pH‐Dependent Chloride Transport by Pseudopeptidic Cages for the Selective Killing of Cancer Cells in Acidic Microenvironments

Acidic microenvironments in solid tumors are a hallmark of cancer. Inspired by that, we designed a family of pseudopeptidic cage‐like anionophores displaying pH‐dependent activity. When protonated, they efficiently bind chloride anions. They also transport chloride through lipid bilayers, with their anionophoric properties improving at acidic pH, suggesting an H⁺/Cl^? symport mechanism. NMR studies in DPC micelles demonstrate that the cages bind chloride within the lipid phase. The chloride affinity and the chloride‐exchange rate with the aqueous bulk solution are improved when the pH is lowered. This increases cytotoxicity towards lung adenocarcinoma cells at the pH of the microenvironment of a solid tumor. These properties depend on the nature of the amino‐acid side chains of the cages, which modulate their lipophilicity and interactions with the cell membrane. This paves the way towards using pH as a parameter to control the selectivity of cytotoxic ionophores as anticancer drugs.     

Synthesis of an Aluminum Hydroxide Octamer through a Simple Dissolution Method

Multimeric oxo‐hydroxo Al clusters function as models for common mineral structures and reactions. Cluster research, however, is often slowed by a lack of methods to prepare clusters in pure form and in large amounts. Herein, we report a facile synthesis of the little known cluster Al₈(OH)₁₄(H₂O)₁₈(SO₄)₅ ( Al₈ ) through a simple dissolution method. We confirm its structure by single‐crystal X‐ray diffraction and show by ²⁷Al NMR spectroscopy, electrospray‐ionization mass spectrometry, and small‐ and wide‐angle X‐ray scattering that it also exists in solution. We speculate that Al₈ may form in natural water systems through the dissolution of aluminum‐containing minerals in acidic sulfate solutions, such as those that could result from acid rain or mine drainage. Additionally, the dissolution method produces a discrete Al cluster on a scale suitable for studies and applications in materials science.