Bimetallic complexes are important sites in metalloproteins but are often difficult to prepare synthetically. We have previously introduced an approach to form discrete bimetallic complexes with MII-(μ-OH)-FeIII (MII = Mn, Fe) cores using the tripodal ligand N,N′,N″-[2,2′,2″-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido) ([MST]3–). This series is extended to include the rest of the late 3d transition metal ions (MII = Co, Ni, Cu, Zn). All of the bimetallic complexes have similar spectroscopic and structural properties that reflect little change despite varying the MII centers. Magnetic studies performed on the complexes in solution using electron paramagnetic resonance spectroscopy showed that the observed spin states varied incrementally from S = 0 through S = 5/2; these results are consistent with antiferromagnetic coupling between the high-spin MII and FeIII centers. However, the difference in the MII ion occupancy yielded only slight changes in the magnetic exchange coupling strength, and all complexes had J values ranging from +26(4) to +35(3) cm–1.

The interplay between the primary and secondary coordination spheres is crucial to determining the properties of transition metal complexes. To examine these effects, a series of trigonal bipyramidal Co–OH complexes have been prepared with tripodal ligands that control both coordination spheres. The ligands contain a combination of either urea or sulfonamide groups that control the primary coordination sphere through anionic donors in the trigonal plane and the secondary coordination sphere through intramolecular hydrogen bonds. Variations in the anion donor strengths were evaluated using electronic absorbance spectroscopy and a qualitative ligand field analysis to find that deprotonated urea donors are stronger field ligands than deprotonated sulfonamides. Structural variations were found in the CoII–O bond lengths that range from 1.953(4) to 2.051(3) Å; this range in bond lengths were attributed to the differences in the intramolecular hydrogen bonds that surround the hydroxido ligand. A similar trend was observed between the hydrogen bonding networks and the vibrations of the O–H bonds. Attempts to isolate the corresponding CoIII–OH complexes were hampered by their instability at room temperature.

Cupredoxins are electron-transfer proteins that have active sites containing a mononuclear Cu center with an unusual trigonal monopyramidal structure (Type 1 Cu). A single Cu–Scys bond is present within the trigonal plane that is responsible for its unique physical properties. We demonstrate that a cysteine-containing variant of streptavidin (Sav) can serve as a protein host to model the structure and properties of Type 1 Cu sites. A series of artificial Cu proteins are described that rely on Sav and a series of biotinylated synthetic Cu complexes. Optical and EPR measurements highlight the presence of a Cu–Scys bond, and XRD analysis provides structural evidence. We further provide evidence that changes in the linker between the biotin and Cu complex within the synthetic constructs allows for small changes in the placement of Cu centers within Sav that have dramatic effects on the structural and physical properties of the resulting artificial metalloproteins. These findings highlight the utility of the biotin-Sav technology as an approach for simulating active sites of metalloproteins.

High-valent Fe-OH species are often invoked as key intermediates but have only been observed in Compound II of cytochrome P450s. To further address the properties of non-heme FeIV-OH complexes, we demonstrate the reversible protonation of a synthetic FeIV-oxo species containing a tris-urea tripodal ligand. The same protonated FeIV-oxo species can be prepared via oxidation, suggesting that a putative FeV-oxo species was initially generated. Computational, Mössbauer, XAS, and NRVS studies indicate that protonation of the FeIV-oxo complex most likely occurs on the tripodal ligand, which undergoes a structural change that results in the formation of a new intramolecular H-bond with the oxido ligand that aids in stabilizing the protonated adduct. We suggest that similar protonated high-valent Fe-oxo species may occur in the active sites of proteins. This finding further argues for caution when assigning unverified high-valent Fe-OH species to mechanisms.

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.

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.

The structural and electronic properties of a series of manganese complexes with terminal oxido ligands are described. The complexes span three different oxidation states at the manganese center (III–V), have similar molecular structures, and contain intramolecular hydrogen-bonding networks surrounding the Mn–oxo unit. Structural studies using X-ray absorption methods indicated that each complex is mononuclear and that oxidation occurs at the manganese centers, which is also supported by electron paramagnetic resonance (EPR) studies. This gives a high-spin MnV–oxo complex and not a MnIV–oxy radical as the most oxidized species. In addition, the EPR findings demonstrated that the Fermi contact term could experimentally substantiate the oxidation states at the manganese centers and the covalency in the metal–ligand bonding. Oxygen-17–labeled samples were used to determine spin density within the Mn–oxo unit, with the greatest delocalization occurring within the MnV–oxo species (0.45 spins on the oxido ligand). The experimental results coupled with density functional theory studies show a large amount of covalency within the Mn–oxo bonds. Finally, these results are examined within the context of possible mechanisms associated with photosynthetic water oxidation; specifically, the possible identity of the proposed high valent Mn–oxo species that is postulated to form during turnover is discussed.

Photosynthetic water oxidation is catalyzed by a Mn4O5Ca cluster with an unprecedented arrangement of metal ions in which a single manganese center is bonded to a distorted Mn3O4Ca cubane-like structure. Several mechanistic proposals describe the unique manganese center as a site for water binding and subsequent formation of a high valent Mn–oxo center that reacts with a M–OH unit (M = Mn or CaII) to form the O–O bond. The conversion of low valent Mn–OHn (n = 1, 2) to a Mn–oxo species requires that a single manganese site be able to accommodate several oxidation states as the water ligand is deprotonated. To study these processes, the preparation and characterization of a new monomeric MnIV–OH complex is described. The MnIV–OH complex completes a series of well characterized Mn–OH and Mn–oxo complexes containing the same primary and secondary coordination spheres; this work thus demonstrates that a single ligand can support mononuclear Mn complexes spanning four different oxidation states (II through V) with oxo and hydroxo ligands that are derived from water. Moreover, we have completed a thermodynamic analysis based on this series of manganese complexes to predict the formation of high valent Mn–oxo species; we demonstrated that the conversion of a MnIV–OH species to a MnV–oxo complex would likely occur via a stepwise proton transfer-electron transfer mechanism. The large dissociation energy for the MnIVO–H bond (∼95 kcal mol−1) diminished the likelihood that other pathways are operative within a biological context. Furthermore, these studies showed that reactions between Mn–OH and Mn–oxo complexes lead to non-productive, one-electron processes suggesting that initial O–O bond formation with the OEC does not involve an Mn–OH unit.

Complexes [MnMST(NH3)]n−3 (Mn = FeII, FeIII, GaIII) were prepared and each contains an intramolecular hydrogen bonding network involving the ammonia ligand. Deprotonation of the FeIII–NH3 complex afforded a putative [FeIIIMST(NH2)]− species whose reactivity has been explored.

High-valent iron species are known to act as powerful oxidants in both natural and synthetic systems. While biological enzymes have evolved to prevent self-oxidation by these highly reactive species, development of organic ligand frameworks that are capable of supporting a high-valent iron center remains a challenge in synthetic chemistry. We describe here the reactivity of an Fe(II) complex that is supported by a tripodal sulfonamide ligand with both dioxygen and an oxygen-atom transfer reagent, 4-methylmorpholine-N-oxide (NMO). An Fe(III)–hydroxide complex is obtained from reaction with dioxygen, while NMO gives an Fe(III)–alkoxide product resulting from activation of a C–H bond of the ligand. Inclusion of Ca2+ ions in the reaction with NMO prevented this ligand activation and resulted in isolation of an Fe(III)–hydroxide complex in which the Ca2+ ion is coordinated to the tripodal sulfonamide ligand and the hydroxo ligand. Modification of the ligand allowed the Fe(III)–hydroxide complex to be isolated from NMO in the absence of Ca2+ ions, and a C–H bond of an external substrate could be activated during the reaction. This study highlights the importance of robust ligand design in the development of synthetic catalysts that utilize a high-valent iron center.

The effects of redox-inactive metal ions on dioxygen activation were explored using a new FeII complex containing a tripodal ligand with 3 sulfonamido groups. This iron complex exhibited a faster initial rate for the reduction of O2 than its MnII analog. Increases in initial rates were also observed in the presence of group 2 metal ions for both the FeII and MnII complexes, which followed the trend NMe4+ < BaII < CaII = SrII. These studies led to the isolation of heterobimetallic complexes containing FeIII-(μ-OH)-MII cores (MII = Ca, Sr, and Ba) and one with a [SrII(OH)MnIII]+ motif. The analogous [CaII(OH)GaIII]+ complex was also prepared and its solid state molecular structure is nearly identical to that of the [CaII(OH)FeIII]+ system. Nuclear magnetic resonance studies indicated that the diamagnetic [CaII(OH)GaIII]+ complex retained its structure in solution. Electrochemical measurements on the heterobimetallic systems revealed similar one-electron reduction potentials for the [CaII(OH)FeIII]+ and [SrII(OH)FeIII]+ complexes, which were more positive than the potential observed for [BaII(OH)FeIII]+. Similar results were obtained for the heterobimetallic MnII complexes. These findings suggest that Lewis acidity is not the only factor to consider when evaluating the effects of group 2 ions on redox processes, including those within the oxygen-evolving complex of Photosystem II.

Heterobimetallic cores are important units within the active sites of metalloproteins but are often difficult to duplicate in synthetic systems. We have developed a synthetic approach for the preparation of a complex with a MnII–(μ-OH)–FeIII core, in which the metal centers have different coordination environments. Structural and physical data support the assignment of this complex as a heterobimetallic system. A comparison with analogous homobimetallic complexes, MnII–(μ-OH)–MnIII and FeII–(μ-OH)–FeIII cores, further supports this assignment.

Development of electrocatalysts for the conversion of water to dioxygen is important in a variety of chemical applications. Despite much research in this field, there are still several fundamental issues about the electrocatalysts that need to be resolved. Two such problems are that the catalyst mass loading on the electrode is subject to large uncertainties and the wetted surface area of the catalyst is often unknown and difficult to determine. To address these topics, a cobalt monolayer was prepared on a gold electrode by underpotential deposition and used to probe its efficiency for the oxidation of water. This electrocatalyst was characterized by atomic force microscopy, grazing-incidence X-ray diffraction, and X-ray photoelectron spectroscopy at various potentials to determine if changes occur on the surface during catalysis. An enhancement of current was observed upon addition of PO43– ions, suggesting an effect from surface-bound ligands on the efficiency of water oxidation. At 500 mV overpotential, current densities of 0.20, 0.74, and 2.4 mA/cm2 for gold, cobalt, and cobalt in PO43– were observed. This approach thus provided electrocatalysts whose surface areas and activity can be accurately determined.

Alfred Werner described the attributes of the primary and secondary coordination spheres in his development of coordination chemistry. To examine the effects of the secondary coordination sphere on coordination chemistry, a series of tripodal ligands containing differing numbers of hydrogen bond (H-bond) donors were used to examine the effects of H-bonds on Fe(II), Mn(II)–acetato, and Mn(III)–OH complexes. The ligands containing varying numbers of urea and amidate donors allowed for systematic changes in the secondary coordination spheres of the complexes. Two of the Fe(II) complexes that were isolated as their Bu4N+ salts formed dimers in the solid-state as determined by X-ray diffraction methods, which correlates with the number of H-bonds present in the complexes (i.e., dimerization is favored as the number of H-bond donors increases). Electron paramagnetic resonance (EPR) studies suggested that the dimeric structures persist in acetonitrile. The Mn(II) complexes were all isolated as their acetato adducts. Furthermore, the synthesis of a rare Mn(III)–OH complex via dioxygen activation was achieved that contains a single intramolecular H-bond; its physical properties are discussed within the context of other Mn(III)–OH complexes.The effects of the secondary coordination sphere are evaluated in a series of metal complexes containing tripodal ligands with varying numbers of hydrogen bond donors.

The use of the tripodal ligands tris[(N′-tert-butylureaylato)-N-ethyl]aminato ([H3buea]3−) and the sulfonamide-based N,N′,N″-[2,2′,2″-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzene-sulfonamidato) ([MST]3−) has led to the synthesis of two structurally distinct In(III)–OH complexes. The first example of a five-coordinate indium(III) complex with a terminal hydroxide ligand, K[InIIIH3buea(OH)], was prepared by addition of In(OAc)3 and water to a deprotonated solution of H6buea. X-ray diffraction analysis, as well as FTIR and 1H NMR spectroscopic methods, provided evidence for the formation of a monomeric In(III)–OH complex. The complex contains an intramolecular hydrogen bonding (H-bonding) network involving the In(III)–OH unit and [H3buea]3− ligand, which aided in isolation of the complex. Isotope labeling studies verified the source of the hydroxo ligand as water. Treatment of the [InIIIMST] complex with a mixture of 15-crown-5 ether and NaOH led to isolation of the complex [15-crown-5⊃NaI-(μ-OH)-InIIIMST], whose solid-state structure was confirmed using X-ray diffraction methods. Nuclear magnetic resonance studies on this complex suggest it retains its heterobimetallic structure in solution.The isolation of new In(III)–OH complexes was achieved using intramolecular hydrogen-bonding networks

Oxomanganese(V) species have been implicated in a variety of biological and synthetic processes, including their role as a key reactive center within the oxygen-evolving complex in photosynthesis. Nearly all mononuclear MnV–oxo complexes have tetragonal symmetry, producing low-spin species. A new high-spin MnV–oxo complex that was prepared from a well-characterized oxomanganese(III) complex having trigonal symmetry is now reported. Oxidation experiments with [FeCp2]+ were monitored with optical and electron paramagnetic resonance (EPR) spectroscopies and support a high-spin oxomanganese(V) complex formulation. The parallel-mode EPR spectrum has a distinctive S = 1 signal at g = 4.01 with a six-line hyperfine pattern having Az = 113 MHz. The presence of an oxo ligand was supported by resonance Raman spectroscopy, which revealed O-isotope-sensitive peaks at 737 and 754 cm–1 assigned as a Fermi doublet centered at 746 cm–1(Δ18O = 31 cm–1). Mn Kβ X-ray emission spectra showed Kβ′ and Kβ1,3 bands at 6475.92 and 6490.50 eV, respectively, which are characteristic of a high-spin MnV center.

The use of water as a reagent in redox-driven reactions is advantageous because it is abundant and environmentally compatible. The conversion of water to dioxygen in photosynthesis illustrates one example, in which a redox-inactive CaII ion and four manganese ions are required for function. In this report we describe the stepwise formation of two new heterobimetallic complexes containing CoII/III and CaII ions and either hydroxo or aquo ligands. The preparation of a four-coordinate CoII synthon was achieved with the tripodal ligand, N,N′,N″-[2,2′,2″-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido, [MST]3–. Water binds to [CoIIMST]− to form the five-coordinate [CoIIMST(OH2)]− complex that was used to prepare the CoII/CaII complex [CoIIMST(μ-OH2)CaII⊂15-crown-5(OH2)]+ ([CoII(μ-OH2)CaIIOH2]+). [CoII(μ-OH2)CaOH2]+ contained two aquo ligands, one bonded to the CaII ion and one bridging between the two metal ions, and thus represents an unusual example of a heterobimetallic complex containing two aquo ligands spanning different metal ions. Both aquo ligands formed intramolecular hydrogen bonds with the [MST]3– ligand. [CoIIMST(OH2)]− was oxidized to form [CoIIIMST(OH2)] that was further converted to [CoIIIMST(μ-OH)CaII⊂15-crown-5]+ ([CoIII(μ-OH)CaII]+) in the presence of base and CaIIOTf2/15-crown-5. [CoIII(μ-OH)CaII]+ was also synthesized from the oxidation of [CoIIMST]− with iodosylbenzene (PhIO) in the presence of CaIIOTf2/15-crown-5. Allowing [CoIII(μ-OH)CaII]+ to react with diphenylhydrazine afforded [CoII(μ-OH2)CaIIOH2]+ and azobenzene. Additionally, the characterization of [CoIII(μ-OH)CaII]+ provides another formulation for the previously reported CoIV–oxo complex, [(TMG3tren)CoIV(μ-O)ScIII(OTf)3]2+ to one that instead could contain a CoIII–OH unit.

The synthesis of MII2 complexes (MIICo, Mn) with terminal hydroxo ligands has been achieved utilizing a dinucleating ligand containing a bridging pyrazolate unit and appended (neopentyl)aminopyridyl groups. Structural studies on the complexes revealed that the MII–OH units are positioned in a syn-configuration, placing the hydroxo ligands in close proximity (ca. 3 Å apart), which may be a prerequisite for water oxidation.

The formation of nanoparticle-polymer composites that can be processed by injection molding from superparamagnetic magnetite (Fe3O4) nanoparticles (MNPs) and the polymerizable molecule styryl acetylacetonate (stacac) is described. The best composites were created by first synthesizing MNPs in the presence of a surfactant followed by replacement with an excess of stacac monomer in a surfactant exchange reaction. Polymerization of the stacac–MNP mixture produced a dense packing of nanoparticles within a polymer matrix, resulting in a magnetic, monolithic material that was characterized with a combination of transmission electron microscopy (TEM), Fourier transform infrared absorption spectroscopy (FTIR), powder X-ray diffraction (XRD) and vibrating sample magnetometry (VSM). The material exhibited superparamagnetic properties similar to pure MNP samples, albeit with a lower total magnetic saturation. An advantage of this polymer-based composite material is its ability to be processed with methods such as mold-casting or microfluidics into a variety of 3-dimensional structures (e.g., toroids) for different electronics applications.

A series of transition metal chloro complexes with the tetradentate tripodal tris(2-amino-oxazoline)amine ligand (TAO) have been synthesized and characterized. X-Ray structural analyses of these compounds demonstrate the formation of the mononuclear complexes [MII(TAO)(Cl)]+, where MII = Cr, Mn, Fe, Co, Ni, Cu and Zn. These complexes exhibit distorted trigonal-bipyramidal geometry, coordinating the metal through an apical tertiary amine, three equatorial imino nitrogen atoms, and an axial chloride anion. All the complexes possess an intramolecular hydrogen-bonding (H-bonding) network within the cavity occupied by the metal-bound chloride ion. The metal–chloride bond distances are atypically long, which is attributed to the effects of the H-bonding network. Nuclear magnetic resonance (NMR) spectroscopy of the Zn complex suggests that the solid-state structures are representative of that observed in solution, and that the H-bonding interactions persist as well. Additionally, density functional theory (DFT) calculations were carried out to probe the electronic structures of the complexes.

The functionalization of C–H bonds has yet to achieve widespread use in synthetic chemistry in part because of the lack of synthetic reagents that function in the presence of other functional groups. These problems have been overcome in enzymes, which have metal–oxo active sites that efficiently and selectively cleave C–H bonds. How high-energy metal–oxo transient species can perform such difficult transformations with high fidelity is discussed in this tutorial review. Highlighted are the relationships between redox potentials and metal–oxo basicity on C–H bond activation, as seen in a series of bioinspired manganese–oxo complexes.

There have been numerous efforts to incorporate dioxygen into chemical processes because of its economic and environmental benefits. The conversion of dioxygen to water is one such example, having importance in both biology and fuel cell technology. Metals or metal complexes are usually necessary to promote this type of reaction and several systems have been reported. However, mechanistic insights into this conversion are still lacking, especially the detection of intermediates. Reported herein is the first example of a monomeric manganese(II) complex that can catalytically convert dioxygen to water. The complex contains a tripodal ligand with two urea groups and one carboxyamidopyridyl unit; this ligand creates an intramolecular hydrogen-bonding network within the secondary coordination sphere that aids in the observed chemistry. The manganese(II) complex is five-coordinate with an N4O primary coordination sphere; the oxygen donor comes from the deprotonated carboxyamido moiety. Two key intermediates were detected and characterized: a peroxo−manganese(III) species and a hybrid oxo/hydroxo−manganese(III) species (1). The formulation of 1 was based on spectroscopic and analytical data, including an X-ray diffraction analysis. Reactivity studies showed dioxygen was catalytically converted to water in the presence of reductants, such as diphenylhydrazine and hydrazine. Water was confirmed as a product in greater than 90% yield. A mechanism was proposed that is consistent with the spectroscopy and product distribution, in which the carboxyamido group switches between a coordinated ligand and a basic site to scavenge protons produced during the catalytic cycle. These results highlight the importance of incorporating intramolecular functional groups within the secondary coordination sphere of metal-containing catalysts.

The synthesis of a (carboxyamido)pyridinepyrazolate (H5bppap) dinucleating ligand is described. Bimetallic iron and cobalt complexes of H5bppap ([MII2H2bppap]+) showed structural differences in both their primary and secondary coordination spheres. The binding of small molecules into the preorganized ligand cavity is verified by the hydration of [FeII2H2bppap]+ and [CoII2H2bppap]+, leading to the formation of complexes [{CoII(OH)}CoIIH3bppap]+ and [{FeII(OH)}FeIIH3bppap]+, in which one of the metal centers has a terminal hydroxo ligand.

A tetradentate tripodal ligand containing 2-amino-oxazoline moieties has been developed. This system tautomerizes upon chelation of a metal ion, forming a flexible cavity capable of accommodating ligands via an intramolecular hydrogen bonding network.

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.

Intramolecular hydrogen bonds in metalloproteins are key in directing reactivity yet these effects have been difficult to achieved in synthetic systems. We have been developing a synthetic system that uses hydrogen-bonding interactions to modulate the secondary coordination around a transition metal ion. This was accomplished with the ligand bis[N-(6-pivalamido-2-pyridylmethyl)]benzylamine (H2pmb), which contains two carboxyamido units appended from pyridine rings. Several nickel complexes were prepared and structurally characterized. In particular, we found that the appended carboxyamido groups either provide intramolecular H-bond donors or can be converted to bind directly to a metal center. We established that the complex NiIIH2pmb(Cl)2 can be sequentially deprotonated with potassium tert-butoxide, causing coordination of the carboxyamido oxygen atoms and concomitant loss of the chloro ligands. The chloro ligands were also removed with silver(I) salts in the presence of acetate ions and the complex NiIIH2pmb(κ2-OAc)(κ1-OAc) was isolated, in which an intramolecular H-bonding network occurs between the H2pmb ligand and the coordinate acetato ligands.The control of the primary and secondary coordination spheres is illustrated using a new multidentate ligand containing carboxyamidopyridyl groups.

The nickel(II) chemistry with the tridentate ligands bis[(N′-R-ureido)-N-ethyl]-N-methylamine (H41R, R = isopropyl, tert-butyl) is described. The Ni(II)–OH complexes, [NiIIH21R(OH)]− were generated using water as the source of the hydroxo ligand. These complexes are pseudo-square planar, in which the primary coordination sphere contains three nitrogen donors from [H21R]2− and the oxygen atom from the hydroxide (Ni–O(H), 1.857(1) Å). The Ni(II)–OH unit also is involved in two intramolecular hydrogen bonds between the urea groups of the [H21R]2− and the hydroxo oxygen atom. Attempts to deprotonate the Ni(II)–OH unit to produce Ni(II)–oxo complexes were unsuccessful. A variety of bases with pKa of less than 15 (in DMSO) were unable to deprotonate the hydroxo ligand. Treating the Ni(II)–OH complexes with KOBut (pKa∼ 29) afforded the ligand substitution product, [NiIIH21R(OBut)]−. Ni(II)–siloxide complexes were isolated when the [NiIIH21R(OH)]− complexes were allowed to react with K[N(TMS)2].

Hydrogen bonds stabilize and direct chemistry performed by metalloenzymes. With inspiration from enzymes, we will utilize an approach that incorporates intramolecular hydrogen bond donors to determine their effects on the stability and reactivity of metal complexes. Our premise is that control of secondary coordination sphere interactions will promote new function in synthetic metal complexes. Multidentate ligands have been developed that create rigid organic structures around metal ions. These ligands place hydrogen bond (H-bond) donors proximal to the metal centers, forming specific microenvironments. One distinguishing attribute of these systems is that site-specific modulations in structure can be readily accomplished, in order to evaluate correlations with reactivity. A focus of this research is consideration of dioxygen binding and activation by metal complexes, including developing structure–function relationships in metal-assisted oxidative catalysis.

Mononuclear iron(III) complexes with terminal hydroxo ligands are proposed to be important species in several metalloproteins, but they have been difficult to isolate in synthetic systems. Using a series of amidate/ureido tripodal ligands, we have prepared and characterized monomeric FeIIIOH complexes with similar trigonal-bipyramidal primary coordination spheres. Three anionic nitrogen donors define the trigonal plane, and the hydroxo oxygen atom is trans to an apical amine nitrogen atom. The complexes have varied secondary coordination spheres that are defined by intramolecular hydrogen bonds between the FeIIIOH unit and the urea NH groups. Structural trends were observed between the number of hydrogen bonds and the Fe−Ohydroxo bond distances: the more intramolecular hydrogen bonds there were, the longer the Fe−O bond became. Spectroscopic trends were also found, including an increase in the energy of the O−H vibrations with a decrease in the number of hydrogen bonds. However, the FeIII/II reduction potentials were constant throughout the series (∼2.0 V vs [Cp2Fe]0/+1), which is ascribed to a balancing of the primary and secondary coordination-sphere effects.

Hydrogen bonding networks proximal to metal centers are emerging as a viable means for controlling secondary coordination spheres. This has led to the regulation of reactivity and isolation of complexes with new structural motifs. We have used the tridenate ligand bis[(N′-tert-butylureido)-N-ethyl]-N-methylaminato ([H21]2−) that contains two hydrogen bond donors to examine the oxidation of the FeII–acetate complex, [FeIIH21(η2-OAc)]− with dioxygen, amine N-oxides, and xylyl azide. A complex with FeIII–O–FeIII core results from the oxidation with dioxygen and amine N-oxides, in which the oxo ligand is involved in hydrogen bonding to the [H21]2− ligand. A distinctly different hydrogen bonding network was found in FeIII dimer isolated from the reaction with the xylyl azide: a rare FeIII–N(R)–FeIII core was observed that does not have hydrogen bonds to the bridging nitrogen atom. The intramolecular H-bond networks within these dimers appear to adjust to the presence of the bridging species and rearrange to its size and electron density.The oxidation of a hydrogen bond (H-bond) containing FeII–acetate complex with dioxygen and xylyl azide results in the formation of dimers with FeIII–X–FeIII (X = oxo or imido) cores that display distinct intramolecular H-bond networks.

The preparation and characterization of two NiII complexes are described, a terminal NiII–OH complex with the tripodal ligand tris[(N)-tert-butylureaylato)-N-ethyl)]aminato ([H3buea]3−) and a terminal NiII–OH2 complex with the tripodal ligand N,N′,N″-[2,2′,2″-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido) ([MST]3−). For both complexes, the source of the –OH and –OH2 ligand is water. The salts K2[NiIIH3buea(OH)] and NMe4[NiIIMST(OH2)] were characterized using perpendicular-mode X-band electronic paramagnetic resonance, Fourier transform infrared, UV–vis spectroscopies, and its electrochemical properties were evaluated using cyclic voltammetry. The solid state structures of these complexes determined by X-ray diffraction methods reveal that they adopt a distorted trigonal bipyramidal geometry, an unusual structure for 5-coordinate NiII complexes. Moreover, the NiII–OH and NiII–OH2 units form intramolecular hydrogen bonding networks with the [H3buea]3− and [MST]3− ligands. The oxidation chemistry of these complexes was explored by treating the high-spin NiII compounds with one-electron oxidants. Species were formed with S = 1/2 spin ground states that are consistent with formation of monomeric NiIII species. While the formation of NiIII–OH complexes cannot be ruled out, the lack of observable O–H vibrations from the putative Ni–OH units suggest the possibility that other high valent Ni species are formed.A terminal NiII–OH complex and a terminal NiII–OH2 complex, both supported by tripodal ligands, have been prepared and characterized. The solid state structures of these complexes reveal that they adopt distorted trigonal bipyramidal primary coordination spheres, an unusual geometry for NiII complexes. Treating these complexes with one-electron oxidants formed species with S = 1/2 spin ground states, which are consistent with formation of monomeric NiIII species.

Rate enhancements for the reduction of dioxygen by a MnII complex were observed in the presence of redox-inactive group 2 metal ions. The rate changes were correlated with an increase in the Lewis acidity of the group 2 metal ions. These studies led to the isolation of heterobimetallic complexes containing MnIII–(μ-OH)–MII cores (MII = CaII, BaII) in which the hydroxo oxygen atom is derived from O2. This type of core structure has relevance to the oxygen-evolving complex within photosystem II.

High spin oxoiron(IV) complexes have been proposed to be a key intermediate in numerous nonheme metalloenzymes. The successful detection of similar complexes has been reported for only two synthetic systems. A new synthetic high spin oxoiron(IV) complex is now reported that can be prepared from a well-characterized oxoiron(III) species. This new oxoiron(IV) complex can also be prepared from a hydroxoiron(III) species via a proton-coupled electron transfer process—a first in synthetic chemistry. The oxoiron(IV) complex has been characterized with a variety of spectroscopic methods: FTIR studies showed a feature associated with the Fe−O bond at ν(Fe16O) = 798 cm−1 that shifted to 765 cm−1 in the 18O complex; Mössbauer experiments show a signal with an δ = 0.02 mm/s and |ΔEQ| = 0.43 mm/s, electronic parameters consistent with an Fe(IV) center, and optical spectra had visible bands at λmax = 440 (εM = 3100), 550 (εM = 1900), and 808 (εM = 280) nm. In addition, the oxoiron(IV) complex gave the first observable EPR features in the parallel-mode EPR spectrum with g-values at 8.19 and 4.06. A simulation for an S = 2 species with D = 4.0(5) cm−1, E/D = 0.03, σE/D = 0.014, and gz = 2.04 generates a fit that accurately predicted the intensity, line shape, and position of the observed signals. These results showed that EPR spectroscopy can be a useful method for determining the properties of high spin oxoiron(IV) complexes. The oxoiron(IV) complex was crystallized at −35 °C, and its structure was determined by X-ray diffraction methods. The complex has a trigonal bipyramidal coordination geometry with the Fe−O unit positioned within a hydrogen bonding cavity. The FeIV—O unit bond length is 1.680(1) Å, which is the longest distance yet reported for a monomeric oxoiron(IV) complex.

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 tris[N′-tert-butylureaylato)-N-ethylene]aminato ([H3buea]3-) 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.

The nickel(II) chemistry with the tridentate ligands bis[(N′-R-ureido)-N-ethyl]-N-methylamine (H41R, R = isopropyl, tert-butyl) is described. The Ni(II)–OH complexes, [NiIIH21R(OH)]− were generated using water as the source of the hydroxo ligand. These complexes are pseudo-square planar, in which the primary coordination sphere contains three nitrogen donors from [H21R]2− and the oxygen atom from the hydroxide (Ni–O(H), 1.857(1) Å). The Ni(II)–OH unit also is involved in two intramolecular hydrogen bonds between the urea groups of the [H21R]2− and the hydroxo oxygen atom. Attempts to deprotonate the Ni(II)–OH unit to produce Ni(II)–oxo complexes were unsuccessful. A variety of bases with pKa of less than 15 (in DMSO) were unable to deprotonate the hydroxo ligand. Treating the Ni(II)–OH complexes with KOBut (pKa∼ 29) afforded the ligand substitution product, [NiIIH21R(OBut)]−. Ni(II)–siloxide complexes were isolated when the [NiIIH21R(OH)]− complexes were allowed to react with K[N(TMS)2].

A series of transition metal chloro complexes with the tetradentate tripodal tris(2-amino-oxazoline)amine ligand (TAO) have been synthesized and characterized. X-Ray structural analyses of these compounds demonstrate the formation of the mononuclear complexes [MII(TAO)(Cl)]+, where MII = Cr, Mn, Fe, Co, Ni, Cu and Zn. These complexes exhibit distorted trigonal-bipyramidal geometry, coordinating the metal through an apical tertiary amine, three equatorial imino nitrogen atoms, and an axial chloride anion. All the complexes possess an intramolecular hydrogen-bonding (H-bonding) network within the cavity occupied by the metal-bound chloride ion. The metal–chloride bond distances are atypically long, which is attributed to the effects of the H-bonding network. Nuclear magnetic resonance (NMR) spectroscopy of the Zn complex suggests that the solid-state structures are representative of that observed in solution, and that the H-bonding interactions persist as well. Additionally, density functional theory (DFT) calculations were carried out to probe the electronic structures of the complexes.

The effects of redox-inactive metal ions on dioxygen activation were explored using a new FeII complex containing a tripodal ligand with 3 sulfonamido groups. This iron complex exhibited a faster initial rate for the reduction of O2 than its MnII analog. Increases in initial rates were also observed in the presence of group 2 metal ions for both the FeII and MnII complexes, which followed the trend NMe4+ < BaII < CaII = SrII. These studies led to the isolation of heterobimetallic complexes containing FeIII-(μ-OH)-MII cores (MII = Ca, Sr, and Ba) and one with a [SrII(OH)MnIII]+ motif. The analogous [CaII(OH)GaIII]+ complex was also prepared and its solid state molecular structure is nearly identical to that of the [CaII(OH)FeIII]+ system. Nuclear magnetic resonance studies indicated that the diamagnetic [CaII(OH)GaIII]+ complex retained its structure in solution. Electrochemical measurements on the heterobimetallic systems revealed similar one-electron reduction potentials for the [CaII(OH)FeIII]+ and [SrII(OH)FeIII]+ complexes, which were more positive than the potential observed for [BaII(OH)FeIII]+. Similar results were obtained for the heterobimetallic MnII complexes. These findings suggest that Lewis acidity is not the only factor to consider when evaluating the effects of group 2 ions on redox processes, including those within the oxygen-evolving complex of Photosystem II.

Hydrogen bonds stabilize and direct chemistry performed by metalloenzymes. With inspiration from enzymes, we will utilize an approach that incorporates intramolecular hydrogen bond donors to determine their effects on the stability and reactivity of metal complexes. Our premise is that control of secondary coordination sphere interactions will promote new function in synthetic metal complexes. Multidentate ligands have been developed that create rigid organic structures around metal ions. These ligands place hydrogen bond (H-bond) donors proximal to the metal centers, forming specific microenvironments. One distinguishing attribute of these systems is that site-specific modulations in structure can be readily accomplished, in order to evaluate correlations with reactivity. A focus of this research is consideration of dioxygen binding and activation by metal complexes, including developing structure–function relationships in metal-assisted oxidative catalysis.

The synthesis of MII2 complexes (MIICo, Mn) with terminal hydroxo ligands has been achieved utilizing a dinucleating ligand containing a bridging pyrazolate unit and appended (neopentyl)aminopyridyl groups. Structural studies on the complexes revealed that the MII–OH units are positioned in a syn-configuration, placing the hydroxo ligands in close proximity (ca. 3 Å apart), which may be a prerequisite for water oxidation.

Complexes [MnMST(NH3)]n−3 (Mn = FeII, FeIII, GaIII) were prepared and each contains an intramolecular hydrogen bonding network involving the ammonia ligand. Deprotonation of the FeIII–NH3 complex afforded a putative [FeIIIMST(NH2)]− species whose reactivity has been explored.

A tetradentate tripodal ligand containing 2-amino-oxazoline moieties has been developed. This system tautomerizes upon chelation of a metal ion, forming a flexible cavity capable of accommodating ligands via an intramolecular hydrogen bonding network.

Photosynthetic water oxidation is catalyzed by a Mn4O5Ca cluster with an unprecedented arrangement of metal ions in which a single manganese center is bonded to a distorted Mn3O4Ca cubane-like structure. Several mechanistic proposals describe the unique manganese center as a site for water binding and subsequent formation of a high valent Mn–oxo center that reacts with a M–OH unit (M = Mn or CaII) to form the O–O bond. The conversion of low valent Mn–OHn (n = 1, 2) to a Mn–oxo species requires that a single manganese site be able to accommodate several oxidation states as the water ligand is deprotonated. To study these processes, the preparation and characterization of a new monomeric MnIV–OH complex is described. The MnIV–OH complex completes a series of well characterized Mn–OH and Mn–oxo complexes containing the same primary and secondary coordination spheres; this work thus demonstrates that a single ligand can support mononuclear Mn complexes spanning four different oxidation states (II through V) with oxo and hydroxo ligands that are derived from water. Moreover, we have completed a thermodynamic analysis based on this series of manganese complexes to predict the formation of high valent Mn–oxo species; we demonstrated that the conversion of a MnIV–OH species to a MnV–oxo complex would likely occur via a stepwise proton transfer-electron transfer mechanism. The large dissociation energy for the MnIVO–H bond (∼95 kcal mol−1) diminished the likelihood that other pathways are operative within a biological context. Furthermore, these studies showed that reactions between Mn–OH and Mn–oxo complexes lead to non-productive, one-electron processes suggesting that initial O–O bond formation with the OEC does not involve an Mn–OH unit.

The functionalization of C–H bonds has yet to achieve widespread use in synthetic chemistry in part because of the lack of synthetic reagents that function in the presence of other functional groups. These problems have been overcome in enzymes, which have metal–oxo active sites that efficiently and selectively cleave C–H bonds. How high-energy metal–oxo transient species can perform such difficult transformations with high fidelity is discussed in this tutorial review. Highlighted are the relationships between redox potentials and metal–oxo basicity on C–H bond activation, as seen in a series of bioinspired manganese–oxo complexes.