Natural biomolecules have been used extensively as chiral scaffolds that bind/surround metal complexes to achieve stereoselectivity in catalytic reactions. ATP is ubiquitously found in nature as an energy-storing molecule and can complex diverse metal cations. However, in biotic reactions ATP-metal complexes are thought to function mostly as co-substrates undergoing phosphoanhydride bond cleavage reactions rather than participating in catalytic mechanisms. Here, we report that a specific Cu(II)-ATP complex (Cu²⁺·ATP) efficiently catalyses Diels-Alder reactions with high reactivity and enantioselectivity. We investigate the substrates and stereoselectivity of the reaction, characterise the catalyst by a range of physicochemical experiments and propose the reaction mechanism based on density functional theory (DFT) calculations. It is found that three key residues (N7, β-phosphate and γ-phosphate) in ATP are important for the efficient catalytic activity and stereocontrol via complexation of the Cu(II) ion. In addition to the potential technological uses, these findings could have general implications for the chemical selection of complex mixtures in prebiotic scenarios.

天然生物分子已被广泛用作手性支架，可结合/包围金属配合物以在催化反应中实现立体选择性。ATP 作为一种能量储存分子在自然界中普遍存在，可以络合多种金属阳离子。然而，在生物反应中，ATP-金属配合物被认为主要作为共同底物发挥作用，经历磷酸酐键断裂反应，而不是参与催化机制。在这里，我们报告了一种特定的 Cu(II)-ATP 复合物 (Cu ²⁺·ATP) 高效催化Diels-Alder 反应，具有高反应性和对映选择性。我们研究了反应的底物和立体选择性，通过一系列物理化学实验表征了催化剂，并基于密度泛函理论 (DFT) 计算提出了反应机理。发现 ATP 中的三个关键残基（N7、β-磷酸和 γ-磷酸）对于通过 Cu(II) 离子络合的有效催化活性和立体控制很重要。除了潜在的技术用途外，这些发现还可能对益生元情景中复杂混合物的化学选择产生普遍影响。