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We report a method for the synthesis of azafluoranthenes under neutral reaction conditions in a highly atom-economical manner by the iridium-catalyzed [2 + 2 + 2] cycloaddition of 1,8-dialkynylnaphthalenes with nitriles. A variety of nitriles react with methyl- or phenyl-substituted 1,8-dialkynylnaphthalenes to give a wide range of azafluoranthenes. Azafluoranthenes bearing an amino group show intense fluorescence at around 500 nm. Comparison of the fluorescence properties of amine-substituted azafluoranthenes with related compounds revealed the importance of the amine moiety for obtaining a high fluorescence quantum yield. The choice of the solvent affected the emission maxima and the fluorescence quantum yield. Azafluoranthenes bearing pyrrolidine exhibited blue-shifted emission bands in a non-polar solvent and gave a fluorescence quantum yield of 0.76 in toluene. A Lippert-Mataga plot and computational studies provide insight into the origin of the fluorescence of azafluoranthenes. Furthermore, cellular experiments using human breast adenocarcinoma cells SK-BR-3 demonstrated the feasibility of using azafluoranthenes as fluorescent probes.

Binding constants between polycyclic aromatic hydrocarbons (PAHs) and tetranuclear rutheno macrocycles are successfully manipulated via covalent post-assembly modification (PAM).

Triazole phosphonates are valuable structural motifs in chemical biology and the subject of growing recent interest. A novel methodology to synthesize triazolyl phosphonates starting from furfuryl phosphonate alcohols and organo-azides was developed. This method involved an intermolecular copper-catalyzed dearomatized [3 + 2] cycloaddition/furan ring-opening cascade reaction. A strategy involving a three-component reaction was realized for quick access to triazole phosphonates.

Isoxazoles, enamines, TiCl4(THF)2, and Ti powder can efficiently make a variety of pyridine derivatives. DFT investigation of the mechanism suggests a possible pathway involving ring-opening followed by amine loss.

Tetrazine-based bio-orthogonally activated fluorogenic probes have drawn great attention due to their excellent performance in bioimaging; however, most of them suffer from aggregation-caused quenching (ACQ) problems. Herein, we developed a set of novel tetrazine-modified tetraphenylenes (TPEs) as bio-orthogonally activated aggregation-induced emission (AIE) fluorogenic probes. Both the fluorescence and AIE features are quenched by tetrazine, which is mediated by the through-bond energy-transfer (TBET) mechanism, and are activated upon converting tetrazine to pyridazine

An enantioselective synthesis of polycyclic fluorinated pyrrolidines has been achieved by Cu-catalyzed intramolecular 1,3-dipolar cycloaddition of azomethine ylides with fluorinated dipolarophiles. The method displays a wide scope and afforded the desired cycloadducts in high yields with up to 99% ee. These results demonstrate that fluoroalkyl substituents are excellent activating groups in this transformation.

A facile chiral phosphoric-acid catalyzed asymmetric inverse-electron-demand aza-Diels-Alder reaction of 1,3-diazadienes with 3-vinylindoles was established. By using this mild and practical protocol, a broad range of benzothiazolopyrimidines with three contiguous stereogenic centers were prepared in good yields and excellent diastereo- and enantio-selectivities (43 examples, up to 83% yield,99% ee and all20 : 1 dr). A plausible concerted reaction pathway enabled by the dual hydrogen-bonding effect was proposed to account for the observed excellent enantioselectivity and specific

In this paper, a new type of δ-vinylvalerolactone was designed and synthesized, and used as a new precursor in Pd-catalyzed [6+3] cycloaddition with azomethine imines, leading to nine-membered 1,2-dinitrogen-containing heterocycles in 77-98% yields with20 : 1 d.r. These nine-membered ring-fused products were further transformed into unusual tetracyclic bridged-ring compounds without loss of the diastereoselectivities.

Pyrazole is an essential structural component of many pharmaceuticals and agrochemicals. The synthesis of pyrazoles has been a subject of intense research for several decades. Many transformations are now available to conveniently access pyrazoles from readily available starting materials. Conventionally, the synthesis of pyrazoles involves the condensation reaction of hydrazines with 1,3-dicarbonyl compounds or their synthetic equivalents and 1,3-dipolar cycloaddition reactions of diazo compounds with dipolarophiles. The present review provides comprehensive information on the development of synthetic approaches to access pyrazoles

An inverse-electron-demand oxa-Diels-Alder reaction of 5-alkenyl thiazolones with β,γ-unsaturated carbonyl compounds enabled by quinine thiourea was studied, which allows the enantioselective synthesis of a broad range of highly functionalized pyranthiazoles bearing three continuous stereocenters. This protocol is adaptable to a wide scope of substrates and has great potential for scale-up synthesis and facile transformation.

Herein, we describe a methodology for iminosydnone chlorination and we demonstrate the high beneficial effect of this modification on the reactivity of these mesoionic dipoles in strain-promoted cycloaddition reactions. Exploiting their reaction with cyclooctynes, we used these new iminosydnones for bioorthogonal release of amide, urea and sulfonamide containing drugs. Notably, drugs containing a terminal amide function were released for the first time with good kinetic constants.

The iridium-catalyzed azide-thioalkyne cycloaddition was found to proceed much faster with benzyl azide than with phenyl azide. The high azido-type selectivity was also observed in other combinations of azides with different steric environments. This finding enabled the efficient assembly of three azidophilic molecules to triazido platforms by three sequential triazole-forming reactions.

A facil route to spirocyclic oxazole derivatives via the [3 + 2] cycloaddition reactions between 2-arylidene cycloalkanones and azaoxyallyl cations was developed.

Refereed/Peer-reviewed Engineered T-cell therapies have proven highly efficacious for the treatment of haematological cancers, but translation of this success to solid tumours has been limited, in part, due to difficulties in maintaining high doses at specific target sites. Hydrogel delivery systems that provide a sustained release of T-cells at the target site are emerging as a promising strategy. Therefore, in this study we aimed to develop an injectable hydrogel that gels in situ via efficient Diels-Alder cycloaddition (DAC) chemistry and provides a sustained release of T-cells through gradual hydrolysis of the hydrogel matrix. Hydrogels were prepared via the DAC between fulvene and maleimide functionalised poly(ethylene glycol) (PEG) derivatives. By adjusting the concentration and molecular weight of the functionalised PEGs in the hydrogel formulation the in vitro gelation time (Tgel), initial Young's modulus (E) and degradation time (Td) could be tailored from 15-150 min, 5-179 kPa and 7-114 h, respectively. Prior to gelation, the formulations could be readily injected through narrow gauge (26 G) needles with the working time correlating closely with the Tgel. A 5 wt% hydrogel formation with conjugated cyclic RGD motif was found to be optimal for the encapsulation and release of CD3+ T-cells with a near linear release profile and >70% cell viability over the first 4 d and release continuing out to 7 d. With their tuneable Tgel, Td and stiffness, the DAC hydrogels provide the opportunity to control the release period and profile of encapsulated cells

We report herein a concise total synthesis of streptovertidione, and its transformation to streptovertidine A and formicapyridine A through a bioinspired pyridination. This strategy features: (1) a one-pot Ti(O

Herein we report our study on the development of a catalytic one-pot process, showing the challenges and advantages encountered all over the way. At the end, we developed a regioselective, environmentally friendly, and operationally simple method to explore the reactivity of functionalized propargylic alkynes through three copper-catalysed reactions in a single reaction vessel. The sequence consisted of a hydroboration, azidation, and 1,3-dipolar cycloaddition and led to the regioselective formation of vinyl 1,2,3-triazoles in good yields.

A catalytic asymmetric construction of the bispiro[pyrazolone-dihydropyrrole-oxindole] skeleton catalyzed by chiral DMAP-derived catalyst was successfully achieved by employing recently explored pyrazolone-derived MBH carbonate in high yields with excellent stereoselectivities. The proposed transition state indicated that the intermolecular hydrogen bonds and π-π interactive forces played an essential role in stereoselective chemical transformation.

An endoperoxide-containing COF was constructed to deliver extracellular singlet oxygen into cancer cells to realize light- and oxygen-independent oxidative damage for cancer therapy.

Heterocyclic rings are the fundamental building blocks of biological systems and have wide applications in synthetic chemistry and medicinal science. The development of novel synthetic methodology for heterocyclic skeletons from a variety of starting materials has made great progress in the past decades. Meanwhile, highly strained cyclopropenes as reactive reagents in organic transformations have drawn much attention from chemists. The rich chemical reactivity and reaction routes have been well investigated, and some review articles related to the reactivity of cyclopropenes and the construction of carbocycles and acyclic compounds have appeared in these years. Thus, this review mainly focuses on the progress in the construction of heterocyclic rings starting from various cyclopropenes including the reactions of commonly available stable cyclopropenes

Bioorthogonal prodrug activation holds great promise for balancing efficacy and safety of drugs. Visualizable bioorthogonal prodrug activation could allow elucidation of drug liberation events in situ for their correlation with therapeutic efficacy.

Herein, an enantioselective total synthesis of (-)-panduratin D, a novel secondary metabolite against human pancreatic PANC-1 cancer cell, from commercially available 3-methoxyphenol is reported. The synthesis was completed in nine steps and the key features include

An important but often overlooked feature of Diels-Alder (DA) cycloadditions is the ability for DA adducts to undergo mechanically induced cycloreversion when placed under force. Herein, we demonstrate that the commonly employed DA cycloaddition between furan and maleimide to crosslink hydrogels results in slow gelation kinetics and "mechanolabile" crosslinks that relate to reduced material strength. Through rational computational design, "mechanoresistant" DA adducts were identified by constrained geometries simulate external force models and employed to enhance failure strength of crosslinked hydrogels. Additionally, utilization of a cyclopentadiene derivative, spiro[2.4]hepta-4,6-diene, provided mechanoresistant DA adducts and rapid gelation in minutes at room temperature. This study illustrates that strategic molecular-level design of DA crosslinks can provide biocompatible materials with improved processing, mechanical durability, lifetime, and utility.

α,β-Unsaturated acyl ammonium species are versatile intermediates that have been applied in a variety of transformations including Michael additions, domino reactions and cycloadditions. Many of these transformations are promoted by chiral Lewis base catalysts, enabling the rapid generation of molecular complexity with high stereochemical control. This review highlights recent developments in the generation and application of α,β-unsaturated acyl ammonium intermediates reported since a previous review of this area in 2016. Particular emphasis will be placed on reports providing mechanistic insight into catalytic transformations and observed selectivities. A perspective on current challenges and potential future developments in the field of α,β-unsaturated acyl ammonium catalysis is also provided.

Sodium pyruvate, a natural intermediate produced during cellular metabolism, is commonly used in buffer solutions and media for biochemical applications. Here we show the use of sodium pyruvate (SP) as a reducing agent in a biocompatible aqueous photoinduced azide-alkyne cycloaddition (CuAAC) reaction. This copper(I)-catalyzed 1,3-dipolar cycloaddition is triggered by SP under UV light irradiation, exhibits oxygen tolerance and temporal control, and provides a convenient alternative to current CuAAC systems, particularly for biomolecular conjugations.

The tetrazole-based photoclick chemistry has attracted considerable attention in virtue of its good biocompatibility, exclusive molecular reaction, and spatiotemporally controllable properties. Using this photoclick reaction, we designed an in situ, real-time fluorescence imaging system that targeted mitochondria and lysosomes in a spatiotemporally controllable manner. Upon irradiation, the pyrazoline fluorophore was generated in situ by the intramolecular tetrazole-alkene cycloaddition reaction ("photo-click chemistry"). This strategy exhibits features such as fast response, high efficiency, strong fluorescence intensity without background and superior stability. In addition, by integrating with an organelle-specific group, it has a good application for subcellular targeting imaging. Furthermore, the photo-responsive moiety Tet facilitates the probes, Mt-Tet and Ly-Tet, for the super-resolution imaging of subcellular structures.

A highly concise method for 1,4-diazabicyclo[2.2.2]octane (DABCO) catalyzed [4+2] annulations of o-amino-acylation of aryl MBH carbonates with isocyanates has been developed. For the first time, MBH carbonates served as 1,4-dipoles, providing functionalized 3,4-dihydroquinazolinones in mild conditions with good to excellent yields. The density functional theory calculations of the mechanism supports our hypothesis.

Covering: 2010 to 2020Benzocycloheptane is a fundamental and unique structural motif found in pharmaceuticals and natural products. The total syntheses of natural products bearing the benzocycloheptane subunit are challenging and there are only a few efficient approaches to access benzocycloheptane. Thus, new methods and innovative strategies for preparing such natural products need to be developed. In this review, recent progress in the total syntheses of natural products bearing the benzocycloheptane motif is presented, and key transformations for the construction of benzocycloheptane are highlighted. This review provides a useful guide for those engaged in the syntheses of natural products containing the benzocycloheptane motif.

Dimeric natural products are a collection of molecules with diverse molecular architectures and significant bio-activities. In this tutorial review, total synthesis of complex dimeric natural products accomplished in recent years are summarized and various dimerization strategies are discussed. By highlighting the selected representative examples, this review aims to demonstrate the recent tactics of dimerization which is an important process integrated into the whole synthetic sequences of dimeric natural products, provide insights on structural and chemical properties of monomers and dimers of related natural products, and promote further technological advances in organic synthesis and biological studies of complex dimeric natural products.

Pyrroloindolines are important and privileged polycyclic indoline motifs that are widely present in natural products and bio-significant molecules. From an organic chemistry perspective, their rigid tricyclic molecular architectures with a fully substituted carbon center at the C3a-position pose a great challenge to synthetic chemists. In a biological context, pyrroloindoline-containing alkaloids display a plethora of promising activities, making them significant in biological sciences and drug development. In the past few decades, pyrroloindoline and its analogues have emerged as appealing synthetic targets, attracting tremendous attention from the synthetic community. In this review, we summarize the state-of-the-art catalytic asymmetric synthesis of pyrroloindolines, as well as the related applications to the total synthesis of natural products.

To understand the structure and ensuing function of RNA in various cellular processes, researchers greatly rely on traditional as well as contemporary labeling technologies to devise efficient biochemical and biophysical platforms. In this context, bioorthogonal chemistry based on chemoselective reactions that work under biologically benign conditions has emerged as a state-of-the-art labeling technology for functionalizing biopolymers. Implementation of this technology on sugar, protein, lipid and DNA is fairly well established. However, its use in labeling RNA has posed challenges due to the fragile nature of RNA. In this feature article, we provide an account of bioorthogonal chemistry-based RNA labeling techniques developed in our lab along with a detailed discussion on other technologies put forward recently. In particular, we focus on the development and applications of covalent methods to label RNA by transcription and posttranscription chemo-enzymatic approaches. It is expected that existing as well as new bioorthogonal functionalization methods will immensely advance our understanding of RNA and support the development of RNA-based diagnostic and therapeutic tools.

Experimental and DFT investigation of the α,α-cyclopropanation of amino acids via nucleophilic addition of the deprotonated glycine Ni(ii)-Schiff-base complex, containing the (S)-proline derivatives as an auxiliary chiral moiety, to alkyl α-bromoacrylates was performed. It was demonstrated that the predominant configuration of the newly formed α-stereocenter is (S), regardless of the solvent used but the smart choice of solvent allows high diastereoselectivity at the removed β-stereocenter to be obtained, which commonly is rather rare. DFT analysis of the reaction path provides a rationale for the stereochemical outcome observed. The cyclopropanated complexes exhibit stereodependent redox activity, thus supporting that this is a general phenomenon inherent to this class of Ni Schiff-base derivatives, accounting for the influence of the peripheral groups in the metal coordination environment on the relative impact of different parts of the molecule in the frontier orbitals via conformational changes.

Herein, we report the chemoenzymatic synthesis of a heterodimeric (-)-rugulosin B, homodimeric (-)-rugulosin C, and several rugulin analogues in three to four steps starting from anthraquinones. This work supports dimerization between variously substituted putative monomeric intermediates during the biosynthesis of naturally occurring (+)-rugulosin B and C.

Covering: 2013-2018 Natural products bearing quaternary carbon stereocenters have attracted tremendous interest from the synthetic community due to their diverse biological activities and fascinating molecular architectures. However, the construction of these molecules in an enantioselective fashion remains a long-standing challenge because of the lack of efficient asymmetric catalytic methods for installing these motifs. The rapid progress in the development of new-generation efficient chiral catalysts has opened the door for several asymmetric reactions, such as Michael addition, dearomative cyclization, polyene cyclization, α-arylation, cycloaddition, allylation, for the construction of quaternary carbon stereocenters in a highly enantioselective fashion. These asymmetric catalytic methods have greatly facilitated the synthesis of complex natural products with improved output and overall efficiency. In this concise review, we highlight the progress in the last six years in complex natural product synthesis, in which at least one quaternary carbon stereocenter has been constructed via asymmetric catalytic technologies, with particular emphasis on the analysis of the stereochemical model of each enantioselective transformation.

Single nucleotide polymorphisms (SNPs) have been proven to be important biomarkers for disease diagnosis, prognosis and disease pathogenesis. Here, taking the advantages of a self-assembled oligonucleotide sandwich structure and robust chemical reactions, we have developed a simple, high-throughput and effective colorimetric analytical technique termed CuAAC-based ligation-assisted assays (CuAAC-LA) for SNP detection using a DNA-BIND 96-well plate. With the 5'-azide and 3'-alkyne groups labelled on two oligonucleotide probes, the target DNA can direct a Cu(i)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction. Since the small difference in duplex stability caused by a single-nucleotide mismatch was amplified by the steric effects of these reactive groups for the ligation reaction of an unstable duplex, CuAAC-LA exhibited an ultra-sensitive discrimination ability for a mutant type target in the presence of large amounts of wild type targets. As low as 0.05% SNP could be clearly detected, which was better than most previously reported methods by various DNA ligases, indicating that a simple and rapid synthetic method i.e., the DNA template-directed click reaction held the potential to replace the ligase for SNP detection.

Strain-release driven transformations give access to attractive bioisosteric motifs highly prized by medicinal chemists and they are characteristic of molecules possessing distorted bond lengths and angles. By broadening the chemical space in drug discovery, recently, these compounds have attracted a lot of interest. Their reactivity stems mainly from an increased energy and destabilization. As a result, the opening of the bridging bond occurs under the action of both nucleophiles and electrophiles as well as radical species and transition metals. Though the bridge bond dominates their reactivity, it is also influenced by the substitution pattern. This feature article focuses on strain-release driven strategies paying particular attention to the most recent (year > 2010) advances.

Thio-substituted nucleobases have received long-standing interest from experimental and theoretical scientists due to their potential applications in photodynamic therapy and crosslinking studies. Though the thymidine:4-thiothymidine dimer is an important structure in the DNA duplex, the molecular-level photoreaction mechanisms are still obscure. Herein, high-level QM/MM methods were adopted to investigate the photoinduced cycloaddition and (6-4) reactions of the thymidine:4-thiothymidine dimer in the DNA duplex, namely, d(ACCT(4ST)CGC:TGGAAGCG). Based on the calculated results, we identified five efficient nonadiabatic decay pathways to populate the T1 state from the initially occupied S2 state of Tp4ST via two crucial intersection structures, i.e., S2/S1 and S2/T2/S1/T1. Such photophysical processes are mainly localized on the 4-thiothymidine chromophore. After hopping to the T1 state, the light-induced [2+2] cycloaddition reaction could take place via a stepwise and nonadiabatic reaction pathway, which starts from Tp4ST via T1cc or T1cs intermediates in the T1 state and ends up with S5-thietane in the S0 state. By contrast, the concerted and thermal cycloaddition pathway in the ground state has a remarkable energy barrier, which is mechanistically less important. The subsequent generation of S5-(6-4) from S5-thietane is a concerted process in the S0 state with the simultaneous fission of the C4-S8 bond and the formation of the S8-H9 bond. In the end, we believe our present work will provide important mechanistic insights into photo-isomerization of thio-substituted nucleobases in DNA duplexes.

A bio-orthogonal chemistry-based approach for fluorescent labelling of ribosomal RNA is described. It involves an adenosine analogue modified with trans-cyclooctene and masked 5'-phosphate group using aryl phosphoramidate. The incorporation into rRNA has been confirmed using agarose gel electrophoresis, as well as a highly sensitive UHPLC-MS/MS method. Fluorescent labelling of rRNA has been achieved in live HeLa cells via an inverse electron demand Diels-Alder reaction with a tetrazine conjugated to an Oregon Green fluorophore. This communication describes the stepwise approach that led to the development and characterization of the probe. The results demonstrate a new strategy towards development of future fluorescent probes to investigate the biochemistry of nucleic acids.

4-Oxime-1,8-naphthalimide was reported as a novel bioorthogonal turn-on probe based on 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxide and alkenes/alkynes. The resulting isoxazole products displayed dramatically strong fluorescence enhancement upon photoirradiation through isoxazole-oxazole photoisomerization. This new methodology was successfully applied for in situ fluorogenic protein labeling.

Synthesis of novel triazole fused iminocyclitol-δ-lactams is described. The synthetic sequence involves the intermolecular [3 + 2] cycloaddition reaction of five-membered iminocyclitol derived azides with diethylacetylene dicarboxylate followed by intramolecular lactamisation, decarboxylation/reduction and final deprotection. Compound 3 is found to be a selective inhibitor of α-glucosidase from baker's yeast while two other compounds (2 and 4) that possess an additional hydroxymethyl group in the triazole ring are selective against β-galactosidase from E. coli. Docking studies suggest the significance of the lactam carbonyl group for effective binding of these inhibitors with the active sites through hydrogen bonding.

Organic azides are useful synthetic intermediates, which demonstrate broad reactivity. Unlike most organic azides, allylic azides can spontaneously rearrange to form a mixture of isomers. This rearrangement has been named the Winstein rearrangement. Using allylic azides can result in low yields and azide racemization in some synthetic contexts due to the Winstein rearrangement. Effort has been made to understand the mechanism of the Winstein rearrangement and to take advantage of this process. Several guiding principles can be used to identify which azides will produce a mixture of isomers and which will resist rearrangement. Selective reaction conditions can be used to differentiate the azide isomers in a dynamic manner. This review covers all aspects of allylic azides including their synthesis, their reactivity, the mechanism of the Winstein rearrangement, and reactions that can selectively elaborate an azide isomer. This review covers the literature from Winstein’s initial report to early 2019.

Three new luminescent conjugates between dinuclear rhenium complexes and an estradiol, namely E2-Re, are described. The derivatives have the general formula [Re2(μ-Cl)2(CO)6(μ-R-pydz-17α-ethynylestradiol)] (R-pydz = functionalized 1,2-pyridazine), where the estradiol moiety is covalently bound to the β position of the pyridazine ligand. Different synthetic pathways are investigated, including the inverse-type [4 + 2] Diels Alder cycloaddition reaction between the electron poor 1,2,4,5-tetrazine and 17α-ethynylestradiol for the synthesis of E2-Re1. The three E2-Re conjugates are purified on silica gel and isolated in a spectroscopically pure form in moderate to good yields (28-50%). All the E2-Re conjugates are comprehensively characterized from the spectroscopic and photophysical points of view. Cellular internalization experiments on human MCF-7 and 231 cells are also reported, displaying interesting staining differences depending on the nature of the spacer linking the estradiol unit to the organometallic fragment. Furthermore, the suitability of these conjugates to also stain simple multicellular organisms, i.e. Ciona intestinalis embryos and larvae at different stages of development, is reported here for the first time.

Triggering antibody-mediated innate immune mechanisms to kill cancer cells is an attractive therapeutic avenue. In this context, recruitment of endogenous antibodies to the cancer cell surface could be a viable alternative to the use of monoclonal antibodies. We report on antibody-recruiting polymers containing multiple antibody-binding hapten motifs and cyclooctynes that can covalently conjugate to azides introduced onto the glycocalyx of cancer cells by metabolic labeling with azido sugars.

Microreactors are emerging as an efficient, sustainable synthetic tool compared to conventional batch reactors. Here, we present a new numbering-up metal microreactor by integrating a flow distributor and a copper catalytic module for high productivity of a commercial synthetic drug. A flow distributor and an embedded baffle disc were manufactured by CNC machining and 3D printing of stainless steel (S/S), respectively, whereas a catalytic reaction module was composed of 25 copper coiled capillaries configured in parallel. Eventually, the numbering-up microreactor system assembled with functional modules showed uniform flow distribution and high mixing efficiency regardless of clogging, and achieved high-throughput synthesis of the drug "rufinamide", an anticonvulsant medicine, via a Cu(i)-catalyzed azide-alkyne cycloaddition reaction under optimized conditions.

By coupling in situ [2+3] Huisgen cycloaddition with an in vitro transcription/translation luminescence assay in a crude ribosomal extract, a robust and accurate high-throughput platform was successfully developed and applied for efficient identification of novel structural types of ribosomal inhibitors with antimicrobial activity against drug-resistant bacteria.

Tau amyloid formation and deposition are responsible for the onset of Alzheimer's disease. In particular, the seeding activity of the tau protein plays an important role in the spreading of tau pathology via its propagation in the human brain. Here we demonstrate that catalytic photo-oxygenation markedly suppresses tau seeding activity, resulting in the inhibition of amyloid formation, both in vitro and in cultured cells.

We report the synthesis and use of sydnone-based profluorophores as tools for imaging applications. These new probes display exquisite reactivity towards strain promoted cycloaddition reactions with cycloalkynes allowing fast, efficient and selective labeling in biological media. Styryl-pyridinium sydnone probes were found particularly interesting for click reactions to proceed selectively inside cells.

Biotinylated pharmaceuticals are of great interest due to the strong interactions between biotinyl-functionality and streptavidin/avidin, which opens up avenues for efficient targeting and localisation. Three new carbon monoxide-releasing molecules (CO-RMs) have been synthesised and characterised using chemical and biological analysis. An alkyne-containing CO-RM 2 was found to be toxic to RAW 264.7 murine macrophages; and thus therapeutically viable CO-RM 1 was employed as the alkyne precursor for [3 + 2] cycloaddition chemistry enabling a new acid-containing CO-RM 4 and biotin-bioconugate-CO-RM (BiotinCORM 5) to be prepared. CO-RM 4 showed significantly improved solubility and BiotinCORM 5 acts as a photo-CO-RM. We have found that an avidin-CORM adduct of 5 is a CO-releasing protein, releasing CO on irradiation with light (400 nm). The avidin-biotinCORM adduct of 5 was found to have a binding energy of 10 kcal mol-1.

Total synthesis of isatindigotindoline C, a 3,3’-spiropyrrolidine oxindole alkaloid, is achieved in two steps using an exo-selective decarboxylative [3+2]-dipolar cycloaddition as the key step. The synthesis verifies the originally assigned relative anti-stereochemistry for the bis-oxindole core of isatindigotindoline C.

An injectable in situ fast-forming hydrogel was easily fabricated through the inverse electron demand Diels-Alder click reaction between trans-cyclooctene and tetrazine. This hydrogel system simultaneously encapsulated bone morphogenetic protein-2 and BMSCs which showed potential applications in 3D bio-printing and tissue engineering.

The inverse electron-demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO) facilitates the efficient radiosynthesis of 225Ac-labelled radioimmunoconjugates in a two-step method, outperforming conventional approaches based on isothiocyanate couplings.