Chelate effect and cooperativity Flashcards
Chelate effect
Multidentate ligands result in more stable complexes than comparable systems with multiple monodentate ligands
This enhanced stability arises from a combination of enthalpic and entropic factors
Why is an ethylene diamine complex 10^8x more stable than an ammonia complex?
Entropic factors: intramolecular ring formation - as one N from ethylene diamine binds, it is easy for the second N to ‘swing round’ and bind
Enthalpic factors: N in ethylene diamine has a higher electron density than N in NH3 due to induction from the alkyl chains, therefore forms a stronger bond with the metal centre
Ethylene diamine complex also kinetically stabilised - K-1 is very small, because it is easier for the dissociated N to add back on than it is for the second N to break off
Macrocyclic effect
Refers to the high affinity of metal cations for macrocyclic ligands compared to their acyclic analogues - macrocyclic hosts with multiple binding sites result in even more stable complexes
Stabilisation arises from the chelate effect plus the pre-organisation of the macrocyclic ligand
Pre-organisation
A host is said to be pre-organised if it requires no significant conformational change to bind a guest species
Pre-organisation results in a significant increase in the stability of complexes
Macrocyclic complexes are…
…even more stable than would be expected from cooperative/chelate effects alone
Cooperativity
Arises from the interplay of 2 or more interactions, so that the system as a whole behaves differently from expectations based on the properties of the individual interactions acting in isolation
Positive cooperativity
If the overall stability of the complex is greater than the sum of the interaction energy of the guest with the binding sites individually
Negative cooperativity
If unfavourable steric/electronic effects cause the overall binding energy for the complex to be less than the sum of its parts
“All or nothing” behaviour
As a system approaches the limit of strong positive cooperativity, only the extreme states (unbound/bound) are populated (i.e. very low conc of intermediates)
The key consequence of positive cooperativity
Occurs widely in biology where switching between ‘on’ and ‘off’ states results from a small change in conditions
Positive cooperativity at the molecular level
Any individual molecule is likely to be fully bound or fully unbound - it spends little time in intermediate states
Positive cooperativity at the macroscopic level
The behaviour of the ensemble is characterised by a population switch from mainly free to mainly bound over a small change in conditions - leading to sigmoidal curves/sharp transitions between states e.g. binding of O2 to Hb
Under most conditions, one state predominates
Allosteric ligand binding
2 monodentate ligands (B) interacting with a receptor with 2 covalently-connected binding sites (AA) Receptor has 3 possible states: Free (AA) Partially bound (AA.B) Fully bound (AA.B2)
- equations *
Alpha
= K2/K1
Interaction parameter
Describes the cooperativity of the system at the molecular level
Alpha = 1
No cooperativity Association constants (K1 and K2) are identical to the value for the corresponding reference receptor with one binding site i.e. K1 = K2 = K
ThetaA
Binding occupancy of the receptor
Defines the total fractions of receptor sites bound to ligand
Speciation curve for no cooperativity
Alpha = 1
K1 = K2
The ThetaA curve is identical to that of the one-site reference system
Speciation curve for negative cooperativity
Alpha = 0.01
K1 > K2
The intermolecular interaction in the intermediate AA.B is stronger than in the fully bound state AA.B2
Formation of the fully bound complex takes place over a wider conc range than for the reference system
AA.B is the dominant species at intermediate concs