S02 Review of Functional Groups

Learning Objective 1: Describe the chemical structure of alkanes, alkenes, and aromatic hydrocarbons, and list the physical and chemical properties of these functional groups

What is the general formula for alkanes?

CₙH₂ₙ₊₂

What is the general formula for alkenes?

CₙH₂ₙ

What type of bonds do alkanes contain?

Only single bonds.

What type of bonds do 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 type of Van der Waals interaction occurs in alkanes and alkenes?

London forces.

Why are smaller alkanes and alkenes gases at room temperature?

Their Van der Waals attractions are not strong enough to hold the molecules together.

How many carbon atoms are typically present in the smaller alkane/alkene molecules that are gases at room temperature?

1-4 carbons.

What state are larger alkanes and alkenes generally in at room temperature?

Liquid.

How many carbon atoms are generally present in larger alkanes and alkenes?

5-20 carbons.

What causes stronger interactions in larger alkanes and alkenes?

Induced-dipole dipole interactions.

Are alkanes and alkenes water-soluble?

No.

Why are alkanes and alkenes immiscible in water?

They cannot form intermolecular interactions with water.

Are alkanes and alkenes soluble in lipids?

Yes, they dissolve readily in lipids.

What is the general chemical stability of alkanes?

Alkanes are generally stable/inert.

Why are alkenes more reactive than alkanes?

Because of their double bond(s).

When is an alkane carbon atom considered asymmetric?

When it is substituted with four different substituents.

What does an asymmetric carbon atom indicate?

A chiral molecule.

What biological effect can chirality have?

It can lead to significant biological differences between stereoisomers.

What type of isomerism can result from a double bond in an alkene?

Geometric isomerism.

What is the structure of an aromatic hydrocarbon?

A planar, hydrophobic ring structure.

What type of intermolecular interactions do aromatic rings mainly form?

Van der Waals interactions.

Do aromatic compounds have isolated single and double bonds?

No.

What is present above and below an aromatic ring?

A cloud of electrons.

What property of aromatic rings allows them to form stronger Van der Waals interactions?

High electron density and a flat structure.

What is a cation-π interaction?

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

What is an example of an electron-rich π system in a cation-π interaction?

An aromatic ring.

What are examples of cations that can participate in cation-π interactions?

Li, Na, K, and ammonium salts.

What type of interaction occurs between two aromatic hydrocarbons?

π-π interaction.

What is the dominant interaction of alkanes?

Van der Waals (London forces).

How do alkanes affect water solubility?

They decrease water solubility.

How do alkanes affect lipid solubility?

They increase lipid solubility.

Learning Objective 2: Describe the chemical structures of the most common functional groups in biological systems/commonly used drugs

What is a functional group?

A chemical group/component possessing specific properties and behaviors that allows drug molecules to exert pharmacodynamic and pharmacokinetic effects.

What are the six carbon-oxygen functional groups listed in the lecture?

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

How do alcohols differ structurally from phenols?

Alcohols have an OH group attached to an aliphatic chain, whereas phenols have an OH group attached directly to an aromatic ring.

What functional group is present in alcohols and phenols?

Hydroxyl (OH).

What is the structural feature common to aldehydes and ketones?

A carbon atom attached to an oxygen atom through a double bond.

What is this C=O group called?

A carbonyl.

Is the carbonyl itself considered a functional group?

No.

What functional groups contain a carbonyl?

Aldehydes, ketones, and carboxylic acids.

What is the key structural feature of ethers?

An oxygen atom connecting two groups.

How are ethers described in the lecture?

As resulting from the combination of two alcohols or an alcohol and a phenol.

What is the composition of a carboxylic acid functional group?

A carbonyl and a hydroxyl group.

What are the two carbon-nitrogen functional groups listed?

Amines and quaternary amines.

What are the three types of amines listed?

Primary, secondary, and tertiary amines.

What is a quaternary ammonium salt?

A compound in which nitrogen is covalently bound to four carbon atoms.

What are the two carbon-sulfur functional groups listed?

Sulfhydryl (thiol) and disulfides.

What are the four ester/amide-related functional groups listed?

Esters, thioesters, phosphoesters, and amides.

What is an ester?

A carboxylic acid derivative in which the hydrogen is replaced with an alkyl group.

What does intramolecular cyclization of an alcohol and carboxylic acid form?

A lactone.

What are the physical and chemical properties of lactones compared with esters?

They are the same.

What ring sizes can lactones have according to the lecture?

Five-membered to 14-unit rings.

What are amides formed from?

A polar carboxylic acid combined with a weakly polar primary or secondary amine or ammonia.

What type of amide results from combining a carboxylic acid with a primary amine?

A monosubstituted amide.

What type of amide results from combining a carboxylic acid with a secondary amine?

A disubstituted amide.

What type of amide results from combining a carboxylic acid with ammonia?

An unsubstituted amide.

What bonds link amino acids together in peptides and polypeptides?

Amide bonds.

What is the most common type of amide in peptides and polypeptides?

Secondary amides.

What is the structure of an amide group?

Planar.

Can the amide group rotate?

No.

How stable are amides?

They are relatively stable functional groups.

What does intramolecular cyclization of an amine and carboxylic acid form?

A lactam.

How do lactams compare with open-chain amides in hydrogen bonding?

Lactams can form hydrogen bonds like open-chain amides.

Learning Objective 3: Describe the type of intermolecular interactions formed by common functional groups in biological systems

What type of interaction can the hydroxyl group of alcohols and phenols form?

Hydrogen bonding.

Why is the hydrogen of an OH group slightly positive?

Oxygen has higher electronegativity, causing unequal electron sharing.

Why is the oxygen of an OH group slightly negative?

Oxygen has higher electronegativity than hydrogen.

Which atom of an OH group acts as a hydrogen bond acceptor?

Oxygen.

Which atom of an OH group acts as a hydrogen bond donor?

Hydrogen.

What type of interaction allows alcohols to interact with water?

Hydrogen bonding.

What type of interaction can the carbonyl oxygen in ketones form?

Hydrogen bonding.

Is the carbonyl oxygen a hydrogen bond donor or acceptor?

Hydrogen bond acceptor.

How many hydrogen bonding interactions can the carbonyl group in a ketone form with a binding site?

Two.

Why can carbonyl groups participate in dipole-dipole interactions?

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

What type of interaction can ethers form?

Hydrogen bonding.

Which atom of an ether acts as a hydrogen bond acceptor?

The electron-rich oxygen.

What is the dominant bonding in ethers?

Weak Van der Waals interactions.

What types of hydrogen bonding can carboxylic acids participate in?

They can act as hydrogen bond donors or acceptors.

What additional type of interaction can the carboxylate ion participate in?

Ionic interactions.

What type of hydrogen bonding can the carboxylate ion participate in?

It can act as a hydrogen bond acceptor.

What can the carboxylate ion bind to in enzymes?

Metal ion cofactors.

What type of interaction can quaternary ammonium salts form with a carboxylate group?

Ionic interactions.

Which amines can participate in hydrogen bonding because they contain N-H groups?

Primary and secondary amines.

What part of a primary or secondary amine acts as a hydrogen bond acceptor?

The nitrogen lone pair.

What part of a primary or secondary amine acts as a hydrogen bond donor?

The N-H hydrogen.

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

Their lone pair is delocalized because of the aromatic or heteroaromatic ring.

What happens to the hydrogen bond acceptor ability of an amine when it becomes ionized?

It can no longer act as a hydrogen bond acceptor.

Can an ionized amine still act as a hydrogen bond donor?

Yes.

How does hydrogen bonding by an ionized amine compare with the non-ionized form?

The ionized amine forms stronger hydrogen bonds.

What type of interaction can esters form with a binding site?

Hydrogen bonding as an acceptor only.

Which ester oxygen is more likely to participate in hydrogen bonding?

The carbonyl oxygen.

Why is the carbonyl oxygen of an ester more likely to hydrogen bond than the alkoxy oxygen?

It has less steric hindrance and higher electron density.

What type of interaction can the carbonyl group of an amide participate in?

Hydrogen bonding.

Which part of an amide acts as a hydrogen bond acceptor?

The carbonyl oxygen.

How many hydrogen bonds could the carbonyl atom of an amide potentially form?

Two.

Learning Objective 4: Demonstrate the role of intermolecular interactions in water/lipid solubility

What is one major factor functional groups influence in drugs?

Overall water/lipid solubility.

Why are alkanes immiscible in water?

They cannot form intermolecular interactions with water.

How do alcohols affect water solubility?

They increase water solubility.

How do alcohols affect lipid solubility?

They decrease lipid solubility.

What interaction between an alcohol's OH group and water increases water solubility?

Hydrogen bonding.

What type of functional group has Van der Waals interactions as its dominant interaction?

Alkane.