Promoting Photocatalytic Direct C-H Difluoromethylation of Heterocycles using Synergistic Dual-Active-Centered Covalent Organic Frameworks.

Difluoromethylation reactions are increasingly important for the creation of fluorine-containing heterocycles, which are core groups in a diverse range of biologically and pharmacologically active ingredients. Ideally, this typically challenging reaction could be performed photocatalytically under mild conditions. To achieve this separation of redox processes would be required for the efficient generation of difluoromethyl radicals and the reduction of oxygen. A covalent organic framework photocatalytic material was, therefore, designed with dual reactive centers. Here, anthracene was used as a reduction site and benzothiadiazole was used as an oxidation site, distributed in a tristyryl triazine framework. Efficient charge separation was ensured by the superior electron-donating and -accepting abilities of the dual centers, creating long-lived photogenerated electron-hole pairs. Photocatalytic difluoromethylation of 16 compounds with high yields and remarkable functional group tolerance was demonstrated; compounds included bioactive molecules such as xanthine and uracil. The structure-function relationship of the dual-active-center photocatalyst was investigated through electron spin resonance, femtosecond transient absorption spectroscopy, and density functional theory calculations.

Evaluation of Nanoparticles Covalently Bound with BODIPY for Their Photodynamic Therapy Applicability.

Photodynamic therapy (PDT) relies on the combined action of a photosensitizer (PS), light at an appropriate wavelength, and oxygen, to produce reactive oxygen species (ROS) that lead to cell death. However, this therapeutic modality presents some limitations, such as the poor water solubility of PSs and their limited selectivity. To overcome these problems, research has exploited nanoparticles (NPs). This project aimed to synthesize a PS, belonging to the BODIPY family, covalently link it to two NPs that differ in their lipophilic character, and then evaluate their photodynamic activity on SKOV3 and MCF7 tumor cell lines. Physicochemical analyses demonstrated that both NPs are suitable for PDT, as they are resistant to photobleaching and have good singlet oxygen (1O2) production. In vitro biological analyses showed that BODIPY has greater photodynamic activity in the free form than its NP-bounded counterpart, probably due to greater cellular uptake. To evaluate the main mechanisms involved in PDT-induced cell death, flow cytometric analyses were performed and showed that free BODIPY mainly induced necrosis, while once bound to NP, it seemed to prefer apoptosis. A scratch wound healing test indicated that all compounds partially inhibited cellular migration of SKOV3 cells.

Triazine Frameworks for the Photocatalytic Selective Oxidation of Toluene.

Investigations into the selective oxidation of inert sp3 C-H bonds using polymer photocatalysts under mild conditions have been limited. Additionally, the structure-activity relationship of photocatalysts often remains insufficiently explored. Here, a series of thiophene-based covalent triazine frameworks (CTFs) are used for the efficient and selective oxidation of hydrocarbons to aldehydes or ketones under ambient aerobic conditions. Spectroscopic methods conducted in situ and density functional theory (DFT) calculations revealed that the sulfur atoms within the thiophene units play a pivotal role as oxidation sites due to the generation of photogenerated holes. The effect of photogenerated holes on photocatalytic toluene oxidation was investigated by varying the length of the spacer in a CTF donor-acceptor based photocatalyst. Furthermore, the manipulation of reactive oxygen species was employed to enhance selectivity by weakening the peroxidative capacity. As an illustrative example, this study successfully demonstrated the synthesis of a precursor of the neurological drug AMG-579 using a photocatalytic protocol.

Dipeptide coacervates as artificial membraneless organelles for bioorthogonal catalysis.

Artificial organelles can manipulate cellular functions and introduce non-biological processes into cells. Coacervate droplets have emerged as a close analog of membraneless cellular organelles. Their biomimetic properties, such as molecular crowding and selective partitioning, make them promising components for designing cell-like materials. However, their use as artificial organelles has been limited by their complex molecular structure, limited control over internal microenvironment properties, and inherent colloidal instability. Here we report the design of dipeptide coacervates that exhibit enhanced stability, biocompatibility, and a hydrophobic microenvironment. The hydrophobic character facilitates the encapsulation of hydrophobic species, including transition metal-based catalysts, enhancing their efficiency in aqueous environments. Dipeptide coacervates carrying a metal-based catalyst are incorporated as active artificial organelles in cells and trigger an internal non-biological chemical reaction. The development of coacervates with a hydrophobic microenvironment opens an alternative avenue in the field of biomimetic materials with applications in catalysis and synthetic biology.

Effective delivery and selective insecticidal activity of double-stranded RNA via complexation with diblock copolymer varies with polymer block composition.

BACKGROUND: Chemical insecticides are an important tool to control damaging pest infestations. However, lack of species specificity, the rise of resistance and the demand for biological alternatives with improved ecotoxicity profiles means that chemicals with new modes of action are required. RNA interference (RNAi)-based strategies using double-stranded RNA (dsRNA) as a species-specific bio-insecticide offer an exquisite solution that addresses these issues. Many species, such as the fruit pest Drosophila suzukii, do not exhibit RNAi when dsRNA is orally administered due to degradation by gut nucleases and slow cellular uptake pathways. Thus, delivery vehicles that protect and deliver dsRNA are highly desirable. RESULTS: In this work, we demonstrate the complexation of D. suzukii-specific dsRNA for degradation of vha26 mRNA with bespoke diblock copolymers. We study the ex vivo protection of dsRNA against enzymatic degradation by gut enzymes, which demonstrates the efficiency of this system. Flow cytometry then investigates the cellular uptake of Cy3-labelled dsRNA, showing a 10-fold increase in the mean fluorescence intensity of cells treated with polyplexes. The polymer/dsRNA polyplexes induced a significant 87% decrease in the odds of survival of D. suzukii larvae following oral feeding only when formed with a diblock copolymer containing a long neutral block length (1:2 cationic block/neutral block). However, there was no toxicity when fed to the closely related Drosophila melanogaster. CONCLUSION: We provide evidence that dsRNA complexation with diblock copolymers is a promising strategy for RNAi-based species-specific pest control, but optimisation of polymer composition is essential for RNAi success. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Tuning the Functionality of Self-Assembled 2D Platelets in the Third Dimension.

The decoration of 2D nanostructures using heteroepitaxial growth is of great importance to achieve functional assemblies employed in biomedical, electrical, and mechanical applications. Although the functionalization of polymers before self-assembly has been investigated, the exploration of direct surface modification in the third dimension from 2D nanostructures has, to date, been unexplored. Here, we used living crystallization-driven self-assembly to fabricate poly(ε-caprolactone)-based 2D platelets with controlled size. Importantly, surface modification of the platelets in the third dimension was achieved by using functional monomers and light-induced polymerization. This method allows us to selectively regulate the height and fluorescence properties of the nanostructures. Using this approach, we gained unprecedented spatial control over the surface functionality in the specific region of complex 2D platelets.

Surface Hybridization Chain Reaction of Binary Mixture DNA-PEG Corona Nanostructures Produced by Low-Volume RAFT-Mediated Photopolymerization-Induced Self-Assembly.

DNA-polymer hybrids have been attracting interest as adaptable functional materials by combining the stability of polymers with DNA nanotechnology. Both research fields have in common the capacity to be precise, versatile, and tunable, a prerequisite for creating powerful tools which can be easily tailored and adapted for bio-related applications. However, the conjugation of hydrophilic DNA with hydrophobic polymers remains challenging. In recent years, polymerization-induced self-assembly (PISA) has attracted significant attention for constructing nano-objects of various morphologies owing to the one-step nature of the process, creating a beneficial method for the creation of amphiphilic DNA-polymer nanostructures. This process not only allows pure DNA-polymer-based systems to be produced but also enables the mixture of other polymeric species with DNA conjugates. Here, we present the first report of a DNA-PEG corona nano-object's synthesis without the addition of an external photoinitiator or photocatalyst via photo-PISA. Furthermore, this work shows the use of DNA-macroCTA, which was first synthesized using a solid-support method resulting in high yields, easy upscaling, and no need for HPLC purification. In addition, to the formation of DNA-polymer structures, increasing the nucleic acid loading of assemblies is of great importance. One of the most intriguing phenomena of DNA is the hybridization of single-stranded DNA with a second strand, increasing the nucleic acid content. However, hybridization of DNA in a particle corona may destabilize the nanomaterial due to the electrostatic repulsive force on the DNA corona. Here, we have investigated how changing the DNA volume fraction in hybrid DNA-polymer self-assembled material affects the morphology. Moreover, the effect of the corona composition on the stability of the system during the hybridization was studied. Additionally, the hybridization chain reaction was successfully applied as a new method to increase the amount of DNA on a DNA-based nano-object without disturbing the morphology achieving a fluorescence signal amplification.

pH-Triggered Recovery of Organic Polymer Photocatalytic Particles for the Production of High Value Compounds and Enhanced Recyclability.

Pseudo-homogeneous polymeric photocatalysts are an emerging class of highly efficient and tunable photocatalytic materials, where the photocatalytic centers are easily accessible. The creation of highly efficient photocatalytic materials that can be rapidly separated and recovered is one of the critical challenges in photocatalytic chemistry. Here, we describe pH-responsive photocatalytic nanoparticles that are active and well-dispersed under acidic conditions but aggregate instantly upon elevation of pH, enabling easy recovery. These responsive photocatalytic polymers can be used in various photocatalytic transformations, including CrVI reduction and photoredox alkylation of indole derivative. Notably, the cationic nature of the photocatalyst accelerates reaction rate of an anionic substrate compared to uncharged species. These photocatalytic particles could be readily recycled allowing multiple successive photocatalytic reactions with no clear loss in activity.

Tunable Photocatalytic Selectivity by Altering the Active Center Microenvironment of an Organic Polymer Photocatalyst.

The favored production of one product over another is a major challenge in synthetic chemistry, reducing the formation of byproducts and enhancing atom efficacy. The formation of catalytic species that have differing reactivities based on the substrate being converted, has been targeted to selectively control reactions. Here, we report the production of photocatalytic self-assembled amphiphilic polymers, with either hydrophilic or hydrophobic microenvironments at the reactive center. Benzothiadiazole-based photocatalysts were polymerized into either the hydrophilic or the hydrophobic compartment of a diblock copolymer by RAFT polymerization. The difference in the reactivity of each microenvironment was dictated by the physical properties of the substrate. Stark differences in reactivity were observed for polar substrates, where a hydrophilic microenvironment was favored. Conversely, both microenvironments performed similarly for very hydrophobic substrates, showing that reagent partitioning is not the only factor that drives photocatalytic conversion. Furthermore, the use of secondary swelling solvents allowed an additional reagent exchange between the continuous phase and the heterogeneous photocatalyst, resulting in a significant 5-fold increase in conversion for a radical carbon-carbon coupling.

Hairy Conjugated Microporous Polymer Nanoparticles Facilitate Heterogeneous Photoredox Catalysis with Solvent-Specific Dispersibility.

Substrate accessibility is a key limiting factor for the efficiency of heterogeneous photoredox catalysis. Recently, a high photoactive surface area of conjugated microporous polymer nanoparticles (CMP NPs) has made them promising candidates for overcoming the mass transfer limitation to achieve high photocatalytic efficiency. However, this potential has not been realized due to limited dispersibility of CMP NPs in many solvents, particularly in water. Here, we report a polymer grafting strategy that furnishes versatile hairy CMP NPs with enhanced solvent-specific dispersibility. The method associates hundreds of solvent-miscible repeating units with one chain end of the photocatalyst surface, allowing minimal modification to the CMP network that preserves its photocatalytic activity. Therefore, the enhanced dispersibility of hairy CMP NPs in organic solvents or aqueous solutions affords high efficiency in various photocatalytic organic transformations.

Temperature- and pH-Responsive Polymeric Photocatalysts for Enhanced Control and Recovery.

The emergence of heterogeneous photocatalysis has facilitated redox reactions with high efficiency, without compromising the recyclability of the photocatalyst. Recently, stimuli-responsive heterogeneous photocatalytic materials have emerged as a powerful synthetic tool, with simple and rapid recovery, as well as an enhanced dynamic control over reactions. Stimuli-responsive polymers are often inexpensive and easy to produce. They can be switched from an active "on" state to an inert "off" state in response to external stimuli, allowing the production of photocatalyst with adaptability, recyclability, and orthogonal control on different chemical reactions. Despite this versatility, the application of artificial smart material in the field of heterogeneous photocatalysis has not yet been maximized. In this Minireview, we will examine the recent developments of this emerging class of stimuli-responsive heterogeneous photocatalytic systems. We will discuss the synthesis route of appending photoactive components into different triggerable systems and, in particular, the controlled activation and recovery of the materials.

Membrane Manipulation of Giant Unilamellar Polymer Vesicles with a Temperature-Responsive Polymer.

Understanding the complex behavior and dynamics of cellular membranes is integral to gain insight into cellular division and fusion processes. Bottom-up synthetic cells are as a platform for replicating and probing cellular behavior. Giant polymer vesicles are more robust than liposomal counterparts, as well as having a broad range of chemical functionalities. However, the stability of the membrane can prohibit dynamic processes such as membrane phase separation and division. Here, we present a method for manipulating the membrane of giant polymersomes using a temperature responsive polymer. Upon elevation of temperature deformation and phase separation of the membrane was observed. Upon cooling, the membrane relaxed and became homogeneous again, with infrequent division of the synthetic cells.

Aerobic Photobiocatalysis Enabled by Combining Core-Shell Nanophotoreactors and Native Enzymes.

Biocatalysis has become a powerful tool in synthetic chemistry, where enzymes are used to produce highly selective products under mild conditions. Using photocatalytically regenerated cofactors in synergistic combination with enzymes in a cascade fashion offers an efficient synthetic route to produce specific compounds. However, the combination of enzymes and photocatalysts has been limited due to the rapid degradation of the biomaterials by photogenerated reactive oxygen species, which denature and deactivate the enzymatic material. Here, we design core-shell structured porous nano-photoreactors for highly stable and recyclable photobiocatalysis under aerobic conditions. The enzymatic cofactor NAD+ from NADH can be efficiently regenerated by the photoactive organosilica core, while photogenerated active oxygen species are trapped and deactivated through the non-photoactive shell, protecting the enzymatic material. The versatility of these photocatalytic core-shell nanoreactors was demonstrated in tandem with two different enzymatic systems, glycerol dehydrogenase and glucose 1-dehydrogenase, where long-term enzyme stability was observed for the core-shell photocatalytic system.

Photocatalytic polymer nanomaterials for the production of high value compounds.

Nanotechnology has provided a platform for producing new photocatalytic materials, where the reduction in length scales has been used to amplify the efficiency of these light active materials. The progression to nano-based photocatalysts has been driven by the increase in surface area that is achieved. Furthermore, nanophotocatalysts based on porous polymers or gel materials are often more active as reagents can more easily partition across the whole photocatalyst. Here, reducing the diffusional path length for substrates across the porous/gel material increases the quantity of accessible active sites in the photocatalytic material. The formation of nanophotocatalytic materials has also enabled the formation of functional nanoparticles that can be used in different conditions traditionally inaccessible to bulk catalysts. Specifically, aqueous compatible nanophotocatalytic materials have been reported, enabling greener reaction conditions and new applications of photocatalysts.

Dual-Responsive Photocatalytic Polymer Nanogels.

Selective activation of photocatalysts under constant light conditions has recently been targeted to produce multi-responsive systems. However, controlled activation, with easy recovery of the photocatalysts, induced by external stimuli remains a major challenge. Mimicking the responsiveness of biological systems to multiple triggers can offer a promising solution. Herein, we report dual-responsive polymer photocatalysts in the form of nanogels consisting of a cross-linked poly-N-isopropylacrylamide nanogel, copolymerised with a photocatalytically active monomer. The dual-responsive polymer nanogels undergo a stark decrease in diameter with increasing temperature, which shields the photocatalytic sites, decreasing the activity. Temperature-dependent photocatalytic formation of NAD+ in water demonstrates the ability to switch photocatalysis on and off. Moreover, the photocatalysed syntheses of several fine chemicals were carried out to demonstrate the utility of the designed material.

pH-responsive polymer microcapsules for targeted delivery of biomaterials to the midgut of Drosophila suzukii.

Drosophila suzukii or spotted wing Drosophila is an economically important pest which can have a devastating impact on soft and stone fruit industries. Biological pesticides are being sought as alternatives to synthetic chemicals to control this invasive pest, but many are subject to degradation either in the environment or in the insect gut and as a result require protection. In this study we identified a sharp change in pH of the adult midgut from neutral to acidic (pH <3), which we then exploited to develop poly(2-vinylpyridine) (P2VP) microcapsules that respond to the change in midgut pH by dissolution and release of their cargo for uptake into the insect. First, we used labelled solid poly(methyl methacrylate) (PMMA) particles to show that microcapsules with a diameter less than 15 µm are readily ingested by the adult insect. To encapsulate water-soluble biological species in an aqueous continuous phase, a multiple emulsion template was used as a precursor for the synthesis of pH-responsive P2VP microcapsules with a fluorescent (FITC-dextran) cargo. The water-soluble agent was initially separated from the aqueous continuous phase by an oil barrier, which was subsequently polymerised. The P2VP microcapsules were stable at pH > 6, but underwent rapid dissolution at pH < 4.2. In vivo studies showed that the natural acidity of the midgut of D. suzukii also induced the breakdown of the responsive P2VP microcapsules to release FITC-dextran which was taken up into the body of the insect and accumulated in the renal tubules.

The sexually dimorphic behaviour of adult Drosophila suzukii: elevated female locomotor activity and loss of siesta is a post-mating response.

The polyphagous Drosophila suzukii is a highly invasive species that causes extensive damage to a wide range of berry and stone fruit crops. A better understanding of its biology and especially its behaviour will aid the development of new control strategies. We investigated the locomotor behaviour of D. suzukii in a semi-natural environment resembling a typical summer in northern England and show that adult female D. suzukii are at least 4-fold more active during daylight hours than adult males. This result was reproduced in several laboratory environments and was shown to be a robust feature of mated, but not virgin, female flies. Both males and virgin females kept on a 12 h light:12 h dark (12LD) cycle and constant temperature displayed night-time inactivity (sleep) followed by weak activity in the morning, an afternoon period of quiescence (siesta) and then a prominent evening peak of activity. Both the siesta and the sharp evening peak at lights off were severely reduced in females after mating. Flies of either sex entrained in 12LD displayed a circadian pattern of activity in constant darkness confirming the importance of an endogenous clock in regulating adult activity. This response of females to mating is similar to that elicited in female Drosophila melanogaster by the male sex peptide (SP). We used mass spectrometry to identify a molecular ion (m/z, 5145) corresponding to the poly-hydroxylated SP of D. suzukii and to show that this molecule is transferred to the female reproductive tract during copulation. We propose that the siesta experienced by male and virgin female D. suzukii is an adaptation to avoid unnecessary exposure to the afternoon sun, but that mated females faced with the challenge of obtaining resources for egg production and finding oviposition sites take greater risks, and we suggest that the change in female behaviour is induced by the male SP.