Rouse, Charlotte Kirsty
Description
This thesis describes work towards the development of a range of
supramolecular devices and materials based on cyclodextrin
host-guest interactions, and/or short peptide structures.
The first such device targeted was a photoswitchable molecular
lariat composed of a [c2] (cyclic, two-component) asymmetric
daisy chain. Upon combining the two hetero monomer units it was
found that a [c2]-dimer was not formed.
The next phase of research involved the design...[Show more] of a second type
of supramolecular device, also based on cyclodextrin host-guest
inclusion complexes, this time serving to produce a change in
peptide secondary structure. A range of devices were synthesised
giving several modifications; increasing the stability of
hexavaline beta sheets, reducing the PPII (polyproline type II)
helicity in pentaalanine and introducing beta sheet character to
pentaalanine. Furthermore, an azobenzene moiety was introduced as
a photo-switchable cyclodextrin guest, enabling PPII helicity to
be switched between states of increased and decreased structure
via photoirraditation.
This principle was then developed to give a device which not only
produced a change in peptide structure but also brought about a
change in function, in this case metal-binding ability. Upon
cyclodextrin host-guest [c2]-dimer formation, beta sheet
structure was induced in a short peptide strand which facilitated
the arrangement of histidine residues in order to bind to a metal
ion in a pseudo-chelating arrangement. The unmodified peptide,
with no cyclodextrin or guest attached did not bind to zinc ions,
whereas the cyclodextrin dimer was found to bind to Zn2+ with a
Ka of 2,223 M-1. The system was then investigated in the
solid-phase and a crystal was grown wherein [c1]-complexes were
bound to Zn2+ in tetrameric assemblies. In addition, the same
crystal structure was observed in the absence of Zn2+ showing
that the system pre-assembles to form a crystal lattice with
vacant metal binding sites.
A number of smaller studies were also performed to explore the
possibility of the application of peptide chemistry techniques
and principles to supramolecular concepts. The solid-phase
synthesis technique used to make peptide sequences was
investigated as a method for the preparation of rotaxanes.
Despite several attempts no interlocked structures were
synthesised, however a method was established for the
mobilisation of a cyclodextrin onto a stationary phase. -Sheet
peptide-peptide interactions, in conjunction with cyclodextrin
host-guest interactions were then explored as a method for the
generation of self-assembling polymers. A range of polymeric
structures were considered, however within all the systems
examined it was found that none formed.
Finally, it was observed that a peptide amphiphile (PA),
synthesized during the preparation of a metal-binding
cyclodextrin dimer, formed a gel in acetonitrile/water mixtures,
DMF and acetone at just 0.06 wt.%. The compound did not form a
gel in water, despite its structural similarity to previously
reported PAs, but did obey the structure-property relationships
determined for these hydrogels. This suggests that despite the
difference in solvents, assembly of these organo and hydrogels is
the same and indicates a new strategy for the modification of PAs
in order to gel target solvents.
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