Fundamental Intermolecular Forces

Why This Matters

Intermolecular forces are the invisible glue holding biological systems together—and they're foundational to everything you'll encounter in this course. You're being tested on your ability to explain why water behaves the way it does, how proteins fold into functional shapes, and what drives molecules to dissolve, aggregate, or bind to each other. These concepts connect directly to topics like enzyme function, membrane structure, and the physical properties of biological molecules.

Don't just memorize that hydrogen bonding is "strong"—know when each force dominates, why it matters for biological function, and how to compare forces in different contexts. The exam will ask you to predict molecular behavior, explain solubility trends, and connect intermolecular forces to macroscopic properties. Master the underlying principles, and you'll be ready for any question they throw at you.

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Universal Forces: Present in All Molecules

Every molecule experiences London dispersion forces, regardless of polarity. These arise from instantaneous, temporary dipoles created by electron movement.

London Dispersion Forces

• Temporary dipoles—arise from momentary fluctuations in electron distribution, inducing dipoles in neighboring molecules
• Polarizability determines strength; larger atoms with more electrons are more easily distorted, leading to stronger interactions
• Dominant force in nonpolar substances, explaining why noble gases and hydrocarbons can still condense into liquids at low temperatures

Van der Waals Forces

• Umbrella term encompassing London dispersion forces, dipole-dipole interactions, and sometimes hydrogen bonds
• Collectively responsible for molecular recognition—the way enzymes "find" their substrates depends on the sum of many weak interactions
• Distance-dependent; these forces drop off rapidly as molecules move apart, making close contact essential for strong binding

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Permanent Dipole Interactions

Polar molecules have uneven electron distribution, creating regions of partial positive ($\delta^+$) and partial negative ($\delta^-$) charge that attract each other.

Dipole-Dipole Interactions

• Permanent partial charges attract—the $\delta^+$ end of one molecule aligns with the $\delta^-$ end of another
• Stronger than London dispersion in molecules of similar size, but weaker than hydrogen bonds
• Influence boiling points and solubility; polar molecules like acetone have higher boiling points than nonpolar molecules of similar mass

Hydrogen Bonding

• Special case of dipole-dipole interaction—occurs when H is bonded to N, O, or F (the most electronegative elements)
• Unusually strong due to hydrogen's small size and the high electronegativity difference, typically 10-40 kJ/mol
• Critical for life—stabilizes DNA's double helix, determines water's unique properties, and maintains protein secondary structures like $\alpha$-helices and $\beta$-sheets

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Ion-Involved Interactions

Charged species create strong electric fields that interact powerfully with dipoles—either permanent or induced.

Ion-Dipole Interactions

• Strongest intermolecular force in solutions—occurs between ions and polar molecules like water
• Drives solvation; when NaCl dissolves, water molecules orient their $\delta^-$ oxygen toward $Na^+$ and $\delta^+$ hydrogens toward $Cl^-$
• Essential for biological ion transport—membrane proteins use ion-dipole interactions to shuttle $K^+$, $Na^+$, and $Ca^{2+}$ across hydrophobic barriers

Ion-Induced Dipole Interactions

• Ion distorts electron cloud of a nearby nonpolar molecule, creating a temporary dipole
• Weaker than ion-dipole because the induced dipole is temporary and depends on polarizability
• Relevant in enzyme active sites where metal ions interact with nonpolar portions of substrates

Electrostatic Interactions

• Full charges attract or repel—follows Coulomb's law: $F = k\frac{q_1 q_2}{r^2}$
• Strongest of all intermolecular forces when comparing ion-ion interactions to other types
• Salt bridges in proteins—interactions between charged amino acid side chains (like lysine and glutamate) stabilize tertiary structure

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Aromatic and π-System Interactions

Aromatic rings contain delocalized electrons in π orbitals, creating electron-rich surfaces that participate in unique interactions.

Cation-π Interactions

• Positive ion attracted to electron-rich π cloud—common between $K^+$, $Na^+$, or protonated amines and aromatic rings
• Surprisingly strong—can rival hydrogen bonds in biological systems (5-80 kJ/mol)
• Key for molecular recognition—neurotransmitter receptors often use cation-π interactions to bind acetylcholine and other charged ligands

π-π Stacking

• Aromatic rings align in face-to-face (sandwich) or edge-to-face (T-shaped) orientations
• Stabilizes nucleic acid structure—DNA base pairs stack vertically, contributing significantly to double helix stability
• Important in drug design—many pharmaceuticals contain aromatic rings that stack with target biomolecules

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Entropy-Driven Interactions

Not all "forces" involve direct attraction—some molecular behaviors emerge from the system's drive to maximize entropy.

Hydrophobic Interactions

• Not a true attractive force—nonpolar molecules cluster because it increases water's entropy, not because they attract each other
• Water forms ordered "cages" around isolated nonpolar molecules; clustering reduces this ordering, releasing water to move freely
• Drives protein folding—hydrophobic amino acids bury themselves in the protein interior, away from aqueous surroundings

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Quick Reference Table

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Self-Check Questions

1. Which two intermolecular forces both involve permanent dipoles, and what distinguishes the stronger one from the weaker?

2. A nonpolar molecule dissolves poorly in water but clusters with other nonpolar molecules. Which interaction explains this behavior, and what is the thermodynamic driving force?

3. Compare ion-dipole and hydrogen bonding: which is typically stronger, and in what biological context would each be most important?

4. An enzyme active site contains a tryptophan residue (aromatic) near a bound $K^+$ ion. What type of interaction stabilizes this arrangement, and why is it effective?

5. (FRQ-style) Explain how intermolecular forces contribute to the stability of a protein's tertiary structure. Include at least three different types of forces and describe where in the protein each would be most significant.