Umpolung (polarity reversal) strategies of aldehydes and imines have dramatically expanded the scope of carbonyl and iminyl chemistry by facilitating reactions with non-nucleophilic reagents. Herein, we report the first visible light photoredox-catalyzed β-selective reductive coupling of alkenylpyridines with carbonyl or iminyl derivatives with the aid of a Lewis acid co-catalyst. Our process tolerates complex molecular scaffolds (e.g. sugar, natural product, and peptide derivatives) and is applicable to the preparation of compounds containing a broad range of heterocyclic moieties. Mechanistic investigations indicate that the key step involves single electron transfer (SET) reduction of aldehydes or imines followed by the addition of resulting ketyl or α-aminoalkyl radicals to Lewis acid-activated alkenylpyridines.

The development of biosafe nanoplatforms with diagnostic and therapeutic multifunction is extremely demanded for designing cancer theranostic medicines. Here, a facile methodology is developed to construct a multifunctional nanotheranostic that gathers five functions, upconversion luminescence (UCL) imaging, T1-weighted magnetic resonance imaging (MRI), X-ray computed tomography (CT) imaging, photothermal therapy (PTT), and chemotherapy, into one single nanoprobe (named as UCNP@PDA5-PEG-DOX). For generating the UCNP@PDA5-PEG-DOX, a near-infrared light (NIR)-absorbing polydopamine (PDA) shell is directly coated on oleic-acid-capped β-NaGdF4:Yb(3+),Er(3+)@β-NaGdF4 upconverting nanoparticle (UCNP) core for the first time to form monodisperse, ultrastable, and noncytotoxic core-shell-structured nanosphere via water-in-oil microemulsion approach. When combined with 808 nm NIR laser irradiation, the UCNP@PDA5-PEG-DOX shows great synergistic interaction between PTT and the enhanced chemotherapy, resulting in completely eradicated mouse-bearing SW620 tumor without regrowth. In addition, leakage study, hemolysis assay, histology analysis, and blood biochemistry assay unambiguously reveal that the UCNP@PDA5-PEG has inappreciable cytotoxicity and negligible organ toxicity. The results provide explicit strategy for fabricating multifunctional nanoplatforms from the integration of UCNP with NIR-absorbing polymers, important for developing multi-mode nanoprobes for biomedical applications.

Polybrominated diphenyl ethers (PBDEs) are widely distributed persistent organic pollutants. In vitro and in vivo research using various animal models have shown that PBDEs might be transformed to hydroxylated PBDEs, but there are few studies on in vivo metabolism of PBDEs by intact whole plants. In this research, pumpkin plants (Cucurbita maxima × C. moschata) were hydroponically exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). A debromination product (BDE-28) and four hydroxylated metabolites (5-OH-BDE-47, 6-OH-BDE-47, 4'-OH-BDE-49, and 4-OH-BDE-42) were detected in different parts of the whole plant. In addition, 4-methoxylated-2,2',3,4'-tetraBDE (4-MeO-BDE-42) was observed as a methoxylation product. Root exudates in solution were found to play an important role in metabolizing BDE-47 to a specific OH-PBDE: 4'-OH-BDE-49. BDE-28 was found to translocate more easily and accumulate in shoots than BDE-47 due to the lower hydrophobicity and molecular weight. The concentration ratio between metabolites and parent compound BDE-47 was lower for OH-PBDEs than that for both BDE-28 and 4-MeO-BDE-42. The metabolism pathway of BDE-47 in young whole plants was proposed in this study.

Combining 2-formylphenylboronic acid with 4-hydrazinylbenzoic acid in neutral aqueous solution at low, equimolar concentrations of the reagents results in a single, stable product, a 1,2-dihydro-1-hydroxy-2,3,1-benzodiazaborine, in a matter of minutes with no side products. Application of this reaction to protein conjugation demonstrates that the reaction is orthogonal to protein functional groups, and the resulting conjugate withstands SDS-PAGE analysis. This reaction should be particularly useful for couplings that must be performed with low concentrations of reagents under physiologically compatible conditions.

A recent addition to the suite of fast bioorthogonal reactions combines hydrazines and hydroxylamines with ortho-carbonyl substituted phenylboronic acids. Carbohydrazides are easily incorporated into biomolecules, making them appealing substrates in these reactions. Here we show that simple alkyl carbohydrazides form a single product with ortho-formylphenylboronic acid in an organic solvent and in the solid state. The solution structures of the products formed from the carbohydrazides in buffered aqueous solution, however, are markedly different from those identified in the organic solvent and solid state. The reactants form a mixture of hydrazone and heterocyclic products, the relative composition of which varies with pH. The observed reversibility of bioconjugates using carbohydrazide can thus be explained by the reversibility of the boron-nitrogen bond in the heterocycle. In contrast, the inclusion of an α-amine into the carbohydrazide substrate yields a single product in which both nitrogens are bonded to boron. These tricyclic structures are the same in organic solvent, solid state and aqueous solution from pH 4 to pH 9. Bioconjugates formed with α-amino carbohydrazides are stable to SDS-PAGE, while those formed with simple alkyl carbohydrazides are not. We propose that the inclusion of an intramolecular stabilizing ligand into a carbohydrazide substrate is a generally applicable principle that may be exploited to form boronic acid-based bioconjugates with a defined structure and resistance to hydrolysis.

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Background/Aims: Monitoring the appearance and progression of tumors are important for improving the survival rate of patients with ovarian cancer. This study aims to examine circulating tumor cells (CTCs) in epithelial ovarian cancer (EOC) patients to evaluate their clinical significance in comparison to the existing biomarker CA125. Methods: Immuomagnetic bead screening, targeting epithelial antigens on ovarian cancer cells, combined with multiplex reverse transcriptase-polymerase chain reaction (Multiplex RT-PCR) was used to detect CTCs in 211 samples of peripheral blood (5 ml) from 109 EOC patients. CTCs and CA125 were measured in serial from 153 blood and 153 serum samples from 51 patients and correlations with treatment were analyzed. Immunohistochemistry was used to detect the expression of tumor-associated proteins in tumor tissues and compared with gene expression in CTCs from patients. Results: CTCs were detected in 90% (98/109) of newly diagnosed patients. In newly diagnosed patients, the number of CTCs was correlated with stage (p=0.034). Patients with stage IA-IB disease had a CTC positive rate of 93% (13/14), much higher than the CA125 positive rate of only 64% (9/14) for the same patients. The numbers of CTCs changed with treatment, and the expression of EpCAM (p=0.003) and HER2 (p=0.035) in CTCs was correlated with resistance to chemotherapy. Expression of EpCAM in CTCs before treatment was also correlated with overall survival (OS) (p=0.041). Conclusion: Detection of CTCs allows early diagnose and expression of EpCAM in CTC positive patients predicts prognosis and should be helpful for monitoring treatment.

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