Download Drug Action (D8) - Dr. More Chemistry

Drug Action (D )
8
Pages 425-427
1) Definitions
2) Geometrical Isomerism
3) Chirality
4) Beta-lactam ring (Penicillin)
5) Heroin
Definitions

Isomerism:


The existence of two or more molecules having
the same molecular formula, but with different
bonding arrangements of atoms, or different
orientation of their atoms in space
Stereo-isomerism:


Isomerism arising from differences in the shapes
of molecules (includes geometric and optical
isomerism)
Same molecular and structural formulas, but
different arrangement of the atoms in space
Definitions: Types of Stereo-Isomerism

Geometric Isomerism:



Occurs in alkenes (double bond: CNH2N) when there is
restricted rotation around the C-C double bond.
It can also occur in ring system where there is restricted
rotation about a C-C single bond
Optical Isomerism:


Typically occurs when a molecule has no plane of
symmetry and can exist in left and right-handed, nonsuper imposable, mirror images.
The molecule must possess a chiral center (asymmetric)


Chiral: the carbon atom is attached to 4 or more
different atoms or functional groups
Optical isomers rotate plane-polarized light
Objective One:
Explain the importance of geometrical isomerism
in drug action

Physical Properties of Geometric Isomers




Different polarity (dipole movement changes)
Different boiling and melting points
Change in solubility
Chemical Properties of Geometric Isomers


Some properties are similar because the isomers
have identical functional groups attached.
But, can have different pharmacological effects

Due to cis (same side) vs. trans (opposite)
arrangements


Cis: 1,2-disubsituted alkenes with functional groups
or atoms which are on the same side of the molecule
Trans: 1,2-disbustituted alkenes with functional
groups or atoms on opposite sides of a double bond
Example: Cis vs. Trans

Pt(NH ) Cl
3


2
2
cis-isomer: cisplatin
 Anticaner, used in chemotherapy
trans-isomer:
 Chemotherapeutically inactive
cis: same side
NH3
H3N
Pt
Cl
Cl
trans: opposite side
NH3
Cl
Pt
NH3
Cl
Example: Cis vs. Trans (continued)

Cisplatin

DNA strand

NH3
Square planar molecule, heavy metal
complex
Can enter the nucleus of a cancerous
cell

G
Pt
H3N

Cl atoms are replaced by bonds with
guanine of the same DNA strand
Prevents replication, disrupts strand
G

Trans-isomer

Cl atoms are in the wrong position so
cannot form bond with guanine
Objective Two:
Discuss the importance of chirality in drug action

Enantiomers


Non-super imposable mirror images (optical isomers)
Differ in their optical activity (aka their ability to
rotate the plane of polarized light)



One isomer rotates the light clockwise
Other isomer rotates the light counterclockwise the
same amount (equal and opposite)
Example
H
C
H3C
H
C2H5
OH
mirror
C
H5C2
CH3
OH
Affect on Medicine

Racemic Mixtures



Equimolar mixtures of two enantiomers of the same
compound
Because the rotation of plane-polarized light is equal
but opposite ,the mixture is not optically active
Source of Drugs


Racemic mixtures not found in nature, so drugs from
natural sources (natural or semi-synthetic) are single
enantiomers
Synthesized drugs are usually racemic mixtures to
reduce costs

No refining costs
Racemic Mixtures in Medicine

Penicillin V (natural)


Ibuprofen (synthetic drug)



Synthetic enantiomer (not found in natural source) is
not pharmacologically active
First enantiomer=analgesic and anti-inflammatory
Other enantiomer=no effects
Thalidomide (synthetic drug)



Both enantiomers=active
First=relieve morning sickness
Second=deformities in limbs, birth defects
Objective Three:
Explain the importance of beta-lactam ring action
penicillin

Structure of Penicillin

3 structural groups:

R group, beta-lactam ring, carboxylic acid group
O
C
NH
S
CH3
R
N
R Group
O
beta-lactam
ring
C
OH
CH3
O
carboxylic acid
group
Beta-lactam ring

Heteroatomic, 4-membered:


1 Nitrogen, 3 Carbon
Square planar shape



Would prefer to be tetrahedral (has a nonbonding pair of electrons, nitrogen)
90 degree angle puts the ring under chemical
stress, increasing reactivity
Increased reactivity opens the ring
Open Ring

Can covalently bond to transpeptidase


Blocks the action of transpeptidase



Enzyme responsible for the synthesis of bacterial
cell walls
No bacterial growth is possible
Bacteria bursts with out the linkage between the
cell walls
Penicillin can fight infections!
Objective Four:
Explain the increased potency of diamorphine
(heroin) compared to morphine

Structural Differences




Heroin has same Carbon
skeleton
Two OH groups replaced by
CH3COO (ester)
Ester is less polar, more fat
soluble, than OH.
 More rapidly absorbed
into the nonpolar central
nervous system and
brain
Heroin



Semisyntehtic narcotic
More potent, stronger
painkiller
Highly addictive