Chemistry Dipole Interactions and Hydrogen Bonding

Dipole Interactions

• Ion-dipole interactions occur when the charge on one molecule interacts with the dipole moment of another.
• This is stronger than a dipole-dipole interaction.
• The strength of this interaction falls off less rapidly with distance compared to a dipole-dipole interaction.
• Dipole-dipole interactions occur between polar molecules.

Hydrogen Bonding

• A type of dipole-dipole interaction where the proton of a group X-H (where X is an electronegative atom) interacts with other electronegative atoms containing a pair of nonbonded electrons.
• The interaction is denoted as -X-H…..Y- to indicate that a covalent bond still exists between X and H, but an interaction between H and Y occurs as well.
• There are intramolecular and intermolecular hydrogen bonds which play a significant role in biological activity.
• Hydrogen bonding plays a crucial role in maintaining the structural integrity of secondary structures like the α-helix and β-sheet conformation of peptides and proteins, as well as the double helix of DNA.

Van der Waals Interactions

• Very weak interactions that occur between hydrophobic regions of the drug and the target.
• Transient areas of high and low electron densities cause temporary dipoles.
• Interactions drop off rapidly with distance.
• The drug must be close to the binding region for these interactions to occur.
• Despite their individual weakness, the overall contribution of van der Waals interactions is crucial for drug binding.

Hydrophobic Interactions

• Hydrophobic regions of a drug and its target are not solvated by water molecules efficiently.
• Water molecules form an ordered layer around hydrophobic regions, resulting in a negative entropy change.
• Interactions between the hydrophobic regions of a drug and its target "free up" the ordered water molecules, resulting in an increase in entropy.
• This increase in entropy contributes favorably to the binding energy.

Reversible Enzyme Inhibitors

• Slow down or block enzyme catalysis by binding reversibly to the active site.
• The enzyme is not available for catalysis when the inhibitor is bound and the substrate is blocked from the active site.
• Increasing substrate concentration reverses the inhibition.
• The inhibitor is likely to be similar in structure to the substrate, product, or cofactor.

Competitive and Non-Competitive Inhibition

• Competitive Inhibition: The inhibitor competes with the substrate for binding to the active site.
• Non-Competitive Inhibition: The inhibitor binds to a different site on the enzyme, altering its conformation and reducing its activity.

Irreversible Inhibitors

• Bind irreversibly to the active site, permanently inactivating the enzyme.
• The inhibitor typically forms a covalent bond with the enzyme.
• This type of inhibition is not generally reversible.

Transition-State Inhibitors

• Mimic the transition state of the reaction catalyzed by the enzyme.
• Bind tightly to the active site, preventing the enzyme from forming the product.
• Often more potent than substrate-based inhibitors.