Engineering the Oxidative Potency of Non-Heme Iron(IV) Oxo Complexes in Water for C-H Oxidation by a cis Donor and Variation of the Second Coordination Sphere

Article abstract of DOI:10.1021/acs.inorgchem.0c03441

A series of iron(IV) oxo complexes, which differ in the donor (CH2py or CH2COO-) cis to the oxo group, three with hemilabile pendant donor/second coordination sphere base/acid arms (pyH/py or ROH), have been prepared in water at pH 2 and 7. The νFe= O values of 832 ± 2 cm-1 indicate similar FeIV= O bond strengths; however, different reactivities toward C-H substrates in water are observed. HAT occurs at rates that differ by 1 order of magnitude with nonclassical KIEs (kH/kD = 30-66) consistent with hydrogen atom tunneling. Higher KIEs correlate with faster reaction rates as well as a greater thermodynamic stability of the iron(III) resting states. A doubling in rate from pH 7 to pH 2 for substrate C-H oxidation by the most potent complex, that with a cis-carboxylate donor, [FeIVO(Htpena)]2+, is observed. Supramolecular assistance by the first and second coordination spheres in activating the substrate is proposed. The lifetime of this complex in the absence of a C-H substrate is the shortest (at pH 2, 3 h vs up to 1.3 days for the most stable complex), implying that slow water oxidation is a competing background reaction. The iron(IV)= O complex bearing an alcohol moiety in the second coordination sphere displays significantly shorter lifetimes due to a competing selective intramolecular oxidation of the ligand.

Full text of DOI:10.1021/acs.inorgchem.0c03441

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Article
Engineering the Oxidative Potency of Non-Heme Iron(IV) Oxo
Complexes in Water for C−H Oxidation by a cis Donor and Variation
of the Second Coordination Sphere
Christina Wegeberg, Mathias L. Skavenborg, Andrea Liberato, James N. McPherson, Wesley R. Browne,
Erik D. Hedegård, and Christine J. McKenzie*
Cite This: Inorg. Chem. 2021, 60, 1975−1984
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sı Supporting Information
ABSTRACT: A series of iron(IV) oxo complexes, which differ in
−
the donor (CH py or CH COO ) cis to the oxo group, three with
2
2
hemilabile pendant donor/second coordination sphere base/acid
arms (pyH/py or ROH), have been prepared in water at pH 2 and
1
IV
7
. The ν
values of 832 ± 2 cm− indicate similar Fe O
FeO
bond strengths; however, different reactivities toward C−H
substrates in water are observed. HAT occurs at rates that differ
by 1 order of magnitude with nonclassical KIEs (k /k = 30−66)
consistent with hydrogen atom tunneling. Higher KIEs correlate
with faster reaction rates as well as a greater thermodynamic
stability of the iron(III) resting states. A doubling in rate from pH
H
D
7
to pH 2 for substrate C−H oxidation by the most potent
IV 2+
complex, that with a cis-carboxylate donor, [Fe O(Htpena)] , is
observed. Supramolecular assistance by the first and second coordination spheres in activating the substrate is proposed. The lifetime
of this complex in the absence of a C−H substrate is the shortest (at pH 2, 3 h vs up to 1.3 days for the most stable complex),
implying that slow water oxidation is a competing background reaction. The iron(IV)O complex bearing an alcohol moiety in the
second coordination sphere displays significantly shorter lifetimes due to a competing selective intramolecular oxidation of the
ligand.
12
INTRODUCTION
in water. The precatalyst and resting state for these systems is
iron(III), and aggregation by oxo-bridged formation is
presumably alleviated due to the already high anionic charge
of the ligands and complexes. Reactivity spanning the oxidative
destruction of organic water pollutants through C−H
activation to water oxidation is tuned by minor structural
variations in the planar tetradentate TAML ligands and
■
Synthetic iron(IV) oxo complexes are models for the active
sites of mononuclear non-heme iron enzymes capable of
substrate C−H oxidation. Both hydrogen atom transfer (HAT)
and oxygen atom transfer (OAT) mechanisms are proposed
1
−7
for these reactions;
however, the generation and spectro-
scopic characterization of the transient iron oxidant and high-
valent iron oxo species have been performed predominantly in
organic solvents, below room temperature, conditions that are
of limited biological relevance. Studies in water are often
hampered by the insolubility of the complexes; however, pH
and especially ligand dissociation are significant and
complicatingfactors for the stability and reactivity of
iron(IV) oxo species and their precursors, not least since
iron(III) complexes tend to aggregate through oxo-bridge
formation, even at low pH. Reactions in water are quite
simply more difficult to study in comparison to those in
organic solvents, and the reactivity trends of non-heme
iron(IV) oxo complexes in an aqueous milieu have yet to be
established.
13−21
experimental conditions.
ligands have also been reported to oxidize water,
Iron complexes of aminopyridyl
2
2−26
and
8
while the oxidation of water is sought for in the field of artificial
9
27
photosynthesis, it is a show-stopping competing reaction
1
0
when organic substrates are the targets for oxidation under
aqueous conditions. The crucial O−O bond forming step in
water oxidation to O and C−H bond cleaving steps are
2
mechanistically distinct (Scheme 1), and reactivity in one
11
Received: November 23, 2020
Published: January 20, 2021
The work of Collins and co-workers with the “first to fourth”
generation tetraamido macrocyclic ligand (TAML) high valent
iron oxo systems stands out with respect to a focus on working
©
2021 American Chemical Society
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2,53,55
Article
5
III
Scheme 1. Alternative Pathways: What Are the Supporting
Ligand and Environmental Factors That Determine if the
Reaction Proceeds toward the Right or toward the Left for
an Iron(IV) Oxo Complex?
anol.
Equivalent (N4O)Fe OOH/R complexes oxidize
methanol rapidly, precluding the use of this solvent for a
determination of comparable spectroscopic data, and intra-
molecular ligand amine or aryl oxygenation reactions
56,58
occur.
To date spectroscopic data have been gathered
for only one biomimetic cis carboxylato iron peroxide which is
supported by N,N,N′-tris(2-pyridylmethyl)ethylenediamine-
4
3,57−60
N′-acetate (tpena).
The Rtpen system (Scheme 2), which includes tpena, offers
a convenient scaffold for probing the importance of the
position cis to the oxo ligand. This can be a pyridine
6
1,62
or
43,57
−
carboxylato
donor when R = CH py or CH COO . The
reaction type does not imply reactivity in the other. Mutual
exclusion or possible competition between these reactions
might be engineered through a modification of the supporting
ligand. In general, the field of non-heme iron modeling is
lagging in the rate of attaining a comparable level of maturity in
the knowledge of the structure−activity relationship (SAR) in
comparison to that which was achieved in the field of noble
organometallic catalysts in the last half of the 20th century.
In comparison to the planar anionic Fe-TAML systems,
many of the cationic iron(IV) oxo complexes are more
reminiscent of the iron(IV) oxo intermediates which play a
crucial role in the oxidation of strong C−H bonds catalyzed by
2
2
potentially hexadentate ligands are hemilabile, and six-
coordinated metal oxo complexes will be bifunctional through
pentadenticity and the genesis of the nonchelating methylpyr-
idyl arm or ethyl alcohol arm. This will furnish a stereochemi-
cally appropriate proximal acid/base group in the second
coordination sphere. A systematic investigation of the Rtpen
iron(IV) oxo systemat two pH values in waterusing six
structurally related non-heme iron(IV) oxo complexes
(
Scheme 2) differing in the cis donor and second coordination
sphere is described in the present study. The trans donor (a
tertiary amine) is identical in all six complexes, and two of the
IV
2+/3+
IV
28−30
complexes, [Fe O((H)tpen)]
and [Fe O((H)-
non-heme iron-dependent enzymes.
Minor variations in
tpena)]+ , have acidic and basic forms depending on the
pH due to the pyridyl group in the second coordination
sphere.
/2+
the active site environments in this class of enzyme tune the
31−35
reactivities, allowing for a wide diversity in function.
A
systematic exploration of the comparative potencies of cationic
iron oxo models toward C−H bondsin wateris now
RESULTS AND DISCUSSION
timely. Since common features of the mononuclear O -
■
2
52
53
53
63
activating non-heme iron enzymes are an Asp/Glu O donor
Iron(II) complexes of metpen, ettpen, bztpen, tpen,
55
43,64
in the first coordination sphere cis to putative O binding
and tpenOH and an iron(III) complex of Htpena
2
2
8,36
sites
and hydrogen-bonding motifs in the second
(Scheme 2) were used as the solid-state starting materials for
the aqueous species, which were oxidized by cerium
ammonium nitrate (CAN) (3 equiv) to generate the
3
7−39
coordination sphere,
systems that can address the
influence of these features should be targeted. Influences
from the second coordination sphere have been probed for
model systems in nonaqueous solvents through the introduc-
IV
2+
IV
2+
IV
complexes [Fe O(metpen)] , [Fe O(ettpen)] , [Fe O-
2
+
IV
3+
IV
2+
(bztpen)] , [Fe O(Htpen)] , [Fe O(tpenOH)] , and
40−44
45−47
IV
2+
tion of pendent basic groups
and Lewis acids.
[Fe O(Htpena)] , respectively (Scheme 2c; for an explan-
ation of proton placement in the formulations see Scheme 2b).
These reactions occur with a final pH of 2 at room
temperature. The iron(II) complexes of the neutral ligands
metpen, ettpen, bztpen, and tpen are oxidized according to eqs
1a and 1b. Equation 1b only applies to the iron(III) complexes
Trends in reactivity, efficiency and selectivity in aqueous
solution are not known. To date the supporting ligand
influence on the properties of Fe(IV) oxo complexes,
predominantly studied in organic solvents, show that trans
donors, not unexpectedly, have a significant influence on the
48,49
III
2+
spectroscopic properties and reactivity.
The cis position as
of tpena and deprotonated tpenOH ([Fe (tpenO)] is
II
part of a chelating ligand to the oxo ligand has been more
scantily probed. Notably, it was recently found that (in organic
solvent) using a N3O macrocycle analogue of cyclam through
replacement of one of the tertiary amine donors with a neutral
ether oxygen atom enhances the rate of HAT reactions by 5
spontaneously generated on dissolution of [Fe Cl(tpenOH)]-
5
8
(PF ) under ambient conditions ). Given the pK of
6
a
pyridinium (ca. 5.5) noncoordinated methylpyridine arms in
the complexes of tpen and tpena will be protonated at pH
5
9,65
2.
Likewise, on the basis of the pK values of alcohols vs
a
50
orders of magnitude. In the only SAR study to be carried out
pyridinium, decoordination and protonation of the alkoxide
51
III
2+
in water, Chartarojsiri et al. have shown that an increase in
correlates with an increase in HAT and OAT rates
donor in [Fe (tpenO)] can be anticipated when this
IV
2+
ν
complex converts to [Fe O(tpenOH)] .
FeO
within a series of iron(IV) oxo complexes supported by
pentadentate pentapyridyl ligands, where the para substituent
on the pyridyl donor trans to the oxo group is varied (H, CH3,
CF3).
Fe + Ce + H O → Fe −OH + Ce + H+
II
IV
III
III
(1a)
(1b)
2
Fe −OH + Ce → Fe O + Ce + H+
III
IV
IV
III
−
Our earlier work shows clearly that a biomimetic
monodentate carboxylato donor in the cis position of non-
heme iron peroxides and oxides exerts significant influence on
the reactivity of non-heme iron systems in comparison to
The addition of hypochlorite (ClO ) to aqueous solutions
of the precursor complexes also produces iron(IV) oxo
complexes (eqs 2a−2d), and in this case the final pH is 7.
At this pH, noncoordinated py arms can be expected to
dominantly exist as the free base. Again the alcohol arm of
tpenOH will be uncoordinated in the iron(IV) oxo complex. It
is reasonable to expect that the pH is important for the ensuing
reactivity of these iron(IV) oxo complexes and that the
52−58
systems based on analogous neutral N-only donor ligands.
One manifestation of this is the difference in the solvents in
III
which peroxide adducts can be detected. (N5)Fe OOH/R
complexes have been characterized predominantly in meth-
1
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Article
II
−
IV
−
Scheme 2. (a) Generic Chemical Structure of the Ligands N-
Fe + ClO → Fe O + Cl
(2d)
a
R-N,N′,N’-tris(2-pyridylmethyl)ethane-1,2-diamine, (b)
The X-ray structures of the stable isostructural and isovalent
complexes [V O(Htpena)](ClO ) ·H O, [V O(tpen)]-
ClO ) , and [V O(tpenOH)](PF ) (Figure 1, see the
4 2 6 2
Drawing Specifying Protonation Sites in the tpenaH/tpena/
Htpena and tpenOH/tpenO/HtpenO Designations in
Complex Formulations, and (c) the Iron(IV) Oxo
43
IV
IV
4
2
2
IV
(
b
Complexes at pH 2
IV
Figure 1. Crystal structures of the cations in (a) [V O(Htpena)]-
(
4
ClO ) (H O) (included for facile comparison, coordinates from ref
4 2 2 2
IV
IV
3), (b) [V O(tpen)](ClO ) , and (c) [V O(tpenOH)](PF ) .
4
2
6
2
Thermal ellipsoids are shown at 50% probability. Hydrogen atoms,
except those on the dangling methylpyridyl and ethyl alcohol arms of
IV
2+
IV
2+
[
V O(Htpena)] and [V O(tpenOH)] , respectively, are omitted
for clarity.
a
R = methyl, ethyl, or benzyl group in metpen, ettpen, and bztpen,
Supporting Information for crystallographic details) exemplify
the bifunctionality of the ligand scaffolds and perhaps suggest
the most likely isomers of the analogous iron(IV) oxo
compounds. Importantly, a tertiary amine donor is trans to
the vanadium(IV) oxo moiety in all three structures.
Consequently, the VO distances in these complexes are
respectively; N,N,N′,N′-Tetrakis(2-pyridylmethyl) ethylenediamine =
tpen. N,N,N′-Tris(2-pyridylmethyl)ethylenediamine-N′-ethanol =
tpenOH. N,N,N′-Tris(2-pyridylmethyl)ethylenediamine-N′-acetate =
b
tpena. The pyridiniums in the second coordination spheres are
deprotonated at pH 7 and shown in red.
43
similar at 1.59(15), 1.5943(13), and 1.591(3) Å, respectively.
The structures support that, in solution, the second
pyridinium H atom donor (pH 2), pyridine H atom acceptor
+
coordination sphere arms (−CH pyH , −CH py, or
2
2
(
pH 7), and alcohol (pH 2 and 7) groups in the second
−
CH CH OH) are sterically capable of interacting (by an
electrophilic interaction or by H-bonding) with the cis Fe O
2 2
coordination spheres might potentially play a role in C−H
oxidation reactions by these complexes.
IV
moiety and potentially proximal substrates. Equally, they are
+
II
−
III
−
nucleophiles (in the case of −CH pyH , and −CH CH OH,
2
Fe + ClO + H O → 2Fe −OH + Cl
(2a)
(2b)
(2c)
2
2
2
2
after deprotonation) and are sterically capable of replacing the
oxo ligand to become hexadentate ligands. In the solid state,
the pyridinium of [V O(Htpena)] H-bonds to the non-
III
−
III
−
Fe −OH + ClO → Fe −OCl + OH
IV
2+
III
IV
•
43
Fe −OCl → Fe O + Cl
coordinated carboxyl group of an adjacent complex cation
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1
Figure 2. H NMR (400 MHz) from 50 to −20 ppm of [Fe O(Htpena) ](ClO ) dissolved in D O (1 mM) and oxidized with CAN (6 equiv)
2
2
4
4
2
with an inset showing the range from 9 to 8 ppm.
and the disordered alcohol arm of [V O(tpenOH)]2+ H-
IV
potentially be either protonated or deprotonated. We
investigated all variants (i.e., protonated fully N-coordinated
[Fe O(tpenaH)] and O-coordinated [Fe O(Htpena)]
bonds to a counteranion, while the free pyridine N of
V O(tpen)] does not show any significant supramolecular
IV
2+
IV
2+
IV
2+
[
interaction. Interestingly, the complexes achieve the same
overall cationic charge in the crystal structures, despite the
support of an effectively pentadentate monoanionic (tpena) or
neutral (tpen and tpenOH) first coordination sphere because
of the charge-compensating ionizable dangling pendant arms.
Protonationor notof the uncoordinated py arm is,
however, likely to be driven by crystal-packing forces since
and the corresponding deprotonated systems). The calcu-
lations predict that the energy differences between the N4O
and N5 coordination are about half of those for the
corresponding tpenOH complexes; hence, it could not
unequivocally be concluded on the basis of the DFT
calculations which of the isomers was the most stable.
1
IV
2+
The H NMR spectrum of [Fe O(Htpena)] (generated in
situ from [Fe O(Htpena) ](ClO ) and CAN) in D O shows
pK values of the noncoordinated functional groups are not
a
2
2
4 4
2
expected to vary significantly. The N(CH py) (N1, N2, N3)
narrow and well-defined resonances in the range of −17 to 45
ppm (Figure 2). Significantly, one set of pyridyl resonances at
8.7 ppm (d, J = 6.2 Hz, 1H), 8.5 ppm (t, J = 8.1 Hz, 1H), 8.0
ppm (d, J = 7.8 Hz, 1H), and 7.9 ppm (t, J = 6.9 Hz, 1H)
(Figure 2 insert) is not paramagnetically shifted, consistent
with noncoordination of one pyridyl arm at this pH. The
2
2
tridentate end is consistently facial in all of the known
structures of the Rtpen ligands. We note that the arrangement
of the remaining tertiary amine and py donors in the
IV
2+
pentadentate tpenOH of [V O(tpenOH)] is opposite to
II
+
55
II
IV
that in [Fe Cl(tpenOH)] : i.e., the Fe −Cl and V =O units
cannot simply be substituted from one to the other structure.
The bifunctionality of the ligands tpenaH/tpena/Htpena
and tpenOH/tpenO/HtpenO in the iron(IV) oxo complexes
IV
2+
spectrum is reminiscent of that of [Fe O(bztpen)] recorded
6
6
in d -MeCN, where the presence of one isomer was
3
concluded. Thus, the two coordinating pyridyl units are
(
(
Scheme 2) was investigated with density functional theory
DFT). Using the crystal structures of the V O complexes as a
oriented parallel with the FeO axis, exactly as in the
IV
IV
2+
structures of [V O(Htpena)] (Figure 1). Solution-state
NMR spectroscopy and the crystal structure of the vanadium
complex analogue indicate that the relevant solution species is
starting point, we investigated the feasibility of interchanging
either the carboxyl O1 with pyridine nitrogen (N3) in Figure
1
IV
2+
a or the pyridine N4 with the (deprotonated) O2 in Figure 1c
[Fe O(Htpena)] at pH 2. It is important to note that the
IV
2+
for the coordination to the iron(IV) oxo unit. Additionally, we
also investigated other potential isomers with DFT, but they
were generally found to be less stable. The results of these
DFT calculations are given in Tables S4 and S5.
The DFT calculations indicate that, for iron(IV) oxo
complexes of the HtpenO/tpenOH ligand, the complex with
the first coordination sphere comprised of only N donors is the
most stable, by more than 50 kJ/mol. This is the structure
iron speciation is not 100% [Fe O(Htpena)] in the NMR
sample that produces the spectrum in Figure 2. At pH 2 the
remaining iron speciation takes the form of antiferromagneti-
cally coupled iron(III) centers in [Fe O(Htpena) ] . This
situation allows for the tractable H NMR spectrum shown. At
43
III
2
4+
2
1
1
pH 7 the H NMR spectrum is too broad to allow extracting
any useful information (Figure S1). This is due to the fact that
IV
+
the concentration of [Fe O(tpena)] will be lower at pH 7
IV
IV
2+
obtained for the analogue [V O(tpenOH)](PF ) (Figure
than that of [Fe O(Htpena)] at pH 2, due to the shorter
6
2
1
c). The situation is more complex for the Htpena/tpenaH
lifetime, and significantly, that the dominant resting state
speciation ([Fe 2O(Htpena)2] ⇄ 2[Fe (OH)(tpena)] +
III
4+
III
+
ligand, where both free pyridine and free carboxylate arms can
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H O) is now in the form of the high-spin complex
that the variation in the cis donor from a negatively charged
2
III
+
43
[
Fe (OH)(tpena)] (S = 5/2). This will broaden the
carboxylato group to softer neutral aromatic N atoms has
IV
NMR resonances. The UV/vis spectra at pH 2 and pH 7 are
the same (vide infra); thus, it is likely that the first
coordination sphere is the same at both pH values, i.e., N4O
coordination sphere for the iron(IV) oxo complexes of Htpena
negligible influence on the Fe O bond strength. The
IV
electronic structures, however, differ slightly, with [Fe O-
2
+
(Htpena)] exhibiting the most red shifted λmax (by ca. 300
−
1
cm , 730 nm vs 712−723 nm).
(
pH 2) and tpena (pH 7).
The UV/vis absorption and Raman spectra (Figure 3, Figure
The iron(IV) oxo complexes at pH 2 show differences in
their ability to oxidize water-soluble alcohols (Table 1). The
substrates 1-phenylethanol, benzyl alcohol, cyclohexanol, and
isopropanol have C−H bond dissociation energies (BDEs) of
S2, and Tables 1 and 2) for the series of iron(IV) oxo
−
1
8
5, 88, 93, and 95 kcal mol , respectively, for the C−H bonds
68
of the alcohol carbon atom. Pseudo-first-order rate constants,
kobs, and second-order rate constants, k , for substrate
2
oxidation were determined from the decay in NIR absorbance
(
Figures S3−S9). The only products, determined by gas
chromatography, were acetophenone, benzaldehyde, cyclo-
hexanone, and acetone, respectively. For all complexes, k2
values for the oxidation of cyclohexanol fall within 1 order of
magnitude of that of [Fe O(Htpena)] , which is significantly
the most reactive (43 mM s ). At pH 2 the rates of
oxidation for the individual substrates are similar for
IV
2+
−
1
−1
IV
2+
IV
2+
IV
[
(
[
(
Fe O(metpen)] , [Fe O(ettpen)] , and [Fe O-
3
+
Htpen)] , and these are slow in comparison to those for
IV
2+
IV
2+
IV
Fe O(bztpen)] , [Fe O(tpenOH)] , and [Fe O-
2
+
Htpena)] . The rate constants for benzyl alcohol oxidation
for all of the complexes, apart from that generated from the
tpenOH ligand, are less spread at pH 7 (Table 2). Notably,
however, benzyl alcohol oxidation is 2.5 times slower when it is
IV
+
IV
2+
catalyzed by [Fe O(tpena)] (pH 7) vs [Fe O(Htpena)]
(
IV
2+
pH 2). [Fe O(Htpena)] , generated electrochemically in
water (pH 4), showed k values for oxidation of benzyl alcohol,
2
−
3
−3
isopropanol, and cyclohexanol of 2.1, 16 × 10 , and 47 × 10
−
1
−1
59
M
s , respectively, similar to those seen here at pH 2.
Given the pK of propanoic acid is 4.88, it can be expected that
a
IV
2+
in both cases the speciation is [Fe O(Htpena)] . Hence, the
reactivity of the complexes in water is intrinsic and independent of
the method of preparation (chemical or electrochemical).
Tunneling effects can be a major contributor to the reaction
rates and selectivity in H atom transfer from C−H bonds as a
69−71
consequence of the hydrogen atom’s low mass.
High KIEs
IV
2+
are characteristic of tunneling mechanisms and have been
reported for the HAT reactions performed by enzymatic
iron(IV) oxo intermediates: 37 in the α-ketoglutarate-depend-
Figure 3. (a) UV/vis absorption spectra of [Fe O(tpenOH)]
IV
2+
(
[
blue, λ , 723 nm), [Fe O(Htpena)] (green, λ
Fe O(Htpen)] (purple, λ 712 nm), [Fe O(bztpen)] (black,
λmax 722 nm), [Fe O(ettpen)] (orange, λmax 718 nm), and
Fe O(metpen)] (red, λmax 714 nm) in water. Conditions: [Fe]
730 nm),
max
max
IV
3+
IV
2+
max
72
IV
2+
ent dioxygenases (TauD “J”) and 50−100 for methane
IV
2+
73
IV
[
monooxygenase.
The KIEs (Table 1) for [Fe O-
2
+
I V
2 +
I V
=
1.5 mM, 3 equiv of CAN. The dashed line indicates λ = 722 nm. (b)
(metpen)] , [Fe O(ettpen)]
(Htpen)] (generated using CAN) in the oxidation of benzyl
alcohol were ca. 30, while [Fe O(bztpen)] , [Fe O-
tpenOH)] , and [Fe O(Htpena)] show KIEs of ca. 63
,and [Fe O-
IV
2+
3+
Raman spectra of [Fe O(Htpena)] generated in H O (green) and
2
18
H2 O (gray). Conditions: [Fe] = 4 mM, pH 2, [CAN] 12 mM, λexc
=
IV
2+
IV
785 nm, rt.
2+
IV
2+
(
and their k ′ values (where k ′ is k divided by the number of
2
2
2
complexes are identical at pH 2 and pH 7. The iron(IV) oxo
complexes are blue to green with a narrow λmax range of 712−
equivalent substrate C−H bonds that can be attacked)
correlate with the bond dissociation energies of the substrates
(Figure 4). Hence, the data we report here are consistent with
C−H bond cleavage as the rate-determining step, as expected
for HAT reactions.
−
1
7
30 nm and a ν
Raman band at 832 ± 2 cm , typical for
FeO
8
18
18
non-heme iron(IV) oxo complexes. In H O, the Fe O
2
IV
2+
IV
stretching bands for [Fe O(Htpena)] and [Fe O-
2
+
−1
(
ettpen)] are shifted to 795 and 796 cm (Figure 3b),
respectively, as expected (Δ = 36 cm using the two-atom
approximation). A change in the trans position will typically
For comparison, nonclassical, but lower, k /k KIE values
H
D
−
1
(10−30) were noted for non-heme iron(IV) oxo (S = 1)
48,74−77
complexes prepared in organic solvents.
Klein et al.
IV
48,49,67
exert a significant influence on the Fe O bond;
thus,
have reported a KIE of 80 (−20 °C, 9,10-dihydroanthracene,
in methanol) for a tetramethylcyclam iron(IV) oxo complex
with a thiolate donor trans to the oxo, significantly higher than
that when acetonitrile occupies this position (KIE = 10, 25
the lack of variation in the Raman spectroscopic data supports
that the trans donor, a tertiary amine, remains a constant
throughout the series in aqueous solutions and that the crystal
structures in Figure 1 are representative. It is especially notable
78
°C). The large KIE was attributed to tunnelling. The
1
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Table 1. Spectroscopic Characterization, Half-Life for Spontaneous Decrease in Absorbance at λmax (t1/2), k , and Kinetic
2
Isotope Effect (k /k ) of Iron(IV) Oxo Complexes in Water Generated by the Addition of 3 equiv of CAN to the Precursors
H
D
a
(
pH 2, 22 °C)
2
k (PhCH(OH)
b
18
ν
Fe=O ( O-H
2
O)
k
2
(CyOH)
k
2
((CH
(10 M
3
)
2
CHOH)
CH
3
)
k
2
(PhCH
(10 M
2
OH)
2 2
k (PhCD OH)
3
−
1
3
−1 −1
3
−1 −1
(10 M s−1
3
−1
3
−1 −1
−1 −1
λmax (nm)
(cm
)
t
1/2
(10 M
s
)
s
)
)
s
)
(10 M
19
s
)
H D
k /k
IV
3+
[
[
[
[
Fe O(Htpen)]
712
833
1.1
days
1.3
days
1.3
days
1.1
days
5
7
6
−
−
510
27
39
25
60
IV
2+
Fe O(metpen)]
714
718
722
723
831
−
−
5
−
630
470
16
19
19
IV
2+
Fe O(ettpen)]
833 (796)
831
−
IV
2+
Fe O(bztpen)]
19
950
1120
IV
2+,
c
[
Fe O(tpenOH)]
832
80 s
3 h
30
43
5
630
990
16
30
62
66
IV
2+
43
[
Fe O(Htpena)]
730
831 (795)
17
1870
1980
a
b
c
IV
2+
Legend: −, data not available. λexc 785 nm. The competing ligand oxidation of [Fe O(tpenOH)] has been taken into account in the
determination of C−H rate constants.
−
Table 2. Spectroscopic Data, t1/2, and k for Iron(IV) Oxo Complexes in Water Generated with 3 equiv of ClO to the
Precursors (pH 7, 22 °C)
2
a
b
(cm−1
k (CyOH) [10 M s−1
3
−1
k (PhCH OH) [10 M s−1
3
−1
λmax (nm)
ν
FeO
)
t1/2
]
]
2
2 2
IV
2+
[
[
[
[
[
[
Fe O(tpen)]
712
714
718
722
723
730
832
832
833
830
np
1.5 h
4.5 h
1.5 h
1.5 h
60 s
−
−
−
16
#
550
600
580
890
#
IV
2+
Fe O(metpen)]
IV
2+
Fe O(ettpen)]
IV
2+
Fe O(bztpen)]
IV
2+
Fe O(tpenOH)]
Fe O(tpena)]+
IV
831
1.5 h
20
780
a
Legend: np, not possible due to short t1/2; −, not performed; #, experiment not possible due to competing regioselective oxidation of the ligand to
b
tpena under these conditions (see text). λ 785 nm.
exc
Figure 4. (left) Plot of kobs against substrate concentration of benzyl alcohol to determine k and KIE. (right) Plot of log k ′ vs C−H BDEs of
2
2
IV
2+
IV
2+
IV
2+
substrates. Color code: black, [Fe O(bztpen)] ; blue, [Fe O(tpenOH)] ; green, [Fe O(Htpena)] .
IV
+/2+
different donors in these cases, however, clearly attenuate the
FeO bond; Fe−O distances are 1.65 and 1.70 Å for the trans
[Fe O(TMC)(X)]
complexes correlated with increasing
k (and decreasing free energy of activation ΔG*), in line with
the two-state-reactivity (TSR) model. We here focus on
2
79,80
77
MeCN and thiolate complexes, respectively.
The latter
distance is the longest recorded for an S = 1 iron(IV) oxo
specific isomers of the iron(IV) oxo complexes of tpenOH/
HtpenO and tpenaH/tpena/Htpena (chosen on the basis of
ligand conformations found in crystal structures of the
vanadium(IV) oxo complexes and spectroscopic indications).
For these complexes, calculations were performed for both S =
and S = 2 spin states; we only discuss B3LYP results here,
but TPSS was also investigated. The two functionals in almost
all cases agree that the most stable spin state is the S = 1 state
the exception is [Fe O(HtpenO)] ). This result is
consistent with the prediction that can be based on the
spectrochemical series. Thus, a carboxylate donor is also
expected to be a weaker ligand than pyridine; hence, higher
spin states will favored.
8
complex. Given that it is the cis donor we vary, the
expectation for the present series is that the length of the
FeO bonds, which all show the same ν
values, are close
FeO
IV
2+ 81
to the 1.67 Å found for [Fe O(bztpen)] . The structures of
the vanadyl complexes (Figure 1) illustrate that little variation
is expected with VO distances of 1.593 ± 0.002 Å.
1
To understand the observed reactivity in more detail, we
also calculated the energy difference ΔE
(Q = quintet, T =
Q−T
IV
2+
(
triplet), as this parameter is often invoked in discussions of
8
2−84
(
two-state) reactivity in HAT reactions.
previous studies (in organic solvents) have found that a
decreasing spin-state splitting ΔE (spanning −6 to +20 kJ/
We note that
Q−T
mol with the B3LYP functional) for a series of 11
1
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Article
IV
2+
IV
2+
For [Fe O(tpenOH)] and [Fe O(Htpena)] the
calculations are consistent with the TSR model where a
half-lives are over 1 day (Table 1 and Figure 6a). All of the
complexes decay relatively more quickly at pH 7.
IV
2+
lower ΔE
correlates with a larger k . An interesting
In the case of [Fe O(tpenOH)] at both pH 2 and 7, the
shorter lifetime in both the presence and absence of C−H
substrates is due to an intramolecular ligand C−H oxidation
(Figure 6b). Signals corresponding to those observed for the
Q−T
2
observation is that N4O coordination generally lowers ΔEQ−T.
Perez and co-workers have reported that the iron(IV) oxo
complex of an ether-substituted cyclam (N3O) also results in a
́
76
43
lower ΔE
relative to that of the cyclam (N4) analogue;
iron complexes of tpena appear in the ESI mass spectra of
Q−T
IV
2+
−
thus, changing the cis donor appears to provide a route to
control ΔEQ−T. This is important information for the rational
design of complexes for specific HAT reactivity. We also note
[Fe O(tpenOH)] mixed with CAN or ClO (Figure S10).
Thus, the alcohol group of tpenOH is converted to a
carboxylate group and hence the ligand Htpena is generated
IV
2+
18
18
18
that ΔE
for [Fe O(tpena)] is larger than that of its
in situ. O labeling (Na OCl in H O) shows that this peak
Q−T
2
1
8
protonated congener and this seems to be reflected in the k
value measured at pH 7 (Table 2), which is approximately half
that measured at pH 2.
appropriately shifts 2 mass units, consistent with a single O-
labeled tpena (Figure S10). Thus in water, as its iron complex,
tpenOH is susceptible to regioselective oxidation by oxidants,
and under catalytic conditions, the C−H oxidation of external
substrates competes with this selective intramolecular
oxidation of the ligand scaffold.
In contrast to [Fe O(tpenOH)] , [Fe O(Htpena)] is
robust in aqueous solvent: e.g., it can be stoichiometrically
regenerated on the addition of further oxidant. The shorter
lifetime for [Fe O(Htpena)] in comparison to the
complexes of the N-only ligands in the absence of C−H
substrates is proposed to be due to competing water oxidation.
This is consistent with previous work using electroactivation to
generate the iron(IV) oxo complexes of tpena/Htpena. Rate
2
Other parameters besides ΔE
are most likely also
Q−T
important in determining the reactivity of the complexes,
particularly at different pH values. Supramolecular interactions
immediately prior to substrate oxidation will depend on pH,
the second coordination sphere, and possible water involve-
ment. At pH 2 we have now established that the Htpena-
supported iron(IV) oxo complex possesses biomimetic first
IV
2+
IV
2+
IV
2+
(
carboxylate O) and second coordination (carbonyl/pyridinium)
sphere moieties that will potentially assist H atom/proton
movements. A DFT structure optimization on the adduct
IV
2+
between [Fe O(Htpena)] and cyclohexanol visualizes these
features (Figure 5). The protonated pyridyl arm steers the
−
3
−4
−1 −1
constants of 1.2 × 10 and 4 × 10
M
s
were deduced
IV
+
respectively for the decay of [Fe O(tpena)] at pH 6−7 and
IV
2+
60
[
Fe O(Htpena)] pH 3−4 in buffered water. This was
ascribed to slow water oxidation. While our work shows that
IV
2+
[
Fe O(Htpena)] is the most potent aqueous iron(IV) oxo
complex for C−H oxidation in the present series, slow
background water oxidation might marginally compromise this
activity, when C−H substrates are limited.
CONCLUSIONS
■
Finding the optimal conditions and robust catalysts for the
selective oxidation of organic substrates in water without
suppression due to competing water oxidation by high-valent
iron complexes is a task with high priority for green chemistry
applications. The intrinsic reactivities of a series of closely
structurally analogous iron(IV) oxo complexes have been
ascertained using bifunctional ligands where the differences lie
−
in the cis position (py or COO ) and the second coordination
sphere (none, a pyridinium/pyridine at pH 2/7 or an alcohol
at pH 2 and 7). This series, studied in water alone, has
uncovered some biorelevant SARs. In stark contrast to
iron(IV) oxo complexes in which the trans effect has been
explored, differences in reactivities are not accompanied by a
correlation with measurable spectroscopic parameters. The
change of a cis equatorial donor from a neutral pyridine to an
anionic carboxylate causes only a marginal change in the λmax
value by a few nanometers at pH 2 and 7 and has no effect on
IV
Figure 5. Optimized structure of the cyclohexanol [Fe O-
Htpena)]2+ adduct (B3LYP). H atoms participating in hydrogen
(
bonding are shown in green.
IV
IV
substrate to the Fe O moiety, and the H atom that will be
removed in the HAT to Fe O is proximate to the O atoms of
the Fe O bond stretching frequency. However, the rate
IV
constants for HAT during C−H oxidation vary by 1 order of
magnitude with a clear trend for faster reactions and enhanced
hydrogen atom tunneling, in the complex with a cis carboxylato
in comparison to complexes based on solely N donors in the
first coordination sphere. Electronic changes have been linked
to reactivity trends, and a formally spin forbidden transition of
both the coordinated carboxylate and oxo group. Hydrogen
bonding between a C−H substrate (methanol) in water and a
ruthenium(IV) oxo complex has previously been experimen-
85
tally confirmed as the driving force for adduct formation.
IV
With half-lives of 80 s and 3 h at pH 2 for [Fe O-
2
+
IV
2+
IV
(
tpenOH)] and [Fe O(Htpena)] , respectively, the
the conversion of a S = 1 Fe O complex to the
III
stabilities of these complexes in water in the absence of C−
H substrates are significantly shorter in comparison to the four
complexes formed using the neutral N5 ligands, for which the
corresponding S = 5/2 Fe complex has been proposed to
transverse a spin-crossover process from S = 1 to S = 2 prior to
4
7,75,77,84,86,87
the HAT and has been coined TSR.
DFT
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IV
2+
IV
2+
Figure 6. (a) Absorbance at λ (NIR) over time showing the decay of iron(IV) oxo species: [Fe O(tpenOH)] (blue), [Fe O(Htpena)]
max
IV
3+
IV
2+
IV
2+
IV
2+
(
1
green), [Fe O(Htpen)] (purple), [Fe O(ettpen)] (orange), [Fe O(metpen)] (red), and [Fe O(bztpen)] (black). Conditions: [Fe] =
IV
2+
III
2+
.5 mM, 3 equiv of CAN. At the right is an expansion of the blue plot for [Fe O(tpenOH)] . (b) Conversion of [Fe (tpenO)] to
III
2+
[
Fe (tpena)] .
calculations show that O coordination lowers the energy
difference between the triplet and quintet states for the
iron(IV) oxo complexes of Htpena/tpenaH and HtpenO/
tpenOH in comparison to complexes of N5 ligands, making
the more reactive S = 2 spin state more accessible. This
advantage is supplemented by high thermodynamic stability of
the iron(III) states for the complexes of the monoanionic N5O
ligands compared to the iron complexes of the neutral Rtpen
Nature’s preference for incorporating a Asp/Glu O donor in
the first coordination sphere cis to the putative O binding site
2
of the O -activating non-heme iron enzymes and the
2
hemilabile pendant arms of the potentially hexadendate ligands
furnish biomimetic second coordination spheres that clearly
influence the reactivity.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c03441.
■
5
8
III
II
ligands. In MeCN, the E°(Fe /Fe ) value for the tpena-
sı
*
supported system is approximately 350 mV lower than its tpen
5
8
counterpart (and other systems based on neutral N-only
donor ligands which otherwise dominate the field of modeling
non-heme iron). With this work we have now demonstrated
greater reactivity, in water, for HAT to iron(IV)oxo complexes
from alcohol substrates when a carboxylate donor is cis to the
oxo group.
Experimental section, computational details, extended
DFT results including relative free energies and
calculated spectroscopic and structural parameters,
kinetic data for reactivity studies toward C−H bonds,
and crystallographic and structural details for CCDC
The pH and the presence of H-bond donors and acceptors
in the first and second coordination spheres will be important
in water. Ultimately our study of eight closely related iron(IV)
1971388 and 2017382 (PDF)
Accession Codes
IV
2+
IV
2+
oxo complexes, [Fe O(metpen)] , [Fe O(ettpen)] ,
CCDC 1971388 and 2017382 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
IV
2+
IV
3+
IV
2+
+
[
[
Fe O(bztpen)] , [Fe O(Htpen)] , [Fe O(tpenOH)]
Fe O(Htpena)] , [Fe O(tpen)] , and [Fe O(tpena)] ,
IV
2+
IV
2+
IV
shows that subtle structural differences in the first and second
coordination spheres tune their individual reactivity, producing
large differences by orders of magnitude in reactivityexactly
IV
as seen in nature for the non-heme enzymes. [Fe O-
2
+
(
Htpena)] (pH 2) shows k values for C−H HAT from
AUTHOR INFORMATION
Corresponding Author
2
■
IV
+
alcohols which are twice those for [Fe O(tpena)] (pH 7).
The modeling suggests favorable substrate C−H association
with both the cis carboxylate O donor and noncoordinated
carbonyl and the FeO group, with the pendant pyridinium
in the second coordination sphere furnishing a H atom donor
for the O atom acceptor of the alcohol substrate. This type of
interaction can be translated directly to non-heme enzymes
themselves because either an Asp or Glu donor is cis to the oxo
site and interactions with surrounding amino acids steer the
substrate selectivity. The enhanced reactivity and tunneling
effects for the complex with a cis-carboxylate donor parallels
Christine J. McKenzie − Department of Physics, Chemistry
and Pharmacy, University of Southern Denmark, 5230
Odense M, Denmark; orcid.org/0000-0001-5587-0626;
Phone: +45 6550 2518; Email: mckenzie@sdu.dk
Authors
Christina Wegeberg − Department of Physics, Chemistry and
Pharmacy, University of Southern Denmark, 5230 Odense M,
Denmark; Molecular Inorganic Chemistry, Stratingh Institute
for Chemistry, Faculty of Science and Engineering, University
1
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Article
of Groningen, 9747 AG Groningen, The Netherlands;
orcid.org/0000-0002-6034-453X
Mathias L. Skavenborg − Department of Physics, Chemistry
and Pharmacy, University of Southern Denmark, 5230
Odense M, Denmark; Water Research Centre, School of Civil
and Environmental Engineering, University of New South
Wales, Sydney, New South Wales, Australia; orcid.org/
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000-0003-2240-1692
Andrea Liberato − Universidad de Cádiz, Facultad de
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Ingeniería Metalúrgica y Química Inorgánica, Cádiz 11510,
Spain
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James N. McPherson − Department of Physics, Chemistry and
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Wesley R. Browne − Molecular Inorganic Chemistry,
Stratingh Institute for Chemistry, Faculty of Science and
Engineering, University of Groningen, 9747 AG Groningen,
The Netherlands; orcid.org/0000-0001-5063-6961
Erik D. Hedegård − Division of Theoretical Chemistry, Lund
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.0c03441
̀
́
ez, L.; Pla, J. J.;
(
Notes
(
̀
The authors declare no competing financial interest.
(
ACKNOWLEDGMENTS
■
(
The work was supported by the Danish Council for
Independent Research (Grant 9041-00170B to C.J.M.) and
The Netherlands Ministry of Education, Culture and Science
2
(
(
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W.R.B., Gravity Program 024.001.035). The Carlsberg
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