PHAR5315: Drug Action - Functional Groups: Drug Principles

Comprehensive vocabulary flashcards detailing the chemical properties, geometry, pKa values, ionization states, and reactivity of key functional groups from the lecture transcript.

Alkane

Properties: Hydrophobic, non-polar, lipophilic, chemically stable, tetrahedral geometry.

Alkyl Halide

Properties: Hydrophobic, lipophilic, chemically stable ($X = \text{F}, \text{Cl}, \text{Br}, \text{or } \text{I}$). May be displaced by nucleophiles or eliminated by bases.

Alkene

Properties: Non-polar, hydrophobic, lipophilic, chemically stable, planar geometry.

Alkyne

Properties: Non-polar, hydrophobic, lipophilic, chemically stable, linear geometry.

Aromatic Hydrocarbon; Arene

Properties: Non-polar, hydrophobic, lipophilic, planar ($4n+2e^-$), chemically stable.

Aromatic Halide

Properties: Hydrophobic, lipophilic, chemically stable ($X = \text{F}, \text{Cl}, \text{Br}, \text{or } \text{I}$).

Benzylic Carbon

Properties: Non-polar, hydrophobic, lipophilic, chemically stable.

Alcohol

Properties: Polar, hydrophilic, chemically stable; can be $1^\circ$, $2^\circ$, or $3^\circ$.

Enol

Properties: Tautomer of a ketone, acidic ($\text{pKa}$ highly variable).

Phenol

Properties: Very weakly acidic, hydrophilic, chemically stable, with a $\text{pKa} = 10$.

Catechol

Properties: Polar, very weakly acidic, hydrophilic, prone to oxidation, with a $\text{pKa} = 9.4$.

Ether or Dialkylether

Properties: Intermediate polarity, hydrophilic, chemically stable, but diethyl ether and THF can form unstable peroxides.

Epoxide

Properties: Intermediate polarity, strained, attacked by nucleophiles.

Peroxide

Properties: Intermediate polarity, unstable, and reactive with reducible groups.

Aldehyde / Arylaldehyde

Properties: Polar, hydrophilic, oxidizes to carboxylic acid, reacts with primary amines to form imines, electron withdrawing ($R = \text{Ar}$ for arylaldehyde).

Ketone / Arylketone

Properties: Polar, hydrophilic, chemically stable, electron withdrawing group ($R = \text{Ar}$, $R' = \text{Ar}, \text{alkyl}$).

Carboxylic Acid

Properties: Protonated form is polar, weak acid, hydrophilic, stable. Anion form is polar, hydrophilic, stable, electron withdrawing. Ion state at $\text{pH} = 7$ is ANION; $\text{pKa} = 5$.

Benzoic Acid (benzoate)

Properties: Protonated form is polar, weak acid, hydrophilic, stable. Anion form is polar, weak acid, chemically stable, hydrophilic. Ion state at $\text{pH} = 7$ is ANION; $\text{pKa} = 4$.

Ester (Lactone if cyclic) / Arylester / Phenolate Ester

Properties: Intermediate polarity, yet simple examples are soluble in organic solvent, stable under neutral conditions.

Carbonate

Properties: Intermediate polarity, yet simple examples are soluble in organic solvent, stable under neutral conditions.

Amide (Lactam if cyclic)

Properties: Polar, hydrophilic, neutral, planar, stable, electron withdrawing ($R = \text{alkyl}, \text{H}, \text{Ar}$).

Urea

Properties: Polar, hydrophilic, neutral, planar, stable, electron withdrawing ($R = \text{alkyl}, \text{H}, \text{Ar}$).

Carbamate; Urethane

Properties: Similar properties to amide.

Amine

Properties: Polar, basic, hydrophilic, simple examples are soluble in organic solvents, nucleophiles, free base can oxidize in air. $\text{pKa} = 11$, exists as CATION.

Aromatic amine; Arylamine

Properties: Polar, weakly basic, hydrophilic, chemically stable. Also an aromatic amine if the aromatic ring is other than phenyl; $\text{pKa} = 5$, exists as CATION.

Quaternary amine

Properties: Polar, hydrophilic, cationic at ALL pHs (fixed cation).

Amidine (amidinium)

Properties: Polar, basic, hydrophilic; $\text{pKa} = 12$, exists as CATION.

Guanidine (guanidium)

Properties: Polar, basic, hydrophilic, planar, chemically stable; $\text{pKa} = 13$, exists as CATION.

Nitro

Properties: Neutral, stable, strongly $e^-$ withdrawing.

Nitrile

Properties: Neutral, stable, linear, strong $e^-$ withdrawing group.

Thiol (aka Mercaptan)

Properties: Weakly polar, very weakly acidic, forms disulfides in oxidizing environments; $\text{pKa} = 10$.

Thioether (aka sulfide)

Properties: Weakly polar, chemically stable, forms sulfoxides in oxidizing environments.

Disulfide

Properties: Chemically stable, reduced to thiols, and oxidized to sulfonates. Prefers \pm 90^\circ torsion angle.

Sulfoxide

Properties: Polar, chemically stable; if $R \neq R'$, the $S$ center is chiral (the lone pair is the smallest when determining R vs S).

Sulfone

Properties: Polar, chemically stable.

(Sulfonate) Sulfonic acid

Properties: Polar, strongly acidic, hydrophilic, stable, exists as ANION with $\text{pKa} < 0$.

Sulfonamide (alkylsulfonamide)

Properties: Polar, hydrophilic, chemically stable.

Aromatic Sulfonamide (aka arylsulfonamide)

Properties: Polar, very weakly acidic, hydrophilic, chemically stable; some sulfonamide drugs have a lower pKa and are anions at pH 7 due to added $e^-$ withdrawing groups; $\text{pKa} = 10$.

Sulfate monoester

Properties: Polar, strongly acidic, hydrophilic, can eliminate if hydrogen is present on $\beta$-carbon, exists as ANION with $\text{pKa} < 0$.

Phosphate monoester

Properties: Polar, acidic, hydrophilic; exists as ANION at pH 3, DIANION at pH 7; $\text{pKa} = 2 / \text{pKa} = 6$ (dianion).