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).

We report the facile ambient temperature generation of size tunable and well-defined (pro)fluorescent single-chain nanoparticles (SCNPs) via the photoinduced nitrile imine intramolecular cross-ligation of linear precursor polymers, constituting a platform technology as novel imaging agents. A set of three linear precursor polymers (M n ≈ 14000 g mol −1 , Đ ≈ 1.25) was synthesized via nitroxide-mediated statistical copolymerization of styrene and 4-(chloromethyl)styrene (CMS), followed by a postpolymerization modification of the resulting copolymer installing protected maleimide (PG-Mal) as well as tetrazole (Tet) moieties. The tetrazole content (% Tet) along the lateral polymer chains was varied between 12 and 24% in order to preselect not only the size of the corresponding SCNPs, but also their fluorescence and reactive properties. Finally, the applicability of the profluorescent SCNPs for fluorescence labeling was demonstrated utilizing residual surface expressed Tet moieties on the SCNPs surface in a reaction with maleimide functional polymeric microspheres. The (pro)fluorescent single-chain nanoparticles were in-depth characterized by 1 H NMR spectroscopy, dynamic light scattering (DLS), size exclusion chromatography (SEC), and atomic force microscopy (AFM), as well as UV/vis and fluorescence spectroscopy. S ingle-chain nanoparticles (SCNPs) with diameters <20 nm, prepared via intramolecular cross-linking of single polymer chains, have attracted significant attention over the past few years due to their potential applications in catalysis, sensing, and drug delivery. 1−3 A further attractive area of their application is as cell transport and imaging agents, yet no viable, size tunable, and easy to prepare nanoparticle systems that display fluorescence and the corresponding excitation in the visible light region exist. Together with examples for polymer chains that have been folded at selective points along the backbone, 4−6 such single-chain architectures can be additionally regarded as potential synthetic mimics of proteins or peptides. The intramolecular cross-links in SCNPs can for instance be dynamic, 7,8 dynamic-covalent, 9,10 or covalent. 11−13 For covalently cross-linked SCNPs, to the best of our knowledge, only a small number of examples exists that take advantage of mild, phototriggered cross-linking approaches, and none present inherent fluorescent properties. 14−16 An example for fluorescent SCNPs was published by Oria et al. in 2010. 11 However, the fluorescence properties had to be imparted by employing a suitable cross-linker, and the fluorescence (391 and 410 nm), which has to be excited at λ exc = 390 nm, is not suitable for biological applications.In the present contribution, we introduce a powerful, intramolecular cross-linking chemistry for the fast preparation of inherently (pro)fluorescent SCNPs, which is based on the photoinduced nitrile imine mediated tetrazole-ene cycloaddition (NITEC). 17,18 UV-irradiation of tetrazole derivatives leads to the formation of nitrile imines, which are ...

We introduce the light-induced collapse of single glycopolymer chains in water generating fluorescent glyco singlechain nanoparticles (SCNPs) and their subsequent functionalization onto nanodiamonds. The glycopolymer precursors are prepared by polymerizing an acetylated mannose-based methacrylate monomer followed by a deprotection and postpolymerization functionalization step, introducing profluorescent photoactive tetrazole groups and furan-protected maleimide moieties. Subsequent UV irradiation in highly diluted aqueous solution triggers intramolecular tetrazole-mediated cycloadditions, yielding glyco SCNPs featuring fluorescence as well as lectin binding properties. The obtained SCNPs are coated onto nanodiamonds by adsorption, and the obtained hybrid nanoparticles are in depth characterized in terms of size, functionality, and bioactivity. Different coating densities are achieved by altering the SCNP concentration. The prepared nanoparticles are nontoxic in mouse RAW 264.7 macrophages. Furthermore, the fluorescence of the SCNPs can be exploited to image the SCNP-coated nanodiamonds in macrophage cells via confocal fluorescence microscopy.

A λ-orthogonal reaction system is introduced, where visible light induced radical thiol-ene and UV light induced NITEC (Nitrile-Imine mediated Tetrazole-Ene Conjugation) ligations are consecutively employed to fabricate and functionalize PEG-based hydrogels. The fluorescent pyrazoline cycloadducts from the NITEC reaction are exploited to visualize the written structures within the hydrogels as well as to attach RGD containing functional groups to promote spatially resolved cell attachment on the hydrogel surface.

A light-triggered strategy to functionalize nanodiamonds (NDs) with well-defined functional polymers is presented. The employed grafting approach is based on o-methylbenzaldehydes, which upon UV irradiation form oquinodimethanes that undergo Diels−Alder reactions with dienophiles. A series of well-defined maleimide end-group functional polymers, i.e., poly(styrene) (M n = 5800 g mol −1 ; Đ = 1.2), poly(N-isopropylacrylamide) (M n = 5800 g mol −1 , Đ = 1.2), and poly(2-(2′,3′,4′,6′-tetra-O-acetyl-α-D-mannosyloxy)ethyl methacrylate) (M n = 24 300, 39 000, and 58 800 g mol −1 , Đ ≤ 1.3), were prepared via reversible addition−fragmentation chain transfer (RAFT) polymerization of protected maleimide functional RAFT agents. After deprotection of the furan-protected maleimide end groups, the polymers were photografted to omethylbenzaldehyde functional NDs and characterized in detail via infrared (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The grafting density decreases with increasing polymer chain length (6.9−3.8 μmol g −1 ). Moreover, the binding of the glycopolymer functional NDs to the lectin Concanavalin A was demonstrated with a turbidity assay.

Looped flow processes are an efficient and versatile tool to synthesize cyclic macromolecular materials.

We report the light-driven grafting and controlled simultaneous co-grafting of various functional polymers to graphitic nanodiamonds (grNDs).