Cu(I) and Cu(II) Complexes Based on Lonidamine-Conjugated Ligands Designed to Promote Synergistic Antitumor Effects.

Bis(pyrazol-1-yl)- and bis(3,5-dimethylpyrazol-1-yl)-acetates were conjugated with the 2-hydroxyethylester and 2-aminoethylamide derivatives of the antineoplastic drug lonidamine to prepare Cu(I) and Cu(II) complexes that might act through synergistic mechanisms of action due to the presence of lonidamine and copper in the same chemical entity. Synchrotron radiation-based complementary techniques [X-ray photorlectron spectroscopy and near-edge X-ray absorption fine structure (NEXAFS)] were used to characterize the electronic and molecular structures of the complexes and the local structure around the copper ion (XAFS) in selected complexes. All complexes showed significant antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human tumor cell lines, and were able to overcome oxaliplatin and multidrug resistance. Noticeably, these Cu complexes appeared much more effective than cisplatin against 3D spheroids of pancreatic PSN-1 cancer cells; among these, PPh3-containing Cu(I) complex 15 appeared to be the most promising derivative. Mechanistic studies revealed that 15 induced cancer cell death by means of an apoptosis-alternative cell death.

Combined micro X-ray absorption and fluorescence spectroscopy to map phases of complex systems: the case of sphalerite.

Combining micro-X-ray absorption spectroscopy (µXAS) and micro-X-ray fluorescence spectroscopy (µXRF) is a promising approach for the investigation of complex multi-phase systems. In this work, we have employed this approach to investigate natural sphalerite, the most common form of Zinc Sulfide. Spatially resolved elemental distribution maps of common 3d metal atoms (Zn, Cu, Ni, Co, and Fe) are superimposed with chemical speciation and structural parameter maps in order to understand the sphaleriteore-formation process and metamorphosis. Chemical speciation and structural parameters have been obtained by analyzing the µXAS spectra collected in several representative points of the sample, after µXRF mapping. In the present case, this X-ray based approach has permitted to determine the spatial distribution of the Zn species in sphalerite. The presence of two main zincite and smithsonite inclusions has been established, with the latter located close to copper impurity center. Since copper is known to remarkably reduce the corrosion resistance of zinc, resulting in the formation of carbonate as the corrosion product, this implies a possible role of Cu in the growth of the carbonate inclusions. The results obtained highlight the efficiency of this method in univocally identifying the spatial distribution of phases in complex systems, thanks to the simultaneous access to complementary information.

Investigating structural aspects to understand the putative/claimed non-toxicity of the Hg-based Ayurvedic drug Rasasindura using XAFS.

XANES- and EXAFS-based analysis of the Ayurvedic Hg-based nano-drug Rasasindura has been performed to seek evidence of its non-toxicity. Rasasindura is determined to be composed of single-phase α-HgS nanoparticles (size ∼24 nm), free of Hg(0) or organic molecules; its structure is determined to be robust (<3% defects). The non-existence of Hg(0) implies the absence of Hg-based toxicity and establishes that chemical form, rather than content of heavy metals, is the correct parameter for evaluating the toxicity in these drugs. The stable α-HgS form (strong Hg-S covalent bond and robust particle character) ensures the integrity of the drug during delivery and prevention of its reduction to Hg(0) within the human body. Further, these comparative studies establish that structural parameters (size dispersion, coordination configuration) are better controlled in Rasasindura. This places the Ayurvedic synthesis method on par with contemporary techniques of nanoparticle synthesis.