The functions of metal complexes are directly linked to the local environment in which they are housed; modifications to the local environment (or secondary coordination sphere) are known to produce ...changes in key properties of the metal centers that can affect reactivity. Noncovalent interactions are the most common and influential forces that regulate the properties of secondary coordination spheres, which leads to complexities in structure that are often difficult to achieve in synthetic systems. Using key architectural features from the active sites of metalloproteins as inspiration, we have developed molecular systems that enforce intramolecular hydrogen bonds (H-bonds) around a metal center via incorporation of H-bond donors and acceptors into rigid ligand scaffolds. We have utilized these molecular species to probe mechanistic aspects of biological dioxygen activation and water oxidation. This Account describes the stabilization and characterization of unusual M–oxo and heterobimetallic complexes. These types of species have been implicated in a range of oxidative processes in biology but are often difficult to study because of their inherent reactivity. Our H-bonding ligand systems allowed us to prepare an FeIII–oxo species directly from the activation of O2 that was subsequently oxidized to form a monomeric FeIV–oxo species with an S = 2 spin state, similar to those species proposed as key intermediates in non-heme monooxygenases. We also demonstrated that a single MnIII–oxo center that was prepared from water could be converted to a high-spin MnV–oxo species via stepwise oxidation, a process that mimics the oxidative charging of the oxygen-evolving complex (OEC) of photosystem II. Current mechanisms for photosynthetic O–O bond formation invoke a MnIV–oxyl species rather than the isoelectronic MnV–oxo system as the key oxidant based on computational studies. However, there is no experimental information to support the existence of a Mn–oxyl radical. We therefore probed the amount of spin density on the oxido ligand of our complexes using EPR spectroscopy in conjunction with oxygen-17 labeling. Our findings showed that there is a significant amount of spin on the oxido ligand, yet the M–oxo bonds are best described as highly covalent and there is no indication that an oxyl radical is formed. These results offer the intriguing possibility that high-spin M–oxo complexes are involved in O–O bond formation in biology. Ligand redesign to incorporate H-bond accepting units (sulfonamido groups) simultaneously provided a metal ion binding pocket, adjacent H-bond acceptors, and an auxiliary binding site for a second metal ion. These properties allowed us to isolate a series of heterobimetallic complexes of FeIII and MnIII in which a group II metal ion was coordinated within the secondary coordination sphere. Examination of the influence of the second metal ion on the electron transfer properties of the primary metal center revealed unexpected similarities between CaII and SrII ions, a result with relevance to the OEC. In addition, the presence of a second metal ion was found to prevent intramolecular oxidation of the ligand with an O atom transfer reagent.
Alfred Werner proposed nearly 100 years ago that the secondary coordination sphere has a role in determining the physical properties of transition-metal complexes. We now know that the secondary ...coordination sphere impacts nearly all aspects of transition-metal chemistry, including the reactivity and selectivity in metal-mediated processes. These features are highlighted in the binding and activation of dioxygen by transition-metal complexes. There are clear connections between control of the secondary coordination sphere and the ability of metal complexes to (1) reversibly bind dioxygen or (2) bind and activate dioxygen to form highly reactive metal−oxo complexes. In this Forum Article, several biological and synthetic examples are presented and discussed in terms of structure−function relationships. Particular emphasis is given to systems with defined noncovalent interactions, such as intramolecular H-bonds involving dioxygen-derived ligands. To further illustrate these effects, the homolytic cleavage of C−H bonds by metal−oxo complexes with basic oxo ligands is described.
Copper–hydroperoxido species (CuII–OOH) have been proposed to be key intermediates in biological and synthetic oxidations. Using biotin–streptavidin (Sav) technology, artificial copper proteins have ...been developed to stabilize a CuII–OOH complex in solution and in crystallo. Stability is achieved because the Sav host provides a local environment around the Cu–OOH that includes a network of hydrogen bonds to the hydroperoxido ligand. Systematic deletions of individual hydrogen bonds to the Cu–OOH complex were accomplished using different Sav variants and demonstrated that stability is achieved with a single hydrogen bond to the proximal O-atom of the hydroperoxido ligand: changing this interaction to only include the distal O-atom produced a reactive variant that oxidized an external substrate.
We describe herein the hydrogen-atom transfer (HAT)/proton-coupled electron-transfer (PCET) reactivity for FeIV–oxo and FeIII–oxo complexes (1–4) that activate C–H, N–H, and O–H bonds in ...9,10-dihydroanthracene (S1), dimethylformamide (S2), 1,2-diphenylhydrazine (S3), p-methoxyphenol (S4), and 1,4-cyclohexadiene (S5). In 1–3, the iron is pentacoordinated by trisN′-tert-butylureaylato)-N-ethyleneaminato (H3buea3‑) or its derivatives. These complexes are basic, in the order 3 ≫ 1 > 2. Oxidant 4, FeIVN4Py(O)2+ (N4Py: N,N-bis(2-pyridylmethyl)bis(2-pyridyl)methylamine), is the least basic oxidant. The DFT results match experimental trends and exhibit a mechanistic spectrum ranging from concerted HAT and PCET reactions to concerted-asynchronous proton transfer (PT)/electron transfer (ET) mechanisms, all the way to PT. The singly occupied orbital along the O···H···X (X = C, N, O) moiety in the TS shows clearly that in the PCET cases, the electron is transferred separately from the proton. The Bell–Evans–Polanyi principle does not account for the observed reactivity pattern, as evidenced by the scatter in the plot of calculated barrier vs reactions driving forces. However, a plot of the deformation energy in the TS vs the respective barrier provides a clear signature of the HAT/PCET dichotomy. Thus, in all C–H bond activations, the barrier derives from the deformation energy required to create the TS, whereas in N–H/O–H bond activations, the deformation energy is much larger than the corresponding barrier, indicating the presence of a stabilizing interaction between the TS fragments. A valence bond model is used to link the observed results with the basicity/acidity of the reactants.
Hydrogen bonds influence secondary coordination spheres around metal ions in many proteins. To duplicate these features of molecular architecture in synthetic systems, urea-based ligands have have ...been developed that create rigid organic frameworks when bonded to metal ions. These frameworks position hydro-gen bond donors proximal to metal ion(s) to form specific chem-ical microenvironments. Iron(II) and manganese(II) complexes with constrained cavities activate O2, yielding MIII (MIII = Fe and Mn) complexes with terminal oxo ligands. Installation of anionic sites within the cavity assists the formation of complexes with MII/III−OH and MIII−O units derived directly from water. Opening the cavity promotes M(μ-O)2M rhombs, as illustrated by isolation of a cobalt(III) analogue, the stability of which is promoted by the hydrogen bonds surrounding the bridging oxo ligands.
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 pK a 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 pK a 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 pK a(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.
Metalloproteins contain actives sites with intricate structures that perform specific functions with high selectivity and efficiency. The complexity of these systems complicates the study of their ...function and the understanding of the properties that give rise to their reactivity. One approach that has contributed to the current level of understanding of their biological function is the study of synthetic constructs that mimic one or more aspects of the native metalloproteins. These systems allow individual contributions to the structure and function to be analyzed and also permit spectroscopic characterization of the metal cofactors without complications from the protein environment. This Current Topic is a review of synthetic constructs as probes for understanding the biological activation of small molecules. These topics are developed from the perspective of seminal molecular design breakthroughs from the past that provide the foundation for the systems used today.
Metalloproteins with active sites containing di-Fe cores exhibit diverse chemical reactivity that is linked to the precise transfer of protons and electrons which directly involve the di-Fe units. ...The redox conversions are commonly corroborated by spectroscopic methods, but the associated structural changes are often difficult to assess, particularly those related to proton movements. This report describes the development of di-Fe complexes in which the movements of protons and electrons are pinpointed during the stepwise oxidation of a di-FeII species to one with an FeIIIFeIV core. Complex formation was promoted using the phosphinic amido tripodal ligand poat3– (N,N′,N″-nitrilotris(ethane-2,1-diyl)tris(P,P-diphenylphosphinic amido)) that provided dynamic coordination spheres that assisted in regulating both electron and proton transfer processes. Oxidation of an FeII–(μ-OH)–FeIII complex led to the corresponding di-FeIII species containing a hydroxido bridge that was not stable at room temperature and converted to a species containing an oxido bridging ligand and protonation of one phosphinic amido group to form Hpoat2–. Deprotonation led to a new species with an FeIII–(μ-O)–FeIII core that could be further oxidized to its FeIIIFeIV analogue. Reactions with phenols suggest homolytic cleavage of the O–H bond to give products that are consistent with the initial formation of a phenoxyl radicalspectroscopic studies indicated that the electron is transferred to the FeIV center, and the proton is initially transferred to the more sterically hindered oxido ligand but then relocates to poat3–. These findings offer new mechanistic insights related to the stability of and the reactions performed by di-Fe enzymes.
High-valent nonheme FeIV–oxido species are key intermediates in biological oxidation, and their properties are proposed to be influenced by the unique microenvironments present in protein active ...sites. Microenvironments are regulated by noncovalent interactions, such as hydrogen bonds (H-bonds) and electrostatic interactions; however, there is little quantitative information about how these interactions affect crucial properties of high valent metal–oxido complexes. To address this knowledge gap, we introduced a series of FeIV–oxido complexes that have the same S = 2 spin ground state as those found in nature and then systematically probed the effects of noncovalent interactions on their electronic, structural, and vibrational properties. The key design feature that provides access to these complexes is the new tripodal ligand poat3–, which contains phosphinic amido groups. An important structural aspect of FeIVpoat(O)− is the inclusion of an auxiliary site capable of binding a Lewis acid (LAII); we used this unique feature to further modulate the electrostatic environment around the Fe–oxido unit. Experimentally, studies confirmed that H-bonds and LAII s can interact directly with the oxido ligand in FeIV–oxido complexes, which weakens the FeO bond and has an impact on the electronic structure. We found that relatively large vibrational changes in the Fe–oxido unit correlate with small structural changes that could be difficult to measure, especially within a protein active site. Our work demonstrates the important role of noncovalent interactions on the properties of metal complexes, and that these interactions need to be considered when developing effective oxidants.
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