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a warm welcome to buy an organic chemistry course let me introduce first myself this is dr. s P Roth professor in the Department of Chemistry at IIT Kanpur and the Bionic chemistry is a meeting point of chemistry and biology and this has been designed to understand the role of inorganic elements in biological processes and this by organic chemistry is a highly interdisciplinary subject and meeting point of various field - like inorganic chemistry physics biochemistry microbiology nanotechnology physiology pharmacology etc the main avenues of this study would be understanding the role of naturally occurring inorganic elements in biology metal ions at the core of biomolecules control many key processes understanding structure and function of the metallo enzymes and rolls of metal ion there in practical application of the knowledge gained and use of inorganic molecules edge probes and drugs for example cisplatin are enough in cardio light several such examples are there I'll now take a joy ride to highlight what would be so cast in the next few hours of my journey in this short course of bioinorganic chemistry please note that only few selected topics will be chosen to cover during this time the most abundant element in the earth crust is oxygen and you see their earth there can be many chemical reactions with oxygens however all these reactions are thermodynamically favorable and exothermic however it never happens just like mixing the redox chemistry of molecular oxygen is shown over here and the most important reactions is when dioxygen converts to water with the help of 4 proton and 4 electron with a redox potential of zero point eight one five volt the reduction potential of the four electron reduction of dioxin is a measure of great oxidizing power of dioxin if this being so then what protects vulnerable species from the full oxidizing power of dioxygen the percent of atoms in human bodies shown over here as you can see that hydrogen is around sixty two point eight percent oxygen twenty five point four carbon nine point four nitrogen one point four and other elements together is just one percent at first sight the idea of inorganic chemistry associated with life may appear to be rather narrow field of study as we tend to think of living matters as being just organic however it is a fact that without certain inorganic elements no organism could exist the term by on organic which is a composite of biology and inorganic is used to describe the occurrence and properties of inorganic elements in living system and these elements are extremely important for our day-to-day life I have shown here the periodic tables of element and edge one can see that some of these elements are highlighted blue green pink brown the brown color is for the elements which are present in bulk amount in biological system then the blue one which is believed to be the essential for a wide range of bacteria plants and animals including humans then green which is for elements that may possibly be essential for some species whereas pink is for those elements which are believed to be essential for some species as you can see that most of the elements are not even used in biology now we will discuss that how nature has selected only certain elements from large number of elements presents in the periodic table now what role does the metal ions play the metal ions are present at the active site of biomolecules spatially metalloenzymes and they have been doing a some functional role as also structural role however metalloenzymes without metal ions are simply inactive I will now show you a example of a metal ion in a functional role say carbonic anhydrase is actually responsible for conversion of carbon dioxide and water to bicarbonate and h+ and this is the active site structure of carbonic anhydrase where you can see that three stood in Earth ligated and the fourth position is occupied by weak water leak at the uncatalyzed reaction is too slow it's just seven into 10 to the power minus 4 second inverse they have reactions when it is catalyzed by carbonic anhydrase is 10 to the power 7 times faster turnover number of this reaction is 10 to the power 6 second inverse huge turnover number we'll discuss that how this enzyme actually increases the rate of these reactions extra structure of carbonic anhydrase is shown over here you see that there is a huge protein chains wrapping around this molecule and inside this protein this zinc ion is sitting and once we remove this protein chain you can see the active site structure of this carbonic anhydrase now you will see that how the metal ion is responsible for its conversion to bicarbonate this is the protein structure with carbon dioxide as a substrate you see that carbon dioxide is sitting over there again once I removed this protein chains you can see that carbon dioxide is sitting close to metal centre and this is also the protein structure of carbonic anhydrase and formation of bicarbonate is clearly visible and once I remove this protein chains you can see that the bicarbonate is formed over here and this is ligated to the zinc metal center so you can see yourself yet how is responsible for this transformation of carbon dioxide to bicarbonate I'll now show you a metal which is in a structural role zinc finger protein now finger proteins are essential to recognize and bind to DNA they have finger like projection which fit inside the grooves of the helix as one can see that this is the polypeptide chain and zinc is sitting inside with ligated with nitrogen and sulfur now once you remove the zinc the entire structure collapse so this suggests that how crucial judging metal ion is now question is that how the elements transport it across the cell membrane so you can see that the elements in high concentration comes through the biological membrane to the low concentration very easily across the concentration gradient this is passive transport now if the elements have to go to the opposite direction like from low concentration to high concentration you must need an energy to do that because it is not spontaneous though this is called active transport now elements like iron zinc copper molybdenum comes inside the cell against the concentration gradient since their concentration increases by many thousand poles inside the cell it would be interesting to discuss how the specific receptor proteins allows only some selected element to come inside the cell so it can be passive diffusion it can be through an ion specific channel but it would be very selective so that not every element can come inside the cells so we'll be talking about how i owns are selected by the specific receptor proteins for example these potassium channels is sewn over here and this is very much specific for the potassium and it only allows potassium to go through this channel and Roderick MacKinnon was awarded the Nobel Prize in Chemistry in 2003 for structural and mechanistic study of ion channels so we'll be discussing all these in details in my subsequent lectures now I have shown here the same terms of element deficiency in humans as you can see that large number of deficiencies or diseases can happen once you have a deficiency of a particular element for example calcium that is skeletal growth magnesium iron jiaying copper molybdenum cobalt nickel chromium silicon chlorine iodine selenium arsenic all these elements have to be present within a certain concentration range if it is present in more concentration or less concentration than the desire amount then one would be having diseases and some of these symptoms are tabulated over here now some of these effects of metal deficiencies are sown over here and if you have the deficiency you have to take medicines to supplement those metals and go to the doctor and doctor will write this medicines indeed now two most important biological reactions are shown here for example that we take dioxygen and dioxygen is being circulated in the blood and it religious lots of energy and carbon dioxide during the respiration and this carbon dioxide transported through blood goes out of our body and it is being utilized by green plant and in presence of light they undergo a photosynthesis reactions and it liberate oxygen which we inhale so this is being a the cycle of two important reaction one is photosynthesis another on each respiration now the dioxygen carrying proteins are shown here in hemoglobin and myoglobin in our body and as you can see that deoxyhemoglobin myoglobin which is five coordinated convert to six coordinated upon dioxin binding and iron two getting oxidized to iron 3 whereas dioxin getting reduced to superoxides now hemoglobin and myoglobin are responsible for this dioxin transport and storage in our body however hemoglobin is tetrameric in nature as you can see that these heme centers are here 1 2 3 4 however huge proteins are wrapping around these heme centers similarly myoglobin there is only one him centers and basically the structure of this heme center is shown over here this being the case now we need to understand that how nature design this molecules the hemoglobin selected for transporting oxygen while myoglobin stores oxygen myoglobin is monomer while hemoglobin is tetra Mar of the same structural units discriminating oxygen from other available gases in the environment so we will be talking all this and try to understand the nature's design for example this distal histidine which is not ligated directly to the iron Center it's responsible for discriminating between carbon monoxide and oxygen as one can see that this distal histidine while facilitating the angular coordination of dioxygen comfortably while the perpendicular and linear carbon monoxide moiety cannot bind like this it is forced to have any angular fashion in the respiration the most important transformations that happens is dioxin convert to water with the help of poor proton and for electron dioxin completely reduced in this way however if it is reduced partially what would happen so dioxin after one electron reduction converts to superoxides superoxide then convert to peroxides peroxides after reduction converted to water in which radical and this way radical converts to water as you can see that partial reduction produces superoxide peroxides hydroxy radical these are actually called reactive oxygen species and very harmful for our biological system and this reactive oxygen is responsible for aging and age-related is in our body so I have shown here how reactive oxygen species actually changes our faces and this antioxidants are also there to fight against this reactive oxygen species and some of these food items are shown here which are strongly an antioxidant which destroy those ross the reactive oxygen species and this is what one can use at home without losing much you can stay in also at very old days now secret of anti-aging agent is superoxide dismutase as one can see the superoxide getting converted to oxygen and co2 2 - peroxide however this is a dis mutation reaction means this is a continuous process thermodynamically feasible Delta G negative now this being the case why Nature design enzyme called superoxide dismutase this is because the rate of this transformations has increased enormously it becomes 2 into 10 to the power 9 mole inverse second inverse and that's the reason why Nature has designed an enzyme because super oxides are extremely poisonous however the super oxides also produce peroxides which is another poisons now this peroxides is on desire and also extremely harmful however nature utilized this undesired product harmful product to something very useful and some of the enzymes such as catalyst peroxidase chloro peroxidase lignin peroxidase cytochrome super oxidase there are lots of injured which actually converts this auntie's are intermediate into something very useful molecules in our biological system now what could be the better choice management then this cytochrome p450 is a another very important enzymes in our body which is responsible for oxidative metabolism of drugs steroids and carcinogen it actually protect our body from toxification and hydrolyzed undesired compound so that it can excrete to our body now the cytochrome p450 catalyst and peroxidase all go through a highly reactive intermediates that is called iron for oXXO species and they are all similar only difference is their axial coordination the sixth position is occupied in some cases it is histidine in some cases each tyrosine in some cases it is system however their structures are indeed very similar now it is very surprising to see that their activity is very different for example in cytochrome p450 it is actually responsible for oXXO transfer to substrate while cattle age and peroxidase it is electron transfer to substrate now it is interesting to see that how design principle makes all these differences in reactivity we have also learned from nature and implemented the knowledge gained for the betterment of our day-to-day life catalyst and peroxidase at resting state is like this and one of our friend from us has this bio-friendly catalyst tamil which is doing miracles in cleaning large number of pollutants from our environment he also in deterrence he was amount of money out of that the active form of this catalyst is the same for both biology and bio catalyst this is an alternative based on nature's oxidant oxygen or hydrogen peroxide now as I have discussed that in our body hemoglobin and myoglobin is responsible for oxygen transport in our body now what is exactly happening that iron to convert it to iron 3 while dioxygen reduced to superoxide and once this dioxin leaves this iron 3 converts back to iron 2 again so this is completely reversible which is happening all the time in our body now dioxygen binding slowly causes irreversible oxidation of iron 2 to iron 3 in deoxyhemoglobin and in that way the overall efficiency of hemoglobin decreases over the time now what's the nature solution for it yes nature has a solution so him decomposition and regeneration of the blood is what is the solution and we all know that red blood cell lasts only for 120 days so this is what the theme decomposition process catalyzed by him oxygen is like hemoglobin converted to believe hardened bilirubin which is yellow in color however insoluble then bilirubin converted to bilirubin die Glocke or o'night and excrete through urine so this is what is happening all the time and it is better that you donate your blood otherwise it undergo this types of decomposition process all the time as I have already said that red blood cell has a lifespan of only 120 days and after that it decomposes so this is what is happening and it is a spontaneous process if you have this balance then this bilirubin which is your Lewin color will be deposited on the body and creates this jaundice you can see this normal person is shown over here however the person which is having jaundice which is his body color turns yellow and you can see this is a very common disease in our life if it is not spontaneous now I will be talking that why the rate of this electron transfer is so fast in some of these enzymatic proteins or enzymatic system I am showing here a blue copper protein an example where the rate of electron transfer is increased to 10 to the power 8 to 10 to the power 10 times faster in this blue color protein the rate is 10 to the power 4 to 10 to the power 6 mol inverse second inverse however what is happening in blue copper protein this copper to converts to copper one and copper one religious one electron convert to cover 2 so copper to become copper 1 and copper 1 become copper 2 so one takes electron 1 release elec so this is what is happening during this process there is a he was structural reorganization energy required say copper 2 is 4 coordinated species always square planar copper 1 which is detailed system it prefers tetrahedral now converting a square planar to tetrahedral and tetrahedral to square planar there's a huge reorganization energy required and these slows down the rate of electron transfer now this being the case then how the electron transfer in blue copper protein increases to 10 to the power 8 to 10 to the power 10 times faster so we will talk about all these in details you must have seen that potato and Apple turns brown if you cut it and keep it per few hours and this is because that the surface is getting protected out of this brown color and the enzyme which is responsible for this browning of the surface is tyrosinase we'll talk about in details the mechanism of this brown color and how tyrosine is actually responsible for converting this apple and potato to brown the coin game b12 dependent enzymes is shown here basically coenzyme b12 is a medium-sized molecule with a molecular mass of about 1350 dalton which exhibits eight characteristic specificity and high reactivity only in combination with corresponding apuane chain and as you can see that this bitumen b12 is the only vitamin known to contain a metal and also now we will look at the design and nature selection of the metal and the macro cycle this coenzyme bit will be so important that poor Nobel Prize or in 1934 people minute Murphy got the Nobel Prize for the discovery of anti pernicious anemia factor now we call vitamin b12 1964 Dorothy hot Kim C solve the excess structure of this complicated molecule 1965 Woodward for its outstanding achievements in the art of organic synthesis 1981 Fukai and Hofmann for quantum mechanical studies of chemical reactivity you all know that woodward hoffmann rules how important it is for pericyclic reactions now how inert is the nitrogen gas this nitrogen bond dissociation energy is very high - 25 kcal per mole indeed we run our reactions under nitrogen assuming that it will maintain inert atmosphere the reaction this nitrogen plus 3 h 2 gives rise to two molecule of ammonia it's also thermodynamically favorable but the kinetic barrier is too high as one can see out of this diagram indeed the industrial production of ammonia which is popularly known as the haber-bosch process is nitrogen plus 3 molecule of hydrogen converts to ammonia which eventually transformed to urea this ammonia requires a very drastic condition of more than 200 atmospheric pressure 450 degree centigrade temperature and iron molybdenum catalyst at idea is very important for our farmers it has been used as a fertilizers and the Haber and both got Nobel Prize in 1918 and 1931 respectively conversion rate is only 15% now in contrast if you look at the biological catalysts nitrogenous this is the leguminous plant and this is the root nodules have those nitrogenous which silently fixes the aerial nitrogen converting them to ammonia and fertilizers so the nitrogen is this enzyme has this iron protein and iron molybdenum protein and once you remove the protein as you can see this iron sulfur clusters and iron molybdenum clusters are actually responsible for fixing the aerial nitrogen and converting them to ammonia and other useful products we will discuss in details in the subsequent lectures so the reaction which is actually happening is converting aerial nitrogen to ammonia at room temperature and normal atmospheric pressure so it is interesting to see that how aerial nitrogen can so easily be fixed and so easily be utilized and we'll be discussing these in details in subsequent lectures now I'll also talk about the inorganic molecules used in medicines and some of these examples popular examples are sown over here this is cisplatin which is an anti-cancer drug or of him which is arthritis drug cardio light it is an imaging agent there are many such molecules which are used in medicine and I will be talking all details in my lectures and I hope our journey would be very pleasant and you will all enjoy going through this course thank you so much for your attention [Music] [Music]