Alfred Werner proposed nearly 100 years ago that the secondary coordination sphere has a role in determining 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 the 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 M–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 non-covalent interactions, such as intramolecular hydrogen bonds involving dioxygen-derived ligands. To further illustrate these effects, the homolytic cleavage of C–H bonds by M–oxo complexes with basic oxo ligands is described.

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 O(2), yielding M(III) (M(III) = Fe and Mn) complexes with terminal oxo ligands. Installation of anionic sites within the cavity assists the formation of complexes with M(II/III)-OH and M(III)-O units derived directly from water. Opening the cavity promotes M(mu-O)(2)M 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 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.

Non-heme iron and manganese species with terminal oxo ligands are proposed to be key intermediates in a variety of biological and synthetic systems; however, the stabilization of these types of complexes has proven difficult because of the tendency to form oxo-bridged complexes. Described herein are the design, isolation, and properties for a series of mononuclear Fe(III) and Mn(III) complexes with terminal oxo or hydroxo ligands. Isolation of the complexes was facilitated by the tripodal ligand tris[(N'-tert-butylureaylato)-N-ethyl]aminato ([H(3)1](3-)), which creates a protective hydrogen bond cavity around the M(III)-O(H) units (M(III) = Fe and Mn). The M(III)-O(H) complexes are prepared by the activation of dioxygen and deprotonation of water. In addition, the M(III)-O(H) complexes can be synthesized using oxygen atom transfer reagents such as N-oxides and hydroxylamines. The [Fe(III)H(3)1(O)](2-) complex also can be made using sulfoxides. These findings support the proposal of a high valent M(IV)-oxo species as an intermediate during dioxygen cleavage. Isotopic labeling studies show that oxo ligands in the [M(III)H(3)1(O)](2-) complexes come directly from the cleavage of dioxygen: for [Fe(III)H(3)1(O)](2-) the nu(Fe-(16)O) = 671 cm(-1), which shifts 26 cm(-1) in [Fe(III)H(3)1((18)O)](2-) (nu(Fe-(18)O) = 645 cm(-1)); a nu(Mn-(16)O) = 700 cm(-1) was observed for [Mn(III)H(3)1((16)O)](2-), which shifts to 672 cm(-1) in the Mn-(18)O isotopomer. X-ray diffraction studies show that the Fe-O distance is 1.813(3) A in [Fe(III)H(3)1(O)](2-), while a longer bond is found in [Fe(III)H(3)1(OH)](-) (Fe-O at 1.926(2) A); a similar trend was found for the Mn(III)-O(H) complexes, where a Mn-O distance of 1.771(5) A is observed for [Mn(III)H(3)1(O)](2-) and 1.873(2) A for [Mn(III)H(3)1(OH)](-). Strong intramolecular hydrogen bonds between the urea NH groups of [H(3)1](3-) and the oxo and oxygen of the hydroxo ligand are observed in all the complexes. These findings, along with density functional theory calculations, indicate that a single sigma-bond exists between the M(III) centers and the oxo ligands, and additional interactions to the oxo ligands arise from intramolecular H-bonds, which illustrates that noncovalent interactions may replace pi-bonds in stabilizing oxometal complexes.