Understand the behavior of mirror-image molecules. Behavior depends on the environment (chiral/achiral) to which the molecule is exposed. When both the players (the target and the drug molecule) are chiral, there is a need for chiral perspective.

1. Valliappan Kannappan
Valliappan Kannappan
VALLIAPPAN K
Professor of Quality Assurance (Retd.)
Department of Pharmacy
Annamalai University
INDIA
Behaviour of chiral twins 2021
10 min.

2. Valliappan Kannappan
Valliappan Kannappan
Environment
Environment and Behavior
Behavior
 Behaviour of a chiral molecule depends on the
environment in which it is present or it is exposed to.
 Environment can be either chiral or achiral
 In an isotopic/achiral environment, enantiomers
exhibit identical physicochemical properties, and
B
E
H
A
V
I
O
U
R
Behaviour of chiral twins 2021
exhibit identical physicochemical properties, and
therefore are indistinguishable under these
conditions.
 Differences between chiral twins (biomolecules) are
hard to detect normally, but becomes pronounced
in a chiral environment”.

3. Valliappan Kannappan
Valliappan Kannappan
Chiral Twins
Chiral Twins
OH
O
H
CH3
HO
O
H
H3C
(R) (S)
Ibuprofen, is normally assayed by Alkalimetry / HPLC-
ODS Column; the environment is Achiral.
B
E
H
A
V
I
O
U
R
Chiral center
Chiral center
Behaviour of chiral twins 2021
In both the cases (Alkalimetry/ HPLC – ODS column) the environment is achiral;
hence one will not be able to quantify each enantiomers of the chiral drug; to
measure enantiomers of a chiral twin one need to perform the assay in a chiral
environment, viz. chiral analysis.
Ibuprofen - Chiral twins
mirror

4. Valliappan Kannappan
Valliappan Kannappan
Chirality and Biological Action
Chirality and Biological Action
Interestingly,
Bio-logical systems and human body at molecular level are
intensely chiral environments being composed of homochiral
homochiral
biopolymers) and can discriminate / differentiate left handed
molecules from the right handed molecules.
B
E
H
A
V
I
O
U
R
Behaviour of chiral twins 2021
Limonene is a molecule with single chiral/stereogenic center; and
can exist as a pair of enantiomers; R-Limonene and S-Limonene.
Olfactory receptors can differentiate these chiral twins; R-form has
smells Orange where as the mirror-image form (S- form) exhibits
Lemon smell; the molecule and the bio-environment both are
chiral.

5. Valliappan Kannappan
Valliappan Kannappan
O
D
O
U
R
P
E
R
C
E
P
T
limonene
The nose knows!
Behaviour of chiral twins 2021
(R
(R)
)-
-(+)
(+)-
-Limonene
Limonene
(S)
(S)-
-(
(-
-)
)-
-Limonene
Limonene
T
I
O
N
limonene
mirrored - configuration

6. Valliappan Kannappan
Valliappan Kannappan
Biological targets are chiral and so are the
Behaviour of chiral twins 2021
Biological targets are chiral and so are the
molecules (drugs) that interact with them
Source: Christopher Welch, Chiral India, 2016.
Hence there is need for chiral / mirror-image perspective

7. Valliappan Kannappan
Valliappan Kannappan
Thanks for you time
Thanks for you time
Behaviour of chiral twins 2021
valliappan
valliappan
Chirally Yours
Chirally Yours