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.

氯离子是生命系统中含量最丰富的阴离子。大多数天然或合成的氯化物阴离子载体通过氢键相互作用起作用。然而，动态金属阴离子配位也可以是跨膜运输氯化物的有效方式。在这里，我们研究了锰 (III)内消旋四苯基卟啉氯化物 {[Mn(TPP)Cl], TPP = 内消旋四苯基卟啉} 复合物的阴离子传输，该复合物表现出不稳定的轴向配位。[Mn(TPP)Cl]在双层囊泡模型中显示出高氯离子转运活性，EC ₅₀值为4.42 × 10 ^-3 mol %。在活细胞中，[Mn(TPP)Cl] 诱导氯离子快速流入和自噬。Ca ²⁺的释放和 5'-三磷酸腺苷 (ATP) 以及钙网蛋白的重新定位表明 [Mn(TPP)Cl] 导致免疫原性细胞死亡。蛋白质组学分析表明 [Mn(TPP)Cl] 损害了几个生理过程，包括 DNA 合成、转录、线粒体呼吸、RNA 翻译和免疫反应。我们的研究表明，跨膜的动态金属阴离子相互作用可能为干扰氯稳态提供了一种实用的策略。