pharmacokinetics - IMFs Flashcards
(12 cards)
outline the importance of ionic/electrostatic interactions in drug development
these are the strongest of the intermolecular bonds and therefore are initially the most important as a drug enters the binding site
ionic/electrostatic bond definition
a type of intermolecular interaction that takes place between oppositely charged groups
how is strength of ionic interactions related to distance?
inversely proportional - as distance increases strength decreases, however it drops off less rapidly than most other IMFs
hydrogen bond definition
a type of intermolecular interaction between electron deficient Hs and electron rich heteroatoms (N, O, F) - the electron deficient H is often attached to a very electronegative heteroatom
why does positioning matter more for hydrogen bonds than ionic interactions?
hydrogen bonds involve orbitals and are directional, there is an optimum orientation
(optimum X-H—Y bond angle = 180)
outline the importance of van der waals interactions in drug development
these are weak interactions but at short distances and in large numbers they can be very strong, this is the main type of IMF displayed between organic hydrophobic regions - crucial when drug is already inside binding site to strengthen + improve binding
van der waals forces definition
a type of intermolecular interaction which occurs between hydrophobic groups when transient areas of high and low electron density cause temporary dipoles which interact
how is strength of van der waals related to distance?
strength drops off very quickly as distance increases
what is a desolvation penalty?
polar regions of a drug + its target are solvated prior to interaction, due to aqueous environment - in order for the two to interact, they must both be desolvated, the energy cost for this process = desolvation penalty
why are polar regions solvated in aqueous environments?
this is stabilising, so reaction is spontaneous, releases energy
why is binding of hydrophobic regions of the drug and its target more favourable than for polar regions?
hydrophobic groups cannot interact with water, meaning no desolvation penalty, however instead water molecules form an ordered later next to these regions, essentially interacting with itself more since it cannot interact with the drug/receptor, this decreases entropy
when hydrophobic regions of the drug + target interact this frees up the ordered water molecules, resulting in entropy increase, so it is beneficial to binding energy
why is a fine balance necessary when considering IMFs and binding of drug and target?
binding interactions must be strong enough to hold the substrate/drug sufficiently for the reaction to occur but also weak enough to allow it to leave after
- designing a drug with stronger binding interactions results in active site being blocked, good for inhibitors
