MnIII-Peroxo adduct supported by a new tetradentate ligand shows acid-sensitive aldehyde deformylation reactivity

Article abstract of DOI:10.1039/c8dt02300j

The new tetradentate L⁷BQ ligand (L⁷BQ = 1,4-di(quinoline-8-yl)-1,4-diazepane) has been synthesized and shown to support Mn^II and Mn^III-peroxo complexes. X-ray crystallography of the [Mn^II(L⁷BQ)(OTf)₂] complex shows a monomeric Mn^II center with the L⁷BQ ligand providing four donor nitrogen atoms in the equatorial field, with two triflate ions bound in the axial positions. When this species is treated with H₂O₂ and Et₃N at-40 °C, a Mn^III-peroxo adduct, [Mn^III(O₂)(L⁷BQ)]⁺ is formed. The formation of this new intermediate is supported by a variety of spectroscopic techniques, including electronic absorption, Mn K-edge X-ray absorption and electron paramagnetic resonance methods. Evaluation of extended X-ray absorption fine structure data for [Mn^III(O₂)(L⁷BQ)]⁺ resolved Mn-O bond distances of 1.85 ?, which are on the short end of those previously reported for crystallographically characterized Mn^III-peroxo adducts. An analysis of the X-ray pre-edge region of [Mn^III(O₂)(L⁷BQ)]⁺ revealed a large pre-edge area of 20.8 units. Time-dependent density functional theory computations indicate that the pre-edge intensity is due to Mn 4p-3d mixing caused by geometric distortions from centrosymmetry induced by both the peroxo and L⁷BQ ligands. The reactivity of [Mn^III(O₂)(L⁷BQ)]⁺ towards aldehydes was assessed through reaction with cyclohexanecarboxaldehyde and 2-phenylpropionaldehyde. From these experiments, it was determined that [Mn^III(O₂)(L⁷BQ)]⁺ only reacts with aldehydes in the presence of acid. Specifically, the addition of cyclohexanecarboxylic acid to [Mn^III(O₂)(L⁷BQ)]⁺ converts the Mn^III-peroxo adduct to a new intermediate that could be responsible for the observed aldehyde deformylation activity. These observations underscore the challenges in identifying the reactive metal species in aldehyde deformylation reactions.

Full text of DOI:10.1039/c8dt02300j

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MnIII-Peroxo adduct supported by a new
tetradentate ligand shows acid-sensitive
Cite this: DOI: 10.1039/c8dt02300j
aldehyde deformylation reactivity†
Melissa C. Denler,‡ Gayan B. Wijeratne, §‡ Derek B. Rice, Hannah E. Colmer,¶
Victor W. Day and Timothy A. Jackson
*
The new tetradentate L7BQ ligand (L7BQ = 1,4-di(quinoline-8-yl)-1,4-diazepane) has been synthesized
and shown to support MnII and MnIII-peroxo complexes. X-ray crystallography of the [MnII(L7BQ)(OTf)2]
complex shows a monomeric MnII center with the L7BQ ligand providing four donor nitrogen atoms in
the equatorial field, with two triflate ions bound in the axial positions. When this species is treated with
H2O2 and Et3N at −40 °C, a MnIII-peroxo adduct, [MnIII(O2)(L7BQ)]+ is formed. The formation of this new
intermediate is supported by a variety of spectroscopic techniques, including electronic absorption, Mn
K-edge X-ray absorption and electron paramagnetic resonance methods. Evaluation of extended X-ray
absorption fine structure data for [MnIII(O2)(L7BQ)]+ resolved Mn–O bond distances of 1.85 Å, which are
on the short end of those previously reported for crystallographically characterized MnIII-peroxo adducts.
An analysis of the X-ray pre-edge region of [MnIII(O2)(L7BQ)]+ revealed a large pre-edge area of 20.8 units.
Time-dependent density functional theory computations indicate that the pre-edge intensity is due to Mn
4p–3d mixing caused by geometric distortions from centrosymmetry induced by both the peroxo and
L7BQ ligands. The reactivity of [MnIII(O2)(L7BQ)]+ towards aldehydes was assessed through reaction with
cyclohexanecarboxaldehyde and 2-phenylpropionaldehyde. From these experiments, it was determined
that [MnIII(O2)(L7BQ)]+ only reacts with aldehydes in the presence of acid. Specifically, the addition of
cyclohexanecarboxylic acid to [MnIII(O2)(L7BQ)]+ converts the MnIII-peroxo adduct to a new intermediate
that could be responsible for the observed aldehyde deformylation activity. These observations under-
score the challenges in identifying the reactive metal species in aldehyde deformylation reactions.
Received 4th June 2018,
Accepted 27th August 2018
DOI: 10.1039/c8dt02300j
rsc.li/dalton
level intermediates have also been proposed for the dinuclear
enzymes manganese catalase9 and the manganese-dependent
Introduction
Peroxomanganese(III) adducts have been proposed as inter- version
of
ribonucleotide
reductase
(Mn-RNR).10,11
mediates for several manganese-dependent enzymes, includ- Mechanistic understanding for a majority of these enzymes is
ing manganese superoxide dismutase,1,2 manganese dioxygen- incomplete, which warrants detailed studies of synthetic
ase,3,4 oxalate oxidase5,6 and oxalate decarboxylase.7,8 Peroxo- model systems. To this end, small molecule model complexes
have long served as useful tools in understanding the mecha-
nisms of metalloenzymes.12–14 In addition to these biological
motivations, a better understanding of the structure and reac-
tivity of peroxomanganese(III) intermediates is also of relevance
for synthetic manganese catalysts used in substrate oxidation
reactions.15–21
Solid-state X-ray diffraction structures have been reported
for several peroxo-manganese species, including both side-on
(η2) peroxomanganese(III) adducts,22–28 and end-on (η1) alkyl-
peroxomanganese(III) adducts.29,30 Apart from these, the
majority of peroxomanganese(III) species have been observed
under cryogenic conditions and have been thoroughly charac-
terized using a combination of spectroscopic and compu-
tational methods.31–41 Complementary investigations of the
The University of Kansas, Department of Chemistry and Center for Environmentally
Beneficial Catalysis, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA.
E-mail: taj@ku.edu; Tel: +1 (785) 864-3968
†Electronic supplementary information (ESI) available: Crystal data and struc-
ture refinement, NMR data for ligand and organic substrates, additional spectro-
scopic data for Mn intermediates, DFT-optimized cartesian coordinates,
TD-DFT-calculated spectra. CCDC 1844299. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c8dt02300j
‡The contributions of these authors were of equal merit.
§Current address: The University of Alabama at Birmingham, Department of
Chemistry, Center for Biophysical Sciences and Engineering, 1025 18th Street
South, Birmingham AL 35205, USA.
¶Current address: University of Saint Mary, 4100 S 4th Street, Leavenworth, KS
66048, USA.
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chemical reactivity of peroxomanganese(III) complexes have Me2EBC
is
the
cross-clamped
macrocyclic
ligand
revealed several modes of reactivity, including common decay 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]-hexadecane) with
pathways (such as the formation of dimers), which are sum- [MnII(Cl)2(Me2EBC)], which provided evidence for the for-
marized in Scheme 1.
The ability of peroxomanganese(III) complexes to perform ducts.43 Both of these reactions are presumed to proceed
aldehyde deformylation has been known for some time.42 There through
mation of a mixture of mononuclear MnIV and MnIII pro-
a
μ-peroxodimanganese(II,III) intermediate. Quite
are several reports of MnIII-peroxo adducts that deformylate cyclo- recently, McDonald and co-workers have provided spectro-
hexanecarboxaldehyde (CCA; see Scheme 1, top), although the scopic evidence for a μ-peroxodimanganese(II,III) species sup-
mechanism for deformylation is not fully understood.25,26,32,34,37 ported by the dinucleating ligand HPTB (HPTB = N,N,N′,N′-
Support for nucleophilic attack of the peroxo ligand on the alde- tetrakis(2-(benzimidazolyl))-2-hydroxy-1,3-diaminopropane).44
hyde carbonyl carbon comes from kinetic studies that showed
In contrast to these modes of reactivity that rely on the
faster decay of MnIII-peroxo adducts in the presence of electron- nucleophilicity of the MnIII-peroxo unit, there are several
poor, para-substituted benzaldehydes. Hammett analyses of examples of peroxomanganese(III) adducts acting as hydrogen-
these systems yielded ρ+ values from +1.5 to +2.5.26,32
atom acceptors (Scheme 1, bottom). Borovik and co-workers
The nucleophilicity of MnIII-peroxo adducts is likely also showed that a peroxomanganese(III) adduct supported by a tri-
responsible for a commonly identified decay pathway, where podal ligand with a hydrogen-bonding cavity forms a hybrid
the MnIII-peroxo unit attacks unreacted MnII complex to form MnIII-oxo/hydroxo species after reaction with the hydrogen-
oxo-bridged MnIIIMnIV product (Scheme 1, center). For atom donor diphenylhydrazine.37 More recently, Sastri and co-
example, the peroxomanganese(III) complex, [MnIII(O2)(κ4- workers showed that a MnIII-peroxo supported by an aminopyr-
N4py)]+ (where N4py is the neutral N5 ligand N,N-bis(2-pyridyl- idyl ligand effects the deformylation of 2-phenylpropionalde-
methyl)-N-bis(2-pyridyl)methylamine) was observed to convert hyde (PPA) by a hydrogen-atom transfer mechanism.45 This
to a bis(μ-oxo)dimanganese(III,IV) complex upon addition of alternate mechanism for deformylation was supported by the
[MnII(N4py)(OTf)]+.35 More recently, we have reported spectro- observation of an H/D kinetic isotope effect when the benzylic
scopic studies of the reaction of [MnIII(O2)(Me2EBC)]2+ (where C–H bond of PPA was substituted for deuterium.
Scheme 1 Common reactions for peroxomanganese(III) complexes.
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The ability of the MnIII-peroxo unit to abstract hydrogen L7BQ ligand (L7BQ
=
1,4-di(quinolin-8-yl)-1,4-diazepane),
atoms from benzylic C–H bonds, such as those of PPA, offers a which lacks benzylic linkers, and describe the corresponding
new perspective on the decay pathways of MnIII-peroxo adducts MnII complex, [MnII(L7BQ)(OTf)2]. As anticipated, the
supported by aminopyridyl ligands. This includes the decay [MnII(L7BQ)(OTf)2] complex reacts with H2O2 and Et3N to gene-
reaction of the [MnIII(O2)(MeTPEN)]+ complex (where MeTPEN rate the peroxomanganese(III) complex, [MnIII(O2)(L7BQ)]+,
is
N-methyl-N,N′,N′-tris(2-pyridylmethyl)ethane-1,2-diamine; which has been characterized by a variety of spectroscopic
see Scheme 2),41 which resulted in the eventual formation of a techniques. Although the [MnIII(O2)(L7BQ)]+ complex does not
MnII complex coordinated by two pyridinecarboxylate ligands show enhanced stability relative to the [MnIII(O2)(L7py2R)]+ ana-
(Scheme 2) derived from the oxidation of the parent MeTPEN logues, the reactivity of this complex with respect to aldehydes
ligand. Anxolabéhère-Mallart and co-workers postulated that is distinct and highly sensitive to the presence of acid,
this decay pathway, which required the addition of strong acid, suggesting a ligand influence on reactivity.
proceeded through a MnIII-hydroperoxo species that under-
went O–O cleavage to afford a strong oxidant (i.e., a high-
valent MnIV-oxo adduct) capable of initiating oxidation of the
Experimental methods
Materials
MeTPEN ligand at the benzylic linkers.41 In light of the more
recent studies that suggest that MnIII-peroxo and MnIII-hydro-
peroxo adducts can attack benzylic C–H bonds, it is unclear if
it is necessary to invoke formation of a high-valent manga-
nese-oxo species to rationalize the observed chemistry.
Unless otherwise noted, all chemicals and solvents were
obtained from commercial vendors at ACS grade or better and
were used without further purification. Acetonitrile, methanol,
and ether were dried and degassed using a Pure Solv (2010)
solvent purification system. Toluene was made anaerobic by
either sparging and then drying over activated alumina using a
PPT Glass Contour solvent purification system, or dry toluene
(99% purity) from Acros Organics was degassed by four freeze–
pump–thaw cycles using Schlenk techniques. All dried,
degassed solvents were immediately taken into an argon-filled
glove box and were stored in tightly-sealed Schlenk glassware
Because of the potential for MnIII-peroxo and MnIII-hydro-
peroxo adducts to attack C–H bonds of moderate strength (ca.
80–85 kcal mol−1), the design and synthesis of a novel ligand
platform excluding benzylic –CH2 linkers is of interest, as this
ligand could avoid hydrogen atom abstraction as a decay
pathway. To develop such a ligand, we chose a ligand topology
quite similar to that of the L7py2 family that we had pre-
R
viously used to generate a series of MnIII-peroxo adducts
(Fig. 1).31,32,34 In this study, we report the synthesis of the
1
until use. CCA was distilled prior to use; however, a H-NMR
Scheme 2 The proposed formation and ligand oxidation pathway of a MnIII-peroxo and MnIII-hydroperoxo species supported by the N-methyl-N,
N’,N’-tris(2-pyridylmethyl)ethane-1,2-diamine ligand (MeTPEN). The XRD structure, taken from ref. 41, shows the final manganese decay product in
the presence of acid, where the metal center is coordinated to two pyridine carboxylate molecules (pyCO2–) that resulted from ligand oxidation.
Fig. 1 The schematic structures of (A) [MnIII(O2)(L7py26-Me)]+ (B) L7py2
lighted in red), and (C) the new L7BQ ligand described in this work.
ligand (with benzylic groups potentially susceptible to oxidation high-
6-Me
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analysis of the material following distillation revealed the per- and the percentage of ethyl acetate was gradually increased over
sistence of acid impurities (vide infra). Syntheses of L7BQ and time. The clean ligand was isolated as a yellow oil in 69% yield
1
[MnII(L7BQ)(OTf)2] were carried out under inert conditions, as (292 mg) and was characterized by H NMR, 13C NMR, HSQC
described below. Product analysis for PPA was performed by and ESI-MS. 1H NMR data (600 MHz, Fig. S1†) for L7BQ (CDCl3,
running reaction mixtures through a silica plug with excess δ) = 8.86 (dd, J = 4.1, 1.9 Hz, 2H), 8.09 (dd, J = 8.3, 1.9 Hz, 2H),
EtOAc, and 1,2,4,5-tetrachloro-3-nitrobenzene was used as an 7.40 (t, J = 7.8 Hz, 2H), 7.35 (dd, J = 8.2, 4.1 Hz, 2H), 7.31 (dd,
internal standard for 1H NMR quantification in CD3CN.
J = 8.2, 1.3 Hz, 2H), 7.21 (dd, J = 7.6, 1.4 Hz, 2H), 4.09 (s, 4H),
3.96–3.76 (m, 4H), 2.38 (p, J = 5.7 Hz, 2H). 13C NMR data
(400 MHz, Fig. S2†) for L7BQ (CDCl3, δ) = 149.85, 147.39,
Instrumentation
NMR spectra were collected on a Bruker DRX 400 MHz spectro- 142.61, 136.43, 130.03, 126.82, 120.81, 119.64, 115.61, 55.16,
meter and a 600 MHz AVAN CE III spectrometer with a BBO 53.55, 29.06. HSQC for L7BQ in included in the ESI (Fig. S3†).
probe or a QNP probe. Data were collected at room tempera- ESI-MS (Fig. S4†): [L7BQ + H]+ m/z = 355.1902 (calc. = 355.1917).
ture in CDCl3 (δ = 7.26 ppm), unless stated otherwise. Mass
Synthesis of [MnII(L7BQ)(OTf)2]
spectrometry experiments were performed using an LCT
Primers MicroMass electrospray time-of-flight instrument. An equimolar mixture of L7BQ and [MnII(OTf)2(MeCN)2]n pro-
Electronic absorption spectra were obtained on a Varian Cary duced high yields (>90%) of [MnII(L7BQ)(OTf)2] when stirred
50 Bio spectrophotometer interfaced with a Unisoku cryostat overnight in MeCN under an inert atmosphere at room temp-
(USP-203-A) capable of maintaining temperatures between 150 erature. [MnII(OTf)2(MeCN)2]n was synthesized according to lit-
and 373 K. EPR spectra were collected on an X-band (9 GHz) erature procedures.25 A detailed procedure for the metalation
Bruker EMXPlus spectrometer equipped with an Oxford of L7BQ is as follows. To a stirred MeCN solution (5 mL) of
ESR900 continuous flow liquid helium cryostat and an Oxford L7BQ (100 mg, 0.282 mmol), an equimolar quantity of
ITC503 temperature system. Both parallel- and perpendicular- MnII(OTf)2 (99 mg, 0.282 mmol) was added in the same
mode spectra were collected using a Bruker ER4116DM dual- solvent (5 mL) and was stirred overnight under an inert atmo-
mode cavity. All spectra were collected under nonsaturating sphere. The mixture was then filtered using a syringe filter and
conditions at 2.0 mW microwave power, 4 G modulation ampli- dried under reduced pressure. The solid product was recrystal-
tude, 100 kHz modulation frequency and 83 ms time constant. lized with MeCN and Et2O by vapor diffusion. Light yellow
Spin quantification of the product of [MnIII(O2)(L7BQ)]+ with crystals suitable for X-ray diffraction analysis were obtained by
cyclohexanecarboxylic acid (termed intermediate A) was deter- subsequent recrystallization with the same solvent system.
mined against a 2.5 mM sample of [MnII(L7BQ)(OTf)2] in [MnII(L7BQ)(OTf)2] was further characterized by the effective
1
MeCN. Gas chromatography-mass spectrometry data were col- magnetic moment analysis by the H NMR method of Evans46
lected using a Quattro Micro GC quadrupole mass analyzer via in CD3CN at 25 °C, and by ESI-MS and EPR methods. The
an Agilent 6890 N gas chromatograph. A 5% phenyl methyl effective magnetic moment of [MnII(L7BQ)(OTf)2] at 25 °C was
silicone stationary phase (HP-5 MS) 12 meter column was used found to be 5.7μB in CD3CN (a diamagnetic correction, χD, of
along with a helium carrier gas at a flow rate of 2 ml min−1
.
−277.24 × 10−6 emu mol−1 was included in the calculation of
The injector port was heated to 240 °C and 1 μL of sample was the molar magnetic susceptibility, χM).47 This value agrees
injected with a split ratio of 20 : 1. The GC thermal gradient with the expected value (5.9μB) for a monomeric high-spin
was an initial 50 °C, which was held for 1 minute before MnII center. ESI-MS (Fig. S5†): [MnII(L7BQ)(OTf)]+ m/z =
increasing 50 °C min−1 to 300 °C and held for two minutes. 558.0342 (calc. = 558.0745). The perpendicular-mode X-band
Elemental analysis was done through Micro-Analysis, Inc.
EPR spectrum of a frozen MeCN solution of [MnII(L7BQ)
(OTf)2] exhibits features at 230 mT and 350 mT at 5 K
(Fig. S6,† left), which are characteristic of a monomeric MnII
Synthesis of the L7BQ Ligand
8-Bromoquinoline (500 mg, 2.4 mmol), homopiperazine species.35 Additionally, the parallel-mode EPR spectrum shows
(120 mg, 1.2 mmol), and NaOtBu (324 mg, 3.4 mmol) were no signal (Fig. S6,† right). Elemental Analysis [MnII(L7BQ)
combined in a Schlenk tube in dry, degassed toluene (40 mL), (OTf)2]·H2O C25H24F6MnN4O7S2 calc (%): C 41.38, H 3.33,
along with 4 mol% Pd2(dba)3 (110 mg, 0.12 mmol), and N:7.72; Found (%): C 41.60, H: 3.23, N: 7.73.
10 mol% BINAP (150 mg, 0.24 mmol) within an argon-filled
X-ray diffraction data collection and analysis for [MnII(L7BQ)
(OTf)2]
glove box. The tube was sealed with an air-tight septum, and
stirred at 110 °C for three days. Although no difficulties were
encountered, heating a sealed vessel can result in explosion of A light-yellow single-domain crystal of [MnII(L7BQ)(OTf)2] was
the reaction vessel. Because of this, all reactions were performed suspended with Paratone N oil on a MiteGen MicroMount and
behind a blast shield. After heating for three days, the reaction placed on a goniometer head in a cold nitrogen stream at
mixture was cooled to room temperature and was diluted with 100 K for a single-crystal X-ray structure determination.
excess diethyl ether. This mixture was filtered through Celite Monochromatic X-rays were provided by a Bruker diffracto-
and evaporated to dryness under reduced pressure. The crude meter equipped with Helios multilayer optics, an APEX II CCD
product was purified by flash chromatography over silica gel detector, and
a
Bruker MicroStar microfocus rotating
using ethyl acetate and hexane (1 : 20) as the beginning eluent anode X-ray source operating at 45 kV and 60 mA. Intensity
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data (5238 0.5°-wide ω- or ϕ-scan frames with counting times Product analysis
of 2–3 seconds each) were collected with the Bruker program
GC-MS was used for analysis of organic products from the
reactions of Mn complexes with CCA, and the percent yield
of these reactions was determined by comparing the ratio of
the product signal to that of an internal standard and compar-
ing the ratio to a standard curve for the product. A detailed
procedure is a follows: a 2.5 mM solution of [MnIII(O2)(L7BQ)]+
was reacted with 165 equivalents of CCA at −40 °C in MeCN.
When the reaction was completed, it was allowed to warm to
room temperature, napthalene was added as an internal stan-
dard, and the reaction solution was run through a silica plug
with excess EtOAc. The reaction was performed in triplicate.
The work-up procedure was tested using a standard sample of
known substrate and product concentrations, and the pro-
cedure was not found to change the substrate : product ratio.
SMART,48 and diffracted intensities were measured with the
Bruker program SAINT.49 The space group50 and crystallo-
graphic data are summarized in Table S1.† The Bruker soft-
ware package SHELXTL was used to solve the structure and
locate all nonhydrogen atoms with “direct methods” tech-
niques. Hydrogen atoms were located from a difference
Fourier and included in the structural model as independent
isotropic atoms whose parameters were allowed to vary in
least-squares refinement cycles. All stages of weighted full-
matrix least-squares refinement were conducted using Fo2 data
with the SHELXTL Version 2010.3-0 software package.51 The
final structural model incorporated anisotropic thermal para-
meters for all non-hydrogen atoms and isotropic thermal para-
meters for all hydrogen atoms.
XAS data collection
Generation and characterization of [MnIII(O2)(L7BQ)]+
The Mn K-edge XAS data for all samples were collected over an
energy range of 6300 to 7250 eV. Under all conditions, a
manganese foil was used as reference for each scan by assign-
ing the zero crossing of the second derivative of the K-edge
energy of the foil to 6539.0 eV. All XAS data were obtained via
fluorescence excitation. Data for [MnIII(O2)(L7BQ)]+ and the
product of [MnIII(O2)(L7BQ)]+ with cyclohexanecarboxylic acid
(termed intermediate A) were collected at beamline 9-3 at SSRL
at 7 K using a Si(220) monochromator and a 100-element Ge
array detector. Data for [MnII(L7BQ)(OTf)2] were collected at
beamline X3B at the National Synchrotron Light Source (NSLS)
using a Si(111) monochromator and a 31-element Ge array
detector.
The peroxomanganese(III) complex [MnIII(O2)(L7BQ)]+ was gen-
erated by treating a 2.5 mM MeCN solution of [MnII(L7BQ)
(OTf)2] with 5 equiv. H2O2 and 1.0 equiv. Et3N at −40 °C.
Reactions using less than 5 equiv. hydrogen peroxide resulted
in substantially lower formation of the MnIII-peroxo adduct.
We presume that water, which is added with the H2O2, is a
strong enough base to remove the second proton required for
formation of the side-on peroxomanganese(III) species. When
greater equiv. Et3N were used, we observed the decay of
[MnIII(O2)(L7BQ)]+ to be more rapid. One equiv. Et3N gave the
cleanest formation and the best thermal stability.
Because this species was sensitive to the temperature of the
added reagents, syringes and stock solutions were chilled prior
to addition in order to minimize any thermal decay.
Additionally, the stock solutions were re-made often to avoid
the base-catalyzed decomposition of hydrogen peroxide.52
Characteristic changes in the electronic absorption spectrum
were evident of the formation of [MnIII(O2)(L7BQ)]+, where the
growth of two bands at 450 nm (ε = 260 M−1 cm−1) and 660 nm
(ε = 75 M−1 cm−1) marked the formation of this species. ESI-MS
[MnIII(O2)(L7BQ)]+ m/z = 441.1135 (calc. = 441.1123 m/z);
[MnIII(18O2)(L7BQ)]+ m/z = 445.1156 (calc. = 445.1208 m/z)
(Fig. S7 and S8†). EPR samples of [MnIII(O2)(L7BQ)]+ were pre-
pared at −40 °C in MeCN using cryogenic techniques and were
analyzed at 5 K (Fig. S9†). Attempts to characterize [MnIII(O2)
(L7BQ)]+ by vibrational methods were unsuccessful. We note
that, to date, vibrational studies of side-on MnIII-peroxo adducts
have commonly been unsuccessful.35,40
XAS data analysis
Processing of the XAS data for [MnII(L7BQ)(OTf)2] was done
using EXAFSPAK53 using previously described methods.43
Analysis of EXAFS data for [MnIII(O2)(L7BQ)]+ and intermediate
A were performed using DEMETER.54 The AUTOBK algorithm,
as implemented in ATHENA, was used for background
removal. The edge-step normalization procedure was used for
each data set. EXAFS refinement in ARTEMIS was carried out
on k3χ(k) data, using phase and amplitude functions obtained
from FEFF, version 6,55 and a structural model of [MnIII(O2)
(L7BQ)]+ from DFT computations. For each fit, the parameters
r (average distance between Mn and scattering atom), E0
(a single value for all paths), and σ2 (Debye–Waller factor) were
optimized, while n, the number of atoms in the shell, was kept
fixed. n was varied by integer steps systematically to achieve
better goodness of fit. The goodness of fit was evaluated using
the R-factor:
XAS sample preparation
Frozen solution samples of [MnII(L7BQ)(OTf)2] at 11 mM and
[MnIII(O2)(L7BQ)]+ at 2.5 mM were prepared from 400 μL of
solution in MeCN that was frozen in a precooled sample cup.
A frozen solution sample of the product of [MnIII(O2)(L7BQ)]+
with cyclohexanecarboxylic acid (termed intermediate A) was
N
N
X
X
ꢀ
ꢁ
ꢀ
ꢁ
2
2
R ¼
χdi ata ꢀ χfiit
=
χdi ata
i¼1
i¼1
Fits of the pre-edge area were performed using the FityK
prepared from 400μL of a 2.5 mM solution in MeCN that was software.56 Pre-edge intensity was normalized relative to the
frozen in a precooled sample cup following the addition of most intense fluorescence peak. The pre-edge was fit using
cyclohexanecarboxylic acid to [MnIII(O2)(L7BQ)]+.
pseudo-Voight line shapes and varied full-width at half-
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maximum, energy position, and height. The contribution from
the rising edge and the background were also fit using a
pseudo-Voight function. Manganese K-edge energy values were
Results and analysis
Synthesis of L7BQ ligand
determined based on the position of the inflection point of Given the observed ligand oxidative decay pathway of
the rising edge upon taking the first derivative of the edge [MnIII(O2)(MeTPEN)]+,41 the L7BQ ligand was designed in
region.
order to generate a peroxomanganese(III) adduct lacking
benzylic linkers. The synthesis of this ligand involved the
coupling of two quinolinyl moieties with both secondary
amine groups in homopiperazine (Scheme 3). Coupling of sec-
ondary amines with aryl halides can be attained via the Pd-
catalyzed Buchwald–Hartwig cross-coupling reactions.70–72 In
this case, 8-bromoquinoline and homopiperazine could be
coupled to generate the desired aminoquinolinyl L7BQ ligand
in moderate yields (∼69%).
Density functional theory
All calculations were performed using the ORCA 4.0 software
package.57 Geometries for [MnIII(O2)(L7BQ)]+ were performed
starting from the MnII crystal structure and adding the peroxo
moiety. The high-spin S = 2 spin state was used for all compu-
tations. Optimizations were carried out using the B3LYP func-
tional with the inclusion of dispersion interactions via
Grimme’s D3 correction with the Becke–Johnson damping
scheme.58–61 The def2-TZVP basis set was utilized for Mn, N,
and O and the def2-SVP basis set was used for C and H.62,63
A larger DFT integration grid, Grid6 in ORCA nomenclature,
was utilized. The RIJCOSX approximation was used with a
larger COSX grid (GridX6) and the def2/J auxiliary basis
sets. Solvent was included implicitly through the SMD sol-
vation model with the default parameters in ORCA for aceto-
nitrile.64 Structures were confirmed to be a minima through
numerical frequency calculations performed at the same level
of theory.
Structural properties of [MnII(L7BQ)(OTf)2]
The [MnII(L7BQ)(OTf)2] complex could be readily generated by
the reaction of [Mn(OTf)2(MeCN)2]n with the L7BQ ligand. The
XRD structure of [MnII(L7BQ)(OTf)2] contains a six-coordinate
manganese center (Fig. 2) in a pseudo-octahedral geometry.
Significant bond lengths and angles of [MnII(L7BQ)(OTf)2] are
summarized in Table 1. In this structure, the L7BQ ligand is
coordinated in a tetradentate fashion occupying the equatorial
plane (N1–N4), with the MnII ion being displaced by 0.08 Å
from the mean plane through these four coordinated nitro-
gens. The axial sites are occupied by the two triflate ions with
an O11–Mn–O21 bond angle of 155.06°. The Mn–N distances
vary between 2.2–2.3 Å, with the amine Mn–N distances being
longer than the aromatic Mn–N distances; the Mn–O distances
are ∼2.2 Å (Table 1). All of these are values typical for high-
The manganese pre-K-edge spectra of [MnIII(O2)(L7BQ)]+
models were calculated using time-dependent density func-
tional theory (TD-DFT) within the Tamm-Dancoff approxi-
mation using the B3LYP functional.65,66 Calculations were per-
formed using the zeroth-order approximation (ZORA) with the
ZORA-def2-TZVP(-f) basis sets used for all atoms.67,68 The pre-
edge area was calculated using a previously published method
based on calibration using a series of MnII and MnIII com-
plexes, where the origin adjusted intensity(I) is calculated from
the sum of the electric dipole, electric quadrupole, and mag-
netic dipole contributions. These values are used in the
empirically derived equation A = 6.01I + 1.79 for B3LYP.69
Simulations of the spectra were performed with a 1 eV
linewidth.
The electronic absorption spectra of [MnIII(O2)(L7BQ)]+
models were calculated using TD-DFT methods utilizing the
B3LYP functional. The def2-TZVPP basis set was used for Mn,
N, and O and the def2-TZVP basis set for C and H. Solvation
was included implicitly using the SMD solvation model with
the default values for acetonitrile.
Fig. 2 ORTEP diagram (left; 50% thermal probability) and space-filling
model (right) for [MnII(L7BQ)(OTf)2]. Hydrogen atoms and the non-coor-
dinating solvent molecule have been removed for clarity. Coordination
bond lengths and angles are listed in Table 1.
Scheme 3 Synthetic scheme for the L7BQ ligand.
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Table 1 Selected bond lengths and angles for [MnII(L7BQ)(OTf)2]
(OTf)2] are very similar to those previously observed for MnII
complexes of the L7py2R ligands.31,32,34
Bond length (Å)
Mn–N1
Mn–N2
Mn–O11
2.1846(14)
2.3011(15)
2.1869(12)
Mn–N4
Mn–N3
Mn–O21
2.2109(14)
2.2841(14)
2.2152(13)
Oxidation of [MnII(L7BQ)(OTf)2] by H2O2
The electronic absorption spectrum of [MnII(L7BQ)(OTf)2] in
MeCN at 25 °C is featureless in the visible region, only
showing the onset of intense absorption features at wave-
lengths below 400 nm (Fig. 3, left). The reaction of a 2.5 mM
solution of [MnII(L7BQ)(OTf)2] with 5 equiv. H2O2 and 1.0
equiv. Et3N in MeCN at −40 °C gives rise to a new species
characterized by two prominent absorption bands centered at
Bond angle (°)
O11–Mn–O21
N1–Mn–O11
N2–Mn–O11
N3–Mn–O11
N4–Mn–O11
N1–Mn–O21
N2–Mn–O21
N3–Mn–O21
155.05(5)
85.22(5)
95.27(5)
111.49(5)
88.82(5)
86.37(5)
105.57(5)
88.43(5)
N4–Mn–O21
N1–Mn–N2
N2–Mn–N3
N3–Mn–N4
N1–Mn–N3
N2–Mn–N4
N1–Mn–N4
81.48(5)
76.73(5)
71.47(5)
75.84(5)
145.04(5)
146.23(5)
137.04(5)
450 nm (ε = 260 M−1 cm−1) and 660 nm (ε = 75 M−1 cm−1
Fig. 3, left).74 The intensity of the feature at 450 nm and the
spin MnII centers.31,34,73 A highly distorted 6-coordinate geo- peak to trough ratio between 560 and 660 nm were observed to
metry for the MnII center in [MnII(L7BQ)(OTf)2] is indicated by vary to
small degree between sample preparations
;
a
the angles between coordinated atoms: N–Mn–N, 71° to 137°; (0.7 : 1–1 : 1), due to the temperature sensitive nature of the
O–Mn–N, 81°–111°; and O–Mn–O, 155.06°. These angles for peroxo. The positions and intensities of the bands at 450 and
the MnO2N4 polyhedron more closely resemble a pentagonal 660 nm are strikingly similar to those of other side-on peroxo-
bipyramid with
a missing equatorial ligand than an manganese(III) complexes prepared using analogous N4
octahedron. This polyhedron would ideally have equatorial ligands and similar reaction conditions.31,32,34 The mass spec-
N–Mn–N angles of 72° and 144°, O–Mn–N angles of 90° and trum of the solution of [MnII(L7BQ)(OTf)2] following treatment
an O–Mn–O angle of 180°. Nonbonded O⋯H interactions with H2O2 and Et3N displays an ion peak at 441.1135 m/z
between coordinated triflates and the ethyl and propyl linkers (Fig. S7†), which compares well with that expected for
joining N2 and N3 cause the triflates to move off the vertical [MnIII(O2)(L7BQ)]+ (calc. = 441.1123 m/z). When H218O2 was
axis in this molecule toward the “missing” equatorial coordi- used to generate the peroxo intermediate, the corresponding
nation site. Even though the N1⋯N4 separation is 4.09 Å, an ion peak shifted to 445.1156 m/z (Fig. S8†), providing further
acetonitrile solvent molecule of crystallization present in evidence for the presence of a peroxo ligand derived from
the asymmetric unit does not interact with the metal center H2O2. It should be noted that these peaks corresponding to
(Mn–N distance of 6.729 Å) and is not shown in Fig. 2. the MnIII-peroxo intermediates are of modest intensity in the
Hydrogen atoms on the two carbons adjacent to N1 and N4 are mass spectrometric data collected at room temperature. This is
separated by 3.51 Å and block access to the fifth equatorial anticipated, given the low thermal stability of this intermediate
coordination site. The bond angles observed for [MnII(L7BQ) at temperatures higher than −40 °C (vide infra).
Fig. 3 Left: Electronic absorption spectral changes of [MnII(L7BQ)(OTf)2] (solid black trace) upon the addition of 5 equiv. H2O2 and 1.0 equiv. Et3N in
MeCN at −40 °C. Inset: Time evolution of absorption features at 450 nm and 660 nm. Right: Perpendicular mode X-band EPR spectra corresponding
to 2.5 mM frozen MeCN solutions of [MnII(L7BQ)(OTf)2] (solid black trace) and [MnIII(O2)(L7BQ)]+ (solid red trace) collected at 5 K.
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The [MnIII(O2)(L7BQ)]+ complex was further characterized somewhat lower than that observed for other MnII and MnIII-
by X-band EPR spectroscopy. As integer spin systems, high- peroxo pairs (3.2 and 2.4 eV; see Table 2). However, the sample
spin MnIII centers (S = 2) do not show signals in perpendicu- size for comparison is small, and the MnII complexes in these
lar-mode EPR experiments. Parallel-mode signals have been pairs all have different ligand spheres. Thus, variations in the
observed for some, but certainly not all, of the reported MnIII- MnII edges due to the different coordination environments
peroxo adducts.37,40,41,75 A moderate zero-field splitting can could influence the observed shift between the MnII and MnIII-
render MnIII centers silent even in parallel-mode at X-band fre- peroxo species.
quencies. In contrast, mononuclear MnII and spin-coupled
MnIIMnIII and MnIIIMnIV adducts will show prominent signals band at 6540.3 eV, with an area of 6.8 units. The pre-edge tran-
in perpendicular mode. sitions of Mn coordination complexes arise from Mn 1s-to-3d
The pre-edge region of [MnII(L7BQ)(OTf)2] shows one weak
The perpendicular-mode EPR spectrum of [MnII(L7BQ) transitions. These transitions are electric-dipole forbidden
(OTf)2] shows a positive feature at ca. 220 mT and a six-line and, for low-symmetry complexes, their intensity predomi-
signal centered near 350 mT. The six-line signal shows an nantly derives from Mn 3d–4p mixing aided by structural devi-
average hyperfine splitting of 9.3 mT. The parallel-mode ations from centrosymmetry. The small pre-edge area of
X-band EPR spectrum of [MnIII(O2)(L7BQ)]+ shows no features [MnII(L7BQ)(OTf)2] is consistent with a small degree of Mn 3d–
at 5 K, which can occur for MnIII compounds with large zero- 4p mixing, as expected on the basis of the XRD structure
field splitting (Fig. S9,† top right).76 The perpendicular mode (Fig. 2). In contrast, the pre-edge region of [MnIII(O2)(L7BQ)]+
X-band EPR spectra of [MnIII(O2)(L7BQ)]+ collected at 5 K (the shows a prominent pre-edge peak at 6540.4 eV, with a shoulder
red trace in Fig. 3, right), reveals a low-intensity derivative- at 6542.3 eV (Fig. 4, inset). The total area of these peaks are
shaped signal at 350 mT and a weak feature at 220 mT (this 20.5 units, which is greatly increased relative to that of
latter feature is more apparent in a zoomed-in spectrum [MnII(L7BQ)(OTf)2] (Table 2 and Fig. 4 and S10†). We had
shown in Fig. S9,† bottom). These signals are most likely previously reported a ca. 2.5-fold increase in pre-edge area
associated with unreacted [MnII(L7BQ)(OTf)2], as an overlay of for the [MnIII(O2)(Me2EBC)]+ complex compared to its
the perpendicular-mode EPR spectra of [MnII(L7BQ)(OTf)2] [Mn(Cl)2(Me2EBC)] analogue (Table 2).43 The intensity increase
with that of the [MnIII(O2)(L7BQ)]+ solution reveal strong simi- observed for the MnII and MnIII-peroxo pair of the L7BQ ligand
larities (Fig. S9,† bottom). The dominant hyperfine features of is comparable, with a ca. 3-fold larger area for the latter
[MnII(L7BQ)(OTf)2] are retained in the perpendicular-mode complex.
spectrum of the [MnIII(O2)(L7BQ)]+ solution (splitting of
The Fourier transform EXAFS spectrum of [MnIII(O2)
9.7 mT). The additional fine structure (with a smaller splitting (L7BQ)]+ consists of a prominent peak near 1.6 Å and a weaker
of 6.5 mT) could be due to superhyperfine interactions associ- feature at 2.7 Å (Fig. 4, bottom). Results of fits to these data to
ated with the nitrogen ligands of L7BQ, which are now resolved obtain Mn-scatterer distances are summarized in Table 3.
due to the lower concentration of MnII. Importantly, spin These features are best fit with an O shell at 1.85 Å (number of
quantification shows that the perpendicular-mode EPR signal scatterers, n = 2), one N shell at 2.22 Å (n = 4) and two C shells
observed for the solution of [MnIII(O2)(L7BQ)] represents only at 3.10 and 3.59 Å (n = 5 and 3, respectively). The Mn–O dis-
10% of the total Mn. Thus, the EPR signal arises from a min- tances are on the short end of those observed for crystallogra-
ority species, clearly establishing that the bulk of Mn in the phically characterized MnIII-peroxo adducts (Mn–O distances
[MnIII(O2)(L7BQ)]+ solution is EPR silent.
of 1.841–1.901 Å), while the Mn–N distances are typical for
high-spin MnIII complexes with amine, pyridine, and quino-
line ligands.12
XAS characterization of [MnIII(O2)(L7BQ)]+
The [MnII(L7BQ)(OTf)2] and [MnIII(O2)(L7BQ)]+ complexes
showed Mn K-edge values of 6547.8 and 6549.2 eV, respectively
(Table 2). The 1.6 eV lower edge energy for [MnII(L7BQ)(OTf)2]
DFT structure of [MnIII(O2)(L7BQ)]+ and pre-edge properties
from time-dependent (TD) DFT computations
compared to [MnIII(O2)(L7BQ)]+ is consistent with the higher The structure of the L7BQ ligand provides two unique faces for
Mn oxidation state for the latter complex. The edge shift is the peroxo unit to bind to the manganese center, one on the
Table 2 Edge and pre-edge energies (eV), pre-edge peak heights and areas for MnII and MnIII-peroxo complexes
Complex
Medium
Edge energy
Pre-edge energy
Height
Area
Ref.
a
a
[MnII(L7BQ)(OTf)2]
[MnIII(O2)(L7BQ)]+
[MnII(Cl)2(Me2EBC)]
[MnIII(O2)(Me2EBC)]+
[MnII(13-TMC)]2+ b
[MnIII(O2)(13-TMC)]+ b
MeCN
MeCN
Solid
CH2Cl2
CH3CN
CH3CN
6547.8
6549.2
6547.1
6550.3
6545.5
6547.9
6540.3
6540.4, 6542.3
6540.8
6540.8
NR c
0.022
0.031, 0.056
0.041
6.8
20.8
3.9
77
43
78
78
0.051
9.5
NRc
NRc
NRc
NR c
NRc
a This work. b 13-TMC = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclotridecane. c Not reported.
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similar computations for [MnIII(O2)(L7py2H)]+.31 All values dis-
cussed here are from the lower energy structure of [MnIII(O2)
(L7BQ)]+, but simulated XANES for both complexes are given in
the ESI (Fig. S12†). TD-DFT simulated UV-vis absorption
spectra of [MnIII(O2)(L7BQ)]+ with the peroxide bound on the
propyl face are also included in the ESI (Fig. S13†).
Metric parameters for the DFT structure of [MnIII(O2)
(L7BQ)]+ species with the peroxide bound on the propyl face
are reported in the ESI (Table S2†). The Mn–O bond lengths
are 1.862 Å and 1.856 Å, while the O–O bond is 1.418 Å. The
calculated Mn–O distances are in excellent agreement with the
best fit of the experimental EXAFS data, which included a 2
atom O shell at 1.85 Å (Table 3). The calculated Mn–O and
O–O distances also agree well with corresponding bond lengths
for crystallographically characterized MnIII-peroxo complexes,
in which the Mn–O and O–O bond lengths range from 1.838 to
1.901 Å and 1.402 to 1.43 Å respectively.12,22–27 Additionally,
the average Mn–N bond lengths of 2.22 Å for the DFT model of
[MnIII(O2)(L7BQ)]+ is the same as the Mn–N distances from
EXAFS (2.22 Å; see Table 3) and is accordant with corres-
ponding bond lengths of other high-spin MnIII complexes with
nitrogen-based ligands. The two C shells from EXAFS analysis
at 3.10 and 3.59 Å (n = 5 and 3, respectively) are also in good
agreement with average distances of the closest carbons from
the L7BQ ligand determined in the DFT optimized structure,
which come from the propyl and ethyl arms of the diazocy-
cloalkane backbone as well as from several carbon atoms from
the quinoline moieties (DFT distances of 2.98–3.54 Å).
The TD-DFT calculated pre-edge spectra for [MnIII(O2)
(L7BQ)]+ shows two overlapping bands with energies of 6540.2
and 6541 eV, which is similar to the two peaks seen in the
experimental pre-edge spectrum at 6540.8 and 6542.3 eV.
Using a coordinate system where the MnIII–O2 unit lies in the
xy plane, the first peak arises from excitations into the MnIII
β-3dyz, 3dx2−y2, and 3dxz orbitals, and the second peak arises
from excitations into the MnIII α-3dxy orbital and the MnIII
Fig. 4 Top: Overlay of XANES regions for [MnII(L7BQ)(OTf)2] (black) and
[MnIII(O2)(L7BQ)]+ (red). Bottom: Fourier transform of Mn K-edge EXAFS
data and raw EXAFS spectra (insets), experimental (⋯) and fits (—), for
[MnIII(O2)(L7BQ)]+. The parameters used for the EXAFS fit are in Table 3.
side of the ethyl linker and the other on the side of the propyl β-3dz2 and 3dxy orbitals (where α and β refer to majority and
linker. Structures for these isomeric forms of [MnIII(O2) minority spin electrons, respectively). The calculated pre-edge
(L7BQ)]+ were optimized (Fig. S11†), and the structure with the area of 14.7 units underestimates the experimentally deter-
peroxide bound on the propyl face is calculated to be 5 kcal mined pre-edge area of 20.8 units, but reproduces an increase
mol−1 lower in energy than the structure with the peroxide in area when compared to that previously calculated for the
bound on the ethyl face. This result is in agreement with [MnIII(O2)(Me2EBC)]+ complex (Table 4). The summed Mn 4p
Table 3 EXAFS fitting results for [MnIII(O2)(L7BQ)]+ in MeCN (Δk = 10 Å−1
)
Mn–O/N
Mn–N
Mn–C
Fit
n
r (Å)
σ2
n
r (Å)
σ2
n
r (Å)
σ2
E0
R
1
2
3
4
0
2
2
2
6
4
4
4
2.07
2.22
2.23
2.22
0.00404
0.00722
0.00819
0.00792
−47.79
3.58
4.87
0.41
0.28
0.13
0.12
1.85
1.85
1.85
0.00413
0.00367
0.00376
4
4
6
3
6
3
5
3.10
3.59
3.10
3.59
3.10
3.59
3.10
0.08631
0.00705
0.00394
0.00457
0.00388
0.00420
0.00256
4.13
5
2
1.85
0.00373
4
2.22
0.00802
4.35
0.12
6
2
1.85
0.00373
4
2.22
0.00799
4.13
0.11
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Table 4 Experimental and TD-DFT-calculated pre-edge area and Mn 4p contributions for [MnIII(O2)(L7BQ)]+ and [MnIII(O2)(Me2EBC)]+
Experimental
Calculated
Ref.
a
Complex
Pre-edge energy
Height
Area
21
Pre-edge energy
Area
14.7
Mn 4p (%)
3.6
[MnIII(O2)(L7BQ)]+
6540.4
6542.3
6540.8
0.03
0.06
0.05
6540.2
6541
6541
[MnIII(O2)(Me2EBC)]+
9.5
6.1
3.0b
43
a This work. b The percent Mn 4p-character differs from the previously published values; after re-evaluation of the computational output, it was
determined that the previous value was in error.
character in the Mn 3d-based orbitals involved in the six pre-
edge transitions of [MnIII(O2)(L7BQ)]+ is 3.6%, with significant
contributions from multiple MnIII-based orbitals. This 4p-3d
mixing across the MnIII 3d-manifold implies that geometric
distortions induced by both the peroxo and L7BQ ligands drive
the large pre-edge area of [MnIII(O2)(L7BQ)]+. This mechanism
for orbital mixing is different than [MnIII(O2)(Me2EBC)]+,
where a sizeable 4p contribution was observed only in the
Mn–O peroxo σ-antibonding MO.43
Stability and thermal decay of [MnIII(O2)(L7BQ)]+
A 2.5 mM solution of [MnIII(O2)(L7BQ)]+ prepared using
5 equiv. H2O2 and 1.0 equiv. Et3N in MeCN at −40 °C decays
slowly over the course of an hour, with a half-life of ca.
10 minutes. In comparison, the [MnIII(O2)(L7py2)]+ complex is
shown to be stable for several hours at −40 °C (t1/2
=
15 minutes at 0 °C), and the identity of the decay product was
not determined.31 The decay of [MnIII(O2)(L7BQ)]+ is character-
ized by an increase in absorbance at 450 and 550 nm, as
shown in Fig. 5. The perpendicular-mode X-band EPR spec-
trum of this decay species is quite similar to that of [MnIII(O2)
(L7BQ)]+, showing only a low-intensity derivative-shaped signal
at 350 mT, with a multi-line hyperfine pattern indicative of a
multinuclear manganese species along with no features in par-
allel mode (see Fig. S14†). These data suggest that the decay
product is EPR silent. Thus, the decay product could be a sep-
Fig. 5 Electronic absorption spectral changes upon the self-decay of
[MnIII(O2)(L7BQ)]+ (solid red trace) at −40 °C in MeCN. Inset: Time evol-
ution of absorption features at 450 nm and 560 nm, which highlights
the formation of a decay species over 50 minutes.
We also explored the formation of [MnIII(O2)(L7BQ)]+ over a
arate monomeric MnIII species or an S = 0 antiferromagneti- variety of temperatures (−40 °C to room temperature) in
cally coupled dimer. The rate of decay of [MnIII(O2)(L7BQ)]+ is different solvents (including methanol, propionitrile, butyroni-
sensitive to the amount of base used to prepare the MnIII- trile, ethanol, dichloromethane, tetrahydrofuran and 2-methyl-
peroxo adduct, as [MnIII(O2)(L7BQ)]+ formed using triethyl- tetrahydrofuran). Of these solvents, [MnIII(O2)(L7BQ)]+ could
amine in excess of 1.0 equiv. is observed to decay more only be generated in propionitrile, but the species was much
rapidly.
less stable. When formed in propionitrile at −40 °C, the elec-
We have previously reported that the decay pathways of the tronic absorption bands associated with the MnIII-peroxo
MnIII-peroxo adducts [MnIII(O2)(κ4-N4py)]+ and [MnIII(O2) species at 450 and 660 nm loses definition within 15 seconds,
(Me2EBC)]+ proceed by reaction of the MnIII-peroxo center with indicating a substantially more rapid decay in this solvent (the
unreacted MnII starting material.35,43 To investigate if this half-life here is estimated to be ca. 1 minute). The limited
decay pathway is possible for the [MnIII(O2)(L7BQ)]+ complex, variability of the solvent and temperature for [MnIII(O2)
we added 1.0 equiv. of [MnII(L7BQ)(OTf)2] to [MnIII(O2)(L7BQ)]+ (L7BQ)]+ formation has prevented additional spectroscopic
at −40 °C, after the latter had maximally formed. We observed characterization. For example, characterization of [MnIII(O2)
no change in the electronic absorption spectrum upon the (L7BQ)]+ by magnetic circular dichroism (MCD) spectroscopy is
addition of the MnII complex, and the [MnIII(O2)(L7BQ)]+ not feasible due to the poor glassing capabilities of MeCN. We
species continued along its self-decay path (see Fig. S15†). have previously shown that MCD spectroscopy can provide
Thus, the decay of [MnIII(O2)(L7BQ)]+ does not occur by reac- useful insights into understanding the geometric and elec-
tion with the MnII starting material.
tronic structures of peroxomanganese(III) species.28,31,34
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Furthermore, unlike the closely related [MnIII(O2)(L7py2R)]+ expected deformylation product (acetophenone) under these
series of peroxo compounds,31,34 [MnIII(O2)(L7BQ)]+ could not conditions. Further investigations showed that this lack of
be generated using KO2 as the oxidant.
reactivity was highly dependent on the purity of PPA. Only in
cases where PPA lacked any acid impurities did [MnIII(O2)
(L7BQ)]+ fail to show a reaction with PPA. In cases where acid
impurities were present (as assessed by 1H-NMR investigations
of PPA; see Fig. S16†), the addition of PPA to [MnIII(O2)
(L7BQ)]+ resulted in electronic absorption changes very similar
to those observed when [MnIII(O2)(L7BQ)]+ was treated with
CCA. Specifically, the signals associated with [MnIII(O2)
(L7BQ)]+ show a rapid initial change to give an intermediate
with features near 595 and 450 nm (blue trace), and this new
chromophore would slowly decay (Fig. 6, right). In addition,
acetophenone formation was observed only for reactions of
[MnIII(O2)(L7BQ)]+ with PPA containing acid contaminants.
On the basis of these observations, we attribute the initial
rapid change in the electronic absorption spectrum of
[MnIII(O2)(L7BQ)]+ when treated with CCA (or PPA with acid
impurity) to a reaction of the MnIII-peroxo unit with acid.
McDonald and co-workers have noted that CCA commonly
contains a small percentage of cyclohexanecarboxylic acid,
which is challenging to completely remove by distillation.79
1H-NMR experiments performed for CCA before and after dis-
tillation show the persistent of both formic acid and cyclohexa-
necarboxylic acid (Fig. S17†).
To test our hypothesis that an acid impurity accounts for
the initial reaction of [MnIII(O2)(L7BQ)]+ with CCA, we investi-
gated the reactivity of [MnIII(O2)(L7BQ)]+ with cyclohexane-
carboxylic acid. For this reaction, we used concentrations of
cyclohexanecarboxylic acid (2 equivalents relative to Mn) com-
parable to those present when 165 equivalents CCA are added
to [MnIII(O2)(L7BQ)]+. From these experiments, we found that
when a 2.5 mM solution of [MnIII(O2)(L7BQ)]+ is treated with
2.0 equivalents of cyclohexanecarboxylic acid in MeCN at
−40 °C, the electronic absorption signals associated with
[MnIII(O2)(L7BQ)]+ were replaced with new features at 580 and
450 nm (Fig. 7, left). This process is complete within
Reactivity of [MnIII(O2)(L7BQ)]+ with aldehydes
When a 2.5 mM solution of [MnIII(O2)(L7BQ)]+ at −40 °C in
MeCN is treated with an excess (165 equivalents) of cylcohexane-
carboxaldehyde (CCA), the absorption features for the
peroxomanganese(III) species decay (Fig. 6, left). Analysis of the
resulting solution by GC-MS showed cyclohexanone in 38%
yield compared to the starting concentration of [MnII(L7BQ)
(OTf)2]. The formation and percent yield of cyclohexanone are
similar to those previously reported for CCA deformylation by
other MnIII-peroxo complexes.32,37 We attempted to investigate
the kinetics of the reaction of [MnIII(O2)(L7BQ)]+ with CCA by
following the disappearance of the MnIII-peroxo electronic
absorption bands at 450 and 660 nm (Fig. 6, left). This
approach was used previously to determine second-order rate
constants for the reactions of [MnIII(O2)(L7py2R)]+ complexes
with CCA.31 However, the disappearance of the electronic
absorption bands associated with [MnIII(O2)(L7BQ)]+ upon the
addition of excess CCA did not follow pseudo-first-order behav-
ior. Instead, we observed a rapid initial drop in absorption
intensity within the first 5 seconds of the reaction, followed by
a slow decay (Fig. 6, left inset). Furthermore, this rapid drop
led to the appearance of a new chromophore, which we have
termed intermediate A, with band maxima at 595 and 450 nm
(Fig. 6, left, blue trace). This kinetic behavior suggests that
[MnIII(O2)(L7BQ)]+ shows an initial rapid reaction with CCA to
give a new intermediate that then more slowly decays.
To better understand this deformylation chemistry, we also
explored the reactivity of [MnIII(O2)(L7BQ)]+ with the aldehyde
PPA. Unexpectedly, the addition of 40 equivalents of PPA to a
2.5 mM solution of [MnIII(O2)(L7BQ)]+ at −40 °C in MeCN did
not show evidence of a reaction but instead followed the self-
decay pathway of [MnIII(O2)(L7BQ)]+ (Fig. 6, center). Additional
analysis provided no evidence for the formation of the
Fig. 6 Left: Electronic absorption changes when 2.5 mM [MnIII(O2)(L7BQ)]+ are treated with 165 equiv. CCA in MeCN at −40 °C. Center: Electronic
absorption changes when 2.5 mM [MnIII(O2)(L7BQ)]+ are treated with 40 equiv. pure PPA in MeCN at −40 °C. Right: Electronic absorption changes
when 2.5 mM [MnIII(O2)(L7BQ)]+ are treated with 40 equiv. acid-contaminated PPA in MeCN at −40 °C.
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Fig. 7 Left: Electronic absorption changes for [MnIII(O2)(L7BQ)]+ + 2 equiv. cyclohexanecarboxylic acid in MeCN at −40 °C to generate a new
species (solid blue trace). Right: Overlay of electronic absorption features of the new species (solid blue trace) and intermediate A formed from the
treatment of [MnIII(O2)(L7BQ)]+ with excess CCA (dashed blue trace).
10 seconds. The electronic absorption features of this new 2 equiv. cyclohexanecarboxylic acid are treated with 40 equiva-
intermediate are almost identical to those of intermediate A lents of PPA, we observe the formation of a small amount of
(see Fig. 7, right). Under these conditions, the intermediate acetophenone (10% relative to the starting Mn concentration).
formed from the reaction of [MnIII(O2)(L7BQ)]+ with cyclohexane- These observations suggest that intermediate A is competent
carboxylic acid is stable for over 100 seconds at −40 °C in for aldehyde deformylation.
MeCN, which permitted its further characterization by
additional spectroscopic methods. On the basis of the dis-
appearance of the optical features of intermediate A, the half-
life of this species is ca. 10 minutes.
Discussion
Combined EPR and XAS characterization of intermediate A Peroxomanganese(III) adducts have been proposed as key inter-
reveal spectroscopic signatures associated with [MnII(L7BQ) mediates for a number of manganese-dependent enzymes, as
(OTf)2] in MeCN. For example, no signals were observed for well as for small-molecule catalysts featuring manganese
intermediate A in the parallel-mode spectrum at X-band fre- centers.1–6,15,16,80 Compared to analogous iron systems,
quency, but perpendicular-mode data revealed the presence of mechanistic knowledge of manganese-dependent biological
a six-line feature, centered at 350 mT, that is essentially identi- processes is still rather limited. Furthermore, due to numerous
cal in appearance to that of [MnII(L7BQ)(OTf)2] in MeCN challenges involved in enzymatic studies, small-molecule
(Fig. S18†). Spin quantification of the 6-line signal of inter- model complexes of Mn enzymes have been widely used to
mediate A relative to [MnII(L7BQ)(OTf)2] in MeCN indicates understand the properties of these enzymes.12,34,35,81–84
that the signal represents 80 15% of the Mn in the sample. Although η2-peroxomanganese(III) complexes are the most
However, as [MnII(L7BQ)(OTf)2] is colorless, a minority species, common example of Mn-peroxo species,22–28,31–41 η1-alkylper-
which is not observed by EPR spectroscopy, must give rise to oxomanganese(III), η1-hydroperoxomanganese(III), and trans-
the electronic absorption signals of intermediate A at 450 and μ-1,2-peroxo-bridged dimanganese(III,III) dimeric species have
595 nm. XAS data collected for intermediate A reveal XANES also been structurally and/or spectroscopically character-
data significantly perturbed relative to [MnIII(O2)(L7BQ)]+, but ized.29,30,85 However, a limitation in the thorough characteriz-
very similar to those of [MnII(L7BQ)(OTf)2] in MeCN ation of the structural properties and chemical reactivity of
(Fig. S19†). Notably, the XANES data of intermediate A are not these complexes stem from their commonly observed low
identical to those of [MnII(L7BQ)(OTf)2], suggesting the pres- chemical yields and impaired thermal stability.12
ence of additional Mn species. Collectively, the EPR and XAS
Sastri and co-workers have recently shown that a MnIII-
data suggest that the species responsible for the 450 and peroxo adduct supported by a neutral N5 ligand is able to
595 nm electronic absorption bands of intermediate A rep- deformylate PPA by a hydrogen-atom transfer mechanism
resents a small fraction of the total Mn in the sample, with the involving attack at the weak benzylic C–H bond of the sub-
bulk of Mn having reverted back to the MnII starting material.
strate.45 This work suggested that a MnIII-peroxo adduct sup-
As we can observe intermediate A by electronic absorption ported by a ligand with benzylic C–H bonds may be especially
spectroscopy, we are able to monitor the response of this susceptible to ligand degradation. Motivated by these obser-
species to added aldehydes. When [MnIII(O2)(L7BQ)]+ with vations, we designed the L7BQ ligand, which features a topo-
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logy similar to that of the L7py2 family that has shown much ence of acid impurities in aldehyde substrates.79 Our present
success in supporting MnIII-peroxo ligands, but lacks the observations underscore this point. Here, we provide strong
R
benzylic arms, which may be prone to oxidation.31,32,34
evidence that acid impurities in CCA convert the [MnIII(O2)
The MnII complex of the new L7BQ ligand, [MnII(L7BQ) (L7BQ)]+ species to a new, colored intermediate. Additional
(OTf)2], was structurally characterized by X-ray diffraction. As spectroscopic data also suggest the reaction of [MnIII(O2)
anticipated, the structure of this complex is similar to the (L7BQ)]+ with acid regenerates the corresponding MnII
R
related MnII salts of the L7py2 ligand family.31,32,34 When complex, with the chromophoric intermediate representing
treated with 5 equiv. of H2O2 and 1.0 equiv. of triethylamine, only ∼20% of Mn in the sample (Scheme 4).
[MnII(L7BQ)(OTf)2] produced a new intermediate in MeCN
While the identity of this intermediate is unclear, we postu-
solution at −40 °C. Electronic absorption and EPR spec- late that this new intermediate, and not [MnIII(O2)(L7BQ)]+, is
troscopy, mass spectrometry, and Mn K-edge XAS data provide responsible for the observed deformylation reactivity. Support
support for the formulation of this intermediate as the mono- for this proposal is provided by the reactions of [MnIII(O2)
nuclear MnIII-peroxo adduct [MnIII(O2)(L7BQ)]+. This inter- (L7BQ)]+ with PPA. When [MnIII(O2)(L7BQ)]+ is treated with pur-
mediate must be generated at cryogenic temperatures and ified PPA, lacking acid impurities, we observe no reaction. In
decays over the course of 50 minutes at −40 °C in MeCN. contrast, when [MnIII(O2)(L7BQ)]+ is treated with PPA that con-
Unlike several other MnIII-peroxo adducts, the decay of tains acid impurities, we observe changes in the electronic
[MnIII(O2)(L7BQ)]+ does not appear to be through the reaction absorption spectrum consistent with the formation of inter-
with the MnII starting material.
mediate A, and this intermediate decays further. Moreover,
The half-life of [MnIII(O2)(L7BQ)]+ at −40 °C in MeCN is ca. [MnIII(O2)(L7BQ)]+ treated first with 2 equiv. cyclohexanecar-
10 minutes. Thus, [MnIII(O2)(L7BQ)]+ does not display boxylic acid and then PPA shows evidence for a small amount
enhanced thermal stability relative to its [MnIII(O2)(L7py2R)]+ of acetophenone, the expected product of PPA deformylation.
analogues (the [MnIII(O2)(L7py2H)]+ complex was stable for
One of several possibilities for the identity of intermediate
hours at −40 °C and had a half-life of 15 minutes at 0 °C).31 A is a MnIII-hydroxperoxo adduct. To the best of our knowl-
For both [MnIII(O2)(L7BQ)]+ and [MnIII(O2)(L7py2R)]+ complexes, edge, the only examples of well-characterized MnIII-hydroxo-
the products of thermal decay have not been identified.31 In peroxo adducts come from the work of Nam and co-
addition to the different thermal stabilities, the [MnIII(O2) workers.78,86 By protonating the corresponding MnIII-peroxo
(L7BQ)]+ complex also showed reactivity with aldehydes dis- species, they have generated the [MnIII(OOH)(14-TMC)]+
tinct from that of the [MnIII(O2)(L7py2R)]+ complexes. and [MnIII(OOH)(13-TMC)]+ complexes (where 13-TMC is
Treatment of the [MnIII(O2)(L7py2R)]+ complexes with alde- 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclotridecane and 14-TMC
hydes (such as CCA and benzaldehydes) led to a decay that fol- is
1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane).78,86
lowed pseudo-first-order behavior. Experiments using different Kinetic investigations have revealed that the MnIII-hydroperoxo
concentrations of CCA showed an increased decay rate with adducts react more rapidly with CCA than their MnIII-peroxo
increasing CCA concentration, which permitted the determi- counterparts. Specifically, the second-order rate constants (k2)
nation of second-order rate constants.32
for the reactions of [MnIII(OOH)(13-TMC)]+ and [MnIII(O2)
Unlike those systems, the reaction of [MnIII(O2)(L7BQ)]+ and (13-TMC)]+ with CCA are, respectively, 1.2(1) × 10−1 M−1 s−1 (at
CCA did not follow pseudo-first-order kinetics. Instead, the −10 °C) and 2.0(1) × 10−2 M−1 s−1 (at 10 °C). In addition, the
addition of CCA led to the rapid formation of intermediate A, reaction of acid with [MnIII(O2)(14-TMC)]+ to generate
characterized by band maxima at 595 and 450 nm (Fig. 6, left). [MnIII(OOH)(14-TMC)]+ was quite rapid compared to both of
This intermediate then slowly decayed. Nonetheless, analysis these processes. Thus, in cases where acid impurities are
of the solution obtained at the end of the reaction provided present in the aldehyde substrate, it could be that the metal-
evidence for roughly 40% cyclohexanone formation, suggestive hydroperoxo adduct, rather than the metal-peroxo, is the active
of aldehyde deformylation. Additional experiments showed species for aldehyde deformylation.
that the intermediate observed by electronic absorption
Similar kinetic studies have been performed for iron
spectroscopy (intermediate A) resulted from the reaction of systems, where there are also examples of interconversion of
[MnIII(O2)(L7BQ)]+ with acid impurity present in CCA.
FeIII-peroxo and FeIII-hydroperoxo adducts using acid–base
McDonald and coworkers have previously emphasized the chemistry.87,88 Most relevant to this present work are investi-
challenge in assigning the identity of the active metal species gations of the reactivity of FeIII-peroxo and FeIII-hydroperoxo
in reactions with aldehydes precisely because of the persist- adducts of the 14-TMC ligand with aldehydes. Specifically, the
Scheme 4 Summary of reactivity observed upon addition of cyclohexanecaboxylic acid to [MnIII(O2)(L7BQ)]+.
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[FeIII(OOH)(14-TMC)]+ complex was observed to readily react
with PPA at low temperatures, whereas the corresponding
[FeIII(O2)(14-TMC)]+ complex only reacted with PPA at higher
temperatures. The higher nucleophilic reactivity of the iron-
hydroperoxo species was attributed to the end-on binding
mode. The same trend was observed for electrophilic reactions,
where the FeIII-hydroperoxo was more active towards weak C–H
bonds than the FeIII-peroxo species.88
2 L. E. Grove and T. C. Brunold, SECOND-SPHERE TUNING
OF THE METAL ION REDUCTION POTENTIALS IN IRON
AND MANGANESE SUPEROXIDE DISMUTASES, Comments
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Thus, it has been seen in both Fe and Mn chemistry that
metal(III)-peroxo and metal(III)-hydroperoxo adducts can have
large, and somewhat unexpected, differences in reaction rates
with aldehydes substrates. Given these collective observations,
we echo McDonald in suggesting that the role of acid impuri-
ties in obfuscating understanding of aldehyde reactivity
should be considered in all studies of aldehyde deformylation
by metal-peroxo complexes.79
4 W. A. Gunderson, A. I. Zatsman, J. P. Emerson,
E. R. Farquhar, L. Que, J. D. Lipscomb and M. P. Hendrich,
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8 A. Tanner, L. Bowater, S. A. Fairhurst and S. Bornemann,
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This
work
was
supported
by
the
U.S.
NSF
(CHE-1565661). M. C. D. was supported by the NIH Graduate
Traineeship T32 GM08545. The U.S. NSF is acknowledged for
funds used for the purchase of the EPR spectrometer
(CHE-0946883). Support for the NMR instrumentation was pro-
vided by NIH Shared Instrumentation Grant # S10OD016360
and NIH Shared Instrumentation Grant # S10RR014767. Use of
the Stanford Synchrotron Radiation Lightsource, SLAC
National Accelerator Laboratory, is supported by the U.S.
Department of Energy, Office of Science, Office of Basic Energy
9 A. J. Wu, J. E. Penner-Hahn and V. L. Pecoraro, Structural,
Spectroscopic, and Reactivity Models for the Manganese
Catalases, Chem. Rev., 2004, 104(2), 903–938.
Sciences under Contract No. DE-AC02-76SF00515. The SSRL 10 J. A. Cotruvo, T. A. Stich, R. D. Britt and J. Stubbe,
Structural Molecular Biology Program is supported by the DOE
Office of Biological and Environmental Research, and by the
National Institutes of Health, National Institute of General
Medical Sciences (including P41GM103393). The contents of
this publication are solely the responsibility of the authors and
Mechanism of Assembly of the Dimanganese-Tyrosyl
Radical Cofactor of Class Ib Ribonucleotide Reductase:
Enzymatic Generation of Superoxide Is Required for
Tyrosine Oxidation via a Mn(III)Mn(IV) Intermediate, J. Am.
Chem. Soc., 2013.
do not necessarily represent the official views of NIGMS or 11 J. J. A. Cotruvo and J. Stubbe, Metallation and mismetalla-
NIH. XAS experiments at Brookhaven National Lab were sup-
ported by the Case Western Reserve University Center for
Synchrotron Biosciences NIH grant, P30-EB-009998, from the
tion of iron and manganese proteins in vitro and in vivo:
the class I ribonucleotide reductases as a case study,
Metallomics, 2012, 4(10), 1020–1036.
National Institute of Biomedical Imaging and Bioengineering 12 D. Leto and T. Jackson, Peroxomanganese complexes as an
(NIBIB). The NSF (CHE-0923449) and the University of Kansas
are acknowledged funds to purchase the X-ray instrumenta-
tion, computers, and software used in this study.
aid to understanding redox-active manganese enzymes,
J. Biol. Inorg. Chem., 2014, 19(1), 1–15.
13 R. A. Baglia, J. P. T. Zaragoza and D. P. Goldberg,
Biomimetic Reactivity of Oxygen-Derived Manganese and
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