 So, today's class is on inorganic chemistry in biology. What is inorganic chemistry? We have seen so far is the role of metal in different field. Let us say we have seen role of metal in periodic table of course, they are full of them and then we have seen extraction techniques there again we have metal. Subsequently, we have seen crystal field theory or the coordination chemistry chapter of course, metal was there. In the last class we were discussing magneto chemistry or you know that is that is the chapter right or whatever that name of the chapter was it is essentially magnetic chemistry or in a magnetism we are trying to discuss. Now, today we will try to see if there is any role of metal in biological system or in us. It is a vast topic it is literally impossible to do justice in one class. So, we will try to bring few topics trying to keep it as brief as possible and try to convince you that there is an essential role of metal in our body or biological system or in nature in general ok. That is that is the roughly going to be the topic. So, role of metal ions in biology ok. Now, I was I think discussing little bit that nearly 50 percent actually greater than 50 percent body weight is having metal is due to the metal of course, there must be some role. See in nature the most important thing to understand is nothing is done in nature without a cause. We may not understand right now or we may not discuss in the class or maybe it is not understood by scientist yet, but nothing absolutely nothing in our body is without a reason that is I think definitely a big take home message ok. Now, of course, metal complexes can act as drugs the drugs we take the drugs the doctors prescribe a lot of them are having metal. Some of them may not be life saving some of them it could be for flu for fever for you know indigestion this that some of them could be life saving such as cancer like at one stage of cancer there is a metal. Metal actually is saving human being from getting demolished or from getting you know dead or being killed in lot of cases. There are some examples see I am not expecting again this chapter I am not expecting each and every details of things you have to remember I do not think say so. I am saying that it is important to understand what is there in terms of medicine in terms of biology. So, there are for example, there are some drugs it is shown in here which is operating on our different parts of body for example, you know any anything you can pick up I think we will go for one of those let us say platin cisplatin you have heard of it is a platinum containing drug carboplatin these are specific drugs for some specific type of cancer. Of course, as you know cancer truly has no you know 100 percent cure medicine so far different medicines are effective for cancer for different type of cancer. So, cisplatin carboplatin happen to be two specific platinum containing drug which are effective for a particular type of cancer and it saves a lot of people. Of course, it has side effect lot of side effect, but nothing is more precious than life. So, you know when there is no alternative I think still better not every medicine has side effect I think I mean not every medicine has huge side effect almost every medicine has some side effect for sure, but some of them has more some of them have less, but essentially at the end we end up having the best possible one at this given time ok. This is what is cisplatin all about cisplatin is a simple platinum containing molecule. So, once again we are trying to keep this class as simple as possible so that we can correlate, but there are more complex thing which definitely you can understand just we do not have time to discuss that much it is a one class we will try to give you an overview. So, this is a cisplatin this is the transplatin why it is cis? You can see that two chloro are cis, two amino groups are or ammonia are cis. So, this is cisplatin trans means they are trans to each other. Now, transplatin is not effective as drug only cisplatin is that is mainly because the cisplatin this amino group let us say which is labile I think let us say this is the amino group or whatever there are there are these amino group which are labile. Labile means they can fall off ok they can fall off under a given condition let us say if you give a better ligand metal is nothing, but hold with the ligand. If you provide a better ligand that better ligand can displace the existing ligand it is like exchange right. So, what happens this cisplatin can exchange let us say two of it is ligand as is drawn in here let us say two of these ligands and it can coordinate with the better picture is not there it is this question is also there in the tutorial part we will come and show you a little better picture how it coordinates with the DNA ok. So, the major problem of the cancer prescence is you know you cannot prevent the growth of the cancerous cell cancer is nothing, but uncontrolled growth of your DGGS cell or DGGS cell right that is why we see that swelling right tumor you see it is growing there is no control if something like let us say any part is having cancer if it grows of course, almost everything will get affected inside our body right. So, since the growth cannot be controlled people are trying different way to stop the growth of the cancerous cell. One of the way to stop you know to stop the growth is to just cleave the DNA you have DNA all of you have studied even if you do not at this point may not understand 100 percent that is ok. So, the DNA is a base pair right it is a helical system. So, this drug particularly can go and intercalate or two of its ligand can be displaced by let us say two guanine you know guanine is there adenine is there. So, two base pair can displace let us say this ammonia definitely two of this ammonia can be displaced by those of those of the base pair of the DNA. Therefore, what happens is once you have such displacement you will not be of course, there are more involved strategy how it exactly prevents the moment such easy complex forms over there in DNA you will not be able to carry out carry out the cell growth it gives a message thereby you know your cell growth process you have heard of mitosis definitely that overall process stops. Thereby you are able to prevent the cell growth indirectly you are killing the cancer or you know cancerous cell. If you do not allow cancerous cell to grow it is that is it perhaps that is that you know one of the cure of the cancer right and then of course, you can do other treatment thereby of by once it binds actually then there is a mechanism called apoptosis by which it can kill the cell even those cancerous cell. So, what we have learned so far a simple compound such as cisplatin which is a platinum complex you can write down the crystal field splitting and everything ok. It is a 4 ligand over there on platinum 2 of the ligand can be displaced by the DNA base pair you have heard of adenine guanine guanine thymine cytosine uracil and so on. Let us say guanine 2 of the guanine from the nearby residue let us say it is a big thing right DNA means it is a big thing it is a long polymer type of thing it is a peptide right. From peptide backbone from that protein backbone you are taking 2 selective cord selective ligand those are ligand again right. If you look at guanine this is nothing, but a ligand for metal they can also undergo hydrogen bonding that is how they are giving the helical structure and so on ok, but once again they can be ligand ligand are nothing, but having a heteroatom what is heteroatom nitrogen oxygen sulfur it has lone pair usually or a negative charge and those negative charge is going to bind with the positively charged metal ion. There by if you give an opportunity for all those ligand present in our body some of them not definitely all of them some of them will bind with the metal and form metal complex ok. So, that is what is happening in cisplatin as I say the base pair or this backbone protein backbone can bind with the platinum center displacing 2 of the ammonia let us say and then we get a complex which will not allow the cancerous cell to grow if you let us say break the DNA base pair. So, that the region where the cisplatin binds from there on this DNA duplex will not exist DNA structure will not exist. So, the moment that collapses lot of things changes it triggers lot of thing. So, your mitosis or the cell division will not be progressing further. This is a simple way to explain of course, it is little more complex, but essentially that is how we see that it can be prevented ok. So, I think you got an idea how simple complex can be effective as drug as deadly as cancer which are even you know very late stage of cancer can be cured by this drug. Of course, this drug has lot of side effect, but still I think when the cisplatin was not there nearly 90 or 85 percent patient was dying for now after cisplatin. So, these are cisplatin and carboplatin carboplatin is specific specifically for prostate cancer ok. These these disease now can be cured up to 95 percent which is a lot 95 to 90 percent people who are dying before this medicine. Now, the people having this specific type of cancer where cisplatin is effective nearly 90 to 95 percent people are surviving. Of course, you know it comes with a side effect, but still people are using it and it is not that costly another thing is cost how costly it is right. Anyway let us move on, but then essentially what this example shows you that you have control on things cisplatin works transplatin does not work ok. Therefore, you would be able to understand where to design your drug or how to design your drug one component is which metal to choose ok. For example, let us say you take a drug with iron or copper iron center can get oxidized iron 2 plus 2 iron 3 plus and that is how we see the rust formation right. Copper you know copper 1 plus copper 2 plus these oxidation state occurs very quickly because that potential is achievable right. Therefore, these these are called redox active metal center because you can switch between not you know switch between these oxidized state reduced form and the oxidized form reduced form is what iron 2 plus is reduced form oxidized form is iron 3 plus copper 1 is reduced form copper 1 plus copper 2 plus is oxidized form. Now these are the things you may not be able to use as drug because let us say you use iron 2 plus iron 2 plus in air is also not stable you put it in body it may not be iron 2 plus it got oxidized to iron 3 plus. Let us say iron 3 plus is not drug anymore right. So, you have problem. So, you usually do not use some metal center which are having easily oxidizable or reducible center ok. Now these center such as iron copper they can be electron carrier because they can travel between the two oxidation state very easily lot of reactions are happening in our body where we need electron you have done the balancing of electron some equation A plus B goes to C plus D. You see that some electron is required somewhere oxygen plus 4 proton plus you know 4 electron going to water that electron where those electrons are coming from those are coming from some of these redox active site. These are nothing, but enzyme what is enzyme I mean it is let us loosely define enzyme. Enzyme is some center or some place in our body where a particular thing is going on. Let us say we are inhaling oxygen we will discuss today oxygen is going to bind with something that is the porphyrin center hemoglobin you have heard of right. That one we will be calling metalloenzyme because it has metal in it it is not necessary that every enzyme has to have metal in it, but those enzyme which are having metal we will be calling it metalloenzyme. Enzyme are nothing, but made of these peptides lot of those amino acid ok. So, we have heard of amino acid one amino acid can be put together with another amino acid those are called amide bonding right. So, small small amino acid put together I have slide I will discuss briefly put together will be a peptide backbone. Let us say we have how many 23 amino acids naturally occurring essential amino acid. Different sequence sequence of these you can put let us say you know different different type all these in different sequence let us say amino acid one amino acid two amino acid three then again one two and three these show a different sequence you can give amino acid will form peptide backbone. Those peptide backbone ok are the one can organize in different fashion alpha seat beta seat all those you may have heard of if not do not worry then thereby we will give you a big enzyme structure. So, essentially if you look at enzyme and cut it down into pieces what you get is amino acid different orientation of amino acid there could be hydrogen bonding among them there could be covalent bonding they can you know form the amide bond, but enzyme is nothing, but collection of amino acid in different sequence I will be coming ok all right. So, over here you have different way to control or design a drug you can control the metal center you can control the different ligand what type of ligand you want whether you want a high spin complex whether you want a low spin complex how the properties can differ even from high spin to low spin this conversion is crucial for our existence we will when we will discuss the oxygen binding with the porphyrin iron center hemoglobin ok. We will show how this high spin low spin change is essential for our surviving without that oxygen not even bind will not even bind ok. So, it all depends on coordination chemistry principles and the interaction of the compound with biomolecules or cells or tissue or organs ok sometime you know amino acids are there and in between some metals are there the role of metal could be different ok sometime what metal does is very simply metal can hold different protein backbone together how because metal can have ligand the way metal stage in our body is either if nothing is there water is there as a ligand if water can be displaced with those amino acid backbone amino acid has some ligand let us say histidine which is like a 5 membered ring with a nitrogen it. So, everywhere you will see if whatever is binding with the metal it has a heteroatom nitrogen oxygen sulfur this sort of thing are there either those lone pair or the negative charge is binding with the metal. So, as I said amino acid has these units where it can act as a ligand these are mono dented ligand it is not bidented ligand we have discussed bidented ligand right where you bind like a you know bind very tightly, but the mono dented ligand may not bind tight, but if they are in the right place where the metal is there metal binding site is there if there is a space for metal to sit down metal sits down there those amino acid backbone can hold metal tightly enough to do lot of chemistry ok. It can act as drug it can destroy a drug it can it can create a lot of things. So, that that is this is what essential. So, bioinorganic chemistry is nothing, but structural and functional activities of the different metal ions that is what we will try to discuss you just read I will essentially discuss these in the class ok. Now of course, every element in the periodic table is not readily available you have learned. So, therefore, what we see in our body is usually the one which is available in large quantity iron for example, it is available in decent quantity bulk element like carbon, hydrogen, nitrogen, oxygen, phosphorus, sulphur these are present in our body in large amount in any biological system like organic molecules are made of these carbon, hydrogen mostly and then nitrogen, oxygen, sulphur. So, those are bulk, but then there are trace elements although very little present, but still they are there in our body iron, zinc, copper and so on. Other different you know percentage of metal makes it makes the makes really our body overall I think every time I see that there is a question let us say given example of trace element this is one trace element which is essential for bio essential for biological activity. Let us say over here these are the one in the blue which are trace elements, but it is essential for biological activity this is kind of periodic table with the biological perspective. You do not have to remember all these one or two example if you remember I think that is good enough. Trace element means small amount present, but those are going to be very important for us anyway these are possibly essential forget it let us move on. Now, what is essential element I will not go through all these writing that is for you you can read I will explain this ok this chart this chart is very simple. See every metal is good may not be for our body for other purpose, but those metal which are good for our body is not good if you give a lot to our body. Let us say iron if you keep on taking iron tablet or calcium tablet like supplements you take even over the counter you can get without without prescription do you think it is going to be good for your body no. So, there is always this curve if you have a very less amount of some metal then your survival is questioned you may not survive ok. If of course, you may be dead if you do not have a certain percentage of metal ok. If you do not have enough then it is going to be deficient you do not want to be deficient you do not have want to be super deficient then you will die you want to stay in this region where it is optimal pretty understandable right. If let us say 5 milligram is optimal for your body you should have around 4 to 6 milligram. If you go 1 milligram range you may be not surviving, but if 5 milligram is good if you have 5 gram of it you may be again going to here ok. So, that is all this graph is going to tell you it is going to be toxic up to certain level after that ok we will see you in after life ok. Now, what determines which metal is going to be in our body or in biological system ok. What actually determines what controls the selectivity let us say in porphyrin that hemoglobin there is iron right what controls these things. First criteria is definitely the metal has to be abandoned somewhat abandoned on the earth crust. We should have some enough amount in nature for those metal to be here. Of course, every metal or every element that present on the earth may not be relevant in biological system, but whatever is in our biological system in any biological system those should be somewhat abandoned that is the natural abundance has to be somewhat there it need not be the maximum somewhat is there. In addition it should be soluble you know if something is not soluble how can you really have in our bodies during you know our growth we are eating food. So, from food we get let us say iron we copper lot of other metal it should be soluble. So, that body can intake it body can you know digest it and it can be delivered ok. So, essentially what happens is let us say we are eating food, food had some minerals food had these metal center different things and then from our intestine let us say it is a series of events one it is almost like a pizza delivery. Pizza is made somewhere you place an order the delivery guy with a bike nowadays will come now it will deliver to a desired or to a order place wherever the order has come from. So, that is how it happens. So, your food gets in from there on whatever essential lot of things are going on and then there are different enzyme and of course, they are specific they are very very selective as well. Let us say iron is there some guy is there ok I have to deliver iron he picks up iron goes and then dump it somewhere right they dump it somewhere then it could be further transported to some other place or it could be stored it is not necessarily everything we are eating is going to be digested or you know it is useful right away it can be stored at a certain point right it can be stored or it can be delivered at a desired point ok. Anyway so, solubility is essential oxidation state is essential you know oxidation state determines size ok. So, let us say that delivery guy if you give a huge pizza it is not going to fit in in his bucket right he is not going to deliver. So, size is going to matter ionic radius ligating atoms see always no metal ions is free metal ions comes with a luggage of ligand. Now, that delivery guy if you do not give him enough money he is not going to deliver right you have to pay him salary. Similarly, the metal ions if they do not find the right ligand they will not be ready to go they will not be transported they will not be storing right. So, all those things are essential to form or to do anything with the metal ion how they are delivered how they are they are in the very first place how they came it depends on lot of factor it is not just it has to be abandoned. It has to be abandoned we have to have it on the earth crust in addition to that what is other they are you know what is their characteristic what they are made of that determines. Let us say some zinc 2 plus you know zinc 2 plus is not redox active right. So, if you have some active site active site means where the chemistry is happening where you are doing some organic reaction that is the active site in our body lots of active site is there ok where a particular reaction is going on which is essential for our survival right. Now, if you put something like zinc 2 plus in such site where a redox activity is required it is not going to do it right. Zinc 2 plus let us say usually can do a structural job means it does not change the oxidation state it stays there and thereby if different protein backbone has to be hold together. Zinc 2 plus is best, but then if you in that site in instead of zinc 2 plus if you end up putting copper 1 plus or 2 plus or iron 2 plus they can undergo oxidation reaction they can undergo redox reaction. Therefore, though your structural job what you want may not be done by them you want somebody spectator some dumb guy to be there like zinc 2 plus which is feeling like a dumb because they can do any chemistry they cannot do any redox chemistry. You want somebody to hold the structure of the protein backbone you want somebody to be just there. See you have the heart of these Alzheimer disease lot of movies been made ok. Parkinson's disease right these are again very deadly diseases usually not many medicines are there you know it is it is painful diseases. Usually what happened let us say for Alzheimer's diseases if somehow you know your body starts accumulating some metal center in a in an appropriate manner in an inappropriate manner means where it should not be there it started concentrating it could be at brain it could be at lungs usually Alzheimer's disease these could be at brain let us say. So, what happens this let us say you are storing copper 1 plus then those protein backbone start connecting with those copper copper 1 plus let us say and then it can agglomerate it can precipitate out you do not want that sort of things to happen, but you know it is happening that is basically let us say Alzheimer's disease you know the in presence of a metal center your protein backbone or proteins are getting kind of precipitated if it is precipitating some in some important place such as brain your brain definitely getting affected and lot of side effect lot of things happens over the time right. So, that is how important the metal centers are they are good chelator or when they are the metal center they can do interact with lot of things and thereby can change the biological activity ok let us move on yeah sorry spin pairing stabilization. So, of course, high spin low spin let us say ok. So, sometime what happens let us say if you have unpaired electrons those unpaired electron means you are going to have a paramagnetic complex right compared to that if you have a paired not in every situation sometime it can be paired if it is high spin to low spin it can be paired thereby those reactivity of those unpaired electrons can be somewhat minimized right yeah you can exchange the ligand right I am coming to that how can you exchange the ligand one let us say water is there you replace that with another nitrogen ligand pyridine let us say you put pyridine instead of water what happens if it is if it can change the spin state then that chemistry will be completely different right ok. So, these are you know all these points you may not have to memorize, but I think it is essential that at least few points you understand what exactly brings out ok.