N,N-Ru(ii)-p-cymene-poly(N-vinylpyrrolidone) surface functionalized gold nanoparticles: from organoruthenium complex to nanomaterial for antiproliferative activity

The first report of a Ru(arene)metallopolymer–gold nanoconjugate to enhance the in vitro anticancer activity of Ru–arene complex in colorectal cancer cells.

Using bioorthogonally catalyzed lethality strategy to generate mitochondria-targeting antitumor metallodrugs in vitro and in vivo

Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anticancer therapies. To exploit the synthetic lethality concept in the design of chemical anticancer agents, we developed a bioorthogonally catalyzed lethality (BCL) strategy to generate targeting antitumor metallodrugs both in vitro and in vivo. Metallodrug Ru-rhein was generated from two nontoxic species Ru-N3 and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The nontoxic species Ru-arene complex Ru-N3 and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (> 83%) and showed high antitumor efficacy in vitro. This BCL strategy achieved a remarkable tumor suppression effect on the tumor-bearing mice models. It is interesting that the combination of metal-arene complexes with rhein via CuAAC reaction could transform two nontoxic species into a targeting anticancer metallodrug both in vitro and in vivo, while the product Ru-rhein was nontoxic towards normal cells. This is the first example that exclusive endogenous copper was used to generate metal-based anticancer drugs for cancer treatment. The anticancer mechanism of Ru-rhein was studied and autophagy was induced by increased reactive oxygen species and mitochondrial damage. The generality of this BCL strategy was also studied and it could be extended to other metal complexes such as Os-arene and Ir-arene complexes. Compared with the traditional methods for cancer treatment, this work presented a new approach to generate targeting metallodrugs in vivo via the BCL strategy from nontoxic species in the metal-based chemotherapy.

Fully Solvated, Monomeric Re(II) Complexes: Insights into the Chemistry of [Re(NCCH3)6]2+

^{The chemistry of rhenium complexes covers oxidation state +VII to -I. Some oxidation states such as +II are only rarely found in literature. One of the reasons is the lack of a suitable stable precursor for the oxidation state +II. However, we have developed a two step synthesis to the fully solvated Re(+II) complex [Re(NCCH}₃⁾₆^]2+^{from [ReO}₄^]-^{via the rhenium bis-arene complex [Re(C}₁₀^H₈⁾₂^]+^{. This fully solvated Re(+II) was fully characterized by various spectroscopic manners, cyclic voltammetry, and X-Ray diffraction analysis. Its potential as a precursor for Re(+II) chemistry was explored with various substitutions reactions with phosphines and halides, and the obtained products were as well fully characterized.<br>}

Fully Solvated, Monomeric Re(II) Complexes: Insights into the Chemistry of [Re(NCCH3)6]2+

^{The chemistry of rhenium complexes covers oxidation state +VII to -I. Some oxidation states such as +II are only rarely found in literature. One of the reasons is the lack of a suitable stable precursor for the oxidation state +II. However, we have developed a two step synthesis to the fully solvated Re(+II) complex [Re(NCCH}₃⁾₆^]2+^{from [ReO}₄^]-^{via the rhenium bis-arene complex [Re(C}₁₀^H₈⁾₂^]+^{. This fully solvated Re(+II) was fully characterized by various spectroscopic manners, cyclic voltammetry, and X-Ray diffraction analysis. Its potential as a precursor for Re(+II) chemistry was explored with various substitutions reactions with phosphines and halides, and the obtained products were as well fully characterized.<br>}