Non-Covalent Interactions + Energy

Question 1

Define:

What is biochemistry?

(According to Wikipedia)

Answer 1

The study of chemical processes within and relating to living organisms

(Source: Wikipedia)

Question 2

List:

Give three key fields that come under the umbrella of biochemistry

Answer 2

1. Structural Biology
2. Enzymology
3. Metabolism

Question 3

Fill-in-the-Blank:

‘Life is almost entirely ____’

Answer 3

Bacterial

But ‘extremely diverse’!

Question 4

Explain:

Why may biochemistry be analogised to a black box of life function?

Answer 4

It deals with studying the processes within organisms that convert ‘inputs’ to ‘outputs’

‘Inputs’ : food, water, energy, oxygen, signals, etc.
‘Outputs’ : work, CO2, offspring, water, waste, etc.

Question 5

Define:

What are metabolic networks?

Answer 5

A way of organising molecules through chemical reactions and interactions

These are enzyme-reliant (due to their catalysis of each reaction step)

Question 6

Explain:

Why are non-covalent interactions so important in biochemical systems?

(Also referred to as weak forces)

Answer 6

They give rise to selectivity & reversibility of reactions and thus dynamic processes required to sustain life

These non-covalent/weak interactions are constantly breaking and reforming under the physiological conditions of the organism

Question 7

List:

State the FOUR main non-covalent interactions / weak forces:

Answer 7

1. Van der Waals Interactions
2. Hydrogen Bonds
3. Ionic Interactions
4. Hydrophobic Interactions

Several of these weak interactions may work in conjunction at one time to increase the strength of the overall interactions of the system/structure (e.g. in protein structure)

Question 8

Fill-in-the-Blank:

____ is mediated by non-covalent interactions

Answer 8

Biochemical Recognition

(i.e. the specific interactions between molecules)

The binding of a substrate to the active site of an enzyme is a perfect example of this

Question 9

Fill-in-the-Blank:

‘Weak forces restrict organisms to a ________________’

Answer 9

Narrow range of environmental conditions

e.g. the denaturing of enzymes above their optimal pH or temperature ranges

Question 10

Define:

Enthalpy (H)

Answer 10

A measure of the total heat content of a system

It is the sum of the internal energy plus the product of the pressure and volume (H = E + PV)

Question 11

Without using the word disorder, describe what Entropy (S) is:

(i.e. an alternative definition to ‘the level of disorder’ one)

Answer 11

A measure of states with distributed energy within a system

(i.e. how dispersed the energy of a system is)

Question 12

Define and Explain:

State the Gibbs Free Energy Equation and describe what it represents:

Answer 12

ΔG = ΔH − TΔS
The value (positive, negative, zero) of ‘ΔG’ predicts the spontaneity of a chemical reaction

Note: the above equation displays that reactions can either be enthalpy or entropy driven (i.e. both do not have to be favourable)

Question 13

Define:

Van der Waals interactions/forces

Answer 13

Non-specific and non-directional attractions between atoms/molecules whose valence electron clouds become sufficiently proximal to each other.

This typically involves temporary dipole changes/electrical fluctuations.

Question 14

What are THREE key factors that contribute to/enhance the relative strength of Van der Waal forces?

Answer 14

1. Structural Complementarity - how ‘tightly’ the atoms/molecules can pack together.
2. Polarisability - larger electron clouds/density available for dipole/dispersive interactions.
3. Surface Area - force increases with increase molecular SA.

Structural complementarity can be seen in the example of more linear isomers of a molecule packing together more efficiently, and thus having stronger VDW forces.

The above notion relates to surface area as well, due to the more linear isomers having greater molecular surface area in contact with each other (and thus increased cummulative VDW interactions).

Question 15

Define:

Hydrogen Bonding

Answer 15

Bonds that form between a ‘donor group’ and an ‘acceptor group’.

Donor Groups = an electronegative atom (e.g. O, N, S) + a hydrogen (H) bonded to it.

Acceptor Groups = an electronegative atom with a lone pair (e.g. O, N, S).

Question 16

Fill-in-the-Blank:

Hydrogen bonding between molecules forms very ____ ____.

Answer 16

organised arrangements.

This is particularly poignant when it comes to the emergent properties of water.

It also means that entropy of the system decreases, but the high bond enthalpy helps counteract this (thermodynamics).

Question 17

Define:

Ionic Interactions

Answer 17

Electrostatic attractions between oppositely charged ions/groups.

These contribute to stabilising protein structures through interactions of amino acid side-chains from different sections of polypeptide chains.

However, ionic interactions often dissacoiate in water, and so they are not ‘permanent’ and still considered a ‘weak interaction’.

Question 18

What are the TWO terms describing the break-down & reformation of protein/enzyme structure?

Answer 18

Denaturation & Renaturation.

Question 19

Fill-in-the-Blank:

Bond-formation processes ____ entropy.

Answer 19

decrease

They lead to the order of the system increasing.

However, sometimes bond-formation can lead to water molecule displacement (i.e. disrupting the organised structure of a network of liquid water) and thus increase entropy in this sense.

This is because water molecules break hydrogen bonds with each other to bond with other (solute) molecules/atoms.

Question 20

Fill-in-the-Blank:

Water is a ____ solvent, and therefore dissolves ____ substances. It cannot dissolve ____ substances as it cannot form ____ ____ with the ____ regions of these molecules.

Answer 20

Water is a polar solvent, and therefore dissolves polar substances. It cannot dissolve nonpolar substances as it cannot form hydrogen bonds with the hydrophobic regions of these molecules.

Question 21

Describe:

Bonding between water molecules in the liquid state.

Answer 21

Water molecules are continuously forming & breaking hydrogen bonds as they ‘slide’ past each other, and have an average of ~2.3 bonds with other surrounding molecules at one time.

Recent findings from scientists in Japan (2020) show that a mixture of tetrahedral and similar to ‘ring-and-chain’ structures are formed (but with a majority being tetrahedral in the liquid).

Question 22

Describe:

A Clathrate Cage.

Answer 22

This is a bonding formation/pattern formed (by water molecules) under certain conditions whereby the polar solvent molecules ‘form a cage’ around the non-polar solute molecules.

Although the water molecules forming the cage have decreased entropy, it minimises the number of molecules affected as the rest can still move about freely.

This is because it causes the solute to ‘clump together’ and minimises its disruption of the rest of the liquid’s structure (i.e. it increases the entropy of the solvent when the solute molecules coalesce).

Question 23

Define:

The Dielectric Constant (D).

Answer 23

A measure of a substance/compound’s ability to and capacity for storing electrical energy.

Physical chemists also refer to this as its relative permittivity.

Question 24

What is significant about the dielectric constant for substances such as water?

Answer 24

Its high value means that…

• It is capable of ‘screening/insulating charges’.
• It is highly polarisable.

Water’s strong ability to ‘screen’ charges plays a crucial role in the dissolving of polar/ionic solutes, as it is able to overcome the ionic forces of attraction between cations and anions, separate, and then surround/isolate them from each other.

Question 25

Fill-in-the-Blank:

“____ ____ through ____ ____ is the principle that guides the ____ ____” that are characteristic of life.

Answer 25

“Molecular recognition through structural complementarity is the principle that guides the biomolecular interactions” that are characteristic of life.

(Source: BIOL244 Lecture 1 Slides)

Question 26

Describe:

Couloumb’s Law and how the dielectric constant (D) relates to it.

Answer 26

An equation representing the fact the magnitude of electrostatic force between two charged species is directly proportional to the product of the two charges divided by the product of the dielectric constant and distance between the charges.

This means, the larger the dielectric constant and/or radius/distance, the weaker the electrostatic attraction.

Question 27

Define:

Hydrophobic Interactions

Answer 27

The aggregation of non-polar/hydrophobic substances in a water environment in order to minimise contact with water molecules.

This is important in processes such as protein folding whereby non-polar regions of the polypeptides undergo ‘** hydrophobic collapse**’, resulting in most of the non-polar regions being located internally in the final protein structure.

Question 28

Explain:

The changes in potential/interaction energy with changes in the distance between atomic radii.

Answer 28

The closer the atomic radii, the stronger the attractive interactions, up until an optimum/critical distance, beyond which increased proximity leads to the positive nuclei repelling each other.

This is particularly important for Van der Waals interactions, as the strength of these non-covalent interactions increase with proximity, but only to a certain point.

Beyond this optimum distance, the positively charged atomic radii become too close to each other and begin to repel due to their like-charges (depicted by the asymptote in the above graph).

The ‘dramatic dip’ in the graph is caused by repulsive interactions between electron clouds as the distance between the two atomic radii increase.

Question 29

Define:

An isolated system.

Answer 29

A system in which there is no exchange of matter nor energy with its surroundings.

Note: this would spell disaster for biological systems, as they are actively avoiding reaching a state of equilibrium - which is achieved in isolated systems when reactions are allowed to ‘run their course’.

Question 30

Define:

A closed system.

Answer 30

A system in which matter cannot be transferred with the surroundings, but energy transfers are able to occur.

Question 31

Define:

An open system.

Answer 31

A system in which both energy and matter are able to be transferred with the surroundings.

This encapsulates biological systems, as transfers of energy/matter are vital for driving life-sustaining processes.

Question 32

State:

The 1st Law of Thermodynamics.

Answer 32

‘The total energy of the universe remains constant’.

(i.e. ‘Energy can neither be created nor destroyed, only transferred and transformed’).

This is because the ‘universe’ is made up of systems + their surroundings, so any energy/matter exchanges between the two constructs, has no overall change on the total energy/matter of the universe.

Question 33

State:

The 2nd Law of Thermodynamics.

Answer 33

‘Systems tend to proceed towards higher entropy states, and the overall entropy of the universe is constantly increasing’.

This means if the entropy of a particular system has a net decrease, the net change in entropy of its surroundings must increase.

(i.e. so long as the overall entropy of the universe increases).

Question 34

State:

The 3rd Law of Thermodynamics.

Answer 34

‘The entropy of a system approaches a constant value the closer it gets to absolute zero’.

Note: This relates to the entropy of a ‘pure crystalline substance’ being exactly zero when it reaches absolute zero (kelvin).

https://www.sciencedirect.com/topics/chemistry/third-law-of-thermodynamics#:~:text=of%20the%20Game)-,The%20third%20law%20of%20thermodynamics%20states%20that%20the%20entropy%20of,different%20ground%20states%20it%20has.

Question 35

Define:

A ‘system’.

Answer 35

A ‘portion of the universe’ of which we are observing/concerned with.

Question 36

Define:

‘Surroundings’.

(In the context of thermodynamics)

Answer 36

Anything else in the universe that is not the ‘system’ we are concerned with.

Question 37

Fill-in-the-Blank:

‘The entropy change of a system + its surroundings is ____ in reversible processes, and ____ for irreversible processes’.

Answer 37

unaffected/unchanged
&
positive

Question 38

What do all processes proceed towards?

Answer 38

Equilibrium

(i.e. minimum potential energy).

Question 39

True or False:

Entropy of a system is increased if energy is dispersed because of a reaction.

Answer 39

True

Question 40

True or False:

A reaction with a high rate must be spontaneous.

Answer 40

False

Reaction rates are determined by the activation energy/energy barrier (i.e. the amount of initial energy required in order for it to reach the transition state).

Contrastingly, spontaneity is determined by the Gibb’s free energy difference between the reactants and products.

Question 41

True or False:

A reaction with a slow rate CANNOT be spontaneous.

Answer 41

False

Reaction rates are determined by the activation energy/energy barrier (i.e. the amount of initial energy required in order for it to reach the transition state).

Contrastingly, spontaneity is determined by the Gibb’s free energy difference between the reactants and products.

Question 42

True or False:

Ionic interactions impose directionality constraints on the electrostatic attraction of ions.

Answer 42

False

Question 43

True or False:

It would be entropically unfavourable but enthalpically favourable for hydrogen bonding to occur between two molecules (in a vacuum).

Answer 43

True

Their level of ‘order’ would increase, but a relatively large energy release will result from the bond formation and stabilisation.

Question 44

What TWO parameters must a reaction be either of in order to proceed?

Answer 44

It must be either sponatneous or coupled with an exergonic reaction.

Hydrolysis of high energy molecules (e.g. ATP) is a common example of an exergonic reaction that many non-spontaneous reactions are coupled with.

Question 45

Define:

‘Standard States’

Answer 45

A reference point for thermodynamic calculations that allows for increased consistency across data/experiments etc.

Note: Complete consistency is practically impossible though, especially when considering biological systems.

Question 46

State:

The Gibbs Free Energy equation for when conditions are not standard.

Answer 46

You adjust the Gibbs Free Energy equation that includes the ‘equilibrium constant (K)’ to factor in any non-standard product/reactant concentrations.

The above measures ‘how far cellular conditions are from the standard state’.

This is important in biochemical systems, since the standard state of 1M does not typically apply H+ concentrations in living organisms.

Thus, using the above equation, you would substitue in [H+] for reactions in which H+ is produced (for consumed, you need to reverse the +RT to -RT).

Question 47

What inference can you make from the equation in the image below?

Answer 47

‘How far standard state conditions are from equilibrium’.

Question 48

In regards to available energy, what happens the further away you get from equilibrium?

Answer 48

The more energy there is available to be drawn from spontaneous processes.

(i.e. the more energy released and potentially available for doing work in living systems etc.)

Question 49

Complete the Sentence:

The further the equilibrium constant (K) is from 1, the…

(Hint: TWO effects)

Answer 49

…further the reaction is from standard conditions and the larger the ΔG°.

Question 50

List:

TWO types of biomolecules that assist in energy transfers to drive biochemical reactions.

Answer 50

• Reduced Coenzymes (NADH, FADH2).
• High-Energy Phosphate Compounds.

Note: The high-energy phosphate compounds need to have a free energy pf hydrolysis more negative than -25 kj/mol.

Question 51

What is significant about the specific G energy changes in regards to ATP phosphoryl group transfer reactions?

(i.e. nucleophilic attack and hydrolysis of phosphate groups within ATP molecules).

Answer 51

It has a significantly larger activation energy compared to the energy released from hydrolysing the unstable phosphoric anhydride bond.

The activation energy for this reaction is around 200-400 kj/mol, and the free energy potential instead is around -30.5kj/mol.

However, overall, the hydrolysis of the phosphoric anhydride linkages is highly favourable.

Question 52

List:

The THREE main reasons for the large negative free energy, G, change for phosphoric acid anhydride hydrolysis.

Answer 52

• Electrostatic Repulsion.
• Stabilisation of products via ionisation and resonance.
• Entropy considerations.

• Electrostatic repulsion comes from the interacting electron clouds of the oxygens in each of the negatively-charged phosphate groups.
• Entropy is **increased ** due to the the fact there are a greater number of molecules/compounds produced than the original reactant(s) in hydrolysis reactions.

Question 53

How do metal ions (cofactors) such as Mg help facilitate reactions like ATP hydrolysis.

Answer 53

It enables the oxygen of water molecules to access electrophiles in the bonded phosphate groups and carry out a nucleophilic attack/substitution reaction.

Mg does this by ‘temporarily storing’ electrons of the negatively charged oxygen atoms of the phosphates, and minimising their repulsion of the approaching water molecule oxygen atom.

Question 54

Why are coupled processes/reactions vital in living systems?

Answer 54

Living systems are constantly ‘avoiding reaching states of equilibrium’ and thus often need to use energy released from exergonic/favourable reactions to power reactions that are thermodynamically unfavourable/endergonic.

The hydrolysis of ATP is a common example of an exergonic reaction used to power less favourable ones (such as pumping ions against their electrochemical gradients).