Synthesis and Structural Studies of Gallium(III) and Iron(III) Hemicryptophane Complexes

Article abstract of DOI:10.1021/acs.inorgchem.5b02750

New gallium(III) and iron(III) endohedral complexes were obtained from a hemicryptophane ligand bearing suitable binding sites for octahedral metal coordination. The solid-state structures of the free host and of the complexes were determined by single-cr

Full text of DOI:10.1021/acs.inorgchem.5b02750

Communication
pubs.acs.org/IC
Synthesis and Structural Studies of Gallium(III) and Iron(III)
Hemicryptophane Complexes
Isabelle Gosse,†,∥ Koen Robeyns,‡ Catherine Bougault,§ Alexandre Martinez,†,⊥ Bernard Tinant,*,‡
and Jean-Pierre Dutasta*,†
†
́
Laboratoire de Chimie, Ecole Normale Super
́
ieure de Lyon, CNRS, UCBL, 46 allee
́
d’Italie, F-69364 Lyon 7, France
‡Universite
́
Catholique de Louvain, MOST, 1 Place Louis Pasteur, B-1348 Louvain-la-Neuve, Belgium
§Institut de Biologie Structurale, UMR5075 CNRS-CEA, Universite
France
́
J. Fourier Grenoble, 41 rue Jules Horowitz, F-38027 Grenoble,
S
* Supporting Information
Herein, we report on the design and synthesis of a
heteroditopic molecular receptor, which presents the octahedral
environment for M3+ metal ions, and maintains the C3 symmetry
of the cyclotribenzylene (CTB) platform. Our efforts have
yielded a compound that forms complexes with GaIII and FeIII
ions, which are encapsulated into the polar part of the molecular
cavity. These complexes contain a lipophilic space in close
proximity to the metal ion, and the possibility to increase the
length of the side chains opens the route to a new family of size-
modular molecular cavities for the simultaneous encapsulation of
metal ions and neutral substrates.
ABSTRACT: New gallium(III) and iron(III) endohedral
complexes were obtained from a hemicryptophane ligand
bearing suitable binding sites for octahedral metal
coordination. The solid-state structures of the free host
and of the complexes were determined by single-crystal X-
ray diffraction analysis. The metal ion is linked to the
hydrazone nitrogen and the phenolate oxygen atoms,
yielding a distorted octahedral geometry around the
encapsulated metal. The two isomorphous structures of
the metal complexes reveal the exclusive formation of PΔ/
MΛ enantiomeric pairs.
The synthetic pathway that led to the hemicryptophane 1 is
outlined in Scheme 1 and follows the strategy recently developed
for the preparation of tren-hemicryptophane derivatives.10 The
CTB 2 is synthesized in three steps from vanillyl alcohol
according to the published procedure.11 Selective monoallylation
of 2,3-dihydroxybenzaldehyde gave compound 3,12 which
reacted with 1,4-dibromobutane in acetonitrile in the presence
of K2CO3 to afford compound 4 in 61% yield. The CTB 2 reacted
with an excess of 4 in N,N-dimethylformamide/hexamethyl-
phosphoramide in the presence of NaOH to give the
tripropenyloxy-protected compound 5 in 55% yield. Depro-
tection of the phenol groups in 5 was performed following the
known procedure by using palladium(III) acetate/triphenyl-
phosphine in ethanol in the presence of formic acid and
triethylamine to give the precursor 6 in 70% yield. The reaction
ryptophanes, with their spherical molecular cavity, are well-
Cknown for their high propensity to form van der Waals
host−guest complexes. Because of their essentially lipophilic
character, the binding properties are restricted to neutral organic
guests, rare gas, and ammonium salts.1 Recent investigations with
water-soluble derivatives allowed extension of the recognition
properties of cryptophane hosts to metal ions.2 The related
hemicryptophane hosts have been designed to introduce
endohedral functionalities in the molecular cavity, giving a
ditopic character to these molecules. One of the first examples of
a hemicryptophane supramolecule was based on a phospho-
trihydrazone moiety and showed an affinity for aromatic guest
molecules.3 From such a structure, it appeared that adding
specific binding sites having an affinity for metal ions could lead
to new metal hemicryptophane complexes. This has been
achieved by the synthesis of several hemicryptophanes bearing
suitable coordinating substituents. For instance, oxidovana-
dium,4 zinc,5 and copper complexes6 have been reported. In
these structures, the metal atom is located inside the molecular
cavity, leading to an endohedral complex. Some of these
complexes present interesting and original catalytic properties,7
and the inner space of the molecular receptor behaves like a
chemical reactor at the nanoscale. Similarly, proazaphosphatrane
superbases8 and their conjugate acid azaphosphatranes9 have
been incorporated into the cavity of a tren-hemicryptophane
ligand, where the highly reactive center is encapsulated in the
molecular cavity. Such supramolecular systems are obviously of
prime importance in the design of new catalysts that are expected
to be more robust and highly selective.
13
of 6 with phosphotrihydrazide P(S)(NMeNH2)3 in tetrahy-
drofuran led to the hemicryptophane 1 in 54% yield, which was
characterized by 1H, 13C, and 31P NMR, electrospray ionization
mass spectrometry, and X-ray diffraction.
The gallium and iron complexes Ga@1 and Fe@1 were
obtained by treating a solution of 1 in 1,1,2,2-tetrachloroethane
with Ga(acac)3 or Fe(acac)3, respectively (Scheme 1). Ga@1 was
obtained in 70% yield as a bright-yellow solid. Similarly, Fe@1
gave a dark-blue crystalline compound in 86% yield. The
diamagnetic Ga@1 complex was characterized by mass
spectrometry and 1H, 13C, and 31P NMR spectroscopy in
CDCl3. The signal of the phenolic protons disappears and the
resonance of the imine protons is low-field-shifted by 0.3 ppm
because of the electronic deficiency of the gallium ion, in
Received: November 26, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.5b02750
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Communication
Scheme 1. Synthesis of the Hemicryptophane 1 and Metal Hemicryptophane Complexes Ga@1 and Fe@1
accordance with complexation of the metal ion in the
phosphorylated part of the host molecule. The Fe@1 complex
was characterized by mass measurement, and its electron
paramagnetic resonance (EPR) spectrum (g = 4.1; X band) is
consistent with a high-spin FeIII iron in an octahedral
environment. The 1H NMR spectrum shows diamagnetic signals
assigned to the protons of the CTB moiety (Figure S11). This
confirms that the iron ion is located in the phosphotrihydrazone
core of the host molecule.
with the pseudo-3-fold axis of the molecule. The complexes
present two stereogenic centers: the CTB unit (P or M
configuration) and the octahedral coordination site (Δ or Λ
configuration; Figure S15), which should lead to the existence of
two diastereomeric racemates (MΔ/PΛ) and (PΔ/MΛ).
The isostructural Ga@1 and Fe@1 complexes consist of only
one racemate (PΔ/MΛ) (Figures 2 and S16). Most likely,
The molecular structures of the hemicryptophane 1 and both
metal complexes were obtained from single-crystal X-ray
diffraction studies. The solid-state structure of host 1 is shown
in Figure 1. The molecule adopts a pseudo-C3 symmetry, where
Figure 2. Stereoview of the X-ray molecular structure of the Fe@1
complex (the MΛ enantiomer is shown). Color code: C, gray; N, blue;
O, red; Fe, light blue; P, magenta; S, yellow.
formation of the complex is diastereoselective because of the
significant conformational strains that should occur in the MΔ/
PΛ diastereomers, where nonfavorable interactions between the
linking chains [O(CH2)4O] and the methoxy groups are
expected. The octahedral metallic center and the chiral CTB
unit induce a right- and left-handed helical arrangement of the
O(CH2)4O linkers in the PΔ and MΛ enantiomers, respectively.
A parallel comparison can be made with the structure of the free
hemicryptophane ligand 1 described above, where the
configuration of the CTB unit controls the clockwise or
anticlockwise helical arrangement of the linkers.
In conclusion, we have shown that the CTB and
phosphotrihydrazone moieties can be combined to lead to a
hemicryptophane structure, which presents a ditopic character
with polar and lipophilic binding sites inside the same molecular
cavity. The new thiophosphorylated hemicryptophane 1 bearing
three phenol groups is able to form octahedral metal complexes
with GaIII and FeIII ions. NMR and X-ray diffraction studies of the
complexes showed that the metal is nested inside the
thiophosphorylated part of the molecule. Both metal complexes
exhibit a helical structure induced by the octahedral metal center;
the chirality of the CTB moiety induces exclusive formation of
the PΔ/MΛ racemates.
Figure 1. X-ray molecular structures of C7H8@1: (left) P-α-helix and
(right) M-β-helix enantiomers (the encapsulated toluene molecule is
green).
the P−S bond is oriented outward and aligned along the C3 axis
of the CTB unit. This arrangement defines a molecular cavity
occupied by one toluene molecule. The linkers that bind the
phosphotrihydrazone moiety to the CTB unit adopt a clockwise
or anticlockwise orientation, inducing α or β helicity, which can
define diastereomeric isomers due to the M or P configuration of
the CTB cap (namely, the two enantiomeric pairs M-α-helix/P-
β-helix and M-β-helix/P-α-helix). Interestingly, the centrosym-
metric crystal of 1 contains only the M-β-helix/P-α-helix pair of
enantiomers, indicating that the configuration of the CTB unit
directs the helical arrangement of the linkers.
In the Ga@1 and Fe@1 hemicryptophane complexes, the
metal atom is nested in the phosphotrihydrazone core and bound
to the three imine nitrogen atoms and the three phenol oxygen
atoms, leading to a distorted octahedral geometry of the metal
center (selected bond distances and angles are given in Table
S1). The P−S bond is directed outward from the molecular
cavity, and the sulfur, phosphorus, and metal atoms are aligned
B
DOI: 10.1021/acs.inorgchem.5b02750
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Communication
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.5b02750.
■
S
Materials and instrumentation, synthetic procedures,
NMR and EPR spectra, electrospray ionization mass
spectra, crystal data, and details of structure refinement
(PDF)
Crystallographic data in CIF format (CIF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: bernard.tinant@uclouvain.be.
*E-mail: jean-pierre.dutasta@ens-lyon.fr.
■
Present Addresses
∥I.G.: Institut des Sciences Molec
́
ulaires, Universite
ation, F-33405 Talence, France.
⊥A.M.: Chirosciences, UMR CNRS 7313-iSm2, Aix Marseille
Universite, Ecole Centrale de Marseille, Avenue Escadrille
́
de Bordeaux,
357 cours de la Liber
́
́
Normandie-Niemen, 13397 Marseille France.
Notes
The authors declare no competing financial interest.
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DOI: 10.1021/acs.inorgchem.5b02750
Inorg. Chem. XXXX, XXX, XXX−XXX