S02 REVIEW OF FUNCTIONAL GROUPS

What are functional groups?

Different chemical components that possess specific properties and behaviors allowing drug molecules to exert pharmacodynamic and pharmacokinetic effects.

How do functional groups influence overall drug solubility?

They influence overall water and lipid solubility.

How do functional groups affect drug administration?

They determine the route of administration.

How do functional groups affect drug interaction with biological targets?

They influence the ability of drug molecules to interact with specific target binding sites.

How do functional groups affect drug action?

They affect the mechanism of action and the duration of action.

Which pharmacokinetic parameters are determined by functional groups?

Metabolism and elimination.

How do functional groups affect therapeutic application?

They influence suitability for a specific therapeutic situation.

How do functional groups affect drug safety?

They play a significant role in the drug's tendency to cause adverse effects or drug interactions.

What is the general formula for alkanes?

CnH2n+2.

What is the general formula for alkenes?

CnH2n.

What type of bonds do carbon chains in alkanes contain?

Single bonds only.

What type of bonds do carbon chains in alkenes contain?

One or more double bonds.

What is the only type of intermolecular bonding possible for alkanes and alkenes?

Van der Waals attraction.

What physical state do alkanes and alkenes with 1 to 4 carbons exist in at room temperature?

Gaseous state.

Why do 1 to 4 carbon alkanes and alkenes exist as gases at room temperature?

Van der Waals attractions are not strong enough to hold smaller backbone molecules together.

What physical state do alkanes and alkenes with 5 to 20 carbons generally exist in at room temperature?

Liquid state.

Why do 5 to 20 carbon alkanes and alkenes exist in the liquid state?

Stronger induced dipole-dipole interactions occur between the larger molecules.

What is the water solubility of alkanes and alkenes?

Immiscible in water because they cannot form intermolecular interactions with water.

What is the lipid solubility of alkanes and alkenes?

High, they dissolve readily in lipids.

What dominant interaction type occurs in aliphatic alkane carbon chains?

Van der Waals forces (London forces).

How does an aliphatic alkane chain alter water and lipid solubility?

Decreases water solubility and increases lipid solubility.

How does the chemical stability of alkanes compare to alkenes?

Alkanes are chemically stable (inert), whereas alkenes are more reactive due to double bonds.

What defines an asymmetric or chiral carbon atom in branched-chain alkanes?

A carbon atom substituted with four different substituents.

What is the biological significance of chirality in drug molecules?

Chirality leads to significant biological differences between stereoisomers.

What type of stereoisomers can form in alkenes due to the double bond?

Geometric isomers.

What are the structural characteristics of aromatic hydrocarbon rings?

They are planar, hydrophobic structures that mainly form Van der Waals interactions.

Rather than isolated single and double bonds, what electron structure do aromatic compounds possess?

A cloud of electrons above and below the aromatic ring.

Why do aromatic rings form stronger Van der Waals interactions than aliphatic chains?

Due to their flat nature and high electron density.

What is a cation-π interaction?

An electrostatic chemical bond between an electron-rich π system and a cation.

Which cations can participate in cation-π interactions with aromatic rings?

Lithium, sodium, potassium, and ammonium salts.

What type of interaction occurs between two aromatic hydrocarbon rings?

π-π interaction.

What are the six carbon-oxygen functional groups?

Alcohols/phenols, aldehydes, ketones, carboxylic acids, ethers, and acid anhydrides.

How does the attachment of the hydroxyl group differ between alcohols and phenols?

In alcohols, OH is attached to an aliphatic chain; in phenols, OH is attached directly to an aromatic ring.

Why is hydrogen slightly positive and oxygen slightly negative in a hydroxyl group?

Oxygen has higher electronegativity, leading to an unequal sharing of electrons.

In a hydroxyl group, which atom acts as a hydrogen bond acceptor?

Oxygen.

In a hydroxyl group, which atom acts as a hydrogen bond donor?

Hydrogen.

How does a hydroxyl group affect water solubility?

Increases water solubility by forming hydrogen bonds with water.

What is the IUPAC name for methyl alcohol (wood alcohol)?

Methanol.

What is the IUPAC name for ethyl alcohol (Alcohol USP)?

Ethanol.

What is the IUPAC name for isopropyl alcohol (rubbing alcohol)?

2-Propanol.

What is the IUPAC name for tert-butyl alcohol?

2-Methyl-2-propanol.

How reactive are alcohols in the presence of oxidizing agents compared to alkanes?

Alcohols are more reactive than alkanes.

What is produced by the sequential oxidation of a primary alcohol?

Oxidation yields an aldehyde, which further oxidizes to a carboxylic acid.

What is produced by the oxidation of a secondary alcohol?

A ketone.

What happens to a tertiary alcohol in the presence of oxidizing agents?

It is stable and does not oxidize.

What is a carbonyl group?

A carbon atom double-bonded to an oxygen atom.

Is carbonyl by itself considered a functional group?

No, carbonyl is part of multiple functional groups like aldehydes, ketones, and carboxylic acids.

How many hydrogen bonding interactions can a ketone carbonyl oxygen form with a target binding site?

Two hydrogen bonding interactions (acting as a hydrogen bond acceptor).

Why can carbonyl groups participate in dipole-dipole interactions?

They possess a significant dipole moment due to the electronegativity difference between carbon and oxygen.

What is the IUPAC name for formaldehyde?

Methanal.

What is the IUPAC name for acetaldehyde?

Ethanal.

What is the IUPAC name for propionaldehyde?

Propanal.

What is the IUPAC name for dimethylketone (acetone)?

2-Propanone.

What is the IUPAC name for ethylmethylketone?

2-Butanone.

What is the IUPAC name for methylphenylketone (acetophenone)?

1-Phenylethanone.

What two forms exist in equilibrium for ketones?

Keto and enol forms.

How are ethers formed?

From the combination of two alcohols or an alcohol and a phenol.

What are the physical boiling point and stability properties of ethers?

Ethers have low boiling points and are almost chemically inert.

When do liquid ethers become chemically reactive?

When they come into contact with peroxide oxygen.

What hydrogen bonding role does an ether group play?

It acts as a hydrogen bond acceptor through its electron-rich oxygen atom.

What is the dominant type of bonding in ethers?

Weak Van der Waals interactions.

What is the IUPAC name for ethylmethylether?

Methoxyethane.

What is the IUPAC name for diethylether (Ether USP)?

Ethoxyethane.

What is the IUPAC name for methylphenylether (anisole)?

Methoxybenzene.

What two groups make up a carboxylic acid functional group?

A carbonyl group and a hydroxyl group.

What hydrogen bonding roles can a carboxylic acid play?

It can act as both a hydrogen bond donor and a hydrogen bond acceptor.

What interactions can a carboxylate ion form at a binding site?

Ionic interactions and hydrogen bonds (acting as a strong hydrogen bond acceptor).

Why is the carboxylate ion significant for metalloproteinases like zinc metalloproteinases?

It acts as a good binding ligand for metal ion cofactors.

What is the IUPAC name for formic acid?

Methanoic acid.

What is the IUPAC name for acetic acid (vinegar)?

Ethanoic acid.

What is the IUPAC name for propionic acid?

Propanoic acid.

What is the IUPAC name for caproic acid?

Hexanoic acid.

What biosynthesis pathway involves mevalonic acid?

Mevalonic acid converts to squalene, which converts to steroids (cholesterol).

What are four structural analogues of carboxylic acids?

Esters, primary alcohols, primary amides, and ketones.

What are the three classes of simple amines?

Primary, secondary, and tertiary amines.

Why are amine functional groups particularly important in medicinal chemistry?

They are the most common functional group found in medicinal agents.

What hydrogen bonding roles do primary and secondary amines perform?

Nitrogen acts as a hydrogen bond acceptor (HBA); nitrogen-bound hydrogen acts as a hydrogen bond donor (HBD).

Why do aromatic and heteroaromatic amines act ONLY as hydrogen bond donors?

Their nitrogen lone pair is delocalized into the aromatic or heteroaromatic ring.

How does ionization affect an amine's ability to act as a hydrogen bond acceptor?

An ionized amine can no longer act as a hydrogen bond acceptor.

How does ionization affect an amine's ability to act as a hydrogen bond donor?

It still acts as an HBD and forms stronger hydrogen bonds than the non-ionized form.

What defines a quaternary ammonium salt?

A nitrogen atom bound to four carbon atoms through covalent bonds.

Why are quaternary ammonium salts chemically stable?

A considerable amount of energy is required to break the carbon-nitrogen bond.

How do quaternary ammonium salts interact with binding site carboxylate groups?

Via ionic interactions.

What is the typical water solubility of pharmaceutical quaternary ammonium salts?

Most quaternary ammonium salts found in pharmacy are water-soluble.

What are two common carbon-sulfur functional groups?

Sulfhydryl (thiol) and disulfides.

What are four functional group classes categorized under esters and amides?

Esters, thioesters, phosphoesters, and amides.

What is an ester?

A carboxylic acid derivative where the hydroxyl hydrogen is replaced with an alkyl group.

What hydrogen bonding role can an ester play?

Hydrogen bond acceptor ONLY.

Why is hydrogen bonding in esters more likely to occur at the carbonyl oxygen than the alkoxy oxygen?

The carbonyl oxygen has less steric hindrance and higher electron density.

Why do esters have a short in vivo lifetime?

They are susceptible to hydrolysis by esterase enzymes in vivo.

What is a lactone?

A cyclic ester formed by the intramolecular cyclization of an alcohol and a carboxylic acid.

How do physical and chemical properties of lactones compare to open-chain esters?

They are identical to esters.

What ring size range can lactones exhibit?

From 5-membered rings (e.g., spironolactone) up to 14-unit rings (e.g., erythromycin).

How are monosubstituted, disubstituted, or unsubstituted amides formed?

By combining a polar carboxylic acid with a primary amine, secondary amine, or ammonia, respectively.

What type of bond links amino acids together in peptides and polypeptides?

Amide bonds (most commonly secondary amides).

What are the planarity and rotation characteristics of an amide group?

The amide group is planar and does NOT rotate.

How stable is the amide functional group chemically?

Amides are relatively stable functional groups.

How many hydrogen bonds can an amide carbonyl oxygen potentially accept?

Up to two hydrogen bonds.

What is a lactam?

A cyclic amide formed by the intramolecular cyclization of an amine and a carboxylic acid group.

What are two key drug classes that contain lactam functional groups?

Penicillins and cephalosporins.