Molecular Guests Flashcards
What is a key example of a molecular host?
Cyclodextrins. Made up of sugars, linked via a 1-4-glycosidic link.
How are cyclodextrins synthesised?
Formed by degradation of starch to give oligodextrins. To separate cyclodextrins from linear dextrins, guest is added so that the cyclodextrin guest complexes crystallise out of solution via host-guest chemistry.
What factors can impact binding constants?
Steric fit, release of high energy water, hydrophobic effects, Van der Waals interactions, dispersive forces, dipole-dipole interactions, charge transfer interactions, electrostatic interactions, hydrogen bonding
What types of molecules do cyclodextrins bind and what are the biggest factors to consider?
Bucket shape of cyclodextrins makes them good for binding small aromatic molecules.
Hydrogen bonding interactions can happen at the top. Bucket shape means that steric interactions (for example, ortho substituted at bottom) can play a distinct role.
Solvation effects need to be considered if cyclodextrins begin solvated.
What properties make cyclodextrins suitable enzyme mimics?
Water solubility at physiological pH, reversible, non-covalent guest binding, well-defined structures and guest-binding modes, wide range of accessible derivatives by reaction at OH, juxtaposition of hydroxyl groups enables active role in catalysis and hydrophobic cavity enables guest binding, chiral molecular cavity and catalytic activity has been seen.
How can cyclodextrins catalyse ester hydrolysis?
Example: Me-COOPh
Cyclodextrin deprotonated by base. Binding of this molecule places the ester group near the O-, which is then able to hydrolyse the ester. Water/excess base then able to regenerate deprotonated cyclodextrin.
NB. this reaction becomes first order due to binding, rate enhancement within an order of magnitude of enzymes.
What is the first example of an artifical host molecule?
Diphenylmethane group by Koga. Diphenylmethane bridges diamine groups. Amines protonated at acidic pH, enables solubility at low pH.
What NMR evidence can be used for binding studies, in the context of the Koga host?
Pi-stacking interactions can cause a huge chemical shift between bound and unbound forms due to the ring current effect. Ring current forms two distinct regions - above the ring is very shielded and to the side is deshielded. Species held above the ring will have a very low chemical shift, potentially even negative.
How can fluorescence titrations indicate binding in the context of the Koga host?
Koga host able to bind ANS, common fluorescence agent. Fluorescence of ANS quenched by H2O. Through titration, see an increase in fluorescence as enhanced when ANS binds into cavity - reduced access of H2O.
What are the key problems with the Koga host?
Only soluble at low pH so need to work in strongly acidic solutions.
Proximity of the polar amine groups needed for water solubility and guest-binding site makes more difficult to tell whether salt-bridge effects or hydrophobic binding causing selectivity patterns.
Flexibility of diamine chains, leading to poor preorganisation.
Achiral species.
What has been done to refine the design of the Koga host?
Introducing carboxylate groups further away from the cavity to give a wider solubility range.
Remote solubilising groups like quaternary nitrogen centres and spiro compounds to remain far away.
Inducing more rigidity and higher preorganisation.
Introducing chirality to species.
Bringing in inspiration from cryptands, adding further rigidity, enhancing hydrophobic effect and larger surface area for binding.
What design choices enable guest inclusion by hydrogen bonding in cyclophanes?
Set of hydrogen bond donors and aromatic stacking effects to bind quinones.
Can confirm binding by change in NMR spectra due to hydrogen bonding and change in redox chemistry as thermodynamics of ring significantly perturbed.
How does solid-state host-guest chemistry arise?
Inefficient packing of host molecules allows crystallisation of guest in spaces.
