A Mild and Efficient Approach to Functional Single-Chain Polymeric Nanoparticles via Photoinduced Diels–Alder Ligation

Abstract

We present a new ambient temperature synthetic approach for the preparation of single-chain polymeric nanoparticles (SCNPs) under mild conditions using a UV-light-triggered Diels–Alder (DA) reaction for the intramolecular cross-linking of single polymer chains. Well-defined random copolymers with varying contents of styrene (S) and 4-chloromethylstyrene (CMS) were synthesized employing a nitroxide-mediated radical polymerization (NMP) initiator functionalized with a terminal alkyne moiety. Postpolymerization modification with 4-hydroxy-2,5-dimethylbenzophenone (DMBP) and an N-maleimide (Mal) derivative led to the functional linear precursor copolymers. The intramolecular cross-linking was performed by activating the DMBP groups via irradiation with UV light of 320 nm for 30 min in diluted solution (c Polymer = 0.017 mg mL–1). The ensuing DA reaction between the activated DMBP and the Mal groups resulted in well-defined single-chain polymeric nanoparticles. To control the size of the SCNPs, random copolymers with varying CMS contents (i.e., different functional group densities (FGD)) were employed for the single-chain collapse. Additionally, monotethered nanoparticles were prepared via the copper-catalyzed azide–alkyne cycloaddition between the alkyne bearing copolymer with the highest FGD and an azide-terminated poly(ethylene glycol) (PEG) prior to UV-induced cross-linking. The formation of SCNPs was followed by size exclusion chromatography (SEC), nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM).

A brief user's guide to single-chain nanoparticles

“…Many groups have examined similar chemistry in SCNP synthesis. 31 UPy dimerization has been used to study the effect of several variables in SCNP formation. This is demonstrated in several publications by Meijer and coworkers involving 2-uriedopyrimidinone (UPy) dimerization (Fig.…”

“…Light scattering is an absolute method; the molar mass of large macromolecules is calculated based on first principles and consequently does not produce data relative to standards. 31,37,80 Viscometry Another valuable technique in the characterization of SCNPs is solution viscometry. Work from our laboratory has shown that using a MALS detector in-line with an SEC can prove that the molecular weight is consistent from parent polymer to SCNP.…”

Advances in single chain technology

“…8,117 In this sense, the morphology change suffered by SCNPs on passing from solution to the solid state is of paramount importance for the construction of efficient biosensors based on immobilized protein-mimic nano-objects and for the development of transient vitamin-binding systems, among other applications (see Section 3). 8,117 In this sense, the morphology change suffered by SCNPs on passing from solution to the solid state is of paramount importance for the construction of efficient biosensors based on immobilized protein-mimic nano-objects and for the development of transient vitamin-binding systems, among other applications (see Section 3).…”

Single‐Chain Folding of Synthetic Polymers: A Critical Update

“…UV light‐induced cycloadditions often constitute an alternative, convenient, atom‐efficient reaction class for single‐chain folding that can be carried out quantitatively at ambient temperature without the need for any metal catalyst. A number of photoinduced reactions have been examined for SCNP formation, including the light‐induced Diels–Alder reaction (DA; strictly speaking, the photochemical provision of an ene or diene species, which subsequently under goes a rapid ambient temperature DA reaction), the photoinduced nitrile‐imine mediated tetrazole‐ene cycloaddition, the photodimerization of anthracene, as well as the photodimerization of coumarin . Light‐triggered protocols, especially at higher wavelengths, are particularly attractive if, during the self‐folding process, temperature‐sensitive molecules are to be included into the SCNP.…”