Ph.D Thesis

Ph.D StudentSolel Moroshko Ephrath
SubjectComponents for Supramolecluar Architeture
DepartmentDepartment of Chemistry
Supervisor PROFESSOR EMERITUS Ehud Keinan
Full Thesis textFull thesis text - English Version


The notion that molecular containers can be obtained by assembly of synthetic small molecules is largely inspired by the fascinating architecture of the spherical viral capsids. Our proposed strategy to meet this challenge is based on the construction of non-protein molecular capsids of icosahedral symmetry by self-assembly of 12 pentagonal tiles that bear appropriate “sticky” edges. For the synthesis of the desired tiles we focused on the corannulene molecule due to its bowl shape, rigid nature and pentagonal symmetry. The interest in corannulene-based building blocks for such architectures led us to explore the properties of the corannulene molecule, its reactivity and applications, as described by the first chapter.

We’ve demonstrated that the Ullmann condensation reaction provides a convenient entry to 1,3,5,7,9-penta-alkoxycorannulenes, starting from aliphatic alcohols and sym-pentachlorocorannulene. These poly-ethers react with either chlorine or bromine to produce novel symmetric hetero-deca-substituted corannulene, bearing two different substituents. The availability of these heterosubstituted compounds offers interesting opportunities for further reactions that could produce more complicated corannulene derivatives for multiple applications. 

We used DFT calculations to estimate the corannulene bowl depth as a function of various substituents. Thus, the optimized structures of decakis(alkylthio)corannulene derivatives displaying a broad range of steric and electronic properties were calculated. We showed by both computation and experiments that the strong steric hindrance in decakis(t-butylthio)corannulene destabilizes the bowl-shaped conformation to such an extent that the core carbon skeleton of the molecule becomes perfectly planar. Flat corannulene has been considered so far only as a transition-state of the bowl-to-bowl inversion process, and this is the first example for a stable organic molecule having this structure.

In addition, we explored the reactivity and selectivity of corannulene in the chlorination reactions with iodine monochloride. We predict that this reaction may proceed under thermodynamic control to produce high proportions of the symmetrical product. 

In order to achieve capsids by self-assembly we aimed at various binding mechanisms that would form thermodynamically stable but kinetically dynamic binding interactions. This approach could facilitate movement from the local minima of various aggregates to the global energy minimum of the desired spherical capsid. Accordingly, we chose to employ DNA base-pairing and dynamic covalent bonds of hydrazone groups. We have synthesized a variety of building blocks according to this design and explored various conditions for self-assembly. Achieving the desired capsid using this strategy requires further efforts in order to overcome problems of solubility and sluggish reversibility.

The second chapter describes research that was driven by the hypothesis that heteroatom replacement in bambus[6]urils could modify their anion binding properties. Indeed, calculations with various glycoluril and bambus[6]uril analogs predict that such replacements alter their molecular electrostatic potential and binding properties. Both polarization and electrostatic interactions contribute to anion binding, leading to a general affinity trend among the neutral molecules. Higher affinities to anions are a function of the heteroatom aptitude to serve as an electron sink. Additionally, our DFT calculations predict that aza-bambusurils could function as anion channels.