Investigating reactivity and electronic structure of copper(II)-polypyridyl complexes and hydrogen peroxide

Article abstract of DOI:10.1016/j.ica.2020.120168

This work presents a detailed study of the reactivity of three mononuclear Cu^II complexes supported by derivatives of the tetradentate ligand N,N'-bis(2-pyridylmethyl)-1,2-ethylenediamine (bispicen). The Cu^II complexes are capable of performing C[sbnd]H bond activation in the presence of NEt₃ and H₂O₂ through what has been proposed computationally to be a [CuO]⁺ intermediate. A wavefunction-based quantum chemical investigation into the electronic structure of the proposed [CuO]⁺ intermediate reveals a triplet ground state predominantly consistent with an S = ? Cu^II center ferromagnetically coupled to an oxyl radical, though contributions from the corresponding biradicaloid Cu^I-oxene resonance structure may be nontrivial. Furthermore, correlation of the electronic structure of the proposed intermediate with analogous high-valent metal-oxo species capable of olefin epoxidation suggests that the Cu^II complexes might be also capable of olefin epoxidation in the presence of NEt₃ and H₂O₂. To test this hypothesis experimentally, the Cu^II complexes are treated with NEt₃ and H₂O₂ in the presence of alkene substrates, resulting in the formation of epoxides.

Full text of DOI:10.1016/j.ica.2020.120168

Inorganica Chimica Acta 516 (2021) 120168
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Research paper
Investigating reactivity and electronic structure of copper(II)-polypyridyl
complexes and hydrogen peroxide
a
a
b
Thomas M. Khazanov , Niharika Krishna Botcha , Sandugash Yergeshbayeva ,
b
a,*
Michael Shatruk , Anusree Mukherjee
a
Department of Chemistry, University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899, United States
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, United States
b
A R T I C L E I N F O
A B S T R A C T
This work presents a detailed study of the reactivity of three mononuclear CuII complexes supported by de-
Keywords:
Cu-mediated oxidation
Enzyme modeling
II
rivatives of the tetradentate ligand N,N’-bis(2-pyridylmethyl)-1,2-ethylenediamine (bispicen). The Cu com-
plexes are capable of performing C
–
H bond activation in the presence of NEt
3
and H
2
O
2
through what has been
C
–
H bond activation
+
proposed computationally to be a [CuO] intermediate. A wavefunction-based quantum chemical investigation
Epoxidation
+
into the electronic structure of the proposed [CuO] intermediate reveals a triplet ground state predominantly
II
consistent with an S = ½ Cu center ferromagnetically coupled to an oxyl radical, though contributions from the
I
corresponding biradicaloid Cu -oxene resonance structure may be nontrivial. Furthermore, correlation of the
electronic structure of the proposed intermediate with analogous high-valent metal-oxo species capable of olefin
II
epoxidation suggests that the Cu complexes might be also capable of olefin epoxidation in the presence of NEt
3
2 2 3 2 2
O and H O in the
. To test this hypothesis experimentally, the CuII complexes are treated with NEt
and H
presence of alkene substrates, resulting in the formation of epoxides.
1
. Introduction
Decades of enzymatic and modelling studies have established that
mononuclear copper-oxygen complexes may belong to one of three
II
In biology, copper plays a variety of essential roles primarily related
categories: 1:1 Cu:O
2
complexes, Cu -alkyl/hydroperoxide complexes,
+
2+
to electron transfer [1]. In particular, a number of enzymes that utilize
copper as a cofactor are dedicated to O binding, activation, and
or high valent [CuO] / [CuOH] species [3]. While detailed structural,
spectroscopic, and mechanistic understanding has been obtained from
2
+
+
+
reduction, typically coupling this process with the oxidation of exoge-
nous substrates [2–4]. This oxidation chemistry is accomplished by the
generation of reactive copper-oxygen intermediates in mononuclear,
binuclear, and even trinuclear and tetranuclear active sites [1,5].
Binuclear sites, in particular, have been implicated in the binding and
the study of systems featuring [CuO
2
] or [CuOOH] / [CuOOR] cores,
+
higher valent [CuO] intermediates have remained particularly elusive
as they have only been observed experimentally in the gas phase [1,3].
+
High valent [CuO] species have been proposed as reactive in-
termediates in enzymes such as dopamine β-monooxygenase, [10,11]
peptidylglycine -hydroxylating monooxygenase [12,13], LPMO [14],
activation of O
2
for substrate oxidation, though the discovery of mon-
α
ooxygenase metalloenzymes containing mononuclear copper active sites
such as lytic polysaccharide monooxygenase (LPMO) has resulted in
as well as in pMMO [15,16]. However, the formulation of high valent
+
III
[CuO] species as Cu -oxo intermediates, in analogy to other high
IV
increased interest in monocopper-O
2
species [1,5,6]. The enzyme par-
valent metal-oxo species of biological relevance such as Fe -oxo
IV
ticulate methane monooxygenase (pMMO), responsible for the oxida-
tion of methane to methanol (bond dissociation energy 104 kcal/mol)
[17–20] or Mn -oxo [21–23] intermediates, is challenging. Initial
theoretical investigations have suggested that [CuO] systems should be
+
[
7], has been shown to only contain mononuclear copper sites [8,9]. As
similar or even more powerful oxidants than the analogous and exten-
IV
the active site was generally believed to be multinuclear until 2019, the
mechanism of methane oxidation at a mononuclear copper site remains
an open question.
sively studied Fe -oxo complexes [24], and the study of their electronic
structure and reactivity seeks to address fundamental questions in both
metalloenzymology and inorganic chemistry.
*
Corresponding author.
E-mail address: anusree.mukherjee@uah.edu (A. Mukherjee).
https://doi.org/10.1016/j.ica.2020.120168
Received 24 August 2020; Received in revised form 6 November 2020; Accepted 27 November 2020
Available online 1 December 2020
0
020-1693/© 2020 Elsevier B.V. All rights reserved.

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
Recently we reported experimental and theoretical results that
carried out with the density functional BP86 [31,32] using the crystal
structures of 1 and 2 as a starting point. Calculations employed the def2-
TZVP basis set [33,34] for copper and directly coordinated atoms;
remaining atoms were calculated using the def2-SV(P) basis set [35].
Dispersion effects were included using the atom-pairwise correction
with Becke-Johnson damping scheme (D3BJ) as it has been adopted in
the ORCA program [36,37]. The density fitting and “chain of spheres”
(RIJCOSX) [38] approximations were employed in conjunction with the
auxiliary basis set def2/J [39]. Stationary points were verified by ana-
lytic computation of vibrational frequencies. Damping parameters were
adjusted as needed in order to reach convergence using the keyword
SlowConv. Electron paramagnetic resonance (EPR) parameters were
obtained from single-point calculations on the previously optimized
geometries using the hybrid density functional B3LYP [40,41]. Scalar
relativistic effects were included with the zeroth order regular approx-
imation (ZORA) [42–44] employing the core property basis set CP(PPP)
on copper, the ZORA-def2-TZVP(-f) basis set [33,34] on nitrogen and
oxygen atoms, and the ZORA-def2-SVP basis set [35] on all remaining
atoms. Auxiliary basis sets were generated automatically (AutoAux)
[45]. Picture change effects were included. Electronic absorption
spectra were calculated for 1–3 within the time-dependent density
functional theory (TDDFT) formalism employing the Tamm-Dancoff
approximation (TDA) [46] with the same functional and combination
of basis sets. Consistent with experiment, solvation effects associated
with acetonitrile were accounted for by using the conductor-like
polarizable continuum model (CPCM) as implemented in ORCA [30].
+
implicated a [CuO] species as the reactive intermediate for C
–
H bond
activation [25]. Reactive intermediates were generated from mono-
II
nuclear Cu complexes supported by tetradentate polypyridyl ligands
2 2
with H O in an analogous manner to the biological peroxide shunt
pathway, bypassing the need for external electrons [26]. In these ex-
periments, substrate oxidation was observed when each copper complex
was treated with H
CHD) or dihydroanthracene (DHA). On the basis of isotope labeling
studies, spectroscopic analysis of degradation products, and density
2 2
O and base in the presence of either cyclohexadiene
(
functional theory (DFT) calculations, a mechanism for C
–
H bond
+
oxidation by a [CuO] species largely analogous to the radical rebound
mechanism of other high-valent metal-oxo species was proposed [27].
Herein we report the reactivity of three mononuclear copper com-
plexes supported by bispicen ligand variants (Fig. 1) toward C H bond
–
activation. This study further refines our understanding of the electronic
+
structure of the [CuO] species generated from 1 to 3 with H
2
O
2
. In
addition to C H bond activation, we use an ab initio quantum me-
–
chanical investigation into the electronic structure of the proposed
+
[
CuO] intermediates and the knowledge of the electronic structure of
well-understood epoxidation catalysts to predict complexes 1–3 as being
able to perform O-atom transfer to alkenes to form epoxides. As a proof
of concept, we further support this claim with reactivity studies of 1–3
toward exogenous alkene substrates.
2
. Experimental
+
+
+
The geometries of [1-O] , [2-O] , and [3-O] were optimized on the
broken symmetry (BS) potential energy surface. Single-point calcula-
tions were carried out to obtain singlet–triplet gaps and quasi-restricted
orbitals (QROs) using the same combination of basis sets described
2
.1. Materials and methods
All reagents and solvents were purchased from MilliporeSigma and
Fisher Scientific and directly used for synthesis without further purifi-
cation unless mentioned otherwise. Copper complexes and ligands were
synthesized following reported procedures [28,29]. 9,10-dihydroan-
thracene (DHA) was purchased from MilliporeSigma and recrystallized
from ethanol prior to use. All electronic absorption spectra were
measured using an Agilent Cary 8454 UV–Vis Spectrophotometer.
Samples for optical spectroscopy were prepared in quartz cells with an
optical path length of 1 cm. Graphical representation and data analysis
were performed in Origin. Quantification of the oxidized products was
carried out using an Agilent 6890 Gas Chromatograph (GC) equipped
with an Agilent 5973 Network Mass Selective Detector and Flame
Ionization Detector (FID) using naphthalene as an internal standard.
above at the B3LYP, M06 [47], and
ω
B97X [48] levels of theory. To
correct for biradical character in the singlet structures, wavefunctions
were calculated employing the complete active space self-consistent
field (CASSCF) [49] method. In the CASSCF calculations, an active
space consisting of twelve electrons in seven orbitals was chosen (CAS
+
+
(12,7)). QROs from the single-point calculations of [1-O] , [2-O] , and
+
[3-O] were used as starting orbitals for the CASSCF calculations.
Dynamical correlation effects were explicitly introduced as described by
second-order N-electron valence perturbation theory (NEVPT2) to
obtain singlet–triplet splittings [50,51]. To better account for dynamical
correlation effects, the Cu-4d orbitals were also included, giving rise to a
final active space of 12 electrons in 12 orbitals (CAS(12,12)) for the
CASSCF/NEVPT2 calculations.
Alternative active spaces and multireference configuration interac-
tion procedures were explored. An active space consisting of fourteen
electrons in the five Cu-3d based molecular orbitals (MOs) and three O-
2
.2. General procedure for substrate oxidation
Forty equivalents of substrate with respect to the complex were
2
p orbitals was chosen (CAS(14,8)). Orbitals with an occupation less
added to solutions of complexes 1–3, followed by the addition of H
and NEt solutions in acetonitrile (10 eq. with respect to the complex)
2 2
O
than 1.98 and greater than 0.02 from the CAS(14,8) calculations were
used to construct reference spaces of 10 electrons in 6 orbitals (10,6) for
subsequent spectroscopy oriented configuration interaction calculations
3
under aerobic conditions at 298 K. Reaction progress was monitored via
electronic absorption spectroscopy and products were identified after
removal of the copper complex using a microscale alumina column.
Product yields were calculated with respect to the copper complexes.
(
SORCI) [52]. While (8,5) reference spaces may have been sufficient for
+
+
[
1-O] and [3-O] , a (10,6) reference space was required to describe the
+
electronic structure of [2-O] based on orbital occupation, so (10,6)
reference spaces were constructed for all three compounds for consis-
tency. All CASSCF and SORCI calculations were carried out with the
ZORA-def2-TZVP(-f) basis set on copper, nitrogen, and oxygen atoms
and the ZORA-def2-SVP basis set on all other atoms.
2
.3. Computational methods
All computations were carried out using the computational chemis-
try software package ORCA 4.2 [30]. Geometry optimizations were
2
.4. X-ray crystallography
Single-crystal X-ray diffraction was performed on a Rigaku-Oxford
Diffraction Synergy-S diffractometer equipped with a HyPix detector
and a Mo-K
α
radiation source (λ = 0.71073 Å). In a typical experiment, a
single crystal was suspended in Parabar® oil (Hampton Research) and
mounted on a cryoloop that was cooled to the desired temperature in an
◦
Fig. 1. Copper complexes studied in the present work.
N
2
cold stream. The data sets were recorded as
ω
-scans at 0.5 step width
2

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
and integrated with the CrysAlis [53] software package. Empirical ab-
sorption correction was applied as implemented in the SCALE3
ABSPACK algorithm [54]. The crystal structure solution and refinement
were carried out with SHELX [55] using the interface provided by Olex2
structure (Table 1). While the equatorial Cu–N distances are generally
slightly overestimated and the axial Cu–N/O bond slightly under-
estimated in the DFT-optimized structure, the elongation of the axial
Cu–N/O relative to the equatorial Cu–N bonds of the ligand is correctly
predicted by the computational model. These small discrepancies be-
tween experimental and calculated bond lengths may be attributed to
crystal packing forces [64]. The computed optical parameters of 1 and 2
(Table S2) were in broad agreement with the experimentally obtained
results, slightly overestimating the absorption maximum of 2. The
calculated EPR spin Hamiltonian parameters (Tables S3-4) for 1–2 were
in similar agreement. The rhombicity of the g-tensor was apparent for 2
at X-band, slightly deviating from axial symmetry as predicted by the
computational studies (Table S3). Higher frequencies are required to
observe similar deviations for 1 and 3, and all are compared under
approximate axial symmetry for consistency. This agreement between
the observed and calculated spectroscopic parameters for 1–2 suggests
that the computationally derived structure of 3 can be correlated to the
experimentally obtained optical and EPR spectra within the same
computational methodology. As crystals of 3 suitable for crystallog-
raphy could not be obtained, this provides some insight into the geo-
metric structure of 3 and allows for comparison with complexes 1–2.
The electronic absorption spectrum of 3 is well reproduced by the
computed electronic transitions (Table 2), exhibiting one optical band
centered at approximately 600 nm assigned to a d-d transition at the
[
56]. The final refinement was performed with anisotropic atomic
displacement parameters for all atoms. Full details of the crystal struc-
ture refinement and the final structural parameters have been deposited
with the Cambridge Crystallographic Data Centre (CCDC). The CCDC
registry numbers and a brief summary of data collection and refinement
parameters are given in Table S1.
3
. Results and discussion
3
.1. Synthesis and characterization
The syntheses of L1-3 were performed according to previously pub-
lished procedures [28,29,57,58]. Copper complexes were similarly
synthesized according to published procedures [28,29]. Complexes 1–3
exhibit broad optical absorption bands with maxima in the 588–620 nm
range. These bands are assigned to d-d transitions, typical of mono-
nuclear Cu(II) compounds in square pyramidal geometry [28,59–63].
We previously reported the crystal structure of 1 and herein report the
structures of 2 obtained under two different conditions [28].
X-ray quality single crystals of 2a were obtained by vapor diffusion
of diethyl ether into an acetone solution of the complex at room tem-
perature. The copper center is coordinated in a distorted square-
II
metal center [28]. This is consistent with mononuclear Cu complexes in
II
square pyramidal geometry, as it is known that mononuclear Cu
pyramidal geometry (
τ
= 0.16) with four coordination sites occupied
complexes in a trigonal–bipyramidal geometry typically exhibit ab-
sorption maxima at longer wavelengths [65–67]. The calculated elec-
by the nitrogen atoms of the ligand and the fifth axial site occupied by
one oxygen atom from the perchlorate counterion (Fig. 2). The Cu–N
bond lengths are consistent with known Cu(II) complexes supported by
N4 ligands in a distorted square pyramidal geometry. X-ray quality
single crystals of 2b were obtained by vapor diffusion of diethyl ether
into an acetonitrile solution of the complex at room temperature. When
crystals were obtained from an acetonitrile solution, the coordinating
perchlorate ion in 2a is replaced by a molecule of coordinating solvent
tronic g-tensor for 3 is approximately axial (g
1
> g
2
3 e
≳ g > g ), consistent
with a square pyramidal or elongated octahedral geometry with the
unpaired electron residing mainly in the 3d
2
2
orbital [63,68,69]. The
x ꢀ y
calculated g-values are slightly underestimated compared to the exper-
imentally obtained values. Taking the 63Cu hyperfine coupling tensor as
axial, an increased A
‖
value and reduced A value is obtained relative to
⊥
experiment. The spectral parameters are generally in agreement, how-
ever, and consistent with the proposed structure.
(
MeCN). The copper center is similarly coordinated in a distorted square
pyramidal geometry (
τ
= 0.26) in which ligand nitrogen atoms occupy
the equatorial coordination sites and the axial site is occupied by coor-
dinating acetonitrile. The distortion from square pyramidal geometry is
greater than in 2a but the observed geometry is still consistent with
other square pyramidal copper(II) complexes in the literature [28,63].
Axial coordination of solvent when crystals were obtained from
acetonitrile attests to the lability of the axial coordination site. This was
also observed in the previously reported crystal structure of complex 1 in
which water is axially coordinated [28]. For this reason, computational
models were constructed with axially coordinated MeCN as consistent
with experiment. The calculated bond distances in the DFT-optimized
geometries of 2a and 2b are in reasonable agreement with the crystal
2 2
3.2. Reactivity toward H O
2 2
Addition of H O (10 eq.) to a solution of 1 in MeCN in the presence
of NEt (10 eq.) resulted in an initial redshift of the d-d transition band
3
centered at 588 nm and subsequent decay to a well-defined optical band
centered at 641 nm with a shoulder above 400 nm (Fig. 3). In the case of
2 2 3
2, treatment with H O in the presence of NEt resulted in rapid decay of
the broad d-d transition band centered at 620 nm (Fig. S1). This
absorbance band decayed to a new feature centered at 634 nm and lower
in intensity than that of the starting material. A more narrow, intense
feature was observed for 2 at 492 nm after the decay of the original
Fig. 2. Left: ORTEP view of complex 2a crystallized from acetone/diethyl ether; right: ORTEP view of complex 2b crystallized from acetonitrile/diethyl ether.
3

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
Table 1
Selected bond distances and bond angles for complexes 2a and 2b.
Bond Distances (Å)
Bond Angles (degrees)
2
a
2b
2a
2b
Exp.
Calc.
Exp.
Calc.
Exp.
82.60
Calc.
Exp.
81.77
Calc.
Cu1–N1
Cu1–N2
Cu1–N3
Cu1–N4
Cu1–O1
Cu1-N5
2.007
2.018
2.009
2.002
2.308
–
2.018
2.073
2.131
1.994
2.127
–
2.012
2.037
2.034
2.027
–
2.012
2.094
2.087
2.030
–
N1–Cu1–N2
N2–Cu1–N4
N2–Cu1–N3
N1–Cu1–N3
N1–Cu1–O1
N1–Cu1–N5
82.0
164.9
85.9
137.8
127.3
–
80.9
139.5
85.4
163.3
–
165.80
85.20
156.10
103.10
–
149.03
85.23
164.66
–
2.176
2.118
92.17
94.8
Table 2
Optical and magnetic parameters for complex 3. The g-tensor axes were assumed
to be collinear with the Cu hyperfine coupling tensor principal axes. Experi-
mental values obtained from ref. 30.
Absorption Maxima (nm)
g values
Cu hyperfine
coupling constants
(
MHz)
g
‖
g
⊥
A
‖
A
⊥
Experimental
Theoretical
606
572
2.216
2.148
2.051
2.047
540
587
60
37
Fig. 4. Left: Reaction of 1 with 10 eq. H
MeCN monitored for 6 h via electronic absorption spectroscopy. Right: reaction
of 1 with 10 eq. H , 10 eq. NEt , and 40 eq. DHA in MeCN monitored for 6 h
2 2 3
O , 10 eq. NEt , and 40 eq. CHD in
2
O
2
3
via electronic absorption spectroscopy. Optical path length 1 cm.
absorbance in the 400–500 nm region compared to treatment with only
NEt and H O (Fig. 3), prompting us to analyze the reaction mixtures
3 2 2
for oxidized substrate. Similar increases in absorbance in the 400–500
nm region of the final spectra were observed for 2 and 3, as well (Fig. S3-
6
). Analysis of the product solutions by gas chromatography-mass
spectrometry (GC–MS) established the oxidation of both substrates by
1
–3. In the case of DHA, anthraquinone, anthracene, and anthrone were
identified as products, while benzene was obtained as the major product
of CHD oxidation. Similar yields were obtained for all three complexes
(Table 4), despite the variations in the ligand architecture. The reactivity
Fig. 3. Reaction of 1 with 10 eq. H
2 2 3
O and 10 eq. NEt in MeCN monitored for
6
h via electronic absorption spectroscopy. Optical path length 1 cm.
of 1–3 toward NEt
3 2 2
/H O , CHD, and DHA was consistent with the pre-
viously reported reactivity of copper complexes supported by other
bispicen-type ligands in which computational studies suggested the
optical band at 620 nm and formation of the feature around 634 nm.
Treatment of 3 with 10 eq. NEt /H elicited similar spectral changes
+
3
2
O
2
feasibility of a [CuO] intermediate as the reactive intermediate
to those observed for 1 (Fig. S2). As observed with other known copper
responsible for CHD and DHA oxidation [25]. This similarity in reac-
+
complexes mimicking peroxide shunt chemistry, the spectral changes
tivity led us to further investigate the electronic structure of the [CuO]
observed for 1–3 were dependent on the presence of both NEt
3
and H
2
O
2
species generated from 1 to 3 to better understand their reactivity.
[
25,70]. From this we infer the formation of at least one new species in
solution upon addition of H
.3. C–H bond activation
Having previously observed similar reactivity towards NEt
2
O
2
and NEt
3
.
+
3
.4. Electronic structure of [LCuO]
+
Computation of the electronic structure of [CuO] species proves
3
somewhat challenging due to its multiconfigurational nature. As a single
determinant theory, Kohn-Sham (KS) DFT is not sufficient for the study
of systems not well described by a single Slater determinant [71,72].
Multiconfigurational approaches such as the complete active space self-
consistent field (CASSCF) method and multireference second-order
perturbation theory (CASPT2) have been applied to the problem at
hand in a related system to overcome these limitations inherent to KS
DFT [24]. Here, we consider an analogous approach in which second-
order N-electron valence perturbation theory (NEVPT2) is applied to
/H
3 2
O
2
with related complexes [25], we were curious whether these complexes
would also be capable of oxidizing exogenous hydrocarbon substrates.
The reactivity of 1–3 toward 1,4-cyclohexadiene (CHD) and 9,10-dihy-
droanthracene (DHA) in the presence of NEt
explored spectroscopically. Treatment of 1 with 10 eq. NEt
presence of 40 eq. of CHD or DHA resulted in final absorption spectra
Fig. 4) that lacked a well-defined optical band due to increased
3
2
/H O
2
was similarly
3
2 2
/H O in the
(
4

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
II
the CASSCF wavefunction to obtain corrections to the energy.
electronic structure does not rigidly conform to a simple Cu -oxyl pic-
Dioxygen may be considered as a test case for the CASSCF/NEVPT2
method for which the CASSCF/CASPT2 method has already been
applied and experimental data is available [24], allowing for parallels to
be drawn between the well-understood electronic structure of diatomic
molecules and the [CuO] core of the more complex polyatomic mole-
ture as expected. Rather, the MOs occupied by the two radicals are more
covalent in nature, complicating the analysis. Similar electronic struc-
+
+
tures were predicted for [2-O] and [3-O] with an active space of 12
electrons in 12 orbitals (Figs. S8–9, Tables S6-7). The CAS(12,12) results
are best described as existing on a continuum between the extremes of a
II
I
cules reported here. Diatomic O
2
possesses five low-lying states that
Cu -oxyl formulation and a Cu -bound biradicaloid oxene, somewhat to
our surprise. This is not, however, an unprecedented result for first-row
transition metals and intermediates with similar electronic structures
3
ꢀ
have been rigorously examined spectroscopically: the ground state Σ ,
g
1
1
+
3
+
3
ꢀ
u
and the four excited states Δg, Σ , Σ , and Σ [73]. We first examine
g
u
II
have been proposed as in the case of a biradicaloid Co -oxene species
the transition between the 3
Σ
ꢀ
and 1Δg states, separated by 0.98 eV
g
[
78], and even isolated and studied spectroscopically in the case of a
ꢀ
1
(
22.6 kcal mol ) [24,74]. A singlet–triplet gap of 1.00 eV (23.13 kcal
mol ) was predicted by the CASSCF/NEVPT2 method employing a full-
I
similar S = 1 Cu -nitrene intermediate [79].
ꢀ 1
+
Without any spectroscopic data on [CuO] compounds available in
the literature to calibrate our understanding of the CAS(12,12)/NEVPT2
results, we further extended our computational investigation to probe
the sensitivity of the results to active space composition and computa-
tional procedure. Alternative active spaces consisting of 14 electrons in
8 orbitals were constructed from MOs derived from the five Cu 3d or-
bitals and the three O 2p orbitals. The occupation of the resulting or-
bitals from this step were inspected and those with an occupation less
than 1.98 and greater than 0.02 were used as reference spaces for sub-
sequent Spectroscopy ORiented Configuration Interaction (SORCI) cal-
culations (Figs. S10–12). The sufficiency of the reference space was
evaluated by ensuring that the weight of the reference configuration in
each CI state was greater than 0.90 (Tables S8-10). In each case, a triplet
ground state was predicted below a low-lying open shell singlet state. In
valence active space, reaching the desired chemical accuracy of ± 1 kcal
ꢀ 1
1
mol [75]. The Δg state is well described by a single configuration.
Considering additional excited states, the CASSCF/NEVPT2 method
correctly predicts a multiconfigurational state located 1.65 eV (38.00
kcal/mol) above the ground state, consistent with the experimentally
observed singlet biradical 1
Σ
+
state located 1.63 eV (37.51 kcal/mol)
g
3
ꢀ
above the Σ state [76,77]. This is an important test case for the study
g
of the electronic structure of [CuO]+ species because the formally CuIII-
1
oxo formulation is a closed-shell singlet, as is the Δg excited state of O
2
.
However, previous theoretical investigations have identified a low-lying
singlet biradical excited state in analogy to the 1
Σ
+
excited state of O
g
2
+
for [CuO] species similar to the ones described here [24], and as such
the ability to distinguish between these three cases is necessary to
+
the case of [1-O] , a multiconfigurational ground state derived from a
+
correctly identify the ground state of the [CuO] species generated from
I
what is possibly best described as a Cu -oxene (CI coefficient 0.39)
1
to 3.
Active spaces of 12 electrons in 12 orbitals were first constructed
from MOs derived from the Cu 3d orbitals, the O 2p orbitals, and the Cu
II
configuration and two Cu -oxyl configurations (CI coefficients 0.37 and
+
0
.15, respectively) (Fig. 5, Table S8). The ground state of [2-O] was
well-described by a single configuration (CI coefficient 0.75) (Table S9)
4
d orbitals (Figs. S7–9). Applying the CASSCF/NEVPT2 method to [1-
II
and consistent with the Cu -oxyl formulation. A multiconfigurational
+
O] , an S = 1 ground state is predicted with a low-lying S = 0 excited
+
ground state was predicted for [3-O] , however its primary configura-
ꢀ 1
state separated by 0.215 eV (4.97 kcal mol ) (Table S5). The triplet
ground state is well-described by a single configuration, however, the
II
tion is well-described as a Cu -oxyl (CI coefficient 0.63) with some
Fig. 5. Subspace of the 10-electron, 6-orbital reference space used to depict leading configurations of the S = 1 ground state of [1-O]+ generated from a SORCI
calculation. Surface plots of the average atomic natural orbitals are displayed at an isovalue of 0.03 [a.u].
5

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
+
+
triplet ground state, O-radical character – suggest that [1-O] , [2-O] ,
+
and [3-O] should be capable of performing substrate epoxidation. This
is curious as reports of epoxidation catalyzed by mononuclear copper
complexes in the literature are extremely rare.
3
.5. Olefin epoxidation
To verify that 1–3 could perform O-atom transfer to alkene sub-
strates, we explored their reactivity toward styrene and cyclooctene as
3 2 2
we did for CHD and DHA. Treatment of 1 with 10 eq. NEt /H O in the
presence of 40 eq. of styrene or cyclooctene resulted in final absorption
spectra (Fig. 6) with increased absorbance in the 400–500 nm region
compared to treatment with only NEt and H O (Fig. 3). Treatment of 2
3 2 2
with 10 eq. NEt
in noticeable changes to the final absorption spectrum when compared
to treatment with only NEt /H , though this was not the case in the
3 2 2
/H O in the presence of 40 eq. of styrene did not result
3
2 2
O
presence of 40 eq. of cyclooctene (Figs. S13–14). Complex 3 behaved
similarly to complex 1 (Figs. S15–16). Analysis of the product solutions
by GC–MS confirmed the presence of cyclooctene oxide (Table 4).
Benzaldehyde, rather than styrene oxide, was observed – but it is
important to note that styrene oxide has been reported to be further
oxidized to benzaldehyde under similar reaction conditions and thus its
initial formation cannot be rejected [90]. Treatment of cyclooctene with
2 2 3
Fig. 6. Left: Reaction of 1 with 10 eq. H O , 10 eq. NEt , and 40 eq. styrene in
MeCN monitored for 6 h via electronic absorption spectroscopy. Right: Reaction
of 1 with 10 eq. H , 10 eq. NEt , and 40 eq. cyclooctene in MeCN monitored
2
O
2
3
for 6 h via electronic absorption spectroscopy. Optical path length 1 cm.
I
admixture of the Cu -oxene configuration (CI coefficient 0.16)
NEt
formation of cyclooctene oxide, but in a lower yield than observed with
–3, suggesting that the ligand supporting the copper center does play a
role in modulating its reactivity.
3 2 2
/H O in the presence of copper(II) perchlorate did result in some
(
Table S10). The results, though unexpected, were fairly robust to
changes in active space and even computational method. Interestingly,
we did not identify any state in which the oxidation state could be
1
III
unambiguously assigned as Cu .
As both methods predicted either a multiconfigurational or open
4
. Summary
shell singlet excited state, we calculated the singlet–triplet energy gap
(
(
ΔE) for each intermediate within the framework of broken-symmetry
A detailed investigation of the reactivity of three mononuclear CuII
BS) DFT at the B3LYP, M06, and B97X levels of theory. All methods
ω
complexes supported by [N4] polypyridyl ligands using a combined
experimental and theoretical approach is presented herein. Consistent
+
+
+
conclude that the ground states of [1-O] , [2-O] , and [3-O] possess
spin angular momentum S = 1 and the calculated ΔE values are
II
with previously reported Cu -bispicen complexes, 1–3 were capable of
generally of the same order of magnitude (Table 3) except for in the case
3 2 2
C H bond activation in the presence of NEt and H O (Fig. 7). A
–
+
of [3-O] when ΔE was calculated with the
the amount by which the singlet state was predicted to be lower in en-
ω
B97X functional. However,
computational investigation into the electronic structure of the pro-
+
posed [CuO] reactive intermediates revealed a complex triplet ground
+
ergy for [3-O] with the
ω
B97X functional seems to be within the un-
state. Mapping the spatial distribution of the radicals localized to the
certainty of the functional’s general performance [48]. All of the
computational methods considered here generally converge to same
conclusion: two radicals are localized to the [CuO] core of the ground
+
[
CuO] core of the proposed [CuO] intermediates onto a single electron
configuration proved challenging. The predicted electronic structures
II
were generally consistent with a Cu -oxyl species, noting the corre-
+
+
+
state of [1-O] , [2-O] , and [3-O] with spin angular momentum S = 1.
I
sponding Cu -oxene species as a possibly significant resonance structure.
The analogous high-valent Fe- and Mn-oxo species are powerful
+
Correlating the electronic structure of the proposed [CuO] in-
oxidants capable of C H bond activation and functionalization, but in
–
some cases have also been reported to perform O-atom transfer to olefins
termediates to those of analogous high-valent metal-oxo species capable
of performing substrate epoxidation, we predicted that 1–3, too, should
be capable of substrate epoxidation when treated with NEt /H O and
3 2 2
to generate epoxides. Cytochrome P450, for example, catalyzes the
IV
epoxidation of alkene substrates with an Fe -oxo porphyrin cation-
alkenes. Cyclooctene oxide was obtained as the product upon treatment
/H in the presence of cyclooctene (Fig. 7). These
radical species [80–83]. Indeed, synthetic iron and manganese por-
phyrins have been extensively studied for their use as epoxidation cat-
alysts [22,83–87]. However, in some of these reports, the ability to
perform epoxidations has been attributed to the oxyl or oxene character
of 1–3 with NEt
3
2 2
O
results represent one of the first reports of epoxidation performed by
mononuclear copper complexes, to our knowledge, warranting further
investigation into the complex electronic structure and diverse reac-
–
described in different terms over the last few decades - of the active
+
tivity of high-valent [CuO] species.
oxidant [80,88,89]. Whether referred to as triplet character, oxenoid
character, triplet oxenoid character, or oxyl character, nonzero spin
density at the metal-bound oxygen has been cited as necessary for the
observed reactivity. If we take this as an assumption, aspects of the
CRediT authorship contribution statement
Thomas M. Khazanov: Conceptualization, Methodology, Investi-
gation, Formal analysis, Visualization. Niharika Krishna Botcha:
Investigation, Formal analysis, Visualization. Sandugash Yergesh-
bayeva: Investigation, Resources. Michael Shatruk: Investigation, Re-
sources, Supervision, Funding acquisition. Anusree Mukherjee:
Conceptualization, Methodology, Supervision, Project administration,
Funding acquisition.
+
calculated electronic structure of the proposed [CuO] intermediates –
Table 3
+
+
Singlet-triplet energy gaps (ΔE = Etriplet – Esinglet) [eV] for [1-O] , [2-O] , and
+
[
3-O] .
CAS(12,12)/NEVPT2
SORCI (10,6)
B3LYP
M06
ωB97X
+
+
+
[1-O]
[2-O]
[3-O]
ꢀ 0.215
ꢀ 0.230
ꢀ 0.219
ꢀ 0.134
ꢀ 0.270
ꢀ 0.224
ꢀ 0.158
ꢀ 0.158
ꢀ 0.152
ꢀ 0.245
ꢀ 0.214
ꢀ 0.239
ꢀ 0.163
ꢀ 0.153
0.033
Declaration of Competing Interest
The authors declare that they have no known competing financial
6

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
Table 4
Reaction mixture product analysis.
Complex
Benzene
Anthraquinone
Anthracene
Anthrone
Benzaldehyde
Styrene Oxide
Cyclooctene Oxide
1
2
3
47 ± 4%
52 ± 7%
52 ± 4%
0%
20 ± 0%
21 ± 0%
21 ± 1%
0%
19 ± 1%
19 ± 0%
20 ± 0%
0%
3 ± 0%
3 ± 0%
4 ± 0%
0%
8 ± 1%
10 ± 1%
9 ± 1%
0%
0%
16 ± 2%
15 ± 1%
18 ± 1%
8 ± 1%
1 ± 0%
0%
Cu(ClO
No Cu
4
)
2
0%
3 ± 0%
2 ± 0%
2 ± 0%
0%
0%
0%
1 ± 0%
methane monooxygenase, Nat Commun 10 (1) (2019) 2675, https://doi.org/
0.1038/s41467-019-10590-6.
1
[
10] T. Kamachi, N. Kihara, Y. Shiota, K. Yoshizawa, Computational exploration of the
catalytic mechanism of dopamine β-monooxygenase: modeling of its mononuclear
copper active sites, Inorg. Chem. 44 (12) (2005) 4226–4236, https://doi.org/
1
0.1021/ic048477p.
[
[
[
11] K. Yoshizawa, N. Kihara, T. Kamachi, Y. Shiota, Catalytic mechanism of dopamine
β-monooxygenase mediated by Cu(III)ꢀ oxo, Inorg. Chem. 45 (7) (2006)
3
034–3041, https://doi.org/10.1021/ic0521168.
12] A. Decker, E.I. Solomon, Dioxygen activation by copper, heme and non-heme iron
enzymes: comparison of electronic structures and reactivities, Curr. Opin. Chem.
Biol. 9 (2) (2005) 152–163, https://doi.org/10.1016/j.cbpa.2005.02.012.
13] K. Rudzka, D.M. Moreno, B. Eipper, R. Mains, D.A. Estrin, L.M. Amzel,
Fig. 7. Summary of the proposed reactivity of 1–3.
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Coordination of peroxide to the CuM center of peptidylglycine
monooxygenase (PHM): structural and computational study, J. Biol. Inorg. Chem.
α
-hydroxylating
1
8 (2) (2013) 223–232, https://doi.org/10.1007/s00775-012-0967-z.
[
[
[
14] S. Kim, J. Ståhlberg, M. Sandgren, R.S. Paton, G.T. Beckham, Quantum Mechanical
Calculations Suggest That Lytic Polysaccharide Monooxygenases Use a Copper-
Oxyl, Oxygen-Rebound Mechanism, Proc Natl Acad Sci U S A 111 (1) (2014)
Acknowledgements
1
49–154, https://doi.org/10.1073/pnas.1316609111.
This work was made possible in part by a grant of high-performance
computing resources and technical support from the Alabama Super-
computer Authority. T.K. graciously thanks the Lancaster research
group at Cornell University for use of computing resources. M.S. and Y.S.
acknowledge support by the National Science Foundation (award CHE-
15] L. Cao, O. Caldararu, A.C. Rosenzweig, U. Ryde, Quantum refinement does not
support dinuclear copper sites in crystal structures of particulate methane
monooxygenase, Angew. Chem. Int. Ed. 57 (1) (2018) 162–166, https://doi.org/
1
0.1002/anie.201708977.
16] K. Yoshizawa, Y. Shiota, Conversion of methane to methanol at the mononuclear
and dinuclear copper sites of particulate methane monooxygenase (PMMO): a DFT
and QM/MM study, J. Am. Chem. Soc. 128 (30) (2006) 9873–9881, https://doi.
org/10.1021/ja061604r.
17] S.T. Kleespies, W.N. Oloo, A. Mukherjee, L. Que, C-H bond cleavage by bioinspired
nonheme oxoiron(IV) complexes, including hydroxylation of n-butane, Inorg.
Chem. 54 (11) (2015) 5053–5064, https://doi.org/10.1021/ic502786y.
18] A.N. Biswas, M. Puri, K.K. Meier, W.N. Oloo, G.T. Rohde, E.L. Bominaar, E. Münck,
L. Que, Modeling TauD-J: a high-spin nonheme oxoiron(IV) complex with high
reactivity toward C-H bonds, J. Am. Chem. Soc. 137 (7) (2015) 2428–2431,
https://doi.org/10.1021/ja511757j.
19] C. Krebs, D. Galoni ´c Fujimori, C.T. Walsh, J.M. Bollinger, Non-Heme Fe(IV)–Oxo
intermediates, Acc. Chem. Res. 40 (7) (2007) 484–492, https://doi.org/10.1021/
ar700066p.
[20] J. Hohenberger, K. Ray, K. Meyer, The biology and chemistry of high-valent iron-
oxo and iron-nitrido complexes, Nat Commun 3 (1) (2012) 720, https://doi.org/
1
955754). The Rigaku Synergy-S single-crystal X-ray diffractometer
used for crystallographic work was acquired through the NSF MRI
program (award CHE-1828362 to M.S.). T.K., N.K.B., and A.M.
acknowledge support from the University of Alabama in Huntsville for
conducting this research work.
[
[
Appendix A. Supplementary data
[
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ica.2020.120168.
1
0.1038/ncomms1718.
References
[
21] M. Balamurugan, N. Saravanan, H. Ha, Y.H. Lee, K.T. Nam, Involvement of high-
valent manganese-oxo intermediates in oxidation reactions: realisation in nature,
nano and molecular systems, Nano Convergence 5 (1) (2018) 18, https://doi.org/
10.1186/s40580-018-0150-5.
[
1] E.I. Solomon, D.E. Heppner, E.M. Johnston, J.W. Ginsbach, J. Cirera, M. Qayyum,
M.T. Kieber-Emmons, C.H. Kjaergaard, R.G. Hadt, L. Tian, Copper active sites in
biology, Chem. Rev. 114 (7) (2014) 3659–3853, https://doi.org/10.1021/
cr400327t.
[22] M. Guo, T. Corona, K. Ray, W. Nam, Heme and nonheme high-valent iron and
manganese oxo cores in biological and abiological oxidation reactions, ACS Cent.
Sci. 5 (1) (2019) 13–28, https://doi.org/10.1021/acscentsci.8b00698.
[
[
2] J.J. Liu, D.E. Diaz, D.A. Quist, K.D. Karlin, Copper(I)-dioxygen adducts and copper
enzyme mechanisms, Isr. J. Chem. 56 (2016) 9–10, https://doi.org/10.1002/
ijch.201600025.
3] C.E. Elwell, N.L. Gagnon, B.D. Neisen, D. Dhar, A.D. Spaeth, G.M. Yee, W.
B. Tolman, Copper-oxygen complexes revisited: structures, spectroscopy, and
reactivity, Chem. Rev. 117 (3) (2017) 2059–2107, https://doi.org/10.1021/acs.
chemrev.6b00636.
[23] R.L. Halbach, D. Gygi, E.D. Bloch, B.L. Anderson, D.G. Nocera, Structurally
characterized terminal manganese(IV) oxo tris(Alkoxide) complex, Chem. Sci. 9
(19) (2018) 4524–4528, https://doi.org/10.1039/C8SC01164H.
[24] S.M. Huber, M.Z. Ertem, F. Aquilante, L. Gagliardi, W.B. Tolman, C.J. Cramer,
Generating CuII–Oxyl/CuIII–Oxo species from CuI– -ketocarboxylate complexes
α
and O2. In silico studies on ligand effects and C H-activation reactivity, Chem. – A
Eur. J. 15 (19) (2009) 4886–4895, https://doi.org/10.1002/chem.200802338.
[25] N. Singh, N.K. Botcha, T.M. Jones, M.Z. Ertem, J. Niklas, E.R. Farquhar, O.
G. Poluektov, A. Mukherjee, Reactivity of bio-inspired Cu(II) (N2/Py2) complexes
with peroxide at room temperature, J. Inorg. Biochem. 197 (2019), 110674,
https://doi.org/10.1016/j.jinorgbio.2019.03.014.
[
[
4] C. Citek, S. Herres-Pawlis, T.D.P. Stack, Low temperature syntheses and reactivity
of Cu2O2 active-site models, Acc. Chem. Res. 48 (8) (2015) 2424–2433, https://
doi.org/10.1021/acs.accounts.5b00220.
5] R. Trammell, K. Rajabimoghadam, I. Garcia-Bosch, Copper-promoted
2
functionalization of organic molecules: from biologically relevant Cu/O model
systems to organometallic transformations, Chem. Rev. 119 (4) (2019) 2954–3031,
https://doi.org/10.1021/acs.chemrev.8b00368.
[26] A.W. Munro, K.J. McLean, J.L. Grant, T.M. Makris, Structure and function of the
cytochrome P450 peroxygenase enzymes, Biochem. Soc. Trans. 46 (1) (2018)
183–196, https://doi.org/10.1042/BST20170218.
[
[
6] E.I. Solomon, P. Chen, M. Metz, S.-K. Lee, A.E. Palmer, Oxygen binding, activation,
and reduction to water by copper proteins, Angew. Chem. Int. Ed. 21 (2001).
7] J.Y. Lee, K.D. Karlin, Elaboration of copper-oxygen mediated C-H activation
chemistry in consideration of future fuel and feedstock generation, Curr. Opin.
Chem. Biol. 25 (2015) 184–193.
[27] J.P.T. Zaragoza, T.H. Yosca, M.A. Siegler, P. Mo ¨e nne-Loccoz, M.T. Green, D.
P. Goldberg, Direct observation of oxygen rebound with an iron-hydroxide
complex, J. Am. Chem. Soc. 139 (39) (2017) 13640–13643, https://doi.org/
10.1021/jacs.7b07979.
[
[
8] M.O. Ross, F. MacMillan, J. Wang, A. Nisthal, T.J. Lawton, B.D. Olafson, S.L. Mayo,
A.C. Rosenzweig, B.M. Hoffman, Particulate methane monooxygenase contains
only mononuclear copper centers, Science 364 (6440) (2019) 566–570, https://
doi.org/10.1126/science.aav2572.
9] S.Y. Ro, L.F. Schachner, C.W. Koo, R. Purohit, J.P. Remis, G.E. Kenney, B.W. Liauw,
P.M. Thomas, S.M. Patrie, N.L. Kelleher, A.C. Rosenzweig, Native top-down mass
spectrometry provides insights into the copper centers of membrane-bound
[28] B.J. Pella, J. Niklas, O.G. Poluektov, A. Mukherjee, Effects of denticity and ligand
rigidity on reactivity of copper complexes with cumyl hydroperoxide, Inorg. Chim.
Acta 483 (2018) 71–78, https://doi.org/10.1016/j.ica.2018.07.035.
[29] P.H.A. Kankanamalage, D.M. Ekanayake, N. Singh, A.C.P. Morais, S. de Mazumder,
C.N. Verani, A. Mukherjee, M. Lanznaster, Effect of ligand substituents on nickel
and copper [N4] complexes: electronic and redox behavior, and reactivity towards
protons, New J. Chem. 43 (32) (2019) 12795–12803, https://doi.org/10.1039/
C9NJ01283D.
7

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
[
[
[
[
30] Software update: the ORCA program system, version 4.0 – Neese – 2018 – WIREs
Computational Molecular Science – Wiley Online Library https://onlinelibrary.
wiley.com/doi/abs/10.1002/wcms.1327 (accessed Jan 10, 2020).
[58] S.L. Esarey, J.C. Holland, B.M. Bartlett, Determining the fate of a non-heme iron
oxidation catalyst under illumination, oxygen, and acid, Inorg. Chem. 55 (21)
(2016) 11040–11049, https://doi.org/10.1021/acs.inorgchem.6b01538.
[59] S.J. Brudenell, L. Spiccia, E.R.T. Tiekink, Binuclear copper(II) complexes of bis
(pentadentate) ligands derived from alkyl-bridged Bis(1,4,7-Triazacyclonane)
macrocycles, Inorg. Chem. 35 (7) (1996) 1974–1979, https://doi.org/10.1021/
ic951146f.
[60] S.S. Massoud, F.R. Louka, R.N. David, M.J. Dartez, Q.L. Nguyn, N.J. Labry, R.
C. Fischer, F.A. Mautner, Five-coordinate metal(II) complexes based pyrazolyl
ligands, Polyhedron 90 (2015) 258–265, https://doi.org/10.1016/j.
poly.2015.02.014.
[61] S.S. Massoud, F.R. Louka, L.T. Nguyen, M. Mikuriya, J.H. Albering, F.A. Mautner,
Structural and magnetic characterization of 1-D complexes constructed from
pyrazole-3,5-dicarboxylate bridging multi copper(II) centers, Inorg. Chim. Acta
366 (1) (2011) 394–398, https://doi.org/10.1016/j.ica.2010.11.014.
[62] G.A. McLachlan, G.D. Fallon, R.L. Martin, L. Spiccia, Synthesis, structure and
properties of five-coordinate copper(II) complexes of pentadentate ligands with
pyridyl pendant arms, Inorg. Chem. 34 (1) (1995) 254–261, https://doi.org/
10.1021/ic00105a041.
31] A.D. Becke, Completely numerical calculations on diatomic molecules in the local-
density approximation, Phys. Rev. A 33 (4) (1986) 2786–2788, https://doi.org/
1
0.1103/PhysRevA.33.2786.
32] J.P. Perdew, Density-functional approximation for the correlation energy of the
inhomogeneous electron gas, Phys. Rev. B 33 (12) (1986) 8822–8824, https://doi.
org/10.1103/PhysRevB.33.8822.
33] F. Weigend, R. Ahlrichs, Balanced basis sets of split valence, triple zeta valence and
quadruple zeta valence quality for H to Rn: design and assessment of accuracy,
Phys. Chem. Chem. Phys. 7 (18) (2005) 3297–3305, https://doi.org/10.1039/
B508541A.
[
[
[
[
34] A. Sch ¨a fer, C. Huber, R. Ahlrichs, Fully optimized contracted gaussian basis sets of
triple zeta valence quality for atoms Li to Kr, J. Chem. Phys. 100 (8) (1994)
5
829–5835, https://doi.org/10.1063/1.467146.
35] A. Sch ¨a fer, H. Horn, R. Ahlrichs, Fully optimized contracted gaussian basis sets for
atoms Li to Kr, J. Chem. Phys. 97 (4) (1992) 2571–2577, https://doi.org/10.1063/
1
.463096.
36] S. Grimme, S. Ehrlich, L. Goerigk, Effect of the damping function in dispersion
corrected density functional theory, J. Comput. Chem. 32 (7) (2011) 1456–1465,
https://doi.org/10.1002/jcc.21759.
37] S. Grimme, J. Antony, S. Ehrlich, H. Krieg, A consistent and accurate ab initio
parametrization of density functional dispersion correction (DFT-D) for the 94
elements H-Pu, J. Chem. Phys. 132 (15) (2010), 154104, https://doi.org/10.1063/
[63] N. Singh, J. Niklas, O. Poluektov, K.M. Van Heuvelen, A. Mukherjee, Mononuclear
nickel (II) and copper (II) coordination complexes supported by bispicen ligand
derivatives: experimental and computational studies, Inorg. Chim. Acta 455 (2017)
221–230, https://doi.org/10.1016/j.ica.2016.09.001.
[64] J.N. Harvey, On the accuracy of density functional theory in transition metal
chemistry, Annu. Rep. Prog. Chem., Sect. C: Phys. Chem. 102 (2006) 203, https://
doi.org/10.1039/b419105f.
1
.3382344.
[
38] F. Neese, F. Wennmohs, A. Hansen, Becker U. Efficient, Approximate and parallel
hartree-fock and hybrid DFT calculations. A ‘chain-of-spheres’ algorithm for the
hartree-fock exchange, Chem. Phys. 356 (1) (2009) 98–109, https://doi.org/
[65] R.R. Jacobson, Zoltan Tyeklar, K.D. Karlin, Jon Zubieta, Fluoride as a terminal and
bridging ligand for copper: isolation and x-ray crystallographic characterization of
copper monomeric and dimeric complexes [CuII(TMPA)F]Nn+ (n = 1 or 2; TMPA
= Tris[(2-Pyridyl)Methyl]Amine), Inorg. Chem. 30 (9) (1991) 2035–2040, https://
doi.org/10.1021/ic00009a017.
1
0.1016/j.chemphys.2008.10.036.
[
[
[
39] F. Weigend, Accurate coulomb-fitting basis sets for H to Rn, Phys. Chem. Chem.
Phys. 8 (9) (2006) 1057–1065, https://doi.org/10.1039/b515623h.
[66] B.J. Hathaway, The correlation of the electronic properties and stereochemistry of
mononuclear CuN 4–6 chromophores, J. Chem. Soc., Dalton Trans. 12 (1972)
1196–1199, https://doi.org/10.1039/DT9720001196.
40] A.D. Becke, Density-functional thermochemistry. III. The role of exact exchange,
J. Chem. Phys. 98 (7) (1993) 5648–5652, https://doi.org/10.1063/1.464913.
41] C. Lee, W. Yang, R.G. Parr, Development of the Colle-Salvetti correlation-energy
formula into a functional of the electron density, Phys. Rev. B 37 (2) (1988)
[67] A. Kaur, T.G. Ribelli, K. Schr o¨ der, K. Matyjaszewski, T. Pintauer, Properties and
ATRP activity of copper complexes with substituted Tris(2-Pyridylmethyl)amine-
based ligands, Inorg. Chem. 54 (4) (2015) 1474–1486, https://doi.org/10.1021/
ic502484s.
7
85–789, https://doi.org/10.1103/PhysRevB.37.785.
[
[
[
42] E. Lenthe, E.J. van Baerends, J.G. Snijders, Relativistic regular two-component
hamiltonians, J. Chem. Phys. 99 (6) (1993) 4597–4610, https://doi.org/10.1063/
[68] N. Hall, M. Orio, M. Gennari, C. Wills, F. Molton, C. Philouze, G.B. Jameson, M.
A. Halcrow, A.G. Blackman, C. Duboc, Multifrequency Cw-EPR and DFT studies of
an apparent compressed octahedral Cu(II) complex, Inorg. Chem. 55 (4) (2016)
1497–1504, https://doi.org/10.1021/acs.inorgchem.5b02287.
1
.466059.
43] E. van Lenthe, E.J. Baerends, J.G. Snijders, Relativistic total energy using regular
approximations, J. Chem. Phys. 101 (11) (1994) 9783–9792, https://doi.org/
1
0.1063/1.467943.
[69] E. Garribba, G. Micera, The determination of the geometry of Cu(II) complexes: an
EPR spectroscopy experiment, J. Chem. Educ. 83 (8) (2006) 1229, https://doi.org/
10.1021/ed083p1229.
[70] A. Kunishita, M. Kubo, H. Ishimaru, T. Ogura, H. Sugimoto, S. Itoh, H2O2-
reactivity of copper(II) complexes supported by Tris[(Pyridin-2-Yl)Methyl]amine
ligands with 6-phenyl substituents, Inorg. Chem. 47 (24) (2008) 12032–12039,
https://doi.org/10.1021/ic801568g.
[71] S. Ye, G. Xue, I. Krivokapic, T. Petrenko, E. Bill, L. Que Jr, F. Neese, Magnetic
circular dichroism and computational study of mononuclear and dinuclear iron(IV)
Complexes, Chem. Sci. 6 (5) (2015) 2909–2921, https://doi.org/10.1039/
C4SC03268C.
[72] Christopher J Kramer. Essentials of Computational Chemistry: Theories and
Models, Second Edition.; John Wiley & Sons.
44] C. van Wüllen, Molecular density functional calculations in the regular relativistic
approximation: method, application to coinage metal diatomics, hydrides,
fluorides and chlorides, and comparison with first-order relativistic calculations,
J. Chem. Phys. 109 (2) (1998) 392–399, https://doi.org/10.1063/1.476576.
45] G.L. Stoychev, A.A. Auer, F. Neese, Automatic generation of auxiliary basis sets,
J. Chem. Theory Comput. 13 (2) (2017) 554–562, https://doi.org/10.1021/acs.
jctc.6b01041.
[
[
[
46] S. Grimme, A simplified Tamm-Dancoff density functional approach for the
electronic excitation spectra of very large molecules, J. Chem. Phys. 138 (24)
(
2013), 244104, https://doi.org/10.1063/1.4811331.
47] Y. Zhao, D.G. Truhlar, The M06 suite of density functionals for main group
thermochemistry, thermochemical kinetics, noncovalent interactions, excited
states, and transition elements: two new functionals and systematic testing of four
M06-class functionals and 12 other functionals, Theor. Chem. Account 120 (1)
[73] Moffitt, W. The Electronic Structure of the Oxygen Molecule. Proceedings of the
Royal Society of London. Series A, Containing Papers of a Mathematical and
Physical Character 1951, 210, 224–245.
(
2008) 215–241, https://doi.org/10.1007/s00214-007-0310-x.
[
[
[
[
48] J.-D. Chai, M. Head-Gordon, Systematic optimization of long-range corrected
hybrid density functionals, J. Chem. Phys. 128 (8) (2008), 084106, https://doi.
org/10.1063/1.2834918.
[74] W. Orellana, A. da Silva, A. Fazzio, O2 diffusion in SiO2: triplet versus singlet,
Phys. Rev. Lett. 87 (15) (2001), 155901, https://doi.org/10.1103/
PhysRevLett.87.155901.
49] B.O. Roos, P.R. Taylor, P.E.M. Sigbahn, A complete active space SCF method
[75] F. Neese, M. Atanasov, G. Bistoni, D. Maganas, S. Ye, Chemistry and quantum
mechanics in 2019: give us insight and numbers, J. Am. Chem. Soc. 141 (7) (2019)
2814–2824, https://doi.org/10.1021/jacs.8b13313.
(
(
CASSCF) using a density matrix formulated super-CI approach, Chem. Phys. 48 (2)
1980) 157–173, https://doi.org/10.1016/0301-0104(80)80045-0.
50] C. Angeli, R. Cimiraglia, S. Evangelisti, T. Leininger, J.-P. Malrieu, Introduction of
N-electron valence states for multireference perturbation theory, J. Chem. Phys.
[76] S. Jockusch, N.J. Turro, E.K. Thompson, M. Gouterman, J.B. Callis, G.E. Khalil,
Singlet molecular oxygen by direct excitation, Photochem. Photobiol. Sci. 7 (2)
(2008) 235–239, https://doi.org/10.1039/B714286B.
1
14 (23) (2001) 10252–10264, https://doi.org/10.1063/1.1361246.
51] C. Angeli, R. Cimiraglia, J.-P. Malrieu, N-electron valence state perturbation
theory: a spinless formulation and an efficient implementation of the strongly
contracted and of the partially contracted variants, J. Chem. Phys. 117 (20) (2002)
[77] C. Schweitzer, R. Schmidt, Physical mechanisms of generation and deactivation of
singlet oxygen, Chem. Rev. 103 (5) (2003) 1685–1758, https://doi.org/10.1021/
cr010371d.
9
138–9153, https://doi.org/10.1063/1.1515317.
[78] D.W. Crandell, S. Ghosh, C.P. Berlinguette, M.H. Baik, How a [Co IV ${^
{\underline{.....}}}$O] 2+ Fragment Oxidizes Water: Involvement of a
Biradicaloid [Co II -(⋅O⋅)] 2+ Species in Forming the O O Bond. ChemSusChem
2015, 8 (5), 844–852. https://doi.org/10.1002/cssc.201403024.
[79] K.M. Carsch, I.M. DiMucci, D.A. Iovan, A. Li, S.-L. Zheng, C.J. Titus, S.J. Lee, K.
D. Irwin, D. Nordlund, K.M. Lancaster, T.A. Betley, Synthesis of a copper-supported
triplet nitrene complex pertinent to copper-catalyzed amination, Science 365
(6458) (2019) 1138–1143, https://doi.org/10.1126/science.aax4423.
[80] D. Ostovic, T.C. Bruice, Mechanism of alkene epoxidation by iron, chromium, and
manganese higher valent oxo-metalloporphyrins, Acc. Chem. Res. 25 (7) (1992)
314–320, https://doi.org/10.1021/ar00019a007.
[
52] F. Neese, A spectroscopy oriented configuration interaction procedure, J. Chem.
Phys. 119 (18) (2003) 9428–9443, https://doi.org/10.1063/1.1615956.
53] CrysAlis, Oxford Diffraction Ltd., Abingdon, England, 2006.
54] SCALE3 ABSPACK – An Oxford Diffraction Program (1.0.4,Gui:1.0.3), Oxford
Diffraction Ltd., Abingdon, England, 2005.
[
[
[
[
55] G.M. Sheldrick, Crystal structure refinement with SHELXL, Acta Crystallogr. C
Struct. Chem. 71 (1) (2015) 3–8, https://doi.org/10.1107/S2053229614024218.
56] O.V. Dolomanov, L.J. Bourhis, R.J. Gildea, J.A.K. Howard, H. Puschmann, OLEX2:
a complete structure solution, refinement and analysis program, J. Appl.
Crystallogr. 42 (2) (2009) 339–341, https://doi.org/10.1107/
S0021889808042726.
[81] J. Rittle, M.T. Green, Cytochrome P450 compound I: capture, characterization, and
C-H bond activation kinetics, Science 330 (6006) (2010) 933–937, https://doi.org/
10.1126/science.1193478.
[
57] M.S. Chen, M.C. White, A predictably selective aliphatic C-H oxidation reaction for
complex molecule synthesis, Science 318 (5851) (2007) 783–787, https://doi.org/
1
0.1126/science.1148597.
[82] D. Kumar, B. Karamzadeh, G.N. Sastry, S.P. de Visser, What factors influence the
rate constant of substrate epoxidation by compound I of cytochrome P450 and
8

T.M. Khazanov et al.
Inorganica Chimica Acta 516 (2021) 120168
analogous iron(IV)-oxo oxidants? J. Am. Chem. Soc. 132 (22) (2010) 7656–7667,
porphyrins with hypochlorite, Proc. Natl. Acad. Sci. 85 (3) (1988) 641–644,
https://doi.org/10.1073/pnas.85.3.641.
https://doi.org/10.1021/ja9106176.
[
[
[
[
[
83] J.T. Groves, M.K. Stern, Synthesis, characterization, and reactivity of
oxomanganese(IV) porphyrin complexes, J. Am. Chem. Soc. 110 (26) (1988)
[88] D. Ricciarelli, Q.M. Phung, L. Belpassi, J.N. Harvey, P. Belanzoni, Understanding
the reactivity of Mn-oxo porphyrins for substrate hydroxylation: theoretical
predictions and experimental evidence reconciled, Inorg. Chem. 58 (11) (2019)
7345–7356, https://doi.org/10.1021/acs.inorgchem.9b00476.
8
628–8638, https://doi.org/10.1021/ja00234a009.
84] R.D. Arasasingham, G.X. He, T.C. Bruice, Mechanism of manganese porphyrin-
catalyzed oxidation of alkenes. Role of manganese(IV)-Oxo species, J. Am. Chem.
Soc. 115 (18) (1993) 7985–7991, https://doi.org/10.1021/ja00071a008.
85] J.T. Groves, M.K. Stern, Olefin epoxidation by manganese (IV) porphyrins:
evidence for two reaction pathways, J. Am. Chem. Soc. 109 (12) (1987)
[89] G.H. Loew, C.J. Kert, L.M. Hjelmeland, R.F. Kirchner, Active site models of
horseradish peroxidase compound I and a cytochrome P-450 analog: electronic
structure and electric field gradients, J. Am. Chem. Soc. 99 (10) (1977)
3534–3536, https://doi.org/10.1021/ja00452a074.
3
812–3814, https://doi.org/10.1021/ja00246a067.
[90] T.A.G. Duarte, A.C. Estrada, M.M.Q. Sim o˜ es, I.C.M.S. Santos, A.M.V. Cavaleiro, M.
G.P.M.S. Neves, J.A.S. Cavaleiro, Homogeneous catalytic oxidation of styrene and
styrene derivatives with hydrogen peroxide in the presence of transition metal-
substituted polyoxotungstates, Catal. Sci. Technol. 5 (1) (2015) 351–363, https://
doi.org/10.1039/C4CY00702F.
86] J.T. Groves, Yoshihito Watanabe, The Mechanism of Olefin Epoxidation by Oxo-
Iron Porphyrins. Direct Observation of an Intermediate, J. Am. Chem. Soc. 108 (3)
(
1986) 507–508, https://doi.org/10.1021/ja00263a026.
87] R.W. Lee, P.C. Nakagaki, P.N. Balasubramanian, T.C. Bruice, Observations and
comments on the mechanism of epoxidation of alkenes by manganese(III)
9