Zhaoying Wang

Synthesis,Characterization, and in Vitro Antitumor Activity of Ruthenium(II)Polypyridyl Complexes Tethering EGFR-Inhibiting 4‑Anilinoquinazolines

Ruthenium-based anticancer complexes are promising antitumor agents for their low system toxicity and versatile chemical structures. Epidermal growth factor receptor (EGFR) has been found to be overexpressed in a broad range of tumor cells and is regarded as a drug target in developing novel antitumor drugs. In this work, five ruthenium(II) polypyridyl complexes containing EGFR-inhibiting 4-anilinoquinazoline pharmacophores were synthesized and characterized. These complexes showed both high EGFR-inhibiting activity and strong DNA minor groove-binding activity. In vitro antiproliferation screening demonstrated that the prepared ruthenium complexes are highly cytotoxic against a series of cancer cell lines, in particular non-small-cell lung A549 and human epidermoid carcinoma A431. Fluorescence-activated cell sorting analysis and fluorescence microscopy revealed that the most active complex, K4, induced much more late-stage cell apoptosis and necrosis than gefitinib, the first EGFR-targeting antitumor drug in clinical use. These results indicate that the ruthenium(II) polypyridyl complexes bearing EGFR-inhibiting 4-anilinoquinazolines possess highly active dual-targeting anticancer activity and are promising in developing new anticancer agents.

In Situ Mass Spectrometric Monitoring of the Dynamic Electrochemical Process at the Electrode–Electrolyte Interface: a SIMS Approach

The in situ molecular characterization of reaction intermediates and products at electrode-electrolyte interfaces is central to mechanistic studies of complex electrochemical processes, yet a great challenge. The coupling of electrochemistry (EC) and mass spectrometry (MS) has seen rapid development and found broad applicability in tackling challenges in analytical and bioanalytical chemistry. However, few truly in situ and real-time EC-MS studies have been reported at electrode-electrolyte interfaces. An innovative EC-MS coupling method named in situ liquid secondary ion mass spectrometry (SIMS) was recently developed by combining SIMS with a vacuum compatible microfluidic electrochemical device. Using this novel capability, we report the first in situ elucidation of the electro-oxidation mechanism of a biologically significant organic compound, ascorbic acid (AA), at the electrode-electrolyte interface. The short-lived radical intermediate was successfully captured, which had not been detected directly before. Moreover, we demonstrated the power of this new technique in real-time monitoring of the formation and dynamic evolution of electrical double layers at the electrode-electrolyte interface. This work suggests further promising applications of in situ liquid SIMS in studying more complex chemical and biological events at the electrode-electrolyte interface.

Discovery of a dual-targeting organometallic ruthenium complex with high activity inducing early stage apoptosis of cancer cells

Ruthenium based complexes are promising antitumour candidates due to their lower toxicity and better water-solubility compared to the platinum antitumour complexes. An epidermal growth factor receptor (EGFR) has been found to be overexpressed in a large set of tumour cells. In this work, a series of organoruthenium complexes containing EGFR-inhibiting 4-anilinoquinazoline pharmacophores were synthesised and characterised. These complexes exhibited excellent inhibitory activity against EGFR and high affinity to interact with DNA via minor groove binding, featuring dual-targeting properties. In vitro screening demonstrated that the as-prepared ruthenium complexes are anti-proliferating towards a series of cancer cell lines, in particular the non-small-cell lung cancer cell line A549. Fluorescence-activated cell sorting analysis and fluorescence microscopy revealed that the most active complex 3 induced much more early-stage cell apoptosis than its cytotoxic arene ruthenium analogue and the EGFR-inhibiting 4-anilinoquinazolines, verifying the synergetic effect of the two mono-functional pharmacophores.

Argon Cluster Sputtering Source for ToF-SIMS Depth Profiling of Insulating Materials: High Sputter Rate and Accurate Interfacial Information

AbstractThe use of an argon cluster ion sputtering source has been demonstrated to perform superiorly relative to traditional oxygen and cesium ion sputtering sources for ToF-SIMS depth profiling of insulating materials. The superior performance has been attributed to effective alleviation of surface charging. A simulated nuclear waste glass (SON68) and layered hole-perovskite oxide thin films were selected as model systems because of their fundamental and practical significance. Our results show that high sputter rates and accurate interfacial information can be achieved simultaneously for argon cluster sputtering, whereas this is not the case for cesium and oxygen sputtering. Therefore, the implementation of an argon cluster sputtering source can significantly improve the analysis efficiency of insulating materials and, thus, can expand its applications to the study of glass corrosion, perovskite oxide thin film characterization, and many other systems of interest. Graphical Abstractᅟ

Luminescent cyclometallated platinum(II) complexes: highly promising EGFR/DNA probes and dual-targeting anticancer agents

Cyclometallated platinum(II) complexes, [(C^N^N)PtII(L)]n+ (n = 0 or 1), have attracted much attention due to their potency as luminescent probes for nucleic acids and anticancer agents. Reported herein are four [(C^N^N)PtII(L)]+ complexes (5–8, L = 4-anilinoquinazoline derivative) which exhibit a weak fluorescence emission over 605 to 627 nm upon excitation at 405 nm. The ligation of the cyclometallated platinum cores with EGFR-inhibiting anilinoquinazolines not only confers the resulting complexes with excellent EGFR-inhibiting potency with IC50 values at the nanomolar level, but also enhances their affinity to DNA, in particular to G-quadruplex (G4) DNA. Such interactions produce strongly luminescent EGFR and DNA complexes, respectively, allowing the easy tracing of the cellular uptake and distribution of the platinum complexes and make them potential fluorescent probes for both EGFR and DNA in living cells. Complexes 5 and 6 are highly cytotoxic to the cancer cell lines A549, HeLa, A431 and MCF-7, and selectively inhibit the EGF-stimulated growth of the MCF-7 cell line. Secondary-ion mass spectrometry imaging and ICP-MS analysis demonstrated that the platinum complexes localize both on the cell membrane and in the nuclei of cells associated with EGFR and DNA binding, respectively, further verifying their dual-targeting feature as anticancer agents.

Probing Liquid Surfaces and Interfaces Using Time-of-Flight Secondary Ion Mass Spectrometry

1. Atmospheric Sciences and Global Climate Change Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA. 2. W. R & Wiley Environmental Molecular Science Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354, USA. 3. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA. 4. SPI Supplies/Structure Probe, Inc., West Chester, PA 19380, USA. 5. School of Mechanical and Materials Engineering, Washington State University, WA, 99164, USA. 6. Chemical and Materials Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.