2. “ Chemistry that studies properties of
stereoisomers”
Or
“The way in which drug is oriented in space”
Physiological properties of a drug are governed
to a great extent by it stereochemistry.
Even optical isomers of a drug can have
different physiological effect.
3. Isomers that have same molecular formula
and connectivity but differ in a way that
atoms are oriented in space – i.e; Difference
between isomers lies only in 3 D
arrangements of atoms .
6. “Optical isomerism of drugs is very common ,
many drugs molecules only contain one or
two chiral centers”
7. Chirality is define as
“ When a compound has no
symmetry ab0ut a particular carbon atom ,
the carbon is said to be as chiral carbon “
8. Chiral center arises when a carbon atom has
four structurally different groups attach to it.
When a compound contain one or more
chiral center it is able to rotate plane
polarized light to the right (+) or the left (-)
E.g; Adrenaline can exist as two enantiomers
that are mirror images of each others and
thus known as non-superimposable
9.
10. Adrenaline enantiomers have identical
,physical and chemical properties , the only
difference in their properties is that the
enantiomers rotate plane polarize light in
opposite direction , both enantiomers have
different biological properties
The negative enantiomer exert stronger
effect i.e; Heart rate increases
11. Device which is used to determine the
direction in which a molecule rotate plane
polarize light is polarimeter.
X-ray crystallography of adrenaline
enantiomers shown that negative form has R
configuration and the positive form has S
configuration
12. “ Isomers that differ in their spatial
arrangements about a double bond “
Relatively uncommon
Zimeldine antidepressant drug is example
of geometrical isomer
13. The mixture containing equals amount of
dextro and levo enantiomers of any drug
known as racemic mixture , this mixture will
not rotate plain polarize light
Physical separation of isomers in any mixture
as pure form is technically difficult.
Therefore , many of these drugs are used in
form of racemates. For instance , Synthetic
drugs where chiral centers are part of their
structure likeThallidomide
14. “Two compounds that are nonsuperimposable
mirror image of each other “
They have chiral carbon atom.
Have same physical properties.
Both can rotate PPL
15. d / l are used to donate (+) & (-) respectively .
D /L are used to donate (R) & ( S)
respectively.
16. Enantiomers are distinguish only when
placed in a chiral enviornment.
All methods of separation are based in this
principle
EE ( enantiomers excess)
EE% = 100% x ( Xa-Xb)
Where Xa & Xb correspond to mole fraction of
enantiomers
17. Where more than one chiral center is present
in a molecule there is the possibility of
diastereoenantiomers e.g; captoprill ,
labetalol
The number of diastereoisomers arising from
n chiral centered is 2n-1
18. Chromatographic methods : Labetalol two peaks
could be seen in chromatographic trace
The commercial drug is administer as a mixture of
four isomers
BP monograph for labetalol checks the ratio of two
chromatographic peaks produce by the two
enantiomeric pairs of diastereoisomers , in order to
saperate enantiomeric pair a chiral chromatographic
coloum would be required and separation on a chiral
coloum produces four peaks , an example a pair of
diastereoisomers used separately as drug is
betamethasone and dexamethsones
19. These terms refer to relative orientation of
two substituents .
For instance , In betamethasone Hydroxyl
group at 17 and methyl group 18 are trans (at
opposite side of ring )
In Dexamethasone Hydroxyl group 18 and
methyl group 17 are cis ( on the same side of
ring)
20. It is describe as quality control check oblige
parameter in the monograph ofTimolol
maleate ,Tobramycin and phenyl ephrine
HCL.
21.
22.
23.
24.
25.
26.
27. David G –Waston Physiochemical Aspects of
Drugs
Chemistry of chiral center
Organic Chemistry – B.S Bahl