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TRANSCRIPT
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Stereochemistry and conformations
Ref. Books:
Stereochemistry Conformation & Mechanism
- P.S. Kalsi
Organic Chemistry - L.G. Wade
Organic Chemistry - I.L. Finar Vol. 2
Stereochemistry of Carbon Compounds
- E.L. Eliel
Stereochemistry
The branch of chemistry that deals with spatial
arrangements of atoms in molecules and the
effects of these arrangements on the chemical
and physical properties of substances.
Stereochemistry refers to the 3-dimensional
properties and reactions of molecules.
Deals with:
Determination of the relative positions in
space of atoms, group of atoms
Effects of positions of atoms on the properties
Conformation: An atomic spatial arrangement
that results from rotation of carbon atoms
about single bonds within an organic molecule.
Conformation generally means structural
arrangement and may refer to:
Conformational isomerism, a form of
stereoisomerism in chemistry
Stereoisomers are isomeric molecules that
have the same molecular formula with same
connectivity, but differ in the three-dimensional
orientations of their atoms in space.
Stereoisomers
Interconverted by rotation about single bond ?
Yes
H
H
CH3
H3C
H
H
H3C
HH
CH3
HH
Conformational
No
Configurational
Optical
Yes
isomerism at a tetrahedral central ?
compounds non-superimposable
mirror image ?
No
Geometric
No
Diastereomers
H
H
H3C
Br
Cl
H3C
Cl
H
H3C
Br
H
H3C
Yes
EnantiomersCl
H3CH2C
Cl
CH2CH3HH
CH3H3C
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Conformation : interconvertible by rotations about single
bonds
Configuration : an atomic spatial arrangement that isfixed by the chemical bonding in a molecule and thatcannot be altered without breaking bonds
To change the configuration, you must always cleave and form
new covalent bonds
Different conformations, can be made identical with a rotation
of 180 about the central single bond.
Definitions
Stereoisomers – compounds with the same
connectivity, different arrangement in space
Enantiomers – stereoisomers that are non-
superimposible mirror images; only properties that
differ are direction (+ or -) of optical rotation
Diastereomers – stereoisomers that are not
mirror images; different compounds with different
physical properties
Optical activity – the ability to rotate the plane of
plane –polarized light
Polarimeter – device that measures the optical
rotation of the chiral compound
Arises from restricted rotation about a C=C
double bond.
Stereoisomerism
Stereoisomerism is the arrangement of atoms in
molecules whose connectivity remains the same but
their arrangement in space is different in each isomer.
Geometrical Isomerism
cannot be inter-converted
at lower temperatures
This process of rotation is associated with high energy
(271.7 kJ mol-1). Thus at ordinary temperatures, rotation
about a double bond is prevented and hence
compounds such as CH3CH =CHCH3 exist as isolable
and stable geometrical isomers.
H
C C
H
H3C CH3
CC
cis-but-2-ene trans-but-2-ene
H3C
CH3H
H
cis-cinnamic acid trans-cinnamic acid
HH
C C
H
COOH
CC
COOH
HH5C6 H5C6
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Necessary and sufficient condition for
geometric isomerism
No two stereoisomers are possible for CH3HC=CH2,
(CH3)2C=CH2 and Cl2C=CHCl.
Compounds existing in two stereo-isomeric forms are:
Geometrical isomerism will not be possible if one of the
unsaturated carbon atoms is bonded to two identical groups.
where a b and c d
Determination of the configuration of the geometric isomers
Physical methods
(a) Melting points and boiling points:
Trans isomer has a higher m.p. due to symmetrical packing.
Cis isomer has a higher b.p. due to higher dipole
moment which cause stronger attractive forces.
(b) Solubility: Cis-isomers have higher solubilities.
Maleic acid 79.0g/100mL at 293K in H2O
Fumaric acid 0.7g/100mL at 293K in H2O
(c) Dipole moment: In general, cis isomers have the
greater dipole moment.
HH
C C
H
CH3
CC
= 0.4 D = 0
CH3
HH3C H3C
ClCl H
Cl
= 0 = 1.85 D
C C
Cl
H
CC
H H
(d) Spectroscopic data :
IR: Trans isomer is readily identified by the appearance
of a characteristic band near 970-960 cm-1. No such
band is observed in the spectrum of the cis isomer.
NMR: The protons in the two isomers have different
coupling constants e.g. trans – vinyl protons have a
larger value of the coupling constant than the cis-isomer,
e.g. cis- and trans-cinnamic acids.
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E/Z notation
If there are three or four different groups attached
to the Cs of C=C double bond
E/Z notation rather than the trans/cis notation is
used to name the stereoisomers of a molecule.
E : in opposition to trans
Z : together cis
ZE
This method, which is called the E and Z system, is based on apriority system originally developed by Cahn, Ingold and Prelog foruse with optically active substance
CC
1
2
2
1 2
1
2
1
C C
E Z
Z-But-2-ene-1,4-dioic acid
(Maleic acid)
E-But-2-ene-1,4-dioic acid
(Fumaric acid)
C C
COOH
HHOOC
HHOOC
H H
COOH
CC
2
1
2
1
1
2
2
1
C C
F
ClI
Br
1
2
1
2
2
12
1
Br
I
Cl
F
CC
Z-1-Bromo-2-chloro-
2-fluoro-1-iodoethene
E-1-Bromo-2-chloro-
2-fluoro-1-iodoethene
Z-2-Butene
2
1
2
1 H3C
H H
CH3CC C C
CH3
H
H
H3C1
2 1
2
E-2-Butene
Number of geometrical isomer of compounds containing
two or more double bonds with non-equivalent terminii
Dienes in which the two termini are different (i.e.
XHC=CH–CH=CHY), has four geometrical isomers .
It means the number of geometrical isomers is 2n where n is
the number of double bonds.
C
C
X
H
H
H
HY
C
CC
C
H
H
Y
C
C
H
H
X
Z,E, or cis-trans
C
C
Y
H
H
C
C
H
H
X
Z,Z, or cis-cis E,E or trans-trans
C
C
H Y
H
H
H
X
C
C
E,Z or trans-cis
Geometric isomerism of oximes
They should also exhibit geometric isomerism if groups
R1 and R2 are different.
Beckmann (1889) observed that benzaldoxime existed in
two isomeric forms and Hantzsh and Werner (1890)
suggested that these oximes exist as the following two
geometric isomers (I and II).
For fixing priority the lone pair of electrons on nitrogen is
taken as group of lowest priority.
or
The carbon and nitrogen atoms of oximes are sp2-
hybridized, as in alkenes.
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Nomenclature of aldoximes
The prefixes syn and anti are used in different
context for aldoximes and ketoximes
In case of aldoximes, the syn form is the one in
which both the hydrogen and the hydroxyl (-OH)
group are on the same side of the C=N, whereas in
the anti form, they are on the opposite side.
H
H5C6
C N
OH
anti-benzaldoxime
OH
NC
H5C6
H
syn-benzaldoxime
Nomenclature of ketoximes
syn-ethylmethylketoxime syn-methylethylketoxime
anti-ethylmethyketoxime or
anti-methyethylketoxime or
In case of ketoximes, the syn and anti
descriptor indicate the spatial relationship
between the first group cited in the name and
the hydroxyl group
The system of E-Z nomenclature has also been adopted
for oximes.
For fixing priority the lone pair of the electrons on
nitrogen is taken as group of lowest priority.
E-Methylphenylketoxime
CH3H5C6
C
N
OH
(2)
(2)
(1)
(1) HO
N
C
CH3H5C6(1)
(1)
(2)
(2)
E-Acetaldoxime
OH
N
C
H3C H H3C H
C
N
HO
Z-Methylphenylketoxime
Z-Acetaldoxime
Chiral Carbons
Carbons with four different groups attached
are chiral.
It’s mirror image will be a different compound
(enantiomer).
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Achiral Compounds
Take this mirror image and try to
superimpose it on the one to the left matching
all the atoms. Everything will match.
When the images can be superimposed the
compound is achiral.
Chirality - optical activity: discovery
French chemist Louis Pasteur (1848) discovered thatcrystalline optically inactive sodium ammoniumtartarate was a mixture of two types of crystalswhich were mirror images of each other.
Each type of crystals when dissolved in water wasoptically active. The specific rotations of the twosolutions were exactly equal, but of opposite sign.
In all other properties, the two substances were identical.
As the rotation differs for the two samples in solution inwhich shapes of crystals disappear, Pasteur proposedthat like the two sets of crystals, the molecules makingup the crystals were themselves mirror - images of eachother and the difference in rotation was due to 'moleculardissymmetry'
Chirality
An object which cannot be superimposed on its mirror-
image is said to be chrial [Greek : Cheir 'Handedness']
and the property of non-superimposability is called
chirality. Thus our hands are chiral.
The presence of a chirality centre usually leads to
molecular chirality. Such a molecule has no plane of
symmetry and exists as a pair of enantiomers. Such a
carbon atom is sometimes also referred to as asymmetric
carbon atom.
Asymmetric Carbons
The most common feature that leads to chirality
in organic compounds is the presence of an
asymmetric (or chiral) carbon atom. (A carbon
atom that is bonded to four different groups)
no asymmetric C usually achiral
1 asymmetric C always chiral
> 2 asymmetric C may or may not be chiral
In general:
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C
OH
H CH3
C2H5 C
OH
HH3C
C2H5
Mirror images of each other
Non-superimposable with each other
Enantiomers
(+) or (-)butan-2-ol
Enantiomers Enantiomers: stereoisomers that are non-
superimposible mirror images
The direction of optical rotation cannot be
predicted from the structural formulae.
It can only be determined experimentally.
Fischer mirror images
Easy to draw, easy to find enantiomers
Enantiomers
CH3
CH3
Cl
H
H
Cl
CH3
CH3
H
Cl
Cl
H
Properties of enantiomers
Same boiling point, melting point, and density.
Same refractive index.
Rotate the plane of polarized light in the samemagnitude, but in opposite directions.
Different interaction with other chiral molecules:
Active site of enzymes is selective for a specificenantiomer.
Taste buds and scent receptors are also chiral.Enantiomers may have different smells.
Stereochemistry
The properties of many drugs depends on
their stereochemistry:
(R)-ketamineanesthetic hallucinogen
(S)-ketamine
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Resolution of enantiomers
The process of separating enantiomers is
called resolution.
Since enantiomers have identical physical
properties, they cannot be separated by
conventional methods.
- Distillation and recrystallization fail.
Methods of resolution:
1. Mechanical separation
2. Preferential crystallization
3. Resolution through the formation of diastereomers: chemical method
4. Biochemical method
5. chromatographic method
Enantiomers, racemic
C(+)C(+) C(-)C(-)
2P(+)2P(+)
C(+)P(+)C(+)P(+) C(-)P(+)C(-)P(+)
Separate diastereomers
C(+)P(+)C(+)P(+)
C(-)P(+)C(-)P(+)
P(+)P(+)
P(+)P(+)
C(+)C(+)
C(-)C(-)
Resolution of enantiomers (chemical method)
pure
pure
Add pure
enantiomer
()Tartaric acid(racemic mixture)
+ (-)cinchonidine(resolving agent)
(+)tartaric acid (-)cinchonidine
(-)tartaric acid (-)cinchonidine+ Diastereomers
(separable)
dil. H2SO4
(+)tartaric acid(crystalize out)
dil. H2SO4
(-)tartaric acid(crystalize out)
Biochemical Method
Microorganisms or enzymes are highly stereoselective.
(+)-Glucose plays an important role in animalmetabolism and fermentation, but (-)-glucose is notmetabolized by animals, and furthermore cannot befermented by yeasts.
Penicillium glaucum, consumes only the (+)-enantiomerwhen fed with a mixture of equal quantities of (+)-and(-)-tartaric acids.
Hormonal activity of (-)-adrenaline is many times morethan that of its enantiomer.
Limitations:
(i) These reactions are to be carried out in dilute solutions, soisolation of products becomes difficult.
(ii) There is loss of one enantiomer which is consumed by themicroorganism. Hence only half of the compound is isolated(partially destructive method).
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Chiral biological macromolecules
Proteins
Enzimes
Structural elements of membrances
Receptors
Carbohydrates
Nucleic acids
Chiral ‘building blocks’ of L-amino acids
and D-carbohydrates
Biological discrimination of enantiomers
Enantiomers can be distinguished through the use of
chiral probes. A polarimeter is one example of a chiral
probe.
Enzymes are a type of chiral probe that are found in
living systems.
In general, enantiomers do not interact identical with
other chiral molecules
Enzymes are chiral, and are capable of distinguishing
between enantiomers
Either one has no effect or has a totally different
Usually, only one enantiomers of a pair fits properly into
the active site of an enzyme
Biological significance of chirality
A schematic diagram of an enzyme surface capable of binding with
(R)-glyceraldehyde but not with (S)-glyceraldehyde.
Since most of the natural (biological) environment consists ofenantiomeric molecules (amino acids, nucleosides,carbohydrates and phospholipids are chiral molecules), thenenantiomers will display different properties. Then, in our body:
This enantiomer of glyceraldehyde fits the three
specific binding sites on the enzyme surface.
This enantiomer of glyceraldehyde
does not fit the same binding sites.
R-glyceraldehyde S-glyceraldehyde
Discrimination of enantiomers
Enzymes are
capable of
distinguishing
between
stereoisomers
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Expressed mathematically:
enantiomeric excess = % of major enantiomer - % of
minor enantiomer.
Enantiomeric excess (ee): The excess of one
enantiomer over the other in a mixture of enantiomers.
Example: A mixture composed of
86% R enantiomer
14% S enantiomer
ee of the mixture = 86% - 14% = 72%
X 100e.e =d-l
d+l
X 100=(excess of one over the other)
(entire mixture)
Optical Purity : The optical purity is a measure of
enantiomeric purity of a compound and is given in terms
of its enantiomeric excess (ee). Optical purity is
expressed as a percentage.
A pure enantiomer would have an optical purity and
enantiomeric excess of 100%.
A fully racemised compound has 0% optical purity.
If the enantiomeric excess is 90%, means 90% pure
enantiomer, remaining 10% contains equal amounts
of each enantiomer (i.e. 5% + 5%).
Enantiomeric excess of a mixture of enantiomers is
numerically equal to its optical purity.
Optical Purity
Optical Purity
Optical purity (o.p.) is sometimes called
enantiomeric excess (e.e.).
One enantiomer is present in greater amounts.
X 100o.p. = rotation of pure enantiomer
observed rotation
Problem: The specific rotation of (S)-2-iodobutane is
+15.90. Determine the % composition of a mixture of (R)-
and (S)-2-iodobutane if the specific rotation of the mixture
is -3.18.
= 20%X 100o.p. =3.18
15.90
l = ee + (100-20)/2 = 60%
d = (100-20)/2 = 40%
Enantiomeric Excess (e.e.)
Problem : When optically pure (R)-(-)-2-bromobutane is heated
with water, 2-butanol is the product. Twice as much (S)-2-
butanol forms as (R)-2-butanol. Find the e.e. and the observed
rotation of the product. [α]=13.50° for pure (S)-2-butanol.
Let consider x = amount of (R) enantiomer formed
= 33% 100=2x-x
2x+x 100e.e =
| d-l |
d+l 100=x
3x
100o.p. = rotation of pure enantiomer
observed rotation
We know, e.e. = o.p.
100observed rotaion =
33 13.50= 4.5
2x = amount of (S) enantiomer formed
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Conformational mobility of cyclohexane
Chair conformations readily interconvert, resulting
in the exchange of axial and equatorial positions by
a ring-flip
Substituted cyclohexanes
The planar diagram predicts achiral and
optically inactive.
But we know the structure is not planar.
Chirality of conformationally mobile systems
(1S,2R)
Br Br
Cis-1,2-dibromocyclohexane
Chirality of conformationally mobile systems
This is a chiral structure and would be expected to be
optically active
cis-1,2-dibromocyclohexane
Consider the chair interconversion….
Br
Br
Br
Br
Chirality of conformationally mobile systems
Br
Br
Br
Br
cis-1,2-dibromocyclohexane
The two chair forms are enantiomers but not isolatable
Two structures have the same energy. Rapid
interconversion. 50:50 mixture. Racemic mixture.
optically inactive.
Planar structure predicted correctly
SR(ax,eq) SR(eq,ax)
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No mirror planes. Predicted to
be chiral, optically active.
Each structure is chiral. Not mirror images! Not the
same! Present in different amounts. Optically active
R,R (eq.eq) R,R (ax,ax)
Trans 1,2 dibromocyclohexane
(1S,2S)
Br Br
trans-1,2-dibromocyclohexane
Br
Br
Br
Br
Mobile conformers
If equilibrium exists between two chiral
conformers, the molecule is not chiral.
Judge chirality by looking at the most
symmetrical conformer.
Cyclohexane can be considered to be planar,
on average.
Subs. Cis Trans
1,2-X2
eq,ax ax,eq
interconverting
enantiomers
eq,eq ax,ax
isolable enantiomers
two conformations each
1,2-XY
eq,ax ax,eq
isolable enantiomers
two conformations each
eq,eq ax,ax
isolable enantiomers
two conformations each
1,3-X2
eq,eq ax,ax
meso compound
two conformations
eq,ax ax,eq
isolable enantiomers
two conformations each
Nonmobile conformers
The planar conformation of the biphenyl derivative is too
sterically crowded. The compound has no rotation
around the central C—C bond and thus it is
conformationally locked.
The staggered conformations are chiral: They are
nonsuperimposable mirror images.
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The different spatial arrangements that a
molecule can adopt due to rotation about σ
bonds are called conformations and hence
conformational isomers or conformers.
The study of the energy changes that occur
during these rotations is called conformational
analysis.
Conformational AnalysisStructure of ethane
Definitions
Gauche(staggered) - A low energy
conformation where the bonds on
adjacent atoms bisect each other
(60o dihedral angle), maximizing the
separation.
Eclipsed - A high energy
conformation where the bonds on
adjacent atoms are aligned with
each other (0o dihedral angle).
Definitions
Anti - Description given to two
substituents attached to adjacent
atoms when their bonds are at
180o with respect to each other.
Syn - Description given to two
substituents attached to adjacent
atoms when their bonds are at 0o
with respect to each other.
Syn
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Types of strain
Torsional strain- The potential
energy arises due to the repulsion
between pairs of bonds caused by
the electrostatic repulsion of the
electrons in the bonds. Groups
are eclipsed.
Steric strain- The potential
energy arises due to the
repulsion between the electron
clouds of atoms or groups.
Groups try to occupy some
common space.
Types of strain
Angle strain – The potential energy arises due to
distortion of a bond angle from it's optimum
value caused by the electrostatic repulsion of
the electrons in the bonds. e.g. cyclopropane
Rotational conformations of ethane
staggered, = 60
Sawhorse structures
Newman projections
eclipsed, = 0skew, = anything else
rotate rear
carbon 60
60o Rotation causes torsional or eclipsing strain
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Potential energy diagram of ethane
P.E
Dihedral angle
Ethane molecules have enough energy
to surmount this barrier, except at
extremely low temp. (−250 °C),
The Newman projection of propane
rotate rear
carbon 60
Propane conformations: larger barrier to rotation Butane conformations (C2-C3)
Gauche interaction in butane
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2 Different eclipsed conformations
Total : 16.0 kJ/mol
6.0 kJ/mol
6.0
kJ/m
ol
4.0
kJ/m
ol
4.0
kJ/m
ol
4.0
kJ/m
ol
4.0
kJ/m
ol
11.0 kJ/mol
Total : 19.0 kJ/mol
Strain energy can be quantified
Energy for interactions in alkane conformers
Potential energy diagram of butane
Dihedral angle between methyl groups
CyclopropaneAngle and Torsional Strain
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Newman projection of cyclopropane
All dihedral angles = 0o
Cyclobutane is not Planar Cyclopentane
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Chair conformation of cyclohexane
Viewed along the ‘seat’ bonds
Boat conformation of cyclohexane
axial up
eq. up
Axial methyl group is gauche to C3 in the ring
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Equatorial methyl group is anti to C3 in the ring
cis 1,3-dimethylcyclohexane
trans 1,3-dimethylcyclohexane
trans 1,3-dimethylcyclohexane
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cis 1-Chloro-4-t-butylcyclohexane
Cyclohexane conformationsMethods for determining conformations
A number of methods have been used to
determine configuration;
X-ray and electron diffraction, IR, Raman, UV,
NMR spectra, photoelectron spectroscopy,
Optical Rotatory Dispersion (ORD) and
Circular Dichroism (CD) measurements.
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Polarimeter
Clockwise
Dextrorotatory (+)
Counterclockwise
Levorotatory (-)
Not related to (R) and (S)
Polarimeter: Device that measures the optical
rotation of the optically active substance
Specific Rotation []D
= observed rotation
c = concentration ( g/mL )
l = length of cell ( dm )
D = yellow light from sodium lamp (5893 Å)
t = temperature ( Celsius )
Specific rotation calculated
in this way is a physical
property of an optically active substance.
You always get the same value of
It is defined as the number of degrees of rotation
caused by a solution of 1.0 g of compound per ml of
solution taken in a polarimeter tube 1.0 dm (10 cm)
long at a specific temperature and wavelength.
The specific rotation is calculated from
observed angle of rotation, as below:
Optical rotation: the rotation of linearly
polarized light by the sample
Optical Rotatory Dispersion (ORD): the
variation of optical rotation as a function of
wavelength. The spectrum of optical rotation.
Circular Dichroism (CD): the difference in
absorption of left and right circularly light.
Chiral structure can be distinguished and
characterized by polarized light
Dichroism is used to denote direction-dependent
light absorption.
Circular Dichroism (CD) The production of an
elliptically polarized wave when a linearly polarized
light wave passes through a substance that has
differences in the extinction coefficients for left- and
right-handed polarized light.
Birefringence refers to the direction-dependent
index of refraction
Circular birefringence A phenomenon in which
there is a difference between the refractive indices
of the molecules of a substance for right and left-
circularly polarized light
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Optical rotation
When a plane polarized light (PPL) is passed
through optically active compound due to it’s
circular birefringence results in unequal rate of
propagation of left and right circularly
polarized rays.
This unequal rate of propagation of both left
and right circularly polarized light deviates the
PPL from it’s original direction and it is called
as optical rotation
Optical rotation caused by compound changed
with wavelength of light was first noted by Biot
in 1817.
Light and Polarization
Light can be represented as a transverse electromagnetic
wave made up of mutually perpendicular, fluctuating
electric and magnetic fields. The left side of the following
diagram shows the electric field in the xy plane, the
magnetic field in the xz plane and the propagation of the
wave in the x direction. The right half shows a line tracing
out the electric field vector as it propagates. Traditionally,
only the electric field vector is dealt with because the
magnetic field component is essentially the same.
Polarized Light
Consider two light waves, one polarized in the YZ plane and the
other in the XY plane. If the waves reach their maximum and minimum points at the same
time (they are in phase), their vector sum leads to one wave,
linearly polarized at 45 degrees.
Similarly, if the two waves are 180 degrees out of phase, the resultant
is linearly polarized at 45 degrees in the opposite sense.
If the two waves are 90 degrees out of phase (one is at an
extremum and the other is at zero), the resulting wave is circularly
polarized.
In effect, the resultant electric field vector from the sum of the
components rotates around the origin as the wave propagates.
The following diagram shows the sum of the electric field vectors for
two such waves.
The most general case is when the phase difference is at an
arbitrary angle (not necessarily 90 or 180 degrees.) This is called
elliptical polarization because the electric field vector traces out anellipse (instead of a line or circle as before.)
These concepts can be rather abstract the first time they are
presented. The following simulation allows the user to change thephase shift to an arbitrary value to observe the resultant polarization
state.
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The basics of polarisation
To really understand circular dichroism, one must first
understand the basics of polarisation.
Linearly polarised light is light whose oscillations are
confined to a single plane.
All polarised light states can be described as a sum of two
linearly polarised states at right angles to each other, usually
referenced to the viewer as vertically and horizontally
polarised light. This is shown in the animations below.
Vertically Polarised Light Horizontally Polarised Light
If we take horizontally and vertically polarised light
waves of equal amplitude that are in phase with each
other, the resultant light wave (blue) is linearly polarised
at 45 degrees, as shown in the animation below:
45 Degree Polarised Light
If the two polarization states are out of phase, the resultant
wave ceases to be linearly polarized. For example, if one of
the polarized states is out of phase with the other by a
quarter-wave, the resultant will be a helix and is known as
circularly polarized light (CPL).
The helices can be either right-handed (R-CPL) or left-
handed (L-CPL) and are non-superimposable mirror images.
The optical element that converts between linearly polarized
light and circularly polarized light is termed a quarter-wave
plate. A quarter-wave plate is birefringent, i.e. the refractive
indices seen by horizontally and vertically polarised light are
different.
A suitably oriented plate will convert linearly polarized light
into circularly polarized light by slowing one of the linear
components of the beam with respect to the other so that
they are one quarter-wave out of phase. This will produce a
beam of either left- or right-CPL.
Left Circularly Polarised (LCP) Light
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Right Circularly Polarised (RCP) Light
The difference in absorbance of left-hand and right-
hand circularly polarised light is the basis of circular
dichroism. A molecule that absorbs LCP and RCP
differently is optically active, or chiral.
When a ray of monochromatic polarized light
strikes a solution, several phenomenon’s occurs
like:
1. Reflection on the surface
2. Refraction
3. Rotation of plane polarization
4. Absorption
Enantiomers are optically active compounds.
Optically active molecules have different
refractive indices, and different extinction
coefficients for L and R circularly polarized
light.
Optical Rotatory dispersion (ORD)
ORD is defined as the rate of change of
specific rotation or rotatory power with change
in wavelength.
Light is an electromagnetic radiation and
consist of vibrating electric and magnetic
vector perpendicular to each other.
ORD curves in recent years are made use in
structural determination by comparing the
curve obtain from compound believed to have
related structures particularly applied to
carbonyl compounds.
E.g.. ORD curves have been used to locate
the position of carbonyl groups in steroid
molecules.
Rotatory dispersion curves (i.e. plot of optical
rotation against wavelength.) can be classified
into two main types.
1. Plain curves
2. Cotton effect curves.
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According to Fresnel, a plane polarized light may
be considered as the combination of two circularly
polarized light of which one is right circularly
polarized light (RCPL) & other is left circularly
polarized light (LCPL) which are in equal &
opposite in nature.
A circularly polarized light (CPL) is one whose
plane of polarization rotates continuously & in the
same sense around the axis of the polarization of
the wave & it may be described as right handed
screw or helix twisting around the direction of
propagation, where LCPL wave describe the left
handed screw.
Rotation of plane polarized light
(Fresnel’s explanation) -: The figure below represents how the electric vector of
RCPL (ER) & that of LCPL (EL) combined to give a
plane polarized wave (E)
E
El ER
RCPL + LCPL = PPL
Plane of polarization
The two circularly polarized light vibrate in
opposite direction with the same angular
velocity if refractive index is same
Zero resultant
The two circularly polarized light vibrate in
opposite direction with same angular velocity if
refractive index is same.
Variation of E as a resultant of two rotating vector EL and ER
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Specific rotation (Rotatory power):
It is the rotation produced by a solution in 10 cm
length tube having 1 gm of substance in 100 ml.
denoted by [ α ]
The specific rotation depends on following
factors:-
Nature of substance.
Length of the column.
Conc. of the sol.
Temp of the sol.
Nature of the solvent.
Wavelength of the light used.
The angle of rotation per unit path length is,
α = (nL – nR ) π / λ
Where,
λ = wavelength of incident light
n = refractive index
If RCPL travels faster α is positive & the
medium is dextrorotatory,
If LCPL travels faster then α is negative & the
medium is levorotatory.
The combination of circular dichroism and
circular birefringence is known as cotton
effect. Which may be studied by observing the
change of optical rotation with the wavelength
so called ORD.
It was discovered by a French physicist A.
COTTON.
The curves obtained by plotting optical rotation
v/s wavelength down to about 220nm using
photoelectric spectropolarimeters, known as
ORD curves or Cotton effects.
Cotton effect The absolute magnitude of the optical rotation
at first varies rapidly with , crosses zero at
absorption maxima and then again varies
rapidly with but in opposite direction, this is
known as Cotton effect and the curves
describing such effect is called Cotton effect
curves.
They are of two types:
1. Plain curves
2. Anomalous curves
(a) Single cotton effect curves
(b) Multiple cotton effect curves
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Plain curves (Normal smooth curves or single curves)
Cotton effect is not seen for compounds which absorbs
in far UV well below 220nm, because it occurs only
near absorption maximum.
The curves obtained do not contain any peak or
inflections and that the curve do not cross the zero
rotation line and devoid of maxima and minima within
the measurable range.
These curves on the other hand shows a
number of extreme peaks and troughs
depending on the number of absorbing groups
and therefore known as Anomalous dispersion
of optical rotation.
This type of curves is obtained for the
compounds which contain an asymmetric
carbon atom and also contain chromophore,
which absorb near the UV region.
Anomalous curves
These are anomalous dispersion curves which
shows maximum and minimum both of them
occurring in the region of maximum
absorption.
If in approaching the region of cotton effect
from the long wavelength, one passes first
through maximum (peak) and then a minimum
(trough), the cotton effect is said to be
positive.
Single cotton effect curves
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In this type of ORD curves two or more peaks
and troughs are obtained.
E.g. Ketosteroids, camphor etc.
Multiple cotton effect curves Circular dichroism (CD)
Chiral substances show differential absorption
of circularly polarized light which is called
Circular dichroism.
Measurement of how an optical active
compound absorbs right and left circularly
polarized light (ER and EL)
For CD the resultant transmitted light is not
plane polarized but elliptically polarized.
Circular dichroism
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Applications of CD
Determination of secondary structure of proteins that cannot be
crystallized
Investigation of the effect of e.g. drug binding on protein
secondary structure
Dynamic processes, e.g. protein folding
Studies of the effects of environment on protein structure
Secondary structure and super-secondary structure of
membrane proteins
Study of ligand-induced conformational changes
Carbohydrate conformation
Investigations of protein-protein and protein-nucleic acid
interactions
Folding recognition
Difference between ORD & CD
Graphs are obtained by
specific rotation vs
wavelength
Circularly polarized light Plane polarized light
Dispersive phenomena
Plane polarized is used
and is not converted to
elliptical light
Circular polarized is
used and is converted
to elliptical
Absorptive phenomena
Graphs are obtained
molar ellipicity vs
wavelength