Difficulty: Introductory | Prerequisites: Atoms and Molecules study notes (Part A), basic understanding of polarity and electronegativity
Functional groups are the recurring chemical motifs that give organic molecules their properties. This section is about recognising them, ranking their polarity, and understanding how pH changes the charge state of amino acids. Every macromolecule you will study in this course (proteins, nucleic acids, carbohydrates, lipids) is built from carbon skeletons decorated with these functional groups, so knowing them well pays dividends for the rest of the semester.
Functional groups range from strongly polar (charged groups like phosphate and ionised carboxyl/amino) to non-polar (methyl, hydrocarbon chains). Amino acids carry both an amino group and a carboxyl group, and their ionisation state changes with pH. At cellular pH (~7.4), most amino acids exist as zwitterions, with the amino group protonated (NH3+) and the carboxyl group deprotonated (COO-).
Functional group
A specific grouping of atoms within a molecule that determines the molecule's chemical properties and reactivity. Think of functional groups as chemical "personality tags": swap one out and the molecule behaves differently.
Hydroxyl group (-OH)
Found in alcohols and sugars. Polar, because the oxygen is electronegative and pulls electron density away from the hydrogen. Makes molecules soluble in water. Example: ethanol (CH3CH2OH), glucose.
Carbonyl group (C=O)
A carbon double-bonded to oxygen. If at the end of a carbon chain, it forms an aldehyde; if in the middle, a ketone. Moderately polar. Example: acetone (a ketone), formaldehyde (an aldehyde).
Carboxyl group (-COOH)
A carbon double-bonded to one oxygen and single-bonded to a hydroxyl group. Acts as an acid (donates H+). At physiological pH, it is usually deprotonated (-COO-) and negatively charged. Strongly polar when ionised. Example: acetic acid, amino acid side chains of aspartate and glutamate.
Amino group (-NH2)
A nitrogen bonded to two hydrogens (and the rest of the molecule). Acts as a base (accepts H+). At physiological pH, it is usually protonated (-NH3+) and positively charged. Strongly polar when ionised. Example: amino acids, nucleotide bases.
Phosphate group (-OPO3^2-)
A phosphorus atom bonded to four oxygens. Carries negative charges at physiological pH. Strongly polar. Found in ATP, DNA, phospholipids. Contributes to the negative charge of the DNA backbone.
Sulfhydryl group (-SH)
A sulfur bonded to a hydrogen. Weakly polar. Important because two sulfhydryl groups can form a covalent disulfide bond (S-S) that stabilises protein structure. Example: cysteine.
Methyl group (-CH3)
A carbon bonded to three hydrogens. Non-polar. Does not form hydrogen bonds. Important in gene regulation (DNA methylation) and membrane lipids.
Zwitterion
A molecule that carries both a positive and a negative charge simultaneously, with a net charge of zero. At cellular pH (~7.4), most amino acids are zwitterions: the amino group is protonated (NH3+, positive) and the carboxyl group is deprotonated (COO-, negative).
Strongly polar (charged at physiological pH):
Phosphate (-OPO3^2-): carries up to two negative charges. Found in ATP, DNA, RNA, phospholipids.
Carboxyl (-COO-) when ionised: one negative charge. Found in amino acids (Asp, Glu), fatty acids.
Amino (-NH3+) when protonated: one positive charge. Found in amino acids (Lys), nucleotide bases.
Moderately polar (uncharged but capable of hydrogen bonding):
Hydroxyl (-OH): can both donate and accept hydrogen bonds. Found in sugars, alcohols, serine, threonine.
Carbonyl (C=O): the oxygen is a hydrogen bond acceptor. Found in sugars (aldoses and ketoses), peptide bonds.
Carboxyl (-COOH) when protonated: polar but uncharged.
Amino (-NH2) when deprotonated: polar but uncharged.
Sulfhydryl (-SH): weakly polar. Can form disulfide bonds. Found in cysteine.
Non-polar:
Methyl (-CH3): no significant dipole, does not hydrogen-bond. Found in membrane lipids, DNA methylation.
Hydrocarbon chains (-CH2-CH2-): entirely non-polar. Form the hydrophobic tails of fatty acids and phospholipids.
A generic amino acid has two ionisable groups on its backbone: the carboxyl group (pKa ~2) and the amino group (pKa ~9 to 10). Some amino acids also have ionisable R-groups.
At very low pH (below 2):
Both groups are fully protonated. The amino group is -NH3+ (positive), the carboxyl group is -COOH (neutral). The amino acid carries a net positive charge. This is the cationic form.
At physiological/cellular pH (~7.4):
The carboxyl group has lost its proton (-COO-, negative). The amino group is still protonated (-NH3+, positive). The molecule carries both a positive and a negative charge simultaneously: this is the zwitterion form, with a net charge of approximately zero.
At very high pH (above 10):
Both groups are deprotonated. The carboxyl is -COO- (negative), the amino is -NH2 (neutral). The amino acid carries a net negative charge. This is the anionic form.
The form found at cellular pH is the zwitterion. This is the most commonly tested point about amino acid ionisation.
Functional group polarity is the reason medications dissolve differently. A drug with many hydroxyl groups will dissolve in blood (aqueous) but struggle to cross cell membranes (hydrophobic interior). Pharmaceutical chemists modify functional groups to tune how a drug is absorbed, distributed, and excreted.
Amino acid ionisation is exploited in gel electrophoresis and chromatography: proteins can be separated by charge at different pH values, which depends entirely on the ionisation state of their amino acid side chains.
Students often think "polar" and "charged" mean the same thing. A charged group is always polar, but a polar group is not necessarily charged. Hydroxyl is polar but typically uncharged; ionised carboxyl is polar and charged.
Students sometimes assume the zwitterion has no charges. It has two charges (one positive, one negative) that cancel to give a net charge near zero. The charges are still there.
Students often forget that whether a functional group is charged depends on pH. A carboxyl group is -COOH at low pH and -COO- at high pH. You cannot state a group's charge without knowing the pH.
Students sometimes rank sulfhydryl as strongly polar because sulfur is a large atom. Sulfur's electronegativity is relatively low (2.5, close to carbon at 2.5), making -SH only weakly polar.
You will be asked to rank functional groups by polarity. Know the three tiers: strongly polar (charged), moderately polar (uncharged but H-bonding), non-polar.
Be able to draw an amino acid at low pH, physiological pH, and high pH, showing the correct charges on the amino and carboxyl groups.
The zwitterion is the form at cellular pH. This is one of the most commonly tested facts in this unit.
Understand why phospholipids have a strongly polar head (phosphate group) and non-polar tails (hydrocarbon chains), linking this back to membrane formation from Part A.
Fill in the blank: At physiological pH, the amino group on an amino acid is ______ and carries a ______ charge.
True or False: The methyl group is polar and participates in hydrogen bonding.
Fill in the blank: A molecule that carries both a positive and a negative charge simultaneously is called a ______.
True or False: The phosphate group is non-polar.
Fill in the blank: At very high pH, the amino acid carries a net ______ charge.
Answers: 1. protonated (-NH3+), positive, 2. False, 3. zwitterion, 4. False (strongly polar/charged), 5. negative
Q: Classify the following functional groups as strongly polar, moderately polar, or non-polar: phosphate, hydroxyl, methyl, ionised amino group, carbonyl.
A: Strongly polar: phosphate (charged), ionised amino group (charged). Moderately polar: hydroxyl (uncharged, H-bonds), carbonyl (uncharged, H-bond acceptor). Non-polar: methyl.
Q: Draw or describe the structure of an amino acid at pH 1, pH 7, and pH 13. Label the charges.
A: At pH 1: -NH3+ (positive) and -COOH (neutral), net charge +1. At pH 7: -NH3+ (positive) and -COO- (negative), net charge ~0 (zwitterion). At pH 13: -NH2 (neutral) and -COO- (negative), net charge -1.
Q: Why is the sulfhydryl group considered only weakly polar, even though sulfur is a fairly large atom?
A: Sulfur has an electronegativity of about 2.5, which is very close to carbon (2.5). The S-H bond therefore has only a small dipole. Size alone does not determine polarity; electronegativity difference does.
Q: A protein has a glutamate residue (R-group: -CH2-CH2-COO-) exposed on its surface at pH 7. What happens to this residue if the pH drops to 2?
A: The carboxyl group on glutamate's R-group becomes protonated (-COOH), losing its negative charge. This disrupts any ionic interactions (salt bridges) that residue was forming with positively charged residues, potentially destabilising the protein's folded structure.
Functional group chemistry connects directly to macromolecule structure: carboxyl and amino groups form peptide bonds in proteins, hydroxyl groups link sugars in polysaccharides, and phosphate groups bridge nucleotides in DNA and RNA. The ionisation behaviour of amino acids is foundational for understanding protein folding, enzyme active sites, and protein purification techniques you will encounter later in the course.
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