Acid-Base Chemistry: Properties, Theories

Module 1: Physicochemical Properties

• Focuses on the chemical and physical properties of drugs, including their reactions

Acid Base Properties

• An acid is a proton donor, and a base is a proton acceptor.
• Acid + Base results in Conjugate Acid + Conjugate Base.
• Acids donate protons, while bases accept protons

Key Entities

• Conjugate Acid: Formed when an acid donates a proton (Base + H+).
• Conjugate Base: Formed when an acid loses a proton (Acid - H+).

Three Acid-Base Theories

• Arrhenius: Acid is H+ in H2O, base is OH- in H2O.
• Bronsted-Lowry: Acid is a proton donor, base is a proton acceptor.
• Lewis: Acid accepts electrons, base donates electrons.
• Water is amphoteric, acting as both an acid and a base.
• Water can accept a proton (H+) to form a hydronium ion (H3O+), which acts as a conjugate acid.

Acid Strength and pKa

• pKa indicates the strength of an acid (lower pKa = stronger acid).
• pH measures hydrogen ion (H+) concentration in a solution.
• pKa is essential for predicting the direction of acid-base reactions.
• Helps determine the pH needed for a chemical species to donate or accept a proton.
• Henderson-Hasselbalch equation relates pKa and pH.
• pKa is the negative logarithm of the modified equilibrium constant, Ka.

Buffer pH and Ratio

• A buffer containing 0.1M acetic acid (pKa 4.8) and 0.08M sodium acetate has a pH of 4.7, which indicates a weak acid.
• Can determine Ka if the values of conjugate acid and base are known.
• The pH can be calculated with conj. base and untouched acid, using the formula pH = pKa + log ([conj. base]/[acid]).

Reactions Involving Acid/Conjugate Base Pairs

Reaction A

• HCl(acid) + H2O (base) yields H3O+ (conj. acid) + Cl- (conj. base)
• Equilibrium favors the right because strong acids have low pKa
• The acid donates a proton to produce conj. acid and conj. base

Reaction B

• H2O (acid) + NaOH (base) yields H2O (conj. acid) + OH- (Na+) (conj. base)
• Occurs via hydrolysis, where NaOH dissociates in water.

Reaction C

• Sodium dihydrogen phosphate (acid) + Water (base) yields H3O (conj acid) + HPO4- (Na+) (conj base)
• The direction of the reaction either way is due to the conj acid capable of donating protons

Reaction D

• H2O (acid) + HPO4 (Base) yields H2PO4- + OH (conj base)
• The acid is capable of donating a reaction

Reaction E

• Ammonium Chloride (acid) + water (base) yields H2O-Cl (conj acid) + Ammonia (conj base)
• Occurs as a weak acid

Reaction F

• Water (Acid) + ammonia (base) yields H4N conj acide + OH conj base
• Once there is H from the acid, it becomes 4HN

Reaction G

• Acetic acid (acid) + water (base) yields H3O (conj. acid) + Acetate (conj. base)
• Equilibrium lie to the left

Reaction H

• Water (Acid) + Sodium actetate (base) yields ch3Cooh (conj acid) + OH (conj base)
• This is an applicable drug

Reaction I - Indomethacin

• Drug undergoes dehydrogenation
• indomethacin is not stable and conj base

Reaction J - Indomethacin Na

• OH being the conj base
• this reation is applicable to indomethacin

Reaction K - saccharin (not stable:)

• it will be more stable

Reaction L - saccharin Na+ (stable)

• Drug will become stable

Reaction M - Ephedrine (not stable)

• Not in stabel form

Reaction N

• Even if drugs have salts, it gets stabilized

Acid Base Equilibrium

• HA acids go from un-ionized acids to ionized conjugate bases
• In contract, BH acids go from ionized (polar) to un-ionized (nonpolar) conjugate bases

Drug distribution and pKa

• BH complete synthesis while HA complete synthesis is better after
• PH is first where ph ranges form 2 - 6

Forces Involving with Drug-Receptor Interactions

• all Bonds correlate
• The types of bonds
  • Covalent bond
  • Ionic bond
  • Hydrogen bond
  • Hydrophobic bond

Optical Isomerism and Biological Activity

• all have physical properties

IsoSerism

• There are rings of Isoerism