PharmSci Lecture 1 Drug Properties/ functional groups

physicochemical properties

1. solubility in water/lipids

2. acid/base characteristics

3. conformation, configuration, structure

ADME

absorption, distribution, metabolism, excretion

pharmacodynamics vs pharmacokinetics

dynamics= study of drugs and their action on tissues and living organisms

kinetics= ADME of drugs

nonelectrolyte vs electrolyte

non= neutral, un ionized

electrolyte= ionic (weak acid or base)

what can make a hydrogen bond

EN atom (O,N,S,F) and polarized hydrogen

polarized hydrogen

H bound to EN atom

how many hydrogen bonds does S make

2

hydrocarbons

NONELECTROLYTE

Compounds composed of only carbon and hydrogen

-very FAT soluble

halogenated hydrocarbon

contain C, H, and halides

- FAT soluble

alcohols

NON ELECTROLYTE

R-OH

H bond donor AND acceptor

ethers

NON electrolyte

R-O-R

aldehyde

NON electrolyte

CHO

**no H bond donors since H isnt attached to EN atom

ketone

NON electrolyte

R-C=O-R

esters

NON electrolyte

formed by reacting OH with carboxylic acid

R-C=O

|

OR

Nitric Acid Esters

alcohol + nitric/nitrous acid

OH + HNO3 => C-ONO2

OH + HNO2 => C- ONO

NON electrolyte

Sulfuric Acid Ester

OH + H2SO4 -> C-OSO3H

NON electrolyte

lactone

NON electrolyte

Cyclic ester

O-C=O MUST be in ring

amide

NON electrolyte

N attached to carbonyl

primary, secondary, tertiary

lactam

cyclic amide

NON electrolyte

O=C-N must be in ring

lactone vs lactam

lactone- cyclic ester

lactam- cyclic amide

carbamate

carbonyl with OR and N

urea

carbonyl with 2 Ns

NON electrolyte

primary, secondary, tertiary

thiourea

urea but C=S, not C=O

NON electrolyte

Nitro

NO2-

NON electrolyte, but has slightly positive and slightly negative poles

Thioester

R-C(=O)-S-R

like ester, but has S, not O

NON electrolyte

disulfide

R-S-S-R

thiol ether

R-S-R

pKa is a measure of

the tendency to give up a proton (acid strength)

as pKa decreases, the ________ the acid

stronger (easier to give up H)

which is a weaker acid?

Acid A= pKA= 10

Acid B= pKa= 1

B-> pkA 10 is weaker

(higher pKa= weaker acid)

can pKa tell you if something is an acid or base?

no. it only tells you how strong of an acid something is

phenols

1. acids with pKa 8-10

aromatic OH

why is phenol an acid but an alcohol is not?

aromatic ring in phenols contributes to resonance making it more stable and able to give up a proton

carboxylic acids

1. acids with pKa 3-5

B-dicarbonyl compounds

1. Acids with pKa 3-5

* can be keto or enol form

is the acidic proton in B-dicarbonyl compounds an H bond donor?

no, it is not attached to an EN atom

keto-enol

aldehydes and ketones exist in both keto form (more common) and enol form (less common)

imide

1. acid with pKa 9-11

like B-dicarbonyl but NH not CH

acylurea

1. acid with pKa= 9-11

like an imide but carbonyl is attached to another N

sulfonamide

1. acid with pKA= 9-11

H on N is acidic

N-arylsulfonamide

sulfonamide attached to aromatic ring

stronger acid with pKa= 5-6

sulfonimide

more acidic than sulfonamide with pKa= 5-6

like sulfonamide but N attached to carbonyl

amino

BASE electrolyte group with pKa= 9-11

NH2

can be aliphatic or aromatic

acid form of amino group

NH3+

guanidino

BASE electrolyte group

pKa= 12

phosphoryl

acidic with

pKa1= 2-3

pKa2= 6-7

thiol

acid with pKa= 10

R-SH

what are heterocycles

A ring structure that contains at least one atom that is not carbon (heteroatoms)

epoxide

aziridine

(like epoxide but NH)

B-lactam

4 membered lactam ring

tetrahydrofuran

4 carbons and 1 O

furan

five-membered oxygen heterocyclic aromatic

pyrrole

five-membered nitrogen heterocyclic aromatic

thiophene

5 membered aromatic ring with sulfur

oxazole

5 membered, with O-C=N

isooxazole

5 membered with O-N=C

imidazole

thiazole

like azoles but S

1,2,3-triazole

1,2,4- triazole

tetrazole

pyridine

6 membered aromatic N

piperidine

like pyridine but NOT aromatic

pyrimidine

indole

purine

quinoline

pteridine

phenothiazine

acridine

Huckel's rule

If a compound has planar, monocyclic rings with 4n+2 pi electrons (n being any integer, including 0), it is by definition an aromatic compound.

pi electrons must be continuous

how do you know if an aromatic N ring has available lone pairs?

if there are 6pi electrons in ring then N's lone pair will not be used (ex: pyridine)

If there are 4pi electrons in ring then one of N's lone pairs will be used, therefore it cannot H bond (ex: pyrrole)

compounds that dissolve in water are termed ______

hydrophilic

can water dissolve polar or non polar molecules

polar (like dissolves like)

compound that do not dissolve in water are termed

hydrophobic

do hydrophobic or hydrophilic compounds cross membranes

hydrophobic

compounds that have a mix of hydrophobic and hydrophilic groups are called

amphipathic

are most drugs hydrophobic, hydrophilic, or both?

they are both-> amphipathic

water solubility is a competition between ________ interactions. explain

intermolecular interactions

= more interactions with water= more soluble (ex:salt)

= less interactions/ crystal packing= less soluble (ex:oil)

more H bonds in a molecule means it is __________ water soluble

more

charged molecules are more ____(hydrophobic or hydrophilic)______ than uncharged molecules

hydrophilic

(charged molecules are polar, water is polar)

can uncharged or charged molecules cross membranes

uncharged= hydrophobic= cross membrane

4 intermolecular forces contributing to water solubility

1. ionization state= high dielectric constant

2. hydrogen bonds

3. dipole-dipole

4. entropic