Laurea specialistica in Scienza e Ingegneria dei Materiali Curriculum Scienza dei Materiali Chimica Fisica dei Materiali Avanzati Part 2 – Supramolecular chemistry and molecular recognition Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Supramolecular chemistry ...can be defined as the “chemistry beyond the molecule”, bearing on the organized entities of higher complexity that result from the association of two or more chemical species held together by intermolecular forces. (J.-M. Lehn) Molecular interactions form the basis of the highly specific recognition, reaction, transport, regulation, etc. processes that occur in biology Bacteriorhodopsin Ion channels ATP Synthase Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Supramolecular chemistry - 2 However, chemistry is not limited to systems similar to those found in biology but is free to create unknown species and to invent novel processes Rotaxane Dendrimeric structure Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Coordination bonding The scope of coordination chemistry extends to the binding of all kinds of substrates: cationic, anionic and neutral molecular species of either organic, inorganic, or biological nature (J.-M. Lehn) Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Molecular recognition Molecular recognition is defined by the energy and the information involved in the binding and selection of substrate(s) by a given receptor It implies the (molecular) storage and supramolecular read out of molecular information Selective binding of a substrate by a receptor Interaction = ENERGY Selection = INFORMATION receptor and substrate should exhibit Steric complementarity (shape and size) Interactional complementarity Large contact areas Multiple interaction sites Strong overall binding Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

At the origin of molecular recognition 1894: Emil Fischer presents the ‘lock and key’ model for enzymatic chemistry  Molecular recognition Supramolecular function Structure of glutamine synthetase: a homo-dodecamer Active site Binding of Ritonavir inhibitor to a protease Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Spherical recognition Recognition of metal cations Spherical guests: metal cations (Na+, Ca2+, La3+) and halide anions (Cl-, I-, etc.) Crown Ethers Charles Pedersen, 1967 Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Rotaxanes A case of ingenious use of [NHO] and [NCHO] H-bonds between di-alchil-ammonium cations and crown ethers J. Fraser Stoddart et al. (UCLA) Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Rotaxanes as molecular machines Shuttling action by cemical chemical stimulation Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Catenanes With the same interactions it is possible to obtain a different type of interlaced structure: the catenanes Proposed mechanism: Formation of a tri-cationi intermediate Formation of a charge transfer complex Self-assembly promotes the interlaced structure The catenane is afforded (in a 70% yield) Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Molecular recognition portfolio: cavitands Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Anatomy of cyclodextrins Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Bonding by hydrophobic effect Solvated host Solvated guest Complex The hydrophobic effect Strong inclination of water molecules to form H-bonds with each other affects their interacn. with non-polar molecules not forming H-bonds (alkanes, hydrocarbons, fluorocarbons, etc.) Water molecules can pack around the non-polar solute without giving up any of their H-bonding sites (however, the size and shape of non-polar molecules is very critical) The net effect is a reorientation of the water molecules towards a structure more ordered that in the bulk liquid. Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

The hydrophobic effect (cont’d) The increased order in the water cages is entropically unfavourable. For this reason, the hydrocarbons are very little soluble in water: the free energy increases due to the decrease in entropy The free energy of solubilization is roughly proportional to the surface area of the molecules. The hydrophobic interaction It arises primarily from the rearrangement of H-bond configurations in the overlapping solvation zone as two hydrophobic species come together. It is a cooperative effect of much longer range than any typical bond The hydrophobic interaction plays a central role in many surface phenomena, in molecular self-assembly, in micelle formation, in biological membrane structure and in determining the conformation of proteins. Example: Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Application: Molecular-recognition-based Sensors Technology need: sensors which can distinguish extremely low level of gas species in the presence of large quantities of interfering species Required features: sensitivity, selectivity, response time Proposed solution: sensing chemicals by analysis of changes in the refractive index of a thin film of host reagent on a waveguide caused by the formation of guest-host inclusion complexes in the thin film. Advantages:Because the formation of inclusion complexes is reversible, the sensor apparatus can be used for substantially real-time sensing of chemical agents. Sensor sensitivity can be tuned and choice of chemicals to be detected can be made by varying the size of the host reagent cavities and by selecting the chemical functionality of the host reagent molecules. Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat

Application: Molecular-recognition-based Sensors - 2 WAVEGUIDE BASED OPTICAL CHEMICAL SENSOR Abstract The invention provides an apparatus and method for highly selective and sensitive chemical sensing. Two modes of laser light are transmitted through a waveguide, refracted by a thin film host reagent coating on the waveguide, and analyzed in a phase sensitive detector for changes in effective refractive index. Sensor specificity is based on the particular species selective thin films of host reagents which are attached to the surface of the planar optical waveguide. The thin film of host reagents refracts laser light at different refractive indices according to what species are forming inclusion complexes with the host reagents. Corso CFMA. LS-SIMat Corso CFMA. LS-SIMat