Nitrogen Reduction by the Fe Sites of Synthetic [Mo3S4Fe] Cubes

Summary paragraph: N 2 fixation by Nature, which is a crucial process to supply bio-available forms of nitrogen, is performed by nitrogenase. This enzyme employs a unique transition metal-sulfur-carbon cluster as its active-site cofactor ([( R -homocitrate)MoFe 7 S 9 C], FeMoco), 1,2 and the sulfur-surrounded Fe atoms have been postulated to capture and reduce N 2 . 3-6 Whereas synthetic counterparts of FeMoco, metal-sulfur clusters, have displayed binding of N 2 in a few examples, 7,8 the reduction of N 2 by any synthetic metal-sulfur clusters or even by the extracted form of FeMoco 9 have remained elusive despite a near-50-year history of research. Here we show that the Fe atoms in our synthetic [Mo 3 S 4 Fe] cubes 10,11 capture an N 2 molecule and catalyze N 2 silylation to form N(SiMe 3 ) 3 under treatment with excess Na and Me 3 SiCl. These results exemplify the first catalytic N 2 reduction by a synthetic metal-sulfur cluster with an Fe center supported only by S ligands. This work demonstrates the N 2 -reducing capability of Fe atoms in a S-rich environment, which Nature has selected to accomplish a similar purpose. This work also suggests some critical features for successful N 2 reduction by metal-sulfur compounds, which serve as clues to understand the origin of N 2 fixation on Earth. same Overall, the above results represent the first catalytic N 2 reduction by a synthetic M-S cluster and suggest some critical features for successful N 2 reduction. Suppression of inter-molecular aggregation of M-S cores is crucial for a sufficiently long lifetime of N 2 -bound species, while the enzyme buries the M-S core of FeMoco in a protein matrix to block such aggregation. Steric protection around the reaction site is important to enable the terminal binding of N 2 , which facilitates the electrophilic attack at the distal N atom. Thus, appropriate choice of metal ligands is crucial, while the enzyme features an evolutionary developed protein backbone around FeMoco to achieve a similar purpose. Additional conditions for efficient catalysis are installation of a leaving group (Cl in this study and postulated µ 2 -S in FeMoco) and robustness of the M-S cores under reducing conditions. While N 2 reduction to NH 3 or N(SiMe 3 ) 3 may have substantial mechanistic differences, our results confirm the novel N 2 -reducing activity of Fe centers in S-rich environments, as is the case with FeMoco.

Summary paragraph: N2 fixation by Nature, which is a crucial process to supply bio-available forms of nitrogen, is performed by nitrogenase. This enzyme employs a unique transition metal-sulfur-carbon cluster as its active-site cofactor ([(R-homocitrate)MoFe7S9C], FeMoco), 1,2 and the sulfur-surrounded Fe atoms have been postulated to capture and reduce N2. [3][4][5][6] Whereas synthetic counterparts of FeMoco, metal-sulfur clusters, have displayed binding of N2 in a few examples, 7,8 the reduction of N2 by any synthetic metal-sulfur clusters or even by the extracted form of FeMoco 9 have remained elusive despite a near-50-year history of research. Here we show that the Fe atoms in our synthetic [Mo3S4Fe] cubes 10,11 capture an N2 molecule and catalyze N2 silylation to form N(SiMe3)3 under treatment with excess Na and Me3SiCl. These results exemplify the first catalytic N2 reduction by a synthetic metal-sulfur cluster with an Fe center supported only by S ligands. This work demonstrates the N2-reducing capability of Fe atoms in a S-rich environment, which Nature has selected to accomplish a similar purpose. This work also suggests some critical features for successful N2 reduction by metal-sulfur compounds, which serve as clues to understand the origin of N2 fixation on Earth.

Main Text
Nitrogen is an essential element to maintain every known form of life on Earth. Whereas the element is affluent in the atmosphere as N2, only diazotrophs can fix this stable molecule into bio-available forms (e.g. NH3). Other organisms consequently rely on products of the fixation process and limited pre-existing sources to afford necessary nitrogen. In this sense, N2 fixation is one of the most crucial biocapacity bottlenecks on Earth. Key players of N2 fixation are nitrogenase enzymes that reduce N2 into NH3. The most studied one of these, Mo-nitrogenase, employs a unique metal-sulfur-carbon cofactor described as Fig. 1) 1,2 and performs the catalytic reduction at ambient temperature and pressure. Since FeMoco is found only in nitrogenase, its chemical and physical properties have attracted significant interest concerning the desirable N2-reducing activity. How FeMoco reduces N2 has long been studied by biochemical analyses of the enzyme 3,12 and by structural and functional modeling of FeMoco with small-molecule complexes 13,14 and metal-sulfur clusters 15,16 . While the structure of FeMoco has been identified clearly (Fig. 1), the detailed N2-reducing mechanism remains elusive. A growing number of results suggest that FeMoco eliminates one of the µ2bridging S atoms and captures substrates at the produced vacant coordination sites on Fe atoms 4-6 .
Analogously, a common approach to generate small-molecule N2 complexes has been removal of a metalbound ligand under reducing conditions. However, applying this method to available synthetic counterparts of the FeMoco, namely, metal-sulfur (M-S) clusters, has been challenging. As these clusters contain coordinative S atoms in their inorganic cores, a vacant metal site often attracts core S atoms of different M-S clusters rather than N2, which leads to aggregation 16 . Besides, the vacant site of a controlled N2-reducing system must be selected from various and multiple metal atoms in these clusters. M-S clusters capture N2 on rare occasions in this context 7,8 ; nevertheless, a catalytic reduction of N2 by these clusters remains unknown despite its relevance to the natural system. Our approach to overcome these hurdles implements a triangular [Mo3S4] fragment bearing robust Mo-Cp R bonds (Cp R = C5Me5 (Cp*), C5Me4SiMe3 (Cp L ) and C5Me4SiEt3 (Cp XL )) 10,11 as a platform to structurally encumber and protect a fourth metal incorporated into the vertex (Fig. 1). This approach has allowed the observation of the capture and (1.252 Å), suggesting weakened N-N bond. Likewise, the N-N stretching frequencies of 2b and 2c are close to the lower end of those reported for N2 complexes of Fe II or Fe I , 17 and the activation levels are even comparable to an Fe 0 -N2 complex supported by S-and C-based ligands 18 . Successful activation of N2 at the Fe atoms of 2a-c prompted us to pursue the catalytic reduction of N2 using the [Mo3S4Fe] cubes. The clusters did not catalyze the conversion of N2 into NH3 giving at most 2 Na(C 10 H 8 )  10,11 . Nonetheless, more importantly, we discovered that the Cl-clusters 1a-c and N2-clusters 2b and 2c all catalytically reduce N2 to N(SiMe3)3 in the presence of excess Na and ClSiMe3. A minimum of 122.9 ± 2.5 (per 1c) and up to 248.0 ± 12.7 (per 1b) equiv. of N(SiMe3)3 were generated after 100 hours under N2 (1 atm) at room temperature (Table 1).
While the cause of the differences in the activity of these complexes has not been conclusively identified at this point, we assume that the steric effects of the Cp R ligands play a major role (vide infra) because the Cp R substituents did not notably affect the redox behaviors of 1a-c (E1/2 ([Mo3S4Fe] 5+/4+ ) = -0.17 (1a), -0.19 (1b), and -0.24 (1c) V vs. Ag/Ag + ) 11 .
The catalytic activities of 1b and 2c are higher than those of other Fe catalysts reported so far [20][21][22] and comparable to the most active Mo 23 (Fig. 3). The -SiMe3 and -SiEt3 groups of Cp R ligands are forced into the space around the Fe sites of [Mo3S4Fe] cubes ( Fig. 3b and 3c) to minimize steric repulsion between the Cp R ligands. Thus, the -SiR3 groups efficiently offer steric protection of the [Fe-N2] moiety and prevent dimerization of cubes through either an Fe-N2-Fe bridge or an inter-cube Fe-S interaction. On the other hand, the less bulky Cp* ligands lead to a more exposed Fe site (Fig. 3a) and allow the approach of the Fe site of another [Mo3S4Fe] cube to give an Fe-N2-Fe dimer. The bulkiness of Cp R ligands should affect the catalytic activities as well, since we suggest that the first N-Si bond formation occurs at the distal N atom. In an Fe-N2-Fe dimer, both N atoms are protected until one of the Fe-N interactions breaks to generate monomers. In the catalytic reactions using Fe-Cl cubes, chloride abstraction (initiation) is expected to be slower with the bulkier Cp R ligands.

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