Types of Bonds in Drug Receptor

Interaction
 Main Bonding types involved
• Covalent bonding
• Ionic bonding
• Van dar waals forces of interaction
• Electron transfer bonds
• Hydrophobic bonds
• Hydrogen Bonding
• Chelation
 Covalent Bonding
• How is covalent bonding formed?
• Common in organic chemistry (carbon compounds)
• Two atoms participating in bonding share an electron pair
• Covalent bonding is important in understanding the
structure of organic compounds
• Examples of drugs that interact with receptor using
covalent bonds include:
1. Beta lactam antibiotics e.g. penicillins
2. Alkylating anticancer agents
3. Organic phosphates used as insecticides.
 Ionic Bonds
• Drugs capable of ionizing at the receptor site will form ionic bonds
• In general, elements with electron configurations close to that of a noble gas
tend to lose or gain the requisite number of electrons necessary to achieve
the electron configuration of that noble gas.
• The electrostatic attraction between oppositely charged ions such as sodium
cation and chloride anion is called ionic bond. ( common in inorganic chem.)
• Ionic bonds formed between ions of opposite charge are quite strong ( in the
order of 5 Kcal per mol)
• Drugs containing amines, enolic acids and carboxylic acid groups will
generally form ionic bonds
• Example of drugs that undergo this type of bonding with receptor include
• Acetylcholine
• Narcotic analgesics e.g. morphine
• Nsaids e.g. mefenamic acid
• Adrenaline
• etc
 Van dar Waals Forces
• This forces are electrostatic in nature
• Occur between two non polar groups. One may
be the drug and the other the receptor
• Under ordinary conditions covalent bonds are in
a state of vibration. Due to bond vibrations
electron cloud displacement occurs.
• The electron cloud displaced more towards one
carbon acquires a delta negative charge and the
other acquires a delta positive charge.
• Diagram
• This internal vibrations induce temporary dipoles by
displacing the electron cloud. This phenomena is
most prevalent aromatic systems.
• The van dar waals forces are effective in very short
ranges but becomes significant when 2 molecules fit
so well that several pairs of such groups are involved
in bonding. When many such groups are involved,
the strength of that bonding approaches that of ionic
bonding.
• Such closeness is possible between drug and
receptor.
• F is inversely proportional to d7. d is the distance
 Electron Transfer Bonds
• If electron deficient systems and electron excess
systems are brought together, they attract. The
electron deficient system would be part of the drug
while the electron excess system would be part of the
receptor or vice-versa.
• This attraction constitute electron transfer bonds.
• Drugs with phenolic, amine or nitro groups may form
this type of bonding with the receptor. Adrenaline and
morphine interact with the receptor using this
bonding type.
 Hydrophobic Bonds
• Two molecules containing hydrophobic (water
hating) groups may be repelled towards each other
by the surrounding network of water molecules.
• This however not a classical bond.
• A good example is the narcotic analgesic morphine
where the hydrocarbon chain, protonated N and
aromatic ring participate in hydrophobic bonding
with hydrophobic cavity that forms part of the
receptor.
 H-Bonding
• Which atoms participate in H-bonding?
• H atom can form strong bonds linking O or sometimes N
• The h donating group is usually a hydroxyl or amino group. The
electronegative group is usually a carbonyl group. (draw)
• To form h bonds, the attracting atoms must be
1. At a particular distance of about 2.7 A
2. In the same plane

illustration
• This can be shown to be true in the case of quinine where h-bonding
is critical for antimalarial activity. When the orientation of the
groups does not favor h-bonding, no antimalarial activity is
observed.
• Structures for quinine and qinidine
• Hydrogen bonding also involved in the
receptor binding of acetylcholine and
adrenaline
• H bonding is also important in the plasma
binding of drugs and this prolongs their
duration of action ( bound drug not
pharmacological active and is not easily
cleared)
• H bonding also enhances solubility of drugs in
the body. Enables H bonding of drugs with
water molecules.
 Chelation
• This type of bonding is illustrated by chelating
agents e.g. dimercaprol, cysteamine, 8-
hydroxyquinoline, EDTA etc.
• Dimercaprol is used as an antidote for heavy
metal poisoning e.g. mercury, arsenic, antimony
• It forms a chelate with this heavy metals thus
masking their toxic nature.
• The hydroxy group renders the chelate/complex
highly water soluble thus is excreted readily.
• Cysteamine is used to protect against
radiation injury. In radiation injury, iron and
copper are released from bone marrow, liver,
adrenal glands, muscles and kidneys.
(fukushima japan)
• These ions Fe2+ and Cu2+ catalyse destructive
oxidative chain reactions that are responsible
for radiation injury.
• Cysteamine mops up any ions released by
radiation thus rendering them harmless.