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1,2-Diamination of alkenes represents an attractive way to generate differentiated vicinal diamines, which are prevalent motifs in biologically active compounds and catalysts. However, existing methods are usually limited in scope and produce diamines where one or both nitrogens are protected, adding synthetic steps for deprotection and further N-functionalization to reach a desired target. Furthermore, the range of amino groups that can be introduced at the internal position is fairly limited. Here we describe a 1,2-diamination of styrenes that directly installs a free amino group at the terminal position and a wide variety of unprotected nitrogen nucleophiles (primary or secondary alkyl or aromatic amines, sulfoximines, N-heterocycles, and ammonia surrogate) at the internal position. Two complementary sets of conditions encompass electronically activated and deactivated styrenes with diverse substitution patterns and functional groups. Moreover, this strategy can be extended to the 1,2-aminothiolation of styrenes., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Nanoporous materials are of great interest in many applications, such as catalysis, separation, and energy storage. The performance of these materials is closely related to their pore sizes, which are inefficient to determine through the conventional measurement of gas adsorption isotherms. Nuclear magnetic resonance (NMR) relaxometry has emerged as a technique highly sensitive to porosity in such materials. Nonetheless, streamlined methods to estimate pore size from NMR relaxometry remain elusive. Previous attempts have been hindered by inverting a time domain signal to relaxation rate distribution, and dealing with resulting parameters that vary in number, location, and magnitude. Here we invoke well-established machine learning techniques to directly correlate time domain signals to BET surface areas for a set of metal-organic frameworks (MOFs) imbibed with solvent at varied concentrations. We employ this series of MOFs to establish a correlation between NMR signal and surface area via partial least squares (PLS), following screening with principal component analysis, and apply the PLS model to predict surface area of various nanoporous materials. This approach offers a high-throughput, non-destructive way to assess porosity in c.a. one minute. We anticipate this work will contribute to the development of new materials with optimized pore sizes for various applications., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Probes allowing high-contrast discrimination of cancer cells and effective retention are powerful tools for the early diagnosis and treatment of cancer. However, conventional small-molecule probes often show limited performance in both aspects. Herein, we report an ingenious molecular engineering strategy for tuning the cellular uptake and retention of rhodamine dyes. Introduction of polar aminoethyl leads to the increased brightness and reduced cellular uptake of dyes, and this change can be reversed by amino acetylation. Moreover, these modifications allow cancer cells to take up more dyes than normal cells (16-fold) through active transport. Specifically, we further improve the signal contrast (56-fold) between cancer and normal cells by constructing activatable probes and confirm that the released fluorophore can remain in cancer cells with extended time, enabling long-term and specific tumor imaging., (© 2023 Wiley-VCH GmbH.)

TFA promoted deprotection of O-Ts activated N-Boc hydroxylamines triggers aminofunctionalization-based polycyclizations of tethered alkenes. The processes involve intramolecular stereospecific aza-Prilezhaev alkene aziridination in advance of stereospecific C-N cleavage by a pendant nucleophile. Using this approach, a wide range of fully intramolecular alkene anti-1,2-difunctionalizations can be achieved, including diaminations, amino-oxygenations and amino-arylations. Trends associated with the regioselectivity of the C-N cleavage step are outlined. The method provides a broad and predictable platform for accessing diverse C(sp 3 )-rich polyheterocycles of relevance to medicinal chemistry., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

We present a second near-infrared (NIR-II) self-checking molecule, LET-1052, for acidic tumor microenvironment (TME) turn-on photothermal therapy (PTT), followed by viscosity based therapeutic efficacy evaluation by itself in two independent channels, denoted as "self-checking" strategy. In acidic TME, LET-1052 was protonated and turned on NIR-II absorption for PTT under 1064 nm laser irradiation. Subsequently, PTT-induced cellular death increases intracellular viscosity, which inhibited the intramolecular rotation of LET-1052, resulting in the enhancement of NIR-I fluorescence for real-time evaluation of PTT efficacy. After PTT of tumor-bearing mice for different periods of NIR-II laser irradiation, NIR-I fluorescence in the tumor region showed positive correlation with tumor growth inhibition rate, demonstrating reliable and prompt prediction of PTT efficacy. The strategy may be expanded for instant evaluation of other therapeutic modalities for personalized medicine., (© 2022 Wiley-VCH GmbH.)

Discrimination of cancer cells/tissues from normal ones is of critical importance for early diagnosis and treatment of cancers. Herein, we present a new strategy for high-contrast fluorescence diagnosis of cancer cells/tissues based on β-Lapachone (β-Lap, an anticancer agent) triggered ROS (reactive oxygen species) amplification specific in cancer cells/tissues. With the strategy, a wide range of cancer cells/tissues, including surgical tissue specimens harvested from patients, were distinguished from normal ones by using a combination of β-Lap and a Si-rhodamine-based NIR fluorescent ROS probe PSiR3 developed in this work with average tumor-to-normal (T/N) ratios up to 15 in cell level and 24 in tissue level, far exceeding the clinically acceptable threshold of 2.0. What's more, the strategy allowed the fluorescence discrimination of tumor tissues from inflammatory ones based on whether a marked fluorescence enhancement could be induced when treated with PSiR3 and β-Lap/PSiR3 combination, respectively., (© 2021 Wiley-VCH GmbH.)

γ-Glutamyltranspeptidase (GGT) is overexpressed in several types of cancer. Existing GGT-targeting fluorescence probes can image these cancers, but the fluorescent hydrolysis product leaks from the target cancer cells during prolonged incubation or fixation. Here, we present a functionalized fluorescence probe for GGT, 4-CH 2 F-HMDiEtR-gGlu, which is designed to generate an azaquinone methide intermediate during activation by GGT; this intermediate reacts with intracellular nucleophiles to generate a fluorescent adduct that is trapped inside the cells, without loss of the target enzyme activity. Application of the probe to patient-derived xenograft (PDX) mice enabled in vivo cancer imaging for a prolonged period and was also compatible with fixation and immunostaining of the cancer tissue., (© 2020 Wiley-VCH GmbH.)

Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR-α) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near-infrared (NIR) region (650-900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR-α show high non-specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR-1, utilizing a Si-rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker. This probe exhibits very low background fluorescence and afforded a tumor-to-background ratio (TBR) of up to 83 in FR-expressing tumor-bearing mice within 30 min. Thus, FolateSiR-1 has the potential to contribute to the research in the field of biology and the clinical medicine., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)