Antisymmetric Spin Exchange in a μ-1,2-Peroxodicopper(II) Complex with an Orthogonal Cu–O–O–Cu Arrangement and S = 1 Spin Ground State Characterized by THz-EPR

A unique type of Cu2/O2 adduct with orthogonal (close to 90°) Cu–O–O–Cu arrangement has been proposed for initial stages of O2 binding at biological type III dicopper sites, and targeted ligand design has now allowed us to emulate such an adduct in a pyrazolate-based μ-η1:η1-peroxodicopper(II) complex (2) with Cu–O–O–Cu torsion φ of 87°, coined ⊥P intermediate. Full characterization of 2, including X-ray diffraction (dO–O = 1.452 Å) and Raman spectroscopy (ν̃O–O = 807 cm–1), completes a series of closely related Cu2/O2 intermediates featuring μ-η1:η1-peroxodicopper(II) cores with φ ranging from 55° (A, cis-peroxo CP; BrinkmeierA.et al., J. Am. Chem. Soc.2021, 143, 1036134191490) via 87° (2, ⊥P type) up to 104° (B, approaching trans-peroxo TP; KindermannN.et al., Angew. Chem., Int. Ed.2015, 54, 1738). SQUID magnetometry revealed ferromagnetic interaction of the CuII ions and a triplet (St = 1) ground state in 2. Frequency-domain THz-EPR has been employed to quantitatively investigate the spin systems of 2 and B. Magnetic transitions within the triplet ground states confirmed their substantial zero-field splittings (ZFS) suggested by magnetometry. Formally forbidden triplet-to-singlet transitions at 56 (2) and 157 cm–1 (B), which are in agreement with the exchange coupling strengths Jiso inferred from SQUID data, are reported for the first time for coupled dicopper(II) complexes. Rigorous analysis by spin-Hamiltonian-based simulations attributed the corresponding nonzero transition probabilities and the ZFS to substantial antisymmetric (Dzyaloshinskii–Moriya) exchange d and provided robust values and orientations for the d, J, and g tensors. These interactions can be correlated with the Cu–O–O–Cu geometries, revealing a linear increase of Jiso with the Cu–O–O–Cu torsion and a strong linear decrease with the Cu–O–O angle. Relevance of the ⊥P intermediate for O2 activation at type III dicopper sites and a potential role of antisymmetric exchange in the concomitant intersystem crossing are proposed.


Materials and General Methods
All reactions, if not stated otherwise, were carried out using standard Schlenk techniques under argon atmosphere, or in a glovebox (MBRAUN LabMaster) under an atmosphere of dinitrogen with less than 0.1 ppm of O2 and H2O. Solvents were dried according to standard procedures and degassed by at least three freeze-pump-thaw cycles prior to use and were stored over molecular sieve (3 Å). All chemicals were purchased from commercial sources, prepared according to literature protocols, or the synthetic procedure is described below. 5-(Chloroethyl)-3-(chloromethyl) pyrazole hydrochloride was synthesized according to Figure S1, with slight modifications of the reported method. 1

SQUID Magnetometry
For temperature dependent susceptibility measurements, a QUANTUM DESIGN MPMS XL-5 SQUID magnetometer with a 5 T magnet was used. The powdered sample was contained in a gel bucket and fixed in a non-magnetic sample holder. Each raw data file for the measured magnetic moment was corrected for the diamagnetic contribution of the sample holder and the gel bucket. The molar susceptibility data were corrected for the diamagnetic contribution. Magnetic properties of the sample were simulated with the software julX_2s. 4

Frequency-domain Fourier-transform (FD-FT) THz-EPR
FD-FT THz-EPR data of complexes 2 and B were acquired at the THz-EPR experiment of the electron-storage ring BESSY II. The setup is described in detail in the literature. 5,6 Low-α mode linearly polarized coherent synchrotron radiation (CSR) 7 or unpolarized radiation emitted by the Hg arc lamp of a FTIR spectrometer (Bruker IFS 125) were used as broad-band (≈ 3−50 cm −1 and >12 cm −1 , respectively) excitation sources. It was transmitted via an evacuated transmission line through the FTIR spectrometer and focused on the sample contained in the variable temperature insert of a 10 T superconducting magnet (Oxford Spectromag). Spectra were recorded in Voigt geometry, in the case of CSR, with its magnetic field component B1 perpendicular to the static magnetic field B0. The transmitted signal was detected by a Si bolometer detector (IR labs) and Fourier-transformed to yield frequency-domain EPR spectra. The experimental resolution was 1 cm −1 , the temperature 5 K. Samples were prepared by homogenizing in a mortar the polycrystalline sample material (CSR: 44 mg 2, 62 mg B; Hg arc: 21 mg 2, 17 mg B) with polyethylene (PE) powder (11-65 mg) and pressing it into a pellet. To remove the incident background transmission from the spectrum, referencing was done between spectra recorded at different fields. 6,8 Magnetic-field division spectra (MDS) at two magnetic fields Bi and Bj are presented as relative transmittance T, experimentally obtained from the measured spectral intensities I as exp = / , and calculated from the simulated absorbance spectra A as sim = 10 − . A polynomial baseline correction was applied to experimental MDS. Global simulations of FD-FT THz-EPR and magnetometry data were performed using the EasySpin toolbox. [9][10][11] For the FD-FT THz-EPR data collected either using CSR or the Hg arc lamp, the respective polarization of the radiation and excitation geometry was taken into account. Figure S1. Synthetic Route for HL 1,2 ·7 HClO4.

3-(-Hydroxyethyl)-5-Hydroxymethylpyrazole Hydrochloride (II)
A solution of 1,6-dihydroxy-2,4-hexadiyne (2.5 g, 22.7 mmol, 1.0 eq.) and H2N-NH2•H2O (3.41 g, 68.11 mmol, 3.0 eq.) in EtOH (130 mL) was heated to 85 °C for 24 hours. The solvent and excess hydrazine were then removed under vacuum by using a cold trap. After drying the yellow oil overnight, ethanolic HCl was added and the product precipitated by adding Et2O, yielding a brown oil or solid (depending on the quality of the educt). The excess solvent was decanted, and the product was dried in vacuum overnight to give II as a brown oil (3.36, 18.8 mmol, 83%).

3-(-Chloroethyl)-5-Chloromethylpyrazole Hydrochloride (III)
To compound II (3.26 g, 18.3 mmol, 1.0 eq.), thionyl chloride (80 mL) was added slowly at 0 °C. The solution was then heated to 65 °C for one hour, cooled to RT and excess thionyl chloride was removed under vacuum by using a cold trap. The resulting brown oil was dried under vacuum overnight (important!). Addition of Et2O and vigorous stirring for 24 h led to the formation of a brown powder. Excess solvent was decanted, the solid dried under vacuum and the product obtained as a beige powder (3.50 g, 16.2 mmol, 89%).

Synthesis of HL 1,2 ·7 HClO 4
Compound III (1.16 g, 5.39 mmol, 1.0 eq.), TBABr (643 mg. 1.99 mmol, 0.37 eq.) and Na2CO3 (6.46 g, 60.9 mmol, 11.3 eq.) were suspended in MeCN (110 ml) and 1,4-di(iso-propyl)-1,4,7-triazacyclononane (2.5 g, 11.7 mmol, 2.2 eq.) was added via a syringe. The reaction mixture was heated to reflux for 24 h at 100 °C, then cooled to RT and filtered. The residue was washed with MeCN (30-50 ml) and volatiles were removed under vacuum. The resulting brown oil was dissolved in DCM (100 ml) and washed with 1 M NaOH (40 ml). The aqueous phase was extracted with DCM (3 x 80 ml) and the combined organic phases were dried over MgSO4. Subsequently, the solvent was removed under reduced pressure and the residue dissolved in DME (16 ml). Addition of small amounts of HClO4 led to the formation of a precipitate, which began to dissolve again after further addition of HClO4. Then, EtOH/Et2O (1:1, 100 ml) was added to form a brown viscous mass which was stirred for 1-2 hours. Further washing with EtOH (100 mL) and Et2O (100 ml) and subsequent drying under vacuum led to the isolation of a beige powder (3.02 g, 2.43 mmol, 45 %).

FD-FT THz-EPR Spectroscopy
In the following, FD-FT THz-EPR spectra for complexes 2 ( Figure S12) and B ( Figure S13 and Figure S14) are shown alongside simulations with Eq. 1 in the main text assuming antisymmetric exchange without ( Figure S12 and Figure S14) and with ( Figure S13) symmetric anisotropic exchange. Differences in the simulated line shapes obtained with these models are outlined in Figure S15 Figure S13) and simulated curves (TIP = 109  10 -6 cm 3 mol -1 ) for crystalline samples of B. (d, e) Experimental (as in Figure S13) and simulated FD-FT THz-EPR magnetic-field division spectra for pellets of polycrystalline B. Branches of ΔMS,t = -1, ΔMS,t = +1 and ΔSt = -1 transitions are indicated. Simulations in all panels are based on the optimized spin Hamiltonian parameters in Table S1.  Table 2) and those without ̂a ni (bottom , Table S1). Simulated spectra are shown on vertically expanded scales, 3x in (a) (compare Figures 7e, S12e) and 2x in (b) (compare Figure S13e, S14e) for better comparability to the experimental spectra. The field-dependent discrepancies of the relative signal intensities in all our simulations are thought to arise from ordering effects in the samples at high magnetic fields. As indicated on top, the splitting of the ΔMS,t = -1 transitions in the experimental spectra is reproduced only in the presence of symmetric anisotropic contributions, while the ΔMS,t = -1 signal is unsplit in their absence. (Reasons for the remaining mismatch of peak positions, particularly for complex B, are discussed below.) As a consequence, also the relative heigths of the ΔMS,t = -1 and +1 peaks are much better reproduced in the presence of ̂a ni . a For the Euler angles describing the orientations of the g tensors relative to the d frame see Figure S16. b g tensors g1 and g2 of Cu1 and Cu2, respectively, were constrained to be identical. Discussion of remaining deviations between experimental and simulated spectra after inclusion of symmetric anisotropic exchange ̂a ni : Our simulations demonstrate that symmetric anisotropic exchange is the origin of the orientationally dependent ΔMS,t = -1 splitting. However for 2, upon inclusion of the ̂a ni term, discrepancies are still observed in the positions of the ΔMS,t = -1 lines and the very small Zeeman shift of the ΔSt = -1 transition is still overestimated. One reason may be a deviation of the actual d vector orientation from that in ideal C2 symmetry, which however cannot be determined from our data on polycrystalline samples. This is also true for a rotation of the Jani relative to the d frame. Concerning B, it is noted that in C2 symmetry only the y components of the Jani tensor and the d vector are required to be aligned, coinciding with the C2 axis, 12 but computations indicate for model systems that rotations of Jani around the dy axis are small. 13 Further deviations possibly arise from ordering effects in both samples at high magnetic fields, apparent from deviating line intensities and widths in all fits. S16

Uncoupled and Coupled Representations of the 2-Spin System: Effect of Exchange Coupling Terms
To illustrate the contributions of the four spin states in the uncoupled representations |MS,1,MS,2> to the total spin states in the coupled representation |St,MS,t> depending on the various types of exchange interaction considered, we have calculated the respective eigenvectors upon diagonalizing the spin Hamiltonians, employing the optimized coupling parameters of complex 2 ( Table 2). The situations in Tables S3 and S5 correspond to the simulations shown in Figures 7 and S12, respectively, for complex 2 (and Figures S13 and  S14, respectively, for complex B). From Tables S2 and S3, it is seen that inclusion of the DM term adds an imaginary part to the contribution from |MS,1,MS,2> = |+1/2,-1/2> to |St,MS,t> = |1,0> and |0,0> (the linear combinations of |MS,1,MS,2> = |+1/2,-1/2> and |-1/2,+1/2>). This kind of mixing of the states is how the DM interaction engenders non-zero transition probabilities from the St = 1 ground state manifold to the St = 0 excited state. From Tables S4 and S5, it is furthermore seen that the symmetric anisotropic exchange term lifts the degeneracy of the |St,MS,t> = |1,-1> and |1,+1> states, as portrayed in the respective spin state energy schemes (Figures 7a, S13a). It is noted that in the presence of symmetric anisotropic exchange, MS,t = -1 and +1 strictly speaking do not represent good quantum numbers for these states, since in this case they are linear combinations of |MS,1,MS,2> = |+1/2,+1/2> and |-1/2,-1/2>. However, for the sake of a coherent nomenclature and understandability, we are using this notation throughout the manuscript regardless of the model considered.

X-Ray Crystallography
Crystal data and details of the data collections are given in Table S6, selected bond lengths angles in Table  S7, molecular structures are shown in Figure S17 & Figure S18. X-ray data were collected on a STOE IPDS II diffractometer (graphite monochromated Mo-Kα radiation, λ = 0.71073 Å) by use of  scans at -140 °C. The structures were solved with SHELXT and refined on F 2 using all reflections with SHELXL. 14,15 Non-hydrogen atoms were refined anisotropically. Hydrogen atoms were placed in calculated positions and assigned to an isotropic displacement parameter of 1.5/1.2 Ueq(C). Face-indexed absorption corrections were performed numerically with the program X-RED. 16 CCDC 2155127-2155128 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.

1* 2
Cu-N 1.890 (7) All determined values were higher than the experimentally obtained value of Jiso = +25 cm -1 , but indeed confirmed the ferromagnetic exchange coupling. Overlap of the magnetic orbitals was derived by brokensymmetry state analysis of the corresponding orbitals 187α and 187β ( Figure S19), revealing a value of 0.09 for the magnetic overlap integral, confirming the triplet ground state.