10-Fold Increase in Hydrogen Atom Transfer Reactivity for a Series of <i>S</i> = 1 Fe^IVO Complexes Over the <i>S</i> = 2 [(TQA)Fe^IVO]²⁺ Complex via Entropic Lowering of Reaction Barriers by Secondary Sphere Cycloalkyl Substitution

Nonheme iron enzymes utilize S = 2 iron(IV)-oxo intermediates as oxidants in biological oxygenations. In contrast, corresponding synthetic nonheme FeIVO complexes characterized to date favor the S = 1 ground state that generally shows much poorer oxidative reactivity than their S = 2 counterparts. However, one intriguing exception found by Nam a decade ago is the S = 1 [FeIV(O)(Me3NTB)]2+ complex (Me3NTB = [tris((N-methyl-benzimidazol-2-yl)methyl)amine], 1O) with a hydrogen atom transfer (HAT) reactivity that is 70% that of the S = 2 [FeIV(O)(TQA)]2+ complex (TQA = tris(2-quinolylmethyl)amine, 3O). In our efforts to further explore this direction, we have unexpectedly uncovered a family of new S = 1 complexes with HAT reaction rates beyond the currently reported limits in the tripodal ligand family, surpassing oxidation rates found for the S = 2 [FeIV(O)(TQA)]2+ complex by as much as an order of magnitude. This is achieved simply by replacing the secondary sphere methyl groups of the Me3NTB ligand with larger cycloalkyl-CH2 (R groups in 2OR) moieties ranging from c-propylmethyl to c-hexylmethyl. These 2OR complexes show Mössbauer data at 4 K and 1H NMR spectra at 193 and 233 K that reveal S = 1 ground states, in line with DFT calculations. Nevertheless, they give rise to the most reactive synthetic nonheme oxoiron(IV) complexes found to date within the tripodal ligand family. Our DFT study indicates transition state stabilization through entropy effects, similar to enzymatic catalysis.非血红素铁酶（Nonheme iron enzymes）在生物氧化反应中，以自旋态S=2的铁(IV)-氧中间体（S = 2 iron(IV)-oxo intermediates）作为氧化剂。与之形成鲜明对比的是，目前已表征的对应合成非血红素铁(IV)-氧配合物，大多倾向于呈现S=1基态，其氧化反应活性普遍远低于S=2的同类配合物。然而，Nam团队十年前发现了一个有趣的例外：S=1的[FeIV(O)(Me3NTB)]²⁺配合物（其中Me3NTB为三[(N-甲基苯并咪唑-2-基)甲基]胺，记为1O），其氢原子转移（hydrogen atom transfer, HAT）反应活性可达S=2的[FeIV(O)(TQA)]²⁺配合物（其中TQA为三(2-喹啉基甲基)胺，记为3O）的70%。在我们对此方向展开进一步探索的过程中，我们意外发现了一类新型S=1配合物家族，其在三脚架配体家族中展现出超越当前已报道水平的氢原子转移反应速率，氧化反应速率最高可比S=2的[FeIV(O)(TQA)]²⁺配合物高出一个数量级。该性能仅通过将Me3NTB配体第二配位层的甲基替换为更大的环烷基-CH₂基团（即2OR中的R基团）即可实现，这些基团的范围从环丙基甲基延伸至环己基甲基。这些2OR配合物在4 K下的穆斯堡尔（Mössbauer）谱数据，以及193 K和233 K下的¹H核磁共振（¹H NMR）光谱均显示其基态为S=1，这与密度泛函理论（Density Functional Theory, DFT）计算结果一致。尽管如此，它们仍是目前已报道的三脚架配体家族中反应活性最高的合成非血红素氧合铁(IV)配合物。我们的DFT研究表明，过渡态通过熵效应实现稳定化，这与酶催化的作用机制相似。