10.1002/anie.201906327
Angewandte Chemie International Edition
COMMUNICATION
cofactor of nitrogenase.[29] In our system, no visual changes are
observed unless all three reaction components (1, CoCp2, and
N2O) are present. Because complex 1 is in the 4CuI:1S2- redox
state, it is unlikely that reactivity initiates with reduction of 1 by
CoCp2. Instead, we favor a sequence where the π-accepting
molecule N2O binds to 1, likely along the Cu1-Cu2 edge, thus
raising the reduction potential such that CoCp2 can donate to the
newly introduced electron holes of 1·N2O.
Figure 3. (a) Comparisons of the [Cu4S] cores of 1’ and 1, with bond distances
shown in black and NBO charges shown in red; (b) comparisons of the HOMO-
3 orbitals for 1’ and 1 (B3LYP/6-31++G**).
To better understand the sensitivity of N2O reductase activity
of 1 to solvent environment, we decided to examine its solvent-
dependent structure. Repeated attempts at solving the solid-state
structure of 1 using single crystals grown from MeOH-d4 indicated
the presence of hydrogen-bonded solvent molecules in the
second sphere. However, Yam’s [Cu4(µ4-S)(µ2-dppm)4]2+ complex
(1’)[20] can be viewed as a model for the structure of 1 in the
absence of any hydrogen-bonding interactions. The [Cu4S] core
of 1’ has local C2v symmetry, with a rectangle-based pyramidal
core featuring Cu···Cu distances of 2.869(2) and 3.128(1) Å, and
a µ4-S-atom with a 휏4’ parameter[27] of 0.56. Crystals of 1 obtained
from MeOH solution provided a structure with some key
differences (Figure 2b). Two of the N–H groups are acting as
To summarize, the N2O reductase activity of 1 depends on a
subtle interplay of primary and secondary coordination sphere
effects. In the presence of appropriate hydrogen bond acceptor
molecules (MeOH, acetone) in the reaction medium, second-
sphere hydrogen bonding induces structural distortion in the
primary coordination sphere of the [Cu4S] active site. The
resulting strained geometry enhances the active site’s ability to
bind and activate N2O through localization of frontier MO density
along one edge site of the cluster. Upon activation, the N2O
substrate is converted to N2 and H2O with H+ donation directly
from the second coordination sphere. These behaviors closely
mimic phenomena previously hypothesized for the CuZ site of
N2OR and, we hope, provide an entryway to future CuZ modeling
studies.
-
hydrogen bond donors in the solid-state: the N1–H group to a PF6
counterion,
and
the
N4–H
group
initiating
a
-
NH···MeOH···MeOH···PF6 network. The [Cu4S] core of 1 is
highly unsymmetrical, with the three Cu sites distal to the N4–H
hydrogen-bonding network clustered close together (Cu1···Cu2,
2.6969(6) Å; Cu2···Cu3, 2.6690(6) Å) while the Cu4 site is pulled
further away (Cu4···Cu3, 3.0175(7) Å; Cu4···Cu1, 3.542(1) Å).
The S-atom geometry is also perturbed (휏4’ = 0.72) compared to
1’. These metrical parameters are almost identical to what we
previously reported for 1 interacting with acetone molecules.[24]
Furthermore, these parameters are quite similar to the CuZ
structure,[11] which is also highly unsymmetrical with one Cu site
distal (3.00-3.33 Å) from the other three and which has a similar
S-atom geometry (휏4’ = 0.77). Structural comparisons of the two
synthetic [Cu4S] cores are shown in Figure 3a.
Acknowledgements
Funding was provided by NIH/NIGMS (R01 GM116820).
Margaret Kelty and Prof. John Anderson (University of Chicago)
provided access to a UV-Vis/near-IR spectrometer and assisted
with near-IR measurements. This research was supported in part
through computational resources provided by the Advanced
Cyberinfrastructure for Education and Research (ACER) at UIC.
To evaluate the electronic impact of these structural changes,
we studied 1’ and 1 computationally. When examining calculated
NBO atomic charges, a notable difference between the two
complexes is the buildup of additional negative charge on the Cu2
site, i.e. the middle site among the more closely clustered Cu
centers, in unsymmetrical 1 (Figure 3a). When examining the
frontier MOs produced by DFT calculations, another notable
difference involves the HOMO-3 level, which is highly delocalized
across the entire [Cu4S] core for 1’ but is localized mostly at the
Cu1 and Cu2 sites in 1 (Figure 3b) and is also 573 cm-1 closer to
the HOMO level. A similar phenomenon is observed for the LUMO
level, which is localized at the sulfur atom for 1’ but mostly
localized at the Cu2 site for 1 (see Supporting Information, page
S46). Collectively, these observations indicate that for 1,
hydrogen bond-induced structural distortion creates localization
of frontier MO density at the Cu1-Cu2 edge site, both making Cu2
more electrophilic towards N2O binding and making the Cu1-Cu2
edge better able to π-backbond into the π* manifold of bound N2O.
In a related discovery, recently Agapie showed that structural
distortion of tetrametallic models of the oxygen evolving complex
(OEC) of photosystem-II through steric pressure modulates the
clusters’ reduction potentials.[28] The additional contribution of our
system is the correlation between structure and chemical
reactivity with the relevant substrate, N2O. A similar correlation
between substrate activation and localization of frontier MO
density has recently emerged to describe the octanuclear FeMo-
Keywords: cluster compounds • nitrous oxide • hydrogen bonds
• bioinorganic chemistry • second sphere
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