Decorating the lanthanide terminus of self-assembled heterodinuclear lanthanum(iii)/gallium(iii) helicates

Article abstract of DOI:10.1039/c1dt10775e

Arylacylhydrazones of 2,3-dihydroxybenzaldehyde are appropriate ligands for the preparation of heterodinuclear triple-stranded helicates involving high coordinated lanthanide(iii) ions. In the present study, three different kinds of substituents are intro

Full text of DOI:10.1039/c1dt10775e

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PERSPECTIVE:
Metal ion directed self-assembly of sensors for ions, molecules and biomolecules
Jim A. Thomas
Dalton Trans., 2011, DOI: 10.1039/C1DT10876J
ARTICLES:
Self-assembly between dicarboxylate ions and a binuclear europium complex: formation of stable
adducts and heterometallic lanthanide complexes
James A. Tilney, Thomas Just Sørensen, Benjamin P. Burton-Pye and Stephen Faulkner
Dalton Trans., 2011, DOI: 10.1039/C1DT11103E
Structural and metallo selectivity in the assembly of [2 × 2] grid-type metallosupramolecular
species: Mechanisms and kinetic control
Artur R. Stefankiewicz, Jack Harrowfield, Augustin Madalan, Kari Rissanen, Alexandre N. Sobolev
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Dalton Trans., 2011, DOI: 10.1039/C1DT11226K
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PAPER
Decorating the lanthanide terminus of self-assembled heterodinuclear
lanthanum(III)/gallium(III) helicates†
Markus Albrecht,*a Irene Latorre,a Gent Mehmeti,a Konstantin Hengsta,b and Iris M. Oppelb
Received 28th April 2011, Accepted 15th July 2011
DOI: 10.1039/c1dt10775e
Arylacylhydrazones of 2,3-dihydroxybenzaldehyde are appropriate ligands for the preparation of
heterodinuclear triple-stranded helicates involving high coordinated lanthanide(III) ions. In the present
study, three different kinds of substituents are introduced at the ligands in order to modify the organic
periphery of the coordination compounds: (1) alkoxy groups are attached to the terminal phenyl
groups, (2) NH protons of the hydrazones are substituted by phenyl moieties and (3) amino acid
bearing units are attached to the terminus of the ligand. The new ligands nicely form the desired
triple-stranded gallium(III)-lanthanum(III) complexes [(5a-c,7,12,15)3GaLa] of which the highly
phenylated derivative was crystallized and studied by X-ray diffraction.
while in B a kink is introduced by the tetrahedral sulphur atom
leading to back folding of the substituent and a more compressed
overall shape (Fig. 1).
Introduction
Metallosupramolecular chemistry is based on the reversible recog-
nition between metal ions and oligotopic ligands.1 Complicated
structures are obtained by simply mixing of organic ligands with
appropriate metal ions.2 If heterotopic ligands are introduced, it is
possible to isolate coordination compounds containing different
metal ions in well defined positions. Especially the latter are of
high importance in order to study metal-metal communication
phenomena.3
A very simple class of metallosupramolecular compounds are
the helicates.4 They are formed in self-assembly processes starting
from linear oligotopic ligand strands and two or more metal ions.
The introduction of different metal ions to obtain heterodinuclear
complexes is challenging but was described in some cases and
utilizes either different electronic features or different denticity of
ligand units to distinguish between the different metal ions. The
latter allows for example the formation of heterodinuclear p-f or d-
f coordination compounds which in some cases exhibit interesting
energy transfer between complex units.5
Fig. 1 Heteroditopic helicates based on acyl- (A) or tosyl-hydrazones (B)
of 2,3-dihydroxybenzaldehyde.
Recently we introduced a simple system, in which triple-
stranded heterodinuclear complexes are formed from acyl- (A)6 or
tosyl-hydrazones (B)7 of 2,3-dihydroxybenzaldehyde. The catechol
unit acts as a bidentate ligand and coordinates e.g. titanium(IV),
aluminum(III) or gallium(III)ions, while the acyl or tosyl hydrazone
together with the internal catechol oxygen atoms represents a
tridentate ligand for binding of high coordinated metal ions (e.g.
lanthanides). A remarkable difference between the acyl and the
tosyl derivatives is that in A the ligands are more or less linear,
The simple preparation of those ligands for self-assembly
of heterodinuclear compounds allows a facile variation of the
substituents in the periphery. In here we describe different ap-
proaches to functionalized helicates of type A. First, terminal aryl
substituents are introduced, which bear alkyl chains of different
length. This leads to compounds with a hydrophobic lanthanide
moiety. Second, the NH proton of the acylhydrazone is substituted
by a phenyl group, resulting in an accumulation of six phenyl
substituents around the lanthanide complex. Finally, amino acid
based residues are attached to the “lanthanide terminus” of the
ligand in order to provide derivatives which in the future can be
used for the attachment of e.g. short peptides.
aInstitut fu¨r Organische Chemie, Landoltweg 1, 52074, Aachen, Germany.
E-mail: markus.albrecht@oc.rwth-aachen.de
bInstitut fu¨r Anorganische Chemie, Landoltweg 1, 52074, Aachen, Germany
† CCDC reference number 789894. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1dt10775e
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Dalton Trans., 2011, 40, 12067–12074 | 12067
©

The second step of the sequence to afford the ligands was
the preparation of the hydrazides by reaction of the esters with
hydrazine monohydrate. Products 3a and 3b were obtained from
2a and 2b in 70% or quantitative, respectively, after 24 h at room
temperature in MeOH. This probably was possible due to the
good solubility of the intermediates 2a and 2b in polar solvents.
Compound 3c was obtained from 2c and hydrazine after reflux in
MeOH for 48 h in a yield of 51%.
Results and discussion
Alkyl-substituted heterodinuclear triple-stranded helicates
In general, alkyl-functionalization at the acylhydrazone terminus
of the ligand results in coordination compounds in which all
alkyl groups are orientated in the same direction of space. This
is schematically presented in Scheme 1.
Finally, standard hydrazone condensation of derivatives 3a–3c
with 2,3-dihydroxybenzaldehyde 4 in methanol afforded after 24 h
the ligands 5a-H2 - 5c-H2.10
With the obtained ligands, complexes [(5a)3GaLa], [(5b)3GaLa]
and [(5c)3GaLa] were successfully synthesized and were char-
acterized by NMR spectroscopy and MS-spectrometry. The
coordination studies were performed following Scheme 3.
Scheme 1 Schematic representation of the formation of heterodinuclear
helicates which bear an “alkyl-bundle” at the tail.
The preparation of the required ligands 5a-c-H follows the reac-
tion sequence as outlined in Scheme 2. It starts with methylgallate
1 which easily is prepared from commercially available gallic acid.8
The alkyl chains are introduced by a Williamson ether synthesis. It
is found that in this step the length of the carbon chains influences
the conditions required for the reaction.
Scheme
3
Formation of the heterodinuclear La-Ga helicates
[(5a-c)3GaLa] from the corresponding ligands. [(5c)3GaLa] with six
terminal benzyl groups can be described as a generation 0 (G0) dendritic
unit.11
As a representative example the NMR spectra of complex
[(5b)3GaLa] as well as of the free ligand 5b-H2 are depicted
in Fig. 2. The protons of the catecholate OH disappear upon
coordination. Especially the NH proton is strongly influenced and
is shifted from d = 11.12 to 12.45. The other resonances experience
a high field shift. E.g., the aromatic protons are shifted from d =
6.75–6.97 to d = 6.32–6.48.
A hexaphenyl-substituted heterodinuclear triple-stranded helicate
In ligands of type A, substituents at the acyl unit can be easily
varied in the preparation of the ligand. However, it was also of
interest to substitute the NH proton in order to protect this posi-
tion against deprotonation and to introduce additional branching.
Therefore the known phenyl acyl hydrazone 612 was condensed
with aldehyde 4 to obtain ligand 7-H2. Coordination studies with
gallium(III) as well as lanthanum(III) salts resulted in the formation
of the heterodinuclear helicate [(7)3GaLa] (Scheme 4).
The complex [(7)3GaLa] was characterized by spectroscopic
methods. The NMR spectrum shows the peak of the imine proton
at d = 7.84 (s, 3H), the aromatic resonances of the phenyl groups
at d = 7.45 (m, 15 H), 6.98 (t, J = 7.4 Hz, 3 H), 6.76 (d, J = 7.4 Hz,
6 H), 6.50 (d, J = 7.4 Hz, 6 H), and the catechol signals at d =
6.38 (t, J = 7.7 Hz, 3 H), 6.08 (m, 6 H). Positive ESI MS reveals
the dominating molecular peak of the protonated species at m/z =
1199.33.
Scheme 2 Preparation of ligands 5a-c-H2.
The introduction of the propyl chain, to obtain the intermediate
2a, proceeds in 84% yield within 6 h. DMF is used as solvent
instead of acetone, which was reported in the literature.9 With
acetone too long reaction times are required leading to significant
decomposition of the product. In contrast to this, it has been
possible to easily introduce the butyl chain (2b) in acetone
(80%). Both compounds 2a and 2b show good solubility in water
indicating only weak hydrophobic influence of the alkyl chains.
As aromatic substituent a benzylic group was introduced
following as well the Williamson ether synthesis. 2c was obtained
after 24 h by reflux in acetone (92%).
12068 | Dalton Trans., 2011, 40, 12067–12074
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Fig. 2 Proton NMR spectra of [(5b)3GaLa] as well as of the free ligand 5b-H2 in DMSO-d6.
Fig. 3 Molecular structure of [(7)3GaLa] in the solid phase. Side view as
ball and stick (a) as well as CPK model (b). Top view down the La-Ga (c)
and the Ga-La axis (d). For clarity DMF is either only indicated (a) or
omitted (b-d).
Scheme 4 Preparation of the ligand 7-H2 and its heterodinuclear helicate
[(7)3GaLa].
Amino acid functionalized ligands and complexes
X-ray quality crystals of [(7)3GaLa] were obtained. In the
crystal, one molecule of ether was observed as well as a dmf
molecule, which coordinates to the lanthanum(III) ion. Fig. 3a
shows the coordination environment at the gallium of [(7)3GaLa]
which is bound by three catecholate units and at the lanthanum
chelated by three acylhydrazones and additionally by the internal
oxygen atoms of the catecholate units. Finally dmf is binding to the
lanthanum(III) ion resulting in CN = 10 at this ion. Fig. 3b depicts
a CPK model revealing the helical twist of the heterodinuclear
complex. In addition, views down the La-Ga axis (c) as well as the
Ga-La axis (d) are presented.
The structure of [(7)3GaLa]·dmf is well comparable to the ones
earlier described for complexes like A in which an NH is present
instead of the N-Ph moiety. The three “new” phenyl substituents
are located at the lower side of the complex (“lanthanide termi-
nus”) and are orientated towards the “outside”. Now six phenyl
groups are closely packed at this terminus of the helicate.
The attachment of amino acid residues to the terminus of the
heteroditopic ligands is of special interest. This might act as an
anchor in order to attach peptidic chains. Metal coordination will
preorganize three of the strands in order to generate interactions
between amino acids (or peptides).13
A first amino acid functionalized ligand was obtained starting
from 4-amino benzoic acid methylester (8) and N-acyl valine
(9). The benzoic ester 10 is formed in the presence of HBTU
as amide coupling reagent. Reaction with hydrazine affords
the acyl hydrazide 11. Finally, ligand 12-H2 is obtained after
hydrazone condensation of 11 with 2,3-dihydroxybenzaldehyde
(4) (Scheme 5).
In ligand 12-H2 the amino acid is separated from the co-
ordination side for the metals by the phenyl linker. 15-H2, on
the other hand, represents a related compound in which the
amino acid phenyl alanin is involved in the tridentate lanthanide
binding side. This derivative is made from N-acyl phenylalanine
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Scheme 5 Preparation of the ligand 12-H2.
methyl ester 13 by reaction with hydrazine. The resulting acyl
hydrazide 14 forms the hydrazone 15-H2 by condensation with
2,3-dihydroxybenzaldehyde 4 (Scheme 6).
Fig. 4 Parts of the positive ESI MS spectra showing the molar peaks of
[K(12)3GaLa]+ (top) and [H(15)3GaLa]+ (bottom).
Scheme 6 Preparation of the ligand 15-H2.
Complexes of ligands 12-H2 and 15-H2 are synthesized by
the standard method using three equivalents of the ligand,
lanthanum(III) chloride and gallium tris(acetylacetonate) in the
presence of potassium carbonate. For solubility reasons the
heterodinuclear complexes [(12)3GaLa] and [(15)3GaLa] cannot be
separated from the byproduct potassium chloride. However, the
complexes can be well characterized by proton NMR, resulting
in slightly broadened spectra which reveal one set of signals of
the ligands. Most characteristic are the ESI MS spectra (Fig.
4). In the positive detection mode, peaks of the triple stranded
heterodinuclear coordination compounds are observed at m/z =
1479 for [K(12)3GaLa]+ and at m/z = 1226 for [H(15)3GaLa]+.
The amino acid building blocks in ligands 12-H2 and 15-H2 were
introduced as the naturally occurring S-isomer. Thus the ligands
are obtained in enatiomerically pure form. The two compounds
12-H2 and 15-H2 as well as [(12)3GaLa] do not show significant CD
signals. However, in case of [(15)3GaLa] strong negative Cotton
effects are observed at 260, 330 nm and a slight negative effect at
370 nm. A strong positive Cotton effect is detected around 300 nm.
This is tentatively interpreted by the ability of the phenyl alanine
residue in 15 to induce the helical twist at the dinuclear metal
complex. In [(12)3GaLa] the chiral units are too far away from the
coordination sites and thus cannot influence the stereochemistry
at the helicate unit.
Conclusions
In here the preparation of acylhydrazones of 2,3-
dihydroxybenzaldehyde was presented, which act as ligands for
the self-assembly of heterodinuclear lanthanide(III)-gallium(III)
helicates. The new ligands are substituted at the acylhydrazone
unit which binds the lanthanide ion. Three different types of
ligands are presented: (1) Ligands 5a-c possess alkyl chains of
different length or benzyl groups located at the terminal phenyl
unit. (2) Ligand 7 bears a phenyl group instead of the proton at
the acyl hydrazone unit. (3) In compounds 12 and 15, amino acid
residues are attached to the lanthanide terminus of the ligand.
All ligands nicely form the heterodinuclear metal complexes by
simply mixing the metals (gallium(III) and lanthanum(III)) and
ligands in correct stoichiometry.
12070 | Dalton Trans., 2011, 40, 12067–12074
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For [(7)3GaLa] an X-ray structural analysis could be obtained
revealing the binding situation at the metal centers of the
heterodinuclear complex. In case of [(15)3GaLa] the helical twist
at the heterodinuclear complex is induced by the chiral phenyl
alanine residue.14
It has been demonstrated that the heteroditopic acylhydrazone
ligands of 2,3-dihydroxybenzaldehyde easily can be functionalized
at the “lanthanide terminus”. This will be the motivation for future
studies in order to introduce more sophisticated substituents (e.g.
peptides) and to arrange them in space by metal directed self-
assembly of heterodinuclear complexes.
1.74 (hex, 4H, J = 7.18), 1.64 (hex, 2H, J = 7.18 Hz), 1.03–0.94
(m, 9H). - MS (EI, 70 eV): m/z (%) = 310.3 (24.9%) [M]+, 279.2
(100%) [C16H23O4]+, 237.2 (52.8%) [C13H17O4]+. - IR (KBr): n =
3264, 2963, 2877, 1629, 1584, 1495, 1427, 1341, 1242, 1118, 954,
761, 720 cm-1. - C17H26O5 (310.17): C 61.91, H 8.44, N 9.03; found
C 62.23, H 8.44, N 8.51.
Synthesis of 5a. To a flask charged with a solution of 3a (0.25 g,
0.81 mmol.) in MeOH (20 mL), 0.11 g (0.81 mmol) of 4 were
added. The mixture was refluxed for 24 h. After cooling to 0 ◦C the
precipitate was filtered off and washed with cold MeOH (10 mL).
After drying under high vacuum the product was obtained as a
grey◦ solid in 52% yield (180 mg, 0.418 mmol). Melting point:
237 C. - 1H NMR (300 MHz, DMSO-d6): d = 11.90 (s, 1H), 11.12
(s, 1H), 9.22 (s, 1H), 8.60 (s, 6H), 7.23 (s, 2H), 6.97 (dd, 1H, J =
7.54 Hz, J = 1.61 Hz), 6.86 (d, 1H, J = 7.18 Hz), 6.75 (t, 1H, J =
7.79 Hz), 4.01 (t, 4H, J = 6.31 Hz), 3.92 (t, 2H, J = 6.31 Hz), 1.78
(hex, 4H, J = 6.97 Hz), 1.67 (hex, 2H, J = 6.93 Hz), 1.02 (t, 9H,
J = 7.67 Hz). - MS (EI, 70 eV): m/z (%) = 430.3 (73%) [M]+, 279.2
(100%) [C16H23O4]+, 237.2 (56.4%) [C13H16O4]+. - IR (KBr): n =
3177, 2965, 2934, 1633, 1576, 1472, 1332, 1278, 1220, 1114, 956,
731 cm-1. - C17H26O5 (430.2): C 64.17, H 7.02, N 6.51; found: C
64.06, H 6.81, N 6.46
Experimental Section
NMR spectra were recorded on a Varian Mercury 300 or Inova
400 spectrometer. FT-IR spectra were recorded on a Bruker IFS
spectrometer. Mass spectra were taken on a Thermo Deca XP mass
spectrometer. Elemental analyses were obtained with a Heraeus
CHN-O-Rapid analyser. Compounds 3b,3c9 and 612 were prepared
following literature procedures.
The X-ray intensity data were collected in the w scan mode on
an Oxford Diffraction XcaliburTM2 diffractometer using graphite-
monochromatized Mo-Ka radiation. The data were processed
with CrysAlisPro.15 They were corrected for Lorentz and po-
larization effects. Absorption corrections were carried out semi-
empirically on the basis of multiple-scanned reflections.16 The
crystal structures were solved by direct methods using SHELXS-
97 and refined with SHELXL-97.17 Due to the weak scattering
power and the resulting low number of observed reflections
anisotropic displacement parameters were introduced for all metal
and oxygen atoms only. Hydrogen atoms were placed at geometri-
cally calculated positions and refined with the appropriate riding
model.
Synthesis of 5b. To a flask charged with a solution of 3b
(0.272 g, 0.77 mmol) in MeOH (20 mL), 0.138 g (1.00 mmol) of 4
were added. The mixture was refluxed for 24 h. After cooling to
0 ◦C precipitation occurred. The solid was filtered off and washed
with cold MeOH (10 mL). After drying under high vacuum the
product was obtained as a white solid in 48% yield (170 mg,
◦
1
0.370 mmol). Melting point: 228–229 C. - H NMR(300 MHz,
DMSO-d6): d = 11.90 (s, 1H), 11.12 (s, 1H), 9.22 (s, 1H), 8.60 (s,
6H), 7.23 (s, 2H), 6.97 (d, 1H, J = 7.67 Hz, J = 1.61 Hz), 6.86 (d,
1H, J = 7.66 Hz), 6.75 (t, 1H, J = 7.67 Hz), 4.05 (t, 4H, J = 6.31 Hz),
3.95 (t, 2H, J = 6.18 Hz), 1.75 (quin, 4H, J = 6.80 Hz), 1.67 (quin,
2H, J = 6.80 Hz), 1.54–1.40 (m, 6H),0.97 (t, 6H, J = 7.42 Hz), 0.92
(t, 9H, J = 7.30 Hz). - MS (EI, 70 eV): m/z (%) = 472.4 (53.0%)
[M]+, 321.3 (100%) [C19H29O4]+, 265.2 (63.9%) [C15H21O4]+, 153.1
(31.3%) [C7H5O4]+. - IR (KBr): n = 3484, 2959, 2934, 2873, 1642,
1581, 1558, 1330, 1197, 1108, 958, 727 cm-1. - C49H92O4N2·0.33
CH3OH: C 65.45, H 7.79 N, 5.86; found: C 65.39, H 7.38, N 5.83.
Syntheses
Synthesis of 2a. A mixture of 3,4,5-trihydroxymethylbenzoate
(1 g, 5.39 mmol), propylbromide (2.22 g, 18.0 mmol) and an
excess of K2CO3 (4.2 g, 30 mmol) solved in DMF (50 mL) was
◦
heated to 80 C for 6 h. After cooling, the reaction was poured
onto ice, extracted three times with 50 mL Et2O and dried over
NaSO4. After filtration of the solid, the solvent was eliminated
under reduced pressure. The product was purified by column
chromatography (n-hexan/10% ethylacetate). The product was
Synthesis of 5c. To a solution of 3e (0.091 g, 0.2 mmol) in
MeOH (20 mL), 0.036 g (0.26 mmol) of 4 were added. The mixture
was refluxed for 24 h. After cooling to 0 ◦C a precipitate was
formed, which was filtered and washed with cold MeOH (10 mL).
After drying under high vacuum the product was obtained as a
grey◦solid in 86% yield (100 mg, 0.174 mmol). Melting point: 136–
138 C. - 1H NMR (300 MHz, DMSO-d6): d = 11.95 (s, 1H), 11.05
(s, 1H), 9.23 (s, 1H),8.62 (s, 6H), 7.53–7.36 (m, 17H), 6.99 (dd, 1H,
J = 7.67 Hz, J = 1.48 Hz), 6.87 (dd, 1H, J = 7.92 Hz, J = 1.49 Hz),
6.75 (t, 1H, J = 7.79 Hz), 5.22 (s, 4H),5.04 (s, 2H). - MS (EI, 70 eV):
m/z (%) = 574.4 (19%) [M]+, 91.1 (100%) [C7H7]+. - IR (KBr): n =
3436, 3247, 1580, 1501, 1334, 1222, 1122, 970, 965, 730 cm-1.
1
obtained as yellow oil in 84% yield (1.4 g, 4.5 mmol). H NMR
(300 MHz, CDCl3): d = 7.21 (s, 2H), 3.93 (t, 2H, J = 6.4 Hz),
3.91(t, 4H, J = 6.5 Hz), 3.83 (s, 3H), 1.85–1.68 (m, 6H), 0.98 (t,
6H, J = 7.4 Hz). - MS (EI, 70eV): m/z (%) = 310.3 (100%) [M]+,
184.1 (65.4%) [C8H5O5]+. - IR (KBr): n = 2917, 2849, 1716, 1587,
1504, 1468, 1431, 1336, 1224, 1128, 962, 763, 720 cm-1. - C17H26O5
(310.17): C 65.78, H 8.44; found C 65.86, H 8.73
Synthesis of 3a. To a methanolic solution of 2a (0.16 g,
0.52 mmol), 20 mL hydrazine monohydrate were added drop wise
under stirring and at room temperature within 15 min. After 24
h stirring the precipitate was filtered off, washed with water and
dried under high vacuum. A white solid was obtained in 70%
General procedure for the preparation of the complexes
◦
1
yield (0.112 g, 0.36 mmol). Melting point: 97–99 C. - H NMR
(300 MHz, DMSO-d6): d = 9,65 (br. s, 1H), 7.12 (s, 2H), 4.43
(br. s, 2H), 3.95 (t, 4H, J = 6.43 Hz), 3.87 (t, 2H, J = 6.31 Hz),
To a solution of one of the ligands 5a-H2 to 5c-H2 (3.0 equiv.)
in MeOH (25 mL), 3.0 equiv. of K2CO3 were added. A yellowish
solution formed. 3.0 equiv. of LaCl3·7H20 as well as Ga(acac)3
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©

◦
3
˚
˚
were added. The mixture was stirred over night. The product was
filtered off and washed with MeOH and Et2O.
23.356(3), c = 17.036(2) A, b = 104.622(14) , V = 6107.5(16) A ,
Z = 4, T = 110(2)K, Mo-Ka, r = 1.465 g cm3,m = 1.199 mm-1,
41590 collected data, 9287 unique reflections (qmax = 23.75◦), Rint
=
[(5a)3GaLa]. Yield: 0.040 g (91%). - 1H NMR (300 MHz,
DMSO-d6): d 12.43 (s, 1H), 8.40 (s, 1H), 7.10 (s, 2H), 6.40 (br.s,
3H), 3.88 (br.s, 2H), 3.57 (br.s, 2H), 3.38 (br.s, 2H), 1.66–1.44
(m, 6H), 0.95(t, 3H, J = 7.54 Hz), 0.89 (t, 6H, J = 7.54 Hz).
- MS (ESI-): m/z (%) = 1650.88 (100%) ([LaGa[5a]3+CH3O])-.
- IR (KBr): n = 2966, 2938, 1604, 1567, 1454, 1253, 1217, 1118,
737 cm-1. - C69H84GaLaN6O18·3 H2O: C 53.53, H 5.68, N 5.43;
found: C 53.47, H 5.63, N 5.44.
0.1135, 3360 observed reflections [I > 2s(I)], GOF = 0.606, R1
[I > 2s(I)] = 0.0406, wR2 (all data) = 0.0601. Crystallographic
data for the structure has been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC 789894.† Copies of the data can be obtained free of charge
on application to CHGC, 12 Union Road, Cambridge CB2 1EZ,
UK (Fax: +44-1223-336033 or E-Mail: deposit@ccdc.cam.ac.uk).
Synthesis of 10. N-Acyl-L-valine 9 (330 mg, 2.07 mmol) was
dissolved in 15 mL DMF. EDC (448 m, 2.34 mmol) and HOBt
(316 mg, 2.34 mmol) were added to the solution. After stirring of
the mixture for 30 min, a solution of 4-aminomethylbenzoate 8
(469 mg, 3.10 mmol) in 10 mL DMF was added. The mixture was
stirred for 4 days at room temperature. After that the solvent was
removed under high vacuum and the rest was dissolved in DCM,
washed with NH4Cl, NaHCO3, H2O and brine, dried with Na2SO4
and solvent was removed using rotary evaporation. The product
was purified by column chromatography DCM/MeOH (10 : 1).
A white solid was obtain◦ ed in 38% yield (239 mg, 0.79 mmol).
[(5b)3GaLa]. Yield: 0.042 g (90%). - 1H NMR (300 MHz,
DMSO-d6): d = 12.45 (s, 1H), 8.40 (s, 1H), 7.10 (s, 2H), 6.32–
6.48 (m, 3H), 3.88 (t, 2H, J = 7.45 Hz), 3.60 (br.s, 2H), 3.41 (br.s,
2H), 1.63–1.30 (m, 12H), 0.90 (t, 3H, J = 7.42 Hz), 0.87 (t, 6H, J =
7.17 Hz). - MS (ESI-): m/z (%) = 1491.33 (80%) ([LaGa[5b]3-H)-,
925.33(100%)[Ga[5b]]- - IR (KBr): n = 2958, 2934, 2872, 1600,
1566, 1497, 1453, 1427, 1375, 1337, 1253, 1215, 1105, 1059, 864,
736 cm-1. - C78H102GaLaN6O18·3 H2O: C 55.95, H 6.50, N 5.02;
found: C 55.85, H 6.39, N 5.01.
[(5c)3GaLa]. Yield: 0.013 g (81%). - 1H NMR (300 MHz,
DMSO-d6): d = 12.43 (s, 1H), 8.49 (s, 1H), 7.43–7.08 (m, 17H),
6.46–6.41 (m, 3H), 4.78 (br.s, 2H), 4.60 (br.s, 2H), 3.20 (br.s, 2H). -
IR (KBr): n = 3032, 1567, 1452, 1371, 1337, 1250, 1215, 1103, 973,
847, 823, 733, 694 cm-1. - C105H84GaLaN6O18·12 H2O: C 58.86, H
5.08, N 3.92; found: C 58.27, H 4.10, N 3.85.
1
Melting point: 200–202 C. - H NMR (300 MHz, CD3OD-d4):
d = 7.85 (d, 2H, J = 8.66 Hz), 7.60 (d, 2H, J = 8.66 Hz), 6.54 (d,
1H, J = 8.41 Hz), 2.02 (sept, 1H, J = 6.92 Hz), 1.92 (s, 3H), 0.92 (d,
6H, J = 6.68 Hz). - MS (EI,70eV): m/z (%) = 292.3 (2.09%) [M]+,
190.2 (1.12%) [C11H12NO2]+, 151.2 (53.53%) [C8H8NO2]+, 120.2
(25.07%) [C5H7NO2]+, 114.2 (40.04%) [C6H12NO]+. - IR (KBr):
n = 3308, 3117, 3017, 2965, 2850, 2433, 1925, 1713, 1652, 1602,
1538, 1436, 1410, 1381, 1283, 1175, 1111, 1016, 966, 927, 856,
758, 698, 667, 599, 513 cm-1. - HRMS calculated for C15H20O4Na:
315.13174 found: 315.13153.
Synthesis of 7-H2. A mixture of N¢-phenylbenzhydrazine 6
(550 mg, 2.6 mmol) and 2,3-dihydroxybenzaldehyde 4 (280 mg,
2.0 mmol; 1 eq) was dissolved in 10 mL CHCl3. The mixture was
heated to reflux for 7 h and then was stirred over night. After
recrystallization from 15 mL CHCl3 the product was dried under
vacuum. A brown solid was obtained in quantitative yield (684 mg,
2.0 mmol). Melting point: 170 ◦C. - 1H NMR (400 MHz, 25 ◦C,
CD3OD): d = 7.88 (s, 1 H), 7.68 (d, J = 8.0 Hz, 2 H), 7.62 (t,
J = 7.4 Hz, 1 H), 7.56–7.44 (m, 4 H), 7.39 (m, 3 H), 6.77 (d, J =
7.5 Hz, 1 H), 6.65 (t, J = 7.7 Hz, 1H), 6.62 (dd, J = 7.7 Hz, 1
H). - MS (EI, 70 eV): m/z (%) = 332.1 (6.24) [M]+, 105.1 (100)
[C7H5O]+, 77.2 (44.88) [C6H5]+. - IR (KBr): n = 3351, 3024, 2322,
2079, 1631, 1489, 1410, 1340, 1259, 1211, 1026, 842, 747, 696 cm-1.
- C20H16N2O3·CHCl3: C 55.84, H 3.79, N 6.20; found: C 55.72, H
3.94, N 6.36.
Synthesis of 11. To a methanolic solution of 4-(amino(S)-
N-acylvaline) methylbenzoate 10 (90 mg, 0.31 mmol), 0.5 mL
NH2NH2·H2O were added. The mixture was heated to reflux for
48 h. The solvent was removed under rotary evaporation and the
product was recrystallized from MeOH/Et2O. A white solid was
obtained in 70% yield (63 mg, 0.22 mmol). Melting point: 215.9–
◦
1
217.6 C. - H NMR (300 MHz, CD3OD): d = 7.76 (d, 2H, J =
8.90 Hz), 7.69 (d, 2H, J = 8.90 Hz), 4.29 (d, 1H, J = 7.67 Hz), 2.05
(m, 1H), 1.98 (s, 3H), 1.02 (d, 6H, J = 6.68 Hz). - MS (EI,70eV):
m/z (%) = 292.3 (0.83%) [M]+, 261.3 (7.59%) [C14H17N2O3]+, 151.2
(19.90%) [C8H8NO2]+, 120.2 (100.00%) [C5H7NO2]+. - IR (KBr):
n = 3842, 3283, 2961, 2707, 2421, 2284, 2421, 2284, 2166, 2076,
1992, 1918, 1776, 1634, 1525, 1439, 1405, 1380, 1333, 1252, 1196,
1113, 962, 849, 762, 718, 670 cm-1.- C14H20N4O3·H2O (292.1): C
54.18 H 7.15 N 18.05; found C 52.82 H 6.78 N 18.35; HRMS
calculated for C14H20O3Na: 315.14276 found: 315.14240.
[(7)3GaLa]. Ligand 7-H2 (70 mg, 0.2 mmol), K2CO3 (15 mg,
0.105 mmol), LaCl3·7H2O (26 mg, 0.07 mmol) and Ga(acac)3
¨
(25 mg, 0.07 mmol; 1 Aq) were dissolved in 8 mL MeOH and the
mixture was stirred for 12 h at RT. A yellow solid precipitated,
which was filtered off, washed with MeOH and dried under
high vacuum. The product was obtained in 50% yield (42 mg,
0.035 mmol). 1H NMR (300 MHz, 25 ◦C, DMSO-d6): 7.84 (s, 1H),
7.45 (m, 5 H), 6.98 (t, J = 7.4 Hz, 1 H), 6.76 (d, 2H, J = 7.4 Hz),
6.50 (d, 2H, J = 7.4 Hz), 6.38 (t, 1H, J = 7.67 Hz), 6.08 (m, 2H).
- positive ESI MS: m/z (%) = 1199.33 (100%) [LaGa[6]3+H]+.-
IR (KBr): n = 3666, 3349, 3060, 2745, 2321, 2079, 1567, 1545,
1451, 1424, 1369, 1262, 1209, 1013, 872, 768, 729, 697, 660 cm-1.-
C60H42N6O9GaLa·2H2O: C 58.32, H 3.75, N 6.80, found: C 57.89,
H 3.46, N 6.76.
Synthesis of 12-H2. To a methanolic solution of 4-(amino(S)-
N-acylvaline) methylbenzohydrazid 11 (160 mg, 0.55 mmol),
a methanolic solution of 2,3-dihydroxybenzaldehyde 4 (76 mg,
0.55 mmol) was added. The mixture was stirred for 24 h at room
temperature. The solvent was removed under rotary evaporation
and the product was recrystallized from MeOH/Et2O. A grey
solid was obtained◦in 64% yield (143 mg, 0.35 mmol). Melting
point: 270.8–273.7 C. - 1H NMR (300 MHz, CD3OD): d = 8.45
(s, 1H), 7.92 (d, 2H, J = 8.17 Hz), 7.78 (d, 2H, J = 8.17 Hz), 6.88
(m, 2H), 6.79 (t, 1H, J = 7.66 Hz), 4.29 (d, 1H, J = 7.67 Hz),
Crystal data. [(7)3GaLa]: C67H59N7O11GaLa: formula weight
1346.84, monoclinic, space group P21/n, a = 15.864(3), b =
12072 | Dalton Trans., 2011, 40, 12067–12074
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The Royal Society of Chemistry 2011
©

2.10 (m, 1H), 1.98 (s, 3H), 1.02 (2 s, 6H). - MS (EI,70eV): m/z
(%) = 412.2 (15.11%) [M]+, 261.2 (19.31%) [C14H17N2O3]+, 136.1
(68.40%) [C7H6NO2]+, 120.1 (100.00%) [C5H7NO2]+. - IR (KBr):
n = 3844, 3612, 3487, 3377, 3285, 3054, 2966, 2933, 2876, 2696,
2473, 2321, 2288, 2163, 2058, 1971, 1942, 1923, 1859, 1744, 1688,
1602,1531, 1468, 1409, 1367, 1310, 1185, 1100, 1062, 1018, 902,
851, 783, 761, 731, 686, 659 cm-1. - C21H24N4O5 (412.2): C 61.15
H 5.87 N 13.58; found C 60.81 H 5.05 N 11.58.
obtained as an orange solid in 84% yield (30 mg, 0.024 mmol). 1H
NMR (300 MHz, 25 ◦C, CD3OD): d = 8.19 (s, 1H), 7.2 (m, 5 H,
CHPh) 6.90 (d, J = 8.7 Hz, 1H), 6.63 (d, J = 8.7 Hz, 1H), 6.40 (d,
J = 8.7 Hz, 1H), 4.60 (s, 1H), 3.07 (m, 2H), 1.89 (s, 3H). - positive
ESI MS: m/z (%) = 1226.53 (50%) [LaGa(15)3+H]+.- IR (KBr):
n = 3225, 3030, 2927, 2810, 2616, 2453, 2321, 2231, 2202, 2105,
2051, 1992, 1957, 1886, 1601, 1551, 1453, 1375, 1254, 1216, 1056,
959, 867, 785, 742, 699 cm-1. - C54H51N9O12GaLa ·4H2O·7 KCl: C
35.62, H 3.27, N 6.92, found: C 35.87, H 3.31, N 6.73.
[(12)3GaLa]. Ligand 12-H2 (22 mg, 0.053 mmol), K2CO3
(5 mg, 0.027 mmol), LaCl3·7H2O (6.6 mg, 0.017 mmol) and
Ga(acac)3 (6 mg, 0.017 mmol) were dissolved in 10 mL DMF and
the mixture was stirred for 24 h at RT. Precipitated salt was filtered
off and DMF was removed under high vacuum. The product was
Acknowledgements
This work was supported by the Fonds der Chemischen Industrie
(MA).
1
obtained as yellow solid in 82% yield (20 mg, 0.014 mmol). H
◦
NMR (400 MHz, 25 C, CD3OD): d = 8.67 (s, 1H), 7.94 (d, 2H,
J = 8.9 Hz), 7.58 (d, 2H, J = 8.9 Hz), 6.82 (d, 1H, J = 7.7 Hz),
6.75(d, 1H, J = 7.7 Hz), 6.50 (t, 1H, J = 7.7 Hz), 4.29 (d, 1H,
J = 7.7 Hz), 2.10 (m, 1H), 2.00 (s, 3H), 0.98 (2 s, 6H). - positive
ESI MS: m/z (%) = 1477.3 [(12)3LaGaK]+. - IR (KBr): n = 3850,
3304, 3055, 2967, 2874, 2659, 2321, 2169, 2105, 1997, 1734, 1658,
1602, 1517, 1450, 1376, 1251, 1164, 1035, 855, 745, 686 cm-1.
- C63H66N12O15GaLa·4 KCl: C 43.54, H 3.83, N 9.67, found: C
43.40, H 3.98, N 9.59.
Notes and references
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L. Caulder, D. W. Johnson and K. N. Raymond, Angew. Chem., 1999,
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Synthesis of 14. To a methanolic solution of N-acyl-L-
phenylalanine methylester 13 (286 mg, 1.21 mmol), 0.2 mL of
hydrazinmonohydrate (2.64 mmol) were added and the solution
was stirred at RT for 2 days. The solvent was removed under high
vacuum. A white solid was obtained in quantitative yield (286 mg,
1.21 mmol). Melting point: 177.3–178.3 ◦C. - 1H NMR (400 MHz,
CD3OD): d = 7.13 (m, 5H), 4.45 (dd, 1H, J = 8.6, 2.0 Hz), 2.97
(dd, 1H, J = 13.6 6.6 Hz), 2.77 (dd, 1H, J = 13.6, 8.62 Hz), 1.79
(s, 3H). - MS (EI, 70eV): m/z (%) = 222.1 (2.22%) [M+H]+, 190.1
(54.60%) [C11H12NO2]+, 120.1 (100%) [C5H7NO2]+. - IR (KBr): n =
3299, 3034, 2322, 1740, 1636, 1531,1374, 1292, 1254, 1103, 1035,
939, 750, 699, 667 cm-1. - C11H15N3O2 (221.1): C 59.71, H 6.83, N
18.99; found C 59.41, H 6.12, N 18.87.
3 E.g. (a) X. Sun, W. J. Darren, D. Caulder, R. E. Powers, K. N. Raymond
and E. H. Wong, Angew. Chem., 1999, 111, 1386–1390, (Angew. Chem.,
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2763; (c) A. K. Das, A. Rueda, L. R. Falvello, S.-M. Peng and S.
Batthacharya, Inorg. Chem., 1999, 38, 4365–4368; (d) J. Heinicke, N.
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in Supramolecular ChemistryJ.-P. Sauvage, Ed.; John Wiley & Sons,
New York, 1999; Vol. 5, pp 1-51; (g) R. W. Saalfrank, H. Maid and
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5 (a) C. Piguet, G. Hopfgartner, B. Bocquet, O. Schaad and A. F.
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G. Bernardinelli, J.-C. G. Bu¨nzli, S. Petoud and G. Hopfgartner, Chem.
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Synthesis
of
15-H2.
A
mixture
of
N-acetyl-L-
phenylalaninehydrazide 14 (100 mg, 0.4253 mmol) and 2,3-
dihydroxybenzaldehyde 4 (59 mg, 0.4253 mmol) were dissolved
in 15 mL MeOH and heated to reflux for 7 h. After that the
solvent was removed and the product was recrystallized from
5 mL MeOH/Et2O (1 : 3). A light yellow solid was obtained in
70% yield (101 mg, 0.30 mmol). Melting point: 211.4–214 ◦C. - 1H
NMR (300 MHz, CD3OD): d = 8.16 (s, 1H), 7.25 (m,5H), 6.85 (dd,
1H, J = 7.7, 1.7 Hz), 6.80 (dd, 1H, J = 7.7, 1.7 Hz), 6.72 (t, 1H, J =
7.7 Hz), 4.65 (t, 1H, J = 7.2 Hz), 3.15 (dd, 1H, J = 13.6, 7.2 Hz),
2.97 (dd, 1H, J = 13.6, 7.2 Hz), 1.93 (s, 3H). - MS (EI,70eV): m/z
(%) = 341.1 (5.60%) [M]+, 190.1 (49.09%) [C11H12NO2]+, 120.2
(100%) [C5H7NO2]+. - IR (KBr): n = 3520, 3264, 3061, 2925, 2857,
2738, 2319, 2113, 1756, 1649,1540, 1470, 1362, 1266, 1064, 1038,
958, 845, 782, 731, 697 cm-1. - C18H19N3O4·H2O (341.1): C 60.16,
H 5.89, N 11.69; found C 60.68, H 5.90, N 12.19.
6 M. Albrecht, Y. Liu, S. S. Zhu, C. A. Schalley and R. Fro¨hlich, Chem.
Commun., 2009, 1195–1197.
7 M. Albrecht, I. Latorre, Y. Liu and R. Fro¨hlich, Z. Naturforsch B, 2010,
65B, 311–316.
[(15)3GaLa]. Ligand 15-H2 (30 mg, 0.088 mmol), K2CO3
(15 mg, 0.105 mmol), LaCl3·7H2O (11 mg, 0.029 mmol) and
Ga(acac)3 (10.7 mg, 0.029 mmol) were dissolved in 10 mL DMF
and the mixture was stirred for 48 h at RT. Salts were filtered off
and DMF was removed under high vacuum. The product was
8 K. Dodo, T. Minato, T. Noguchi-Yachide, M. Suganuma and Y.
Hashimoto, Bioorg. Med. Chem., 2008, 17, 7975–7982.
9 M. Li and S. Qu, Tetrahedron, 2007, 63, 12429–12436.
10 E.g. (a) P. Melnyk, V. Leroux, C. Sergheraert and P. Grellier, Bioorg.
Med. Chem. Lett., 2006, 16, 31–35; (b) O. Pouralimardan, A.-C.
Chamayou, C. Janiak and H. Hosseini-Monfared, Inorg. Chim. Acta,
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Dalton Trans., 2011, 40, 12067–12074 | 12073
©

2007, 360, 1599–1608. For related semicarbazone derived ligands and
their mononuclear complexes, see; (c) M. Albrecht, O. Osetska and
R. Fro¨hlich, Dalton Trans., 2005, 3757–3762; (d) M. Albrecht, S.
Mirtschin, O. Osetska, S. Dehn, D. Enders, R. Fro¨hlich, T. Pape and
F. E. Hahn, Eur. J. Inorg. Chem., 2007, 3276–3287.
13 M. Albrecht and P. Stortz, Chem. Soc. Rev., 2005, 34, 496–506.
14 For chiral induction of terminal substituents on helicates, see e.g. M.
Albrecht, Synlett, 1996, 565.
15 CrysAlisPro Version 1.171.33.41, Oxford Diffraction Ltd, Yarnton,
Oxfordshire, UK.
11 E.g. M. Albrecht, M. Baumert, H. D. F. Winkler, C. A. Schalley and
R. Fro¨hlich, Dalton Trans., 2010, 39, 7220–7222.
16 R. H. Blessing, Acta Crystallogr., Sect. A: Found. Crystallogr., 1995, A
51, 33.
12 R. Yamasaki, A. Tanatani, I. Azumaya, H. Masu, K. Yamaguchi and
H. Kagechika, Cryst. Growth Des., 2006, 6, 2007–2010.
17 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008,
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12074 | Dalton Trans., 2011, 40, 12067–12074
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The Royal Society of Chemistry 2011
©