New methods in the synthesis of single-chain polymeric nanoparticles

Abstract

Nanoparticles can be described as nanometer-sized colloidal particles, possessing exceptional optical, electrical, and magnetic properties. Although numerous types of nanoparticles have been utilized, polymeric nanoparticles with controlled characteristics have recently drawn significant attention as a promising research topic within the field of nanoscience. The design of polymeric nanoparticles having controlled size and functionality is essential for application areas such as drug delivery, microelectronics, and catalysis. A variety of conventional methods including emulsion polymerization, interfacial polymerization, self-assembly, solvent evaporation, or supercritical fluid technology have been employed to prepare polymeric nanoparticles. However, size control and the pre-determination of the functional groups remain challenging by utilizing the above-noted methods. To address these problems, single-chain nanoparticles (SCNPs), also known as single-chain polymeric nanoparticles, have emerged as a crucial class of versatile nanomaterials by the contributions of scientists who are inspired by nature. Ever since the intramolecular crosslinking strategy was first introduced, a variety of approaches has been exploited to yield well-defined SCNPs comprising characteristic features. The intramolecular interactions enable the formation of collapsing or folding of an individual polymer chain via various physical or chemical crosslinking reactions. Due to their unique characteristics resulting from nanometer-sized dimensions (1.5-20 nm), self-crosslinked nanoparticles are of considerable scientific value for particular applications such as drug delivery, bioimaging, biosensors, and catalysis. In this regard, this thesis aimed to demonstrate the synthesis of SCNPs by utilizing intramolecular crosslinking approaches conducted under straightforward and robust reaction conditions. The structure of the precursor polymers was prepared using both polycondensation and controlled/living polymerization techniques and the in-chain crosslinking reactions were established by external addition of crosslinking agent under dilute reaction conditions. In the first study, the synthesis and the functionalization of polyester-based SCNPs are demonstrated utilizing Michael addition reactions. For this purpose, condensation polymerization was first performed to yield a polyester precursor containing reactive alkyne units in the main chain. It is widely accepted that the reactive nature of alkyne units is due to the bonding of two electron-withdrawing carbonyl groups, which renders the triple bond highly electron-deficient and thus suitable for Michael addition reactions. Hereby, linear polymer precursor was intramolecularly crosslinked to generate SCNPs through aza-Michael addition reaction in short durations and without using any catalyst. Piperazine, a secondary diamine compound was utilized as a crosslinking agent with varying ratios to adjust the folding degree and thus the size of the self-crosslinked nanoparticles. The folding procedure was conducted at dilute conditions (c = 1.0 mg mL-1 ) to prevent intermolecular interaction between the polymer chains under mild reaction conditions. Later, the feasibility of the functionalization reaction was investigated via thiol-Michael addition since the remaining alkyne units were still reactive toward the nucleophiles. It has been previously shown in the study that the utilization of a nucleophilic catalyst namely, 1,4-diazobicyclo [2.2.2]octane (DABCO) is required to perform the addition reaction of thiol compounds efficiently to the reactive triple bond. Therefore, the obtained SCNPs were functionalized with a thiol nucleophile in the presence of DABCO for 2 minutes at room temperature. In the second study, not only intrachain collapsing but also the further modification reaction was demonstrated by utilizing nucleophilic aromatic substitution reaction. Firstly, a well-defined precursor polymer with controlled molecular weight has been synthesized via ring-opening metathesis polymerization (ROMP) of oxanorbornene monomer comprising dichlorotriazine (DCT) moiety. By taking the benefits of the electrophilic feature of the chlorine atoms on DCT, intramolecular crosslinking has been performed via nucleophilic aromatic substitution reaction with the addition of a dithiol compound as a crosslinker. Double folding strategy and the post-modification reaction of obtained SCNPs were demonstrated by introducing a different dithiol and a thiol compound, respectively, since unreacted chlorine atoms were still present along the structure. Multiple characterization techniques, including NMR, GPC, DLS, and TEM were used to confirm the formation and modification of SCNPs.