Anion-Responsive Manganese Porphyrin Facilitates Chloride Transport and Induces Immunogenic Cell Death
Fang‐Xin Wang, Jiewei Liu, Xiao-Qiao Hong, Cai‐Ping Tan, Li Zhang, Wen‐Hua Chen, Peter J. Sadler, Zong‐Wan Mao
Abstract
Chloride is the most abundant anion in living systems. Most natural or synthetic chloride anionophores function via hydrogen-bonding interactions. However, dynamic metal-anion coordination can also be an efficient way of transporting chloride across membranes. Here, we investigate anion transport by manganese(III) meso-tetraphenylporphyrin chloride {[Mn(TPP)Cl], TPP = meso-tetraphenylporphyrin} complex that exhibits labile axial coordination. [Mn(TPP)Cl] showed high chloride transport activity in a bilayer vesicle model with an EC50 value of 4.42 × 10−3 mol %. In living cells, [Mn(TPP)Cl] induced rapid chloride influx and autophagy. The release of Ca2+ and adenosine 5′-triphosphate (ATP), as well as the relocation of calreticulin, revealed that [Mn(TPP)Cl] caused immunogenic cell death. Proteomic analysis indicated that [Mn(TPP)Cl] impaired several physiological processes, including DNA synthesis, transcription, mitochondrial respiration, RNA translation, and immune response. Our study suggests that dynamic metal-anion interactions across membranes might provide a practical strategy for the interference of chloride homeostasis. \n \n