Green Galon, Ansari Kamal Uddin, Munikrishna Thejasree, Ezov Sagi, Shamali Donia, Nanda Laxmi-Narayan, Gutkin Vitaly, Cohen Orit, Shimon Daphna, Tulchinsky Yuri
Institute of Chemistry, the Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
J Am Chem Soc. 2025 Aug 27;147(34):30647-30660. doi: 10.1021/jacs.5c02637. Epub 2025 Aug 7.
Metal-functionalized cavitands are promising platforms for mimicking the chemical environments of hydrophobic pockets in natural metalloenzymes. However, successfully combining the unique supramolecular capabilities of cavitand scaffolds with the high reactivities of transition metal complexes still remains a major challenge. In this study, we present an original cavitand architecture featuring a coordinatively unsaturated Mn(II) center embedded deep within its pore. This metallocavitand was employed to generate a Mn(IV)-oxo species inside a molecular cavity. This elusive intermediate was fully characterized spectroscopically (UV-vis, EPR, X-ray photoelectric spectroscopy (XPS), and HRMS) and, for the first time for a pseudo-octahedral Mn(IV)-oxo species, also by XRD. The experimental data was corroborated by detailed /time-dependent density functional theory (TDDFT) and natural bond orbital (NBO) calculations, confirming the Mn(IV)-oxo (rather than Mn(III)-oxyl) electronic character of this species. Reactivity and mechanistic studies, including monitoring the decay of this complex in various chlorinated solvents and its reactions with representative substrates, revealed that, despite the steric protection provided by the cavitand scaffold, its Mn(IV)-oxo core remains highly reactive in both H atom abstraction (HAA) and O atom transfer (OAT) reactions. Moreover, this reactivity is subject to a high degree of steric control imposed by the cavitand framework capable of discriminating between potential substrate molecules based on their size and shape. This was further demonstrated by the regioselective oxidation of a bisphosphine substrate, emulating the regioselectivity of natural metalloenzymes.
金属功能化穴状配体是模拟天然金属酶中疏水口袋化学环境的有前途的平台。然而，成功地将穴状配体支架独特的超分子能力与过渡金属配合物的高反应活性结合起来仍然是一个重大挑战。在本研究中，我们展示了一种原始的穴状配体结构，其孔内深处嵌入了一个配位不饱和的Mn(II)中心。这种金属穴状配体被用于在分子腔内生成Mn(IV)-氧物种。这种难以捉摸的中间体通过光谱学（紫外可见光谱、电子顺磁共振、X射线光电子能谱（XPS）和高分辨率质谱）进行了全面表征，并且对于一个伪八面体Mn(IV)-氧物种，首次通过X射线衍射进行了表征。详细的含时密度泛函理论（TDDFT）和自然键轨道（NBO）计算证实了实验数据，确认了该物种的Mn(IV)-氧（而非Mn(III)-氧基）电子特征。反应性和机理研究，包括监测该配合物在各种氯化溶剂中的衰变及其与代表性底物的反应，表明尽管穴状配体支架提供了空间保护，但其Mn(IV)-氧核心在氢原子夺取（HAA）和氧原子转移（OAT）反应中仍然具有很高的反应活性。此外，这种反应活性受到穴状配体框架施加的高度空间控制，该框架能够根据潜在底物分子的大小和形状区分它们。双膦底物的区域选择性氧化进一步证明了这一点，模拟了天然金属酶的区域选择性。
