M.Sc Thesis

M.Sc StudentYefet Karasik Maayan
SubjectSynthesis and Properties of New Host Molecules
DepartmentDepartment of Chemistry
Supervisor PROFESSOR EMERITUS Ehud Keinan


Supramolecular chemistry aims at the creation of functional, organized nanoscale devices in analogy to the familiar biological machines. Thus, macrocyclic host molecules are of great importance in supramolecular chemistry.

Cucurbiturils are highly symmetric, rigid macrocycles with two identical polar carbonyl-lined portals and a hydrophobic cavity. These macrocycles, which are consisted of glycoluril repeating units, have attracted increasing interest owing to their ability to successfully bind various metal cations and organic ammonium salts with extremely high binding constants via charge-dipole interactions and hydrogen bonding at the cucurbituril portals and hydrophobic effect within the interior. Cucurbit[6]uril is the most stable and easy to obtain homolog of this family and therefore has attracted much interest.

In this research we have discovered a new unique interaction between an organic azide function of the guest molecule and the carbonyls of the cucurbit[6]uril host. Initially, we suspected that this interaction was a new type of n→π* interaction between the lone pair orbitals of the carbonyl oxygen and the anti-bonding π orbital on the azide. However, on the basis of crystallographic analysis of the complexes and calculations, which were carried out in collaboration with Prof. Michael Gilson group at UC San Diego, this assumption was ruled out. We can better explain these findings in terms of orthogonal dipole-dipole interactions.

In another study we examined the binding mode and dynamics of various diammonium guest molecules and cucurbit[6]uril using X-ray crystallography, NMR spectroscopy and isothermal titration microcalorimetry. We identified two binding modes - a central binding leading to the formation of a 1:1 complex, and a peripheral binding leading to the formation of a 1:2 complex between the guest and cucurbit[6]uril.

The 1:2 complexes, with peripheral binding of cucurbit[6]uril, which occured at room temperature, were found to be kinetic products that could be converted to the thermodynamically more stable 1:1 complexes upon prolonged heating to 100°C. The latter were found to be very stable rotaxanes despite the fact that they lack bulky end groups. These can be used as design elements of molecular devices for a broad range of applicationes, such as controlled drug release, molecular rotary motors, and chemical sensors.

Although cucurbiturils hold great promise as host molecules, their practical applications are still limited, mainly because of their low solubility in organic solvents. Thus, we attempted to synthesize functional disubstituted cucurbit[5]uril derivatives with a hydrophobic side chain, which could be used as an alternative to the existing avidin-biotin technology. Another effort along this line, which is still in progress, is the idea of creating pH-dependent “daisy-chain” polymers from Cucurbit[5]uril with polyamine side chains.

The group synthetic efforts towards cucurbituril analogs have also resulted in the discovery of a new family of macrocycles - multifarenes. Within this effort we synthesized a non-substituted multifarene[3,3] derivative in the hope that this thiourea derivative could serve as a polydentate ligand for Pd and other metals for metal-catalyzed Heck and Suzuki reactions. The non-substituted multifarene[3,3] was found to be extremely flexible with low solubility in common organic solvents. Its binding properties are still under investigation.