A method was developed to obtain a highly water-soluble C60–γ-CDP inclusion complex, which could efficiently generate ¹O₂ species with UVA irradiation.

Transition metal complexes with substituted high affinity mixed ligands as potential anticancer agents can overcome the drawbacks of platinum-based drugs that are currently being marketed. Here, a new water-soluble asymmetric binuclear iminodiacetato-zinc(II) complex [Zn₂(ida)(phen)₃(NO₃)]·NO₃·5H₂O (1) with a phenanthroline ligand has been synthesized and fully characterized with a wide range of analytical techniques including single crystal X-ray diffraction as well as spectroscopic techniques, such as FT-IR, UV/Vis, photoluminescence spectroscopy, and furthermore by elemental and thermogravimetric analyses. Moreover, unprecedented (H₂O)₁₀ water clusters consisting of a quasi-planar tetramer and six dangling water molecules were observed in the void space of 3D supramolecular assemblies. The conversion behavior of (1) into two monomeric species [Zn(ida)(phen)(H₂O)] (2) and [Zn(phen)₂(H₂O)₂]²⁺ (3) in aqueous solution was first studied by solid-state/solution NMR, ESI-MS, and solution UV/vis spectra. Next, these zinc(II) complexes (1–3), a mixture of (2) and (3) (mole ratio 1/1), ligands (phen and ida) and zinc ions (ZnCl₂ and ZnSO₄) were further evaluated for the in vitro cytotoxic profile in human hepatoma cell lines (HepG2 and SMMC-7721). We found that complex (1) effectively inhibited the proliferation of hepatocellular carcinoma cells, which is similar to a mixture of (2) and (3) in a 1 : 1 molar ratio, and IC₅₀ values of (1) were almost about 20–50% of (2) or (3). Therefore, this binuclear complex (1) mainly acts as a cooperative inhibitor with complexes (2) and (3) toward tumor growth in solution. We further extended the preliminary research of complex (1) and found that (1) could induce cell cycle arrest at the G0/G1 phase. Additionally, overdosing on (1) exhibited low toxicity of mice (LD₅₀ of (1) in ICR mice = 736 mg kg⁻¹, with 95% confidence interval 635–842 mg kg⁻¹). In conclusion, complex (1) with a high antitumor activity and low toxicity provides a new strategy for the treatment of liver cancer.

More than 50% of new drug candidates in drug discovery are lipophilic and exhibit poor aqueous solubility, which results in poor bioavailability and a lack of dose proportionality. Here, we improved the solubility of pedunculoside (PE) by generating a water-soluble inclusion complex composed of PE and the polymer β-cyclodextrin (CDP). We characterized this novel complex by ¹H NMR, FT-IR, UV-vis spectroscopy, powder X-ray diffractometry and thermogravimetric analysis. The ratio of β-cyclodextrin (β-CD) units in CDP to PE was determined to be 2∶1. The K_D value of the inclusion complex was determined to be 4.29×10⁻³ mol•L⁻¹. In contrast to the low solubility of PE, the water-solubility of the PE–CDP complex was greatly enhanced. A preclinical toxicological study indicated that PE–CDP was well tolerated for a single administration. Importantly, the anti-inflammation potency of the PE–CDP complex was higher than that of PE. As a result, the formation of inclusion complexes by water-soluble CDP opens up possible aqueous applications of insoluble drug candidates in drug delivery.