Forgione masterfully reframes green chemistry as a rigorous quantitative discipline rather than a mere ethical preference. This lecture provides a vital blueprint for modern drug discovery where molecular efficiency is the ultimate measure of scientific innovation.
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Aula 2- Minicurso Molecular Strategies for Drug Discovery and Environmental ApplicationsAdded:
at any time and I'll be happy to help.
It could be about directly the material that I talk about or it could be about your project. If you think that I can contribute or add any value to it, I'm always happy to help students as much as I can.
Um so I just want to start maybe just with a few uh uh inputs from the students to say so what would be some of the take-h home messages that you think were important from yesterday and it doesn't have to be there's no right or wrong answers. I just want to get some feedback as to what you think we are trying the message that we're trying to convey and and see if there's anything I can clarify on that part. Does anyone have any like what was the heart of what we talked about yesterday?
Anyone you want to start like what what do you what was the the thing the most and one of the messages from yesterday?
>> We have seen principles of chemistry. Um I think that reuse is better than recycle. We need to take [clears throat] care of the of the hazardousness and we need to be prepared to deal with we we have to be prepared to deal with the problems before the problems.
>> Yeah. Great. That's great. Good ones.
Anyone else?
Yeah.
>> Yes. Very good. Very good. Anyone else?
Yes. the design experience just what generated what about design.
>> Yeah. Yeah.
understanding of your whole process and not just life experiment but more in large scale so we can reproduce our [clears throat] ideas not just [cough and clears throat] >> yeah that's great that's great I think again there's no wrong answers I think all of these are so great but I think that one key word that I think that you said was design, right? I think that's an important aspect of green chemistry is designing um all of these concepts. I think that the 12 principles of green chemistries are not rules to follow, but they're design the ways to design your process, right? I think so. Designing things is a very a very good word. Any other take-h home message?
What I got was that prevention is better control afterwards that I mean we do everything so that we control that.
>> Yes. Excellent. Excellent. Very good answer.
Anything else?
No, these are all really really really good answers. So um uh so ju you know again to to make sure that you understand the the level that you're at right at this stage of your careers is that you all know infinitely more about green chemistry than I did at the same stage of the career of my career right it's like this when I graduated my with my PhD it was just the beginning of green chemistry right the book had just come out so before I really thought about green chemistry was many many many years later and so it's just like to say that you having been exposed to this topic at such a early stage of your career I think that's a huge step in the right direction because then you can start applying these concepts from the beginning not like me who started in the middle right and so the impact that each of you can have based on these concepts is really valuable and and the other thing is that I think that it's it's you know you see the different answers to the questions right and you see that everybody took something a little bit different from the the what we talked about yesterday. And that I think is very interesting because it's it speaks to equity, diversity, and inclusivity, right? Because equity, diversity, inclusivity is really thinking about problems in allowing many different people with many different viewpoints to contribute to solving problems because the way I think about a problem in Canada is very different than the way that you think about solving the same problem in Brazil. Right. and and and having both of us come together to solve problems is going to be if we're open-minded about it is going to be the best way to solve problems, right?
Because I can contribute something, you can contribute something, but you know what the way that based on our histories, our backgrounds, our cultures, right? The the the ways that we solve problems are going to be very different but all valuable, right? And that's why there's no real I want to make sure that like because it's an overwhelming amount of information that I provide to you, right? So I want to make sure that the point is not to memorize all of this stuff. It's it's really knowing it that it's there and knowing that it's important and then when you're designing something then you think, oh yeah, maybe I should access something from the 12 principles to help me with my process that I'm doing here.
And that could be, you know, in your academic careers or it could be if you go into an industry like, you know, then you'll be able to bring those concepts into industries um in Brazil and that's going to really impact things. You know, once you start impacting industries, you start really making a a positive cultural change in your communities and that's really important.
Okay. And again, just stop me at any time if you have any questions or you want me to clarify anything. So, um, turn this off.
Oh, [snorts] don't know why.
Yeah.
Um so uh just to give a couple of examples of u the history of some uh uh progress in green chemistry. So here's like uh an example of a dye. And if you think about, you know, the color um of kings, like, you know, from a long time ago, purple is associated with the color of kings, right? Because they were the only ones that could afford to have colored clothing, right? Because the purple color was very, very, very expensive and difficult to get from certain plant sources. And that was a dye. And so in 1856 um uh Perkin uh uh discovered a vivid purple dye and that basically opened the door to color being something which was no longer exclusive for uh royalty but became generally available for uh populations, right? And so essentially synthetic dyes was you know the progress in terms of color.
uh and then of course when one person makes the synthetic dyes then they open the door to the possibilities of many many others to come into this and uh commodify this and so you ended up with uh huge amounts of different colors. Um essentially efficiency was loan was not enough that but you had to add new value to these dyes because after a few dozens of years that essentially all colors of dyes could be produced in relatively low price. Um and so what was the evolution of these dyes? Well, you know then this is where chemistry gets involved. And so you have reactive dyes. So dyes that can um uh not only be colored on stools but could undergo reactions to generate the dyes. In the 1970s there's thermocchromic dyes. So when you apply heat to the dyes that it can change the color of them. So there there's uh uh niche applications for that. So essentially once everyone knows how to make the core product. So this is the original synthetic dice from 1856.
uh essentially after that then sustainability and the performance of those materials becomes much more important. And so here's now an example of all of the previous um dye examples that we've shown are colored molecules, right? So molecules that have specific colors based on the structure of the molecule, right? So you have to add in you know whatever grams of that molecule to make yellow grams of this molecule to make green right. So that is a synthetic die. But so this is where we we think about function right. So the function the importance of the molecule that makes the dye is not the molecule itself. It's the color that the molecule creates, right? And that's the the the synthetic dye background. But what if we can create color through another process? And butterflies are a great example of this, right? butterflies.
There's no dye in the wings of a butterfly. So butterflies essentially can appear blue without using a blue dye. But essentially this is from the nanocale structure of the dye. And it's the difference in terms of the thickness of the dye that can um um uh be used to create different colors. And so that is essentially um uh the varying the fiber thickness of the material in the wings and the structure of those materials and that's what can color the uh create the different colors. So now we have multiple um um technical ways to make colors. And now if we have that then we can evaluate can we actually reproduce what a butterfly does in uh by doing chemistry, physics, photoics and create color in a different way. And then the question becomes which of those processes is going to be more sustainable? Is it more sustainable to make a synthetic dye or is it more sustainable to make a nano technology that is able to um uh vary the fiber thickness and create the different colors? And there's going to be pluses and minuses of each of them, right?
Maybe it's going to be easier to make some colors via this process and other colors are going to be more diff more more easy more easily made or more difficult through the dye process.
Right? But this is just a good example of the end use, right? That's the function of the thing that you're trying to work with is the important thing.
It's not necessarily the chemical that is important, but what the function of that chemical is.
And so this is just um a self uh promotion slide, but if anyone's interested, so I'm the co-director of the center for nanocience research. So that's I put this in here basically because these are nano materials typically um that are used to make these colors in this way. Um and so we essentially are a group of researchers that are um u based on nano science. So different areas of research you can see here uh nano pattern patterning. We have a large amount of R&D capabilities. So this is all our um um uh equipment that we have based in our center and then we have uh we've we collaborate mostly regionally within the Quebec region but we do u uh wish to collaborate internationally. So if anyone is doing some nanochemistry um feel free to reach out to us and we uh would be happy to talk about potential collaborations.
Okay. So um green chemistry across uh different industrial sectors. So again these are uh very different industries.
So you know you can have very um um uh more commodity uh industries such as uh clothing um uh you could have higher tech industries like electronics. Um uh so the green chemistry crosses essentially all of the industrial sectors and that requires uh chemists inputs to make them more sustainable over time.
And then this is just the essentially what I said before but it you know the the discussions that go on on green chemistry are um much um more significant than it was uh even 20 years ago. And this is just an indication of some of the conferences that go on uh some of the journals that are focused on green chemistry uh and also public education such as this talk and things like beyond benign that is sort of um um highlighting all of the um uh key aspects of green chemistry where we've come from and and some of the challenges that we still have face going forward.
So the future of green chemistry. So um again uh that that word of designing. So uh it's really the design uh for hazard reduction. So thinking about the whole process um avoiding high-risisk molecular structures. And again how do we avoid high-risisk molecular structures is when we can actually uh um think about them from a chemical perspective and understand why that structure is a high-risisk structure.
Right? It's not only the fact that we can measure the toxicity of a structure but what we should try to understand is why is there a particular functional group that is causing the toxicity.
Right? So if we understand molecules we can understand functional groups. If we can understand functional groups then maybe an aldahhide uh will be the toxic part of our molecule and then we can design around the aldahhide. Right? So what is the aldahhide doing in our molecule? Is the aldahhide specifically ne necessary or can we use a caroxilic acid which also has a carbonial group?
So is the carbonial group important or is it the carbonial group of an aldahhide that's important for the function of the material because it might be toxic because of the aldahhide.
And so again that's where chemistry a deep understanding of molecular function is is is really critical. um avoid high uh reduce persistence and exposure. So again, you know, starting to understand some of the issues with persistence and the polyhalogenated molecules that tend to persist in our environments. But again, one thing that I want also want to impart on everyone is that um scientists are human beings and human beings can suffer from dogma. So dogma means that we hear something and then we take it as a factual truth forever and ever and ever right and that is not great science. So it's important to know dogmas, right? So for example, I'm telling you polyhalogenated materials are persistent in the environment, but it's important for you to know that that's true, but not take it as dogmatic because it doesn't mean all polyhogenated materials are persistent.
So the question is is that if you want to design a new molecule that's polyhalogenated, most of them have been persistent in the past. So why is yours not going to be persistent? Right? And that's the design feature. So it's the fact that you understand the dogmas and the general trends, but you can't accept the general trend as the as the conclusion because what we have to do is we have to do experiments to prove if that's true or not true. Right? And that's that's really important because uh I really think that dogma is one of the things that slows progress in any research area because it gets passed down from generation to generation and people say oh you can't do that and the next student just says oh you can't do that right but nobody stops and asks but why can't we do that right that's the important question if you understand why we can't do that then you can design better materials or better uh processes uh again design products and routes before scale up locks in risk. So again, it's not our role because we're not doing industrial chemistry in academia, but it's really our role to sort of start to think about this now so that we can provide better tools to those who are going to make the larger scale reactions so that they don't have to reoptimize everything, but they can start from a process which is much more friendly green uh a green friendly process from the beginning and that's going to essentially accelerate entire uh discovery process of any design of a new material or new process.
So um again I I I think that this is part of the reason why we um like to have these discussions uh you know globally is that um the the the solutions that are required in every community is going to be different right and so that's why giving you the the the the ability to think about these problems is going to allow you to solve the problems that exist here in lavas and and in Brazil, Right? Because for someone to come from the outside and solve those problems, it's not it's not going to be trivial for that to happen. Right? Because the problems the nuances of these problems is difficult for somebody to understand from the outside. And so I think that's why it's really giving the tools globally, but then the solutions I think should be coming more from the community and locally. And I think but again your local solution might impact something in Montreal, right? because even though your solutions are best solved here, but you might get inspiration from Montreal and Montreal might get inspiration from Lavas, right? So, I think that there is still solutions that could be global, but I think that there uh I think both the solutions and I think more importantly the problem like what is the issues that need to be addressed here are probably going to be very different than the problems that are need to be addressed in uh where I come from. And that's why I think that it's really important to give these uh talks uh around the world. And so what and again so understanding what the function is needed. Can the product be safer by design? Can the waste be valuable? So can we take the waste and convert it into something that's uh economically useful? And then you know what role can you play? And I think that the beginning is obviously going to be in your labs.
But then afterwards it's going to be going into industries and trying to um uh look for ways that those industries can incorporate some of these concepts of green chemistry into their uh processes and their design features.
Um so essentially the um the green chemistry is like taking away changing the way that we focus from the control aspect to the design aspect. So it reduces the hazards and wastes at the source. These design principles are uh essentially the 12 principles. And so that's the design checklist that we should be looking at to uh try to optimize any particular process and essentially any area of the economy is going to be affected. So health, climate, resources, regulation, cost, innovation is going to be affected by these green chemistry principles. Um and the future chemical markets will increasingly reward safer and more sustainable design. So we already see this over the last 10 years. There's really been an explosion in uh green chemistry technologies that have been incorporated and that comes through government um um oversight. It can come from consumers who want to um be purchasing products that are more environmentally friendly. Um so there's a a large amount of driving force factors right now. And so I think that this is a great opportunity or a golden opportunity for us to accelerate the um um the development of green chemical processes.
Okay. So that's it for that lecture. Let me switch over to the one [snorts] So this is the one the lecture that I said I would talk um yesterday about just my background and my overview. Uh this is my research group. uh last last summer. Uh there's my Brazilian Mariana.
She's uh uh PhD student who joined my group. And this was in uh uh the defense the PhD defense of master's defense of Sarah Taylor who's back here. Um so you know my path in chemistry my I'm a my parents were born in Italy. Uh, and I was born in small city in Ontario, Canada, near Toronto. Probably the biggest city that you might recognize.
Uh, then I didn't go too far from home.
So that's probably the same distance as um, uh, it's closer in Bellarante. So maybe half the distance from Beljante to here. Uh, so not far. That's where I did my undergraduate degree in chemistry.
Then I went to Ottawa, the capital of Canada for my PhD, a little bit further away, but probably about the same distance as Bellarante from here. Then I went to Ohio State University. I did a post-docctoral fellowship uh uh with Leo Pakquette. Then I went back to Canada to Montreal, Canada where I was working as a research scientist in uh Boringer Ingleheim. and then after I went to Concordia University where I'm currently um [snorts] working.
Uh so my group works on uh so what we do day-to-day is organic synthesis. So we make molecules. Um we make small organic molecules. They tend to be aromatic in uh nature. Uh but what we like to do and this is partly because of my experience in industry is that we like to um That's weird.
Oh, there we go.
So, we tend to um I had a friend of mine when I was doing my PhD. He was uh not an organic chemist. He was in uh physical physical chemist. So he was doing a lot of photo um uh photo measurements of his molecules. So a lot of kinetics. And he would come up to visit me in my research lab. And he would say, "It seems like the point of organic chemists is to make little yellow oils and fill up fridges." Right?
So we would make a reaction. We would finalize our final compound. We'd characterize it and then we would take that and we put it in a fridge for some magical day in the future when we think we might need it. But really at the end of your PhD, you're just going to wash all of that into the waste. And so I always that always struck me is that we weren't making things with an actual um end use in mind, right? We were developing new chemistries without a specific end use. So when I took up the academic position, I sort of thought about that and and so what we try to do more is that even though we're still involved in making those little yellow oils just for the sake of making them because we're trying to develop new chemistries, but we also try to collaborate with a lot of different people. So we have some projects in drug discovery. So we take those molecules and we give them to a biologist and they test them for activity for anti-cancer activity. uh we take we we collaborate with physicists and we look at their opto electronic properties of some of our molecules. We're involved in green chemistry. So essentially trying to uh use some of the principles that I've talked about today to um uh in uh uh improve synthetic processes and then we have a number of industrial collaborations uh um with uh pharmaceutical companies mostly to try to um look for ways that we can help them facilitate their research programs.
And so the first uh uh projects that we work on and so most of our chemistry involves what is highlighted here in blue. And so these are hetereroaromatics. So they're aromatic compounds with at least one heteroatom usually oxygen, nitrogen or sulfur. And these are highly um uh seen in drug-like molecules. So here's just four examples of drugs that you are actually uh commercially available and you see all of them have at least one hetereroaromatic ring and what you'll also note is that usually the hetereroaromatic ring is also bounds to at least one benzene ring. Right? So this is an aerrow substituted hetereroaromatic and essentially that bold bond is the bond that we are interested in making.
And so so this did I skip a slide? Yeah. So this is our research program in um drug discovery. And so this is in collaboration with professor Alisa Pikney in biology at Concordia. And so we discovered this structure which has essentially some uh interesting bi biology where it's uh actually disrupting centrosomes in the duplication of um uh cancer cells. Uh so this is an A549 cancer cell that's shown here. And you can see that with the control uh and then different amounts of our drug that you can see that we're essentially destroying the uh ability of this cell to uh duplicate. And so essentially um uh it also has some selectivity over can cancer cells over healthy cells. So that's very important if you're trying to develop a cancer drug. Uh you don't want to kill the healthy cells at the same rate as you kill the uh unhealthy cells. And essentially what we do is what's called structure activity relationships. So this is kind of related to what we've talked about uh in terms of what in green chemistry they call structure function relationships. So it's u this concept of we modify this chemistry this molecule, we give it to the biologist, they test it for biological activity and then we see if it's going higher or lower and then we modify the structure to try to improve um the compound. And so we have a compound now that has uh we have a compound now that has essentially been improved over this approximately 10fold. So we started something around 500 nanomer IC50 against triple negative breast cancer and now it's down to 50 nanomars and we probably need to go another 10fold more potent for it to become something which is commercially interesting to a partner and right now we formed a spin-off company called Enko Leap Therapeutics to try to commercialize this and we're currently looking for um u larger pharmaceutical companies to partner with um the materials side of things. So a lot of opto electronic materials have this common feature. So they have this thophene ring. Uh the thophene ring is a five membered heteraromatic with a sulfur. And so here's two sort of or advanced materials that have that diaph ring. Uh there's also other um natural products that have hetereroaromatics. So here again the red is showing the hetereroaromatics. And so these are other interesting targets that we focus on. And so to make those we've worked on things like and this is a good example of the greening of chemistry. So in 2008 there was Nobel Prize awarded for palladium catalyzed crossoupling reactions. Palladium catalyzed crossoupling reactions essentially are the reaction of aerrol. There's a a variety of different groups that could be here instead of the hydrogen buronic acids, tins um tins, boronic acids, stan no tins or stanes, zincates, organoates.
So what they do is they replace those groups and they do a crossoupling across this carbon X bond and the carbon metal bond. So in the Suzuki coupling and in the Nobel Prize winning couplings, there's actually a metal here, but you could imagine then you create a bunch of waste which is the metal X group. And so that waste you have to get rid of because it's a stochometric pro uh amount of waste. So here the CH activation that was done developed by these other researchers essentially replaced that organo metallic species with a hydrogen atom. Right? Now the amount of waste that you're gen generating is significantly lower. So that's a huge improvement. The problem is regio selectivity. So can you get this hydrogen to react selectively over this hydrogen that's on this carbon?
Right? So when you have molecules that are complex molecules, they have many hydrogens and to get it selectively over one hydrogen over another, it's a little bit challenging. So this chemistry is exceptional in terms of the atom economy of the reaction, but it's not so great because the selectivity can be problematic in certain cases. And so what ways can we get to improve this is that we can instead of using a boronic acid or organotin, we can use a caroxilic acid. And this is something that my group has been involved in with a number of other groups. And essentially the byproduct of this reaction is the CO2 which can be captured and reused to make the caroxilic acid again.
But here we have sort of an intermediate between the Suzuki coupling uh the tin couplings and the CH activation because now the caroxilic acid is at a specific place and because it's at a specific place the cross coupling can only occur here and cannot occur where the CH bond is right. So the regio selectivity is improved. Typically you have to do a higher amount of temperature to do these reactions. So that's a negative in terms of the greenness of this process. Um but there is uh positives uh over this. So the increased selectivity the increased selectivity but uh a lot of times you also in this case you do not need a co- catalyst here. You need usually copper or silver as a coatalyst for these processes.
We've also worked on this area which is desulfanate of couplings. So essentially we're replacing the caroxilic acid with a sulfonate salt that's shown here and we get similar selectivity in the sense that we get a cross coupling where the sulfonate occurs except now we're generating SO2 as a byproduct. SO2 can also be recycled in these processes to generate more of the starting material in a separate process. And so that is again sort of the way that we think about things in terms of the circular economy that you can take the byproduct and try to recover it to make more starting material and that would be a closed system so that you don't generate waste. Again really great in theory. We haven't been able to do this um super efficiently in a practical sense but that leaves a lot of room for additional research to occur in these areas.
Um so this is another area where we um uh are very interested in. So the United States Department of Energy in about 2004.
Uh they highlighted these uh compounds that are shown here essentially as future building blocks from biomass. So from sustainable sources. And so this is essentially was a document that was trying to uh motivate research in new directions to think about the chemistry that we can do this do with these starting materials and again thinking about the function right and so what they were really think what they really thought about in this original document and I think it was like shortsighted but it's 2004 so it's very early in the process of thinking about green chemistry but they were really trying to do like for like replacements. So, turthalic acid I think that um yeah I have a slide here. Uh so for example this purine dicaroxilic acid turthalic acid is an important monomer in polymer synthesis and so the fact that you have an aromatic ring and then two caroxilic acids. Well tthalic acid has an aromatic ring and two caroxilic acids. So they thought of like a like for like exchange of these two, right? But they're not thinking about function. So what they're thinking about is molecules. And so they're saying this molecule could replace this molecule, but they don't you don't you have to actually think about can the function of the polymer behave the same way with these two different monomers. Right? So that's where the green chemistry that we've talked about is like making sure that we think about function and not just replacing the molecules because they have the same functional groups, right?
The function of the final material. And so even though this is a good idea, I don't think it's uh practically feasible because the furine is much more unstable than the benzene. And so the polymer that gets made from that would be less um uh uh robust. But that might be a positive thing because if it's less robust, maybe you can deppolymerize it more easily. Right? So that's the sort of the the overall thought process that you have to think about if you want to incorporate these into your um uh uh uh material or whatever you're trying to achieve. But I think that what I think that this is kind of uh an important um thought process for everybody in the room in the sense that uh if you know that there are lists and probably as things evolve these lists are going to be to evolve of which chemicals are essentially potential future building blocks. It might be something that you want to incorporate into your research because maybe what you're incorporating currently into your research is very cheap because it comes from the petroleum industry. But that byproduct of the petroleum industry as petroleum becomes more and more scarce that byproduct of the petroleum industry is going to become more and more expensive.
And at some point that byproduct that you're currently using is going to be replaced by something. You're going to need to replace it with something. And these are some of the things that you should start to think about. And again, it might not be costefficient now, but we're thinking about long term, right?
So you want to be the ones that are developing processes with something which is more sustainable than something that's not sustainable.
And so what we what we took at um uh a look at was that HMF is was not on this list. But essentially HMF if you look at the degradation of sugars, HMF is a precursor to FDCA in biomass production.
So um the HMF that we start with is actually upstream from FDCA, the dicaroxilic acid. So it's actually um uh in the sort of the whole um process it would be considered a likely more inexpensive precursor than FDCA uh which I showed on the previous slide and what we showed was by uh doing a mechanochemical process and so I'm going to talk about this maybe uh on Thursday with one of the last lectures about mechanochemistry but we we've recently gotten really interested in mechanochemistry. So mechano chemistry is rather than taking your what a typical organic chemist does which is take one starting material and take another starting material put in a bunch of solvent and then mix it and then heat it over a period of time. Then you do an extraction to remove that solvent to isolate your final product. Then you usually have to do some sort of chromatography or distillation to purify that organic material.
What we're learning is that what we can do and and we're not really learning it but we're relearning it because this is chemistry that was done thousands of years ago um is that you can just take a mortar and pestle and grind two reagents with with respect to one another. And that grinding process creates a lot of energy and that grinding process might be sufficient energy to get those molecules to react. And now you've done a chemical reaction in the complete absence of solvent. Right? And the solvent cost for most organic reactions is the largest cost for the process. So removing solvents completely from the process can have huge impacts on reactivity. Now mortar and pestle is um is a relatively primitive way of doing it, but it's a completely mechanochemical way of doing any process. What we do to make it a little bit more systematic and also so my students don't have to grind all the reactions manually is that we take, you know, u pre-made um ball millers. And so these are essentially things that either they're steel vessels that you put in little steel uh balls into those vessels and it shakes at a very violent speed and you can control the speed at which it's shaking. And the different speed at which it shakes is going to create different energy. The different amount of balls that you put into the um system is going to create different amounts of energy. Whether you put in one or two or three, that puts in a different input of as energy. You can change the material of the balls from stainless steel to teflon. So it'll be softer or harder and that will change the energy input. So you have a lot of controls that you do just like you do in a traditional organic chemistry reaction, but they're different controls, right? And they're different parameters that you play with, but you do this all in the absence of solvent. And so this is really something I found, you know, over the last 10 years quite remarkable that you can do a lot of these reactions. And so this is one example. So that's where when you see these these three balls here, that means that we've done it mechanochemically in the absence of the um solvent. And what we found is that you can take HMF and you can do a disproportionation reaction. So this is an um canazaro reaction. So essentially what you're doing is you're taking one of these molecules to oxidize another one of the molecules. And so you get half of it oxidized to the caroxilic acid, the other half reduced to the um alcohol. And again we showed that you can take this 50% and reoxidize it to the aldahhide and resubject it to these conditions and keep essentially that looped cycle to form this derivative which has a caroxilic acid on one side and an alcohol on the other side. And what's interesting is that we get complete conversion. So it's essentially complete conversion to this and this. So it's a 50% of each of them 100% we are only using KOH uh in the reaction. So we do have sort of a wasting of one equivalent of KOH but that's uh what's required and the reaction is only 5 minutes. Uh and then we just have to do a workup to uh to isolate the caroxilic acid. And so again like I said in terms of the uh public the the publications so green chemistry is the journal that we published this in because it's a relatively simple reaction simple process but the important part of it is the removal of the solvent and the recycling of the materials uh that you showed here. And so uh again every process is not um perfect. So we have no solvent required, very small reaction time, no heat has to be entered. But the there's always the limitation is that we still can only produce in one cycle 50% of that material. We can never get to 100% because of the nature of the disproportionation of the reaction. Uh uh we can also scale these reactions up.
So we can essentially scale from 100 mg to a,000 mg. we have to increase the time a little bit but essentially we still get relatively good yield and this is essentially just showing you oh in this case so there's two systems that we have so one is the um the shaker mill that we call and then this is an or orbital mixer and so this is um this is the the ball miller here and so essentially it's going round and round like this and that centrifugal force is what's causing the balls to spin within the system that's shown here and that's where you get the grinding effect. And here's sort of an example of the reaction at the start. So we mix everything in the start and then at the end of the reaction we have this. And so you know again no solvents for the reaction but you know and this is where in terms of the green chemistry concepts that we uh are talking about is that you have to include the entire process right and so if I talk about no solvent for the reaction what is problematic with what I'm saying what could be a problem with if I'm saying that this is a solventfree process How do I get this stuff out of this jar?
Right? That's that's a question that you need to ask yourself, right? So, can you scoop it out when it's like all caked?
It's all caked onto the side of the walls of this reaction. That's not trivial to do, right? Because I want to get 100% yield and so I got to get it all out. But if it's like that, it's really hard for you to think. So what do you do? You use a solvent, right, to get it out. So now, is it solvent free anymore? So again, you know, this is the thinking about the entire life cycle of a system. And again, we're we're working towards better improvements, right? So we have solvent free in the reaction, but we don't have solvent free in the isolation and in the purification. And so how do you solve that problem? we haven't come up with a good way of solving that problem, right? And so that's an open question that needs to be resolved. There are ways that you can think about this and like you know this is where um collaborating with people in different areas is very important. So polymer chemists have a great way of making polymers which is a twin screw extrusion. I don't know if you know about this, but you have like essentially a screw. Like you can think about like a screwdriver screwing into a piece of wood and polymer chemists have little little screws where you can actually put in chemicals into that the slots of the screw. And then as it's screwing in, the friction is actually causing the polymerization reaction to occur. And they do that in a system where the screw is coming across like that. They're dropping in the chemical like this and then the chemical is being pushed out the other end, right? And so that's a process that you wouldn't have to worry about taking the material out of the ball miller that we have. The problem with twin screws is that they do it on an industrial scale. There's no lab scale twin screw extruder. So in my lab, I'd have to buy something that works on the kilogram scale, right, to see the proof of concept. And that's something that's not trivial for us to do. So we can't use a twin screw on the scale of our reactions. But if you go industrially, you might be able to solve that problem.
But again, that's like you know working with many different scientists, right?
Because now it becomes a chemical engineering problem as much as a chemistry problem.
Uh the decarbox crossoupling. So again we are interested in doing these reactions where we can do make a carbon carbon bond between a caroxilic acid and an aerylhalide and what we've done is we've made these uh illegal what are called iloalines. So we keep adding essentially more and more thophene and so p3t which is the polymeric version of the thophene. So if you did this and M N and M were in the orders of hundreds that would be a long polymer and there's many ways to do that but as you know polymers are poly disperse. So when you make a polymer you say it's a certain molecular weight but it's actually a mixture of all molecular weights around a single molecular weight which is the one that is the most common in that polymeric material. So polymers are not uniform chemicals, right? They're they're a broad range of size of chemicals with all the same repeat units. And so because they have a broad range of size, that means their function could be affected by that broad range of size. And so what we're trying to do is we're trying to say, can we determine what's the minimum number of thophane units that are required for this molecule to behave like a polymer?
Right. And that's why we do this uh as an organic chemist as a as a a small molecule organic chemist as opposed a polymer chemist who's going to make it much more efficiently but the broad range of molecular weights is going to affect the function of that material.
And that's what we're trying to understand is that the structure function can we control it better by doing it this way even though the cost is going to be higher because the cost of doing this stepwise versus a polymer process is going to be hugely different.
Um so uh this is just giving you you know for those who may not uh be uh organic chemists but this is essentially irrespective of which project is going on in my group the thing that my students do on a day-to-day basis is essentially this right so this is just one example is that we're trying to optimize the formation of this bond uh what we're doing is we're modifying the catalysts so we're changing the different types of catalysts We're changing the lians. We're changing the bases. We screen for different solvents, time, temperatures. Um, and then what we do is we uh analyze this.
Oh, first we do a workup or extraction.
So, we remove the material from the organic solvent. We do an analysis which is typically either one HNMR, GCMS or TLC. And then we do purification of these. So the TLC indicates whe how whether we have that pure or not and then we characterize it by NMR uh proton NMR carbon 13 NMR and a high resolution mass spec uh and we determine the uh the percent yield. So this is just an example um of reactions that have different outcomes.
In this case it was highly colored. In most of our cases, we don't really have that highly colored materials.
Okay. So, let's uh take stop there.
We'll take a break uh 10 minutes and we'll come back. We'll get back on the green chemistry bandwagon.
>> [clears throat] [snorts] >> message.
>> [clears throat] >> Good morning.
>> [clears throat and cough] >> Okay, welcome back. Um, so I completely forgot to take the microphone off. I hope that it wasn't on the whole time.
Uh, the funny story is that in Concordia where I'm the professor, we have the same microphone. Um, and I left it on to go to the bathroom.
And so in the room was just the sound of me going to the bathroom, but I was in the bathroom. And then when I came back, everybody was laughing and I didn't know what they were laughing about until I figured it out. So, you got to be careful with the microphones. Um, [clears throat] okay. So, uh, any questions or comments?
Is it Are we good online?
Test. Test.
It's good.
Okay. So, um we'll go on to and again I think that I sent the lecture notes to Tao. Did he uh circulate them yet? Do you have the lecture notes?
>> No. Okay. Maybe um >> I'll uh I'll make sure that they get forwarded so everyone has them. Um yeah so uh I wanted to just start with another sort of uh small advertisement.
So I'm the co-director of the center for nanocience research and I'm also a member of what's called the center for green chemistry and catalysis. So this is a network of 85 researchers in Quebec. So Quebec is a province of Canada like uh Minus uh is a state in um Brazil. So essentially all the researchers in Minus, all the researchers in Quebec who are interested in green chemistry, we've come together at different universities and we are trying to promote green chemistry research in academics. And so uh the research axes that we talk about is the invention of catalytic reactions uh tools for green synthesis transformations of re renewable resources and then these two UAC these two blue axes which are green chemistry energy advantage and evaluation and policy in green chemistry. So again, we're trying to not only do basic research, but we're trying to push different policies uh in the governments to uh promote green chemistry uh going forward. And these are the universities that are involved in this.
And as I said, we have 85 different research groups that are part of this um u uh center.
Okay. So, uh, today's map, uh, again, you know, we're we there's a lot of repetition in these slides, but I think it's sort of we're looking at the concepts of green chemistry, and we're trying to package them in slightly different ways because I think that the concepts uh the uh of uh the concepts of green chemistry like the uh the 12 principles that we show over here can be seen from many different perspectives. And that's why I uh we create the slides in this way. And so what we're trying to do is think about how um some of these principles can be gathered with one another. So essentially if you look at these first six principles they all deal with um uh waste atoms, hazards, products, solvent and energy. The remaining principles feed stock derivatives catalysis uh analysis and acid prevention. and how can we compare these different classes of the 12 principles with respect to one another and for particular design problems. So if we look at it in a different way and we categorize them in these types of groupings. So now if we think about it from reducing waste and improving efficiency, well [snorts] these eight sorry these three um of the 12 principles really are dealing with this in particular. And I say this to say that when you are thinking about designing a route um designing a process with green chemistry in um um in mind that instead of looking at them essentially as 12 individual um uh design concepts, if you look them look at them under this grouping, you'll more effectively see that if you're trying to reduce waste essentially probably all three of these are going to be applicable. So instead of doing it one by one and you group them, then it becomes a little bit easier to manage which ones to think about particularly with your problem in mind. Uh if you want to reduce hazards, well you want to have less hazardous synthesis, you want to design safer chemicals, you want inherently safer chemistry, right? So those are all reducing the hazards.
Improving life cycle. Well, if you have renewable life renewable feed stocks, then that improves the life cycle. If you can degrade the final product that improves the life cycle, right? So those two are really designed for life cycle analysis. Improving processes choices.
So safer solvents, energy efficiency, catalysis, which essentially is closely related related to energy efficiency and real time analysis all are improving the process choices. And so we're going to talk about these in terms of this uh these groupings. Um, so basically traditional chemistry often manages harm after it has already been created. So we've talked about this before and what we're trying to do is design out harm from these processes. And so how can we do that? Well, wasteful synthesis require treatment, transport, and disposal. So essentially inefficient synthesis is going to create a lot of byproducts. It's going to create a lot of solvents. it's going to create a lot of uh uh consequences that needs to be um uh dealt with. Um [snorts] reagents and solvents are often selected for performance before hazard. And so what we mean by that is that we think about as um chemists is that we're looking at a particular transformation and we tend to focus on yield, right? So we change one solvent for another and we say well the yield of our reaction has gone from 40% to 90%. And so that's a good thing, right? But that you're looking at a single factor in the whole process design theories, right? So you have to think about the yield, but then you have to think, well, is that solvent that I've chosen for 90% yield is how how easily can we dispose of that solvent versus the solvent at 40% yield, maybe that solvent is much easier to dispose of, right? So one could be, for example, dchlorommethane and the other one could be water. out. That's not a perfect system either, right? And that's again where we think about, well, oh yeah, if we do reactions in water, it should be much safer than an organic chlorinated system. But the problem is is that water, you have to then decontaminate it from all the organics that you have in there. So you have to purify that water before it becomes useful again for other processes. So just by doing it in water, that's this thinking of well natural is better, right? DLO methane is industrial. It's synthetic. Water is natural. So, it should be better. But we have to look at the whole process. So, it doesn't mean that water is not the better choice, but it's more complicated than just saying water is always better than organic solvents.
Many uh products were not designed with degradation or low toxicity as requirements. I think that's really uh one of the key issues in um uh uh this these processes. It's not easy that if for example and this is like the two contradictory design features that you have in a lot of chemical processes right so if you make a polymer for an industrial application typically you want that polymer to be hu highly stable right you don't want it to degrade under heat because if I design a polymer for a Canadian application in the winter at minus 20 I want that polymer to also be useful in Brazil in the summer at plus 35. Right? So the polymer has to be able to depending on the application perhaps be equally the performance of the polymer has to be equal across a large temperature range. And so that means that has to be highly stable across a large temperature range. So then the question becomes if I want to design it for degradation then how can I degrade it? I've designed it to be highly stable over a large temperature range. Right?
So the design feature inherently means has to be highly stable which contradicts the degradation ability at the end of the life cycle. So you have to come up with some creative ways to do that. So maybe for example you could have something which is light sensitive, right? So maybe for that polymer application is for nonoutdoor uses, right? It has to be something which is not exposed to the light and then maybe you can degrade it by photochemistry. So that could be a design feature that you design into it. So it becomes highly complicated because the function might be contradictory to the degradation process and how do you deal with that that's not trivial and then uh see safety is frequently handled through barriers uh personal protection uh devices ventilation and regulation. So again these are high cost they are have a high human cost because human beings have to deal with these chemicals. So if we can design out um things that are unsafe, then we become a much safer workforce and that is better than uh having a process that has been uh designed with highly volatile chemicals that might cause human problems to the people producing it. So thinking about that in the design process can uh improve things dramatically.
>> [gasps] >> So um essentially uh we we think about um green chemistry mostly through the lens of environmentally protection. Uh but there's a lot of other areas that are affected are benefited from green chemistry. So you know uh human health uh through lower exposure and toxicity uh and the economy is generally um even though there's usually more upfront costs but long-term those costs are oftentimes rec recouped through less waste lower liability because your employees are not exposed to these toxic toxic compounds in the generation of your materials.
uh science benefits because we are pushing the boundaries of what can be done with uh the science um and creating new products and then competitiveness innovation across sectors and I think that most governments this is one of the things that is um a key driver to economic performance is innovation right so uh economies that are mo the most competitive are usually the economies that are the most innovative if you don't have a huge amount of natural resources, right? So natural resources drives economies. The next thing after natural resources is innovation. So if your country has a lot of natural resources, usually you're competitive.
If it doesn't, how do you drive your economic growth is through innovation.
And that's where you know um uh uh I think that all students should be thinking about you know how can I take transition the research that I'm doing to become an innovative contributor to the society and which has educated me right and I think that that can be really I think it's something which is underappreciated by graduate students in physical sciences I think again just like I said before is that I think Brazilian students are competitive globally I I think that the other thing globally that is underappreciated is that graduate students in physical sciences have an exceptional ability to solve problems, solve difficult problems, right? That's what you are great at. Your particular research area that you're involved in, that is a tool, right? That's just a small part of your ability. your ability is to solve very difficult problems with lots of data input and to produce something of value out of that, right?
And that can be applied to so many things including creating new businesses, new technologies that can benefit your communities, right? So I really I think that at this stage of your your careers, you should really be thinking about that is beyond just your science that you're doing. I think you should be thinking about how can I convert this with partners probably right to something that could be something economically beneficial and I think that you have the skill sets to do it. It's just whether you will have the courage to do it. And I think that that I think it's something that uh I wish that I would have thought of earlier in my career. And I think that you like it's not for everybody, right? But it's something that you should at least consider.
Um so, uh essentially, uh we we often talk about hazard. So hazardous chemicals, hazardous materials, but essentially hazard is only one component of risk.
And the other component is obviously exposure, right? So risk is essentially hazard times exposure. And so essentially the higher the hazard, the lower the exposure needs to be and you can still undergo a large amount of risk. Or you could have low hazard but huge exposure and that's going to increase your risk as well. So you need to manage both of those when you're talking about risk. And so essentially uh what traditionally we've done is we've reduced risk by reducing exposure, right? So we just say that for example we get better fume hoods, right? So when you're doing research in a lab, if you have better fumes, that means that exposure is going down, but that's not changing the hazards of the chemicals that you're using, right? So your expo your risk is going down because the the amount of time that you spend breathing in toxic chemicals has been reduced. But what about if we can reduce the amount of toxic chemicals that you use? Now we're reducing exposure and the hazard and that's creating a much more safe work environment. And that's just in your lab as a graduate student. You can imagine that if you take that industrially it's going to have a much huger impact on the workers in those fields.
um waste prevention. So this is we talked about this um superficially but this is one of the take-home uh equations that you should think about when you think about green chemistry and this is E factor. So E factor is the kilograms of waste produced over the kilograms of product. Right? So the less waste that you can produce and the more product that you can produce per the waste then the better the process is. And so here and I think uh is one of those things where it's it's you know this understanding what this means can be very important across different sectors. And so if we take a look at oil refining, right? Oil refining, which we think of I think is like, you know, if we asked everyone is that a dirty business or is it a clean business, right? We would all think of it as a dirty business, right? Oil refining. But the E factor for oil refining is ne is close to zero, right?
That's pretty amazing. And so why is that the kilograms of waste that gets uh produced per kilogram of product why is that so low in the petroleum industry is because they refine everything right it's so valuable that they take every single byproduct that comes out of that process and they commoditize it. So in one way we're depleting the petroleum that is a finite resource on this earth and that's a big problem but maybe we have a lot to learn from the petroleum industry because what they're doing is essentially that whatever they're taking out they're making sure they're using everything right and so that's actually an industry which for eactor is the most competitive industry and then if you go to fine chemicals so things that are more produced you starts to get worse factors sorry bulk chemicals and fine chemicals fine chemicals are usually the starting materials that you use in a graduate lab graduate school uh and then far the pharmaceutical industry then it's even larger right now of course we have to take this into consideration right the amount of oil that gets produced per year right the kilograms of oil versus the kilograms of the pharmaceuticals like a these are not even on the same scale, right? So a tiny E factor multiplied by billions and billions and billions of crude oil still produces waste, right? Whereas the amount of the pharmaceuticals that gets produced is a small fraction of what the amount of oil. So the E factor is worst, but the total cumulative waste that gets produced is not going to be on the same scale, right? So you have to be careful when you look at these numbers, but it just it's a good way to measure efficiency within an industry, right? So I don't think it's fair to compare pharma with oil refining, but within pharma, what you should be doing is aiming for the most efficient process.
And the most efficient process is lowering the E factor uh amount for um uh um uh your process. And and I think that one of the most important things is that E factor essentially when we do an organic process as a graduate student that I've talked about before is that what the first thing that you're thinking about is yield right so you say 40% and 80%. If it's 40% we we calculate yield in moles but ultimately what you get out of the product is grams or milligrams or whatever right so you get a weight weighted material at the end and so 40% or 80% is going to give you if it's the exact same reaction is going to give you 100 milligrams or it's going to give you 40 milligrams if it's you know approximately 40% of 100% right so what you're doing when you're doing the yield of the reaction is that you're completely ignoring this, right? All you're saying is that how much kilograms of product can I produce? So yield is one measurement that completely ignores a huge amount of process which is the kilograms of waste. So this is taking now we have to take into consideration yield because that gives us some indication of the bottom of this equation. But then we have to factor in waste. And when we factor in both, then we sort of get the real um uh consequence of any process, any chemical process.
And so here's just uh uh one example that I pulled out uh uh of the literature. And so this is uh seldinophil citrate. And so if we take a look at the process and again it's not important for this course the exact chemistry that's going on here but essentially what we're do what what they've done is they've done a one two three four five six step process and so there's six linear steps from something which is commercially available that's shown here to get to the drug material you see that the reagents that they've chosen here are relatively simple reagents in general. Um, a lot of these steps are crystallizations.
So, they're not purifying these things by column chromatography on an industrial scale. Column chro silica gel chromatography is essentially not practical when you're doing this uh on an industrial scale. So a lot of these are rec crystallizations uh for all of these steps or extractions that's shown here. So this process uh was the original synthesis uh industrial process um from Fizer for this uh molecule.
What are some of the factors that might be missing if we're trying to analyze whether this is an efficient process in terms of green chemistry um concepts? What are some of the things that could be missing or would be useful to know?
>> So like bypro byproducts. Yeah, exactly.
So it's like what byproducts are being generated and can they be reused? That's a good one that's missing from here.
>> The solvents used for each step. Yeah.
So here they're not indicating the solvent. So that's an important other feature is that was this done without solvent which it might have been but if it's not then the solvent is definitely something that has to be considered in terms of the efficiency of the process.
What about temperature right they don't indicate the temperatures here. So how did they have to heat these reactions?
Uh did they have to cool these reactions? So if you mix nitric acid and sulfuric acid that's a highly exothermic process and so you might have to try to cool that reaction which is an energy input that needs to be taken into consideration. Right? So there's a lot of factors details that are not necessarily shown here. It's just to give the highlight of saying it's not only the number of steps but it's all of these other factors that we have to consider when we look at a process of whether it's uh a green process or not.
And so here this is essentially the uh the optimized synthesis. So after the original one which was good enough to produce the first few years of the product but they were still trying to reduce the um uh environmental impact uh and reduce the cost of making the material and if you see here they essentially are going to one two three four steps. So this is what they call uh so the previous uh example the synthesis is very linear right so every step counts on the previous step so you're doing it one step at a time and the second synthesis is what they call a convergence step. So you make two different processes and then you take two components that are more advanced and you couple them together to make a highly advanced final product. And so usually making a convergent synthesis is much more effective than doing a linear synthesis. And so that can reduce the number of steps in the longest linear sequence and it also can improve the yields of the overall process. And the other thing is that like if you look at the yields of these processes, you know, it's 92 100 90 92%. So really high yielding reactions so that you are getting more of the material um um into the final product. And um a lot of these reactions are highly atom economical. So here you see there is a reduction reaction. So essentially the two hydrogen atoms there are the two hydrogen atoms that get incorporated into the final product. And so from an atom economy and we're going to talk about that in a few slides as well. And so they significantly improved the synthesis. Again, uh it's not uh critical in terms of the um uh every detail that I show here, but the yield went from 36% in the linear sequence to 75 to 82% in the convergent synthesis. The reaction mass efficiency.
So essentially how much of the reactant mass was incorporated into the final product? It improved almost three-fold from 10% to almost 30% and waste intensity the E factor was approximately six when most pharmaceutical processes have an E factor of between 25 and 100.
So that's a significant improvement of the E factor. And this is the amount of solvent that is used for the original synthesis. And this is the the amount of solvent used for the new synthesis. So again, huge reduction in the amount of solvent. And so this is an example of the process. So here it's we you know and this is where I think the pharmaceutical industry is very different than uh um the the petroleum industry is that the function of the final molecule you can't easily change the final molecule and have the same function right to get another molecule that does the exact same thing as sadil is not trivial and that's a huge cost in terms of research costs and so here because the final molecule has to stay the same. The only thing that we can do is this process intensification to optimize all of the ways in which we can actually um um synthesize the molecule to make it the most efficient. So the function is limited by the end product, but there's still ways that we can improve all of these routes. And in the United States they have these uh green chemistry awards um that are given out to um you know academics, industries um u policy makers every year and this uh commercial green process by Fiser was one of the winners in I think about 2010 or so uh for this um um award.
Uh this is yeah this is the same as the last slide.
Uh so uh how else can we optimize processes? So we talked about this before too is that we have process A uh we look for the byproducts and the waste uh and can we divert those into a separate process which is B that could then be converted to some value added product. So again this is going to be highly dependent on the um uh the industry that you're talking about. This might be this is something which is uh this whole process which I was talking about the petroleum industry. This is what the petroleum industry does very well because process B can add a whole lot of solvents or raw chemicals that are used for essentially chemical manufacturing which are the starting materials then for all of our research areas. Um but the further you get into specialized chemicals like pharmaceuticals then it becomes more difficult to uh be able to uh figure out a way to have a process B which will be commercially viable for uh using the byproducts of these reactions because those reactions are just done on such a smaller scale than there in the petroleum industry that it's harder to find a market for these um uh byproducts.
Okay. So uh atom economy. So this is um uh another important feature. So one is yield, the other one is E factor. And now we have to talk about how many of the atoms of the starting material are incorporated into the atoms of the final product. And so different reactions have different uh atom economy uh u uh values. And so if you look at something like the styrene epoxidation and I'll show you in the next slide what I mean by these reactions. So here I just want you to take the take-h home message is that every type of reaction is going to or process is going to incorporate more or less of the atoms in the starting material into the product. The less atoms you convert into the product, the more atoms you have to deal with to get rid of. Right? So if the atom doesn't go into the product, it's going into a byproduct. And if the byproduct is useful, then that's great. If it's not useful, it's waste and it needs to be dealt with. And so if we look at uh um uh two reactions, so this is the dealer reaction. It's a 4 + 2 cycle addition uh uh reaction between a dying and a denophile. This is just a simple example to show, but the take-home message is that essentially these four carbon atoms and those two carbon atoms, all six of those carbon atoms are part of the final product. Right? So in terms of atom economy, you've economically used every atom in the starting material in the final product. If you look at an epoxidation, again, this is a type of reaction that we learn I think in most undergraduate organic chemistry courses.
But if you look at an epoxidation reaction, this is a great reaction. So you take cycllohexene, you epoxidize that, you remove the double bond and you put a carbon oxygen carbon oxygen bond to make this three-membered ring. It's a drawn a little bit funny here, but this is still a six-membered ring.
What you're doing is you're taking this reagent which is metacchloro perenzoic acid and you're just essentially peeling off that single oxygen atom and that single oxygen atom is being attached to this cycllohexene ring.
But the waste then is this entire molecule minus that oxygen atom. Right? So the molecular weight of the byproduct compared to the molecular weight of your target product is huge, right? The [clears throat] number of atoms here, there's more atoms here than there are in your target molecule, right? So this is a very atom noneconomical process. So again, it's a great way to do this reaction if you're doing this at in an academic lab. But if you're going to do this industrially, you have to think about all of this waste that you're generating. But this is the type of thing which if you start to think about it in terms of green chemistry concepts, then it's like, well, how can I do this reaction with a single oxygen atom? where can I get an oxygen atom that's not part of MCPBA and still react in the same way that that oxygen atom right then that becomes a whole area of research which can involve in organic chemistry organo metallic chemistry um uh surface science by uh immobilizing oxygen on the surface of nanomaterials right because what you're trying to do is essentially trying to replicate something which is atom non-economical with something much more atom economical and that's the type of problems or the questions that could be answered that could provide great value to the research community going forward and of course there are people that have solve not solved this problem but have solutions to this problem I've shown you a bad example but there's better epoxidizing agents but this could be an open question in different areas if you look at it from the atom economy of a process um uh less hazardous um uh synthesis. So here's uh uh an example of uh a dipic acid. So the synthesis of dipic acid essentially started from benzene derived feed stocks. So essentially benzines and all of their derivatives are usually um petroleum based um uh in terms of their origin. And so essentially because it's starting from the adypic acid synthesis, so the synthesis of this molecule here, uh starting from this aromatic compound, you have to dearize it to get to the final product at some point. And usually to dearize things, you need to have very strong reactions. So uh nitration reactions which generate nitrous oxide as a byproduct and is a potent greenhouse gas. So the alternative is to take advantage of some biochemistry. So now if we think about glucose as a starting material, we can then modify glucose and then take advantage of um um catalytic biocatalytic processes. And so here's an enzyme which can uh convert this muconic cis muconic acid to adypic acid. And so now we're taking things that are relying on petroleum based feed stocks. Instead we're starting with biomass derived sugars. We're modifying it. We understand that there's enzymes that can do certain catalytic processes very efficiently. So we're starting from biomass. We're using enzymes as part of the process. And so this process ultimately becomes a much um uh greener process because we change the feed stock. We're changing the oxidant. Uh we're changing the solvents because we can use much more water-based solvents here. And uh we're doing this biocatalytically.
So again, this is now uh uh thinking about uh addressing a problem which is coming from petroleum and stealing uh starting from biomass based starting materials. So the function of the final material is the same whether it's sourced from petroleum or biomass but the process has improved significantly because we have incorporated um design principles based on green chemistry concepts uh designing uh uh safer um uh um less toxic chemicals. So again this is uh you know this is a real challenge because we need to really dial in what is the hazard that we want to avoid and how is that hazard um um uh created based on the molecular structure of the hazardous material. Right? So that's where it's the structure activity relationship or in this case the structure hazard relationship is very important. So we think about carcinogenicity.
Often times carcinogenic molecules are things that can alkalate for example DNA right and so if we know that alkalation of DNA is problematic then we have to look for things that are strongly electrophilic and if they're strongly electrophilic then can we dial out the electrophilicity so that it doesn't react with DNA to cause those carromogenic properties. So again, this is really one of the most challenging features because we're now trying to design structures. We're trying to redesign molecules to have the same function but it behaves different in terms of uh uh the toxicity to a living system, right? So it becomes hugely complicated because the toxicity in a living system is a non-trivial thing to deal with. So I think that this is an area which is widely uh underexplored because of that complexity. So for example, if you're trying to do something really complex like make a drug for uh human health, there's great economic incentive to do that, right?
Because you can make a billion dollar drug here. What you're trying to do is change the carcinicity of something. uh there's not a huge economic driver for that because if you change one solvent for the other, you still need a solvent for your process.
It's just that solvent is less carcinogenic, but the economic benefit is not the same as making a drug. But all of the processes that you have to understand that compounds behavior in a human being is the same level of understanding, right? And it's very hard to understand how drugs behave in human systems, right? that's non-trivial and that's part of the reason why drugs essentially novel drugs cost so much because of that process of understanding it biologically. So I think that this is something which is not trivial. I think maybe computational chemistry can have a huge impact on this because I think that we might be able to learn things um through computational chemistry that would be speed this process along because we can understand why the original compounds are toxic or why they're um endocrine activities and then trying to mimic things that might behave similarly in function but not similarly in their toxicity.
Um so uh here's a case study of uh for example uh DDT uh um persistent chemicals. Uh so this is essentially you know showing that uh DDT is um changing the the thickness of eggshells uh through exposure. So essentially uh egg uh like things like chickens can't hatch because the eggs are so um uh um easily broken. So they can't uh nest for long enough. Uh and so essentially uh what we need to do is uh you know deal with things like DDT because their ecological effects can happen very far from where they are actually exposed. So DDT is accumulating globally uh even to this it's not accumulating anymore but it's still having effects despite the fact that we stopped using it uh a long time ago and so essentially what we need to do is have things that are have targeted action and faster degradation right so that's where the problem was with DDT right is that we thought about it only in terms of its function but we didn't think about it in terms of its degradation and if we can have something which behaves like DDT. So the positive effects of DDT but degrades in a very shorter time scale then we would have less of the byproduct by uh the um unsafe by uh products of the use of things like DPT [snorts] uh safer solvents and uh um exposure. So uh this is as I said some areas where I'm working in which is no solvent. to thinking about doing things in mechanochemistry uh is something which is very interesting. Water is uh also an interesting solvent but again we have to think carefully about the contamination of water and if we're able to decontaminate it effectively supercritical CO2 is an interesting uh solvent. So essentially condensing down CO2 so that it becomes a liquid. we can do reactions in that liquid and then essentially you can just release the gas, recapture the CO2 and then do another reaction of CO2. So that's a very interesting way in which we can use CO2, capture it, use it as a solvent and then recycle it to continue using it as a solvent. The nice thing about that is it's great for purification because as long as you're not capturing any other gases that are co-eluding with CO2, you can easily recapture and reuse it. Um, these are design options and so these are not automatic answers, but there's some things to think about uh in terms of changing uh more problematic solvents like dchlorommethane to things that are going to um uh uh be safer. And again this is um you know if you have to use a solvent in any uh chemical process usually and again you should do this calculation one time when you're doing a chemical reaction is calculate because we often times we just calculate the moles of A plus the moles of B and then we put it in you know 1 milll of solvent. We don't actually calculate the moles of the solvent that we use because it's not part of the chemical equation reaction that we're doing. But if you calculate the moles of the solvent, you'll see how astonishingly huge that number is compared to the moles of the reagents that you're using.
And that's just giving you sort of an indirect way of thinking about solvent being the huge problem in any process, right? Because you're just using so much of it. And if you calculate the solvent that you use for extractions, for purifications, it's really problematic. And so if we can solve that problem, make more safer solvents or remove solvents completely, we're going to have a huge impact on uh chemical processes.
Co coffee decaffeination. So, I know this region uh of Brazil is a high coffee producer, but uh sometimes you want to go to sleep and so having too much caffeine too late in the day, I don't know about you, but it affects me.
It does not affect my wife, but some people like decaffeinated coffee and so to decaffeinate um organic solvents have been used for the extraction of caffeine, right? And that can be very problematic for a number of reasons. It has uh a detrimental effect on um the processing.
Uh you also have to make sure that you get low enough concentration of solvent at the end so that you can use it in commercial um uh uh applications. And so that's where something like supercritical CO2 has been used to be an effective way to remove um caffeine from coffee.
Uh so this is um uh there's been since this time a number of different uh guides but MGEN has one guide which is essentially and so again it's not important to uh know exactly what these uh numbers are but it's just to say that um different solvent systems can be evaluated based on their toxicity and uh they are they can also be essentially co- solvents. So essentially here what they're showing is heptanes mixed with you know ethylacetate plus ethanol ethylacetate isopropanol mtb which is an etherbased solvent can be mixed in these ratios of these other solvents and then dcm can be mixed with different ratios of methanol and they're evaluating them all based on their toxicity. So, these are just nice charts to give you an idea of what is considered a more safe solvent system and what's considered a more toxic solvent system. And these are widely available. If you Google them, you can find a whole bunch of different charts like this. And I think it's a knowing that these exist can really have an impact on your research because you can then say to yourself, okay, this solvent that I'm using, is it considered safe or not? on an industrial scale. If it's not, then should I be replacing it? And then what these charts do very well is that they actually provide solvent alternatives that have similar properties to the solvent that you want to be replaced, right? The problem is is that the alternatives are not always perfect, right? And there's always a trial and error, but at least you have a starting point to say if I want to replace, you know, a 3% mixture of methanol and MTPBE, what are the common ways that industry does that? And I think this is one of the great things that industry is starting to do is share these best practices so that we understand them better. And again, there's no perfect solution to this, right? So oftent times in these tables it will be a little bit more nuanced than what's shown here. So it'll be um more like green, yellow and red. And so the red is the ones to avoid. The green is ideal but then they still have the yellow ones which is saying that you know there is some there might be some um applications where the yellow ones are actually useful. Um but uh knowing for example DMF dimethyl formide is on the red list and that's one of the re solvents that we use all the time in my lab. You know it makes my group think about you know can we replace that and so we are consistently trying new solvents. You know unfortunately for a lot of our reactions we have not successfully replaced it. Right? So that's that's an ongoing sort of question in my group, but it's at least we have that always in the back of our mind is that we want to try to get away from DMF because we know that it's a problematic solvent that won't be used industrially.
[snorts] Um I I touched on this before um in terms of uh industrial processes. So heating, cooling, separations, and pumping often de dominate energy use.
And so this is just giving you an energy intens intensification. So reaction temperature contrast, it's just highlighting essentially that things that are uh at low temperatures, so going below 0 degrees C, these have high energy costs industrially. And so these are the processes that they tend to avoid. Heating is uh process has a high process intensification as well but not as much as cryogenic. But if you look here biocatalytic processes so using enzymes to do reactions well enzymes by definition are most effective at body temperature which is around 37° C right so that's a very easy temperature and oftent times the enzymes that are designed industrially can be used even at room temperature right so they might be more effective at 37 but at room temperature so biocatalytic processes in terms of the energy that has to be put in is very low compared to doing something at minus 60° C or at plus 100° C.
Uh use of renewable uh feed stocks. I I think this is an under um explored area that um we are certainly interested in.
Uh I think carbo it's partially underexplored. Carbohydrates I think has been explored much more than any other area because it's um there's relatively mature chemistry in showing how um um biomass from carbohydrates can be um uh used industrially. I think that the areas that are quite underexplored is using lignon. So lignon is a very difficult molecule to work with because it's highly polymeric and highly um uh nonuniform in structure. So being able to use that as a starting material towards benzene derived products I think is going to be uh it's an open question on how that can be done. But if it's solved, I think it can really dramatically push benzene chemistry away from petroleum towards a a more renewable and sustainable future. Uh, and [snorts] fats, proteins, and tarpen are also underststudied. I think the the amount of these that gets produced is um so little that it'll be hard to make an economic case at this point, but I think it's still something that we need to to to be uh studying to for when the the time comes where that's going to be more valuable. And the way to think about this is that the same like to think about E factor and petrole and the petroleum industry. So remember that chart where I showed the E factor was nearly zero for the petroleum industry and it was higher for the fine chemicals and and um um bulk chemicals. Well, this is essentially what what is going to happen what is going to happen have to happen in biomass because essentially in the petroleum industry everything was optimized. In biomass nothing's optimized, right? And so that's why the E factor is huge in bulk chemicals versus in the um uh petroleum industry.
And so essentially that's what we're doing here is we're create we're we're figuring out how to optimize using these things. And the more we are able to do that, the more biomass e the E factor in biomass is going to become closer and closer to petroleum to the point where that's where it's going to essentially replace petroleum and let us move on to the next stage of um um valorization of uh chem u biomass based feed stocks.
Um so uh uh case studies renewable and recoverable materials. I think more and more um essentially uh different products are being designed so that they can be reused either in the same um uh target um uh in the same final product or being used in Here's that require energy system.
So that is the transition state energy for process and with energy transition to And in terms of in terms of green chemistry, the other important thing about cat catalysis is that the catalysts can be reused, right? and they're only used in small amounts, right? That's the definition of a catalyst. So the catalyst can be used as little as you know 0.00001 mole% sometimes, right? And that means that the amount of material catalysts that you are required for any process is lowering the energy with very minimal amount of material that's required. If it's a heterogeneous catalyst, so it's a solid catalyst, usually those are very easy to recover. If it's a homogeneous catalysis, something that dissolves in your solvent system, becomes a little bit more challenging to recover, but it can still be done. Or maybe the cost is low enough that you don't need to recover it because you're using so little of the material. And industrially what's interesting is that there's some catalytic processes that are done industrially on huge reactors but those reactors for example if they do palladium catalysis they actually don't even put any any palladium into that reactor. They only did it for the very first time and then the palladium impregnates into the metal cavities and what they do is they just use that reactor reactor for palladium reactions and then they don't actually have to add in any palladium because the palladium that's there is always in the metal and it just catalyzes the reaction. The problem is that then you have the use of a resource which is one reactor for only one type of reaction. Right? So you can't use that for many different types of reactions because maybe the other reactions will leech out the platium from the metal source. But in terms of uh a greenness, that's a very effective way to do things.
[clears throat] >> [snorts] >> Um so catalysis uh on um uh on an industrial scale so this is uh uh HPPO which is a peroxide uh uh and it's got lower waste water and energy demand. Uh this uh engineered enzyme improved selectivity in the process. So for this synthesis and oxidation catalysts, the oxidation catalyst that was used was a bioinspired one. So it's something from um um [snorts] um an enzyme and that enzyme was an oxidation enzyme. And so therefore that enzyme uh essentially was um the inspiration for the oxidation process to produce some of these uh materials particularly HPPPO which avoided the use of hydrogen peroxide which is a toxic uh byproduct uh design for degradation. So um uh this applies a lot to cleaning products. So a lot of cleaning products uh became very persistent. And so you know um 30 years ago you could see that in waste waters there was a lot of uh uh foam that was in the um um where waste waters were expelled into for example ri rivers and essentially that these uh were caused by uh different types of sulfonated detergents. And what the companies uh um uh have done is that they've changed the detergents such that they still are sulated but they are degraded uh through the system much faster. So you don't see this foaming anymore. So it's designed degradation of the soap. So the soap works at the uh in the time frame that's required to clean the clothes, but then afterwards it's designed for degradation. And so you can see that you know um uh uh this is a hugely important um factor because if we don't design for degradation you know uh when we stop uh um something which persists in the environment in 1972 you can see the concentration of that material still in 2025 is still quite significant because of that persistence. So without designed degradation of the materials uh you get bioaccumulation that can have long-term health effects.
[snorts] Uh plasticizers and plastics. And so this is uh another example where um when we make any material uh there's often times you know the principal material which is the in this case the polymer and then there's things that you add to that polymer material because you want to change the strength or the flexibility of that particular polymer.
And so you could either design out a whole new polymer or you can just start to modify that polymer by adding additives that will change the function of that final polymer. And those additives are essentially what they call plasticizers.
And so those plasticizers in terms of design are hugely valuable. But the problem is is that they can be leeched out of the material. And so the leeching of that material can uh cause uh unintended consequences. And so uh industrially what they've done is try to put in more plasticizers that are more non-toxic. So for example using um uh like either derived um having the polymer itself be non-toxic. So something like lactic acid. So polyactic acid is something which can be easily degraded or using different types of um u plasticizers that reduce phalate related concerns. So removing things like BPA and changing those molecules into something which is less toxic but still has the same function on the polymer material.
uh real- time analysis. So this, you know, I'm an organic chemist, so I tend to focus the green chemistry course mostly on organic chemistry. But again, I think that the real time analysis uh is so important because that can prevent the um uh pollution. It can prevent overuse of energy. If you're not analyzing things in real time and you're only doing it much later than when a reaction is ending or a process is ending, then you are wasting lots of energy, lots of materials, lots of solvents. And so that's why analytical chemistry is really um uh critical to as a part of the um the process for improving green uh um uh green chemistry.
>> [gasps] >> uh process. So here's an example of uh uh a process analytical chemistry which enables control. So here's essentially a reaction uh that is adding on this uh tputal group onto this ethine molecule.
And essentially what they found was that rather than doing this with a liquid acid catalyst. So here like if you think about this being done in an organic solvent with H+ being the ad catalyst by real time monitoring they were able to identify that they could have solid acid alkalation and so this by GC moni monitoring monitored the selectivity of this reaction and then this is in conjunction with continuous flow chemistry. Essentially continuous flow chemistry is that you're doing a reaction under a flow. And so essentially what you can do is flow your reagents on top of that solid acid catalyst. And so your reagent is not touching the catalyst for any longer than is necessary to do the reaction. So when you do things in solution under acid catalysis, your reagent after it reacts is still in contact with the acid. If you do it in flow, you essentially flow your starting material over the acid catalyst. It reacts and then it flows out. And so it doesn't touch the acid catalyst for any longer than is required. And so by doing real-time analysis and flowchemistry, they were able to significantly improve this system uh uh to make this uh product that's shown uh inherently safer chemicals. Uh so just a few examples of this is that um uh substituting volatile liquids with solids or low vapor pressure materials is really important. Avoiding large inventories. So we talked about some of the disasters that we talked about in the beginning of last lecture. So these methyloscyanate bats that were unnecessary using continuous flow which I just said uh helps reduce hazardous waste. uh simplifying processes uh so fewer things can fail. So that's removing reducing the number of steps in any process. Um uh PHA so these are the essentially some of the polymer materials on airplanes. And so what's interesting about these is that the synthesis is a relatively uh straightforward synthesis, but it's uh the fact that that polymer material when it's heated becomes fireresistant. So that's pretty neat in terms of the function of the material, which means that if Okay. So just question Let me ask a question. Do you normally have the time slots for lectures? This is normally at 2 o'clock or it can be any time.
She's trying to protect the can help to improve to avoid stuff and not just prior Yeah.
>> Yeah. I mean, are you a computational chemist?
>> Yeah. So like I it's a whenever I I you know we have lots of computational chemists in our department um as well and when I see their work like I always think that the challenge is is exactly what you're saying is that um how can you do computational chemistry without experimental evidence?
You know what I'm saying? So I always am pushing the computational chemist to say you need to benchmark what you're doing against experiments because otherwise I don't know what you're calculating.
You know what I'm saying? Like because it's like it's it's they look nice and they create beautiful pictures but I'm like but I need to have evidence that what you're calculating translates to a real life experiment. And so I I think to answer your question, there's always going to be to me the trial and error of computational because [clears throat] I don't think you can answer a question without the experimental. But once you have that, then I think you accelerate things tremendously, right? Because once you've benchmarked it, then I'm like, okay, now when you calculate something, then to me then it's a it's a um a huge d-risking Right? Because I'm you're saying you're saying, "Okay, here's this." So, for example, let's say if you take a process that's a five-step process and you can calculate a way to make it two steps and there's you've benchmarked it and now I have a different process and you calculate and you say I think I can take your five step to two steps then I'm like it's worth doing. You know what I'm saying?
So you that's why I feel computational is huge impact. So because it's like if it can remove the number of experiments that needs to be done >> what kind of impact that's a huge impact right because if you remove if you if I have to do a hundred experiments to figure out the solution and you can make me do it in 10 right I only have to do 10 experiments the amount of solvent the amount of waste the amount of risk the amount you know so it's like that's that's incredible amount if you if you can benchmark it right and that's I the key but I do think that there's like like I said before is like um structure toxicity I think is something which is very difficult and nobody wants to do it because structure activity can make me make a billion dollar drug and pharmaceutical companies involve invest huge amounts into that but structure toxicity is kind of like you know the the the the thing nobody wants to do because it's it's it's decreasing the cost. It's not in introducing a new drug into the market. And I think that computational to me could have a huge impact in that area because that area is like something which people um would be more willing to sort of experiment with um non benchmarked studies because if you can at least point me in the direction of alternatives I think that it would be a huge impact. So I don't know if that answers your question but [laughter] >> can I say that is a green to one to improve.
Yeah. I mean, so how how much energy is used when you do computational studies, right? So it's like it's one of those things where I know what you're saying and I I agree with what you're saying, but I'm just saying that there's not a zero cost. You know what I'm saying? So it's like a little bit like and again you I get called out on this all the time with my experiments because with my science because I'm like it's not green, right?
because I use some terrible solvents. I have to do things at 150 degrees. So, you know, so it it's just I think that the way to think about it is that you exactly you're thinking is that the computational is a it is if you can reduce the number of experiments it's it's pushing things in the right direction, but it everything comes with a cost. So that's why I'm just like I don't like to ever say like you know this is green and this is not right.
It's like there's nothing that's perfect. I think that we just need to become complete. We just push things in the good direction and if we're always thinking about it, we can continue to improve and that's all we can really hope for ultimately.
I say because one of the ouratives for our our some of our work and research are just the idea that professional food we can use less solvents less process and better.
>> Yeah. Yeah. And that like and again I there there's just make sure that I to be clear is I I don't want to um prevent you from saying that. You know what I'm saying? Because it's like there's two different things going on. One is we're just philosophically talking about green chemistry and I want everyone to come away from this to say that good and bad is too simple. But then what you're talking about is trying to get a grant or to publish a paper. And to do that, you sell your science in the most positive light. You know what I'm saying? And it's like you can't be so transparent that you if you're so honest, then it becomes the reviewers say it's not so interesting, right? So then you it's not that you hide, but you only highlight the the positives. And I I think that you're absolutely right.
chemistry is like you know theoretically if you can calculate everything if you if your computation was so good that you could predict like you know everything 100% and I only had to go to lab and do one experiment I mean of course like that's the ideal world right like for sure that that would be much greener than what we do right now which is just you know this this trial and error experimentally Yeah. I mean, you know, AI is like, you know, one of those things which is it's underestimated what what we're doing globally in terms of the energy consumption. And I use AI all the time, right? But it's one of those things where you you should think about should I be using AI when I could probably Google it and the amount of energy that would be used from a Google search is going to be a fraction of what the AI searches.
Tough tough questions, right?
>> Water costs. Exactly. These are these are the what like I said economists call negative externalities, right? is society is paying for my AI search, right? And it's not being paid for by me who's doing the search. And it's like we need to think about those things. It's like the people who are doing the searching, if I had to pay $100 because that's the true cost to society. Every time I do an AI search, I would think twice about doing the the search, right?
Yeah, >> in a green really [clears throat] good reward or not and Yeah, I mean that's a that's a really good question and it's a tough one, right? Because if you you know you you you're doing a graduate studies and you want to succeed and so are you going to essentially um limit your options to these green chemical principles to succeed. I mean I think that the answer is yes right we have to start doing that. So it's not it's not that you are you know you can't see it as limiting your options. It's just that you're making better design choices based on these principles and the success I think is likely to be the same but different. I think you just have a little bit the challenge becomes that the history that we know that is non green chemistry quote unquote is just we have a larger amount of knowledge about that the green chemistry knowledge that we have is is a little bit more limited but I think it's limited in terms of our um the history of us thinking about it but I think it's unlimited in terms of its potential So I think in that way you have a lot more ability to discover something which is not known right whereas if you continue to do things which are you know quote unquote non green then you're likely to find something which has already known because there's been so much research done in that with that mentality right so I understand the hesitation to want to do it but I do think that there's more opportunities ultimately and ultimately it's like more positive.
>> Yeah. But but like you know and again just because of my history uh in terms of my research program I think that that's exactly my problem right now because we designed chemistry without thinking about green chemistry and then we're now stuck because we you know it's like you know research is like the branches of a tree right there's so many different ways that paths that we can go down uh But then what we can do is that if we've gone down a path not that far, we can go back up and go down another branch. But sometimes when you've gone down so far down a branch, you're like, you don't want to go all the way back up to the top of that tree to go down another branch. And I think that that's the thing with my chemistry is that we designed it so efficiently for using DMF as a solvent. Now we're trying to get rid of DMF and we're so deep here that we can't get out of it. And that's why we're so stuck with DMF. Whereas if we would have from the beginning said we're not using DMF, I think we would have went down another tree and we would have succeeded, right? But it's just like because going down the other tree is like it's not as simple as just removing DMF. It's a because we have like we have a palladium catalyst, we have a liant, we have an additive and those things have all been optimized for DMF and so now we're just trying to pull out DMF and put in something else but all the other things need DMF, right? So we have to redo everything and it's just like that becomes much more challenging not yeah I mean more challenging but it's more time inensive and now my group just like it's just human nature we don't want to do that because we know this works right so it's like to get anyone to go all the way over that hump to get to the same thing that we're doing here you know what I'm saying like that's the problem right it's like you go all the way over here to get an 80% yield of the same reaction that we're doing over here. So then it's just like, well, let's just keep using DMF, right? Who cares? Well, society cares.
possibility to get a product but you have two possibilities of reactants toxic but it's 100% and one that is more it's not toxic small percentage.
So react is very clean or not.
>> Yeah. I mean it complicated, right? It's like is it green? It's like so you're you're you're changing the risk profile, right? So the risk for that example you're putting on to maybe let's say the employees who are producing the material, right? Because they're the only ones that are going to be exposed to the toxic material. So you know then it's like are is that a risk that you're willing to take? But because the final product to the consumer is has zero toxicity and the cost to society is is better because you're going your atom economy is perfect because all of that toxic material gets converted. So you know that's where that's like sort of an example of like nothing's perfect, right? So maybe that would be acceptable.
Maybe the risk to your to those people is it's unacceptable and then the cost has to go to society which is to the less efficient route but the safer for those people.
complicated questions.
and brought us.
I would like to know right now and it is how they >> Yeah. So it certainly is done industrially by pharmaceutical industry even other chemical industries and yeah it's like it's uh there's processes to to make these proteins or whatever enzymes that they're using on industrial scale. So I I'm certainly not an expert on it but it's like it is done industrially. Yeah.
Yeah.
>> And it's becoming increasingly more it's it's being done even more and more as time goes on. Companies are finding it quite useful for specific transformations.
>> Yeah. So there's like there's an office in Brazil and there's an office in Canada. The office in Brazil is just sales and the research office is in Canada.
Yeah.
>> So we make reference standards for the generic pharmaceutical industry. So um like we make so when a pharmaceut when a a generic company has to make the equivalent of a pharmaceutical that has previously been made by a big pharmaceutical company, they have to make sure that their formulation matches the formulation of the big pharma. And so they have, you know, in their synthesis route there's byproducts. And so they have to characterize those byproducts to make sure that they're low enough concentration that matches or exceeds the previous synthesis. So we provide them those byproducts and those byproducts then they use to test. So these are essentially analytical testing molecules but we make them through organic synthesis. And like I mean the biggest company that I know that we deal with is uh Brain Brain Pharma. I don't know if anyone knows that's a generic company a big apparently a big generic company in Brazil.
Okay, that's good. So, we'll see everyone tomorrow. Oh, I I was gonna uh uh send a um a little um PDF or something to circulate which you maybe if you're interested um I won't force anyone to do it but you can fill in like your research area uh your research topic and like it just has some questions in terms of green chemistry and if you want like you know to make a few slides on PowerPoint and you can present and you can we can sort of discuss your research area and how we think that we might be able to focus it towards uh a green chemistry based on the concepts. So like I said I'll share it with you and if you're interested we can do it tomorrow. If no one's interested that's no problem to I don't I don't want to make anyone feel uncomfortable but I think it would be an interesting exercise.
Okay, see you everyone tomorrow.
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