So it is afternoon.
I'll try to be quick.
I'm very hungry also.
So I thought what I would do today is to organise our talk around the topic of Green Chemistry,
which is one of the topics of this meeting.
And talk some about green chemistry, catalysis and obviously use examples from our chemistry.
I'll give sort of 3 case studies that are related to various topics and metastasis chemistry we're doing.
I'll try to end up with some questions about Green Chemistry which we can spend time talking about later today -
we'll have time this afternoon.
I won't spend too much time on those now.
If we think about Green Chemistry, there's lots of ways of thinking about it:
sustainable chemistry, blue chemistry we heard about last night.
And there are the 12 rules of chemistry etc.
I like to think about it as a person who makes molecules.
And so if you're going to make something you essentially put something in the pot, you do something to it in the pot
and then you take it out.
So we think about starting materials.
And so you think about starting materials:
you can have renewables, you can have some very simple structures.
In processing which is where most people think about it in terms of things, of getting rid of water etc., etc.
I won't spend much time on that, it's just sort of natural with metastasis.
And then I'll talk about a couple of products which I think have some interesting things.
There are obviously lots of other topics associated with energy.
If you think about CO2 increases.
Actually chemistry is going to be a very, very small part in terms of chemical production -
we'll talk only a small amount about that.
The other thing, which is really important to keep in mind, which hasn't been raised very often,
is that not only does it have to be green, it has to be cost effective.
And this is a study which I found impressive, by the group at Procter and Gamble,
which has actually made a real effort in the area of Green Chemistry and sustainable chemistry.
And they basically looked around and said
look, you know, there's a few people who will buy things that are more expensive or don't have as good a property if they're green;
but most people won't.
When it comes right down to it, you buy whatever works.
And so to be green you also have to be cost effective.
So that's a really important thing I think to keep in mind.
So here's our chemistry.
I think Dick did a really good job of giving a good background for this.
So I can skip over a lot of the introductions.
You know this is the reaction which I first found out about in 1968.
And that was really the reaction:
propylene to ethylene into butene.
If you put in an infunctionality, you were dead.
So the idea of being able to make molecules, being able to do organic chemistry by metastasis
was something that we really didn't think about or even dream about until much later on.
And so over the years then, as Dick pointed out, in the early '90's - well actually in the early '80's, in the mid '80's -
we really started doing ruthenium.
Because we found that you could make ruthenium catalyst and they would operate in water.
And that really opened up how you could do chemistry, the kinds of things that you could do.
And so we then sort of eventually made, in the early '90's then, our first well defined catalyst.
And really one of the exciting things about this area has been watching what people can do with the new tool.
So you give them a new tool, a new way to make bonds -
and I'll just go through it rapidly and just point out a few of the things that have been done.
So here is where we started.
Here's our main catalyst which in our group is called Sheng Ding catalyst.
It was made the first time by a student, an undergraduate actually, named Sheng Ding.
So it's always called Sheng Ding in our group.
And it's now being used to make a drug which is now going into phase 3.
And you notice it has a double bond.
The double bond is a cis-double bond which is made by metastasis.
And it turns out to be cis and it's actually just controlled by the structure of the molecule, not by the catalyst.
That should be approved this summer, I understand.
It will be one of the really good first hepatitis C drugs.
It has this basic structure of a peptide that's hooked together by a link which holds it in the right confirmation.
There's another exciting group of compounds, which a small company called Aileron,
which is basically taking peptide sequences, putting these kinds of straps on them, which hold them into helical forms.
And so they're trying to explore the whole area of non-druggable diseases,
where basically it's protein-protein interaction rather than small molecules.
So they're now in humans and so we'll see where that goes.
And it's made possible by this ring-closing chemistry of stabilising peptides.
It's being used to make really big parts:
windmill blades, composites - I won't talk about that.
I'll talk about this, which is the seed oil business, and pheromones which I'll talk about, making things for oil and gas.
And if you have a newer car it has some ruthenium under the hood,
because the nitrile rubber that's used to make your belts is from that.
So the exciting thing is that we started, a long time ago, with something that would be propylene.
It would make and break these carbon-carbon bonds.
And over the years by making better catalysts, now one can find all these other things to do with it.
So I'll talk about 3 cases:
one is the seed oil, the other is the pheromone, and then the last is sort of a polymer kind of project.
And there are different stages in development.
And they also raise very many different questions about Green Chemistry, greenness, whatever you want to call it.
So the first thing is to make the catalyst available for people.
And once you make it available then people can do stuff and so, you know,
you can make it, you can hold it out in the air, you can put it in the big barrel, etc., etc. - it's easy to make.
Then what are you going to do with it?
One of the examples is this seed oil conversion.
Dick pointed out that seed oil is from natural sources.
So it's starting from a natural bio renewable, which is one of the areas in green chemistry that you only think about.
It takes CO2 from the air, reduces it - this is probably the most reduced of the bio starting materials;
it's basically a hydrocarbon chain with a little bit of carboxyl group at the end.
And so it has some interesting possibilities.
Here's a fatty acid and it's got a double bond.
And so you're going to do chemistry.
You're going to cleave the double bond and make 2 pieces.
Now there are some interesting things about this.
First of all, you can do it with no solvents.
And the other thing is too
- which is something that I think you should think about as your designing, and think about what you're going to do next -
is that up until now we've been developing catalysts mostly for starting with hydrocarbons.
We start with hydrocarbons.
You got CH bonds.
To make it functional you need to put in oxygen, nitrogen and all kinds of other stuff.
So we've done mostly functionalisation.
If you start with a bio source they're normally too highly oxidised, have too much nitrogen in them.
So now we got to develop a catalyst for taking out functionality.
For example, if you want to make fuel out of this, it's good to get the oxygen out.
Because you can't use oxygenated things in many cases.
This sort of does that.
I'll show you that in a moment.
Then in line with what Dick was good questioning - I mean, is this commercially viable:
we worked about a half a million turnovers and probably better than that.
Then this was announced by Elevance.
They want to make a £400 million a year plan.
It's pretty interesting, it's a biorefinery.
They essentially start with seed oil instead of a barrel of petroleum - the scheme would be almost the same with petroleum.
Some pre-treatment - you can't do much pre-treatment, if you do it's too expensive.
You then...in regular petroleum you would do a cracking catalyst, high temperature acid catalyst that cracked this.
In this case one does metastasis.
You can put things in to help that along.
Then at the end you do a distillation.
And remember you split the functionality, hydrocarbon, and functionalise stuff.
So it turns out that the hydrocarbon part makes really good fuel.
It also can be alpha-olefins, but it makes jet fuel because it has no oxygen in it.
And then the other part has the esters, and those turn out to be chemicals.
And just like in any refinery is that you make fuel and you make chemicals at the same time.
Chemicals are normally more valuable and so they help balance the whole project.
It turns out that they assume that this is going to be economically viable - number 1 thing for anything that might be green.
At $50 a barrel of oil, we'll probably never see that again.
And it turns out that since you can't do much pre-treatment
- and the first plant is in Indonesia, where there's water everywhere -
this is starting out with ruthenium catalyst, because it tolerates the conditions.
So here's the plant.
I didn't believe it existed, so I had to fly over and take a picture of it.
There it is, there's the plant.
And that's actually starting to be...starting right now.
They're now starting to flow things together and starting to make products; within a year we'll know how this all works.
So it's basically an example of a place where one can start with biorenewables.
At first sight that sounds really good.
It's a cheap source of carbon as petroleum gets more expensive.
It's got to be cost effective, not just green.
There are some cases where the cost doesn't matter, where there's sort of political things.
It turns out there's a product now that's being sold by Victoria's Secret, which contains an oil made by metastasis;
and it's made because they can call the product vegan instead of something else.
And so there's sometimes other cases.
Here's the point that I talked about before, which is that we need new processes for converting biomaterials into chemicals.
But in the end of this you start thinking about it, things get a lot more complicated.
So it's simple:
we take CO2, we turn it into chemicals, we burn them back to CO2 again.
But where do you get the starting materials?
So there are all kinds of social and economic sorts of things.
This is in Indonesia where they're making palm plantations.
And there are lots of issues associated with that:
there's food versus chemicals, land use.
And then the other thing:
if you start thinking about something that's green, where do you start counting?
So if you go all the way back to burning down a forest to make palm plantations etc., etc., it's one thing.
But if the palm oil is there already and you're converting it into something more valuable, is that green?
So I think there's all kinds of interesting issues that are associated with these things that we need to talk about.
And that will be something I think we can have fun with this afternoon.
So that's one sort of thing.
That one has progressed the furthest.
These other 2 things are things that are just happening right now, which are different kinds of issues.
And then the other one is replacing a polluting material with a safer product.
I grew up in the DDT era.
I was in Kentucky where there are farms.
We had DDT sprayed everywhere - DDT had many, many good advantages, there were other problems.
The question is though, is can we replace pesticides and those kinds of things with things called pheromones?
What are pheromones, how does these work and what would it be?
So it's a pretty simple picture that chemists can understand.
It's basically...
one of the ways of using them is in mating disruption.
You can also use them for traps etc.
And in mating disruption what you do is you take advantage of the natural habits of the insects.
And so as I describe this:
during the mating season the females become really good synthetic organic chemists.
They make precisely one compound, very pure, very clean; they release it into the air.
It goes blowing along and the males get to be really good analytical chemists,
and they can do both things an analytical chemist does:
they can detect a molecule at incredibly low levels;
and they can do concentration gradients and concentrations really, really rapidly.
And essentially what happens then is the male starts...
it detects the chemical, starts flying.
If it flies out of the plume, it flies back in again.
And so it leads it right back directly to the female, mates; the female lays eggs in the fruit and causes all the problems.
So the question then is if you could spread this chemical all over the field, then the poor male smells it everywhere.
It can't find the females, it can't mate and you've solved the problem.
And so what you need to do then is to find what the structure is.
And each individual insect has its own chemical.
So if you...it's a precise way of controlling each individual insect.
You don't wipe out the whole insect population as you do now with the pesticide, you can target it toward one.
Then you find out what it is and you make it.
It turns out the levels are incredibly low, and the compounds are pretty unstable so they oxidise pretty rapidly.
In principle this could be a way of eliminating many of the pesticides that are used.
One can actually use pheromones on a crop and still call it organic.
So there are lots of pressures for that.
The big problem is the cost.
The farmer has got to make a living and if it's a lot more expensive than pesticides, they're not going to use it.
So we've been thinking for a long time about how to do this.
Oh, I just put this up:
here's a Larson thing - he understood about pheromones.
'Wash off that gallon of pheromones.'
It turns out there was a problem with that,
because if this young lady went out with gallons of pheromones
she would totally destroy all the sensory organs of every male in sight - anyway.
This has been going on for quite some time now.
This is peach twig borer.
And I like to put the pictures in, because people start feeling bad about insects - these are really ugly.
And so it turns out this one has been made for a long time
because, as Dick pointed out, metastasis tends to make trans-double bonds, or E-double bonds.
And this turns out to use an E-double bond.
And so this is being made now on quite a large scale from 1-hexene hexenyl acetate.
You can put them together and make the stuff.
So this has been made in 100s of kilos now and really frustrated lots, I hope, of these things called peach twig borers,
these ugly things.
But the problem is, as Dick pointed out, is that these like to make E, and Z-double bonds are less stable.
And it turns out that - one can think about a lot of evolutionary reasons why this is true -
is that many of the pheromones have Z-double bonds.
These are now made in multisteps using liquid ammonia.
All the steps are stoichiometric - not catalytic.
And for example there are lots of places in the world where you can't use large volumes of liquid ammonia.
So there are expensive, toxic, sorts of things.
There are 2 ways one can be green in this:
one is you can find more efficient ways of making them, greener ways of making them.
And then also you can use them to replace pesticides - and that's another part of the whole green business.
As Dick pointed out most catalysts we make, make equilibrium mixtures - which is 80/20.
And it would be great if we could have a catalyst that would either make 100% E or 100% Z.
And we started out thinking about making Z a long time ago.
Because it seemed like the hardest.
Now that we've done it, E seems like it's almost impossible.
So we're thinking really hard about that.
I used to say I couldn't retire until I made a Z selective catalyst -
now I've got to make an E selective catalyst before I can retire.
So we spent 15 years working on this, off and on, no progress at all.
A very simple reaction was run for some wrong reasons which ended up being the key to this, which is just treating
- this looks like one of our standard catalysts - just treating with sodium pivalate.
Sodium pivalate turns out to be the magic one.
You turn out the CH activate - and I won't take you through all the gory details of that - but this makes a chelated system.
Part of the reason for that - and the reason for this work, as Dick pointed out -
these systems tend to be very fluctional, and if you make them a chelated it seems to slow that down.
And I'll show you in a moment it really also sets up a lot of other interesting features which we didn't anticipate.
So this was just lucky.
We sort of had a model and we were shooting for it, but we ended up getting there by a way that we didn't anticipate at all.
So we ended up getting that.
And usually these were unstable but this turned out to be nice.
Once you had that, now we can start to make molecules that have pretty high Z selectivity and pretty good turnovers.
They're still not what we'd like, but they're ok.
But then once we have a structure, it's just like in drug discovery,
once you get your lead compound then you can start looking around and changing things - we love to do that.
Once we had our lead, then we could start making things.
And for example putting on a nitrate made it a lot more stable and a lot more active.
And so using that catalyst we could then make a whole family of pheromones.
And you see instead of 8 steps with lots of liquid ammonia etc., we can make a lot of these in one step, starting from seed oils.
So it's naturally functionalised starting materials and then with simple olefins we can make all of these.
So essentially we can make all of these starting out with fatty acids, fatty acid derivatives.
A couple of them are a little more but that's because you got to put in functionalities.
So we were pretty happy about that.
This was just published not long ago - again very ugly insects, not beautiful butterflies.
Why does this work?
We found the structure totally by accident.
And it turns out that by luck, that by making this thing a chelate, it twisted the molecule all around, broke all the symmetry.
And we had no idea why it worked and so we went to Ken Houk, who is a chemist at UCLA who does theory.
He did a lot of calculations and his computed structure looks pretty good.
It's a little hard to see, here's the stick drawing.
So there's the chelate.
Here's this funny ligand, this N-heterocyclic carbene ligand we've been using for a long time.
And remember as Dick talked about, we need to make a metallacycle.
So you start with the carbene, you bring in the olefin.
And the structure of the ultimate olefin is determined by whether those 2 groups are on the same side or opposite sides.
If they're on the same side you get cis, opposite sides you get trans.
So why does the structure make cis-double bonds?
It's hard to see - the blue thing there is the ruthenium.
And we'll wipe out the oxygen so you don't see it.
That green is that carbon, that green dot is that carbon, that green dot is that carbon - so there's the metallacycle.
And then we put on 2 methyl groups.
There's a methyl group and there is a methyl group.
Those are cis.
And why are they cis?
Well, there's this group up here.
It's this big aromatic group.
It's a methanethiol group - it's got methyl groups sticking out there and there, it's a big flat thing; this thing forms a roof.
So we've essentially got this flat thing sitting up here.
And then the metallacycle is doing that.
And if you try to stick a methyl group up, it bumps into the roof.
It makes them hang down out in space.
It's a nice simple model.
I wish I could say we designed it, but we didn't.
We got there in our usual roundabout way.
But we're there and we're very happy.
So now the question is, as we looked at the systems back here.
Some of these were in...
Z's were in 80% and 90%.
So those were good and we were really happy with those.
But we wanted to do better.
So what do you do from this model?
What gives you the Z selectivity, it's this roof up here.
So you make it bigger, it's a really simple thing.
So you put on...instead of methyl groups you put on isopropyl groups.
And as Dick pointed out before, those are really big, they're bigger than methyl groups.
If we make those, we've got a catalyst where everything is greater than 95% Z.
We can run these things to very high conversion, and we see almost no E in the baseline.
They're almost perfectly selective.
Now we can go back and make all of our pheromones in high yields, and we're doing that - this paper was just published.
And so after about 15 years we're finally there.
We can now start to think about making pheromones.
The lead structure was a combination of theory and serendipity; once we found it, it's taken us about a year to optimise it.
Now we're now starting to work with a very large pheromone distributor,
to see if now we can introduce pheromones at a level and at a price where they'll be broadly accepted.
We'll see.
So we're a few years away on that, but we'll see where this gets to.
But at least we now have the system where we can really start to think and explore it.
Now I'll finish up and I think I'm going to be close to time.
The finger runs really fast (laughter).
Functional materials.
Something that we've been doing for years is making polymers.
And one of the early things we found, even before we knew about ruthenium and moly and everything else, was that titanocene -
we could make what were called living polymers.
And living systems really allow you now to start to design polymers very precisely.
Dick talked about controlling the structure of the backbone.
The first thing you want to control is a link to the backbone, and the sequence of things that you put in.
And without a good living system that's quite hard to do.
But with a living system essentially one starts with an initiator, one adds monomers - you see we bring in the monomer.
And this one does what we think, most of it comes in from the bottom; it doesn't come in from the side like the others.
It makes metallacycle, it cleaves.
But you see, by being a ring when you cleave it's still stuck to the ruthenium.
So then you can bring in another one and you keep doing that.
Since these are quite stable, it just does this over and over and over again until you run out of monomer.
When you run out of monomer you can put in another monomer, or else you can cleave it and make a polymer that's very precise.
And this is what's called living:
you grow a polymer chain that doesn't die, it doesn't chain transfer, it doesn't stop.
So this allows you now to start to really make very precise structures.
And the change in polymer chemistry over the last 10 or 15 years has been phenomenal
due to the fact that there's now a large number of these living systems.
And you can use these to make all kinds of topologies.
We've made most of these.
I'll talk today about the brush polymers and show you why we're interested in that in the green context.
So what's a brush polymer?
A brush polymer is:
you grow a side chain of a low molecular weight polymer, 3 to 5 to 6,000 molecular weight.
You then polymerise it to a longer chain so you've got a backbone with -
these things are coming of, that's the reason it's called a brush.
People have tried making these well for years.
And you see the problem is that what you want these to do is that you want these side chains to bump into each other,
so it makes the backbone straight, have a very long persistence swing.
The problem is, is that if you've got a growing end right there, it's really hard for the next monomer to come in,
because they're going to bump into each other.
So the nice thing about the ruthenium system is that it's very stable,
and you've got good driving force, so now one can do this very precisely.
And so you can make these molecules.
This is a huge molecule, many millions molecular weight.
This is an AFM image.
You see it's a big molecule:
150 nanometres long, 50 nanometres wide, sort of flattened out a little bit.
And the other thing is it's fairly straight.
So that's really what we were thinking about, whenever we started making these molecules with these side chains,
is that it's going to make these things start to look like this.
Let's see where that takes us.
The next thing we can do is to make block polymers.
Essentially what you do is you start with a monomer.
You put in an initiator.
It grows.
We run out of that one, then you put in the next one.
What we've done in this case then is we've made our monomers with different kinds of polymers as side chains.
And if you don't know much about polymer chemistry, one of the keys in it is that it's really antisocial.
Polymers hate each other.
They don't like to mix.
And this has been known forever in the polymer area.
And so we picked side chains that really don't like to mix with each other.
This is polylactic acid, this is polystyrene.
We can now make a block polymer which has polylactic acid and polystyrene, so make it blue and green.
What happens when you start making these things interact?
They can't escape because they're covalently attached.
And so what we found in collaboration with Julie Kornfield's group - Yang is the one who really, really made this all work -
is that essentially from SAXS we could see that this is very highly ordered, in fact it almost looks like a crystal.
And the model we have is that these things separate, just like regular linear fluffy polymers do,
by putting all the groups together and then they have these interfaces, which is where the covalent bonds are.
And you see the link scale of this is 160 nanometres.
That's a link scale that's really hard to do in chemistry outside of the biological systems.
And if you cut it in half, so this is 100/100, so you make it 50/50 - now it's about half as long.
So we can control the length and the link scale by just controlling how many monomers we put in per initiator.
What about if we make it bigger?
Well, the problem was that you have to go to ultra-SAXS,
because here's the main peak and this is already off and so it's really hard to do.
But what we looked out...and I had a really, really good student working on this,
because he made a 200/200 and when he concentrated it down, it turned green.
And most people would think that there was an impurity.
But he held it up and looked at it and it's yellow.
Looked at it and it's reflected and it's green.
And he recognised that this thing is called a photonic crystal.
What's a photonic crystal?
A photonic crystal is a layered structure, where you have different refractive indices between the 2.
And so essentially you get reflections off of these.
And the wavelength that's reflected is controlled by the size and the optical density of the 2 -
the refractive index and the link scale.
So by changing the link scale, we can now change the wavelength of light that's reflected.
And why are these interesting?
It turned out these are beautiful insects, I don't want to control these.
And so these are insects that now are coloured -
they're not coloured because of dies, they're coloured because of photonic crystals.
And so these really nice shimmery butterfly wings are a result of these photonic crystal things.
We can now change the structure - and this is still pretty new stuff, I mean we've got a long way to go.
But we basically changed the size, so now we go from reflection.
So this is blue, transmitted light is yellow, this is sort of greenish, that's red.
So one can now go out to the point where you're starting to reflect things at fairly long wavelengths.
And we'll see where we go with that in a moment.
So, about finished.
And we can now basically make molecules that span the whole range of colours.
And if you make a plot - these are reflections -
and you make a plot essentially of the link scale versus - and it's nice and linear - 99 etc., etc.
And so you see what we're doing is we can now march across by changing this.
They have these nice lamellar structures which you can see.
And the point is we can now start to get out into the infrared.
So what can we do with the infrared?
Especially with a structure which when you evaporate it, essentially crystallises and spontaneously assembles.
So if we could make a block polymer of the right link scale so you could paint it on a window, let it dry,
it would spontaneously assemble and then reflect infrared.
You could have a window that reflected infrared.
So the game you got to play is to get these things to order on a really long link scale.
You got to get them so they assemble so that they're transparent in the visible part,
which is really what you'd like to have.
And so this is something we're moving toward.
It's a pretty tough problem, but that's ok.
Again I've been phenomenally lucky over the years to work with lots and lots of really super people.
Koji Endo was the one who really made the breakthrough in our Z selective catalyst.
These people are really keeping it going.
Bill is in the audience I hope - you better be here Bill.
Bill is working on another area which is green, which is turning stoichiometric reactions into catalytic reactions.
And I think that's another whole big field that one could go in.
So again thanks - sorry I took a little longer.
Applause