Nitrogen Fixation

(A) N2 + 3 H2 2 NH3

(B) N2 + 8 H+ + 8 e- 2 NH3 + H2

Equation 1.1. Reactions for (A) the Haber-Bosch process and (B) N2 fixation mediated

by nitrogenase.

Biogeochemical cycles play a critical role in the availability and conversion of massive amounts of elements and molecules throughout the planet. Of the myriad cycles that regulate important elements or molecules, one of the most fascinating is the nitrogen cycle, wherein elemental nitrogen is transformed between its stable gaseous N2 form and

triple bond found in N2 (220 kcal/mol) and its non-polarity make the activation of this

molecule exceptionally challenging and have motivated interest in understanding the conversion of N2 into reduced species such as NH3. Due to the importance of fixed

nitrogen molecules such as NH3 in fertilizing crops, mankind has developed an acute

need of a catalytic process for the production of NH3. The Haber-Bosch process, wherein

N2 and H2 are converted to NH3 over an Fe-based catalyst at high temperatures and

pressures (Equation 1.1A), has been applied on a globally massive scale as a means to effectively feed burgeoning human populations.1

Figure 1.1.X-Ray Diffraction (XRD) structure and chemical line drawing representation of FeMoco. The XRD figure was made with coordinates from Reference 4b.

In nature, N2 is fixed to NH3 by bacteria known as diazotrophs, which are

frequently found on root nodules, via the reaction shown in Equation 1.1B.2 _{The precise}

enzymatic machinery with which these organisms bind N2 and the mechanism they

employ to reduce it have been topics of great interest. Multiple studies have implicated a series of cofactors as the site of NH3 formation (Figure 1.1).3 These cofactors always

consist of primarily Fe and S (FeFeco) and can additionally incorporate Mo (FeMoco) or V (FeVco) when these elements are bio-available. Despite crystallographic information on the structures of these sites, recently revealing a carbon as the central atom of the

cofactor,4 consensus on the atom(s) at which N2 reduction occurs has not been reached.

Because Mo was once thought to be an essential component of all nitrogenases, the site of N2 binding was initially thought to be the single Mo atom in the FeMoco.2 This

assumption found support in studies on synthetic inorganic Mo complexes that bind and reduce N2.5

Figure 1.2. Mo complexes that mediate the catalytic reduction of N2 to NH3. Left:

Schrock’s tri-amidoamine system (Reference 9). Right: Nishibayashi’s PNP system (Reference 11).

Although some ill-defined mixtures with transition metals have been shown to generate NH3 from N2, these systems do not allow for insight into the mechanism of

reduction.6 One avenue of research that has helped to guide discussion about possible N2

reduction mechanisms has been the synthesis of molecular transition metal complexes that bind and reduce N2. Since the discovery of the first N2 complex by Allen and Senoff

in 1965, there has been great interest in developing molecular species that will mimic or provide insight into biological N2 fixation.7 In the context of Mo, discoveries by Chatt,

Hidai, and others have demonstrated that reduced metal centers can bind N2 and

electrochemical reduction of N2 to NH3 was reported by Pickett and co-workers.8 These

studies, as well as the synthesis of a variety of other nitrogenous species, led to the proposal of a mechanism now known as the “Chatt” or “distal” mechanism (Scheme 1.1, bottom) for N2 reduction.5 Despite this understanding, realization of a well-defined

molecular system for the catalytic reduction of N2 to NH3 at atmospheric pressure

remained elusive until Schrock and Yandulov’s landmark discovery in 2003 that a Mo tri-amidoamine (Figure 1.2) system can produce up to 8 equivalents of NH3 per Mo from

N2.9 This report, and the accompanying characterization of multiple proposed

intermediates that implicated a “distal” mechanism for N2 reduction in this system,10

represented the first well-defined molecular system for catalyzing N2 reduction to NH3.

Scheme 1.1. Proposed limiting mechanisms for transition metal mediated N2 reduction.

An “alternating” mechanism is shown on top in blue while a “distal” mechanism is shown on bottom in red. Black intermediates are common to both mechanisms. Not

shown are possible crossover pathways between mechanisms. Note that while M could feasibly be any transition metal, Mo and Fe are the most salient elements for this discussion.

More recently, Nishibayashi and co-workers have reported a phosphine ligated Mo center that improves slightly on Schrock’s system (Figure 1.2).11 _{This PNP ligated}

Mo complex is competent for up to 12 equivalents of NH3 per Mo center. The combined

synthetic studies of Schrock and Nishibayashi were consistent with the hypothesis that Mo serves as the active metal for nitrogenase under turnover conditions.2 Despite these results, however, the functionality of nitrogenases without Mo incorporated into the cofactor and other data began to suggest that Mo was not the active N2 binding site within

nitrogenases.

A number of spectroscopic studies on nitrogenase have recently indicated that Fe may in fact be the site where N2 is bound and reduced, and have further supported an

“alternating” mechanism wherein protons are alternately added to N2 to form

intermediates such as HN=NH and H2N-NH2 (Scheme 1.1 top).3,12 Such a mechanism

directly contrasts with the “distal” mechanism previously mentioned, wherein protons are added consecutively to single nitrogen atoms to generate intermediates such as nitrides (Scheme 1.1 bottom). Due to this proposed binding site and differing mechanism, there has been demand for Fe complexes that can (a) serve as structural, spectroscopic, or functional models of the Fe sites in FeMoco, (b) stabilize putative intermediates along a N2 fixation pathway (Scheme 1.1), or (c) serve as models for the highly reduced states of

towards developing synthetic Fe complexes that can structurally or functionally model nitrogenase or proposed catalytic intermediates.13 _{Indeed, several groups have}

demonstrated various Fe complexes that bind NxHy ligands or display corresponding

reactivity directly relevant to N2 reduction schemes.14

The Peters lab has had an ongoing interest in developing Fe systems that can functionally model the chemistry of nitrogenase enzymes. A guiding hypothesis for this research has been the postulation that N2 reduction occurs at a single Fe site at the

FeMoco and that this site samples multiple geometries in order to mediate catalytic turnover (Scheme 1.2). In order to model such a site, soft electron donating tris-

phosphine ligands have been utilized to stabilize low-valent Fe complexes in a number of geometries. Initially, pseudo-tetrahedral complexes of Fe with the tris-phosphine borate zwitterion PhB(CH2PR2)3- (PhBP3) were targeted.15 These ligands stabilize low-valent

and multiply bonded metal species on Fe. There was, however, a dearth of research into sulfur based chemistry on these scaffolds, which motivated further study into these types of complexes.

Scheme 1.2. Scheme depicting a potential mechanism for N2 binding to FeMoco utilizing

a flexible Fe-C interaction. Possible sites of protonation prior to or concurrent with N2