Water Properties: Hydrogen Bonds Explained

• Water is the most abundant molecule in living organisms and plays both passive and active roles in biochemistry.
• The structure of biomolecules forms in response to interaction with water, such as protein folding driven by hydrophobic residues.
• Water participates in many biochemical reactions, like peptide bond formation that releases a water molecule.
• Water shapes how we look for life and is critical to the molecular basis of life
• The presence of water on other planets is a critical determinant of their habitability by humans.
• Ammonia or formamide are alternate liquids that may be suitable for life.
• The simple structure of water illustrates the structure-function perspective
• Oxygen is more electronegative than hydrogen, giving water a permanent dipole.
• Oxygen has a partial negative charge, and each hydrogen has a partial positive charge.
• Each water molecule can donate or accept two hydrogen bonds
• This influences its ability to:
• Form electrostatic interactions with charged molecules
• Form hydrogen bonds, including with other water molecules

Hydrogen Bonds

• Hydrogen bonds are electrostatic interactions between an electronegative atom with a hydrogen covalently linked (donor) to another electronegative atom with a free electron pair (acceptor).
• Oxygen and nitrogen are common hydrogen bonders within biomolecules
• Oxygen and nitrogen can each serve as hydrogen bond donors and acceptors.
• Hydrogen bonds are relatively weak, about 5% of the strength of a covalent bond.
• Hydrogen bonds are about double the length of a covalent bond.
• The strength of a hydrogen bond depends on its geometry
• Anti-parallel beta sheets are more stable than parallel due to better geometry of hydrogen bonding.

Unusual Properties of Water

• Each water molecule can donate and accept two hydrogen bonds.
• Each water molecule has the potential to participate in four hydrogen bonds with four other water molecules.
• In the liquid phase, each molecule participates in an average of 3.4 hydrogen bonds in dynamic "flickering clusters".
• The hydrogen bonds between water molecules confer great internal cohesion, influencing the properties of water.
• Heat of Vaporization refers to the amount of heat to vaporize a liquid at its boiling temp
• Specific Heat Capacity refers to the amount of heat required to raise the temperature of a substance one degree.
• Water has a higher melting point, boiling point, and heat of vaporization than most common solvents.
• Living organisms burn tremendous amounts of energy, a by-product of which is heat.
• Isothermic organisms need to regulate and maintain their temperatures.
• The high composition of water within bodies, coupled with the high specific heat capacity of water, helps us to regulate heat.
• In ice, each water molecule participates in four hydrogen bonds with other water molecules, resulting in lower density than liquid form
• Ice floats on water as a consequence of lower density
• A Soviet physicist studied the properties of water forced through quartz tubes
• This treatment resulted in polywater, a new water form with a higher boiling point and lower freezing point, and higher viscosity than ordinary water.
• Polywater was proposed to result from a novel arrangement of interaction between water molecules.
• There was considerable concern that the unusual networking of water molecules within polywater was self-propagating and useable as a weapon, but polywater turned out to be bad science.
• An American scientist demonstrated that their own sweat had properties remarkably similar to polywater, with unique properties reflecting impurity influence

Water as a Solvent

• Water molecules can interact and dissolve charged solutes through the formation of hydration layers.
• Small size and permanent dipole enable water molecules to interact with both positively and negatively charged ions.
• Biomolecules have functional groups can form hydrogen bonds.
• These groups can hydrogen bond within the same molecule, other biomolecules, or with water.
• Water molecules are ideal hydrogen bonding partners, due to small size and ability to serve as either donors or acceptors
• The solubility of molecules in water depends on the ability to interact with water molecules.
• Molecules with charge (+ or -) and/or participate in hydrogen bonds have the greatest solubility in water.
• Hydrophilic (water-loving) molecules are polar.
• Hydrophobic (water-fearing) molecules are non-polar.
• Amphipathic molecules contain both hydrophobic and hydrophilic portions (e.g., fatty acids).
• Many biologically important gases, such as CO2 and O2, are non-polar and therefore have limited solubility in water (and blood).
• Specialized transport proteins and strategies transport CO2 and O2.
• The hydrophilic regions interact favorably with water, but the hydrophobic regions cluster together to present the smallest surface to water in amphipathic substances.
• The forces that hold non-polar molecule regions together are called hydrophobic interactions.
• Most biomolecules are amphipathic.
• Hydrophobic drive is a primary driving force in formation and stabilization of biomolecular structures.
• Water molecules around hydrophobic molecules are more ordered than in pure water; introducing the non-polar molecule causes a entropy decrease in the water.
• The association of non-polar molecules (or regions) releases ordered water molecules, resulting in an entropy increase in the water.
• Polypeptide folding decreases polypeptide entropy while increasing entropy of associated water

Weak Interactions

• Most biomolecules are stable polymers of covalently linked building blocks.
• The three-dimensional structures formed by these polymers are largely determined through non-covalent interactions.
• Interactions between biomolecules are also largely determined by non-covalent interactions.
• Non-covalent interactions enable transient, dynamic interactions and flexibility of structure and function.
• Non-covalent forces influence formation and stabilization of structures of biomolecules, recognition/interactions between biomolecules, and binding of reactants to enzymes.
• Non-covalent interactions within biomolecules include hydrogen bonds, ionic (electrostatic) interactions, hydrophobic interactions, and van der Waals interactions.

Hydrogen Bonds

• Many functional groups with biomolecules have hydrogen bonding capacity.
• Groups can form hydrogen bonds with water molecules, groups in the same molecule (intramolecular), or groups in other molecules (intermolecular).
• Hydrogen bonds are critical for the specificity of biomolecular interactions but not for the formation of biomolecular structures.
• In the unfolded state, these groups can hydrogen bond with water, a nearly perfect hydrogen bonder.
• Little is gained, from a hydrogen bonding perspective, with formation of higher order structures.

Ionic (Electrostatic) Interactions

• Electrostatic interactions between charged groups can be attractive (oppositely charged groups) or repulsive (similarly charged groups).
• The magnitude of contribution of ionic interactions to biomolecular structures is reduced by the shielding of these groups by water molecules.
• Water tends to shield the charged groups, greatly diminishing the interaction strength.
• The strength of electrostatic interactions depends on the distance separating the atoms and the nature of the intervening medium.

Van der Waals Forces

• Interaction between permanent and induced dipoles are short range, low magnitude interactions.
• The attraction is maximal when two atoms are separated by the van der Waals radii sum.
• A large number of atoms are brought into van der Waals contact when two surfaces of complementary shapes come together.
• These forces are abundant in the folded proteins core.

Hydrophobic Effect

• There is a drive to have polar groups interacting with water and non-polar regions shielded away from water.
• Non-polar side chains cluster in the protein interior, away from water.
• Polar and charged side chains remain on the outer surface facing water.
• Protein folding involves creation of a more ordered state, which seems to contradict the Second Law of Thermodynamics.

Water Memory

• A paper reported that an extreme dilution of a biomolecule retained biological activity.
• The extent of the dilution was such that there was no possibility that even a single molecule remained.
• Authors suggested water molecules "remember" what the original molecule looked like through retention of interactions between water molecules in the presence of active agent.
• This was published in Nature, the most respected scientific journal.
• In the following issue, Nature offered its conclusion that there is no substantial basis for the claim that (molecule) retains its biological effectiveness at high dilution, and that the hypothesis that water can be imprinted with the memory of past solutes is unnecessary and fanciful.
• Homeopathic remedies are prepared by repeatedly diluting a chosen substance, often 30 sequential dilutions of 1 in 100.
• This corresponds to a dilution of 1 in 1, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000.
• By our current understanding of the natural world, homeopathy makes no sense.
• Countless investigations have failed to find any scientific merit to homeopathy and yet selling water as medicine remains a multi-billion dollar industry.
• The disproven theory that water molecules remember shapes has been used as homeopathy support.

Ionization of Water

• In solution, the structure of water is more complicated than H2O.
• Water has a limited tendency to ionized to hydrogen ions (H+) and hydroxide ions (OH-).
• Kw is the ion product of water.
• It is more convenient to express [H+] as pH.
• pH is a log scale such that the difference of 1 pH unit equals a 10-fold difference in [H+].
• Strong acids and bases dissociate completely in water.
• Weak acids and bases do not dissociate completely in H₂O, but can serve as buffers.
• The extent of dissociation can be quantified.
• Kₐ values often expressed as pKa's (pKa = -log Ka).

Titration of Weak Acids

• The ratio of the acid to the conjugate base changes over the course of the titration curve.
• When pH = pKa then [A-] = [HA].
• When pH = pKa the solution is best able to resist changes in pH.
• Buffering region extends one pH unit on either side of the pKa point.
• For a weak acid of pKa 4.76, the buffering range would be 3.76 to 5.76.
• The line in red represents the weakest acid.
• The line in blue represents the strongest acid.
• The lower the pKa, is the stronger the acid.
• Organisms need to be able to maintain a constant pH.
• Changes to pH could alter the protonation state of biomolecules, potentially changing their structure and function.
• A number of weak acids serve to buffer biological systems.
• The blood pH is maintained by a bicarbonate buffer system.

Henderson-Hasselbalch Equation

• Describes the relationship between pH of the solution, pKa of the weak acid, and relative concentrations of the weak acid (HA) and conjugate base (A- .)
• Given any two of these variables is possible to calculate the third.

Explore the unique properties of water stemming from hydrogen bonds. Understand hydrogen bond strength, beta sheet stability, and water's role in temperature regulation within living organisms. Learn about water's heat of vaporization and dynamic behavior in biochemistry.