Acidity and Basicity of Organic Molecules

functional groups

Atoms or groups of atoms responsible for the characteristic physical properties, interactions and reactions of a particular compound; define individual substructural features within the compound

chemotype

The type of drug based on a prominent chemical structure contained within it; defines the overall chemical or structural class(es) of a therapeutic agent

pharmacophore

Defines the structural elements necessary for pharmacological activity (i.e., potent and productive interaction with the target); usually includes a core structure with key functional groups

SAR (structure-activity relationship)

an evaluation of how changes in molecular structure correlate with changes in target activity; can relate to in vitro or in vivo activity

SPR (structure-property relationship)

Describes how changes in molecular structure correlate with changes in a physical property such as solubility or lipophilicity

SAR-BAFSPM

chemical determinants of drug action

bonding

acidity/basicity

functional groups

stereochemistry

polarity

metabolism

BAFSPM

water

drugs need to be _________-soluble to exert their actions

polarity

water solubility is driven by _____________, which is often influenced by acidity or basicity of a compound

pH

Drugs need to be soluble and stable across a broad ___________ range in order to be absorbed, and to reach their site of action

lipophilicity

helps drugs passively diffuse across membranes; drug is more likely to cross a membrane by passive diffusion than by active transport

polarity

functionality that imparts ______________ also increases risk of arrhythmias from a cardiac potassium channel

lipophilicity

functionality that imparts ______________ also increases risk of drug getting pumped out of the same compartment you want it to be in

bronsted acid

molecule that wants to donate a proton

bronsted base

molecule that wants to accept a proton

lewis acid

molecule that wants to accept electrons

lewis base

molecule that wants to donate electrons

strong acids

completely disssociate

strong bases

completely accept a proton

Ka

ratio of ionized to neutral form of compound

basic

the smaller the Ka, the more _________ the species

acidic

the larger the Ka, the more __________ the species

basic

the larger the pKa, the more _________ the species

acidic

the smaller the pKa, the more _________ the species

neutral

quaternary ammonium is a ____________ functional group

henderson-hasselbalch equation

can be used to determine the % ionization at a particular pH

acidic

the conjugate base is more polar for __________ drugs

basic

the conjugate acid is more polar for __________ drugs

less

the _______ ionizable a drug, the more GI absorption

equilibrium, counteracts

Le Chatlier's Principle:

when any system at equilibrium for a long period of time is subjected to a change in concentration, temperature, volume, or pressure:

1) the system changes to a new _____________

2) the system partially _____________ the applied change