Medchem Exam 2

salts can be used to _______ lipid and water solubility

increase

an acid reacting with a base results in a?

salt (chemical reaction)

what makes a salt different from an ionized acid/base?

salts contain a counter-ion (Cl-)

what are the two types of salts?

1. inorganic

2. organic

what are inorganic salts?

counter-ion is not carbon based

what are organic salts?

counter-ion is carbon based

what are cationic salts?

counter-ion is a cation

cationic salts are commonly produced using?

NaOH, KOH, CaOH

if the counter ion is positive, the drug must be __________

negative (acidic)

what are anionic salts?

counter-ion is an anion

how are anionic salts commonly produced?

HCl, HBr, H2SO4, H3PO4

if the counter ion is negative, the drug must be ____________

positive (basic)

what is the main advantage of inorganic salt formation?

- increased water solubility

- enhances solvation + dissolution of solid drug in water

increased water solubility of inorganic salt formation requires an _____________?

equilibrium between ionized + unionized species

--> takes time

---> not 100%

can inorganic salts enhance lipid solubility?

No

what are the uses of organic salts?

enhance water solubility OR lipid solubility

how are water soluble organic salts commonly produced?

using sugars, sugar analogs, + biosynthetic intermediates (lactate, malate, citrate, etc.)

water soluble salts contain numerous _________ groups capable of H-bonding with water

polar

Why use organic water soluble salts if inorganic salts are available?

• sometimes organic salt formulations are better suited to a particular route of administration

• basic solutions can cause stinging + burning

what routes of administration are inorganic salts not optimal for?

IV and opthalmic

what routes of administration are inorganic salts more optimal for?

oral

what are lipid soluble organic salts used to form?

lipid soluble suspensions (administered via IM depot injections)

lipid soluble organic salts contain substantial _______ _________ that act to enhance lipid solubility

nonpolar hydrocarbons

what drug is a lipid soluble salt that is formulated for IM injection?

Pen G Benzathine

acidic drugs mixed with basic drugs results in __________

drug-drug interactions

--> will form a salt

--> precipitation in an IV can cause serious harm to the patient

Heparin (administered via IV as acidic sodium salt) can never be administered in the same IV line as basic drugs such as _________ and __________

Diazepam and Haloperidol

what type of drug is Atropine Sulfate?

basic

what type of drug is Leucovorin Calcium?

acidic

basic drugs are cations in salt form and thus have ________ counter-ions

anionic

acidic drugs are anions in salt form and thus have ________ counter-ions

cation

what type of drug is Ketorolac tromethamine?

acidic

what type of drug is Erythromycin Stearate?

basic

what are the ways to determine a drug's solubility in either water or lipid?

1. physically measured in a lab experiment (better)

2. estimate how the drug will behave

describe what is needed to physically determine a compound's stability:

1. a separatory funnel + 2 beakers

2. two solvents: water (polar phase) + n-octanol (non-polar phase)

3. the test compound

4. a way of measuring the amount if compound in solution

what does n-octanal closely mimic?

biological membranes (ie phospholipids)

describe the experimental procedure for physically determining a compound's stability:

• add a test compound to a mixture of n-octanol + water

• equilibrate (shake + allow phases to separate)

• drain each phase into a beaker

• determine the concentration of test compound in each phase

What is the partition coefficient (P)?

the ratio of a drugs concentration found in the n-octanol layer to the concentration found in the water layer

what is the formula for the partition coefficient (P)?

charged functional groups (acids + bases) will have the strongest interaction with _________

water

functional groups that are polar but will not H-bond will have properties in between ________ and _________

aqueous and lipid loving

functional groups that are non-polar (such as alkyl groups) will interact well with a _________ environment

lipid/fatty

for an alcohol group, if there are 3 or less carbons per alcohol group, the molecule will be ____________

water-soluble

butyl alcohol, which has 4 carbons is __________

marginally water soluble

pentanol is _______________ due to the 5 carbons it possesses

not water soluble

do you count the carbonyl carbon for the functional groups that have one?

no

# carbons solubilized < actual # carbons

not water soluble

# carbons solubilized > actual # carbons

water soluble

# carbons solubilized = actual # carbons

boderline

what are isomers?

- same formula, different arrangements

- produce different constitutions

what are stereoisomers?

- same atoms, same arrangement

- different placement in 3D space (bold+wedge)

what are the two types of stereoisomers?

geometric isomers and optical isomers

what are geometric stereoisomers?

- different shapes

- different compounds

- different chemical + biological properties

what are cis isomers?

isomers have at least one of the same functional group on the same side

what are trans isomers?

isomers have at least one of the same functional group on opposite sides

maleic acid is the _______ isomer

cis

fumaric acid is the ____ isomer

trans

why is trans-diethylstilbesterol the more active isomer?

because it mimics the natural compound better... not because of sterics

What is a Z isomer?

- an isomer where the functional groups are on the same side

- different R groups

- ZAME

what are E isomers?

- Molecules where the highest priority groups are on opposite sides

- different R groups

what are enantiomers?

- exact opposite

- mirror images

chiral is _____

unsymmetrical

--> cannot contain a mirror plane

achiral is ______

symmetrical

enantiomers have _______ chemical + physical properties

identical

what are the two things enantiomers differ in?

1. the direction they rotate polarized light

2. how they interact with other chiral compounds

each enantiomer will rotate polarized light equally but in _________

opposite directions

What is a racemic mixture?

50/50 mixture of two enantiomers

Do racemic mixtures rotate plane-polarized light?

No

once a racemic mixture has formed, can it be separated by normal means? why?

no bc enantiomers have identical physical + chemical properties

how to calculate the number of isomers?

2^n

n = # of stereocenters

RR --> SS

enantiomers

RS --> SS

diastereomers

any molecule that has a non-identical mirror image is _______

chiral

why is this molecule achiral even though it has two stereocenters?

it contains a mirror plane

R stereocenter

clockwise

S stereocenter

counterclockwise

in an achiral environment enantiomers...

have identical chemical + physical properties

are receptors and enzymes chiral or achiral?

chiral

How is ephedrine related to psuedoephrine?

they are diastereomers

what is a eutomer?

better fitting enantiomer, higher potency/affinity

what is a distomer?

the lower affinity (lower potency) enantiomer

why is there a push for producing single enantiomer drugs?

decrease side effects

what is a disadvantage for producing single enantiomer drugs?

a lot more expensive to make

What is the eudismic ratio (ER)?

represents how much better the eutomer is compared to the distomer

what does ER = 1 mean?

both eutomer and distomer contribute equally to the side effect

when the drug is based on the structure of an amino acid, the "___" enantiomer will be the more potent form

S

Amino acids are the "___" enantiomers in mammals

S

what does "es-" in front a drug's generic name mean?

it is the "S" enantiomer

what enables the drug to bind to the receptor with potency and specificity?

intermolecular forces

what is the ∆G value for covalent bonds?

very strong interaction: ∆G = -40 to -100 kcal/mole

covalent bonds are

irreversible (unless broken or reversed)

what is a bad example of covalent bond?

mercurials

--> reverse this reaction by breaking the covalent bond by giving the Hg+ a thiol SH to bond to

what are examples of good covalent bonds?

1. enzyme inactivators

2. alkylating agents

what are ionic interactions (aka salt bridges)?

opposite charges attract each other

What is Coulomb's Law?

q = charge on group

r = distance

D = dielectric constant

what is the ∆G for ionic interactions?

-5 to -10 kcal/mol

where do we find these charges on our drugs? (ionic interactions)

ionized acidic and basic functional groups + quartenary amines

where do we find these charges on targets? (ionic interactions)

acidic and basic amino acids in proteins + phosphate backbone in nucleic acids

what are the acidic targets? (ionic interactions)

- Asp

- Glu

- Tyr

- Cys

what are the basic targets? (ionic interactions)

- Lys

- Arg

- His

what charge will acidic targets have?

negative = anionic