Intermolecular interactions

Question 1

Electrostatic interactions

Answer 1

• Attraction between molecules that have opposite electronic charges
• Proteins have CO2- and NH3+ residues and these may be present at the binding sites to interact with drugs

Question 2

Ion-ion interactions

Answer 2

• Non-directional
• Effectively stronger in a hydrophobic environment than a polar environment due to competition by water
• Strength of interaction: F = k(q1q2/d^2) (q = charges, d = distances)

Question 3

Ion-dipole interactions

Answer 3

• Double bonded oxygen will have a partial negative charge compared to the carbon that it is bonded to which will have a partial positive charge
• Oxygen pulls elecrons density to itself as it is more electronegative than the carbon
• Favoured arrangement will be delta negative bonded to a positively charged molecule

Question 4

Dipole-dipole interactions

Answer 4

• Antiparallel dipoles are favoured where the dipoles are aligned in opposite directions
• Amide bonds have a long dipole, hydrogen is the least electronegative so you have a large dipole from the hydrogen to the oxygen

Question 5

Hydrogen bonds

Answer 5

• Electrostatic interaction between a polarised (delta positive) proton (H) with a nearby (delta negative) atom bearing a lone pair
• Hydrogen bond acceptor provides an electron pair
• Hydrogen bond donor provides the hydrogen

Question 6

Van der Waals / London dispersion interactions

Answer 6

• Any molecules that are close together will form these forces
• Starts will molecules that have no dipoles, then you’ll get an instantaneous dipole at some point due to the electrons floating around, this causes an induced dipole and an attractive interaction
• Weakest interaction
• More significant in non-polar (hydrophobic) environments

Question 7

Hydrophobic effect

Answer 7

• When a hydrophobic drug is placed into water, the structure of the water around the drug is more ordered and this leads to lower entropy and is not favoured
• Hydrophobic interaction between protein and drug is favoured by higher entropy, when the molecules come together the entropy of the water increases
• Enthalpy also increases when the protein and drug bind due to the new interactions
• Binding sites of proteins are usually hydrophobic in character
• Enthalpy gains may result from van der Waals bonding, displaced water
• Entropy gains may result from displaced water molecules

Question 8

Pi-pi stacking

Answer 8

• Aromatic systems are often observed sitting on top of each other (stacking)
• Benzene rings can sit on top of each other and do pi stacking
• Benzene rings are normally hydrophobic