Water-soluble derivatives of octanuclear iron-oxido-pyrazolato complexes - An experimental and computational study

Article abstract of DOI:10.1002/ejic.201200428

Two water-soluble iron-pyrazolato complexes (compounds 3 and 4), [Fe ₈], have been prepared by introducing twelve hydroxyalkyl groups to the periphery of the approximately spherical octanuclear molecule. They are contrasted with their two organosoluble chloroalkyl analogues (compounds 1 and 2). All four complexes were characterized in solution by ¹H NMR and electrospray ionization mass spectrometry. The one-electron-reduction product of water-soluble 3, [Fe₈]^-, was structurally characterized by single-crystal X-ray diffraction analysis. In aqueous media, the four terminal Fe-Cl bonds of [Fe₈] are partially hydrolyzed, and the resulting chlorido-aqua-hydroxido species form supramolecular nanoscale aggregates, as determined by dynamic light scattering and electron microscopy. Preliminary computational studies with DFT methods were employed to model the H-bonding interactions controlling the competing solvation and aggregation processes. Twelve hydroxyalkyl pendant groups render an octanuclear iron-oxido-pyrazolato complex soluble in water, where partial hydrolysis and extended intermolecular H-bonding interactions result in supramolecular assemblies. Copyright

Full text of DOI:10.1002/ejic.201200428

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DOI: 10.1002/ejic.201200428
Water-Soluble Derivatives of Octanuclear Iron–Oxido–Pyrazolato Complexes –
an Experimental and Computational Study
Soma Das,[a] Indranil Chakraborty,[a] Dmitry Skachkov,[a] Majid Ahmadi,[b]
Yasuyuki Ishikawa,*[a] Peter Baran,[a][‡] and and Raphael G. Raptis*[a]
Keywords: Cluster compounds / Oxido ligands / Iron oxide / Pyrazolato complexes / Electron microscopy / Density
functional calculations
Two water-soluble iron–pyrazolato complexes (compounds 3
tion analysis. In aqueous media, the four terminal Fe–Cl
and 4), [Fe8], have been prepared by introducing twelve hy- bonds of [Fe8] are partially hydrolyzed, and the resulting
droxyalkyl groups to the periphery of the approximately
spherical octanuclear molecule. They are contrasted with
their two organosoluble chloroalkyl analogues (compounds 1
and 2). All four complexes were characterized in solution by
1H NMR and electrospray ionization mass spectrometry. The
one-electron-reduction product of water-soluble 3, [Fe8]–,
was structurally characterized by single-crystal X-ray diffrac-
chlorido–aqua–hydroxido species form supramolecular nano-
scale aggregates, as determined by dynamic light scattering
and electron microscopy. Preliminary computational studies
with DFT methods were employed to model the H-bonding
interactions controlling the competing solvation and aggre-
gation processes.
in water.[3] Insolubility in water can be overcome in some
cases by the use of one of a small number of physiologically
suitable excipients, an approach which, however, does not
eliminate all formulation-related performance issues.[4] For
example, some of the toxicity of Taxol is associated with
Cremophor-EL, the excipient used to carry the insoluble
active ingredient paclitaxel in aqueous media.[5] Clearly,
whether for simplicity, cost effectiveness, or biological con-
siderations, there are advantages to the preparation of di-
rectly water-soluble derivatives of complexes intended for
medical applications. Apart from therapeutic applications,
solubility in water is also a requirement for contrast agents
in diagnostic imaging, which includes contrast agents for
magnetic resonance imaging (MRI). In contrast-agent-as-
sisted MRI, an enhanced image contrast is achieved by the
intravenous injection of water-soluble, paramagnetic metal
complexes, which shorten the magnetic relaxation rate of
water protons.[6–8]
Recently, we studied a group of paramagnetic, redox-
active, octanuclear iron(III)–pyrazolate clusters of the gene-
ral formula [Fe8(μ4-O)4(μ-4-R-pz)12X4], where pz is pyrazol-
ate, R is H, Cl, Br, or CH3, and X is Cl, Br, or NCS (Fig-
ure 1).[9–12] The Fe8O4 motif constituting the core of these
complexes is the same one found in the FeIII minerals
maghemite (γ-Fe2O3) and ferrihydrite (Fe5HO8·4H2O) as
well as in the FeIII/II mineral magnetite (Fe3O4), all of which
are abundantly available in nature.[13–15] This observation
implies that there is an inherent stability associated with the
iron–oxido motif of [Fe8(μ4-O)4(μ-4-R-pz)12X4] complexes.
Indeed, they are stable toward air and humidity, they can
be safely refluxed in organic solvents, and their terminal
Introduction
High-nuclearity metal clusters and polynuclear transi-
tion-metal complexes are rarely studied in aqueous media,
which limits their applications in the fields of “green chem-
istry” and biomedicine.[1] The reason for this scarcity of ex-
amples is that, in typical polynuclear complexes, the metal
atoms are surrounded by hydrophobic ligands, such as
phosphanes, pyridines, thiols, or groups based on carbox-
ylic acids. Although rendering metal clusters water-soluble
can be challenging, there are significant rewards for achiev-
ing this goal. For example, the two principal advantages of
water as a reaction medium over volatile organic solvents
for industrial-scale catalytic processes are its obvious envi-
ronmental friendliness and safety.[2]
Solubility in water is of prime importance for com-
pounds intended for any kind of biological, therapeutic, or
medical, diagnostic application. For approximately 40% of
active substances identified through combinatorial screen-
ing programs, difficulties are encountered in subsequent ef-
forts to formulate pharmaceutical products based on these
substances, as a result of their lack of significant solubility
[a] Department of Chemistry and the Institute for Functional
Nanomaterials, University of Puerto Rico,
San Juan, PR 00931-3346, USA
Fax: +1-787-7648242
E-mail: raphael@epscor.upr.edu
[b] Department of Physics, University of Puerto Rico,
San Juan, PR 00931-3343, USA
[‡] Current address: Department of Chemistry, Juniata College,
Huntingdon, PA 16652, USA
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201200428.
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ligands X can be substituted through metathesis. Further- and two water-soluble [R
= CH2CH2OH (3) and
more, they can be reversibly reduced in four consecutive CH2CH2CH2OH (4)] and demonstrate that the introduc-
one-electron steps to afford the corresponding mixed-valent tion of alcohol functionalities on the twelve pyrazole li-
anions. In one case, the first reduction product, [Fe8(μ4-O)4- gands is sufficient to render the intact [Fe8] complex water-
(μ-4-Cl-pz)12Cl4]–, was isolated and fully characterized: it is soluble.
readily recognized by its near-infrared (NIR) intervalence-
charge-transfer (IVCT) band and by a shift of the Fe–O
Results and Discussion
stretching frequency ν(Fe–O) in the IR, but it is structurally
indistinguishable, within the experimental margin of error,
from its all-FeIII parent compound.[11] The three-dimen-
sional model of [Fe8(μ4-O)4(μ-pz)12Cl4] and its space-filling
model (Figure 1c) show that the approximately spherical
surface of the complex is defined by H and Cl atoms, which
render it highly hydrophobic. Consequently, [Fe8(μ4-O)4(μ-
4-R-pz)12X4] complexes with R = H, Cl, Br, or CH3 are
all soluble in common organic solvents (dichloromethane,
chloroform, tetrahydrofuran, acetone, toluene, acetonitrile,
etc.), while they remain insoluble in polar protic solvents,
like methanol, ethanol, and water. To explore the rich redox
chemistry of these octanuclear complexes, or to use them
as possible electron-transfer agents in aqueous catalysis ap-
plications to study their paramagnetism, and to employ
them as MRI contrast agents, it is necessary to synthesize
water-soluble members of this group of [Fe8] compounds.
The four ligands HL1–HL4 used for the synthesis of 1–4
were synthesized by optimized literature procedures[18] and
1
were characterized by H and 13C NMR spectroscopy. The
organosoluble iron complexes 1 and 2 were prepared in
one-pot reactions in CH2Cl2, while 3 and 4 were prepared
in EtOH. All four new complexes were characterized in
1
solution by H NMR spectroscopy and ESI-MS and in the
solid state by IR spectroscopy. In addition, 3–, the one-elec-
tron reduction product of complex 3,was crystallographi-
cally characterized by single-crystal X-ray diffraction. Re-
placing the twelve peripheral chlorine atoms of the pendant
alkyl groups of 1 and 2 with hydroxy groups leads to the
complexes 3 and 4, which are soluble in polar protic sol-
vents and give intensely red-colored solutions. The solubil-
ity of 3 in distilled water is Ͼ36 mm, it decreases in alcohols
in the order MeOH Ͼ EtOH Ͼ PrOH Ͼ BuOH (sparingly
soluble), and the compound is insoluble in octanol. The
solubility of 4 in the same solvents is always slightly lower
than that of 3. The complexes 3 and 4 can be recovered
from their aqueous solutions after solvent removal under
reduced pressure. ESI mass spectra of ethanol solutions of
the recovered materials are identical to those of the as-pre-
pared complexes. Because the four terminal Fe–Cl bonds of
1–4 can undergo solvolysis in H2O and in the polar protic
solvents (R–OH) employed in their synthesis, these com-
plexes are prepared as mixtures of species [Fe8Cl4–n(OH)n]
or [Fe8Cl4–n(OR)n], where the product with n = 0 is the
major component.
Figure 1. Ball-and-stick diagram (a), Fe8(μ4-O)4-core and number-
ing of pyrazolate C-atoms (b), and space-filling model (c) of com-
plex [Fe8(μ4-O)4(μ-pz)12Cl4]. Color coding: Fe (golden yellow), C
(grey), N (blue), O (red), Cl (green).
Solubility in water is usually achieved by the introduction
of polar groups, such as sulfonyl, carboxyl, ammonium,
phosphonium, and hydroxy groups.[16] We chose to tackle
the hydrophobicity problem of the [Fe8] compounds by in-
ESI-MS
Mass spectra were obtained in the ESI+ mode from ace-
troducing hydroxyalkyl groups at the 4-positions of the tone solutions of 1 and 2 and from ethanol solutions of 3
twelve pyrazole ligands (residues denoted as 4-R in the mo- and 4. The nebulization gas flow was set to 500 Lh–1 at a
lecular formula), because of the following considerations: temperature of 300 °C, the cone gas was set to 50 Lh–1, and
The solvation of alcohols, such as methanol and ethanol, the source temperature was set to 150 °C. The capillary and
in water is an exergonic process. Imperfect dissolution and cone voltages were set to 3000 (positive ion) and 60 V,
clustering of the alkyl groups in free solution result in a net respectively. The time-of-flight data were collected in the
decrease in entropy, which counters the large exothermic range m/z = 500–3000 with a low collision energy of 6 eV.
term. For EtOH, ΔGhydr
≈
–5 kcalmol–1, ΔHhydr
≈
Data were collected in the continuum mode with a scan
–12 kcalmol–1, and –TΔShydr ≈ +7 kcalmol–1.[17] In the case accumulation time of 0.5 s. All analyses were performed by
of a hydroxyalkyl-modified [Fe8] compound, in which the using an independent reference spray through the Lockpray
aliphatic part of the alcohol groups will be preorganized interference to assure accuracy and reproducibility. The
by the octanuclear complex, the entropic contribution of molecular weights of 1–4 were determined from the [M +
clustering will be null, and the exothermic hydration en- Na]+ ions, which correspond to a neutral molecule plus an
thalpy term will dominate the energetics of the dissolution. adventitious sodium ion. For each of the four compounds,
Here, we report the synthesis and characterization of the simulated isotopic distribution of this peak matches
four new [Fe8(μ4-O)4(μ-4-R-pz)12Cl4] complexes, two or- faithfully the experimental one (Figure 2 and Supporting
ganosoluble [R = CH2CH2Cl (1) and CH2CH2CH2Cl (2)] Information S1). In methanol solutions of 3 and 4, the mo-
2
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Octanuclear Iron–Oxido–Pyrazolato Complexes
lecular ion attributed to [Fe8O4L12Cl2(OMe)(HOEt)]+ was
detected, which indicates that the terminal chlorido ligands
are exchangeable in solution (Supporting Information S1).
Figure 3. 1H NMR spectrum (500 MHz) of [Fe8O4{4-(1-
chloroprop-3-yl)pz}12Cl4] (2) in CD2Cl2. Adventitious impurities
are marked with an asterisk.
Figure 2. Electrospray mass spectrum of an EtOH solution of com-
pound 3 (a); experimental (curve) and calculated (straight, vertical
lines) isotope patterns for the [Fe8O4L312Cl4]Na+ ion (b).
Scheme 1. Proton labelling in the pyrazolates of the clusters 1–4;
(a) corresponds to compounds 1 and 3, while (b) corresponds to 2
and 4.
1H NMR
1
Table 1. H NMR spectroscopic data (500 MHz) for 1–4 at 298 K
1
The H NMR spectra of the organosoluble compounds
[chemical shifts δ in ppm (Ϯ0.01) and relaxation times T2* in ms].
Proton labelling according to Scheme 1.
1 and 2 were recorded in CD2Cl2, and those of the water-
soluble compounds 3 and 4 were measured in CD3OD, by
using 5–6 mm concentrations for each compound. As ex-
pected, the spectra of 1–4 are paramagnetically shifted and
broadened (Figure 3). The paramagnetism of these octanu-
clear FeIII complexes at ambient temperature arises from a
few excited states that are populated besides their diamag-
netic ground state. A detailed magnetic analysis for the
[Fe8(μ4-O)4(μ-pz)12Cl4] motif has been published earlier.[10]
The assignment of the resonances (Scheme 1) of 1–4 is sum-
marized in Table 1.
Proton X = Cl (1) X = OH (3)
T2* T2*
X = Cl (2)
T2*
X = OH (4)
T2*
δ
δ
δ
T1
δ
Ha,
HaЈ
Hb
Hc
21.75, 3.52, 22.59, 3.47, 22.90, 3.57, 7.07, 23.17, 3.20,
19.50 3.52 21.06 3.52 22.20 3.69 6.89 22.39 3.20
4.56 3.89 4.37 4.49 2.58 4.06 9.04 2.27
[a]
–
–
–
–
3.79 6.90 12.87 3.87 5.20
H3
H5
8.40 0.69 7.66 0.98 7.45 0.75 2.16 7.27 0.87
1.63 8.35 1.21 11.72 1.51 7.00 409.80 1.16 7.95
[a] Because of an overlap with an adventitious impurity, the full
width at half maximum could not be measured.
A single set of two resonances assigned to the pyrazolato
ligands is present in each case, which is consistent with is downfield of and significantly broader than that of H5
twelve magnetically equivalent 4-R-pz groups and the per- (proximal to the outer Fe centers). The methylene reso-
sistence of the solid-state structure in solution. The assign- nances were assigned on the basis of on their transverse
ment of the H3 and H5 resonances of the pyrazole rings is relaxation time values T2*, calculated as T2* = (π w1/2)–1,
agreement with those of previously published data for re- where w1/2 is the spectral width at half maximum. Trans-
lated octanuclear complexes.[10] Of these two resonances, verse relaxation times are affected primarily by through-
the one assigned to H3 (proximal to the Fe4O4 cubane core) bond spin polarization effects, which become less signifi-
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cant further away from the paramagnetic center – here, the crystallization of the former from an ethanol solution. The
[Fe8] core of 1–4. Accordingly, the broader resonances, re- mild reducing ability of ethanol has been reported in the
sulting from shorter T2* values, are assigned to the methyl- literature.[19]
ene groups attached to the pyrazole C4 (Ha), whereas the
sharper ones are assigned to the terminal methylene groups
(Hb or Hc) next to the Cl or O atoms. To corroborate the
T2*-based assignment of resonances, the longitudinal relax-
ation times T1 of complex 2 were also determined by spin-
UV/Vis/NIR Spectroscopy
inversion recovery experiments. T1 values are shortened by
a through-space interaction between the protons in ques-
tion and the paramagnetic center with an r–6 distance de-
pendence of the interaction, where r is the proton–paramag-
netic center distance. The T1 values corresponding to the
three methylene groups of 2 increase in the order (Ha, HaЈ)
Ͻ Hb Ͻ Hc, which is in agreement with their increasing
distances from the metal core and the T2*-based assign-
ment. Interestingly, there is a large variation (by a factor of
approximately 10) between the T2* values of the H3 and H5
atoms of all four complexes as well as between the corre-
sponding T1 values (variation by a factor of approximately
200) of 2, which indicates a quite unsymmetrical distribu-
tion of spin density over the pyrazole rings. An in-depth
analysis of electron-spin distribution and its effect on nu-
clear-spin relaxation in these octanuclear complexes is be-
yond the scope of the present manuscript and will be the
topic of future work. With regard to the resonances of the
aliphatic chains, it is worth noting that for all four com-
pounds the geminal Ha and HaЈ atoms are diastereotopic
and anisochronous, whereas the geminal Hb atoms (and Hc
atoms for 2 and 4) are magnetically equivalent. This indi-
cates that the rotation around the pz–CaH2 single bond is
restricted, whereas there are free rotations around the
CaH2–CbH2 and CbH2–CcH2 bonds under ambient-tem-
perature conditions (vide infra).
The electronic absorption spectra of 1 and 2 in CH2Cl2
and those of 3 and 4 in EtOH consist of broad charge-
transfer (CT) bands in the visible spectral region with λmax
values of 26845 (1), 27053 (2), 28680 (3), and 27890 cm–1
(4). The spectra of 1–4 are featureless in the range 5000–
15000 cm–1. However, monitoring the ethanol solution of 3
over a period of several days revealed the slow emergence
of an IVCT band at 6870 cm–1, which is indicative of a
mixed-valent [Fe8]– species, formally an FeIII7FeII complex.
Slow concentration of such an ethanol solution containing
the [Fe8]0/[Fe8]– mixture gave a few single crystals of 3– (vide
infra), which confirmed the spectroscopic assignment. A
UV/Vis/NIR spectrum (Figure 4) obtained from a solution
of these single crystals revealed a well-defined IVCT band
with an extinction coefficient ε = 4250 Lmol–1 cm–1 and a
full width at half maximum w1/2 = 440 cm–1, which – when
analyzed with the Hush–Sutin method – points to 3– being
a strongly coupled, delocalized type-III species according
to the Robin–Day classification.[20,21] We previously re-
ported the reduction of organosoluble [Fe8]0 to [Fe8]– spe-
cies achieved by electrochemical and chemical means – ad-
dition of stoichiometric amounts of [BH4]–.[10,11]
Vibrational Spectroscopy
The IR spectra of the four complexes are consistent with
those of related [Fe8] compounds featuring differently sub-
stituted 4-R-pz ligands (Supporting Information S2). The
diagnostic absorption peak assigned to an Fe–O vibration
appears between 468 and 475 cm–1 in all four spectra. The
spectra of 3 and 4 additionally show broad bands centered
at 3273 and 3293 cm–1, respectively, assigned to the hydroxy
groups, which are absent in the organosoluble analogues.
Figure 4. UV/Vis/NIR spectrum of 3– in solution. Inset: expanded
IVCT band.
Electrochemistry
Electrochemical analyses by cyclic and differential pulse
voltammetry were performed in CH2Cl2/Bu4NPF6 for 2 and
EtOH/Bu4NClO4 for 3. Both compounds showed reversible
reduction processes at –0.49 V (2) and –0.46 V (3) (vs. ferro-
X-ray Crystallography
Complex 3 is quite hydrophilic, and attempts to grow
cene/ferrocinium; Supporting Information S3). The re- single crystals of it so far failed. Fortunately, however, its
–
¯
duction of these [Fe8] complexes can therefore be readily anion 3 crystallized in the trigonal space group R3 with
achieved with mild reducing agents, which was shown here one third of a molecule per asymmetric unit, and the whole
by the partial reduction of 3 to 3– observed during the molecule is generated by an improper threefold rotation.
4
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Octanuclear Iron–Oxido–Pyrazolato Complexes
Bond lengths and angles for 3– are summarized in Table 2. each vicinal 3–. Six additional H-bonds exist between 3–
The crystal structure of 3– (Figure 5) consists of an Fe4O4 and six interstitial H2O molecules [refined at 50% site occu-
cubane core encapsulated inside a shell of four Fe(4-R-pz)3- pancy, O···O distances of 2.83(3) Å], and six more intermo-
Cl units. The tilting of the pyrazole ligand planes away from lecular H-bonds exist between each 3– and six of its imme-
the Cl–Fe–O axes reduces the molecular symmetry of these diate neighbors [O···O distances of 2.86(2) Å]. Besides the
molecules to that of a T point group. The variation of sub- crystallographically determined interstitial H2O molecules,
stituents at the pyrazole 4-position have no significant effect the presence of additional solvent molecules (EtOH or
on the structural parameters of the Fe8O4 core, which re- H2O) was evident by unaccounted-for electron density
mains practically invariant with bond lengths and angles peaks in the difference maps, which could not be modeled,
statistically indistinguishable from those of related com- and whose electron density was eventually removed by the
pounds in the literature.[9–12] The twelve pyrazole groups use of the SQUEEZE routine.[22]
are organized in six approximately parallel pairs (dihedral
angles of 22.9° and 28.1°), which places the methylene Ca
atoms within each pair at Ca···Ca distances of 4.81–5.00 Å.
Thus, the rotation of the remaining part of the aliphatic
chain is hindered, which is consistent with the dia-
Solution Behavior
Free-chloride concentration (with a chloride-specific
electrode) and pH measurements of aqueous solutions of
3 having concentrations in the range of 0.31–0.87 mm are
consistent with the partial hydrolysis of the four Fe–Cl
bonds, which is described by the multistep equilibria of
Equation (1) and involves neutral all-chlorido and
chlorido–hydroxido species as well as positively charged
chlorido–aqua and chlorido–aqua–hydroxido species.
1
stereotopic behavior of the Ha atoms of 3 detected by H
NMR spectroscopy. Complex 3– crystallized with the mo-
nonuclear counterion [FeII(HL3)6]2+, which has a trivial oc-
tahedral coordination environment, bond lengths, and
angles. The ions of 3– are arranged in hexagonal, H-
bonded, honeycomb-like layers, and the consecutive layers
show an AB repeat pattern similar to that of the well-
known structure of graphite. The mononuclear FeII cations
occupy the centers of the hexagons (Supporting Infor-
mation S4). Each cation forms twelve weak H-bonds [O···O
distances of 2.89(1) and 2.96(2) Å] between its six alcohol
[Fe8Cl4] h [Fe8Cl4–nH2O]n]n+ + n Cl– h
[Fe8Cl4–n(OH)n] + n [H3O]+ (1)
In a 0.50 mm aqueous solution of 3, 0.65 mm of free
moieties and two pendant alcohol groups of each vicinal 3– chloride ions and 0.32 mm of hydronium ions (pH = 3.5)
and six H bonds [N···O distances of 2.847(8) Å] between its were detected. The average formula of all [Fe8] species pres-
six pyrazole NH groups and one pendant alcohol group of ent in this aqueous solution is [Fe8O4(L3)12Cl2.70
-
(H2O)0.65(OH)0.65
]
0.65+. Raising the pH by addition of a
base shifts the equilibria of Equation (1) towards the right,
eventually resulting in coagulation of 3 at pH Ͼ 4.4. The
IR spectrum of solid 3 recovered from an aqueous solution
by solvent evaporation under reduced pressure matches that
of the as-prepared material (Supporting Information S2).
The recovered solid redissolves readily in EtOH, the ESI
mass spectrum of the latter solution contains the same mo-
lecular ion as the original material, and its UV/Vis spec-
trum matches that of as-prepared 3 (Supporting Infor-
mation S5).
The hydrodynamic diameter of 3 in aqueous solution was
estimated by dynamic light scattering (DLS) experiments
(Supporting Information S6), which showed the presence of
two differently sized types of aggregates. The major compo-
nent consists of particles with a mean diameter of 5.8 nm,
whereas the minor component consists of larger aggregates
with a mean diameter of 140 nm. The average ζ-potential
of these particles is of +39 mV, which is consistent with the
presence of charged species, as suggested by Equation (1).
To corroborate the DLS results, we imaged the aggregates
by TEM and scanning electron microscopy (SEM), using a
sample produced by solvent evaporation of a drop of an
aqueous solution of 3 on a copper grid with an ultra thin
carbon film (Figure 6). Two types of objects are apparent
in the TEM micrograph: several approximately spherical
objects with dimensions of 5–7 nm and a few larger ones
with dimensions of 40–60 nm. The difference between the
Table 2. Selected bond lengths [Å] and interatomic angles [°] for
3–.[a]
Fec–O
Fec–N
Fec···Fec
Fec–O–Fec
O–Fec–O
Feo–O
2.045(4)–2.052(4) Feo–N
2.054(6)–2.058(6) O–Feo–Cl
3.074(2)–3.081(2) N–Feo–N
2.018(7)–2.031(6)
179.9(2)–180.0
118.6(2)–121.4(2)
5.823(2)
[b]
97.3(2)–98.1(2)
81.7(2)–82.1(2)
1.926(7)–1.936(4) Feo···Fec
Feo···Feo
Feo···Fec[b] 3.430(2)–3.453(1)
[b]
5.457(6)
2.180(7)
Feo–Cl
2.264(3)–2.273(3) FeII–N
[a] Fec and Feo denote cubane- and outer-Fe atoms, respectively.
[b] There are three short and one long Feo···Fec distances per Fe
atom between the vertices of the two co-centrical tetrahedra formed
by the four Fec and four Feo atoms, respectively.
Figure 5. Ball-and-stick (a) and space-filling (b) diagrams of
[Fe8O4{4-(1-hydroxyeth-2-yl)pz}12Cl4]– (3–) in the same orienta-
tion. Color coding: Fe (golden yellow), C (grey), N (blue), O (red),
Cl (green).
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diameters determined by DLS and TEM is consistent with computational study serve to identify the attractive or re-
solvent-impregnated, larger particles in solution, which be- pulsive intermolecular interactions responsible for the aque-
come desiccated and shrink upon solvent evaporation on ous chemistry of one of the several possible species resulting
the copper grid. Considering both the molecules of 3 and from the hydrolysis of 3. Further analyses, including other
their aggregates as idealized hard spheres, we estimate that [Fe8Cl4–n–m(H2O)n(OH)m]n+ species and their combinations
approximately 13 molecules of 3 can be accommodated in as well as the determination of the entropy changes associ-
a 6 nm particle, whereas approximately 90 molecules will fit ated with the formation of [Fe8] aggregates, will be the focus
in a 50 nm spherical particle. The electron diffraction of a future comprehensive study.
pattern observed on both small and large objects indicates
crystallinity (Supporting Information S7).
Figure 7. Calculated H-bonding interactions between two mo-
lecules of [Fe8Cl3(OH)]: Fe–OH···HO–Fe (a); Fe–OH···Cl–Fe (b).
Conclusions
Figure 6. TEM images of particles of 3 generated from an aqueous
solution.
We have shown that a hydrophobic, octanuclear iron–
oxido cluster (1 and 2) can be converted into a hydrophilic
Molecules of 3 in their nonhydrolyzed neutral form,
one (3 and 4) by the attachment of hydroxyalkyl dangling
[Fe8Cl4], do not aggregate, as the intermolecular Cl···Cl in-
groups around its periphery. Although the water-soluble
teraction is repulsive (8.2 kcalmol–1 at 3.283 Å) and the
compounds are hydrolyzed, their hydrolysis does not lead
intermolecular alcohol–alcohol H-bonds are weaker than
to uncontrolled polymerization through Fe–O(H)–Fe bond
alcohol–water H-bonds.[17] Therefore, only hydrolyzed
formation, presumably because this process is sterically hin-
[Fe8Cl4–n(H2O)n]n+
,
[Fe8Cl4–n–m(H2O)n(OH)m]n+
,
and
dered by the hydroxyalkyl pendant groups.
[Fe8Cl4–n(OH)n] species, where n + m = 0–4, and their com-
binations can lead to aggregates, which account for the par-
ticles observed in the DLS and electron microscopy experi-
ments. Our preliminary computational study to probe the
attractive interactions between [Fe8] units only took
[Fe8Cl3(OH)] into consideration.
The rich supramolecular chemistry of 3 uncovered in the
present work stimulated further in-depth studies, which are
currently in progress in our laboratory.
Experimental Section
The solvation of an individual neutral [Fe8Cl3(OH)] mo-
lecule was modeled with 187 water molecules: after optimi-
General: 2-Ethoxy-3-tetrahydrofurancarbaldehyde diethyl acetal, 2-
zation, there are 3 water–alcohol H-bonds per pendant ethoxy-3-tetrahydropyrancarbaldehyde diethyl acetal, hydrazine di-
hydrochloride, triethyl orthoformate, EtOH (anhydrous), thionyl
chloride, FeCl3 (anhydrous), CH2Cl2 (anhydrous) were purchased
from Sigma–Aldrich and used as received. The CH2Cl2 and THF
solvents used for washing 3 and 4 were distilled from anhydrous
CaCl2. Spectra/Por CE dialysis membranes with a molecular-
weight cut-off (MWCO) of 500–1000 Daltons were purchased from
Spectrumlabs. Chloride ion concentrations were measured in aque-
ous media with an Orion 9617BNWP ionplus Sure-Flow chloride-
specific electrode by using a Thermo Scientific Orion StarTM Series
alcohol group, one water–Cl H-bond per chlorido ligand,
and 3 H-bonds between the OH– ligand and its three near-
est water molecules, which add up to a total of 42 water
molecules in the first coordination sphere of [Fe8Cl3(OH)].
The total hydration enthalpy of this assembly, which in-
cludes the H-bonds formed by the remaining 145 water mo-
lecules of the outer solvation sphere, is approximately
42 kcalmol–1. Aggregation of [Fe8] units can occur by inter-
molecular H-bonding between two Fe–OH groups or be-
1
ISE Meter. H NMR and UV/Vis/NIR spectra were recorded with
tween one Fe–OH and one Cl–Fe group. The formation of a Bruker AVANCE DRX-500 and a Varian Cary 500 spectrometer,
respectively. Attenuated-total-reflectance (ATR) FTIR spectra were
recorded with a Bruker TENSOR 27 FTIR spectrometer with a
HELIOS ATR attachment by using a HeliosTM Diamond Car-
tridge (HLS-CRS-W, Pleasantville, NY). Electrospray ionization
mass spectra (ESI-MS) were recorded with a Q-Tof micro mass
spectrometer (Waters Corp., Milford, MA, USA) by using ethanol
or acetone solutions of 1, 2, 3, or 4. Electrochemical experiments
were carried out with a BAS 50 electrochemical analyzer by using
Pt-disk or glassy-carbon working electrodes, a Pt-bar counter elec-
trode, and an Ag/AgNO3 reference electrode. DLS measurements
an [Fe8]–[Fe8] dimer through reciprocal donor–acceptor Fe–
OH···HO–Fe pairs was also modeled (H···O distance of
1.681 Å, Figure 7a). The two H-bonds between the two OH
groups are accompanied by four weaker alcohol–alcohol H-
bonds, and this leads to a total enthalpy of dimer formation
of 19.8 kcalmol–1. In contrast, the weaker H-bonding Fe–
OH···Cl–Fe interaction and its four accompanying, rein-
forcing intermolecular alcohol–alcohol H-bonds (H···Cl
distance 2.144 Å, Figure 7b) collectively account for a bind-
ing enthalpy of 11.9 kcalmol–1. The results of the above were performed with a Dynapro Titan instrument (Wyatt Technol-
6
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Octanuclear Iron–Oxido–Pyrazolato Complexes
ogy Co.) by using a 657 nm diode laser at a 90° scattering angle.
For the morphological characterization a JEOL JEM-2100F trans-
mission electron microscope (TEM) was used.
under argon with HL3 (preparation of 3, 11.1 mmol, 1.242 g) or
HL4 (preparation of 4, 11.1 mmol, 1.404 g) and anhydrous EtOH
(60 mL). To this solution was added anhydrous FeCl3 (3.6 mmol,
0.6 g), and the color of the solution immediately turned orange-
red. The reaction flask containing the orange-red solution was then
taken out of the glove box, triethylamine (1.5 mL) was added drop-
wise in the presence of atmospheric moisture, and the color grad-
ually darkened. The reaction afforded the water-soluble octanu-
clear iron(III) compound 3 or 4. After 18–20 h, the solution was
filtered to remove a small amount of insoluble solids, and the fil-
trate solvent was removed under reduced pressure. The crude reac-
tion product was washed with CH2Cl2 and then with THF, and it
was dried under vacuum. The dark-red solid was then extracted in
anhydrous EtOH and filtered, and the solvent was removed under
reduced pressure. After the process of extraction and drying was
repeated thrice, the resulting dark red oily material was finally
crushed out with diethyl ether. A brick-red, solid powder was ob-
tained, which was soluble in methanol, ethanol, propanol, and
water. The resulting compound was further dialyzed in n-propanol
for 5 d by using a Spectra/Por CE dialysis membrane with an
MWCO (500–1000 Da), which yielded 3 (170 mg, 18.5%) or 4
(180 mg, 13.0%).
Ligand Synthesis: 4-(2-Hydroxyethyl)pyrazole (HL3) and 4-(3-hy-
droxypropyl)pyrazole (HL4) were synthesized by using a literature
procedure.[18] 4-(2-Chloroethyl)pyrazole (HL1) and 4-(3-chlo-
ropropyl)pyrazole (HL2) were synthesized by chlorination of HL3
and HL4, respectively, by using thionyl chloride. The chlorination
was followed by extraction with hot EtOH and crushing-out by
diethyl ether. The (chloroalkyl)pyrazoles were further extracted
with CH2Cl2 to separate them from the excess starting materials,
(hydroxyalkyl)pyrazoles, and they were finally dried under vacuum.
All four ligands were characterized by 1H and 13C NMR spec-
troscopy.
4-(HOCH2CH2)pzH (HL3): 1H NMR (D2O): δ = 3.56 (t, J =
5.0 Hz, 2 H, α-CH2), 2.54 (t, J = 5.0 Hz, 2 H, β-CH2), 7.37 (s, 2
H, pzH-H3,5) ppm. 13C NMR (D2O): δ = 61.87 (α-C), 25.8 (β-C),
133.63 (pzH-C3,5), 117.3 (pzH-C4) ppm.
1
4-(HOCH2CH2CH2)pzH (HL4): H NMR (D2O): δ = 3.38 (t, J =
7.5 Hz, 2 H, α-CH2), 1.57 (m, 2 H, β-CH2), 2.31 (t, J = 7.5 Hz, 2
H, γ-CH2), 7.33 (s, 2 H, pzH-H3,5) ppm. 13C NMR (D2O): δ =
61.89 (α-C), 32.45 (β-C), 19.34 (γ-C), 133.15 (pzH-C3,5), 120.39
(pzH-C4) ppm.
4-(ClCH2CH2)pzH (HL1): 1H NMR (CD2Cl2): δ = 3.70 (t, J =
7.5 Hz, 2 H, α-CH2), 3.05 (t, J = 5.0 Hz, 2 H, β-CH2), 7.91 (s, 2
H, pzH-H3,5), 12.40 (s, 1 H, NH) ppm. 13C NMR (CD2Cl2): δ =
44.07 (α-C), 27.05 (β-C), 131.44 (pzH-C3,5), 119.30 (pzH-C4) ppm.
1
3: H NMR (CD2Cl2): δ = 22.598 (s, 1 H, β-CH2), 21.063 (s, 1 H,
β-CH2), 7.66 (s, 1 H, H3), 4.37 (s, 2 H, α-CH2), 1.219 (s, 1 H, H5)
ppm. IR: ν = 3273 (w, br.), 2927 (w), 2863 (w), 1435 (w), 1398 (w),
˜
1358 (m), 1295 (m), 1147 (w), 1121 (w), 1043 (vs, br.), 100 (s, br.),
863 (w), 738 (w), 675 (w), 624 (m), 537 (m, br.), 475 (vs, br. Fe–O),
416 (m, br.) cm–1.
1
4-(ClCH2CH2CH2)pzH (HL2): H NMR (CD2Cl2): δ = 3.54 (t, J
1
4: H NMR (MeOD): δ = 23.17 (s, 1 H, γ-CH2), 22.39 (s, 1 H, γ-
= 5.0 Hz, 2 H, α-CH2), 2.05 (m, 2 H, β-CH2), 2.75 (t, J = 5.0 Hz,
2 H, γ-CH2), 7.88 (s, 2 H, pzH-H3,5), 14.74 (s, 1 H, NH) ppm. 13C
NMR (CD2Cl2): δ = 43.86 (α-C), 32.42 (β-C), 20.57 (γ-C), 131.42
(pzH-C3,5), 121.48 (pzH-C4) ppm.
CH2), 7.27 (s,1 H, H3), 3.87 (s, 2 H, α-CH2), 2.27 (s, 2 H, β-CH2),
1.16 (s,1 H, H5) ppm. IR: ν = 3293 (m, br.), 2931 (w), 2860 (w),
˜
1448 (w), 1400 (w), 1354 (m), 1296 (w), 1122 (w), 1121 (w), 1048
(vs, br.), 1014 (s, br.), 849 (w), 668 (w), 615 (m), 552 (m, br.), 469
(vs, br. Fe–O) cm–1.
Synthesis of Organosoluble [Fe8(μ4-O)4(μ-Lx)12Cl4] (R = chloro-
alkyl, x = 1 or 2), Compounds 1 and 2: A conical flask was charged
under argon with anhydrous FeCl3 (1.2 mmol, 0.2 g) and anhy-
drous CH2Cl2 (20 mL). To this suspension was added HL1 (prepa-
ration of 1, 3 mmol, 0.498 g) or HL2 (preparation of 2, 3 mmol,
0.54 g), and the color of the solution turned yellow. Upon dropwise
addition of triethylamine (500 μL), the color changed to dark red,
and dense fumes evolved. The reaction mixture was stirred over-
night and then filtered, and the solvent was removed under reduced
pressure. The resulting residue was dissolved in a minimal amount
of CH2Cl2 and eluted through a chromatographic column packed
with silica gel (60–100 Å) and toluene. The bright-red eluent was
again dried by solvent evaporation under reduced pressure, which
was followed by vacuum desiccation. The dry compound was then
collected and further washed with water (50 mg and 14.5% yield
for 1; 120 mg and 32.5% yield for 2).
An aliquot of the original ethanol reaction mixture was withdrawn
prior to the workup and was allowed to slowly concentrate, which
resulted after 20 d in bright-red single crystals of [3–]2[FeII(HL3)62+]·
3H2O·x(solvent) suitable for X-ray diffraction. The UV/Vis/NIR
spectrum of these crystals in ethanol shows an IVCT band at
6870 cm–1, which confirms the mixed-valent nature of 3– (see Re-
sults and Discussion section). This IVCT band is not present in
aliquots freshly withdrawn from the reaction mixture.
X-ray Crystallography of [3–]2[Fe(HL3)6]: X-ray diffraction data,
collected with a Bruker APEX-2 CCD diffractometer from a single
crystal mounted atop of a glass fiber, were corrected for Lorentz
and polarization effects.[23] The structure was solved by employing
the SHELXS97 program and refined by a least-squares method on
F2 with SHELXL97 incorporated in SHELXTL, Version 5.1.[23–25]
All non-hydrogen atoms were refined anisotropically. Hydrogen
atoms were placed in calculated positions and refined with their
thermal ellipsoids riding on the corresponding carbon or oxygen
atoms. Large solvent-accessible voids in the crystal structure of 3–
are occupied by interstitial solvent molecules, whose crystallo-
graphic disorder could not be modeled satisfactorily. Consequently,
the diffraction data set of 3– was modified by the SQUEEZE rou-
tine of the PLATON package before final refinement.[22] An OR-
TEP diagram and complete tables of bond lengths and angles are
given in Supporting Information S6. C150H222Cl8Fe17N60O41; Mr =
1:1H NMR (CD2Cl2): δ = 21.75 (s, 1 H, β-CH2), 19.50 (s, 1 H, β-
CH2), 8.40 (s, 1 H, H3), 4.56 (s, 2 H, α-CH2), 1.63 (s, 1 H, H5)
ppm. IR: ν = 1451 (w), 1406 (w), 1360 (m), 1341 (m), 1243 (w),
˜
1169 (w), 1090 (w), 1050 (vs), 1003 (m), 865 (w), 771 (w), 628 (m),
554 (w), 474 (vs, br. Fe–O) cm–1.
1
2: H NMR (CD2Cl2): δ = 22.89 (s, 1 H, γ-CH2), 22.20 (s, 1 H, γ-
CH2), 7.44 (s, 1 H, H5), 3.79 (s, 2 H, α-CH2), 2.58 (s, 2 H, β-CH2),
1.51 (s,1 H, H3) ppm. IR: ν = 2958 (w), 2860 (w), 1441 (w), 1404
˜
(w), 1354 (m), 1260 (m), 1163 (w), 1092 (w), 1047 (vs), 1003 (m),
850 (w), 794 (s, br.), 626 (m), 556 (w), 468 (vs, br. Fe–O), 438 (s)
cm–1.
Synthesis of Water-Soluble [Fe8(μ4-O)4(μ-Lx)12Cl4] (R = hydroxy-
alkyl, x = 3 or 4), Compounds 3 and 4: A conical flask was charged
¯
4752.91; space group trigonal; R3 (No. 148); a = 21.260(3) Å, c =
42.441(9) Å; V = 16613(5) Å3; Z = 3; T = (296Ϯ2) K; λ (Mo-Kα) =
0.71073 Å; ρcalcd. = 1.425 gcm–3; μ = 0.832 mm–1. A total of 64186
reflections were collected, 8464 unique (Rint = 0.0829); R1 = 0.0840
Eur. J. Inorg. Chem. 0000, 0–0
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Y. Ishikawa, R. G. Raptis et al.
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Acknowledgments
The authors acknowledge partial financial support of this project
by the National Institutes of Health (NIH-SCoRE S06GM008102,
NIH-NCI U54CA096297), and the National Science Foundation
(RII 1002410) through the Institute for Functional Nanomaterials.
We are thankful to Dr. Fernando González Illán, Luis
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Received: April 29, 2012
Published Online: ᭿
8
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Pages: 9
Octanuclear Iron–Oxido–Pyrazolato Complexes
Coordination Chemistry
Twelve hydroxyalkyl pendant groups ren-
der an octanuclear iron–oxido–pyrazolato
complex soluble in water, where partial hy-
drolysis and extended intermolecular H-
bonding interactions result in supramo-
lecular assemblies.
S. Das, I. Chakraborty, D. Skachkov,
M. Ahmadi, Y. Ishikawa,* P. Baran,
R. G. Raptis* .................................... 1–9
Water-Soluble Derivatives of Octanuclear
Iron–Oxido–Pyrazolato Complexes – an
Experimental and Computational Study
Keywords: Cluster compounds / Oxido li-
gands / Iron oxide / Pyrazolato complexes /
Electron microscopy / Density
functional calculations
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