 that organometallic chemistry is extensively used in the industry in catalysis. However, one often wonders whether it has any implications for everyday life and today in this lecture we will consider some aspects which touch our day to day life. And there are three aspects that I want to talk about one of them is the environmental concerns of organometallic chemistry. And the second one is a biological aspects of organometallic chemistry and lastly medicinal aspects of organometallic chemistry. In this world today we often encounter the question is it safe is it environmentally safe to have these compounds in the laboratory and if they are released into the environment what would happen to them. And so it is important for us to look briefly at some concerns that we might have. First we will look at biological systems are organometallics involved in living systems. It was only recently that people realized that metals have an important role to play in living systems in cells and in biology. It is obvious that people are already aware of the fact that sodium, potassium and calcium are there in large quantities in many living systems. But as detection techniques improved it was obvious the transition metals are often essential for the living systems as well even though they are not found in large amounts. And that is because they are involved in catalytic functions they are not involved in structural roles in many cases they are involved in catalysis. And so it is important that they are there in the body and in the right amount. If you look at some of the elements that are needed apart from the elements the metals that are needed in large amounts you encounter mostly the 3D elements, vanadium, chromium, manganese and up to zinc and probably iron and zinc being there in the largest quantities. Surprisingly molybdenum which is there in the 4th row is also involved in living systems although to a lesser extent. So, these are transition metals are metals which are involved in living systems. But what about organometallics that was a question that we asked in the beginning of this projection. And the answer to this question is actually yes there are some organometallic systems that are found in biological systems. And surprisingly the element that is found which exhibits some organometallic chemistry is cobalt and that is cobalt with surprise note and not a cobalt 1 about 2.5 to 5 milligrams of cobalt is there in the body. And the normal person needs at least 10 micro grams of cobalt per day. It was only recently relatively recently that Dorothy Hodgkin solved the structure of cyanocobalamine. A picture of the protein along with this coenzyme in the cyano form is shown for you as a projection here. Let us take a closer look at it. Here is the structure of the cyanocobalamine the cofactor that is essential for some enzymes to function. And you will notice that cobalt which is pictured as a blue metal in the center of this core and ring is attached to a cyanogrup. Now the organometallic chemistry that involves cobalt and the cobalamine here is not necessarily that of the cyanogrup. But it has often other groups attached to the cobalt as well and we will look at this in a moment. The function of the coenzyme depends on the enzyme to which it is attached. So, it is surprisingly this coenzyme is found attached to different coenzymes different enzymes and their functions are also different. So, in spite of the fact that the structure of this coenzyme is identical in all these enzyme environment the enzyme forms different functions. And the cobalt has different groups attached to it according to the need of the enzyme. There are three major functions which I have listed for you here. One of them is the isomerizer and that is where it is attached to coenzyme. A it is attached to an enzyme which carries out isomerization where a group is transferred to one group attached to a carbon is transferred to an adjacent carbon. So, there is another system which we shall see shortly where it does a methylation function and there the cobalt has got a methyl group attached to it. And lastly it also has a deoxygenation function. It converts ribose to deoxyribose. As you can see this is an extremely important function because this is involved in the deoxyribosynthetics and you need RNA as much as you need DNA in the living system. So, the coenzyme B12 is an extremely important a coenzyme and cobalt is absolutely essential for the body although it is present in such small quantities. Now, here is a closer look the line diagram of the coenzyme and you can see that the current ring has essentially 4 nitrogens. One of them is from a saturated ring and so it is an anionic ligand which is coordinated with cobalt and the 4 nitrogens are in a square planar environment. Approximately square planar environment and cobalt itself is in the plus 3 oxidation state. On the lower half of the cobalt shown in dotted line the lower half is bonded to dimethylbenzimidazole and that leads to an approximate octahedral environment around the cobalt because on the top you have this R group which I shall mark for you right here. This R group which is the variant in various coenzyme in various forms of the cobalamine you find different R groups which are present in this enzyme. Rest of the groups that are present are the same and so the function of the cobalamine really depends on what is present in this apical site of the cobalt 3 plus ion. Sometimes you have a methyl group and so it forms this methylation function cyanocobalamine is often like a resting state for the enzyme you either have a hydroxy group or an adenosyl group sometimes at the cobalt. So, depending on the function that is required the cobalt changes the apical coordination at this octahedral cobalt 3 complex that you have here. Now, the current ring is quite planar and so you have for this cobalt 3 plus ion a nice octahedral framework. In this octahedral framework the R group which is attached in the apical position turns out to be a labile position not because it is a cobalt 3 complex system cobalt 3 plus systems are generally inert, but the R group especially if it is a cobalt carbon bond turns out to be relatively weak. The bond strength has been calculated to be approximately 120 kilo joules per mole and that works out to be about 40 or little less than 40 kilo calories per mole. For those of you are used to kilo calories this is the value that you have for this bond which I shall now color for you in red. So, that bond is readily broken and is responsible for the unique chemistry of the cobalt amine. So, what does it do? Here let us just illustrate it for the methionine synthetase where it transfers a methyl group. In the body there are several groups which are often transferred from one molecule to the other. The folate molecule has got a methyl group at the N 5 position. And this N 5 position the methyl group on the N 5 position is readily transferred to B 12 where it does not have the methyl group. Then it becomes the methyl cobalt amine which I am underlining. So, the B 12 without the methyl group is now methylated and it is ready to do this methylation function. And the folate itself is converted from the N 5 methyl folate to the bare folate without the demethylated form. Now, the homocysteine is converted by the cobalt amine, the methyl cobalt amine to the methionine. So, as this is again an essential function you can see the important role played by the cobalt. It is essential for transferring the methyl group from the folate to the homocysteine. And this cannot be done without the help of this particular enzyme. So, methionine synthetase utilizes the cobalt methyl bond which is fairly weak to transfer the methyl group to the SH group. So apart from cobalt amine there are other systems where augura metallic chemistry plays a role. And one of the important roles in biology is to trigger the ripening of fruits. Ethylene is often used, simple ethylene is used as a ripening agent. And it is being conjectured that the ethylene coordinates to a copper one site on in the fruit. And that is responsible for triggering the ripening. So, an ethylene copper one complex is responsible for this important function in biology, so in the fruits. So, these are systems which we have considered where the augura metallic compounds are playing an important role. Now, we turn our attention to the environment. Metal alkyls especially in the context of mercury alkyls turns out to be very deadly poison, mercury methyl bond for example, is a deadly poison. And this is the reason why mercury itself is notorious. Although it is not so obvious because in the household environment we often use mercury. In the laboratory we use a thermometer and in the hospitals mercury manometers are common. Turns out that mercury performs a function because of its density its conductivity etcetera. A very important function that cannot be replaced by any other liquid common liquid. And so we have to use we have to use mercury and we then ask why is it a poison and how can we counter this situation. And now we turn to the fact that methyl ag plus which is a mercury 2 ion. So, mercury is present in ag 2 plus state. And when it is methylated methyl group is supposed to be an anionic ligand. So, ME ag plus is the easily formed organometallic group which turns out to be poisonous. The surprising thing is it is stable in water unlike many alkyl metal compounds. This methyl mercury plus is stable in water and it is very difficult to decompose this particular compound. And more importantly it exerts its poisoning effect by reacting with proteins which have got H H groups. Because mercury itself is thiophilic you can readily understand this reaction where the protein H H group is converted to S H G ME group. And now the protein with an H H is no longer available to form an SS bond. So, we have a difficulty here the protein which originally would have formed an SS bond. And it forms this SS bond forms very often as structural role is now not there in the protein. And as a result the confirmation that the protein and also be different. And so it turns out to be a bad system. So, mercury turns out to be a poison because it converts the protein from its active form to an inactive form. And it results in a detrimental effect. Now we can ask this question how is this mercury H G plus formed. So, what is the source of methyl the methyl group and how is it formed in the first place. Now many organisms as we just talked about the biological aspect of cobalamin. It is quite obvious for you where the methyl group would have come from. Because you have that N 5 methyl group on the folate. And that is readily transferred to the cobalamin. You have a ready source of a methyl group on the cobalt atom of cobalamin. And this methyl cobalamin reacts with mercury and generates methyl H G plus. And because the methyl group on the cobalt is extremely weak. And the methyl group on the mercury is extremely strong. You have a situation a reaction which goes only in one direction. And that is to form the H G M E compound which is extremely stable. And it is very difficult to destroy because of its aqueous stability. And it is extremely toxic to the protein system. So, this is the reason why one has to worry about mercury in the environment. Because once it is oxidized to H G 2 plus H G 2 plus in a biological medium is immediately converted into the methyl mercury plus cation. So, now let us look at the in vitro systems. It has been demonstrated that simple cyanocobaltate complex a methyl cyanocobaltate complex is capable of converting H G 2 plus to the M E H G plus system. So, this is not just a conjecture which you have. We have some in vitro evidence that it is possible to convert the methyl cobalt system in a 3 plus state. The methyl group is transferred to the mercury and it forms this very stable cation. So, given this information we now have to worry about how exactly is this mercury going to get into the biological system. Now, there are 3 or 4 major disasters that have happened in the world. And it is instructive to look at how these things happened and how we can watch out for these disasters. The first thing that I want to talk about is the disaster that happened in Minamata Bay. This is a bay in Japan where there was an industry which was releasing mercury through its industrial waste. The amount of mercury that was released into the sea was fairly small amount. A small amount of mercury was released into Minamata Bay. But this was the first incident and probably more mercury was released and what would be allowed in today's scenario. This H G 2 plus got rapidly converted by organisms in the sea to M E H G plus. And the phenomenon of bio concentration was responsible for converting the small amounts of methyl H G plus that were that was available in the sea water to a very large concentration in the larger fish. The bio concentration is merely because the small fish tend to ingest this methyl mercury plus. And because the bigger fish are eating the smaller fish slowly the concentration of M E H G plus present in the bigger fish keep increasing. In fact it has been demonstrated that small fish might have as little as 84 P P B parts per billion of the M E H G plus. Whereas the large fish have as much as 250 parts per billion of mercury. So what happens is the fact that people are eating the large fish and because they are eating the large fish you tend to ingest lot more mercury than what you would have if you are eating small fish. So this phenomenon of bio concentration turns out to be a very important principle and it has played a major role in mercury poisoning. Large number of people died in Minamata Bay. But surprisingly in 1970 10 years after this tragedy which happened in Minamata Bay there was another tragedy which was nothing to do with release of toxic waste from chemicals in a factory. This compound which is a ethyl mercury compound is used as a disinfectant turns out to be an extremely good disinfectant. And because this disinfectant can be used for protecting seeds that are stored it was normally kept in warehouses where the seeds that are preserved for the next years showing is protected from other insects and so on by using or bacteria and so on using this disinfectant. And in general nobody eats the seed wheat. So this is specifically referred to as seed wheat. The seed wheat is marked as being disinfected with this particular mercury compound and the warning sign was in fact written in red. It is very unfortunate that the warning was actually in English and not in Arabic the local language that was used in Iraq. As a result people in Iraq who had by some wrong means got hold of the seed wheat they should not have obtained the seed wheat. But they obtained the seed wheat and consumed it probably due to a situation where there was a drought and there was a hardship for wheat and so the seed wheat was taken and consumed. Now this resulted in a major disaster many people were affected by mercury because of this particular incident. So here again you can see that one has to be extremely careful while using mercury and although it plays a very important role it can be a disaster situation due to some wrong information or other. Now it turns out that that was in 1970 in 1975 5 years after this disaster in Iraq incident happened which was again reminiscent of what happened in Japan here in Japan it was released into the sea mercury was released into the sea here a factory was releasing mercury into a river and that river was by Indian settlement. These are West Indian settlements or Red Indian settlement and the people were feeding the cats caught in this vabagon river to the and it turned out that because of this bioconcentration the fishes were having a high concentration of mercury. And so the cats were affected and one realized that they had the typical mercury systems where they lost stability they had some nervous disorders and people realized that there must have been some mercury leakage. And after some investigation it was found out that this factory which was responsible for the release of mercury was in fact in by the side of the river where the river was being contaminated by the sediments that were there which would take nearly 100 years to dissipate. So, this is a river that has been permanently literally permanently contaminated because of this efflux from this factory which was probably a small amount and it was not affecting the native Indians who are also consuming this river water. But because of this fish bioconcentration the cats were affected and fortunately some warning sign has been raised and it is unlikely to cause further damage but it would take a long time for the place to be cleared of mercury. Now, that was in in the year that was in 1975 and those are the three major disasters that I wanted to say and now I wanted to just give you this information that has happened fairly recently and it is a warning sign for those who are working in the laboratories. Here in in a laboratory in the US in Boston as a scientist Karen Wetterhand was in the professor who is working in this Ivy League school and unusual for a professor she was working in the laboratory and she was actually making a measurement making an NMR measurement and dimethylmercury is a standard for organ and mercury compounds. Once again she was well aware of the dangers of dimethylmercury she was using gloves but there was a small pinhole in the glove and although she was using it in the hood she was extremely careful about handling it. On August 14th 1996 a small amount a extremely small amount of this liquid fell on her bare hands through the pinhole that was there in the gloves. She quickly removed the gloves but about 15 seconds of exposure of this methylmercury compound on her hands was enough for the mercury to cross from the skin into the blood and it was sufficient to cross the blood brain barrier. So, this is the incident which clearly told that dimethylmercury is also an extremely poisonous compound and it quickly forms a methyl mercury cysteine complex the same complex which would be found by the SH groups in proteins and it results in widespread poisoning. Pretty soon she lost coordination there was slurring of speech and within a space of 6 to 8 months she encountered severe debilitating effects because of that mercury poisoning. In fact on June 8th when her mercury levels were monitored it was found that she had 4 milligrams per liter of blood and that means more than 15 milligrams about 6 liters a maximum of 6 liters of blood is present in the body and so it must have been more than 15 milligrams. Although it was estimated that the drop that went into her hand would have been anywhere between 15 to 75 milligrams it was found that 4 milligrams per liter of blood was found in of 4 milligrams of mercury was found in her blood. But she died quite right after that she passed away quickly after 1997 and I think it was in August that she passed away. So, that was a very sad incident where chemist who knew the difficulties of handling mercury compounds succumbed to an accident. Closer home in September 2010 there was this article in front line which mentioned that in Kodaikanal a place in South India the ground has been poisoned with mercury which has come out from a factory which was using mercury for making thermometers. So, this is reminiscent of the Wabagon river incident because what is going to happen is we do not know how long it would take for the mercury that has fallen into the ground to dissipate and reach some rivulate. So, it because Kodaikanal is in a hill station this is a matter of concern. The company itself was closed down and in fact it was noticed that some local people who were workers in the factory had severe medical and health problems. But a cursory examination suggested that this was not due to mercury, but hopefully this methyl mercury contamination will not affect us in the future. But it has to be worried about because of what I just mentioned that it takes a very long time for this methyl mercury bond to be broken. And as a result in it is possible that it can have a serious consequence later on. Once it gets into the ecosystem especially the soil and water it can rapidly affect people and living systems. So, it is important for us to look at organo mercury compounds and see how one can disinfect or how one can remove the ill effects of this methyl mercury bond. This is still an unsolved problem, but it both serves as a warning and as a challenge to the organometallic chemist. The stories that have come on the basis of methyl mercury methyl mercury have not stopped yet. This year in January 3rd 2013 there was another incident in Tennessee USA where it was found that there is a mercury poisoning. So, let me end this rather disastrous set of incidents which shows that methyl mercury and organometallic methyl mercury compound is extremely toxic and is a cause for concern. It has been established that it is the organometallics is essential to life especially when it comes to the cobalt methyl bond. And the very same methyl cobalt bond is responsible for converting mercury which is not toxic otherwise to a lethal methyl mercury plus compound. So, is organometallics all bad? I have given you two incidents, one two situations, one where it is essential for life and another incidents where it is quite a disastrous situation. Now, I want to end this discussion with something good and that deals with medicinal organometallic chemistry. Organometallic compounds as we have seen in the introduction provide us with a unique opportunity of combining the good effects of organic chemistry and the good effects of transition metals and main group metals. And not only do they combine the good effects, they give us new properties as a result of combining these two unique elements together. So, these have been utilized very effectively for making therapeutics. Advanced medicines from organometallics have been made and they have been able to tackle diseases as other organic compounds have not been able to. Secondly, they have also been used for diagnostics. Imaging systems are important in today's world where it is now possible to figure out what is going on inside the body without cutting open the body. And so, it is possible to use 99 m technetium. 99 m is a metastable isotope of technetium, the man made metal and 99 m technetium when combined with an organic ligand turns out to be an extremely useful system for imaging the heart. It is called the compound is called cardiolite and we will come to its function. It has also been organometallic compounds have also been used in combination with metal carbonyls for a variety of functions including people are exploring the use of using a strong CO stretch for diagnostics. Lastly, by combining therapy and diagnosis, it is possible to generate compounds which can be used for theranostics. This is the term which just says that both for therapy and for diagnostics you use the same compound. The advantages that one would be able to one can figure out where the compound is present in the body and treat it and follow the treatment as the disease progresses and as the curing progresses. This is an extremely important and valuable tool and this has been possible with some organometallic compounds. Medicinal organometallic chemistry actually has a long history. In 1760, a French military pharmacist they were called pharmacists, but they were actually chemists. This was a chemist who was trying to make not medical compounds, but he was working in a pharmacist pharmacy and he was trying to make a cobalt based invisible ink. Many of you would be familiar with the invisible ink that you can make with cobalt and he was looking for a way to make invisible ink with a cobalt containing mineral. This was for military purposes, but during the course of this he made probably the first main group organometallic compound which was a methyl arsenic compound. That was nearly not necessarily for medical purposes. It was in 1908 that Paul Erlich developed the first real arsenic compound which was called Salverson. Salverson was used for treating syphilis and he quickly got the Nobel prize for this fantastic discovery. What is more amazing is that in 1908 he made the compound and practically within a year, within a year he was able to use it on human subjects. This is now an impossibility because of the controls that we have on using chemicals on human subjects. In those days it was possible to quickly test it. One scientist for example used it on his own daughter because there was no other medicine available. It was possible in those days to speed up this process of bench to bed, bench to clinic so to speak, of converting the medicine that is discovered in the lab to the clinical trials. Interestingly Salverson was reinvestigated recently. The original structure or the structure that was assumed for Salverson was this arsenic dimer where there was an arsenic double bond. This double bond was proposed on the basis of the molecular and the chemical analysis elemental formula that was written to satisfy the trivalent nature of arsenic. But recently there was a reinvestigation of the compounds that were present in Salverson. It turns out to be not a single compound, but a mixture of compounds, polynuclear systems. The simplest of them is a trimeric structure. There is no mistake in the nature of the compound that is there is been nature of the compound or the structure that has been assigned to Salverson. It is just that double bonded arsenic compound would be less stable and it is natural that the dimer converts itself to the trimeric structure that I have shown for you here which would have only signal bonds. This is a common occurrence in many main group chemistry. The cyclic form is a stable form and what is present in Salverson is the cyclic form that I have shown for you. That was discovered only as recently as 2005. From Salverson, when cisplatin was discovered, cisplatin is the dichlorodiamin group attached to platinum 2 plus. This compound excited an extraordinary interest in the inorganic chemist because it was now possible to treat cancer in a way that was not possible earlier. So, 1970 COP and COP mayor, two people decided to investigate CP2-TICL2, a compound which we have encountered earlier for cancer therapy. They found that this was an extremely good anti-cancer agent. In fact, it was so good that it entered phase 2 trials. Unfortunately, the drug had to be abandoned because of the fact that it was not better than the known drugs. This was partly because the way in which it was eliminated and partly because of the way in which the biological systems made or transformed CP2-TICL2 molecules that lost the CP group and became oligomers. These oligomers were in fact nephrotoxic. In other words, they could not be excreted through the kidney. So, there was toxicity to the kidney and they had to abandon the use of this drug. Also, it was shown that although the drug original idea was to use the TICL2 bonds, just like one would use the platinum CLCl bonds. The similarity between cis-platin which had this group and the CP2-TICL2 which has this group was thought of as the reason for its activity. It was thought that they would bind DNA and make DNA inactive, but that did not turn out to be true because of its decomposition in the body. It was shown that it was actually transported through transferent. Now, it turned to Tomoxifen. Tomoxifen is a targeted therapy for breast cancer cells. Breast cancer cells require estrogen. Estrogen binding compound was shown to be a good way to target breast cancer. So, Tomoxifen is like a key broken in the lock preventing the growth of cancer cells. So, interestingly, it does not bind to ER alpha, the estrogen receptor, but the metabolites of Tomoxifen, which is the molecule shown here, are the ones which bind ER alpha. Gerard Joan defined the term bio organometallic chemistry and he was the one who made this ferrocifen, which is an analog of Tomoxifen, which has got a phenyl group in this position. Instead of a phenyl group, we now have a ferrocinyl unit. Interestingly, this particular molecule is successful not only because of the binding to the estrogen receptor, but it is also because it is converted to the oxidized form, which is a quinone methide. The quinone methide structure is well known for its anti-cancer activity and it is because of this transformation, which is possible only with the ion analog. If you replace ferrocifen with the corresponding analog of ruthenium, the molecule loses its activity and it was shown that not only is it active against estrogen receptive cells, but it can also work against other cells. Now, turns out that we can use these molecules organometallic molecules in a variety of ways. Cisplatin only targets DNA and it works against cancer by attaching itself to DNA and preventing the cell replication. Surprisingly, there is more to cancer than just cell replication. One of them is a disastrous fact that cells undergo metastasis. Metastasis is the process by which the cancer, which is present in one part of the body rapidly gets transported to another part. It has been shown that this ruthenium complex, which is shown here, it can stop metastasis. Several analogs of this molecule, including organometallic molecules have been shown to counter metastasis. Not only can one stop replication by binding to the DNA, DNA synthesis has been stopped by a large number of molecules, which have this general structure. These are pianostool structures and people have shown that by changing the AR group that is present here and the L group that is present on the ruthenium, it is possible to modify the activity of this general molecule, which is an excellent anti-cancer agent. Recently, it has been shown using labeled ruthenium, isotopically labeled ruthenium, which is a beta emitter that this framework is capable of rapidly moving from one part of the body to another. Another way to candle cancer is to use kinase inhibitors. Eric Megers is one person who has pioneered this particular methodology and he has also used this ruthenium half sandwich complexes. Here I have shown for you two different protein, two different kinases. One is a cyclin dependent kinase, which helps in the cell cycle, in progressing the cell cycle. Another is a protein kinase, which is responsible for protein synthesis. This protein kinase, which is present in large amounts in the cancer cells and starosporin, which is a molecule, which I will, the framework of which I will mark for you here is, has been used. This particular recognition element is present in starosporin and this has been used to make an organometallic molecule. Now, by hooking it on to the ruthenium CP ring, you have generated a new type of a complex and it is an effective kinase inhibitor. Here is another system, which is a pollen. Again a benzodiazepine moiety, which is this moiety, which is shown for you here. This benzodiazepine is extremely effective in inhibiting some cyclin dependent kinases and these have been this ruthenium complexes have also shown to be anti cancer active. Now, cancer is a problem not only because it spreads rapidly, it metastases. It is also a problem because it develops drug resistance. There are many drugs including cisplatin, which rapidly encounter drug resistance and there are two ways. One is to prevent the drug from getting into the cell. Another is to efflux the drug or push it out from the cell by some proteins. So, the prevention of the drug from going inside is done by glycoproteins and that is one of the major causes for the drug resistance. Benzodiazepine hooked on to the half sandwich system turns out to be an excellent way by which you can prevent that. Here is this glutathione S-transferase, which is responsible for deactivating many drugs. Now, this deactivation can be stopped by the use of ethakranic acid, which is the unit which is shown here. This ethakranic acid which will have a COOH group at this position has been linked on to this half sandwich complex and it has been a dual purpose drug. The ruthenium now functions as anti cancer agent and it is this ethakranic acid, which stops the glutathione S-transferase from bringing about drug resistance. One more example for the metal containing organometallics. Carbon monoxide is a signaling molecule in the body, although it is a poison and large amounts it is used for rapid healing of wounds, especially when there is a transplant wound. It is important to have small amounts of carbon monoxide in the vicinity to rapidly heal the wound and it has been shown that this glycinato ruthenium complex can be used for using it along with some other compounds to heal transplant wounds. This list does not end here. We have oronofin which can be used for arthritis. We can use ferrocene upended for malaria, ruthenium clusters for antiviral activity, silver organometallics for antimicrobials and so on. For a recent article which lists some of these molecules and describes this you can refer to this particular reference which I have listed for you here and tells you how wonderfully organometallics is changing the phase of therapy in the medicinal world. Organometallics is also used for diagnosis I told you about technetium. It is used for radio tracing using technetium 99. In this picture here patient who has an abnormal accumulation in the thyroid, infrared thyroid location can be identified very readily using this technetium compound which is an isocyanide complex of technetium 1. It is a complete organometallic compound that is used. Glucosensors for ferrocene have also been made. In this particular case ferrocene is merely an electron transfer agent. Ferrocene is an excellent molecule because it reversibly transfers an electron and a ferrocene, a glucosensor often utilizes the carotid which flows from the electrode to a system which is oxidizing the glucose using a glucose oxidase enzyme. So, the glucose oxidase and oxygen are present and the amount of glucose is measured very sensitive in a very sensitive fashion using a amperometric detector. And the person who has been spearheading this effort is Claremont and he is in fact suggested that one would be able to make an implantable version of this glucose sensor in the body. So, you can see that organometallic compounds are present ubiquitiously in natural systems although the ubiquitous cobalamin is the only major organometallic which is present in the body. It has a very important effect on the body and it is important for the living system but converts mercury into a very special problem by converting it into methylmercury plus. And lastly we have seen that there are abundant opportunities for making new drugs both for diagnosis and for therapy and almost all diseases could be benefited by making new organometallic compounds which will effectively treat the disease or detect the disease and to this end organometallics, organometallic chemists are pressing all their efforts.