CHEM 191: Molecules in Biological Environments

• CHEM 191 Module 1 Lecture 9 is on Molecules in Biological Environments.

Learning Objectives

• Recognize the structural features of a molecule that make it polar or non-polar
• Understand how water solvates ions and polar molecules
• Understand how the pH of a solution determines the ionization state of a molecule
• Understand how non-polar molecules behave in water
• Understand the structure and fundamental roles of membranes

Polar vs Non-polar Molecules

• Polar molecules form favorable interactions with water molecules
• Polar molecules include those with polar bonds and charged regions
• Polar molecules are hydrophilic, meaning water-loving
• Water is a polar molecule, adhering to the principle of "like dissolves like"
• Alcohols do NOT ionize
• Non-polar molecules do not have polar bonds or charged parts
• Non-polar molecules do not dissolve in water but dissolve in other non-polar solvents
• Non-polar molecules are hydrophobic, meaning water-hating

Water as a Polar Molecule

• Water is the main component of most cells
• Water's polar nature enables electrostatic interaction with charged molecules, known as hydration
• Water molecules themselves participate in hydrogen bonding
• Hydrogen bonding is a powerful driving force

Hydrogen Bonding

• Various types of hydrogen bonding exist in biological molecules
• Examples include solvation by water, interactions within proteins, and interactions within DNA and RNA

Ionisable Functional Groups

• Many molecules or parts of molecules found in biological systems exist in charged and uncharged forms
• Ionization status is influenced by the pH of the aqueous environment and the propensity of the functional group to ionize (pKa)
• pKa represents the pH at which half (50%) of the functional groups of a molecule are ionized
• At >1 pH unit below pKa, ~90% of molecules are protonated
• At >1 pH unit above pKa, ~90% of molecules are deprotonated

Ionisable Functional Groups - Amino Acids

• In the titration curve for glycine, pKa1 relates to the pKa of the carboxylic acid, while pKa2 relates to the pKa of the ammonium ion
• An α-amino group is protonated when charged (+ve), and an α-carboxyl acid group is deprotonated when charged (-ve)
• Side chains of some amino acids have ionizable functional groups, and thus their ionization state depends on the solution's pH
• In proteins, most α-amino and α-carboxyl groups on amino acids are involved in bonds and are unavailable for ionization
• A protein's net charge relies on the ionizable side chains (R groups) and the N- and C-termini

Ionisable Functional Groups - Buffers

• To function properly, biological systems require molecular components to be in a specific ionization state and charge
• Variations in pH in the aqueous environment must be minimized by using buffers
• The blood buffering system utilizes bicarbonate; proteins and other molecules also contribute
• The intracellular buffering system utilizes phosphate; proteins and other molecules also contribute
• Some specialized cell environments may vary more widely in pH
• Many ionizable groups on macromolecules contribute to charge distribution and influence the shape of the molecule
• For example, DNA is negatively charged, so a protein interacting with DNA typically needs to be positively charged

Ionisable Functional Groups - Enzymes

• The ionization state of amino acid side chains is crucial for enzyme operation
• The active site of chymotrypsin, a protease that breaks down proteins, contains a catalytic triad of amino acid side chains

Non-polar Molecules in Water

• Water molecules hydrate a non-polar molecule in an aqueous environment by forming a constrained hydration shell
• Non-polar molecules aggregate together in aqueous solutions
• Non-polar regions of macromolecules (e.g., proteins) "hide" away from the aqueous environment

Molecules with Polar and Non-polar Regions - Phospholipids

• Phospholipids contain polar head groups and non-polar tails
• Polar heads interact with the aqueous environment, while non-polar tails face inward

Membranes

• Biological membranes provide non-aqueous barriers in aqueous cellular environments
• Polar head groups of lipids are arranged in bilayers and interact with the aqueous environment
• The non-polar membrane core formed by the lipid tails constrains molecules to a location either inside or outside the membrane-bound compartment
• Lipid membranes are heterogeneous, the lipid composition varies, the membrane structure is dynamic, and other molecules may be associated with it or inserted into the membrane
• Other molecules (e.g. proteins) may be inserted into the membrane to enable reception and communication of signals or transfer of molecules across the membrane
• The membrane can divide a cell or an organelle within a cell

Membrane-bound Proteins

• A variety of amino acid sequences have evolved for insertion in membranes, forming protein pore structures