Simultaneous Detection of Aldehyde Metabolites by Light-Assisted Ambient Ionization Mass Spectrometry.

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.

Palladium(II)-Catalyzed C(sp2)-H Bond Activation/C-N Bond Cleavage Annulation of N-Methoxy Amides and Arynes.

The Pd(II)-catalyzed C-H bond activation/C-N bond cleavage annulation reaction of N-alkyoxyamide aryne is developed to synthesize 9,10-dihydrophenanthrenone derivatives. This reaction exhibited good functional group compatibility with yields up to 92%. Detailed mechanistic studies showed that the key to C-N bond cleavage is the formed eight-membered palladacycle intermediate undergoing nucleophilic addition to the carbonyl group, which provides a new and practical way for N-alkoxyamide directed C-H bond activation.

In Situ Construction of COF-Based Paper Serving as a Plasmonic Substrate for Enhanced PSI-MS Detection of Polycyclic Aromatic Hydrocarbons.

Accurate detection, quantitation, and differentiation of polycyclic aromatic hydrocarbons (PAHs) and their isomers in diverse samples is elusive for paper spray ionization mass spectrometry (PSI-MS). To address these issues, herein, for the first time, we propose to fabricate a novel, flexible, and stable paper substrate based on covalent organic frameworks (COFs) via an in situ method under room temperature in air. After embedding gold nanoparticles (AuNPs), this paper substrate (COFs-paper) could further serve as a multifunctional plasmonic matrix (AuNPs-COFs-paper) for dual-wavelength laser-assisted PSI-MS detection of PAHs and feasible paper surface-enhanced Raman scattering (pSERS)-aided isomer discrimination. Taking advantage of the synergistic effect between the AuNPs and COFs present on the novel AuNP-embedded COFs-paper substrate, a satisfied LOD of 0.50 ng/µL for phenanthrene was realized, which improved almost 300 times compared with the naked-paper matrix, and the regression coefficient R2 was up to 0.999. Real sample corn oil-containing PAHs can be efficiently detected and identified using this technique. The established platform has promising potential for on-site chemical analysis with portable PSI-MS and pSERS instruments.

Fabrication of a "Selenium Signature" Chemical Probe-Modified Paper Substrate for Simultaneous and Efficient Determination of Biothiols by Paper Spray Mass Spectrometry.

Significant efforts have been made to develop robust and reliable methods for simultaneous biothiols determination in different matrices, but there still exist the problems such as easy oxidation, tedious derivatization, and difficulty in discrimination, which brings unsatisfactory results in their accuracy and fast quantification in biological samples. To overcome these problems, a simultaneous biothiols detection method combining a "selenium signature" chemical probe and paper spray mass spectrometry (PS-MS) was proposed. In the strategy, the modified-paper substrate is used to enhance the analytical performance. Chemical probe Ebselen-NH2 that has a specific response to biothiols was designed and covalently fixed on the surface of an oxidized paper substrate. By the identification of derivatized product with distinctive selenium isotope distribution and employment of the optimized PS-MS method, qualitative and quantitative analysis of five biothiols including glutathione (GSH), cysteine (Cys), cysteinylglycine (CysGly), N-acetylcysteine (Nac), and homocysteine (Hcy) were realized. Biothiols in plasma and cell lysates were measured with satisfactory results. The established method not only provides a novel protocol for simultaneous determination of biothiols, but also is helpful for understanding the biological and clinical roles played by these bioactive small molecules.

Designing a highly stable coordination-driven metallacycle for imaging-guided photodynamic cancer theranostics.

Coordination-driven self-assembly features good predictability and directionality in the construction of discrete metallacycles and metallacages with well-defined sizes and shapes, but their medicinal application has been limited by their low stability and solubility. Herein, we have designed and synthesized a highly stable coordination-driven metallacycle with desired functionality derived from a perylene-diimide ligand via a spontaneous deprotonation self-assembly process. Brilliant chemical stability and singlet oxygen production ability of this emissive octanuclear organopalladium macrocycle make it a good candidate toward biological studies. After cellular uptake by endocytosis, the metallacycle exhibits potent fluorescence cell imaging properties and cancer photodynamic therapeutic ability through enhancing ROS production, with high biocompatibility and safety. This study not only provides a rational design strategy for highly stable luminescent organopalladium metallacycles, but also sheds light on their application in imaging-guided photodynamic cancer therapy.

Coordination-Enhanced Luminescence on Tetra-Phenylethylene-Based Supramolecular Assemblies.

Materials with aggregation-induced emission (AIE) properties have received increased attention recently due to their potential applications in light-emitting devices, chemo/biosensors and biomedical diagnostics. In general, AIE requires the forced aggregation of the AIEgens induced by the poor solvent or close arrangement of AIEgens covalently attached to polymer chains. Here, we report two coordination-enhanced fluorescent supramolecular complexes featuring hierarchically restricted intramolecular motions via the self-assembly of tetraphenylethylene (TPE)-based tetra-dentate (La) and bidentate (Lb) ligands and the cis-Pd(en)(NO3)2 (en = ethylenediamine) unit. While the free ligands are non-emissive in dilute solution and show typical AIE properties in both mixed solvent system and the solid state, the self-assembled complexes maintain their fluorescent nature in the solution state. In particular, the Pd4(La)2 complex shows remarkable 6-fold fluorescent enhancement over La in dilute solution. We anticipate that these kinds of coordination-enhanced emissive supramolecules will find applications in biomedical sensing or labeling.

Self-Assembly of a Tetraphenylethylene-Based Capsule Showing Both Aggregation- and Encapsulation-Induced Emission Properties.

Functional molecular capsules have attracted a lot of attention in recent years because of their potential applications as chemosensors, catalysis, drug carriers, and so on. We report here the coordination-directed self-assembly of a fluorescent-lantern-type molecular capsule from four tetraphenylethylene-based ditopic ligands and two square-planar palladium(II) ions. The capsule has been thoroughly characterized by UV-vis, 1D/2D NMR, electrospray ionization time-of-flight mass spectrometry, and single-crystal X-ray diffraction studies. The aggregation-induced emission performance of the capsule has been studied by tuning the ratio of mixed solvents. Moreover, with an open cavity, the fluorescence of the capsule also displays anion sensitivity, with the best turn-on responsiveness observed for HCO3-, demonstrating for the first time an encapsulation-induced emission property.

Bottom-Up Construction of Mesoporous Nanotubes from 78-Component Self-Assembled Nanobarrels.

Segmental and continuous hexagonal-packed mesoporous metal-organic nanotubes (MMONTs) with outside diameters of up to 4.5 nm and channel sizes of 2.4 nm were hierarchically constructed by a rational multicomponent self-assembly process involving starting from [L2Pd2(NO3)2] (L=o-phenanthroline or 2,2'-bipyridine) and 4-pyridinyl-3-pyrazole. An unprecedented crystallization-driven cross-linking between discrete nanobarrel building units by spontaneous loss of the capping ligands to form infinite nanotubes was observed. Such a barrel-to-tube transformation provides new possibilities for the fabrication of MMONTs using the solution bottom-up approach.

Stereocontrolled Self-Assembly and Self-Sorting of Luminescent Europium Tetrahedral Cages.

Coordination-directed self-assembly has become a well-established technique for the construction of functional supramolecular structures. In contrast to the most often exploited transition metals, trivalent lanthanides Ln(III) have been less utilized in the design of polynuclear self-assembled structures despite the wealth of stimulating applications of these elements. In particular, stereochemical control in the assembly of lanthanide chiral cage compounds is not easy to achieve in view of the usually large lability of the Ln(III) ions. We report here the first examples of stereoselective self-assembly of chiral luminescent europium coordination tetrahedral cages and their intriguing self-sorting behavior. Two pairs of R and S ligands are designed on the basis of the pyridine-2,6-dicarboxamide coordination unit, bis(tridentate) L1 and tris(tridentate) L2. Corresponding chiral Eu4(L1)6 and Eu4(L2)4 topological tetrahedral cages are independently assembled via edge- and face-capping design strategies, respectively. The chirality of the ligand is transferred during the self-assembly process to give either Δ or Λ metal stereochemistry. The self-assembled cages are characterized by NMR, high-resolution ESI-TOF-MS, and in one case by X-ray crystallography. Strict control of stereoselectivity is confirmed by CD spectroscopy and NMR enantiomeric differentiation experiments. Narcissistic self-sorting is observed in the self-assembly process when two differently shaped ligands L1 and L2 are mixed. More impressively, distinct self-sorting behavior between Eu4(L1)6 and Eu4(L2)4 coordination cages is observed for the first time when racemic mixtures of ligands are used. We envisage that chiral luminescent lanthanide tetrahedral cages could be used in chiroptical probes\sensors and enantioselective catalysis.