Hemoglobin - Chemistry Study Notes

DATEHaemoglobinHaemoglobin is made of two PartsGlobinHaem (6%)(94%)(A Protein Part)(A. non-Protein Part)(Prosthetic gfThere are two types of Protein chains, calledX-chain and B-chain in human haemoglobinand these chains differ in terminal acid gp.Two x- chain (141 amino acid each) &Two B- chain ( 146 amino acid each) are Presentin a molecule of Haemoglobin of a normaladult human.Haem is a Prosthetic group that consists ofan iron ion contained in the center of alarge heterocyclic organic ring calledPorphyrin ( (substituted Porphin)form co-ordinate bonds to a metal ionPorphyuin is a chelating agent which canthrough nitrogen It is a cyclic compoundmethine. made of 4 Pyrrole rings joined throughclassmatePAGE DATEPorphyrins are derivatives of Porphinsformed by replacement of hydrogenatoms of the Pyrrole rings, sub situatedat the outer rim. with some other groupof atoms.2x13III4SHHB8NIVIII57r6IPorphin ( Fischer Numbering)352A4620B18HN199H18DN1N1016C1714121513(IUPAC Numbering)( Porphin)classmatePAGE DATEIron can form six co.ordinate bonds Inform a square Planar complex with ironhaem four Pyrrole gps of Proto porphyuinvia Nitrogen atomsTwo remaining coordination position of ironare Perpenticular to the Plane of PorphyrinringThe fifth Position is occupied by an imidazolering of the histidine amino acid residuewhen haemoglobin combins with one moleculeof oxygen to form oxyhaemoglobin. itreplaceing sixth valency of water moleculeif Present. .When the w iron atom is in ferrous state, thecomplex is called Protohaem or haem andthe molecule is neutral.when the iron atom is in ferric state. themolecule carries a unit Positive charge andis called Haemin.It is to be remembered that the generalname of iron free and iron containingcompounds are called Porphyrins andHaeem respectively.PAGEclassmate DATEInside the bodyHaemoglobinOxyhaemoglobinoutside thebodyHaeminACOHNaceMethaemoglobinC34 H32N404Fe (III) ceCH3COOMNa25204Haematin+GlobinHaemC34H32N404C34H32N404Fe (III) OHFe (II)Haemoglobin workinginanimal bodyclassmatePAGE DATEconstitution of Haemin(1)The molecular formula of Haemin isC34H32O4 NyFece.(2)Haemin forms diester with MeOH / HCl. Thisshows that Haemin contains two carboxylicgroups(3)gives telrahydrohaemin it shows Presence ofcatalytic hydrogenation of haemin with H2 / pdtwo double bonds in haemin.(3)On vigours reduction with HI/ACOH or HI/Phosphovigorous-nium iodide haemin gives opsopyrrole (I)haemopyrrole (II) cryptopyrrole (III) andPhyllopyrrole (IV).str. of all the foursubstituted Pyrroles were confirmed bysynthesisHaeminHI / ACOH or HI / PHyIH3CHH5CH3C2HSCH3(2H5+HC+(H3NH3NNHH(I)H32H5(II)IIIH.CCH3NHIVPAGE DATEHaemin molecules contains four Nitrogen atoms.Haemin on degradation gives four PyrrolederivativesTheseresultsshow,thathaemin contains four Pyrrole nuclei havingmethyl gp in B. Position(5)Haemin on reduction with tin and HU givesfour Pyrrole Substituted carboxylic acidVVI ,VII&VIII,)formationoftheseProductsconfirmed that haemin contains fourPyrrole nuclei having methyl gp in13. PositionHaeminSn/HClCH3(H2-CH2-COOHH.C3CH2- CH2COOHNHSNHM( V)(VI)Opso pyrrdecarboxylic acidHaemopyrrolecarboxylic acidH.CCH2-CH2-COOY3CH3CH2 CH2COOHCH3CH3N+M3CNHH(VII)Phyllo PyrroleCrypto Pyrrolecarboylic acidcarboxylicacidclassmate(vii)PAGE DATE(6) Haemin on reduction with iron dust in acetic acidgives Protoporphyrin (1x) which on furtherreduction gives mesoporphyrin (x)Xonoxidationwithchromicacidgivetwomoleculesofethylmethylmaleimideandtwomolecules of haematinic acid.Haeminonoxidationwithchromicacidsimilarconditiongivesonlytwomoleculesof haematinic acidHaeminFe/ACOHProtoporphyuin ( (IX)C34H32O4N4(403/H2SO4RednHECH2 CH2 COOH2Mesoporphyrin( )ONMC34H3804NyHaematinicacidCr03/H2SO42H5H3HSCH2(H2COOH2+2OONNHHEthyl methyeHaematinicmaleimideacidclassmatePAGE DATEStr. of Haematinic acid and ethyl methyl maleinidehave been confirmed by their synthesis formationof haematinic acid and ethyl methylmaleimidefrom Protoporphyein suggest that Pyrrolenuclei are linked through the x- Position(oxidation at x -carbon).(7)PositionofsubstituentsinfourPyrrolenuclei-Meso Porphyrin on decarboxylation givesactioporphyuin which was identified astetraethyl tetra methyl PorphyrinActiporphyrincanexistinfourdifferentisomericform.(Positionalisomers)CH32H5CH3(2H5C2H5CH3CH3C2H5H2C(2H53S H5CH3C2H5CH3C2H5CH3I11CH3CH3(2HSC2H5CH3C2H5CH3C2H5GHSCH3SH5CH3CHH5CH3CH32H5IIIIVclassmateAGE DATEAll the four isomere were synthesised butunfortunately they resembled very much intheir Properties so the actioporphyrinobtained fromhaemincouldnotidentifiedThe correct substitution Pattern wasobtainedfrom the study of the precursor ofactioporphyrin i.e mesoporphyrinC2H5CH3(H3(2H5NN11HHM/N- CO2HSCH3CH2 (H2 COOHCH2CH2COOHmesoporphyrin)GIMSCH3decarboxylateCH3GHSNHNMHHNN-HECH3C2H5TC2H5classmateAetioporphyrinPAGE DATEThe str. of actioporphyeiin was confirmed based onthe structure of mesoporphyrinSince meso Porphyrin (x) is derived from ProtoporPhysinby reduction C-CH. CAD tirentistics - (H3) andremoval of iron. this strompops protoporphyrin andProtoporphyrin is obtained from haemin byHaemin may be represented as follows.CH=CH2(H3CH= (H2HStNFeFe/ACOHH(H3HSC(H2CH21CH2CH2COOHCH=CH2COOH(H3CH3HaeminN(H=CH2MNNHNH3C(H3CH2CH2 CH2 COOHCH2Icook(Proto porphyein)PAGEclassmate