Acid-Base Titrations (L04; chptr 10)

CHEM 310: Foundations of Analytical Chemistry

3 reasons why acid-base chemistry is important in medical chemistry:

1. to know acid-base characteristics of proteins and small molecule drugs in chemistry and biochemistry

2. determine how they will react with substrates due to ionization

   1. determine solubility and permeability of small molecules

acid-base chemistry and the prodrugs of amines and amidines

• amides aren’t commonly used because they’re too stable

• activated amides (low basicity amines or amino acids) are effective because they limit their ability to be protonated

• pKa of amines can be lowered by 3 units by converting to N-Mannich base (X = CH₂NHCOAr) or Imine (Schiff base) prodrug

N-Mannich base (R=CH₂NHCOPh)

will lower pKa of amines and make them more lipophilic

has a log D_7.4 two units greater than the parent compound & has greater lipophilicity

Imine (Schiff base) prodrug

will lower pKa of amines and make them more lipophilic

will improve the pharmaceutical properties of drugs because its functional group has been temporarily modifies to improve its use; easily hydrolyzed

what will lower pKa of amines and make them more lipophilic?

N-Mannich bases (R=CH₂NHCOPh) & Imine (Schiff base) prodrugs

acid

substance that increases the concentration of H₃O⁺ when added to water

base

substance that decreases the concentration of H₃O⁺ when added to water

Brønsted-Lowry acid

proton donor

Brønsted-Lowry base

proton acceptor

salt

strong electrolytes that dissociate nearly completely into ions in dilute aqueous solutions

autoproteolysis (aka auto/self ionization)

the reaction in which two molecules of the same species transfer a proton from one to the other

protic solvents all have a reactive H⁺ and undergo this process

how do you calculate pH?

-log[H₃O⁺]

how do you calculate pOH?

-log[OH^-]

K_w

= 1.0 × 10^{-14 ₌} [H₃O⁺][OH^-]

what is the concentration of H₃O⁺ and OH^- in pure water?

1.0 × 10^-7

how can you tell whether a solution is acidic or basic?

strong acids (7)

1. hydrochloric acid (HCl)

2. hydrobromic acid (HBr)

3. hydroiodic acid (HI)

4. sulfuric acid (H₂SO₄)

5. nitric acid (HNO₃)

6. chloric acid (HClO₃)

7. perchloric acid (HClO₄)

strong bases (8)

1. lithium hydroxide (LiOH)

2. sodium hydroxide (NaOH)

3. potassium hydroxide (KOH)

4. calcium hydroxide (Ca(OH)₂)

5. rubidium hydroxide (RbOH)

6. strontium hydroxide (Sr(OH₂)

7. cesium hydroxide (CsOH)

8. barium hydroxide (Ba(OH)₂)

what should you know about strong acids and bases?

they will completely dissociate in an aqueous solution

weak acids (HA)

donates a proton to water

weak bases (HB)

abstracts a proton from water

most carboxylic acids are…

weak acids

most carboxylate anions are…

weak bases

most ammonium ions are…

weak acids

most amines are…

weak bases

metal cations act as… by …?

weak acids; acid hydrolysis to form MOH^(n-1)+ + H⁺

polyprotic acids and bases

can donate or accept more than one proton

example: oxalic acid is diprotic, and phosphate is tribasic

relationship between K_A and K_B

their product equals K_w

acid-base titrations

titrations involving acids and bases widely employed in analytical control of many commercial products

what are the 3 major types of acid-base titrations?

1. SA-SB

2. WA-SB

3. Diprotic Acid Titration