Energy. Entropy.

Molecular interactions

Learning Objectives
Energy, heat, work, enthalpy Spontaneous processes. Entropy Free energy. Equilibrium constant Noncovalent interactions Water and hydrophobic interactions

Energy
The normal activities of living organisms demand a constant
input of energy (Greek: en, in + ergon, work)

Thermodynamics (Greek: therme, heat + dynamis, power) studies

relationships between heat and other forms of energy

In thermodynamics, a system is a part of the universe

(e.g. a cell), the rest of the universe is called surroundings in the universe is constant, although the form of the energy may change

The First law of thermodynamics: the total amount of energy

Enthalpy
The energy change of a system (!U) is the difference between heat (Q) exchanged with the surroundings and the work (W) done by the system on the surroundings: !U = !Q - W !Q= !U +W Under constant pressure (P), the work is defined by the volume change (W = P!V). Therefore, !Q= !U + P!V Enthalpy (Greek: enthalpien, to warm in) H = Q = U + PV In most biochemical reactions, !V is small and !H = !U

Spontaneous Process
A spontaneous process occurs without the input of energy (heat exchange, gas expansion) When the stopcock is opened, the gas molecules diffuse between the bulbs and eventually become distributed evenly, half in each bulb

Entropy
Entropy (S) indicates the degree of randomness of a system S = kB ln W The Boltzmann constant kB= R/N (Gas constant / Avogardos number) W is the number of energetically equivalent ways of arranging the components of a system The second law of thermodynamics: spontaneous processes are characterized by an increase in the entropy in the universe For a spontaneous process under constant T !S !H/T

Free Energy
Neither ! S nor ! H alone can be used to determine the spontaneity of a process The true criterion for spontaneity: ! H - T! S < 0 (at constant T and P) Free energy: G = H - TS; ! G = ! H - T! S Exergonic process: ! G < 0; Endergonic process: ! G > 0 When reaction A + B
0

C + D is at equilibrium, ! G = 0
K eq [C ] [ D ] G o / RT = =e [ A] [ B ]

[C ] [ D ] G = G + RT ln [ A] [ B ]

! G0 refers to a standard state (all components are at " M )

Cyclohexane Conformations

Cyclohexane Conformations

What is a probability to find cyclohexane in a chair conformation? What is a probability to find cyclohexane in a boat conformation? How often cyclohexane transits between char conformations?

The Boltzmann Equation

Relates probabilities of two states with their energies

p" p2

exp (-E"/RT) exp (-E2/RT)

= exp [(E2-E")/RT]

p" - probability to find the system in state " p2 - probability to find the system in state 2 E" - the energy of state " E2 - the energy of state 2 T - temperature R - the gas constant = ".987 cal K-" mol-"

E2

Example: E2-E"=3 kcal/mol; T= 300 K p"/p2 = e3/(0.00"987300) e5 =2.7"85 "48

E"

The Arrhenius Equation

Relates a reaction rate with the energy barrier

k = A exp (-Ea/RT)
k A Ea R T the reaction rate coefficient (s-") atomic vibration frequency ( 5.8 "0"2 s-") the activation energy the gas constant temperature

Transition State

Examples:

Ea

Ea, kcal/mol 3 9 "2 "7 25

k, s-" 3.9 "0"0 ".8 "06 ".2 "04 2.9 4.6 "0-6

Event rotation around Csp3-Csp3 bond ion current via Ca2+ channel ion channel gating protein folding double bond isomerization

E2

E"
Reaction coordinate

Strong and Weak Bonds

Type of Bond Covale nt Noncovale nt Ionic Hydrogen bond Hydrophobic D ipole-d ipole van der W aals Exa mple O-H C-C -CO O H3 N-O H O < -C4 H9 H9 C4 >C= O >C=O A ny two atoms
+

Strength, kJ/ mol 460 348 20-80 6 - 20 4- 8 3- 9 <"

Noncovalent bonds:
Stabilize 3-D structure of proteins and other biopolymers Enable molecules to recognize each other to accomplish integrated functions Are easily formed and broken providing flexibility to the biological interactions

Nonbonded interactions
Energy kJ/mol R e p u l s i o n

van der Waals attraction

Electrons in a molecule are not static. At a short distance, nonbonded atoms synchronize their electron fluctuations yielding a weak attractive force

2.4
CH3
H H

6.0
CH3
H

- 0."5

CH3
H H

Distance,

CH3

CH3

CH3

Hydrogen Bonds
Donor Acceptor - + +

H-bonds can occur within a molecule and between molecules H-bonds determine:
Properties of water and ice Interaction of water with solutes DNA base pairing

>N-H . . . O=C< >N-H . . . O< >N-H . . . N -O-H . . . O=C -O-H . . . O< -O-H . . . N

H-bonds influence:
Protein folding Recognition of small molecules by biopolymers

Water
Water accounts for about 70% of the body weight

reorients every "0-"2 s Almost all biochemical reactions occur in water In many biochemical reactions, water acts as an acid or base (donates or accepts a proton)

Each water molecule is H-bonded to 3.4 neighbors and

Hydrophobic interactions
Hydrophobic effect is the tendency of water to minimize its contacts with nonpolar molecules

Thermodynamic changes for

transferring hydrocarbons from water to benzene (kJ/mol)
Substance CH4 C2H 6 !H "" .7 9.2 - T! S -22.6 -25. " !G -" 0.9 -" 5.9

Water Molecules in Cages are Unhappy

Ordering of water molecules around a nonpolar solute is entropically unfavorable

Released Water Molecules Are Happy

Aggregation of nonpolar molecules (groups) in water minimizes the entropy loss of the system

pH
In pure water, one water molecule in 500 million is ionized H2O H+ + OHKw = [H+][OH-] = "0-"4 M2 pH = - log [H+]