High Contrast Bioimaging of Tumor and Inflammation with a Bicyclic Dioxetane Chemiluminescent Probe.

The link between inflammation and the evolution of cancer is well established. Visualizing and tracking both tumor proliferation and the associated inflammatory response within a living organism are vital for dissecting the nexus between these two processes and for crafting precise treatment modalities. We report the creation and synthesis of an advanced NIR chemiluminescence probe that stands out for its exceptional selectivity, extraordinary sensitivity at nanomolar concentrations, swift detection capabilities, and broad application prospects. Crucially, this probe has been successfully utilized to image endogenous ONOO- across different inflammation models, including abdominal inflammation triggered by LPS, subcutaneous inflammatory conditions, and tumors grafted onto mice. These findings highlight the significant promise of chemiluminescence imaging in enhancing our grasp of the intricate interplay between cancer and inflammation and in steering the development of potent, targeted therapeutic strategies.

Emission Wavelength-Tunable Bicyclic Dioxetane Chemiluminescent Probes for Precise In Vitro and In Vivo Imaging.

Chemiluminescent probes have become increasingly popular in various research areas including precise tumor imaging and immunofluorescence analysis. Nevertheless, previously developed chemiluminescence probes are mainly limited to studying oxidation reaction-associated biological events. This study presents the first example of bioimaging applicable bicyclic dioxetane chemiluminescent probes with tunable emission wavelengths that range from 525 to 800 nm. These newly developed probes were able to detect the analytes of ß-Gal, H2O2, and superoxide with high specificity and a limit of detection of 77 mU L-1, 96, and 28 nM, respectively. The bioimaging application of the probes was verified in ovarian and liver cancer cells and macrophage cells, allowing the detection of the content of ß-Gal, H2O2, and superoxide inside the cells. The high specificity allowed us to image the xenografted tumor in mice. We expect that our probes will receive extensive applications in recording complex biomolecular events using noninvasive imaging techniques.

Regulating the Anticancer Efficacy of Sgc8-Combretastatin A4 Conjugates: A Case of Recognizing the Significance of Linker Chemistry for the Design of Aptamer-Based Targeted Drug Delivery Strategies.

The unique merits of aptamers, including specificity, high binding affinity, easy cell internalization, and rapid tissue accumulation abilities, have led aptamer-drug conjugates to evolve into one of the most attractive strategies for targeted drug delivery purposes. Nevertheless, the critical role of linkers in regulating anticancer efficacy of these conjugates, especially those engineered by automated modular synthesis techniques, has been rarely explored. In this work, we utilized Sgc8c aptamer and combretastatin A4 to develop three conjugates with either a phosphodiester bond linker, a disulfide bond linker, or a carbamate linker to study their payload release mechanisms and the influence on anticancer efficacy. These investigations allowed us to identify the unique activation pathway of the phosphodiester bond linker that is activated by both nucleophilic attack of glutathione and degradation caused by phosphodiesterase, which is highly associated with the higher cytotoxicity of the conjugate. Importantly, the understanding of the chemistry of phosphodiester bond linker activation allowed us to further design another XQ-2d-CA4 conjugate that can induce pancreatic cancer cells apoptosis in a more efficient manner.

Engineering a Second-Order DNA Logic-Gated Nanorobot to Sense and Release on Live Cell Membranes for Multiplexed Diagnosis and Synergistic Therapy.

Tumor biomarker-based theranostics have achieved broad interest and success in recent years. However, single biomarker-based recognition can cause false-positive feedback, including the on-target off-tumor phenomenon, in the absence of tumor-specific antigen. Multibiomarker-based recognition molecules often elicit nonspecific and undesired internalization when they bind to "bystander" cells. We report a universal DNA tetrahedral scaffold (DTS) that anchors on the cell membrane to load multiple aptamers and therapeutics for precise and effective theranostics. This DNA logic-gated nanorobot (DLGN) not only facilitates precise discrimination among five cell lines, but also triggers synergistic killing of effector aptamer-tethered synergistic drugs (EASDs) to target cancer cells. Logic-gated recognition integrated into aptamer-functionalized molecular machines will prompt fast tumor profiling, in situ capture and isolation, and safe delivery of precise medicine.

Phosphine-catalyzed Friedel-Crafts reaction of naphthols with para-quinone methides: expedient access to triarylmethanes.

We developed a novel phosphine-catalyzed Friedel-Crafts reaction of naphthols with para-quinone methides (p-QMs). This reaction provided a promising method for the synthesis of triarylmethanes, which widely exist in natural products and in molecules which have been shown to have biological and pharmacological activity.

Correction: Phosphine-catalyzed Friedel-Crafts reaction of naphthols with para-quinone methides: expedient access to triarylmethanes.

Correction for 'Phosphine-catalyzed Friedel-Crafts reaction of naphthols with para-quinone methides: expedient access to triarylmethanes' by Tao Zhou et al., Org. Biomol. Chem., 2017, DOI: 10.1039/c7ob00911a.

Ni-Catalyzed Csp2 and Csp3 Coupling for Divergent Bisboronic Ester Synthesis.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

Highly Chemoselective Ni-Catalyzed Protecting-Group-Free 2,2'-Biphenol Synthesis and Mechanistic Insights.

The utilization of readily available starting materials to produce useful molecules is often challenged by selectivity issues. In this study, a Ni-catalyzed protecting-group-free C-C coupling protocol is described for the efficient synthesis of 2,2'-biphenol derivatives. Its remarkable chemoselectivity control ability, wide substrate scope, and excellent functional group tolerance highlight this newly developed strategy. Detailed mechanistic studies have demonstrated that potassium tert-butoxide acts as a critical agent to prevent the occurrence of protonation events.