The Nanozyme Revolution: Enhancing the Performance of Medical Biosensing Platforms.

Nanozymes represent a class of nanosized materials that exhibit innate catalytic properties similar to biological enzymes. The unique features of these materials have positioned them as promising candidates for applications in clinical sensing devices, specifically those employed at the point-of-care. They notably have found use as a means to amplify signals in nanosensor-based platforms and thereby improve sensor detection limits. Recent developments in the understanding of the fundamental chemistries underpinning these materials have enabled the development of highly effective nanozymes capable of sensing clinically relevant biomarkers at detection limits that compete with "gold-standard" techniques. However, there remain considerable hurdles that need to be overcome before these nanozyme-based sensors can be utilized in a platform ready for clinical use. An overview of the current understandings of nanozymes for disease diagnostics and biosensing applications and the unmet challenges that must be considered prior to their translation in clinical diagnostic tests is provided.

Modular Synthesis of Semiconducting Graft Copolymers to Achieve "Clickable" Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting.

Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low-fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9'-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole), in a simple one-step substitution reaction, postpolymerization. Further, by utilizing azide-functionalized PEG, anti-human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site-specifically "clicked" onto the SPN surface, which allows the functionalized SPNs to specifically target HER2-positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics.

Aerobically-initiated C(sp3)-H bond amination through the use of activated azodicarboxylates.

Significant advancements in C-N bond formation via C-H bond functionalisation have made it a staple in the production of nitrogen-containing compounds in both industry and academia. However, transition metal-free synthesis, particularly in the case of C(sp3)-N formation, has remained a significant challenge to the synthetic community. Herein we report a procedure for α-C(sp3)-H amination of ethereal compounds through use of azodicarboxylates as the nitrogen source and freely-available atmospheric oxygen to access ethereal radical intermediates via aerobic C-H activation. The use of fluorinated alcohols as solvent is observed to greatly increase the efficiency of the reaction and we show experimentally and theoretically the key role of H-bonding between fluorinated alcohols and azodicarboxylates. Calculations of the condensed Fukui functions of a H-bonded fluorinated alcohol-azodicarboxylate complex correlates with a significantly increased susceptibility of azodicarboxylates to undergo reaction with radicals, which informs a number of recent reports in the literature.

Fine-tuning thio-pyridazinediones as SMDC scaffolds (with intracellular thiol release via a novel self-immolative linker).

Herein we report the synthesis of a library of thioalkyl- and thioaryl-pyridazinediones for thiol-based self-immolative release of cargo. A bisthioaryl-pyridazinedione is shown to be stable to serum protein albumin but unstable in intracellular conditions. A derivatised analogue underwent self-immolative degradation in cellular thiol conditions as evidenced by LC-MS/release of a turn-on fluorescence fluorophore; versatility of the thiol-pyridazinedione is demonstrated through synthesis of SMDC precursors that contain three different functional groups on the same central molecule.

Understanding the structure and dynamics of cationic surfactants from studies of pure solid phases.

A homologous series of n-alkyl trimethylammonium bromide surfactants, H(CH2)nN+(CH3)3 Br-, from C10TAB to C18TAB have been studied systematically in the bulk over a wide range of temperatures. Common features in the structures are identified, with packing dominated by the co-ordination of the cationic head groups with bromide anions and interdigitation of the hydrocarbon chains. This arrangement provides an explanation for the thin adsorbed bilayers that have been observed at various hydrophilic surfaces from aqueous solutions in previous studies. The molecular volumes and arrangement are comparable with structures of a number of different self-assembled amphiphiles. For these surfactants with bromide counter-ions, formation of crystal hydrates was not observed. The alkyl chains are highly mobile and at high temperatures a plastic phase is found for all materials with a transition enthalpy that is similar to the melting enthalpy of many long alkyl chains. Other unexpected phase transitions depend more markedly on the hydrocarbon chain length and evidently depend on delicate balances of the various contributions to the free energy.

Recent advances in metal-free aerobic C-H activation.

Herein we describe recent developments in selective, metal-free, dioxygen-induced C-H activation. This method of activating C-H bonds is an attractive alternative to traditional methodologies as it uses dioxygen, an inherently sustainable and widely accessible oxidant, in place of expensive or toxic metals and/or hazardous peroxides. Reactions developed on the basis of using aerobic C-H activation are also discussed.

Formation of Synthetically Versatile 2-Aminobenzophenones from Readily Accessed Acyl Hydrazides.

Herein, we report the transformation of readily accessed acyl hydrazides into protected 2-aminobenzophenones via a two-step process involving an aryne-based molecular rearrangement followed by a one-pot addition-elimination procedure. The assembly of the scaffold is tolerant of a wide variety of functional groups, and the carbamate group on the product can be facilely removed to afford highly valuable 2-aminobenzophenones. Application of the protocol was demonstrated in the synthesis of neurological medicine phenazepam.

A facile route to 1H- and 2H-indazoles from readily accessible acyl hydrazides by exploiting a novel aryne-based molecular rearrangement.

Herein we report the transformation of readily synthesised acyl hydrazides into 2-hydrazobenzophenones via a novel molecular rearrangement pathway using aryne chemistry. The developed reaction protocol is performed under relatively mild conditions and is tolerant of a wide variety of functional groups, and the 2-hydrazobenzophenone products provide access to both 1H- and 2H-indazoles from a single intermediate.

An overview of the synthesis of acyl hydrazides from aldehydes and reactions of the products thereof.

Herein a review on the methods for the formation and reaction of acyl hydrazides will be given. There is particular focus on the synthesis of acyl hydrazides from aldehyde precursors with examination of the various approaches (e.g. metal-based (rhodium, copper) and non-metal-based (aerobically- and photoorganocatalytically-initiated)) that have been used to achieve this. Finally, strategies to utilise acyl hydrazides for the formation of an array of useful entities will be detailed.