ICB

Kon / Ka

K for association / formation of lattice

Koff / Kd

K for dissociation / backwards reaction

Ka (Kon, Koff)

Ka = Kon / Koff

common magnitude of Kon

x10(10) mol-1s-1

how to calculate Ka experminetally

Titration
- keep [A] constant
- add B
- plot %A bound (y) vs log[B]
- at [A] = [AB] (50% bound), Ka = 1/[B]

relationship between Ka and Kd

Kd = 1/Ka

Ka = (∆G)

exp(-∆G/RT)

∆H contributions

• Interactions

  • i.e. H bonding

• Desolvation

• Conformational strain

∆S contributions

• biomolecular association

• desolvation

• conformational entropy

Why is measuring ∆H and ∆S separately difficult

Both affected by desolvation, makes things complicated

what is ∆∆G

Free energy contributions, how ∆G changes with changes to non-covalent interactions (i.e. more H bonding increases ∆G)

∆G = (∆∆G)

∑∆∆G

region of change in K doesnt matter

x÷ 2 kJ mol-1

types of non-covalent interactions

• electrostatic/coulomb

• induction/polarisation

• dispersion / ID-ID

• repulsion

• charge transfer

what non-covalent intercations make up VDW

dispersion and repulsion

why do we not consider the charged part of charge transfer interaction

too small to make a difference (effects within the error)

result of molecules having finite volumes

steric effects

Why dont we use hard/soft intercations to justify intercations

relies on contact surface area so not comparable

why is ∆∆G for desolvation = 0?

desolvation cancels out the interactions between molecules

what kind of geomrety do ion pairs favour

doesnt matter, its long range

magnitude of ε inside protein

low

magnitude of ε outside protein

high

in water, will substances with pka < 7 be their acid or c. base

conjugate base

in water, will substances with pKa > 7 be their acid or c. base

acid

attracts H bonds the most

LPs or pi e-

repels H bonds the most

Hs

how to tell there are H bonds in a crystal

look at x ray crystallography, H-bonds penetrate VDW so will have smaller bonds

what is β (H-bonding)

H-bond acceptor parameter

what is α (H-Bonds)

H-bond acceptor parameter

∆∆G = (H-bonds)

-αβ (kJ mol-1)

as electronegativity increase, α…

increases

as hybridisation increases, α…

increases (more s character)

If an EWG is added to a H-bond donor, α…

increases

what group has no effect on α or β in the inductive effect

alkyl groups

as delocalisation increases, α…

increases

as hybridisation increase, β…

increases

if an EWG is added to a molecule, β…

decreases

why dont benzenes stack

they have the 2 pi clouds repelling each other

preferred benzene - benzene interactions

T shaped as δ+ H is sticking into -ve pi cloud

how does benzene stacking become possible

adding polarising groups to change the charge distribution

∆∆G for desolvation

a_sb + ab_s - ab - a_sb_s

what regions of the free energy profile (a vs b) are favourable for desolvation

top right (ab wins), bottom left (asbs wins)

regions of free energy profile where desolvation is unfavourable

top right (abs wins), bottom left (asb wins, hydrophobic region)