Características del medio elaborado de forma impresa

Since the advent of controlled radical polymerisation techniques, the synthesis of well- defined block copolymers has been relatively straight-forward. Block copolymers that consist of quite chemically different, often immiscible, blocks can be synthesised, which can self-assemble, either in bulk, or in solution.1, 2

Amphiphilic block copolymers consist of at least one block that is hydrophilic and at least one block that is hydrophobic. Therefore these polymers will undergo self-assembly in aqueous media in order to minimise the unfavourable interactions between the hydrophobic block and the surrounding water.3_{The morphology adopted upon self-assembly is dependent}

upon the packing parameter,p.

=

where v is the volume of the hydrophobic section, ao is the contact area of the head group

andlcis the length of the hydrophobic section. In general spherical micelles are formed forp ≤ ⅓, cylindrical micelles are formed when ⅓ ≤ p ≥ ½ and when ½ ≤ p ≥ 1 vesicles are

formed.4

Stimuli-responsive polymers are ones which undergo a change in hydrophilicity (i.e. they become either more hydrophilic or more hydrophobic) in response to an external stimulus.5

The application of the stimulus causes a change in the overall amphiphilic balance (the hydrophilic: hydrophobic ratio) of the polymer chain and, if severe enough, can cause a change in the packing parameter and hence the morphology adopted in solution.

There are two ways to cause this change in amphiphilic balance. One method is to change the physical environment of the polymer, for example, changing the concentration of the polymer in solution,6_{or by the addition of salts and additives which promote the solubility of}

Two of the most commonly studied stimuli are temperature5, 9-15 _{and pH.}16-18 _{Within this}

chapter pH as a stimulus to induce a morphology change is explored. The application of pH as a stimulus can cause a reversible change within the polymer,i.e.the protonation of amine units to render them hydrophilic,19-21 _{or can cause an irreversible chemical change, for}

example, the deprotection of hydrophobic tetrahydropyranyl acrylate (THPA) to form hydrophilic acrylic acid (see Scheme 2.1).22-24_{THPA can be deprotected either thermally or}

through the use of acetic acid.22-24_{As the deprotection is acid catalysed, it can be considered}

to be self-catalytic, as once it starts to deprotect, the acrylic acid formed catalyses futher deprotection.

Scheme 2.1: The deprotection of THPA with acetic acid to give acrylic acid

In several examples by Petzetakis et al.22-24 _{THPA was used during the synthesis of}

polylactide-polyTHPA acid block copolymers and then deprotected to form polylactide- poly(acrylic acid) block copolymers, which self-assemble in cylinders via crystallisation- driven self-assembly.

In another example, Klaikherd et al. investigated a system that involved multi stimuli- responsive blocks in which THP-protected 2-(hydroxyethyl) methacrylate (HEMA) was the pH-responsive block and NIPAM was utilised as the temperature responsive block (see Figure 2.1). These two blocks were joined by a redox sensitive disulfide linker and upon self-assembly, below the LCST cloud point of the NIPAM, micelles were observed to form with a THP core and NIPAM corona.

Br O HN O O S S O _Br O O O O O 100 30

Figure 2.1: The multi-responsive triblock synthesised by Klaikherdet al.25

Upon lowering the pH, the THP-protected HEMA deprotected to leave hydrophilic HEMA, rendering the entire polymer water soluble and so a micelle to unimer morphology transition was observed.25_{This morphology transition was utilised to release the hydrophobic dye, Nile}

Red, from within the micelles in response to this change in pH. The polymer could also be made to precipitate out of solution by increasing the temperature to above the LCST of the NIPAM. Cleavage of the redox sensitive linker with a mild reducing agent, resulted in the formation of the constituent homopolymers and therefore dissociation of the micelles (see Figure 2.2).

Figure 2.2: Schematic showing the amphiphilic diblock copolymer and the effect of the three different stimuli25

As shown in the previous example, the disruption of a self-assembled structure can be exploited by the encapsulation and release of cargo and there are many examples of hydrophobic cargo being released from a micelle in response to a stimulus.26-28 Polymeric vesicles on the other hand have an inherent central water pool within the vesicle, which

allows for the encapsulation and delivery of hydrophilic payloads.28, 29_{There are relatively}

few examples of vesicles which undergo a morphology transition to a micelle in response to pH.30 _{Eisenberg and co-workers prepared a triblock copolymer consisting of poly(acrylic}

acid), polystyrene and poly(4-vinyl pyridine) which self-assembled in DMF/THF/H2O

mixtures. At pH 1 the polymers formed vesicles but between pH 3 – 11 solid aggregates were formed.

Herein we report the synthesis of diblock copolymers consisting of a hydrophilic head group, a pH-deprotectable THPA block and a hydrophobic MA block (see Figure 2.3). Two different hydrophilic head groups are investigated; a positively charged quaternary amine head group and a neutral triethyleneglycol head group. The self-assembly behaviour of the polymers is investigated by DLS and TEM. The pH-response of the polymers is demonstrated by treatment with acetic acid to deprotect the THPA and the subsequent vesicle to micelle morphology transition analysed by DLS and TEM.

Figure 2.3: Schematic representation of the deprotection of the THP-functionalised polymer and the resultant change in morphology expected