Dynamic covalent functionalisation and assembly of boronic acid nanoparticles

Abstract

The rapid development in the synthesis and understanding of the properties of various types of nanoparticles has produced a plethora of potential building blocks. In attempts to exploit these novel species, several groups investigated methods to control their assembly and subsequent integration in technological devices. Almost 30 years after the first investigations, a lack of generalisable methods and understanding of the aggregation process still hampers the development of the field. Among lessons learnt from the large number of reports, reversibility of bond forming during the nanoparticle assembly is one crucial requirement. DNA-functionalised nanoparticles have established themselves as the state-of-the-art building blocks for the construction of nanoparticle superlattices. With the inherent limitations of this strategy, dynamic covalent chemistry-enabled gold nanoparticles featuring boronic acid-terminated ligands emerged as an alternative for the elaboration of responsive and robust nanoparticle-based assembled materials. Current limits of the system are moderate affinity for the biscatechol linkers used to connect boronic acid-functionalised nanoparticles and the requirement for high concentrations of tertiary amine based for a consistent reactivity. This thesis aims to improve on the first generation of boronic acid-functionalised nanoparticles and present a step-wise approach to meet this goal. The reactivity of boronic acids with a series of binding partners in non-aqueous media revealed how adjusting the concentration of tertiary amine base to the chosen binding partner allows for the tuning of the association constant for boronate esters over five orders of magnitude. This understanding was exploited to create a molecular switch in which the selectivity of a boronic acid for a catechol or salicylic acid is controlled by the controlled by the concentration of base and that can be actuated several times with high fidelity. These results have directed the next step of the creation of a second generation boronic acid ligand by replacing the arylboronic acid fragment of the original design with a new that forms more stable boronate esters. Subsequently, nanoparticles of different sizes bearing the new ligand were prepared with good size dispersity. The identification of a side-reaction during the nanoparticle synthesis oxidising the boronic acid to phenol motivated an optimisation of the reaction conditions to obtain single-ligand nanoparticles. A systematic comparison of the first- and second-generation nanoparticles was performed to understand the influence of the confinement of the boronic acids on their reactivity. Unexpectedly, these measurements suggest that salicylic acid ester formation is more inhibited than catechol ester formation on nanoparticle compared to their molecular counterparts and that the original nanoparticle design stabilises boronate esters better than the new one. Nevertheless, the general boronate ester stability trend relative to the concentration of base is verified on nanoparticles and a similar selectivity switch for catechol or salicylic acid binding could be created. These measurements finally helped set conditions that should facilitate boronate ester-directed nanoparticle assembly while minimising the base-catalysed degradation of the linkers. Catechol and salicylic acid-based bifunctional linkers were used to aggregate nanoparticles via boronate ester formation. to form similar assemblies to the first generation despite proceeding with slower kinetics. Under supposedly optimised conditions, second generation nanoparticles did not form extended insoluble networks, but smaller colloidally stable structures. Exploiting the reversibility of boronate ester formation, several stimuli could be applied to disassemble them and return colloidally stable isolated nanoparticles.