Biochemistry Prep Notes: Water and Non-Covalent Interactions

Water: The Matrix of Life

Everything in biochemistry occurs within the context of water.
Water is an active participant in all biochemical processes.
A structure-function perspective helps understand biomolecules, but there are still mysteries about water that remain unsolved.

Structure of Water

Water (H2O) consists of an oxygen atom covalently bonded to two hydrogen atoms.
Oxygen is electronegative, pulling electrons towards it and creating a permanent dipole.
Oxygen carries a partial negative charge, while each hydrogen carries a partial positive charge.
Other electronegative atoms in biomolecules include nitrogen and phosphate, but carbon is not very electronegative.

Hydrogen Bonds

Water molecules form hydrogen bonds with each other.
A hydrogen bond is a specialized electrostatic interaction between an electronegative atom (oxygen or nitrogen) covalently linked to a hydrogen atom and another electronegative atom with a free electron pair.
Each water molecule can donate two hydrogen bonds (via its two hydrogen atoms) and accept two hydrogen bonds (via its two free electron pairs).
In ice, each water molecule participates in four hydrogen bonds, maximizing these interactions.
Water molecules like to interact with each other, influencing properties like heat of vaporization.

Heat of Vaporization

High heat of vaporization: Because water molecules associate strongly with each other, it takes a lot of energy to get them to vaporize.

Specific Heat Capacity

Water has a high specific heat capacity, meaning it can absorb a lot of energy before its temperature increases.
This is crucial for life because metabolic processes generate heat as a byproduct of energy transformations.
Water acts as a cooling system, absorbing heat without causing a large increase in body temperature.
$70\%$ of body weight is water.

Density

Ice is less dense than liquid water.
In liquid water, molecules form flickering clusters and exchange hydrogen bonding partners.
As water cools, molecules slow down and lock into stable hydrogen bonding arrangements.
In ice, each molecule forms four stable hydrogen bonds, creating a more ordered lattice that takes up more volume.
This lower density causes ice to float, forming an insulating layer on top of lakes and rivers, preserving ecosystems beneath.

The Mystery of Hot Water Freezing Faster Than Cold Water

Hot water can sometimes freeze faster than cold water.
Zambonis use hot water to melt cracks and divots for a smoother surface, and it freezes faster, allowing the next period to start sooner.
This phenomenon lacks a definitive scientific explanation.
Possible factors: smaller volume due to steam, momentum of cooling, or generation of currents promoting nucleation.

Polywater: A Cold War Scare

A Russian scientist claimed to create "polywater" with altered properties through specific treatments like high-pressure quartz capillaries.
Polywater supposedly had different freezing/boiling points, density, and viscosity.
The fear: polywater could convert ordinary water, disrupting biomolecular interactions and annihilating life.
An American scientist disproved it by showing that sweat contaminated with quartz had similar properties, revealing the original polywater was merely contaminated water.

Water Interactions with Solutes

Water interacts favorably with charged ions due to its partial charges.
Water molecules form hydration layers around positively charged (cations) and negatively charged (anions) ions.
Ions are hydrophilic and have high solubilities in water.

Hydrogen Bonding and Biomolecules

Functional groups in biomolecules can participate in hydrogen bonding.
Water molecules act as both hydrogen bond donors and acceptors.
Water molecules' small size allows them to optimize hydrogen bond geometry.
Water is always present in the context of molecules.

Hydrophilic vs. Hydrophobic Groups

Hydrophilic (water-loving) groups are polar, carrying a charge, or have hydrogen bonding capability.
Hydrophobic (water-fearing) groups are nonpolar, without charge or hydrogen bonding capability.
Hydrophilic = polar, hydrophobic = non-polar.

Amphipathic Molecules

Amphipathic molecules possess both polar and nonpolar portions.
Example: fatty acids with a charged carboxyl group (polar) and a hydrocarbon chain (nonpolar).

Solubility Issues in Biological Systems

Oxygen has low solubility in water; specialized transport proteins like hemoglobin and myoglobin are required to transport it in the blood.
Carbon dioxide, also relatively nonpolar, needs specialized systems for transport away from tissues.

Micelle Formation

Amphipathic molecules in solution form micelles, where nonpolar tails are buried in the core, away from water, and polar head groups are exposed to water.
This is driven by the hydrophobic effect: nonpolar portions try to get away from water, whereas polar portions want to interact with water.

Driving Forces for Biomolecular Structures

The hydrophobic effect, or the desire to bury hydrophobic residues, drives the formation of higher-order biomolecular structures.

Covalent vs. Noncovalent Interactions

Biomolecules are formed from building blocks linked together covalently.
Biological activity arises when these covalently linked strands fold into precise three-dimensional conformations stabilized by noncovalent interactions.
Noncovalent forces:
- Influence how biomolecules form higher order structures.
- Are involved in biomolecular interactions.
- Give structural flexibility to the biomolecules.

Paradigm Shifts in Protein Biochemistry

Proteins can adopt different conformations in response to different environments or interactions with different biomolecules.
This realization changed understanding of diseases like prion diseases, which are infectious proteins.

Prion Diseases

These are infectious diseases caused by misfolded proteins.
The prion protein (PrP) can fold into two conformations: a normal one and a misfolded one (pathological and infectious).
When the misfolded form encounters the properly folded form, it causes it to misfold.
The misfolded prion form on neurons kills the neurons creating a neurodegenerative disease.
Therefore, one becomes two until you die.

Inherently Unstructured Proteins

These proteins float around in an unfolded state and adopt different conformations.
Protein sociopaths are driven by the environment to change their structures.
This dynamic nature makes drug design more complicated because the structure is always changing.

Noncovalent Forces: Structure and Function

Noncovalent forces:
- Influence the types of structures that are formed.
- Influence the recognition and interaction between biomolecules.
- Influence the binding of reactants to enzymes or proteins.

Types of Noncovalent Interactions

There are four main types: hydrogen bonds, electrostatic interactions, hydrophobic interactions, and Van der Waals interactions.
These interactions govern every type of structure.

Hydrogen Bonds Revisited

When considering any functional group, the hydrogen bonding capability is key.
Anything that can form a hydrogen bond must form a hydrogen bond.
Water molecules are potential and highly attractive hydrogen bonding partners.
Hydrogen bonds can occur within the same molecule (intramolecular) or between two different molecules (intermolecular).

Watson-Crick Base Pairing

Adenine (A) pairs with Thymine (T), and Guanine (G) pairs with Cytosine (C) due to their hydrogen bonding potentials.
These base pairings are complementary where one nitrogenous base has a hydrogen bond donor, and the other is going to have a hydrogen bond acceptor.
Hydrogen bonding drives the specificity of DNA strand interactions critical for forming duplex DNA.

Applications of Base Pairing

There's the possibility of genetic predispositions, but then the question becomes, how accurate is it?
DNA can be scanned for specific genetic sequences, such as those associated with genetic diseases, through cheap, and fast techniques.
Duplex DNA is heated to separate strands. Next a nucleic acid probe is created, which has the potential sequence to target for the disease, and it is mixed in with your DNA. The solution is cooled, and the probe finds and binds to the complementary partner.
Insurance companies want your DNA so they know when you're going to die, it is better for their insurance plans, and a professor believes licking the envelop gives them the DNA.

The Importance of Specificity

Hydrogen bonding is important for determining the specificity of the structures that are going to be formed.
Hydrogen bonding is NOT a driving force for the formation of biomolecular structures.
Water gets perfect geometry with hydrogen and bonds.

Electrostatic Interactions

Charge groups within biomolecules: positive or negative.
Same charges repel, opposite charges attract.
These tend to be strong but remember they are occurring in the context of water that is interacting with charge groups, which dampens the strength of these electrostatic interactions.
Ex) Packaging NDA with histones because DNA has a lot of negative charges, so histones have a lot of positive charges.