Chemistry World Podcast - September 2009
00:11- Introduction
02:23-- Researchers find first liquid protein
04:54-- Fuel cell catalysts go sub-nano
06:46-- Paul Docherty talks oxidation with a reducing agent and live blogging
13:54-- Sticky nanotubes detect bacteria
16:32-- Computational chemistry predicts flu mutations
19:50-- Kelly Chibale on drug discovery in South Africa
26:10-- Origin of water on Saturn's moon
29:49-- Martian methane mystery
33:42-- The chemical conundrum - how have scientists managed to erase fearful memories in rats?
(Promo)
Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.
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(00:11 - Introduction)
Interviewer - Chris Smith
Hello! This is the September 2009 edition of the Chemistry World Podcast with Phil Broadwith, Matt Wilkinson, Tom Bond and Nina Notman. In this month's show, is it a liquid, is it a solid -- no it's a protein and one with some pretty spectacular properties too.
Interviewee - Phillip Broadwith
The key thing is that these proteins no longer need to be dissolved in any kind of solvent, they become a solvent themselves. They're actually very good solvents because they behave very similarly to ionic liquids. The great thing about using proteins as these ionic solvents is that you can combine the activity of the protein with that. So if you take a protein such as haemoglobin, you could use it to deliver oxygen in a wound healing kind of scenario.
Interviewer - Chris Smith
Reaches the wounds that other proteins just can't penetrate. Phil Broadwith will be here with more on liquid proteins in just a moment. Also on the way, reacting to controversial chemistry, is this the first example of a trial by blog.
Interviewee - Paul Docherty
The starting materials, the raw compounds that we're working with, they're very common and I guess that we might have some in our small chemical store. The technique they use is really simple. I must admit that the reaction was going on before I thought, hang on this is a good idea, but at that point I started to writing about it and what I had actually conducted in the lab in my blog.
Interviewer - Chris Smith
That's medicinal chemist, Paul Docherty, who joins us later to explain how his web writings have helped to shed some light on a very strange chemical reaction. We've also got some news of a novel way to grab bacteria.
Interviewee - Tom Bond
What they have done is created some sticky nanotubes which can trap bacteria like flypaper and they're able to bind specifically to different types of target molecules when the aptamer is bound to the bacteria, it peels away from the nanotube and this causes a change in conductivity.
Interviewer - Chris Smith
And that change in conductivity can be used to work out how many bacteria that actually are in there and Tom Bond would join us shortly to explain how it works in a bit more detail. Hello, I'm Chris Smith. Welcome to Chemistry World.
(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)
(02:23 -- Researchers find first liquid protein)
Interviewer - Chris Smith
First this month, to the polymer that makes life possible -- the protein, but these normally need to be dissolved in something, such as water to make them work, but now researchers have managed to do something fairly spectacular with them, Phil.
Interviewee - Phillip Broadwith
Well Chris, these proteins are actually liquids, which is very unusual for proteins, normally proteins we see as very highly order structures and they're quite often solids when we isolate them, but what Stephen Mann from Bristol and Helmut C?lfenfrom Golm, Germany have done is modify the protein so that they will stay in the liquid state.
Interviewer - Chris Smith
And tell us how do you do that?
Interviewee - Phillip Broadwith
Well, what they've done is made some modifications to the surface of the protein to make it positively charged, then they take negatively charged polymer chains and through an electrostatic interaction stick those polymer chains on the outside so that they make a sort of very protein that's got these polymer chains sticking out all over it.
Interviewer - Chris Smith
And what do the polymer chains actually do, what's their role?
Interviewee - Phillip Broadwith
They allow the individual protein molecules to interact with each other but over a much longer length scale, so they don't ever get close and pack together. They're held apart to keep the whole thing liquid.
Interviewer - Chris Smith
So, once it actually is behaving as a liquid, what could you do with this, why is this important?
Interviewee - Phillip Broadwith
The key thing is that these proteins no longer need to be dissolved in any kind of solvent. They become a solvent themselves. They're actually very good solvents because they behave very similarly to ionic liquids, which are a new class of solvents, which have been widely talented as very green, they can dissolve a wide variety of different things. The great thing about using proteins as these ionic solvents is that you can combine the activity of the protein with that. So if you take a protein such as haemoglobin, which is one of the ones that they've already modified, you could use it to deliver oxygen in a wound healing kind of scenario or you could use a catalytic enzyme, so that your solvent is also your catalyst.
Interviewer - Chris Smith
Are these things actually practical to make, could you make this in large enough amounts to produce a reasonable quantity that would be useful or are they kind of microgram quantities, going to be a little while yet.
Interviewee - Phillip Broadwith
I think this is just a very early stage at the moment, it's just a brief of concept. They have done it on a variety of different enzymes including ferritin and haemoglobin, myoglobin and also lysozyme which is a catalytic enzyme from egg whites.
Interviewer - Chris Smith
Fantastic. Well, we look forward to seeing some applications of that. Runny proteins and I thought it was just my eggs will run out. Thank you Phil.
(04:54 -- Fuel cell catalysts go sub-nano)
Interviewer - Chris Smith
Now Nina, from runny eggs to nanoparticles, actually now you're going to go sub-nano. Researchers are saying that size is very important on the small scale.
Interviewee - Nina Notman
So, Japanese researchers have designed some sub-nano size platinum catalysts for use in fuel cells. This work is important because platinum supply is becoming limited and it's also expensive. So smaller amounts of platinum in our catalyst means that financially our fuel cells should be cheaper.
Interviewer - Chris Smith
So size is important, we want to go smaller. What size the present catalyst and the surfaces we have inside the average car exhaust pipe at the moment?
Interviewee - Nina Notman
So the average ones at the moment are 2 to 5 nanometres and conventional wisdom says that 3 nanometres is the best compromise between platinum usage and catalytic activity.
Interviewer - Chris Smith
And what's the sub-nano regime then, how big is that?
Interviewee - Nina Notman
It's actually down to 12 atoms.
Interviewer - Chris Smith
But okay, so we are down at 12 atom size, how did they show that that's the critical size and why is that important?
Interviewee - Nina Notman
They were looking at different sizes and they showed that the smaller you went the higher the catalytic activity was, which wasn't what was expected and at 12 atoms size, they went down that had 13 times the activity of commercially available catalysts, which normally have hundred to thousands of atoms within them. This is particularly interesting because it's not actually due to the surface area that these small catalysts are particularly active.
Interviewer - Chris Smith
All right. So just because you've made them smaller and got the individual particle size small, therefore having a bigger surface area to volume ratio, you can't explain the activity on that basis then.
Interviewee - Nina Notman
No the activity is far too high to be explained just by surface area only and they're saying.
Interviewer - Chris Smith
So what other things going on?
Interviewee - Nina Notman
I think it's due to quantum effects and they're not speculating yet on what those are.
Interviewer - Chris Smith
Sounds a bit of a get out clause to me.
Interviewee - Nina Notman
Me too.
Interviewer - Chris Smith
I wonder how long it would take the advertising industry to jump on the sub-nano angle as the selling point. I bet your shampoos and sun creams come first. Thank you, Nina.
(06:46 -- Paul Docherty talks oxidation with a reducing agent and live blogging)
Interviewer - Chris Smith
Most people appreciate the massive impact that the internet has had on the pace and process of scientific discovery. The things have now got even more interesting with the rise of the blogger. Paul Docherty.
Interviewee - Paul Docherty
I've been working as a medicinal chemist for about two years now, prior to that I was doing my Ph.D. and during the course of my Ph.D., I started writing a blog about photosynthesis of organic molecules, initially and very briefly, anonymously but I was very quickly uncovered, so I've been at large in the blogging community for about 3 years now.
Interviewer - Chris Smith
What sorts of things were you covering in the blog?
Interviewee - Paul Docherty
It actually turns to be quite narrow area of science. We look at total synthesis and if somebody comes very close to finishing the synthesis of a natural product, but doesn't finish it, then we don't cover it. What we ever look at completed synthesis and occasionally if there's something very interesting or dramatic in the organic chemistry community, we'll look at that too because of course it's of interest to our scientists working in natural projects as much as anybody else.
Interviewer - Chris Smith
And when you say, you look at it, do you mean, you try to dismantle what they have done and work out if they got it right?
Interviewee - Paul Docherty
We do very little error correction. We tend to just look at recent synthesis published in the top journals and dismantle the thought process behind what they did in trying to understand whether their approach was the most obvious one or whether they've really thought about things in a very lateral sense.
Interviewer - Chris Smith
Who reads this?
Interviewee - Paul Docherty
I tried to look at statistics on this and I would say there's probably a fifty-fifty split between academics and people working in the industry, but I would say it does lend itself more towards a younger audience. So a lot of Ph.D. students or chemists starting on their career in the industry.
Interviewer - Chris Smith
So tell us about how you got into your latest forage, the critiquing let's say, an interesting bit of research that's been done recently.
Interviewee - Paul Docherty
I was actually alerted to this paper published in the Journal of the American Chemical Society after some of my readers posted comments and suggested this paper might contain some really interesting chemistry. The lead author is David Wang of the School of Chemistry at Peking University and his team that works on an approach of oxidizing alcohols using sodium hydride and the consensus is that sodium hydrate as a reductant, so one would expect the opposite to occur. So, they were using a reducing agent to do an oxidation.
Interviewer - Chris Smith
This was in a peer-reviewed journal. So presumably, they managed to satisfy the review process that what they had to say was at least plausible.
Interviewee - Paul Docherty
Yeah, I think there's no doubt that chemistry was done and they used the right approach doing the chemistry. I just think that the conclusions and the rationale which has given a mechanism to try and understand how this chemical process might occur. It's hard to understand how they could come to this conclusion.
Interviewer - Chris Smith
So what did you do about it?
Interviewee - Paul Docherty
Well, unlike a lot of other papers, in organic chemistry, the starting materials, the raw compounds that we're working with, they are very common and I guess that we might have some in our small chemical store and within a couple of minutes I had a representative example and the technique they use is really simple and I must admit that, the reaction was going on before I thought, hang on this is a good idea, but at that point I started writing about it and I've been posting pictures of the reactions and what I had actually conducted in the lab in my blog.
Interviewer - Chris Smith
So what conclusion did you reach and did you agree with them or not?
Interviewee - Paul Docherty
After leaving the reaction for exactly the right amount of time and doing things exactly as they suggested it should be done, I have to conclude that the reaction does work, but only if one allows atmosphere into the reaction. In other words, you are allowing oxygen into the reaction. It's hard to say exactly what role oxygen or perhaps even water could be playing in the reaction, but it seems very clear that it is necessary.
Interviewer - Chris Smith
So in other words, if you conduct this and you do it without allowing any room air or at least oxygen to penetrate the reaction mixture, it doesn't work, but if you do allow room air in, it does work. How did you find that out?
Interviewee - Paul Docherty
I didn't take the most stringent approach to keeping out oxygen and I saw a little of the reaction happening. Some of my commenter, at this point had started to conduct the reactions themselves and some of them work in inorganic chemistry and these guys have a lot of respect for because they're really good at keeping reactions anhydrous and anaerobic. And when they tried that, they saw no reaction whatsoever, but then when they left the atmosphere in, the reaction went beautifully.
Interviewer - Chris Smith
What do you think the bigger implication of this is for people who are publishing chemical synthesis like this?
Interviewee - Paul Docherty
It's telling us that perhaps the author should have tried a different range of reaction conditions, perhaps he should have tried deliberately pumping oxygen into the reaction or tried using equipment that allowed them to be far more stringent and may be then they would have come to the conclusion that I've come to which is that you do need atmosphere in the reaction.
Interviewer - Chris Smith
Don't you think it's amazing though, that without the internet, without your blog, we've now got a, sort of, stage beyond peer review, we've now got blog level peer review, which is putting researchers like you onto interesting things and then getting you looking at them in a new way and finding novel things about them, even catching people out.
Interviewee - Paul Docherty
I think one of the most useful things is we are able to draw some new conclusions very quickly, I think within 40 hours, the reactions were all done, the results were there, but I think very important to this was everybody knew who I was. If I had been anonymous at this point, I could have been saying anything, even if it affected my career. The fact that the blog is identified as being owned by me brings some credibility to the results.
Interviewer - Chris Smith
Indeed and it's a process taking peer-review to a whole new level, beyond just the publication of the piece of research. That was Paul Docherty, who is a medicinal chemist at Arrow Therapeutics in the UK and if you want to check out his blog, it's online at totallysynthetic dot com forward slash blog.
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Interviewer - Chris Smith
You are listening to Chemistry World with me Chris Smith and still to come how computers are helping us to predict what the flu would do, why drug discovery could be said to takeoff in a big way in South Africa and the origins of methane on Mars, Martians or just marsh gas.
(13:54 -- Sticky nanotubes detect bacteria)
Interviewer - Chris Smith
But first, Tom, to the nano equivalent of flypaper for bacteria.
Interviewee - Tom Bond
Yeah, so this is a study that's just been published by a group in Spain, in Tarragona, led by Xavier Rius and Jordi Riu and what they have done is created some sticky nanotubes which can trap bacteria, like flypaper.
Interviewer - Chris Smith
So tell us what are these, what's the anatomy of these nanotubes first of all.
Interviewee - Tom Bond
They comprised of carbon nanotubes, which are coated in aptamers, which are, well they can be made from a variety of genetic material, they're just short sections, but in this case, they're made from RNA and they're able to bind specifically to different types of target molecules, in this case, bacteria. So the aptamer is specific for one type of bacteria.
Interviewer - Chris Smith
So presumably what happens is that the aptamer binds onto the surface of the bacteria selectively, so that you can register the presence of a certain type of bacteria, specifically.
Interviewee - Tom Bond
Yeah, that's correct and at the moment, it's the aptamer is just selective for one type of bacteria, which is the Salmonella typhi which causes typhoid but in the future they hope to be able to create other aptamers, which would be selective for different types of bacteria and the mechanism by which they tell how many bacteria are present is that when the aptamer is bound to the bacteria, it peels away from the nanotube and this causes a change in conductivity, which could be linked to the number of bacteria present.
Interviewer - Chris Smith
Okay. So they are putting a sort of electric charge across the base of the field of nanotubes, are they, so you can then see how the current changes when there's binding of the bacteria.
Interviewee - Tom Bond
Yeah, effectively a conductivity measurement, yeah.
Interviewer - Chris Smith
Are they easy to make, in other words, is this practical? Do you think we could see this on sale as a nanodetector in the near future?
Interviewee - Tom Bond
I think they're probably fairly easy to make, the limitations at present seem to be that you need to have the specific aptamer to bind to the targeted bacteria and also just the cost of the carbon nanotubes, so those are probably the limited factors at present, but in the future the study hopes that the cost of carbon nanotubes will come down to make it more feasible.
Interviewer - Chris Smith
Well, let's hope so. I mean, it sounds like an amazing technology actually and certainly quicker than trying to grow these things in culture to work out what they are which is the present way of doing it, which takes time.
Interviewee - Tom Bond
Yeah, that seems to be the major benefit, it is as much quick as so we can potentially, even in real time or in the hospital, rather than over days as current methods would take.
Interviewer - Chris Smith
Well, let's certainly hope so, I mean, certainly a fascinating piece of research and I will hopefully look forward to seeing that in my lab in the near future.
(16:32 -- Computational chemistry predicts flu mutations)
Interviewer - Chris Smith
Now let's move from something pretty small, detecting bacteria to something even smaller, but still a microbe, viruses and one that's a particular pain at the moment Matt and that's the flu. Tell us about this.
Interviewee - Matt Wilkinson
Yes Chris. Researchers from Stanford University in California led by Peter Kasson have been developing a way of predicting the most virulent types of form and so find out which is going to be the most infectious in the future.
Interviewer - Chris Smith
Obviously big question because flu is a moving target, it is continuously mutating and changing, we have also got new jumps of new viruses out of birds and into other animals including humans. We are always playing catch up. We are trying to work out how to make vaccines and so on rather than pre-empting these things. You're saying that researchers are now able to look forward and they will be able to pre-empt basically what a strain is going to emerge, it's going to be like.
Interviewee - Matt Wilkinson
Well, that's what they are trying to do and this is really, and they caution themselves, so actually this is one of the first steps towards it. What they have done is that they started studying the haemagglutinin protein which binds to the sugars on the outside of host cells and the strength of that binding is actually responsible for how infectious a type of flu will be. And so in this example, they have taken x-ray crystal structure of an avian flu haemagglutinin protein bound to an avian sugar and from that data they have then gone on and done molecular dynamic computational chemistry experiments and combine that with proteins, this protein sequence data to pinpoint the exact mutations that could lead or that could impact on the strength of that binding interaction.
Interviewer - Chris Smith
I see, so now what you're saying is we have a computer model that can workout what mutations we would need to look for to predict if something that we see out there in the environment is likely to be nasty on us, in other words how infectious it is likely to be for us.
Interviewee - Matt Wilkinson
Exactly and by making different mutations in those different points they can predict whether it is more or less infectious, of course what they can't tell us is how nasty that is going to be. We all know that swine flu at the moment is very infectious but actually at the moment, is not that deadly.
Interviewer - Chris Smith
How they actually tested, I mean, obviously they've used various interactions, you said that they have used H5N1 as an example, but how they've actually then set right. Let us put this to the test, we have got his model let's anticipate a few changes and then make a virus with these changes in it and see if what their models says should happen is mirrored when you test that virus.
Interviewee - Matt Wilkinson
Well, they have had a little bit of a luck, but unfortunately there is not that much data out there yet. They even gone back to the 1918 Spanish flu which was again a swine flu type thing and looked at how that affected it, but unfortunately there's just not that much data out there of this type yet. So they are hoping that more people will collect more data and then we will be able to go and build a bigger bank of data so we can actually predict what flu is going to be attacking us next.
Interviewer - Chris Smith
I thought you are going to say for many more people who get flu and then we can study what happened to them and then refine the model that way. But this is certainly looking like it's going to be very important tool, because it means that we can begin to ask those kinds of questions and then also look forward rather than back.
Interviewee - Matt Wilkinson
Yes Chris.
Interviewer - Chris Smith
Time will tell I guess, but it certainly sounds like a powerful tool. Thank you Matt.
(19:50 -- Kelly Chibale on drug discovery in South Africa)
Interviewer - Chris Smith
Drug discovery is big business, but it's something that until very recently has remained fairly rooted in the developed world, but now an organic chemist at the University of Cape Town is on a mission to change all that and in the process to bring some pharmaceutical prosperity to South Africa, his name, Kelly Chibale.
Interviewee - Kelly Chibale
What I am trying to do up in University of Cape Town is set up an adaptive coverage centre specifically focussing on integrating drug metabolism and pharmacokinetics into medicinal chemistry.
Interviewer - Chris Smith
So just explain for a minute what the motivation of doing this is, why do South Africa need to do this, what is it hope to gain by doing it?
Interviewee - Kelly Chibale
The motivation really behind this is the government is really trying to put in place some measures to catalyze biotechnology in the country and I think one of the areas that is really being looked at is the country playing a very important role in solving the health problems that affect most of the countries but the rest of the continent.
Interviewer - Chris Smith
I suppose one area or one way of looking at this is, is the fact that most of the world when they invent something they then license it to rest of the world and that's the revenue stream and I suppose that South Africa is very well placed to do a lot of the primary research to get something patentable, license that to other African countries but also beyond Africa the rest of the world, and that then gives South Africa a revenue stream.
Interviewee - Kelly Chibale
Absolutely, even big companies don't necessarily take things from discovery all the way through to the clinic but whether they go all the way and develop a drug or just license it, they add a lot of value to it, so that they can be able to recoup a lot of resources they have put into the research, including having a very long term sustainable revenue.
Interviewer - Chris Smith
It sounds Kelly, rather like a no-brainer it sounds like an obvious thing to do, why hasn't South Africa done this already.
Interviewee - Kelly Chibale
Because of what happened for a long time during the apartheid era, the country was basically isolated from the rest of the world, so the know-how might have been there but the, you know this is something that you don't necessarily do by yourself that you have to tap into other technologies elsewhere and because most of the companies actually pulled out of the country, there was never an opportunity to develop a base in this area. The biggest challenge to successful blood discovery and development, the major stumbling block is actually what the body does to the drug, in other words, so this is the term we say, pharmacokinetics. So what the body does to the drug is in fact the major stumbling block, so the key missing ingredient in South Africa is to be able to allow at a very early stage, the drug metabolism studies to be able to guide the chemistry, the medicinal chemistry. You modify your chemical structure of the potential drug in fact the way out to be able to address any liabilities or shortcomings to do with metabolism. So that really has been a missing puzzle in South Africa and we think that this centre that I am setting up is uniquely positioned to deliver that very key missing ingredient.
Interviewer - Chris Smith
Now a lot of western drug companies are under considerable pressure to make available some of their lead compounds, which they sell for a lot of money in the west to countries inside the African continent where there are chronic diseases like HIV where these source of medications can make a life or death difference, that means there might be a pressure on you to make your compounds available in the same way. So how will you respond to that?
Interviewee - Kelly Chibale
I do understand why drugs are so expensive, that it is a very expensive process, very risky and I think that the companies have to recoup some of the profit, some of the money, so that I think when it comes to people putting pressure on companies to, you know, lower the cost of research is I think one of the ways our centre will get on that problem, the cost of doing the research itself will be, I think a fraction of what one would pay to do the same research in the western world. So naturally the amount of money that will have to go into that discovering development would be lower compared to what one would put into a similar program in the west. The pricing of any potential drug that come out of this will be quite competitive and of course the fact that some of the research program efforts would be government supported. There will be some kind of level, some level for subsidy if you like in terms of offsetting some of the cost for drug discovery and development.
Interviewer - Chris Smith
When do you see this actually coming to fruition where your unit is actually churning out compounds or has actually uncovered potential drug leads that you could then licence on?
Interviewee - Kelly Chibale
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