A Supramolecular Ice Growth Inhibitor

Safranine O, a synthetic dye, was found to inhibit growth of ice at millimolar concentrations with an activity comparable to that of highly evolved antifreeze glycoproteins. Safranine inhibits growth of ice crystals along the crystallographic a-axis, resulting in bipyramidal needles extended along the <0001> directions as well as and plane-specific thermal hysteresis (TH) activity. The interaction of safranine with ice is reversible, distinct from the previously reported behavior of antifreeze proteins. Spectroscopy and molecular dynamics indicate that safranine forms aggregates in aqueous solution at micromolar concentrations. Metadynamics simulations and aggregation theory suggested that as many as 30 safranine molecules were preorganized in stacks at the concentrations where ice growth inhibition was observed. The simulations and single-crystal X-ray structure of safranine revealed regularly spaced amino and methyl substituents in the aggregates, akin to the ice-binding site of antifreeze proteins. Collectively, these observations suggest an unusual link between supramolecular assemblies of small molecules and functional proteins.番红O（Safranine O）作为一种合成染料，被发现可在毫摩尔浓度下抑制冰的生长，其活性可与高度进化的抗冻糖蛋白（antifreeze glycoproteins）相媲美。番红O可沿冰的晶体学a轴抑制冰晶生长，使冰晶沿<0001>方向延伸形成双锥状针晶，并展现出平面特异性的热滞（thermal hysteresis, TH）活性。番红O与冰的相互作用具有可逆性，这与此前报道的抗冻蛋白行为截然不同。光谱学与分子动力学（molecular dynamics）研究表明，番红O在微摩尔浓度的水溶液中可形成聚集体。元动力学（metadynamics）模拟与聚集理论显示，在观测到冰生长抑制效应的浓度条件下，最多可有30个番红O分子在堆叠结构中完成预组织。通过单晶X射线结构（single-crystal X-ray structure）分析与模拟结果可见，聚集体中存在规则排布的氨基与甲基取代基，这与抗冻蛋白的冰结合位点极为相似。综上，上述观测结果表明，小分子的超分子组装体（supramolecular assemblies）与功能性蛋白之间存在一种非同寻常的关联。