Difficulty: Introductory | Prerequisites: Basic atomic structure (protons, neutrons, electrons, orbitals)
This topic sits at the foundation of BIO 311C. Before you can understand how proteins fold, how membranes form, or how enzymes work, you need a solid grip on the forces that hold molecules together and pull them apart. Everything from DNA replication to drug design depends on bond behaviour. If you skipped general chemistry or feel shaky on electronegativity, start here.
Proteins contain every major type of chemical bond and interaction: covalent, ionic, hydrogen bonds, hydrophobic interactions, and van der Waals forces. Changes in pH and temperature disrupt the weaker interactions first, which is why proteins denature. Polarity determines how molecules interact with water, and phospholipids exploit having both polar and non-polar regions to self-assemble into membranes.
Covalent bond
A bond formed by the sharing of electron pairs between atoms. Think of it as two atoms holding hands, each contributing an electron to the grip. The strongest bond type in biological molecules.
Ionic bond
A bond formed by the electrostatic attraction between oppositely charged ions (one atom donates an electron, the other accepts it). In simple terms, this is the pull between a positive and a negative charge, like Na+ and Cl- in table salt.
Hydrogen bond (H-bond)
A weak attraction between a hydrogen atom bonded to an electronegative atom (N, O, or F) and another electronegative atom nearby. Think of it as a partial positive charge on hydrogen being drawn toward a partial negative charge on a neighbouring atom. Individually weak, but collectively powerful (they hold DNA strands together).
Van der Waals forces (London dispersion forces)
Weak, transient attractions caused by momentary shifts in electron distribution around atoms. In simple terms, these are the weakest intermolecular forces, but they add up when large molecules have lots of surface contact.
Hydrophobic interaction
The tendency of non-polar molecules to cluster together in an aqueous environment, not because they attract each other, but because water molecules prefer to hydrogen-bond with one another rather than surround non-polar surfaces. Think of it as non-polar molecules being squeezed together by water.
Polarity
The uneven distribution of electron density in a molecule, creating a partial positive end and a partial negative end. In simple terms, a polar molecule has a "water-loving" character because its charges interact with water's own partial charges.
Amphipathic (amphiphilic)
Describes a molecule that has both a polar (hydrophilic) region and a non-polar (hydrophobic) region. Phospholipids are the classic example: polar head, non-polar fatty acid tails.
Denaturation
The loss of a protein's three-dimensional shape due to disruption of non-covalent interactions (H-bonds, ionic bonds, hydrophobic interactions, van der Waals forces). The covalent peptide backbone typically remains intact. Think of it as unravelling a folded towel: the material is still there, but the structure is gone.
Electronegativity
A measure of an atom's ability to attract shared electrons in a bond. Oxygen and nitrogen are highly electronegative, which is why O-H and N-H bonds are polar.
Proteins contain a hierarchy of bonds, from the strong covalent peptide bonds along the backbone to the weaker non-covalent interactions that maintain the folded shape.
Covalent bonds (peptide bonds): formed between amino acids during translation. These are the strongest bonds in a protein and are largely unaffected by moderate pH or temperature changes. Only extreme conditions (strong acid hydrolysis, very high heat) will break them.
Disulfide bonds (covalent, S-S): cross-links between cysteine residues. Also strong, but can be broken by reducing agents or extreme conditions.
Ionic bonds (salt bridges): form between oppositely charged R-groups (e.g. lysine NH3+ and aspartate COO-). pH changes alter the ionisation state of these side chains, breaking or forming salt bridges. A shift away from physiological pH (~7.4) disrupts these interactions.
Hydrogen bonds: form between polar R-groups, between backbone N-H and C=O groups, and with surrounding water. Temperature increases weaken H-bonds by increasing molecular motion. pH changes can also disrupt them by altering the charge on donor/acceptor groups.
Hydrophobic interactions: non-polar R-groups cluster in the protein interior, away from water. Rising temperature initially strengthens hydrophobic interactions (up to a point), but at high temperatures the overall increase in kinetic energy overwhelms this effect and the protein unfolds.
Van der Waals forces: contribute to tight packing of atoms in the protein core. Individually the weakest, but collectively significant. Disrupted when the protein structure loosens from temperature or pH stress.
Summary of effects:
Temperature increase: increases kinetic energy of all atoms, progressively disrupting H-bonds, van der Waals forces, and eventually hydrophobic packing. Covalent bonds remain intact until extreme heat.
pH change: alters the protonation state of ionisable R-groups (Asp, Glu, His, Lys, Arg, Cys, Tyr), breaking or creating ionic interactions and hydrogen bonds. The overall folded structure depends on these, so the protein denatures.
Polarity arises when electrons are shared unequally in a bond due to differences in electronegativity. A molecule's overall polarity depends on both bond polarity and molecular geometry.
Polar molecules: water (H2O), ethanol, glucose. These dissolve readily in water because their partial charges interact with water's own dipole.
Non-polar molecules: methane (CH4), fats, oils, hydrocarbons. These do not dissolve well in water.
Both polar and non-polar (amphipathic): phospholipids, cholesterol, fatty acids with a carboxyl head. These have a polar head group and non-polar hydrocarbon tails.
Phospholipids spontaneously form bilayers in water because of the hydrophobic effect.
The polar (hydrophilic) head faces water on both the extracellular and cytoplasmic sides.
The non-polar (hydrophobic) tails face inward, away from water, forming the interior of the membrane.
This arrangement is thermodynamically favourable: water molecules can maximise their hydrogen bonding when non-polar tails are sequestered away from them.
The result is a stable bilayer that forms the basis of all biological membranes.
Intramolecular bonds (within a molecule) are stronger than intermolecular interactions (between molecules).
Intramolecular (strongest to weakest):
Covalent bonds: ~150 to 950 kJ/mol (varies by bond type; C-C ~347 kJ/mol, C=O ~745 kJ/mol, O-H ~463 kJ/mol)
Ionic bonds (in vacuum): ~400 to 4000 kJ/mol, but in aqueous solution they weaken considerably (~20 kJ/mol effective in protein context)
Intermolecular (strongest to weakest):
Ion-dipole interactions: ~50 to 200 kJ/mol
Hydrogen bonds: ~12 to 30 kJ/mol (about 20 kJ/mol typical in biology)
Dipole-dipole interactions: ~5 to 25 kJ/mol
Van der Waals (London dispersion) forces: ~0.05 to 40 kJ/mol (depends on molecular size and surface area)
Bond energies (approximate, in kJ/mol):
Bond Type | Energy (kJ/mol) | Energy (kcal/mol) |
|---|---|---|
C-H | 413 | 99 |
C-C | 347 | 83 |
C=C | 614 | 147 |
C-O | 358 | 86 |
C=O | 745 | 178 |
O-H | 463 | 111 |
N-H | 391 | 93 |
C-N | 305 | 73 |
S-S (disulfide) | 266 | 64 |
H-bond (typical) | 12 to 30 | 3 to 7 |
Van der Waals | 0.4 to 4 | 0.1 to 1 |
Key relationships:
pH = -log[H+]
As pH decreases (more acidic), [H+] increases, protonating carboxyl and amino groups on amino acid side chains
As pH increases (more basic), [H+] decreases, deprotonating these groups
The isoelectric point (pI) is the pH at which an amino acid carries no net charge
Protein denaturation by heat is exactly why cooking an egg turns the white from translucent to opaque: the albumin proteins unfold and aggregate. The same principle underlies pasteurisation, where controlled heating denatures proteins in harmful bacteria without destroying nutrients.
Phospholipid self-assembly is exploited in drug delivery: liposomes (artificial phospholipid vesicles) carry medication to specific tissues, protecting the drug in their hydrophobic core until it reaches the target.
Students often think denaturation breaks covalent (peptide) bonds. It does not. Denaturation disrupts the weaker non-covalent interactions that maintain the 3D shape, but the amino acid chain itself remains covalently linked.
Students often confuse hydrophobic interactions with a direct attraction between non-polar molecules. The driving force is water's preference to maximise its own hydrogen bonding, which effectively pushes non-polar groups together.
Students often assume ionic bonds in proteins are as strong as those in a crystal lattice (like NaCl). In aqueous solution, water molecules screen the charges, making these interactions much weaker than in a dry crystal.
Students often think van der Waals forces are negligible. Individually they are weak, but proteins have thousands of atom-to-atom contacts, so the cumulative contribution is significant.
You will be asked to predict what happens to a protein when pH or temperature changes. Know which bonds are affected and in what order.
Be ready to rank bond strengths from strongest (covalent) to weakest (van der Waals) and give approximate energies.
Understand why phospholipids form bilayers, not micelles or monolayers, in aqueous solution (bilayers minimise the exposure of tails to water while allowing heads to interact with water on both sides).
Know the difference between intramolecular and intermolecular forces and be able to give examples of each.
True or False: Denaturation always breaks covalent bonds in a protein.
Fill in the blank: The weakest intermolecular force is ______.
True or False: Hydrogen bonds are stronger than covalent bonds.
Fill in the blank: A phospholipid's ______ head faces the aqueous environment, while its ______ tails face inward.
True or False: Increasing temperature strengthens hydrogen bonds.
Answers: 1. False, 2. Van der Waals (London dispersion), 3. False, 4. hydrophilic/polar, hydrophobic/non-polar, 5. False
Q: A protein is exposed to a solution at pH 2. Which types of bonds or interactions within the protein are most likely disrupted, and why?
A: Ionic bonds (salt bridges) are disrupted because the extreme acidity protonates negatively charged carboxylate groups (Asp, Glu), eliminating the charge attraction. Hydrogen bonds involving ionisable groups are also affected. Covalent peptide bonds remain intact.
Q: Explain why phospholipids form a bilayer rather than dissolving in water.
A: Phospholipids are amphipathic. Their polar heads interact favourably with water, but their non-polar tails are excluded by water. A bilayer arrangement satisfies both regions: heads face water on each surface, tails are sequestered in the interior, minimising thermodynamically unfavourable contact between non-polar tails and water.
Q: Rank the following from strongest to weakest: hydrogen bond, covalent bond, van der Waals force, ionic bond (in aqueous solution).
A: Covalent bond > ionic bond (in aqueous solution, weakened by solvation) > hydrogen bond > van der Waals force.
Q: Why does boiling an egg cause the egg white to solidify?
A: Heat increases molecular motion, disrupting the hydrogen bonds, hydrophobic interactions, and van der Waals forces that maintain albumin proteins in their folded, soluble state. The unfolded proteins aggregate into an insoluble mass, turning the egg white opaque and solid.
This material connects directly to enzyme function (BIO 311C, later chapters), because enzymes are proteins whose activity depends on maintaining their precise 3D shape through non-covalent interactions. It also underpins membrane biology: the phospholipid bilayer you study here is the structural basis for all cell membranes, transport processes, and cell signalling.
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