Regulating the Basicity of Metal–Oxido Complexes with a Single Hydrogen Bond and Its Effect on C–H Bond Cleavage

The
functionalization of C–H bonds is an essential reaction
in biology and chemistry. Metalloenzymes that often exhibit this type
of reactivity contain metal-oxido intermediates that are directly
involved in the initial cleavage of the C–H bonds. Regulation
of the cleavage process is achieved, in part, by hydrogen bonds that
are proximal to the metal–oxido units, yet our understanding
of their exact role(s) is still emerging. To gain further information
into the role of H-bonds on C–H bond activation, a hybrid set
of urea-containing tripodal ligands has been developed in which a
single H-bond can be adjusted through changes in the properties of
one ureayl N–H bond. This modularity is achieved by appending
a phenyl ring with different para-substituents from
one ureayl NH group. The ligands have been used to prepare a series
of MnIII–oxido complexes, and a Hammett correlation
was found between the pKa values of the
complexes and the substituents on the phenyl ring that was explained
within the context of changes to the H-bonds involving the MnIII–oxido unit. The complexes were tested for their
reactivity toward 9,10-dihydroanthracene (DHA), and a Hammett correlation
was found between the second-order rate constants for the reactions
and the pKa values. Studies to determine
activation parameters and the kinetic isotope effects are consistent
with a mechanism in which rate-limiting proton transfer is an important
contributor. However, additional reactivity studies with xanthene
found a significant increase in the rate constant compared to DHA,
even though the substrates have the same pKa(C–H) values. These results do not support a discrete proton-transfer/electron-transfer
process, but rather an asynchronous mechanism in which the proton
and electron are transferred unequally at the transition state.

碳氢键（C–H bonds）的官能化是生物学与化学领域的一类核心反应。具备此类反应活性的金属酶（metalloenzymes），通常含有直接参与碳氢键初始断裂步骤的金属氧代中间体（metal-oxido intermediates）。该断裂过程的调控，部分借助于靠近金属-氧单元的氢键实现，但目前学界对其确切作用的认知仍在逐步深化。为进一步探明氢键在碳氢键活化过程中的作用机制，研究人员开发了一类含脲基的三脚架配体（tripodal ligands）混合体系，该体系可通过调控其中一个脲基N-H键的性质，实现对单个氢键的精准调节。这种模块化特性通过在单个脲基NH基团上连接带有不同对位取代基的苯基环得以实现。利用该类配体，研究人员合成了一系列三价锰氧代配合物（MnIII–oxido complexes），并发现配合物的pKa值与苯环取代基之间存在哈米特相关性（Hammett correlation），该相关性可通过三价锰氧代单元相关氢键的变化得到合理解释。研究人员对上述配合物与9,10-二氢蒽（9,10-dihydroanthracene, DHA）的反应活性开展测试，结果显示反应的二级速率常数与配合物pKa值之间同样存在哈米特相关性。活化参数测定与动力学同位素效应（kinetic isotope effects）的研究结果，与"限速质子转移是该反应机制的关键贡献环节"的推论相符。不过，针对呫吨（xanthene）的补充反应活性研究发现，尽管该底物与DHA的碳氢键pKa值一致，但其反应速率常数相较DHA出现了显著提升。上述实验结果并不支持独立的质子转移/电子转移过程，反而印证了一种异步反应机制：在过渡态（transition state）中，质子与电子的转移并非同步且均等。