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Conventional Catalytic cycle for hydrogenation with Wilkinson’s catalyst P P P Cl reductive elimination P Rh Cl P Rh 14e P The first step of this catalytic cycle is the cleavage of a PPh3 to generate the active form of the catalyst followed by oxidative addition of dihydrogen. H2 oxidative addition P RCH2CH3 R CH2 H2C H H Rh P H P P P Cl Cl 1, 2 -migratory insertion Rh alkene coordination P H P Rh H Cl R P = PPh3 R AJELIAS L7-S18 catalytic cycle for hydrogenation P Rh P P H2 oxidative addition H H P Rh Cl P Cl P P P P H Cl Rh P H2 oxidative addition H Rh (due to trans effect of H ) P P P Cl RCH2CH3 reductive elimination R CH2 H2C alkene H Rh P P Cl H P H Kinetic studies have shown that the dissociation of PPh3 from the distorted square planar complex RhCl(PPh3)3 in benzene occurs only to a very small extent (k = 2.3 × 10–7 M at 25°C), and under an atmosphere of H2, a solution of RhCl(PPh3)3 becomes yellow as a result of the oxidative addition of H2 to give cisH2RhCl(PPh3)3. Rh 1, 2 -migratory insertion P Cl R The trans effect is the labilization (making unstable) of ligands that are trans to certain other ligands, which can thus be regarded as trans-directing ligands. The intensity of the trans effect (as measured by the increase in rate of substitution of the trans ligand) follows this sequence: H2O, OH− < NH3 < py < Cl− < Br− < I−, < PR3, CH3− < H−, NO, CO AJELIAS L7-S19 Relative reactivity of alkenes for homogenous catalytic hydrogenation • Cis alkenes undergo hydrogenation more readily than trans alkenes •Internal and branched alkenes undergo hydrogenation more slowly than terminal ones, and R > > R > R R > R R R R R R R > R R R > AJELIAS L7-S20 Fine tuning of a catalyst: hydrogenation catalysts which are more efficient than Wilkinsons catalyst + + Ph3P Ph3P Rh PPh3 Rh PPh3 Cl Wilkinson's catalyst PPh3 Ir PF6 N PF6 Crabtree's catalyst Schrock-Osborn's catalyst Catalyst 25°C, 1 atm H2 PCy3 Turnover frequency (TOF) in h–1 for hydrogenation of alkenes Wilkinson’s catalyst 650 700 13 NA Schrock–Osborn catalyst 4000 10 NA NA Crabtree’s catalyst 6400 4500 3800 4000 The cationic metal center is relatively more electrophilic than neutral metal center and thus favours alkene coordination. AJELIAS L7-S21 Hydrogenation with Crabtree’s catalyst Ir PCy3 H PF6 H2 N Ir oxidative addition 16e π PCy3 PF6 H N 18e migratory insertion repeat of cycle with cyclooctene S Ir PCy3 Ir S PCy3 N 16e PF6 reductive elimination solvent coordination Ir PCy3 PF6 H σ N 16e PF6 N S 16e di-solvated active form of catalyst The di-solvated form of the active catalyst generated by the removal of COD [after it gets hydrogenated and leaves] favors coordination of sterically bulky alkenes as well. This mechanism is only for understanding not for the exam AJELIAS L7-S22 Factors which have been found to improve the efficiency (better TOF) of transition metal catalysts for hydrogenation • Making a cationic metal center : makes catalyst electrophillic for alkene coordination • Use of ligands (eg. Cyclooctadiene) which will leave at the initial stages of the cycle generating a di-solvated active catalyst : facilitates binding of even sterically hindered alkenes • Use of chelating biphosphines: Cis enforcing: reduces steric hindrance at the metal centre + S Ir PCy3 N 16e PF6 Ir PCy3 PF6 Rh P P N S 16e di-solvated active form of catalyst Cis enforcing PF6 Problem solving- fill in the blanks Oxidative addition 1,1 Migr. Insertion 1,2 Migr. Insertion Bio Inorganic chemistry Study of Inorganic elements in the living systems 11 20 Na Ca 22.98 40.08 19 12 K 39.09 Mg 24.31 Sodium potassium pump (1/5th of all the ATP used) 29 27 26 Fe 55.85 Hemoglobin Myoglobin Cytochromes Ferredoxin Co 58.94 Vit B12 30 Cu 63.55 Hemocyanin Zn 65.38 Carbonic anhydrase Carboxypeptidase Important roles metals play in biochemistry 1. Regulatory Action Na, K 2. Structural Role Ca, Mg 3. Electron transfer agents Fe2+/Fe3+ 4. Metalloenzymes Zn Sodium potassium channels and pump Nerve signals and impulses, action potential muscle contraction Calcium in bones, teeth provide strength and rigidity Cytochromes: redox intermediates membrane-bound proteins that contain heme groups and carry out electron transport in Oxidative phosphorylation Carbonic anhydrase, Carboxypeptidase biocatalysts, CO2 to HCO3−, protein digestion 5. Oxygen carriers and storage Fe, Cu Hemoglobin, Myoglobin, Hemocyanin 6. Metallo coenzymes Co Vitamin B 12 biomethylation 18 times more energy from glucose in presence of O2 Structure of a metallo-protein : A metal complex perspective Spiral - α helix form of protein Tape - β Pleated sheet form of protein Prosthetic groups – A metal complex positioned in a crevice. Some of the ligands for this complex or some times all of the ligands are provided by the side groups of the amino acid units. The geometry around the metal and bond distances and angles are decided by the protein unit Myoglobin Carbonic anhydrase Metalloenzymes and Oxygen carriers = Protein + Cofactor A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes. Cofactors are either organic or inorganic. They can also be classified depending on how tightly they bind to an enzyme, with loosely-bound or protein-free cofactors termed coenzymes and tightly-bound cofactors termed prosthetic groups. Porphyrins with different metals at its centre are a common prosthetic group in bioinorganic chemistry Coenzyme B12 Cytochrome C Hemocyanin Myoglobin Chlorophyll Protoporphyrin IX and Heme 15 different ways to arrange the substituents around the porphyrin. Only one isomer protopophyrin IX is found in the living system. Porphyrins are planar and aromatic Proteins –consists of different amino acids in a specific sequence connected by the peptide bond – A few important amino acids relevant to the present course HISTDINE This amino acid has a pKa of 6.5. This means that, at physiologically relevant pH values, relatively small shifts in pH will change its average charge. Below a pH of 6, the imidazole ring is mostly protonated. VALINE is a branchedchain amino acid having a hydrophobic isopropyl R group. In sickle-cell disease, valine substitutes for the hydrophilic amino acid glutamic acid in hemoglobin.Valine is hydrophobic GLUTAMIC ACID has carboxylic acid functional group which is hydrophilic, has pKa of 4.1 and exists in its negatively charged deprotonated carboxylate form at physiological pH ranging from 7.35 to 7.45. SERINE Serine is an amino acid having a CH2OH side group. By virtue of the hydroxyl group, serine is classified as a polar amino acid. Serine was first obtained from silk protein, a particularly rich source, in 1865. The primary structure of a protein The four levels of protein structure H bond between side chains, hydrophobic interactions, disulfur linkages, electrostatic interactions See youtube video “protein structure” Univ of Surrey ’ Hemoglobin- a quaternary structure of a protein 4 units Each unit has a prosthetic group (heme) embedded in a crevice and partly coordinated by histidine units Inorganic Active site / Prosthetic group In molecular biology the active site (prosthetic group) is part of an enzyme where substrates bind and undergo a chemical reaction. It can perform its function only when it is associated with the protein unit Ferredoxin (e transfer) Heme in Myoglobin (O2 storage) Carbonic anhydrase Enzyme) Nitrogen Fixation Inorganic Prosthetic group of three well known oxygen carriers Present in Vertebrates Present in molluscs Present in some sea worms Can the prosthetic unit part of a metalloprotein perform its normal function without the protein unit around it ? Fe2+ Fe2+ + O2 O O Free Heme Fe2+ O + Fe2+ 4+ 2 Fe O O Fe4+ O + Fe2+ Fe3+ O Fe3+ Reversible binding of O2 is possible on when protein unit is present around the heme unit Oxygen : A few Questions Why do we need oxygen or why do we breathe? What happens to oxygen in our body and where does it happen? How exactly does oxygen change to water ? What does this reaction produce and how? How exactly is oxygen carried around and stored in the body? How exactly is CO2 removed from the body? Electron transfer agents Fe2+/Fe3+ Cytochromes: redox intermediates membrane-bound proteins that contain heme groups and carry out electron transport in Oxidative phosphorylation Cytochromes are, in general, membrane-bound (i.e. inner mitochondrial membrane) heme proteins containing heme groups and are primarily responsible for the generation of ATP via electron transport. They are found bound on the inner mitochondrial membrane either as monomeric proteins (e.g., cytochrome c) or as subunits of bigger enzymatic complexes that catalyze redox reactions. These heme proteins are classified on the basis of the position of their lowest energy absorption band in the reduced state, as cytochromes a (605 nm), b (~565 nm), and c (550 nm). Electron transfer agents; e.g. Cytochrome C S(Cys) Protein protein H N S(Cys) Protein N N N Fe N S CH3 methionine residue of protein N OH HO O O Mitochondria: The powerhouse of the Animal Cell Bio-units of the electron transport chain are present on the inner walls of the mitochondrion. Analogous powerhouses on the plant cells are chloroplasts Glycolysis + Oxidative phosphorylation: How food is converted into energy Glucose + 36 ADP + 36 Pi + 36 H+ + 6 O2 6 CO2 + 36 ATP + 42 H2O Glucose gives 18 times more energy when oxidized ADP + Pi + H+ + energy ATP + H2O Δ G0 = - 7.3 kCal/mole ATP : Universal currency for energy Different forms of Cytochromes (except Cytochrome P-450) are involved in the electron transfer process leading to ATP synthesis and conversion of O2 to H2O in living systems See youtube video ‘cellular respiration ( electron transfer chain)’ See youtube video ‘gotta get that ATP’ for fun and learning! Actual structure of ATP synthase unit (a molecular machine!) Cytochromes a and a3 Cytochromes b and c1 Cytochrome c oxidase with electrons delivered to complex by soluble cytochrome c (hence the name) Cytochrome c reductase