Conventional Catalytic cycle for hydrogenation with Wilkinson’s catalyst

P P
Rh
P Cl
P P The first step of this
P catalytic cycle is the
reductive Cl Rh H2 oxidative cleavage of a PPh3 to
elimination 14e P addition generate the active
form of the catalyst
RCH2CH3 followed by oxidative
addition of dihydrogen.

R H H
CH2
P P
H2C Rh H Rh
P P
Cl Cl

R
1, 2 -migratory alkene
insertion
P coordination
H H
Rh P = PPh3
P Cl

R
 AJELIAS L7-S18
catalytic cycle for hydrogenation

H
H2 oxidative
P P addition H P Kinetic studies have
Rh Rh
shown that the
P Cl P Cl
dissociation of PPh3
P
from the distorted
P square planar complex
P P
(due to trans RhCl(PPh3)3 in
effect of H ) benzene occurs only
H
to a very small extent
H2 oxidative P
P (k = 2.3 × 10–7 M at
Cl Rh addition H Rh
25°C), and
P P
under an atmosphere
Cl
of H2, a solution of
RCH2CH3 RhCl(PPh3)3 becomes
reductive
alkene
yellow as a result of
elimination
the oxidative addition
of H2 to give cis-
R H P
CH2 H2RhCl(PPh3)3.
P H H
H2C Rh Rh
P 1, 2 -migratory P Cl
insertion
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 PPh3 PPh3 PCy3
Rh Rh PF6 Ir PF6
Ph3P Cl PPh3 N

Wilkinson's catalyst Schrock-Osborn's catalyst Crabtree's catalyst

Catalyst Turnover frequency (TOF) in h–1 for hydrogenation of

25°C, 1 atm H2 alkenes

Wilkinson’s catalyst 650 700 13 NA

Schrock–Osborn 4000 10 NA NA
catalyst
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

H
PCy3 PCy3
Ir PF6 H2 PF6
Ir
N oxidative H
16e addition π
N 18e
migratory
insertion

PCy3
PCy3 reductive Ir PF6
repeat of Ir PF6 elimination
cycle with S H
N solvent
cyclooctene
16e coordination σ N 16e

S PCy3
Ir PF6
S N
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
+
P
S PCy3 Rh PF6
PCy3 Ir PF6
PF6 P
Ir
S N
N
16e
16e di-solvated
active form Cis enforcing
of catalyst
 Problem solving- fill in the blanks

Oxidative addition 1,2 Migr. Insertion

1,1 Migr. Insertion

 Bio Inorganic chemistry
Study of Inorganic elements in the living systems

11 20
Na Ca
22.98 40.08

19 12
K Mg
39.09 24.31
Sodium potassium pump
(1/5th of all the ATP used)

26 27 29 30

Fe Co Cu Zn
55.85 58.94 63.55 65.38
Hemoglobin Vit B12 Hemocyanin Carbonic anhydrase
Myoglobin Carboxypeptidase
Cytochromes
Ferredoxin
 Important roles metals play in biochemistry
1. Regulatory Action Sodium potassium channels and pump
Na, K Nerve signals and impulses, action potential
muscle contraction
2. Structural Role Calcium in bones, teeth
Ca, Mg provide strength and rigidity

3. Electron transfer agents Cytochromes: redox intermediates

Fe2+/Fe3+ membrane-bound proteins that
contain heme groups and carry out electron
transport in Oxidative phosphorylation
4. Metalloenzymes Carbonic anhydrase, Carboxypeptidase
Zn biocatalysts, CO2 to HCO3−, protein digestion

5. Oxygen carriers and storage Hemoglobin, Myoglobin, Hemocyanin

Fe, Cu 18 times more energy from glucose in
presence of O2

6. Metallo coenzymes Vitamin B 12

Co biomethylation
 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

Cytochrome C Coenzyme B12

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 VALINE is a branched- GLUTAMIC ACID has carboxylic acid
acid has a pKa of 6.5. chain amino acid having functional group which is hydrophilic,
This means that, at a hydrophobic isopropyl has pKa of 4.1 and exists in its
physiologically relevant R group. In sickle-cell negatively charged deprotonated
pH values, relatively disease, valine carboxylate form at physiological pH
small shifts in pH will substitutes for the ranging from 7.35 to 7.45.
change its average hydrophilic amino acid
charge. Below a pH of 6, glutamic acid in
the imidazole ring is hemoglobin.Valine is
mostly protonated. hydrophobic

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 Nitrogen Fixation

Enzyme)
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+ + O2 Fe2+ O
O
Free Heme

4+
Fe2+ O + Fe2+ 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 Cytochromes: redox intermediates
Fe2+/Fe3+ 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 S(Cys) Protein

N N
N N CH3
H Fe S
methionine
N N residue of
protein

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

ATP + H2O ADP + Pi + H+ + energy Δ G0 = - 7.3 kCal/mole

ATP : Universal currency for energy

Different forms of Cytochromes (except
Cytochrome P-450) are involved in the in living systems
electron transfer process leading to ATP
synthesis and conversion of O2 to H2O
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!)

Cytochrome c oxidase with electrons

Cytochromes a and a3 delivered to complex by soluble cytochrome c (hence the
name)

Cytochromes b and c1 Cytochrome c reductase