Artificial Photosynthases: Single-Chain Nanoparticles with Manifold Visible-Light Photocatalytic Activity for Challenging "in Water" Organic Reactions.

Photocatalyzed reactions of organic substances in aqueous media are challenging transformations, often because of scarce solubility of substrates and catalyst deactivation. Herein, we report single-chain nanoparticles, SCNPs, capable of efficiently catalyzing four different "in water" organic reactions by employing visible light as the only external energy source. Specifically, we decorated a high-molecular-weight copolymer, poly(OEGMA300-r-AEMA), with iridium(III) cyclometalated complex pendants at varying content amounts. The isolated functionalized copolymers demonstrated self-assembly into noncovalent, amphiphilic SCNPs in water, which enabled efficient visible-light photocatalysis of two reactions unprecedentedly reported in water, namely, [2 + 2] photocycloaddition of vinyl arenes and α-arylation of N-arylamines. Additionally, aerobic oxidation of 9-substituted anthracenes and ß-sulfonylation of α-methylstyrene were successfully carried out in aqueous media. Hence, by merging metal-mediated photocatalysis and SCNPs for the fabrication of artificial photoenzyme-like nano-objects─i.e., artificial photosynthases (APS)─our work broadens the possibilities for performing challenging "in water" organic transformations via visible-light photocatalysis.

Lanthanide-Based Single-Chain Nanoparticles as "Visual" Pass/Fail Sensors of Maximum Permissible Concentration of Cu2+ Ions in Drinking Water.

The maximum permissible concentration (m.p.c.) of Cu2+ ions in drinking water, as set by the World Health Organization (WHO) is m.p.c. (Cu2+)WHO = 30 × 10-6 m, whereas the US Environmental Protection Agency (EPA) establishes a more restrictive value of m.p.c. (Cu2+)EPA = 20 × 10-6 m. Herein, for the first time ever, a family of m.p.c. (Cu2+) "visual" pass/fail sensors is developed based on water-soluble lanthanide-containing single-chain nanoparticles (SCNPs) exhibiting an average hydrodynamic diameter less than 10 nm. Both europium (Eu)- and terbium (Tb)-based SCNPs allow excessive Cu2+ to be readily detected in water, as indicated by the red-to-transparent and green-to-transparent changes, respectively, under UV light irradiation, occurring at 30 × 10-6 m Cu2+ in both cases. Complementary, dysprosium (Dy)-based SCNPs show a yellow color-to-transparent transition under UV light irradiation at ≈15 × 10-6 m Cu2+. Eu-, Tb-, and Dy-containing SCNPs prove to be selective for Cu2+ ions as they do not respond against other metal ions, such as Fe2+, Ag+, Co2+, Ba2+, Ni2+, Hg2+, Pb2+, Zn2+, Fe3+, Ca2+, Mn2+, Mg2+, or Cr3+. These new m.p.c. (Cu2+) "visual" pass/fail sensors are thoroughly characterized by a combination of techniques, including size exclusion chromatography, dynamic light scattering, inductively coupled plasma-mass spectrometry, as well as infrared, UV, and fluorescence spectroscopy.

Why Single-Chain Nanoparticles from Weak Polyelectrolytes Can Be Synthesized at Large Scale in Concentrated Solution?

Here, the unresolved question of why single-chain nanoparticles (SCNPs) prepared from a weak polyelectrolyte (PE) precursor can be synthesized on a large is addresses, unlike SCNPs obtained from an equivalent neutral (nonamphiphilic) polymer precursor. The combination of the standard elastic single-chain nanoparticles (ESN) model -developed for neutral chains- with the classical scaling theory of PE solutions provides the key. Essentially, the long-range repulsion between electrostatic blobs in a weak PE precursor restricts the cross-linking process during SCNPs formation to the interior of each blob. Consequently, the maximum concentration at which PE-SCNPs can be prepared without interchain cross-linking is not determined by the full size of the PE precursor but, instead, by the smaller size of its electrostatic blobs. Therefore, PE-SCNPs can be synthesized up to a critical concentration where electrostatic blobs from different chains touch each other. This concentration can be 30 times higher than that for non-PE polymer precursors. Upon progressive dilution, the size of PE-SCNPs synthesized in concentrated solution increases until it reaches the bigger size of PE-SCNPs prepared under highly diluted conditions. PE-SCNPs do not adopt a globular conformation either in concentrated or in diluted solution. It shows that the main model predictions agree with experimental results.

Metamorphosis of a Commodity Plastic like PVC to Efficient Catalytic Single-Chain Nanoparticles.

We perform the conversion of a commodity plastic of common use in pipes, window frames, medical devices, flexible hoses, etc. like polyvinyl chloride (PVC) to single-chain nanoparticles (SCNPs). SCNPs are versatile, protein-mimetic soft nano-objects of growing interest for catalysis, sensing, and nanomedicine, among other uses. We demonstrate that the metamorphosis process -as induced through metal-free click chemistry- leads to well-defined, uniform SCNPs that are stable during storage in the solid state for months. All the conversion process (from PVC isolation to PVC-SCNPs synthesis) can be run in a green, dipolar aprotic solvent and involving, when required, a simple mixture of ethanol and water (1/1 vol.) as non-solvent. The resulting PVC-SCNPs are investigated as recyclable, metalloenzyme-mimetic catalysts for several representative Cu(II)-catalyzed organic reactions. The method could be valid for the metamorphosis and valorization of other commodity plastics in which it is feasible to install azide functional groups in their linear polymer chains.

Triggering Forces at the Nanoscale: Technologies for Single-Chain Mechanical Activation and Manipulation.

Over the past decades, polymer mechanochemistry has focused on the development and application of advanced force application methods to better understand the mechanochemical response of mechanophores. In this regard, techniques such as ultrasonication and single-molecule force spectroscopy (SMFS) are used to activate and detect up to thousands of chemical events within a polymer single chain, allowing the researchers to probe the mechanochemical reactivity of these stress-responsive motifs. Here, the most recent contributions of the single-molecule force spectroscopy technique to this field are presented, putting emphasis on the fundamental parameters of the technique for triggering specific force responses and on the description of force-extension curves measured for single- and multi-mechanophore polymers. Moreover, new contributions of microscopy-based techniques in the field of polymer mechanochemistry, as well as the potential application of single-chain nanoparticles as mechanoresponsive materials, are highlighted.

Self-Reporting of Folding and Aggregation by Orthogonal Hantzsch Luminophores Within a Single Polymer Chain.

Self-reporting fluorescence methods for monitoring folding and aggregation of proteins have a long history in biochemistry. Placing orthogonal luminophores within individual synthetic polymer chains for self-reporting both folding (i.e., its intramolecular compaction to isolated single-chain nanoparticles, SCNPs) and unbidden aggregation (i.e., the intermolecular association of SCNPs) remains a great challenge. Herein, a simple and efficient platform to identify both single-chain compaction and intermolecular aggregation phenomena via photoluminescence is presented based on simultaneous synthesis through Hantzsch ester formation of orthogonal luminophores within the same polymer chain. Starting from non-luminescent ß-ketoester-decorated chains, intramolecular compaction is visually detected through fluorescence arising from Hantzsch fluorophores generated as intra-chain connectors during folding. Complementary, intermolecular association is identified via aggregation-induced emission (AIE) from orthogonal luminophores displaying intense photoluminescence at redshifted wavelengths after formation of multi-SCNPs assemblies.

Water dynamics and self-assembly of single-chain nanoparticles in concentrated solutions.

Single-chain polymer nanoparticles (SCNPs) are soft nano-objects consisting of uni-macromolecular chains collapsed to a certain degree by intramolecular crosslinking. The similarities between the behaviour of SCNPs and that of intrinsically disordered proteins suggest that SCNPs in concentrated solutions can be used as models to design artificial micro-environments, which mimic many of the general aspects of cellular environments. In this work, the self-assembly into SCNPs of an amphiphilic random copolymer, composed by oligo(ethylene glycol)methyl ether methacrylate (OEGMA) and 2-acetoacetoxy ethyl methacrylate (AEMA), has been investigated by means of the dielectric relaxation of water. Direct evidence of segregation of the AEMA repeating units is provided by comparison with the dielectric relaxation of water in similar solutions of the linear hydrophilic polymer, P(OEGMA). Furthermore, the results of comparative studies with similar water solutions of an amphiphilic block copolymer forming multi-chain micelles support the single-chain character of the self-assembly of the random copolymer. The overall obtained results highlight the suitability of the dielectric spectroscopy to confirm the self-assembly of the amphiphilic random copolymers into globular like core-shell single-chain nanoparticles at a concentration well above the overlap concentration.

Synthesis of Single-Ring Nanoparticles Mimicking Natural Cyclotides by a Stepwise Folding-Activation-Collapse Process.

Cyclotides are small cyclic polypeptides found in a variety of organisms, ranging from bacteria to plants. Their ring structure endows those polypeptides with specific properties, such as improved stability against enzymatic degradation. Optimal cyclotide activity is often observed only in the presence of intra-ring disulfide bonds. Synthesis of soft nano-objects mimicking the conformation of natural cyclotides remains challenging. Here, a new class of natural cyclotide mimics synthesized by a stepwise folding-activation-collapse process at high dilution starting from simple synthetic precursor polymers is established. The initial folding step is carried out by a photoactivated hetero Diels-Alder (HDA) ring-closing reaction, which is accompanied by chain compaction of the individual precursor polymer chains as determined by size exclusion chromatography (SEC). The subsequent activation step comprises a simple azidation procedure, whereas the final collapse step is driven by CuAAC in the presence of an external cross-linker, providing additional compaction to the final single-ring nanoparticles (SRNPs). The unique structure and compaction degree of the SRNPs is established via a detailed comparison with conventional single-chain nanoparticles (SCNPs) prepared exclusively by chain collapse from the exact same precursor polymer (without the prefolding step). The stepwise folding-activation-collapse approach opens new avenues for the preparation of artificial cyclotide mimetics.

Facile Access to Completely Deuterated Single-Chain Nanoparticles Enabled by Intramolecular Azide Photodecomposition.

Access to completely deuterated single-chain nanoparticles (dSCNPs) has remained an unresolved issue. Herein, the first facile and efficient procedure to produce dSCNPs is reported, which comprises: i) the use of commercially available perdeuterated cyclic ether monomers as starting reagents, ii) a ring-opening copolymerization process performed in bulk to produce a neat dSCNP precursor, iii) a standard azidation reaction to decorate this precursor with azide moieties, and iv) a facile intramolecular azide photodecomposition step carried out under UV irradiation at high dilution providing with highly valuable, completely deuterated soft nano-objects from the precursor. dSCNPs are used to investigate by means of neutron-scattering measurements the form factor (radius of gyration, scaling exponent) of polyethylene oxide (PEO) chains in nanocomposites with different amounts of dSCNPs. Moreover, to illustrate the possibilities offered by the synthetic route disclosed in this communication for potential applications, the significant reduction in viscosity observed in a pure melt of polyether-based single-chain nanoparticles when compared to a melt of the corresponding linear polymer chains is shown.

Valuable structure-size relationships for tadpole-shaped single-chain nanoparticles with long and short flexible tails unveiled.

Tadpole-shaped single-chain nanoparticles (TSCNPs) are useful soft building blocks for nanotechnology composed of a flexible polymer chain tethered to an intramolecularly folded single-chain nanoparticle. We disclose herein valuable structure-size relationships for a priori TSCNP design depending on tail length, which are validated by experimental data from multiple TSCNP systems, allowing, for the first time, the prediction of TSCNP size before synthesis.

Mapping the Extra Solvent Power of Ionic Liquids for Monomers, Polymers, and Dry/Wet Globular Single-Chain Polymer Nanoparticles.

Ionic liquids (ILs) have shown advantages in organic synthesis and catalysis, energy storage and conversion, and a variety of pharmaceutical applications. Understanding the miscibility behavior of IL/monomer, IL/polymer, and IL/polymer nanoparticle mixtures is critical for the use of ILs as green solvents in polymerization processes as well as to rationalize recent observations concerning the superior solubility of some proteins in ILs when compared to standard solvents. In this work, the most relevant results obtained in terms of extended three-component Flory-Huggins theory concerning the extra solvent power (ESP) of ILs when compared to traditional nonionic solvents for monomeric solutes (Case I), linear polymers (Case II), dry (i.e., without IL inside) globular single-chain polymer nanoparticles (SCNPs) (Case III), and wet (i.e., with IL inside) globular SCNPs (Case IV) are presented. Moreover, useful ESP maps are drawn for the first time for IL mixtures corresponding to Cases I, II, III, and IV at a constant temperature and pressure. Finally, a potential pathway to improve the miscibility of nonionic polymers in ILs is proposed.

Excellent Stability in Water of Single-Chain Nanoparticles against Chain Scission by Sonication.

In this study the superior stability against degradation induced by ultrasound irradiation of water-soluble single-chain polymer nanoparticles when compared to their parent precursor polymers is reported, and a loop scission mechanism in support of such behavior is suggested.

Advances in Fluorescent Single-Chain Nanoparticles.

Fluorophore molecules can be monitored by fluorescence spectroscopy and microscopy, which are highly useful and widely used techniques in cell biology, biochemistry, and medicine (e.g., biomarker analysis, immunoassays, cancer diagnosis). Several fluorescent micro- and nanoparticle systems based on block copolymer micelles and cross-linked polymer networks, quantum dots, π-conjugated polymers, and dendrimers have been evaluated as optical imaging systems. In this review, we highlight recent advances in the construction of fluorescent single-chain nanoparticles (SCNPs), which are valuable artificial soft nano-objects with a small tunable size (as small as 3 nm). In particular, the main methods currently available to endow SCNPs with fluorescent properties are discussed in detail, showing illustrative examples.

Tunable slow dynamics in a new class of soft colloids.

By means of extensive simulations, we investigate concentrated solutions of globular single-chain nanoparticles (SCNPs), an emergent class of synthetic soft nano-objects. By increasing the concentration, the SCNPs show flattening, and even reentrant behaviour, in the density dependence of their structural and dynamic correlations, as well as a soft caging regime and weak dynamic heterogeneity. The latter is confirmed by validation of the Stokes-Einstein relation up to concentrations far beyond the overlap density. Therefore SCNPs arise as a new class of soft colloids, exhibiting slow dynamics and actualizing in a real system the structural and dynamic anomalies proposed by models of ultrasoft particles. Quantitative differences in the dynamic behaviour depend on the SCNP deformability, which can be tuned through the degree of internal cross-linking.

A Solvent-Based Strategy for Tuning the Internal Structure of Metallo-Folded Single-Chain Nanoparticles.

Controlling the spatial distribution of catalytic sites in metallo-folded single-chain nanoparticles (SCNPs) is a first step toward the rational design of improved catalytic soft nano-objects. Here an unexplored pathway is reported for tuning the internal structure of metallo-folded SCNPs. Unlike the conventional SCNP synthesis in good solvent (protocol I), the proposed new route (protocol II) is based on the use of amphiphilic random copolymers and transfer, after SCNP formation, from selective to good (nonselective) solvent conditions. The size and morphology of the SCNPs obtained by the two protocols, and the corresponding spatial distribution of the catalytic sites, have been determined by combining results from size exclusion chromatography with triple detection, small-angle X-ray scattering and molecular dynamics (MD) simulations. Remarkably, the use of these protocols allows the tuning of the internal structure of the metallo-folded SCNPs, as supported by MD simulations results. While the conventional protocol I yields a homogeneous distribution of the catalytic sites in the SCNP, these are arranged into clusters in the case of protocol II.

Advances in single chain technology.

The recent ability to manipulate and visualize single atoms at atomic level has given rise to modern bottom-up nanotechnology. Similar exquisite degree of control at the individual polymeric chain level for producing functional soft nanoentities is expected to become a reality in the next few years through the full development of so-called "single chain technology". Ultra-small unimolecular soft nano-objects endowed with useful, autonomous and smart functions are the expected, long-term valuable output of single chain technology. This review covers the recent advances in single chain technology for the construction of soft nano-objects via chain compaction, with an emphasis in dynamic, letter-shaped and compositionally unsymmetrical single rings, complex multi-ring systems, single chain nanoparticles, tadpoles, dumbbells and hairpins, as well as the potential end-use applications of individual soft nano-objects endowed with useful functions in catalysis, sensing, drug delivery and other uses.

Simulation guided design of globular single-chain nanoparticles by tuning the solvent quality.

The control of primary and further structures of individual folded/collapsed synthetic polymers has received significant attention in recent years. However, the synthesis of single-chain nanoparticles (SCNPs) showing a compact, globular conformation in solution has turned out so far to be highly elusive. By means of simulations, we propose two methods for obtaining globular SCNPs in solution. The first synthesis route is performed in the bad solvent, with the precursor anchored to a surface. In the second route we use a random copolymer precursor with unreactive solvophilic and reactive solvophobic units, which form a single core-shell structure. Both protocols prevent intermolecular cross-linking. After recovering good solvent conditions, the swollen nanoparticles maintain their globular character. The proposed methods are experimentally realizable and do not require specific sequence control of the precursors. Our results pave the way for the synthesis via solvent-assisted design of a new generation of globular soft nanoparticles mimicking global conformations of native proteins in solution.

Efficient Synthesis of Single-Chain Globules Mimicking the Morphology and Polymerase Activity of Metalloenzymes.

Endowing unimolecular soft nanoobjects with biomimetic functions is attracting significant interest in the emerging field of single-chain technology. Inspired by the compartmentalized structure and polymerase activity of metalloenzymes, copper-containing compact nanoglobules have been designed, synthesized, and characterized endowed with metalloenzyme mimicking characteristics toward controlled synthesis of water-soluble polymers and thermoresponsive hydrogels. When compared to metalloenzymes, artificial nanoobjects endowed with metalloenzyme mimicking characteristics offer increased stability against thermal changes and reduced degradability by hydrolytic enzymes.

Single-chain nanoparticles vs. star, hyperbranched and dendrimeric polymers: effect of the nanoscopic architecture on the flow properties of diluted solutions.

The flow properties of dilute solutions of linear, star, hyperbranched and dendrimeric polymers have been the subject of numerous studies. However, no systematic analysis has been carried out for the case of single-chain nanoparticles (SCNPs) of different nature, which are unimolecular soft nano-objects consisting of individual polymer chains collapsed to a certain degree by means of intramolecular bonding. On the basis of the fractal nature of SCNPs and experimental data of the hydrodynamic radius, a simple predictive power-law between the intrinsic viscosity and molecular weight is proposed. Furthermore, a comparison is made between the intrinsic viscosities of SCNPs and of low-functionality stars, hyperbranched and dendrimeric polymers of the same chemical nature and molecular weight. As a consequence of their complex nanoscopic architecture, the intrinsic viscosities of SCNPs are systematically smaller than those of linear chains and low-functionality stars. When compared with hyperbranched and dendrimeric polymers, a complex behaviour is found, this being highly dependent on the molecular weight and amount of X-linkers of SCNPs.

Multi-orthogonal folding of single polymer chains into soft nanoparticles.

Efficient folding of single polymer chains is a topic of great interest due, mainly, to the challenging possibility of mimicking and controlling the structure and functionality of natural biomacromolecules (e.g., enzymes, drug delivery vehicles, and catalysts) by means of artificial single chain nano-objects. By performing extensive molecular dynamics simulations we investigate the formation of soft nanoparticles by irreversible intramolecular cross-linking of polymer precursors of different lengths. In order to optimize the folding process and to obtain more compact structures we vary the number of chemical species among the linker groups (orthogonal chemistry) which selectively form the bonds. The use of orthogonal chemistry protocols, by increasing the number of different chemical species of the linkers, leads to nanoparticles that are systematically smaller and more spherical than their homofunctional counterparts. We characterize the conformational properties of the resulting nanoparticles. These are intrinsically polydisperse in size, with a significant fraction of sparse topologies. We discuss the relevance of our results for synthesis protocols in real systems.