are about 200 million cases of malaria worldwide and about 2 million deaths and the problem is becoming a lot worse because many of the drugs that we could once rely on to prevent people from getting infected now aren't working and that's because the malarial parasite has become resistant to them. But now researchers have come up with a clever way to combat the problem, Phil Broadwith

Interviewee - Phillip Broadwith 

Well this is some work by a group in Portland Veterans Affairs Medical Center in Oregon led by Jane Kelly and Michael Riscoe. What they have done is taken a molecule which has its own antimalarial activity and combined that with some activity which will reverse the resistance of the malaria parasite to drugs such as chloroquine and quinine.  

Interviewer - Chris Smith

Okay, so this is the way basically of restoring sensitivity amongst malarial parasites, so these drugs which we thought we were going to have to consign to the waste bin.

Interviewee - Phillip Broadwith

Exactly right and that fits in very well with the World Health Organization's stipulation that all new antimalarial drugs should be given in combination to help combat that resistance.

Interviewer - Chris Smith

So how does this new molecule do this amazing resensitizing effect?

Interviewee - Phillip Broadwith

Well what the group at Oregon noticed was that if they took an Acridone which is a tricyclic molecule and had a particular alkyl amine chain hanging off a nitrogen atom in the middle of the molecule, having that functionality in the molecule allowed it to reverse the resistance against chloroquine. What they did with that is engineered the Acridone ring system to have its own antimalarial activity.

Interviewer - Chris Smith

This must presumably rely on us understanding a bit about why the malarial parasite is resistant to these in first place.

Interviewee - Phillip Broadwith

That's exactly right Chris. The malarial parasite has to process blood and particularly haemoglobin to get its amino acids that leaves the heme part of the molecule which is toxic on its own. So what would normally happen would be that the parasite causes the heme to polymerize into something called hemozoin and chloroquine and related drugs interfere with that process, so what the parasite has done is evolved a transport protein called plasmodium falciparum chloroquine resistance transporter which pumps the chloroquine and quinine-type drugs out of their active target area which stops them being effective. So then what this molecule is doing is locking that transport channel, so it stops the chloroquine being pumped out of the target area and allows it to have its effect.

Interviewer - Chris Smith

Is it well tolerated, will it actually mean that you could take this, could this be used as a drug or is it an interesting academic observation that in fact is too toxic for us to use?

Interviewee - Phillip Broadwith

Well at the moment, this is very much an academic lead. It is very much a first kind of generation compound, there's still quite a lot of work to be done in terms of optimizing the activity both as an antimalarial and as this chemosensitization effect, and eventually will have to go through all sorts of clinical trials and whatever, but the real key to this is that it is a new way of thinking about antimalarials having this chemosensitization which gives you the great activity in combination therapy.

Interviewer - Chris Smith

It's intriguing to think that's pretty much the same stunt has been being played in the word of microbiology against bacteria, because there were bacteria that got resistant to antibiotics, chemists then came out with clever molecules that would effectively decoy the bacterial strategy for breaking down the antibiotic leaving the antibiotic to do it's job and this is kind of the same thing, isn't it?

Interviewee - Phillip Broadwith

Exactly right, there's a lot of mechanisms within bacteria and in cancer cells where the resistance mechanism is due to the active molecule being pumped out off the target area, so this kind of strategy could well be applied to those areas as well.

Interviewer - Chris Smith

Thank you Phil, it is intriguing isn't it and I think we've got a chance giving a new lease of life to some drugs that we had previously written off.

(05:44 -- Gel detectors spot cancer biomarkers)

Interviewer - Chris Smith

Now from diseases of the blood, malaria, parasites to diseases of the lung and may be there's evidence to suggest that we might be able to actually, whether as the policeman tells you to blow into a bag or used to, there might be a way of diagnosing lung diseases that way.

Interviewee - Bibiana Campos-Seijo 

Yes, a group of researchers at the University of Michigan in the United States have come up with a device that uses a jelly like substance to detect nitric oxide in exhaled breath.

Interviewer - Chris Smith

Why would there be nitric oxide in exhaled breath?

Interviewee - Bibiana Campos-Seijo

It is a biomarker for lung diseases such as tuberculosis and cancer. By blowing into the device you would be able to detect whether there is nitric oxide in the breath of a patient. 

Interviewer - Chris Smith

And what is the readout. What does it do to this substance in order to tell you that the nitric oxide is there? 

Interviewee - Bibiana Campos-Seijo

The nitric oxide acts as what they call a gelator, which basically is a substance that is capable of forming gels, then we need a substrate which in this case is a molecule that contains a benzene ring with some substituents, a triple bond and then a dihydropyridine ring which has a non-planar confirmation.

Interviewer - Chris Smith

So this is a liquid to start with?

Interviewee - Bibiana Campos-Seijo

Yeah, yes, yes this is a liquid, but when it is exposed to nitric oxide in the presence of oxygen the dihydropyridine ring is oxidized to form a planar pyridine ring.

Interviewer - Chris Smith

Oh, right, so now instead of being spiky effectively it's flat so you can stack them up.

Interviewer - Bibiana Campos-Seijo

Yeah, the molecules stack up very easily and the scientists have discovered that there are pi-pi interactions between the electron rich group of the different molecules with the electron groups of the other molecules and basically what this creates is a gel.

Interviewer - Chris Smith 

Playing devil's advocate for a minute Bibi, I mean that's very nice, but we've got very good E-nose technology and we know bacteria and other lung diseases produce classes of volatile chemicals that we can detect in breath, so why do we need a gel to do this for us.

Interviewee - Bibiana Campos-Seijo

Yeah there are tests to diagnose this diseases and I think that they are based on chemiluminescence but the problems with these devices is that first of all you need a technician to interpret the data, you need to time to prepare the sample and apparently it is very time consuming and it is expensive. So this would provide a means of actually analyzing breath for the presence of nitric oxide in a quick, cheap and a very easy way. You have a very simple visible output there which is the formation of a gel.

Interviewer - Chris Smith

And, devil's advocate mark two, is there actually enough nitric oxide coming out in the average person's breath for this present approach to detect it?

Interviewee - Bibiana Campos-Seijo

No, that's perhaps the.

Interviewer - Chris Smith

It's a slight challenge.

Interviewee - Bibiana Campos-Seijo

Yeah, I think the problem with this technique at the moment is that it is about 1000 times less sensitive that they will like it to be, but the group of researchers are working on changing the substituents in the molecules of the polymers to see how this affects the gelation or the formation of the gel.

Interviewer - Chris Smith

So I wouldn't hold your breath if I was you, there is still a bit of R&D to do. Thank you Bibi.

(09:01 -- Harry McArdle discusses functional foods that could improve health)

Interviewer - Chris Smith

But one thing that you can do to ensure the best chances of enjoying good health is allegedly to eat a good diet, but at the molecular and chemical level, what exactly does that mean. To find out Meera Senthilingam caught up with the Rowett Institute's Harry McArdle.

Interviewee - Harry McArdle 

Under normal circumstances we always think of food as being something you eat just to maintain your health and well being to provide yourself energy for everyday life. We have now identified foods that may have additional purposes other than just simple nutrition and that may play a role in improving our health status. These are generally termed functional foods and can form in to two categories. Either ones that provide some kind of ingredient that helps our health or can provide something that will allow our normal biology to operate in a better fashion than it otherwise would. 

Interviewer - Meera Senthilingam 

How are these foods actually trying to achieve this?

Interviewee - Harry McArdle 

Well if we start of with things like pro and prebiotics, probiotics are foods which actually contain bacteria.   There is data to suggest that you can actually improve your health by modulating the spectrum of bacteria that you have in your stomach and some of these probiotics contain bacteria which is supposed to improve the health of the individual who takes them. 

Interviewer - Meera Senthilingam

But the things like probiotics have been around for quite a while, so what is the area trying to do this new to make them even better than?

Interviewee - Harry McArdle 

There's a whole series of things that don't actually work perhaps as well as they might do. For example, some of the bacteria in probiotics don't last very long. They don't stay and you have to keep on taking them. Also some of them incorporate difficult and complicated biologies, so what's happening is that people are trying to improve the spectrum of bacteria and also the way they survive in the gut, so they will stay there for a longer time and they will also have a clearer metabolic function.

Interviewer - Meera Senthilingam

And other than probiotics what are other types of functional foods are there?

Interviewee - Harry McArdle 

Well what you can also do is you can add certain nutrients, micronutrients and things like that for example, you can make orange juice which has got calcium in it and hydration drinks, boost drinks can actually be considered as functional foods. Whether they are, of course is under debate, but there is also an important group of functional foods which contain bioactive ingredients which are nutraceuticals which are foods that are chemically active and can actually act not as a nutritional supply but act in a way to stimulate nutritional pathways or to stimulate biological pathways.

Interviewer - Meera Senthilingam

And so how do you think one scientist goes about picking one of the many nutrients that have an effect on us and are good for us and deciding to then put them into a different type of food that wouldn't normally contain them?

Interviewee - Harry McArdle 

Well in the best of all worlds, what would happen is that you may identify something that has got a nutritional function. You would then work out what it was doing, you would then consider how it's doing, what it's doing in the original food because, bear in mind that any particular compound in a food matrix is in a very complicated matrix and it may interact with other nutrients within that matrix to generate the effect that you're measuring. If you then took that compound out of its original environment and then put it into a new one, so for example adding calcium in orange juice would be a very good example, you would then test and see whether or not your compound of interest, your nutraceutical had the same effect in its new environment and you would identify whether and how it worked and whether it was as efficacious or more or less efficacious.

Interviewer - Meera Senthilingam

And would you say it's often the case where in the new environment it does still have the same effect or does that really play quite an important role in its outcome?

Interviewee - Harry McArdle 

It can be very important. If you think about my own area of research which is in micronutrient metabolism, if you give somebody an iron supplement, depending on what you give it to them with, you will have a very different effect on the amount of iron that's taken up. Now iron is not a nutraceutical of course, it's actually an essential mineral; but if you give vitamin C, if you given orange juice at the same time as you give somebody iron and that will improve absorption and paradoxically at the same time, the data suggest that if you give orange juice at the same time as you give copper supplement it will reduce copper uptake. So depending on how you manipulate the matrix, how you manipulate the environment, you will get very different effects. 

Interviewer - Meera Senthilingam

So what do you think the future possibilities are for the area of functional foods?

Interviewee - Harry McArdle 

Well I think there's a huge market, I think there's an enormous number of people who are taking functional foods of different kinds and I think the big companies, the big food companies are investing an awful lot of time and effort into it. And it may be, you may be able to get things that really do make a difference for arthritis or do make a difference for osteoporosis and things like that. You may be able to do that nutritionally. And with proper research and with proper science, it may be possible to make those advances and if you did manage to do that then you could end up in a situation where people would remain healthy for much longer than they do at the moment, but I think that without the proper research to do that and proper research to examine whether or not you're actually making a difference, then what's going to happen is people are going to spend lots of money on something which is a doubtful clinical value.

Interviewer - Chris Smith

And right after the program I am off to the Burger bar, to do some research of my own.   I will be having a salad, honest. That was micronutrient metabolism expert Harry McArdle talking with Meera Senthilingam. Harry is based at Scotland's Rowett Institute.  

(Music)

Interviewer - Chris Smith

This is the Chemistry World podcast with me Chris Smith, still to come a new chemical replacement for cartilage that could help us to repair clapped out joints, how scientists are mimicking the chemistry of photosynthesis to provide the energy solutions of the future and the hidden chemical reactions that are going on underneath earthquakes. 

(15:03 -- Force-sensitive catalysts could help damaged polymers self-heal) 

Interviewer - Chris Smith

But first James last month you told us about a polymer that could repair itself using a blast of UV light including the UV found in sunlight, but now researchers have gone a whole step further.

Interviewee - James Mitchell Crow

All these catalysts Chris, are the first activated by mechanical force, so we have had a plenty of catalysts that are activated by things like heat or last month I was talking to you about a material where there was a catalyst embedded in it and that was activated by UV light but this is a work done by Rint Sijbesma at the Eindhoven University of Technology in the Netherlands and what his team have developed is a catalyst where the metal centre is surrounded by two N-heterocyclic carbene ligands and each of those ligands has a long polymer tail on it, so when you apply some sort of force, so in the lab, well they have been using is sonification, basically one of ligands gets plucked off by a style which exposes the metal plus the ligand and then either of those two surfaces can then be reactive to catalyze some sort of reaction. 

Interviewer - Chris Smith

That's ingenious, how do you stop the ligand which has presumably got a very high affinity for that side, how do you stop it just going straight back on and getting in the way of catalyzing the reaction?

Interviewee - James Mitchell Crow

Well the force is enough to pluck you away far enough, the catalyst is active long enough. I mean, the problem is actually more the other way around, what these guys who quite like know to happen is that the ligand is plucked off for a short time and then sucks back on to the metal once the force is removed and so preserving the catalyst for a second run if you like.

Interviewer - Chris Smith

But what sorts of chemical reaction can this catalyst participate in so how much it would be used? 

Interviewee - James Mitchell Crow

They have done a couple of test reactions so far, so if you use silver as the metal at the centre of the catalyst and pluck of one of these N-heterocyclic carbenes, that ligand actually acts as an organic catalyst and so you can catalyze a transesterification reaction. If you put rhodium metal in the centre of the catalyst and the rhodium inside becomes active when you pluck off the ligand and so that promotes olefin metathesis which basically enables you to stick two molecules together and each with alkene groups on. So what they are hoping to do is embed this catalyst into a polymer and then if the polymer is damaged that mechanical force, as the polymer was being damaged would activate the catalyst, and the catalyst would promote the reaction polymer straight back together again. 

Interviewer - Chris Smith

So it's a bit like last month when you reported on the car you could take it for spin in the sunshine and if there were any damages to the polymer the ultraviolet activates the catalyst and that then repairs the damage. Here it would just be a scratch but the pure energy in the scratch would do the repair job.

Interviewee - James Mitchell Crow

Yes that's exactly what they are hoping will happen, so you would not have to live in a sunny country, you could live in a grey England and the scratch would heal itself. 

Interviewer - Chris Smith

Good news for us here in Britain. Thank you very much James. 

(18:08 -- Chemical coatings that behave like cartilage)

Interviewer - Chris Smith

Now telling healing yourself, you can't quite do that if you have got damaged joints Phil. We normally have to resort a joint replacement for that but you say chemists have now come up with a very clever chemical that could be used to coat the surfaces of the bones for example and behave a bit like cartilage.

Interviewee - Phillip Broadwith

Yes Chris, well what this is, is some work by Jacob Klein from the Weizmann Institute in Rehoboth in Israel and he has come up with these what he calls polymer brushes which is a surface with some polymer chains attached to it and they look like the bristles of a brush they stand up an inch on end and they repel each other so they stand up to make these brush, if you take two of these surfaces pushed them together the bristles don't like being pushed into each other, they tend to repel, so you get a surface which has a very low friction. But those surfaces are quite fragile, so what he has done is incorporated charged groups on to the sides of the polymer chains using phosphorylcholine which is the same chemical group that's on the head of our phospholipids which has a negatively charged phosphate part and a positively charged amine. Those two charges make the molecule neutral overall but has these charged sensors which attract layers of water around them.

Interviewer - Chris Smith

So the water, does it behave like a sort of lubricant and so that when you bring these two things together the water molecules can slip past one another meaning the surfaces would glide over, but in itself it adds strength.

Interviewee - Phillip Broadwith

Exactly right, what professor Klein describes is these spheres of water around the charges acting as molecular ball bearings they give the polymer brushes enhanced compressive strength which means that they can stand up to the pressure in a joint for example, they also give a lubrication property so individual water molecules can hop between the hydration spheres around different charges or they can exchange with the bulk water solvent around the brush. But it is very difficult to take all of the water away at once, so you have this constantly held layer of water around the brush. What professor Klein has been doing at the moment is attaching them to a mica surface which is very very smooth that certainly helps with the frictional properties but they do have this very high compressive strength so the idea is sound. They might need some development, I mean similar things have been applied to a hip joint type replacement before, but the problem with that was only one surface was coated with the brushes, so you don't get necessarily the added frictional benefit of having these two surfaces together and also they were using a much rougher surface so they didn't necessarily see the reduction of friction but they did see a massive reduction in wear.

Interviewer - Chris Smith

So there is potentially two advantages here, one, you could apply this to existing replacements to cut down the rate of which they wear out, because we know that when they rub on each other, things like hip replacements produce plastic wear particles that are toxic; so this could mean that the lifetime of hip replacement could be prolonged. But another benefit could then be that you could instead of having to replace the joint, you just resurface the joint that's the person's own joint.

Interviewee - Phillip Broadwith

Exactly, what professor Klein is saying is if you could put this kind of brush coating on to the surfaces of joints, it would give them that low friction coating which wouldn't be rubbed off because it has this extra low friction and can stand up to the pressure in the joint then wouldn't be rubbed off and would allow the cartilage over that surface to regenerate underneath.

Interviewer - Chris Smith

Hopefully they will get that working by the time I get old, thank you very much Phil. 

(21:36 -- John Turner describes efforts towards the artificial leaf)

Interviewer - Chris Smith

And now to spitting water and how scientists are trying to create a test tube equivalent of an artificial leaf. Talking to Meera Senthilingam is John Turner.

Interviewee - John Turner 

Well we are trying to take sunlight and water and use the energy in sunlight to split water into hydrogen and oxygen. And we do that by taking semiconductor materials and instead of putting them in a solar panel we put them in water, water solution and shine light on them and interestingly enough sunlight has enough energy in it to split water into hydrogen and oxygen, fortunately water is transparent, does not absorb this energy but we can find some materials that do absorb that, generate sufficient energy to split water and you can do the experiment and you can see hydrogen gas coming off the illuminated semiconductors. We just haven't found anything that would be commercially viable yet.

Interviewer - Meera Senthilingam

Now you've achieved a water splitting reaction over a decade ago now. So how did you actually go about doing it back then and why wasn't that particularly viable commercially? 

Interviewee - John Turner 

Well we have found a number of rather expensive semiconductor materials. Materials that are used in communication satellite and actually the Mars Rover uses these same materials and for space applications they are perfectly acceptable, but for terrestrial applications where we have to cover a large amount of land area, they are too expensive. The material that I chose is the same material that is used in satellites, it's an expensive material gallium indium phosphide and gallium arsenide, why they are very very good materials with very high efficiencies, they are also expensive to make and so we need to find some lower cost materials that will allow us to do the same reaction, the same sunlight and water to hydrogen and oxygen. 

Interviewer - Meera Senthilingam

Now why is it important for us to have this reaction and why do we need hydrogen and oxygen sources from water?  

Interviewee - John Turner 

Well at some point in human society we won't have our oil and coal and natural gas to burn, I mean, our society is as dependent on energy as it is on food and water, we need another energy carrier that's sustainable and my definition of sustainable are energy systems that will last for millennia. 

Interviewer - Meera Senthilingam

So as you mentioned, to be commercially viable, you need cheap and abundant material. So the current option seemed to be titanium oxide and iron oxide why aren't these feasible?

Interviewee - John Turner 

Well titanium dioxide and iron oxide are not useful, one titanium dioxide is white, it's not absorbing a lot of sunlight, you need something that's coloured dark red like iron oxide. Unfortunately iron oxide, the material properties are not sufficient for good sustainable high efficiency solar conversion, otherwise, it would be a good solar cell, we have to find a new material.   A lot of people think you have to have very very common materials it's not necessarily so, in the 150 odd years of the photographic industry, we made millions of square meters of photographic film using silver and so silver you know is obviously a much rare element because its used in such a small amount in a thin film, we still have lots of silver left, so it's not necessarily we need to use abundant materials but the materials we use, the amount we have to use if they are not as abundant as some others have to be small. And the issue is manufacturing really, we have to be able to manufacture these things at fairly high speeds and high volumes and there's a lot of work to find the right material