22. Which one of the following non-covalent interactions between two non-bonded atoms A and B is most sensitive to the distance between them?

    (1) A and B are permanent dipoles and are involved in hydrogen bonding.
    (2) A and B are fully ionized and are involved in salt bridge formation.
    (3) A and B are uncharged and repel each other.
    (4) A and B are uncharged and attract each other.

Introduction to Non-Covalent Interactions

Non-covalent interactions are vital in biochemical processes such as protein folding, molecular recognition, and membrane stability. They are less strong than covalent bonds but necessary for biological function.

Various kinds of non-covalent interactions are sensitive to distance to different extents, in that their strength differs radically as atoms approach or recede from each other.

Types of Non-Covalent Interactions and Their Sensitivity to Distance

1. Permanent Dipole-Dipole Interactions (Hydrogen Bonding) ❌

Hydrogen bonding happens when a hydrogen atom (H) is shared between two electronegative atoms such as oxygen (O), nitrogen (N), or fluorine (F).

Moderate dependence on distance – Strength of interaction falls off with distance as 1/r³ to 1/r⁶ (where r is distance).

Least sensitive to changes in distance.

2. Fully Ionized Atoms (Salt Bridge Formation) ❌

Salt bridges form between oppositely charged ions (e.g., carboxylate (-COO⁻) and ammonium (-NH₃⁺) groups).

Strong electrostatic forces obeying Coulomb‘s law (1/r dependence).

Less distance-sensitive than van der Waals forces.

3. Uncharged Atoms Repelling Each Other ❌

Uncharged atoms repel each other due to overlap of electron clouds (Pauli exclusion principle).

Accounted for by the A/r¹² term in the Lennard-Jones potential.

Important but not the most distance-sensitive interaction.

4. Uncharged Atoms Attracting Each Other (Van der Waals Forces) ✅

Van der Waals attraction is because of induced dipoles, also referred to as London dispersion forces.

Interaction energy decreases sharply with distance, having 1/r⁶ dependence.

Most distance-sensitive among the options provided.

Correct Answer: (4) Uncharged Atoms Attracting Each Other (Van der Waals Forces) ✅

Why Are Van der Waals Forces the Most Distance-Sensitive?

They are because of weak transient dipoles and are readily destroyed.

Short-range forces – decrease quickly as atoms separate.

Play a critical role in protein folding, membrane stability, and molecular recognition.

Importance of Distance-Sensitive Interactions in Biology

1. Protein Structure & Folding
Van der Waals interactions contribute to the stabilization of tertiary and quaternary protein structures.

2. Drug Binding & Molecular Recognition
Most drugs are based on weak interactions with receptors and enzymes.

3. Membrane Stability
Lipid bilayer is stabilized due to weak van der Waals forces between hydrophobic tails.

Conclusion
Of hydrogen bonding, salt bridges, repulsion, and van der Waals forces, the most distance-sensitive is van der Waals attraction between uncharged atoms. These forces decay very quickly with distance and are therefore essential in biochemical stability and molecular interactions.