Lecture 2 (Intro to MedChem) Flashcards
Free bases or acids are often ____
liquid (oils)
Are they better or worse than a salt?
WORSE
- less water soluble than ionized form
- difficult to measure (because they are hygroscopic)
- difficult to make into a dosage form
- less stable
Why do we want to make a salt out of the free acids/bases?
because they are easier/better to work with (see previous card) and are more stable
Drug absorption across biological membranes is better in the ______ state
unionized
T or F: good drugs have only either lipid or water solubility
FALSE
-most efficient drugs have some degree of water and lipid solubility
explain solubility
for a chemical to dissolve in a particular solvent the compound must be able to form attractive forces with the molecules of the solvent
it is possible to estimate the solubility properties of drug by examining its _____
structure
Can we alter the solubility of a drug?
explain the 3 ways
YES
-use acid or base to make the drug into a salt
OR
-add substituents that are very water soluble:
-adding groups that are H bond donors and acceptors
-adding groups that can ionize
OR
-changing dose form
Are dispersion forces strong or weak?
weak
Dispersion forces are called ??
london forces (wrongly called van der waals attraction)
Where do dispersion forces occur?
between induced and instantaneous formed dipoles
As molecule gets larger, dispersion forces get _____
larger
disperson forces increase as the total area for interaction between molecules increases
Why do larger molecules become liquids? (ex. butane, hexanes, and octane are liquids but methane, ethane, and propane are gases)
increasing size = increasing dispersion forces
also increasing weight is a factor
What is stronger: dispersion forces or dipole-dipole bonds?
dipole-dipole bonding
Where does a dipole-dipole bond occur?
happens between permanent dipoles
note** these are not formal charges (that would be an ionic rxn)
H-bonding is a special kind of ??
dipole-dipole bonding
H-bonding is _____ than ordinary dipole-dipole bonding
stronger
When does H-bonding happen?
-happens between atoms with highly electronegative atoms attached to H
H-bonding plays a big role in making things more ??
hydrophilic (water soluble)
Molecules with many H-bond donors and acceptors are more ____ soluble
water
What is the H-bond donor?
electronegative atom with an attached hydrogen
What is the H-bond acceptor?
electronegative atom with a FREE (not tied up in resonance) lone pair of electrons
Are S, Cl, and F, weak or strong H-bond acceptors?
weak
SH is NOT an H-bond ____
donator
Amide N is NOT an H-bond _____
acceptor (lone pair on amide N cannot accept H-bonding due to resonance)
Why are intermolecular H-bonds between drug molecules in solution very uncommon?
Because H2O molecules will out compete the other drug molecules
in order to form a H-bond between drug molecules, it would first have to break the H-bonds formed with water (and this would require energy)
Explain how intramolecular H-bonds form in water (Note** very different than intermolecular H-bonds which we just previously deduced were very uncommon in water)
Bc the H-bonding pair are always super close in proximity it is easier to form H-bonds
What is intramolecular H-bonds forming in water known as?
effect of local concentration
bc it is similar to having high concentrations of each other
How does having too many H-bonds affect absorption?
those H-bonds have to be broken in order to cross the lipid membrane
**this represents the idea of having a practical limit H-bonds
Breaking H-bonds with water (in order to cross membranes) is _____
unfavorable