Biochemical Foundations: Hydrophilicity, Lipophilicity, and Drug Behavior (Week 2)

A comprehensive set of 30 vocabulary flashcards covering fundamental biochemical principles of hydrophilicity, lipophilicity, solubility, thermodynamic forces, and drug-receptor interactions.

Electronegativity

A measure of how strongly atoms attract bonding electrons to themselves.

Bond dipole moment

The separation of charge created when electrons in a covalent bond connecting two different atoms are unequally shared due to differences in electronegativity.

Non-polar covalent bond

A covalent bond occurring when there is equal or nearly equal sharing of electrons between two atoms, typically characterized by an electronegativity difference of $0.5$ or less.

Polar covalent bond

A covalent bond occurring when there is unequal sharing of electrons between two atoms, typically characterized by an electronegativity difference from approximately $0.5$ up to $1.9$.

Ionic bond

A bond characterized by the complete transfer of electrons between two atoms, generally occurring when the electronegativity difference is greater than $2.0$.

Hydrogen bond donor

A hydrogen atom covalently bound to a strongly electronegative atom, specifically nitrogen or oxygen in drug chemistry, forming a $\text{N-H}$ or $\text{O-H}$ bond.

Hydrogen bond acceptor

An electronegative atom bearing a lone pair of electrons, such as oxygen, nitrogen, or fluorine, that electrostatically interacts with a hydrogen bond donor.

Flickering clusters

The continuous phenomenon in bulk water where hydrogen bonds continually form and break between water molecules.

Bulk water hydrogen bond average

The average number of hydrogen bonds formed per individual water molecule in pure bulk water, which is equal to $3.4$.

Maximum hydrogen bonds per water molecule

The maximum number of hydrogen bonds an individual water molecule is capable of forming with surrounding water molecules, which is equal to $4$.

Net dipole moment

The overall molecular dipole resulting from the vector sum of individual bond dipoles, which can be zero in symmetrical molecules like carbon dioxide despite containing polar covalent bonds.

Hydrophilic

A property describing substances that are water-soluble, including ionized compounds and molecules capable of hydrogen bonding with water.

Lipophilic

A property describing non-polar, water-insoluble substances, such as hydrocarbons, that prefer non-polar environments.

Ionized compounds

Substances carrying full positive or negative charges, such as salts or molecules with quaternary nitrogen atoms, which represent the most water-soluble class of compounds.

Salt dissolution entropy

The large increase in system entropy ($\Delta S$) that occurs when water molecules form interacting shells around free cations and anions, favoring dissolution.

Amphipathic

Describing a molecule that contains both hydrophilic (polar) and lipophilic (non-polar) regions, a common property of cell membrane phospholipids and most drugs.

Passive diffusion

The mechanism by which $95\%$ of orally-administered drugs cross the lipid bilayer of small intestine mucosal cells to enter the bloodstream.

Partition Coefficient

A measure of a solute's differential solubility between two immiscible phases, defined as $\text{PC} = \frac{[\text{concentration of drug in octanol}]}{[\text{concentration of drug in water}]}$.

1-Octanol

The most frequently used lipid phase in pharmaceutical partition coefficient research because its structure contains both polar and nonpolar regions similar to biological membranes.

Optimal Log P range

The recommended guide range of $\text{Log}\,P$ values from $0$ to $3$ required for optimal drug absorption to balance membrane permeability and water solubility.

Fragment Method

A computational approach for calculating a molecule's partition coefficient by summing specific pi ($\pi$) values assigned to each of its chemical fragments.

Enthalpy of solution

The overall enthalpy change ($\Delta H$) associated with dissolving a substance in a solvent, typically expressed in $kJ\,mol^{-1}$ at constant temperature.

Endothermic dissolution steps

The two initial energy-absorbing steps of dissolution: breaking solute-solute interactions and breaking solvent-solvent interactions.

Exothermic dissolution step

The energy-releasing step of dissolution involving the formation of attractive interactions between solute and solvent molecules.

Hydrophobic effect

An entropy-driven process ($\Delta G = \Delta H - T\Delta S$) where non-polar molecules aggregate in aqueous solution to minimize exposed surface area and release ordered cage water molecules.

Water cage structure

A highly organized shell of hydrogen-bonded water molecules that reorients around a diluted non-polar solute, causing an unfavorable decrease in system entropy.

Entropy loss per cage water molecule

The thermodynamic penalty of up to $2$ entropy units (approximately $0.6\,kcal\,mol^{-1}$) lost by each water molecule participating in an ordered cage around a hydrophobic solute.

Hydrophobic effect in protein folding

The driving force that causes globular proteins to bury non-polar amino acid side chains into their interior while exposing polar and charged side chains to water.

Stabilization energy of buried methylene groups

The energetic stabilization gained during protein folding, providing approximately $0.8\,kcal\,mol^{-1}$ of stabilization for each buried $-\text{CH}_2-$ group.

Receptor hydrophobic pocket

A region on a drug receptor composed of non-polar amino acid side chains that binds to the lipophilic portion of an amphipathic drug molecule.