O-H and (CO)N-H bond weakening by coordination to Fe(ii)

Article abstract of DOI:10.1039/c8dt04689a

New N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)-ethane-1,2-diamine derivatives bearing covalently linked OH and (CO)NH groups have been synthesized. The coordination of those pendant hydroxyl/amide groups to a Fe(ii) metal center is demonstrated both in solution, even in the presence of chloride as the counterion, and in solid state, by means of X-ray diffraction crystal structures. As a result of this coordination, the experimental bond dissociation free energies (BDFE) of O-H and (CO)N-H bonds are remarkably diminished down to 76.0 and 80.5 kcal mol^-1 respectively, which is also in agreement with DFT-based theoretical calculations. These BDFE values are in the range of commonly used hydrogen-atom donor reagents. The strategy presented here allows an unequivocal evaluation of the influence of metal coordination in X-H bond weakening in organic solvents which could be easily extended to other metal centers.

Full text of DOI:10.1039/c8dt04689a

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N. Fuentes, L. Crovetto, M. L. Marcos, L. Lezama, D. Choquesillo-Lazarte, V. Blanco, A. G. Campaña, D. J.
Cardenas and J. M. Cuerva, Dalton Trans., 2019, DOI: 10.1039/C8DT04689A.
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ISSN 1477-9226
PAPER
Joseph T. Hupp, Omar K. Farha et al.
Efficient extraction of sulfate from water using
framework
a Zr-metal–organic
rsc.li/dalton

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O–H and (CO)N–H bond weakening by coordination to Fe(II)
Sandra Resa,a Alba Millán,a,* Noelia Fuentes,b Luis Crovetto,c M. Luisa Marcos,d Luis Lezama,e
Duane Choquesillo-Lazarte,f Victor Blanco,a Araceli G. Campaña,a Diego J. Cárdenasb,* and Juan M.
Cuervaa,*
Received 00th January 20xx,
Accepted 00th January 20xx
New N,N’-dimethyl-N,N’-bis(2-pyridylmethyl)-ethane-1,2-diamine derivatives bearing covalently linked OH and (CO)NH
groups have been synthesized. The coordination of those pendant hydroxyl/amide groups to a Fe(II) metal center is
demonstrated both in solution, even in the presence of chloride as counterion, and in solid state, by means of X-ray
diffraction crystal structures. As a result of this coordination, the experimental bond dissociation free energies (BDFE) of
O–H and (CO)N–H bonds are remarkably diminished down to 76.0 and 80.5 kcal mol-1 respectively, which is also in agreement
with DFT-based theoretical calculations. Those BDFE values are in the range of commonly used hydrogen-atom donor
reagents. The strategy presented here allows an unequivocal evaluation of the influence of metal coordination in X–H bond
weakening in organic solvents which could be easily extended to other metal centers.
DOI: 10.1039/x0xx00000x
www.rsc.org/
ribonucleotide reductase.6,7 Hydroxo or aquocomplexes of
manganese/iron clusters have been also identified as cofactors
in Chlamydia trachomatis8 and Mycobacterium tuberculosis9
Introduction
O–H bonds in alcohols and water are among the strongest
covalent bonds, showing bond dissociation free energies (BDFE)
ranging from 122.7 (water) to 100.8 (EtOH) kcal mol-1.1 The
energy of this bond formation is the driving force of many
biological and biomimetic oxidation processes of simple alkanes
(C–H BDFEs ranging from 106 to 88.3 kcal mol-1) and phenols
(O–H BDFEs ranging from 95.5 to 73.8 kcal mol-1) by the
corresponding metal hydroxides and oxides.2 A classic example
is the use of iron hydroxides/oxides in high oxidation state to
generate the corresponding aqua/hydroxide complexes, as
exemplified in many natural occurring processes (Figure 1, left
to right). Thus for example, this transformation is essential in
the proper functioning of Escherichia coli ribonucleotide
reductase, in which tyrosine (Y122) is oxidized by an Fe(III)-
hydroxide, yielding coordinated water (W48) to a Fe(III)/Fe(IV)
cluster.3 Iron aqua and hydroxo complexes4 are also involved in
the PCET processes in the oxidation of ferullic acid by
ribonucleotide reductase.
Less frequent is the opposite transformation in which the BDFE
energy of O–H bonds is considerably diminished by
coordination to a metal, thus transforming the corresponding
O–H bonds in potential hydrogen donors (Figure 1, right to left).
A key example is the behaviour of water coordinated to
manganese cluster in photosystem II (PSII). A hydrogen-atom
transfer from coordinated water molecules to a tyrosine (Yz)
radical is proposed as the responsible of a sequential electron
and proton draining in O2 production by photosynthesis.10-12 In
that situation, the BDFE of the coordinated water must be
similar or even lower than BDE/BDFE of tyrosine (BDE = 86 kcal
mol-1, BDFE = 87.8 kcal mol-1).1 Experimental and theoretical
BDE values of water13,14 and hydroxy15 manganese model
complexes showed that the values ranges between 77 and 94
kcal mol-1, fitting with the original proposal. In fact, this ability
of manganese to diminish the BDE of proximal OH groups has
been considered in the heart of the PSII evolutionary success.16
horseradish peroxydase5 or radical initiation in class
I
H-ATOM DONOR
a. Departamento Química Orgánica, Universidad de Granada (UGR). Avda.
Fuentenueva, s/n, 18071 Granada, Spain. E-mail: jmcuerva@ugr.es
b. Departamento de Química Orgánica, Universidad Autónoma de Madrid. Ciudad
Universitaria de Cantoblanco, 28049 Madrid, Spain.
H-ATOM ACCEPTOR
H
(L)nM(n-1)+-O
(L)nMn+-O
H
H
H
c. Departamento de Fisicoquímica, Facultad de Farmacia, (UGR). Cartuja Campus,
18071 Granada, Spain.
H
Metal in low oxidation state
Metal in high oxidation state
d. Departamento de Química, Universidad Autónoma de Madrid. Ciudad
Universitaria de Cantoblanco, 28049 Madrid, Spain.
e. Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología,
Universidad del País Vasco, UPV/EHU, 48940 Leioa, Spain
Figure 1. Metal hydroxide or aqua complexes as hydrogen atom acceptor or donor.
f. Laboratorio de Estudios Cristalográficos, Instituto Andaluz de Ciencias de la Tierra
(CSIC-UGR), 18100 Armilla, Granada, Spain.
Within this context, we and other groups have recently shown
that the reactivity of Ti(III)17 or Sm(II)18 towards carbon-
centered radicals in the presence of water and methanol can
only be explained assuming a considerably diminishing of the
O–H bond dissociation energy after coordination to such low
† Electronic Supplementary Information (ESI) available: synthesis and NMR spectra
of ligands and iron (II) complexes, magnetic susceptibility graphics, UV-Vis titration
spectra, voltammograms, crystallographic data and atomic coordinates for DFT
calculations. CCDC 1880891-1880897. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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valent metals. These findings have been also extended to N–H
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DOI: 10.1039/C8DT04689A
21
bonds in amides,19,20 imidazoles, imidazolines22 and, in the
N
context of ammonia fixation, to amines.23 Although N–H bonds
Bond dissociation free energies
X
H
H
N
N
-
~
in amides have intrinsic very high BDE values ( 95-110 kcal mol
(BDFEs)
FeII
N
1; BDFEcalc. 93-108 kcal mol ) the corresponding reactivity
-1 24
~
[FeII]
X
H
vs.
X
H
X
and theoretical calculations suggest a considerable decrease of
the BDFE by 34.5 and 66.8 kcal mol-1 after coordination with
Ti(III)19a or Sm(II),20 respectively. Remarkably, no experimental
BDFE values for metal coordinated amides have been reported
so far.
H-atom donor capability?
Figure 2. Working hypothesis
Within this context, the understanding of how to modify the
reactivity of a Mn/Mn+1 couple for hydrogen-atom transfer
reactions can allow the system to work as a reductant (BDFE
values lower than usual in C–H bonds) or an oxidant (BDFE
higher than those described for C–H bonds), depending on the
BDFE values of coordinated OH/NH ligands. Although some
values for the BDFEs of different O–H bonds coordinated to
diverse metals are known,1,25 a large amount of basic
investigation still remains to be done. Thus for example, the
reported BDFE values are in many cases incomparable due to
the influence of different aspects such as solvent effect,
coordination issues or reversibility in the electrochemical
measurement which can affect the value.25d Moreover, some
contradicting works, mainly related with the functioning of
lipoxygenases, have also been published.26,27 Such intriguing
case is related to a polypyridyl Fe(II) aquacomplex, which
showed a remarkable BDFE diminishing of 42 kcal mol–1.26b It is
worth noting that the use of the same polypyridyl based ligands
is able to diminish the BDFE of methanol by only 19.4 kcal mol–
1 and the reasons are not very clear.28 An experimental difficulty
is also the lability of the exogenous ligands (water and
methanol) in solution, which precludes a complete and
comparative analysis. As we commented before, experimental
BDFE values for amides coordinated to metals are lacking.
In this work, we have designed and synthesized new ligands in
which we can explore for the first time how to modify the BDFE
of O–H/(CO)N–HR bonds of series of metal complexes with
different kinds of H-atom transferring groups, using as model
the couple Fe(II)/Fe(III) (Figure 2). In this case, the X–H bonds
studied are not exogenous ligands which prevents their lability
in solution. The significant modification of the heteroatom–H
BDFE by coordination to Fe(II) can be potentially interesting
compared with other common hydrogen atom donors29 in
terms of structural flexibility, simple preparation and
introduction of chirality, especially in the case of amides via the
pendant side chain. As the main results, we estimate that Fe(II)
complexes are able of weakening the coordinated X–H bonds by
10 to 26 kcal mol–1 depending on the nature of the ligands, and
could be potentially used as hydrogen-atom donor (BDFE as low
as 76 kcal mol–1).
Results and discussion
We based our study on the previously described mep ligand (1)
(mep N,N’-dimethyl-N,N’-bis(2-pyridylmethyl)-ethane-1,2-
=
diamine)30 and functionalized derivatives mep(OH) (2),
mep(OH)2 (3), mep(CONHBu)2 (4) (see ESI) and the
corresponding Fe(II) complexes 5 to 8 (Figure 3). Those ligands
possess pendant hydroxyl and amide groups covalently linked
in the ligand framework, thus preventing their lability in
solution. Therefore, the resulting complexes could be studied in
aprotic solvents such as DMSO, in which the binding equilibrium
of the ligand containing the desired hydrogen atom transferring
group is simpler than in protic solvents. In this way, one or two
benzylic alcohols/butyl amides remain coordinated to the
metal, thus avoiding any intermolecular binding equilibrium
measurements. Moreover, we can carry out the analysis of all
the structures in the same aprotic solvent (DMSO), thus being
consistent and comparable. Known ligand 1 was used to
prepare the corresponding non-functionalized model complex
5 with neither hydroxy nor amide groups. We firstly synthetized
ligands 1 to 4 from N,N′-dimethylethylenediamine (see ESI for
details). Addition of FeCl2 to the corresponding ligand solution
in CH3CN gave rise to complexes 5 to 8 that were firstly
characterized by mass spectrometry (HRMS) (see ESI for
details).
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b)
a)
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DOI: 10.1039/C8DT04689A
N
N
N
N
N
N
N
Cl
Cl
Fe
N
1
mep, ( )
5
Fe(II)(mep)Cl2, ( )
+ Cl-
N
N
N
N
N
H
O
H
O
Fe
N
Cl
N
N
6
[Fe(II)(mep(OH))Cl]Cl, ( )
2
mep(OH), ( )
2+ (Cl-)2
N
N
N
N
N
H
H
O
H
O
Fe
N
O
N
H
O
N
7
Figure 4. X-Ray crystal structures of: a) 6, b) 7 and c) 8. Color code: C: gray, O: red, N:
[Fe(II)(mep(OH)2)]Cl2, ( )
3
mep(OH)2, ( )
blue, Fe: orange, Cl: green. H-atoms attached to carbon have been omitted for clarity.
2+ (Cl-)2
NMR and EPR studies for complexes 6-8. Although these X-ray
structures already show the tendency of OH/(CO)NHBu groups
to coordinate to the metal center, a confirmation that this
coordination is maintained in solution is also required.
Therefore, we carried out the corresponding NMR studies in
different solvents using also Fe(II)(mep)Cl2 (5), as model
compound. Although they are paramagnetic d6 species we
O
NHBu
N
N
N
N
O
H
N
Bu
Fe
O
N
H
N Bu
N
N
N
O
H
N Bu
8
[Fe(II)(mep(CONHBu)2)]Cl2, ( )
1
4
mep(CONHBu)2, ( )
could obtain the corresponding H-NMR spectra with signals
spanning from –40 to 160 ppm.
Figure 3. Ligands (1-4) and iron complexes (5-8) synthetized and studied.
Regarding the 1H-NMR spectrum of model compound
Fe(II)(mep)Cl2 (5), it showed nine identifiable signals in CD2Cl2
(See ESI, Fig. S1), corresponding to the expected ones.31,32
We then analysed the behaviour of target complexes in
solution. In the case of complex 6, twelve identifiable signals
can be clearly observed in the 1H-NMR spectrum both in CD2Cl2
and DMSO-d6 (See ESI, Figs. S3-S4). When we used other
coordinating solvents such as CD3OD or D2O, a similar pattern
could be also observed (See ESI, Figs. S5-S6). 1H-NMR spectra of
complex 7 in DMSO-d6 and CD3OD are, as expected, in
agreement with a symmetric structure. In any case, the
presence of a fast equilibrium between different metal-ligand
configurations cannot be strictly excluded. The 1H-NMR of
complex 8, [Fe(II)(mep(CONHBu)2)]Cl2 showed a similar set of
signals using different solvents (CD3OD, CD3CN, CD2Cl2 and
DMSO-d6) ranging from 140 to –20 ppm, thus suggesting a
similar structure in solution (See ESI, Figs. S9-S12). Coordination
of amide group in all cases is then expected.
X-Ray structures of complexes 6-8. Metal center coordination
of the pendant groups is mandatory in this study. Remarkably,
we could obtain the X-ray crystal structure of
[Fe(II)(mep(OH))Cl]Cl (6), [Fe(II)(mep(OH)2)]Cl2 (7), and
[Fe(II)(mep(CONHBu)2)]Cl2 (8) complexes, showing in all cases
that in solid state the hydroxyl/carbonyl groups are coordinated
to the Fe(II) center displacing even the negatively charged
chloride counteranion, being an ideal situation to measure the
BDFE of coordinated OH/(CO)NHBu groups (Figure 4). The
preferred arrangement of the nitrogen ligands in all cases leaves
two mutually cis coordination sites that are occupied by oxygen
atoms. Uncoordinated chloride anions are located near the O–
H bonds presumably interacting with them.
Complexes 6-8 are EPR silent when X-band measurements are
carried out on grounded crystals, in good agreement with the
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expected behaviour for iron systems with high spin (hs) +2
oxidation state (S = 2) and the paramagnetism shown in the
NMR spectra. As a non-Kramer ion, Fe(II) usually results in short
spin-lattice relaxation times and large zero-field splittings,
causing the absence of EPR signals under normal experimental
conditions.33
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DOI: 10.1039/C8DT04689A
The thermal evolution of the magnetic susceptibility shows
similar trends for complexes 6 to 8 (Figure 5, in which only the
results for 8 are displayed, is illustrative of the behaviour of the
three compounds). The m curve increases continuously with
decreasing temperature and no relative maximum is observed.
The Curie-Weiss law is obeyed down to 50 K (See ESI, Figs. S16,
S17) with values of the Curie constants (Cm, 6, 3.18; 7, 3.26; 8,
3.31 cm3 K mol-1) in the range usually found for hs Fe(II)
compounds and small Weiss temperatures (, 6, –0.6; 7, –1.8;
8, –1.9 K). The room temperature mT values (6, 3.17; 7, 3.23; 8,
3.28 cm3 K mol-1) are slightly larger than the spin-only value
(3.00 cm3 K mol-1) predicted for S = 2 complexes due to spin-
orbit coupling. For the three compounds, the mT product
Figure 5. Temperature dependence of mT for 8 measured at 0.1 T. The best fit to the
data is shown as a solid line (see text for details of the fitting procedure). Inset: Field
dependence of the magnetization for 8 measured at 2 K. The Brillouin function for S = 2
is shown for the sake of comparison.
remains roughly constant in the high temperature range (300- BDFE values. Having synthesized and characterized all target
50 K), then decreases abruptly down to 5 K. This behaviour is compounds and once we confirmed that the OH/(CO)NHBu
characteristic of systems with antiferromagnetic interactions, group remains coordinated in NMR scale to the metal center in
but in these cases it is probably due to the zero-field splitting of complexes 6 to 8, we proceeded to measure each homolytic
the Fe(II) ions.34 On the basis of this consideration, the bond dissociation free energy. BDFEs can be experimentally
experimental magnetic susceptibility data were fit to the estimated by combining their pKa values with the oxidation
following analytical expression,35 which describes the thermal potentials of their conjugate bases both estimated in DMSO,
evolution of m for an S = 2 ion undergoing zero-field splitting:
according to the Bordwell´s methodology based on a
thermodynamic cycle following equation 2 (Figure 6).1,38 The
constant CG corresponds to the H+/· standard reduction
potential in the solvent of choice. We selected the revised value
of CG = 71.1 reported by Mayer et al. for DMSO using the redox
6
4
―푥
푒 ―푥 + 4푒 ―4푥
+
+
―푥 ― 푒 ―4푥
)
2푁푔2휇2퐵
(
1 ― 푒
)
(
푒
푥
3푥
풳푚 = 3푘(푇 ― 휃)
(eq. 1)
1 + 2푒 ―푥 + 2푒 ―4푥
[
]
potential referenced to Fc+/0 1
.
where N, B and k have their usual meaning, x = D/kT, D is the
axial single-ion ZFS parameter, g is the average g factor and  is
the Weiss constant. The best least-squares fits (solid lines in
Figs. 5, S16 and S17) were obtained for the ZFS parameters
|D|/k= 10.6, 7.3 and 9.7 K with g = 2.06, 2.08 and 2.09 for
compounds 6 to 8, respectively. The  values were fixed at those
pKa(XH)
-
X H
X
/-
Eo(X )
BDFE
H
X
OH/CONRH = 1.37 pKa(OH/CONRH) + 23.06 Eo(O-/N-) + CG kcal mol
-1 (eq. 2)
-1
BDFE
determined from the plots of m vs T. The calculated |D|
values are similar to those usually observed for hs Fe(II)
complexes and are high enough to explain the absence of X-
band EPR signals.36
Figure 6. Thermodynamic cycle and Bordwell´s equation (eq. 2) for hydrogen atom
dissociation.
Isothermal magnetization data for compound 8 were collected
in a field up to 7 T at various temperatures between 2 and 7 K.
Deviations of the experimental data points from a Brillouin
functions taken at the H/T values of the measurements is
remarkable (inset of Fig. 5) and confirm the large ZFS of Fe(II) in
this compound. Moreover, magnetization plot exhibits
significant separation between the isofield curves (see Fig. S18
in ESI), indicative of strong magnetic anisotropy in the ground
state. The high-field magnetization saturates at 2.41 BM, lower
than the 4 BM expected for an isotropic system with four
unpaired electrons and g = 2, but consistent with significant
axial anisotropy.37
pKa measurements. We firstly measured the pKa values of
ligands 2 to 4 by UV-Vis titration in DMSO (See ESI, Figs. S19-21)
using triphenylmethane anion (TH) as indicator (pKa = 30.6).39
Thus, we obtained the corresponding pKa values (2, 27.6, 3,
28.3/29.4, 4, 22.0), being in agreement with previous reported
data for benzylic alcohols (pKa = 26.93-26.71),40 and benzamides
(23.5).24a In the case of 4 we determined only one pKa value,
thus suggesting that both deprotonation reactions exhibit
similar pKa values.
Comparison of the measured pKa values for free ligands 1 to 4
with the values for the corresponding complexes 6 to 8 is useful
to determine the influence of the Lewis acidity of the metal in
the proton transfer from the ligand.
We then proceeded to measure the corresponding pKa values
for complexes 6 to 8 in DMSO (See ESI, Figs. S22-S24), which are
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indispensable in the BDFE determination. We determined a pKa in equilibrium in the homogeneous phase. To shed light about
View Article Online
DOI: 10.1039/C8DT04689A
value of 26.5 for [Fe(II)(mep(OH))Cl]Cl 6 in DMSO by UV-vis the nature of these species we carried out the corresponding
titration using triphenylmethane anion (TH) as indicator. This cyclic voltammetry (CV) studies of model complex after
small variation with respect to free ligand 2 pKa value (27.6) may counteranion chloride-SbF6 exchange (see ESI, Figure S28). In
be due to the low Lewis acidity of Fe(II) cation, that is very this case, chloride anion coordination can be ruled out.
diminished in this monocationic complex by the presence of Although the electrochemistry was more complex owing to
four donor nitrogenated ligands. Nevertheless, we cannot adsorption processes in the electrode, two peaks were again
exclude either a fast equilibrium between coordinated and observed, which could be attributed to a fast equilibrium
uncoordinated species in solution in the presence of between complexes presenting the pyridyl groups in trans and
coordinating chloride anion.41 The only precedent, measured in cis configurations.
DMSO, for a O–H bond coordinated to Fe(II) using a closely CV of [Fe(II)(mep(OH))Cl]Cl 6 showed reversible oxidation peaks
related ligand showed a striking pKa value of only 8.1.26b It is at –0.35 and –0.06 V, which could be attributable to a similar
worth noting that, in DMSO, the pKa values for water and equilibrium process (Figure 7). In the presence of 1 equiv. of
benzenesulphonic acid are 30 and 7, respectively, and therefore base (dimsyl anion, pKa (DMSO) = 35.1)39 these two peaks
we do not have any plausible explanation for such extremely almost disappeared and a clear new reversible oxidation peak
low value previously reported.
at –0.73 V (Fc/Fc+) is detected. This value is similar to other Fe(II)
Complex [Fe(II)(mep(OH)2)]Cl2 7 showed a pKa of 23.8, being alkoxides with similar chemical environment.45 A peak at a very
more acidic than the free ligand 3 (pKa value around 28). This similar voltage can be also detected before the base addition,
result is consistent with the existence of a much more rigid probably owing to a partial deprotonation in solution. The
dicationic complex in solution in which both hydroxyl groups difference in the reduction potential in the presence and
remain coordinated to the metal center.42 Nevertheless, we absence of base is expected as the addition of base generates a
could not discriminate between the two expected pKa values.
The pKa values for coordinated (CO)N–H bonds in
[Fe(II)(mep(CONHBu)2)]Cl2 8 were also estimated by UV-vis
titrations using again red triphenylmethane anion as indicator,
showing a pKa value of only 19.7. This value is slightly more
acidic that the estimated for the uncoordinated ligand 4 (22.0).
Again, we could not discriminate between the two sequential
deprotonation reactions.
permanent donor alkoxide ligand.
Electrochemical properties. First of all we tried to evaluate the
electrochemical features of ligands 1 to 4. Unfortunately, we
could not obtain the required E0 values for deprotonated
ligands by cyclic voltammetry measurements owing to the
presence of adsorption peaks probably derived from
decomposition reactions in the presence of base.43 We assume
that the BDFE of O–H/N–H bonds in our ligands are similar to
those reported for benzyl alcohol (BDFE = 101.7 kcal mol–1)40
and benzamide (BDE = 107 kcal mol–1; BDFEcalc. = 102.6 kcal mol–
1).24a In the case of benzyl alcohol, there are not many reported
data for parent compounds owing to the benzylic C–H bond has
a lower BDE value (79 kcal mol-1) than the O–H bond. In that
situation, the abstraction of H-atom from the benzylic C–H
position is kinetically favoured with respect to the O–H bond,
which may add a difficulty in the determination of BDE of O–H
bond by other common methods based on H-abstraction
reactivity. For benzamide, its reported BDE value is the same
that the one reported for acetamide (BDE = 107 kcal mol-1),24a
suggesting that the nature of the substituent might not have an
impact in the bond dissociation energy of N–H bond of the
amide group. In this sense, although this assumption is
reasonable, it makes the real decrease of the corresponding
BDFE values after coordination with Fe(II) an estimation.
In the case of model complex (Fe(II)(mep)Cl2) 5 in DMSO, cyclic
voltammetry measurements showed two reversible oxidation
peaks at –0.21 and –0.03 V vs Fc/Fc+ (see ESI, Figure S27).31,44
The relative intensity of these peaks changes depending on the
sweep rate, suggesting the existence of two different structures
Figure 7. Cyclic voltammograms of 6 (4 mM) in DMSO in the absence and in the presence
of potassium dimsyl (internal standard Fc/Fc+, v = 0.1 V s-1).
CV measurement of [Fe(II)(mep(OH)2)]Cl2 7 in DMSO showed
peaks at –0.36 and –0.03 V, in the same range as those obtained
for [Fe(II)(mepOH)Cl]Cl 6, considering also the uncertainties
associated to the irreversibility of the process. In the presence
of an excess of base (dimsyl anion) a clear reversible peak can
be detected at –1.2 V (Figure 8). This shift of the oxidation
potential towards more negative values is also consistent with
a Fe(II) complex with two donating alkoxide groups after the
addition of base. Remarkably, in the presence of only one
equivalent of base, other reversible peaks at –0.78 V was
observed which can be attributed to the mono-deprotonated
complex. In fact, such E0 value is similar to that previously
obtained for 6 in the presence of base (–0.73 V). As in the case
of complex 6, peaks at a very similar voltage can be also
detected before the base addition, resulting of partial
deprotonating events in solution.
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diminished to only 76.0 kcal mol–1 (pKa = 23.8, EV0ie=w A–r1tic.l2e OVnlivnes
+
DOI: 10.1039/C8DT04689A
Fc/Fc ), which is again consistent with an increase of the
electron density in the metal center by the existence of a new
alkoxide ligand. This BDFE value is similar to that recently
reported for a Fe(II) aquacomplexes (68.6 and 84 kcal mol–
)
1 26c,26d and represents an estimated weakening of about 26 kcal
mol–1 by coordination to a Fe(II) center. The resulting value of
just 76.0 kcal mol–1 is in the range of other common hydrogen
atom donors such as 1,4-ciclohexadiene (BDE = 76 kcal mol–1;
BDFE = 67.8 kcal mol–1).1
a)
0
H+
OH
Cl
O
Fe
Fe
pKa= 26.5
Cl
e-
E1/2
Figure 8. Cyclic voltammograms of 7 (4 mM) in DMSO in the absence and in the presence
of potassium dimsyl (internal standard Fc/Fc+, v = 0.1 V s-1).
6
BDFE=
=
90.5 kcal/mol
(71.9 kcal/mol)
-0.732 V
In the case of [Fe(II)(mep(CONHBu)2)]Cl2 8 in DMSO, the CV
showed a complex situation but a reversible peak at –0.38 V
could be assigned to the Fe(II)/Fe(III) pair (Figure 9). In the
presence of an excess of base, a clear and reversible peak was
detected at –0.76 V corresponding to the fully deprotonated
complex. Moreover, clear reversible reduction peaks for 8 were
also observed in the absence (–1.87 V) and presence (–2.39 V)
of base, which are associated with Fe(II)/Fe(I) pair.
Unfortunately, in this case no clear peaks attributed to the
monodeprotonating process could be observed.
O
Fe
Cl
b)
2
0
H+
pKa= 23.8
H+
pKa= 23.8
OH
OH
O
Fe
O
O
Fe
Fe
OH
e-
e-
E1/2
7
BDFE=
85.7 kcal/mol
(74.3 kcal/mol)
BDFE=
76.0 kcal/mol
(64.5 kcal/mol)
E1/2=
=
-0.78 V
-1.2 V
2
O
O
Fe
Fe
O
OH
Figure 10. Thermodynamic cycle for a) [Fe(II)(mep(OH))Cl]Cl,
6
and b)
[Fe(II)(mep(OH)2)]Cl2, 7 developed in DMSO to evaluate the BDE(O–H) with redox
potentials referenced to the Fc/Fc+ couple (DFT-calculated theoretical BDFE values
shown in brackets).
DFT-based theoretical calculations (Gaussian09, B3LYP/6-
31G(d,p)) are in qualitative agreement with all these findings
(Table 1). Thus, coordination of the hydroxyl group with Fe(II)
promotes a calculated diminishing in BDFE of 17.7 and 16.3 kcal
mol–1
for
complexes
[Fe(II)(mep(OH))dmso]
and
Figure 9. Cyclic voltammograms of 8 (4 mM) in DMSO in the absence and in the presence
Fe(II)(mep(OH)2), respectively, as optimized model compounds
for 6 and 7. In the case of the BDFE associated to the second
hydroxyl group of Fe(II)(mep(OH)2) a subsequent decrease of
9.8 kcal mol–1 was also theoretically estimated, which is in
reasonable agreement with the experimentally observed trend.
of potassium dimsyl (internal standard Fc/Fc+, v = 0.1 V s-1).
BDFE estimation. Following equation 2 (Figure 6), we estimated
a BDFE value for [Fe(II)(mep(OH))Cl]Cl 6 of 90.5 kcal mol–1,
which represents an estimated BDFE weakening of around 10
kcal mol–1 by coordination to the metal center (Figure 10a). In
the case of [Fe(II)(mep(OH)2)]Cl2 7 an estimation of the BDFE for
the first and second hydroxyl group could be obtained (Figure
10b). The BDFE value for the first coordinated OH group (pKa =
23.8, E0 = –0.78 V vs Fc/Fc+) is 85.7 kcal mol–1, which is
consistent with the value obtained for [Fe(II)(mep(OH))Cl]Cl 6.
The BDFE of the second hydroxyl group of complex 7 is
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could bear chiral information and work in that direction is now
underway.
Table 1. Calculated BDFE values for the systems studied
View Article Online
DOI: 10.1039/C8DT04689A
Complex
BDFE [kcal/mol]
89.6
mep(OH), (2)
Experimental section
90.9
93.7
mep(OH)2, (3)
mep(CONHBu)2, (4)
General Section. All reagents and solvents (CH2Cl2, EtOAc,
hexane, CH3CN, CH3OH) were purchased from standard
chemical suppliers and used without further purification.
Anhydrous solvents (CH3OH, CH2Cl2, CH3CN and DMSO) were
purchased from standard suppliers. Thin-layer chromatography
analysis was performed on aluminium-backed plates coated
with silica gel 60 (230-240 mesh) with F254 indicator. The spots
were visualized with UV light (254 nm) and/or stained with
phosphomolybdic acid (10% ethanol solution) and subsequent
heating. Chromatography purifications were performed with
silica gel 60 (40-63 μm) or with neutral aluminium oxide (50-200
μm). 1H NMR spectra were recorded on Varian 300, 400 or 500
MHz spectrometers, at a constant temperature of 298 K.
Chemical shifts are reported in ppm using residual solvent peak
as reference (CHCl3: δ = 7.26 ppm, CH3OH: δ = 3.31 ppm, CH3CN:
δ = 1.94 ppm, DMSO: δ = 2.50 ppm, CH2Cl2: δ = 5.32 ppm). Data
are reported as follows: chemical shift, multiplicity (s: singlet, d:
doublet, t: triplet, q: quartet, quint: quintuplet, hept: heptuplet,
m: multiplet, dd: doublet of doublets, dt: doublet of triplets, td:
triplet of doublets, bs: broad singlet), coupling constant (J in Hz)
and integration; 13C NMR spectra were recorded at 75, 101 or
126 MHz using broadband proton decoupling and chemical
shifts are reported in ppm using residual solvent peaks as
reference (CHCl3: δ = 77.16 ppm, CH3OH: δ = 49.00 ppm).
Carbon multiplicities were assigned by DEPT techniques. High-
resolution mass spectra (HRMS) were recorded using EI at 70eV
on a Micromass AutoSpec (Waters) or by ESI mass spectrometry
carried out on a QSTAR ABSciex mass spectrometer. Ligand 1
71.9
Fe(II)(mep(OH))(dmso), (as model of 6)
74.3 (1st)
Fe(II)(mep(OH)2), (as model of 7)
64.5 (2nd
)
90.6 (1st)
80.6 (2nd
Fe(II)(mep(CONHBu)2), (as model of 8)
)
With the experimental data obtained the BDFE value for the
second coordinated (CO)NH group (pKa =19.7, E0 = –0.76 V vs
Fc/Fc+) resulted in 80.5 kcal mol–1. This decrease is less
pronounced than in the case of OH group probably because the
negative charge is stabilized by the carbonyl group, thus having
less influence in the electronic structure of the metal. In any
case, the coordination with Fe(II) promotes a decrease of the
BDFE of N–H bonds in the amide as it has been previously
suggested. Again, theoretical calculations qualitatively support
these findings (ca.
3
and 13 kcal mol–1 diminishing,
respectively).
0
2
NBu
NHBu
NBu
O
O
O
H+
Fe
H+
Fe
Fe
O
O
O
pKa= 19.7
pKa= 19.7
NBu
e-
E1/2
NHBu
NHBu
8
BDFE=
80.5 kcal/mol
=
(80.6 kcal/mol)
-0.76 V
1
was known and the obtained H- and 13C-NMR data matched
with those previously described.46
NBu
Ligand characterization:
O
O
mep(OH) (2). Brownish syrup; 1H NMR (500 MHz, CDCl3): δ 8.51
(ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 7.62 (td, J = 7.8, 1.8 Hz, 1H), 7.60
(t, J = 7.6 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H),
7.13 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.10 (d, J = 7.7 Hz, 1H), 4.72
(s, 2H), 3.69 (s, 4H), 2.64 (s, 4H), 2.27 (s, 6H). 13C NMR (126 MHz,
CDCl3): δ 159.3 (C), 158.6 (C), 158.3 (C), 149.2 (CH), 137.2 (CH),
136.6 (CH), 123.3 (CH), 122.1 (CH), 121.7 (CH), 118.9 (CH), 64.2
(CH2), 63.9 (CH2), 55.5 (CH2), 55.4 (CH2), 43.0 (CH3), 43.0 (CH3).
HRMS (ESI): m/z [M+H]+ calcd for C17H25N4O: 301.2022; found:
301.2014. IR (ATR): 3280, 2920, 2846, 2800, 1660, 1593, 1576,
1455, 1436, 1358, 1070, 1033, 760 cm–1.
Fe
NBu
Figure 11. Thermodynamic cycle for [Fe(II)(mep(CONHBu)2)]Cl2, 8 developed in DMSO
to evaluate the BDE((CO)N–HBu) with redox potentials referenced to the Fc/Fc+ couple
(DFT-calculated theoretical BDFE values shown in brackets).
Conclusions
In conclusion, we have shown that new ligands 2 to 4 are
interesting scaffolds to measure the BDFE values of hydroxyl
and carbamoyl groups interacting with a Fe(II) metallic center.
This study can be extended to other metals in order to evaluate
their properties as hydrogen-atom donors in a consistent way.
The presented results also show that, in certain chemical
environments, hydroxyl and amides groups coordinated to
Fe(II) can be transformed into reasonable hydrogen-atom
donors (BDFEs of 76.0 and 80.5 respectively). It is worth noting
that these kinds of BDFE values are scarce, especially in the case
of iron complexes. Amides are especially attractive as they
1
mep(OH)2 (3). Brownish syrup; H NMR (500 MHz, MeOD): δ
7.77 (t, J = 7.7 Hz, 2H), 7.41 (d, J = 7.8 Hz, 2H), 7.36 (d, J = 7.8 Hz,
2H), 4.67 (s, 4H), 3.66 (s, 4H), 2.63 (s, 4H), 2.26 (s, 6H). 13C NMR
(126 MHz, MeOD): δ 161.8 (C), 159.1 (C), 138.9 (CH), 123.2 (CH),
120.3 (CH), 65.5 (CH2), 64.4 (CH2), 56.0 (CH2), 43.2 (CH3). HRMS
(ESI): m/z [M+H]+ calcd for C18H27N4O2: 331.2129; found:
331.2130. IR (ATR): 3197, 2846, 2814, 1595, 1576, 1441, 1357,
1092, 1072, 1040, 999, 969, 783, 618 cm–1.
mep(CONHBu)2 (4). Brownish solid; 1H NMR (500 MHz, CDCl3):
δ 8.15 (s, 2H), 8.08 (dd, J = 7.7, 1.1 Hz, 2H), 7.78 (t, J = 7.7 Hz,
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2H), 7.54 (dd, J = 7.7, 1.1 Hz, 2H), 3.72 (s, 4H), 3.46 (q, J = 6.8 Hz, Instruments low temperature devices. Samples wVeierweAprtliaclceeOdnlinine
DOI: 10.1039/C8DT04689A
4H), 2.64 (s, 4H), 2.29 (s, 6H), 1.62 (p, J = 7.6 Hz, 4H), 1.42 (h, J = quartz tubes and spectra were recorded at different
7.3 Hz, 4H), 0.96 (t, J = 7.4 Hz, 6H). 13C NMR (126 MHz, CDCl3): temperatures between 5 and 300 K. The magnetic field was
δ 164.3 (C), 158.0 (C), 149.4 (C), 137.6 (CH), 125.3 (CH), 120.6 calibrated by a NMR probe and the frequency inside the cavity
(CH), 63.9 (CH2), 55.4 (CH2), 42.9 (CH3), 39.1 (CH2), 31.8 (CH2), (~9.4 GHz) was determined with an integrated MW-frequency
20.2 (CH2), 13.8 (CH3). HRMS (ESI): m/z [M]+ calcd for counter. Variable temperature (5-300 K) magnetic susceptibility
C26H41N6O2: 469.3285; found: 469.3286. IR (ATR): 3308, 2952, measurements on polycrystalline samples were carried out with
2929, 2804, 1657, 1526, 1453, 712 cm–1.
a Quantum Design MPMS3 SQUID magnetometer under a
Synthesis of the Complexes 5-8. FeCl2·4H2O (1 equiv.) was magnetic field of 0.1 T. The experimental susceptibilities were
added to a CH3CN (0.3 M) solution of the corresponding ligand corrected for the diamagnetism of the constituent atoms by
(1 equiv.) and the mixture stirred at room temperature for 16 h using Pascal’s constants. Magnetization as a function of applied
under Ar atmosphere. Then Et2O was added and the slurry was field (H) was measured using the same magnetometer at
stirred for 15 min. The solid was filtered using a sintered glass several temperatures below 10 K after cooling the samples in
Buchner funnel with paper filter. The solid was washed with zero- field. During the measurement, the field was swept
Et2O several times, dried and collected. Samples constituted of between 0 and 7 T.
single crystals were obtained by vapour diffusion using CH3CN / Measurement of pKa values. pKa measurements were carried
CH3OH or DMF as solvent and Et2O as precipitant. All the out on
measurements were carried out with single crystals to ensure spectrophotometer by UV-vis titration using triphenylmethane
unequivocal composition of the sample. anion as indicator.
a Specord 200 Plus Analytik Jena UV-Visible
Fe(II)(mep)Cl2 (5): 365 mg, 72% yield, yellow powder. After Preparation of potassium dimsyl solution. Under argon
crystallization: brown crystals. HRMS (ESI): m/z [M-Cl]+ calcd for atmosphere, KH in mineral oil was washed with several portions
C16H22N4ClFe: 361.0876; found: 361.0868. HRMS (ESI): m/z [M- of dry hexane. Then, KH (50 mg) was dissolved in dry DMSO (5
Cl2]2+ calcd for C16H22N4Fe: 163.0591; found: 163.0591. IR (ATR): mL) and bubbles appeared immediately. The flask was wrapped
2970, 1601, 1467, 1432, 1303, 1080, 1052, 1013, 978, 817, 777 with aluminum foil and stirred under argon until the bubbling
cm–1. Elemental Analysis of single crystal: Calcd for ceased. The solution was kept under argon at 0°C and it was
C16H22N4FeCl2·0.5H2O: C, 47.67; H, 5.41; N, 14.07; found: C, stable for 1 day.
47.32; H, 5.71; N, 13.80.
Preparation of triphenylmethane anion solution. In a UV-vis
[Fe(II)(mep(OH))Cl]Cl (6): 142 mg, 98% yield, yellow powder. cuvette and under Ar atmosphere, a 0.06 M solution of
After crystallization: brown crystals; HRMS (ESI): m/z [M-HCl]+ triphenylmethane (30 mg) in dry DMSO (2 mL) was prepared.
calcd for C17H23N4OClFe: 390.0904; found: 390.0892. IR (ATR): Three or four drops of potassium dimsyl solution were added
2815, 2714, 1580, 1605, 1443, 1039, 817, 769 cm–1. Elemental and solution turned red. Red color must be constant before
Analysis of single crystal: Calcd for C17H24N4OFeCl2·0.5CH3CN: starting the titration, keeping initial absorbance maximum at
C, 48.29; H, 5.74; N, 14.08; found: C, 48.19; H, 5.61; N, 14.01.
499 nm around 1.0.
[Fe(II)(mep(OH)2)]Cl2 (7): 444 mg, 88% yield, yellow powder. UV-vis titration. Aliquots of a 0.02 M solution of ligand/iron
After crystallization: bright yellow crystals. HRMS (ESI): m/z [M- complex in dry DMSO were added to a triphenylmethane anion
H2Cl2]2+ calcd for C18H24N4O2Fe: 192.0618; found: 192.0625. IR solution in DMSO and UV-vis spectra were recorded between
(ATR): 1604, 1579, 1419, 1029, 816, 770, 745 cm–1. Elemental 400-600 nm at 25 °C. (Final added volume did not exceed the
Analysis of single crystal: Calcd for C18H26N4O2FeCl2·0.5H2O: C, 10% of initial volume in any case). Decrease of absorbance
46.38; H, 5.84; N, 12.02; found: C, 46.29; H, 5.60; N, 11.99.
maximum at 499 nm were plot against concentration of
[Fe(II)(mep(CONHBu)2)]Cl2 (8): 346 mg, 81% yield, red powder. ligand/iron complex.
After crystallization: bright deep red crystals. IR (ATR): 2957, Electrochemistry. Electrochemical measurements were carried
2864, 1626, 1599, 1549, 1465, 826, 767, 532 cm–1. HRMS (ESI): out under Ar atmosphere at 25 °C using a PGSTST204
m/z [M-HCl2]+ calcd for C26H39N6O2Fe: 523.2478; found: potentiostat galvanostat (Metrohm Autola B. V.) with a three-
523.2464; m/z [M-Cl2]2+ calcd for C26H40N6O2Fe: 262.1275; electrode cell in 0.1 M solution of tetra-n-butylammonium
found: 262.1280.
corresponding single crystal could not be obtained.
A
good elemental analysis for the hexafluorophosphate (TBAPF6) in DMSO as the supporting
electrolyte. A glassy carbon disc was used as the working
Single-crystal X-ray Diffraction. The X-ray diffraction data were electrode, a platinum wire as the counterelectrode, and a silver
collected on a Bruker D8 Venture diffractometer equipped with wire as the quasi-reference electrode. The Pt-wire and Ag-wire
a Photon 100 detector using Mo or Cu radiation sources or a were flamed to ensure the absence of impurities. Dry DMSO
Bruker Smart APEX diffractometer with an APEX detector using was used as solvent to prepare a 0.1 M solution of tetra-n-
a Mo radiation source. The structures were solved with butylammonium hexafluorophosphate (TBAPF6) which was
SHELXT47 and refined using the full-matrix least-squares against used as work solution. All of the voltammograms were initiated
F2 procedure with SHELX 201648 using the WinGX3249 software. from the null current potential and the scan was initiated in
Physical Measurements: X-band EPR measurements were both the positive and the negative directions at a scan rate of
carried out on a Bruker ELEXSYS 500 spectrometer equipped 0.1 V/s. Potential values are referred to ferrocene/ferrocenium
with a super-high-Q resonator ER-4123-SHQ, a maximum system (Fc/Fc+), being ferrocene added as internal reference
available microwave power of 200 mW and standard Oxford after each measurement. For the working conditions, the
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electroactive domain was between –2.0 and 1.0 V vs Fc+/Fc. CV
measurements were recorded before and after the addition of
excess of base (potassium dimsyl solution).
Calculation of experimental bond dissociation energies (BDE).
The experimental homolytic bond dissociation of O–H and N–H
bonds in the iron complexes were estimated by combining their
pKa values with the oxidation potentials of their conjugate bases
according to Bordwell´s methodology, following eq. 2.
4
5
6
7
8
A. G. Campaña, E. Buñuel, J. M. Cuerva and DV.ieJw. CArátircldeeOnnalinse,
Chem. Eur. J., 2013, 19, 16187–16191.DOI: 10.1039/C8DT04689A
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Theoretical calculations. DFT theoretical calculations were
performed with Gaussian 09.50 The calculations were carried
out at the B3LYP/6-31G(d,p) level for C, H, N, O and S atoms,
while the LanL2DZ effective core potential of Wadt and Hay and
its basis set was used for Fe.51 The calculations were done in
DMSO using the polarizable continuum model with the integral
equation formalism (IEFPCM) included in Gaussian 09.52
Calculations of Fe(II)(mep(CONHBu)2) complexes were carried
out using a ultra-fine integration grid. Frequency calculations
were performed to confirm the optimized structures
corresponded to an energy minimum. Bond dissociation free
energy (BDFE) theoretical values were calculated as the
difference between the free energy of the deprotonated or
doubly deprotonated Fe(III) complexes and the sum of the free
energies of the starting Fe(II) complexes and a H atom,
calculated independently. The value of the sum of electronic
and thermal free energies was used. High spin systems were
considered for both Fe(II) and Fe(III) complexes. Counterions
were not included in the calculations. A BDFE value in better
agreement with the experimental one was obtained for the
Fe(II)(mep(OH)) system if the coordinated Cl atom was replaced
by a DMSO molecule.
9
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
We thank the Ministerio de Economía y Competitividad
(MINECO, Spain) (CTQ2014-53598-R) and Junta de Andalucía
(FQM2012-790). S.R. thanks the MECD for FPU predoctoral
fellowship. A.M. and A.G.C. thank the MINECO for IJCI-2016-
27793 and RyC-2013-12943 contracts.
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10 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C8DT04689A
Coordination of hydroxyl/amide groups to Fe(II) diminishes BDFEs of O–H and (CO)N–H bonds
down to 76.0 and 80.5 kcal mol-1 respectively.

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DOI: 10.1039/C8DT04689A
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