Mandelohydroxamic acid as ligand for copper(II) 15-metallacrown-5 lanthanide(III) and copper(II) 15-metallacrown-5 uranyl complexes

Article abstract of DOI:10.1002/ejic.200501015

The formation of pentanuclear copper(II) complexes with the mandelohydroxamic ligand was studied in solution by electrospray ionization mass spectrometry (ESI-MS), absorption spectrophotometry, circular dichroism and ¹H NMR spectroscopy. The pr

Full text of DOI:10.1002/ejic.200501015

FULL PAPER
DOI: 10.1002/ejic.200501015
Mandelohydroxamic Acid as Ligand for Copper(II) 15-Metallacrown-5
Lanthanide(III) and Copper(II) 15-Metallacrown-5 Uranyl Complexes
[
a]
[a]
[a]
[a]
Tatjana N. Parac-Vogt,* Antoine Pacco, Peter Nockemann, Yao-Feng Yuan,
[a]
[a]
Christiane Görller-Walrand, and Koen Binnemans
Keywords: Lanthanides / Hydroxamic acid / Metallacrowns / Rare earths / Uranium
The formation of pentanuclear copper(II) complexes with the
complexes synthesized with the enantiomerically pure R- or
mandelohydroxamic ligand was studied in solution by elec- S-forms of mandelohydroxamic acid ligand, showed circular
trospray ionization mass spectrometry (ESI-MS), absorption
spectrophotometry, circular dichroism and H NMR spec-
dichroism spectra which were mirror images of each other.
The pentanuclear complex made from the racemic form of
the ligand showed no signals in the CD spectrum. The UV/
Vis titration experiments revealed that the order in which the
metal salts are added to the solution of the mandelohydrox-
amic acid ligand is crucial for the formation of metallacrown
complexes. The addition of copper(II) to the solutions con-
taining mandelohydroxamic acid and neodymium(III) in a 5:1
ratio lead to the formation of a pentanuclear complex in solu-
tion. In contrary, titration of lanthanide(III) salt to the solution
1
troscopy. The presence of lanthanide(III) or uranyl ions is es-
sential for the self-assembly of the 15-metallacrown-5 com-
pounds. The negative mode ESI-MS spectra of solutions con-
taining copper(II), mandelohydroxamic acid and lantha-
nide(III) ions (Ln = La, Ce, Nd, Eu, Gd, Dy, Er, Tm, Lu, Y) or
uranyl in the ratio 5:5:1 showed only the peaks that could
be unambiguously assigned to the following intact molecular
2
– –
ions: {Ln(NO
3
)
2
3
[15-MC II
Cu N(MHA)
3
-5] } and {Ln(NO )[15-
– –
MC II
-5] } , where MHA represents doubly depro- containing copper(II) and mandelohydroxamic acid did not
Cu N(MHA)
tonated mandelohydroxamic acid. The NMR spectra of the
pentanuclear species revealed only one set of peaks indicat-
ing a fivefold symmetry of the complex. The pentanuclear
show any evidence for the formation of pentanuclear species.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
the deprotonated hydroxamate and carbonyl oxygen atoms,
resulting in the formation of simple mononuclear com-
plexes. The introduction of secondary coordinating groups
can significantly modify the coordination behavior of hy-
droxamate ligands. For instance, aminohydroxamic acids
can coordinate to metals through (O,O) as a singly depro-
tonated hydroxamate, through (N,N) of the amino and the
deprotonated hydroxamic nitrogen, or as a (N,N)-(O,O)
bridging bis-chelating ligand. Very often, the complexation
to metal ions leads to formation of oligomeric or polymeric
Hydroxamic acids, whether naturally occurring or syn-
[
1]
thetic, are an important family of organic bioligands. One
of the first biomedical applications of hydroxamic acids was
associated with the uptake or removal of iron from the
[
2]
body. In recent years it has become evident that these
[
3–7]
weak acids possess other types of biological activities.
Their role as potent and selective inhibitors of a range of
metalloenzymes has been of special interest to inorganic
chemists, because the biological activities of hydroxamic ac-
ids have been mainly attributed to their complexing proper-
ties toward transition-metal ions.[ As a result, the transi-
tion-metal complexes of hydroxamic acids are frequently
used as bioinorganic model compounds to investigate the
enzymatic interactions and binding properties of these bi-
oligands.
[9]
complexes. However, under certain conditions, the forma-
tion of metallacrowns, types of compounds which are anal-
8]
ogous to crown ethers in both structure and function, has
[11–13]
been observed.
For example, a pentanuclear [12-
metallacrown-4]copper() complex is self-assembled from
solutions of copper() and β-alaninehydroxamic acid
(Scheme 1, a). Besides the β-aminohydroxamic acids several
Hydroxamic acid ligands can exhibit different possible
chelation modes, and this results in a rich variety of metal
complex structures.
other ligands like salicylhydroxamic acid (Scheme 1, b), 2-
aminophenylhydroxamic acid, 2-pyridylacetohydroxamic
[
9,10]
By far the most common mode of
acid and 3-naphthohydroxamic acid have also been used in
metal binding is the bidentate coordination mode through
[14]
the 12-metallacrown-4 synthesis.
In addition to the [12-
metallacrown-4]copper() complexes, 12-metallacrown-4
complexes containing other ring metals such as manga-
nese(), manganese(), iron(), oxovanadium() and gal-
[
a] Katholieke Universiteit Leuven, Department of Chemistry,
Celestijnenlaan 200F, 3001 Leuven, Belgium
Fax: +32-16-327992
[
15–21]
E-mail: Tatjana.Vogt@chem.kuleuven.be
lium() have been synthesized.
1466
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2006, 1466–1474

MHa as Ligand for CuII 15-Metallacrown-5 Lanthanide() and Uranyl Complexes
FULL PAPER
In this paper, we show that in the presence of copper()
and lanthanide() ions, mandelohydroxamic acid forms
stable 15-metallacrown-5 complexes in solution by self-as-
sembly. The copper() ion was chosen as the ring metal, as
it can form complexes of square-planar geometry, and be-
cause its relatively labile metal–ligand bonds should allow
the rearrangement of initially formed kinetic products into
the thermodynamically stable product. The role of lantha-
nide() and uranyl ions as central templating ions for the
self-assembly was examined, as well as conditions which are
necessary for the formation of 15-metallacrown-5 com-
plexes.
Results and Discussion
Complexation of Mandelohydroxamic Acid to Copper(II
)
Mandelohydroxamic acid (MHA) was synthesized from
mandelic acid according to Scheme 2. The racemic  and
the enantiomerically pure (S)-(+) and (R)-(–) forms of the
MHA ligand were obtained depending on the stereochemis-
try of the starting material. Our intention to use mande-
lohydroxamic acid (MHA) as the ligand for the formation
of 15-metallacrown-5 complexes was based on the fact that
this ligand possesses a secondary coordinating hydroxy
group, and that bidentate coordination through this hy-
droxy group and the hydroxamate nitrogen would form
five-membered chelate rings. The additional coordination
by two oxygen atoms can lead to the formation of two five-
membered chelate rings (Scheme 3), with an angle of 108°
between the two metal atoms. This is, according to the ra-
tional design, a geometrical prerequisite for the formation
Scheme 1. Precursor ligands used for the synthesis of metallacrown
complexes. (a) β-Alaninehydroxamic acid; (b) salicylhydroxamic
acid; (c) α-aminohydroxamic acid; (d) picolinehydroxamic acid; (e)
mandelohydroxamic acid.
In contrast to the numerous 12-metallacrown-4 struc-
tures reported so far, there are only very few examples of
ligands capable of forming planar rings of the larger 15-
metallacrown-5 structure type. Up to now, only α-aminohy-
droxamic acids and picolinehydroxamic acid (Scheme 1, c–
d) have been found to form planar 15-metallacrown-5 com-
plexes. The key property of these two ligand scaffolds is that
they are able to form two fused five-membered chelate
rings, which allows five metals and five ligands to form a
[21]
of the 15-metallacrown-5 structure.
planar 15-metallacrown-5 structure.[
22,23]
The planar 15-
metallacrown-5 complexes formed in this way are capable
to incorporate in their central cavity cations with a larger
ionic radius and with a higher coordination number than
1
2-metallacrown-4 complexes. As
a
result, lantha-
ions have been in-
[
24–28]
2+ [23,28,29]
nide()
and uranyl (UO2
)
corporated in the center of a 15-metallacrown-5 ring.
The limited number of ligands that are reported to form
planar 15-metallacrown-5 complexes creates a challenge for
the predesigned synthesis of these structural motifs. The ge-
ometry of a particular ligand and its known interaction
with a metal ion should contain all the information re-
quired for the successful self-assembly of the metallacrown
compounds. Therefore, when planning the synthesis of
metallacrowns, the general choice of ligand type, ligand ge-
ometry, metal type and reaction conditions have to be con-
sidered. Although many metal complexes of hydroxamic
acids and their derivatives have been studied in detail, the
coordination chemistry of mandelohydroxamic acid
Scheme 2. Synthesis of mandelohydroxamic acid. Conditions: (i)
ethanol, H SO , (ii) NH OH·HCl, KOH, methanol.
2 4 2
(Scheme 1, e) is virtually unexplored. A few complexes of
Previous studies of the mandelohydroxamic acid (MHA)
divalent cations have been prepared through precipitation ligand have shown that in the presence of divalent metal
in aqueous solution,[
30,31]
and the metal-ligand stability ions 1:1 and 2:1 complexes are formed, in which the coordi-
constants for some mononuclear complexes have been re- nation of the MHA occurs by the formation of five-mem-
[
32]
ported. However, no structural data are available for this bered chelates through the deprotonated hydroxamate and
[
30–32]
type of metal complexes.
carbonyl oxygen atoms.
The coordination of the hy-
Eur. J. Inorg. Chem. 2006, 1466–1474
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1467

T. N. Parac-Vogt et al.
FULL PAPER
presence of the hydroxy group, which is a weaker ligating
group for copper() ions, probably prevents the formation
of the second chelating ring, and thus the formation of a
12-metallacrown-4 metallacrown structure.
Formation of 15-Metallacrown-5 Complex Monitored by
ESI-MS
Our previous studies have shown that lanthanide() and
uranyl ions have a large influence on the structure of the
metallacrown complexes based on α-aminohydroxamic acid
Scheme 3. Rationale for the formation of planar 15-metallacrown-
5
complexes.
[
29,36,37]
and copper() ion.
The addition of lanthanide()
2+
droximato nitrogen and hydroxy oxygen to the metal ions and uranyl ions to [Cu (α-aha) ] induces a complete re-
5
4
has not been observed.
assembly of the 12-metallacrown-4 structure to the 15-
Mixing of copper() and the enantiomerically pure R- metallacrown-5 structure, in which lanthanide() or uranyl
or S-form of MHA in aqueous solutions resulted in the ions occupy the central cavity of the planar ring. Although
formation of a green solid after few hours of stirring. Sim- lanthanide() ions seem to be essential for the synthesis of
ilar reactions occurred when methanol or ethanol were used 15-metallacrown-5 complexes, their exact role has never
[
24]
as solvents. The elemental analyses carried out for the pre- been examined.
Previously, it has been suggested that
cipitate isolated from methanolic or ethanolic solutions lanthanide() ions are being merely recognized end-encap-
indicated the formation of a complex with the stoichiome- sulated by the 15-metallacrown-5 ring, and that this in-
try [CuL]. However, the insolubility of this solid in all con- clusion may contribute to the stability of the whole metalla-
ventional solvents suggests a polymeric nature of the com- crown structure. These findings prompted us to exploit
plex. Polymeric complexes of hydroxamic acids which pos- lanthanide() and uranyl ion as possible templates for the
sess a secondary coordinating group have been previously formation of metallacrown complexes based on mandelohy-
[
33]
reported.
droxamic acid and copper(). When 0.25 equiv. of neodym-
When racemic -mandelohydroxamic acid was used in- ium() were present in an equimolar solution of copper()
stead of the enantiomerically pure S- or R-form, the equi- and (S)-mandelohydroxamic acid, the color of the solution
molar mixture of Cu(OAc) and MHA in methanol or etha- gradually changed from blue to green. The addition of so-
2
nol remained clear during the course of several weeks. The dium formate or sodium acetate salts resulted in the forma-
UV/Vis spectrum of the green solution exhibits an absorp- tion of a microcrystalline solid (see Exp. Section). Unfortu-
tion maximum at 650 nm, which is equal to the values ob- nately, all attempts to isolate crystals of quality good
[
34]
served in [Cu(acetohydroxamate) ] (λ
= 653 nm)
and enough for X-ray single crystal analysis were unsuccessful,
2
max
other copper() complexes with deprotonated hydroxamate but the elemental analysis results were consistent with
and carbonyl oxygen donors.[ The ESI-MS spectra did the stoichiometry Nd[Cu (MHA) ]·3(HCOO)·3(H O) and
35]
5
5
2
not show any evidence for the presence of metallacrown Nd[Cu (MHA) ]·3(CH COO)·(H O), where MHA repre-
5
5
3
2
species, so it is likely that the complex formed in solution sents the doubly deprotonated mandelohydroxamic acid.
is the mononuclear Cu(MHA) complex in which the coor- Crystallization techniques, such as evaporation of the sol-
2
dination to copper() occurs by the deprotonated hydroxa- vent, diffusion techniques (vapor and liquid), and various
mate and carbonyl oxygen donors. This finding is in sharp co-crystallants were used on all three types of metallacrown
contrast to the analogous reaction between α-aminohy- complexes containing racemic  and the enantimerically
droxamic acids and copper(), in which exclusively the pure S-(+)and R-(–) forms of the mandelohydroxamate li-
2
+
[
Cu (α-aha) ] (aha = aminohydroxamic acid) 12-metalla- gand. The only few crystals that were obtained were of in-
5 4
[12]
crown-4 complex is formed in solution. In that metalla- sufficient quality for X-ray diffraction studies. The only re-
crown complex the coordination of aminohydroxamic acid flections that could be observed were weak reflections in
occurs also by the deprotonated hydroxamate and carbonyl the small-angle region and were not suitable for the deter-
oxygen atoms; however, the second five-membered ring is mination of the crystallographic unit cell. The solutions
also formed through the coordination of hydroximato nitro- containing equimolar amounts of (S)-mandelohydroxamic
gen and amino nitrogen to copper(). This leads to the for- acid and copper() acetate, in which 0.2 mol equivalents of
mation of a puckered structure with four copper() ions different trivalent rare-earth ions (Ln = La, Ce, Nd, Eu,
in the backbone of the metallacrown and a cavity which Gd, Dy, Er, Tm, Lu, Y) or uranyl ions (UO22 ) were pres-
+
accommodates the fifth copper() ion.
ent, have been further analyzed by electrospray ionization
Although the coordination geometries of α-aminohy- mass spectrometry (ESI-MS). In recent years, ESI-MS has
droxamic acids and mandelohydroxamic acid are almost been proven very useful for the analysis of self-assembled
identical, the main difference between these two ligands is clusters. The results obtained by ESI-MS have been often
that mandelohydroxamic acid possesses a hydroxy group in- regarded as indicative for the solution behavior of a species
[
38]
stead of the amino group of α-aminohydroxamic acids. The rather than for its gas-phase behavior.
The method has
1468
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2006, 1466–1474

MHa as Ligand for CuII 15-Metallacrown-5 Lanthanide() and Uranyl Complexes
FULL PAPER
also been proven as very useful for confirming the integrity Table 2. Positive-ion mode ESI-MS data for 15-metallacrown-5
of metallacrown complexes in solution.[
indicate that the results obtained by ESI-MS correlate very
14]
complexes derived from (S)-(+)-mandelohydroxamic acid, cop-
per() ions as the ring metal and with different central cavity metals
Several studies
(
M).
well with those obtained by other techniques, such as NMR
2
+
– +
and X-ray diffractometry.[
38,39]
Nonetheless, ESI-MS stud-
Species {M(NO )[15-MC-5]}
3
{M(NO )[15-MC-5] }
3
M
m/z exp.
m/z calcd.
m/z exp.
m/z calcd.
ies of large self-assembled metal complexes remain non-
trivial and often require thorough optimization of the ex-
perimental parameters. All peaks detected in the mass spec-
YIII
645.3
672.2
672.7
674.5
678.3
681.8
683.5
685.7
686.3
689.2
706.4
645.3
672.2
672.8
674.8
678.7
681.3
683.9
686.3
687.2
690.2
–
–
III
La
Ce
Nd
1342.5
1343.9
1347.6
1355.7
1361.7
1366.1
1371.5
–
1343.4
1344.6
1348.7
1356.4
1361.7
1366.9
1371.1
–
III
III
II
III
II
2+
tra of Cu /MHA/Ln and Cu /MHA/UO solutions ap-
2
III
III
pear as cluster peaks, because of the different copper() and Eu
lanthanide() isotopes in the detected complexes. Species Gd
with different degrees of protonation were detected in the
ESI-MS spectra. This may be due to the deprotonation or
protonation during the ionization process, or may be due to
III
Dy
Er
III
III
Tm
III
Lu
–
–
2
+
[a]
[a]
the different degree of protonation of mandeloxydroxamate UO
2
706.8
1412.7
1412.5
ligand. It is possible that the deprotonation of the mande-
lohydroxamate ligand occurs not only on the hydroxamate
a] Values calculated for {M[15-MC-5]}2+ and {M[15-MC-5] } .
– +
[
nitrogen and oxygen atoms, like it was reported for other
hydroxamate ligands that form 15-metalacrown-5,[
24–29]
but
that the hydroxyl group may also be deprotonated. Both
protonated and deprotonated forms of the hydroxyl group
can bind to copper(), and moreover, the Lewis acidity of
the copper() may cause the deprotonation of the hydroxyl
group upon binding. The peaks that were observed in the
ESI-MS spectra are summarized in Table 1 and Table 2.
The reported m/z values are the maxima of the cluster
peaks. All the peaks detected in the negative mode (Table 1)
could be unambiguously assigned to the following two in-
2
– –
tact molecular ions: {Ln(NO ) [15-MC II
-5] }
3
2
Cu N(MHA)
3
– –
and {Ln(NO )[15-MC II
-5] } , where MHA repre-
3
Cu N(MHA)
sents doubly deprotonated mandelohydroxamic acid (man-
delohydroximate) (Figure 1). If the neodymium() perchlo-
rate was used instead of neodynium() nitrate, peaks corre-
2
– –
Figure 1. Negative-ion mode ESI-MS spectra of the methanolic
solutions containing Cu /MHA/La in 5:5:1 ratio.
sponding to {Nd(ClO ) [15-MC II
-5] }
and
4
2
Cu N(MHA)
– 2–
II
III
2
{
Nd(ClO ) [15-MC II
-5] } species with two and
4 3
Cu N(MHA)
three perchlorate counterions were observed. Thus, the pos-
itive charge of the central lanthanide() ions is always com- to a 15-metallacrown-5 species with a lanthanide() ion in
pensated by the negative charge of the ring and by nitrate the central cavity, were observed in the ESI-MS spectra.
or perchlorate anions present in the solution.
In both cases, a peak at m/z = 1222 was detected which
corresponds to a 15-metallacrown-5 species with copper()
Table 1. Negative-ion ESI-MS data for 15-metallacrown-5 com-
plexes derived from (S)-(+)-mandelohydroxamic acid, copper()
ions as the ring metal and with different central cavity metals(M).
2– –
ion in the central cavity: {Cu(OH)[15-MC II
-5] } .
Cu N(MHA)
Another peak at m/z = 993 could be assigned to
2– –
{
Cu(OH)[12-MC-4] } . As thulium() and lutetium()
2
–
–
{M(NO
3
)[15-MC-5]3–}–
Species
M
{M(NO
m/z exp.
3
)
2
[15-MC-5] }
are lanthanide ions with a small ionic radius (87 and 85 pm,
respectively), this probably leads to less effective encapsul-
ation into the central cavity and thus to a reduced stability
of the 15-metallacrown-5 complexes.
The ESI-MS spectra in the positive mode also gave
strong evidence for the existence of 15-metallacrown-5 com-
plexes (Table 2). The peak with the highest intensity corre-
m/z calcd.
m/z exp.
m/z calcd.
YIII
1354.6
1404.6
1405.6
1409.5
1417.5
1422.6
1427.6
1432.6
1434.6
1440.6
–
1354.3
1404.4
1405.6
1409.6
1417.4
1422.7
1427.9
1432.7
1434.4
1440.4
–
1291.9
1341.9
1342.9
1346.9
1353.9
1358.9
1363.9
1369.0
1371.7
–
1291.3
1341.4
1342.5
1346.6
1354.4
1359.7
1364.9
1369.7
1371.4
–
III
La
Ce
Nd
Eu
III
III
III
III
Gd
III
Dy
sponds to the doubly charged {Ln(NO )[15-MCCuIIN(MHA)-
III
3
Er
2+
III
5]} species. Another peak with approx. 10% of the inten-
Tm
Lu
III
sity of the former was detected in all the spectra and could
2
+
[a]
– +
UO
2
1410.9
1410.5
be assigned to the {Ln(NO )[15-MC II
-5] } mo-
3
Cu N(MHA)
3
–
–
lecular ion.
Only one peak at m/z = 1410 was observed in the ESI-
When lutetium() or thulium() were used as central MS spectra taken in the negative mode for the solution con-
cavity ions, additional peaks, that could not be attributed taining the uranyl ion. The mass of this peak could be un-
[
a] Value calculated for {M[15-MC-5] } .
Eur. J. Inorg. Chem. 2006, 1466–1474
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1469

T. N. Parac-Vogt et al.
FULL PAPER
ambiguously assigned to the intact {UO [15-MCCuIIN(MHA)-
The spectra of solutions containing racemic -mande-
2
3
– –
5] } molecular ion. The axial coordination of two oxygen lohydroxamic acid, copper() and neodymium() or uranyl
atoms in the uranyl ion does not allow for additional bind- were also recorded, and the m/z values observed in those
ing of counterions, and the first coordination sphere of the spectra were identical to the m/z values observed when (S)-
uranyl ion is completed by five equatorial oxygen atoms mandelohydroxamic acid was used as coordinating ligand.
from the metallacrown ring. In the positive mode ESI-MS
The presented ESI-MS data indicate that solutions con-
spectra of the solution containing the uranyl ion, two peaks taining copper() salt, mandelohydroxamic acid [- or
at m/z = 706 and 1412 were detected (Figure 2). They corre- (S)-] and a central templating ion in methanolic and etha-
2
+
spond to the {UO [15-MC II
-5]} and {UO [15- nolic solutions are forming pentanuclear species. The only
2
+
Cu N(MHA)
2
–
MC II
-5] } pentanuclear species, respectively. The species detected for the solutions prepared with M = Y, La,
Cu N(MHA–)
peak at m/z = 1412.7 corresponds to a 15-metallacrown-5 Ce, Nd, Eu, Gd, Dy, Er, and UO correspond to the intact
2
species in which the hydroxyl group in one of the ligands is M[15-MCCuIIN(MHA)-5] pentanuclear species. On the basis
deprotonated, and the peak at m/z = 706.4 corresponds to of the previously mentioned geometric considerations, it is
a metallacrown species in which all five hydroxyl groups are very likely that the structure of the pentanuclear species
protonated.
corresponds to the structure of the planar 15-metallacrown-
ring, in which lanthanide() ions or uranyl ions are en-
5
capsulated in the central cavity (Figure 3).
Complexation of Mandelohydroxamic Acid Monitored by
UV/Vis Spectroscopy
Titration experiments were performed in order to gain
insight into the formation of the metallacrown complexes.
Surprisingly, these experiments revealed that the order in
which the metal salts are added to the MHA solution is
crucial for the formation of metallacrown complexes. Ti-
II
tration of Cu /-MHA solution with neodymium() and
uranyl in steps of 0.04 equivalents caused a slight decrease
in the intensity of the broad shoulder between 300 nm and
4
6
50 nm and also the decrease of the d–d transition band at
87 nm. Even after the reaction mixture was let to react for
Figure 2. Positive-ion mode ESI-MS spectra of the methanolic
II
2+
solutions containing Cu /MHA/UO
2
in 5:5:1 ratio.
24 hours, no appearance of new peaks and shifting of the
ligand field or d–d bands was observed. The ESI-MS spec-
tra of these solutions were recorded and they did not show
any evidence for the existence of pentanuclear species.
On the contrary, the titration of copper() to the solu-
tions containing -MHA and neodymium() in a 5:1 ratio
caused significant changes in the UV/Vis spectra. New
bands at 330 nm and 638 nm (Figure 4) appeared, and their
intensity increased until 5 equivalents of copper() were
added, and it leveled off upon addition of 6 equivalents of
copper(). The molar absorptivity of the copper() ligand
field band observed at a Cu/Ln ratio of 5:1 was consistent
with the isolated 15-metallacrown-5 sample, dissolved in
MeOH. The plot of the ratio of concentrations of neodym-
ium() to copper() vs. the molar absorptivity at 330 nm
and 638 nm is shown in Figure 5. The composition of the
sample in which the ratio of Nd/MHA/Cu was 1:5:5 is con-
sistent with the formula Nd[15-MC II
-5]. With the
Cu N(MHA)
further increase of lanthanide concentration, no changes in
the copper() ligand field band were observed, indicating
that the presence of excess of lanthanide or uranyl ions does
not disturb the metallacrown structures. Indeed, the ESI-
MS spectra of the final solution showed exclusively cluster
peaks which could be unambiguously assigned to the 15-
metallacrown-5 species. The UV/Vis spectrum of Nd[15-
Figure 3. Proposed structure of the pentanuclear Nd[15-
Cu N[(S)-MHA]-5] metallacrown complex in solution. The coordi-
nation sphere of neodymium() ion is completed by nitrate or
MC II
water ligands.
MC II
Cu N(MHA)-5] resembles the UV/Vis spectra of other
1470
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Eur. J. Inorg. Chem. 2006, 1466–1474

MHa as Ligand for CuII 15-Metallacrown-5 Lanthanide() and Uranyl Complexes
FULL PAPER
pentanuclear complexes with lanthanide() ions. The band
However, it must be mentioned that factors, such as the
at 330 nm is in agreement with the band at 336 nm observed acidity of the solution and the different protonation states
in the 15-metallacrown-5 complexes with tryptophanhy- of the ligand, may be responsible for the fact that the order
[
40]
droxamic acid.
This band contains most likely contri- in which the metal salts are added to the MHA solution is
–
–
–
–
butions of N –O
charge-transfer transitions.
and N –O
to copper() crucial for the formation of the metallacrown complex. The
determination of the degree of protonation of the ligand
in the presence of copper() and lanthanide() ions would
require thorough potentiometric titrations and evaluation
(nitrogen)
(oxygen)
+
of many possible equilibria involved in the ternary H /
2+
3+
MHA/Cu /Ln system.
CD Spectroscopy of 15-Metallacrown-5 Complexes
Because the R- and S-enantiomeric forms of the MHA
are chiral, their copper() complexes are expected to be op-
tically active as well. The chirality of the 15-metallacrown-
5
complexes formed with R- and S-enantiomeric forms of
the MHA has been studied by circular dichroism (CD)
spectroscopy. The ESI-MS spectra of all the solutions used
for the spectrophotometric measurements were recorded,
and the species observed were consistent with the Ln[15-
Figure 4. Changes in the UV/Vis absorption spectra of NdIII/MHA
solutions in methanol, upon addition of copper() ions. Copper()
ions were added in 0.2 equiv. increments, until the final ratio of
MC II
Cu N(MHA)-5] structure as described earlier in the mass
spectrometric results. The CD spectrum of methanolic solu-
II/
III
III
II
tions of (S)-MHA/Cu Nd (ratio: 1:1:0.2), shows a posi-
tive Cotton effect at 342 nm (∆ε = 2.86 mol·L–1 cm ) and
Nd /MHA/Cu reached 1:5:5 ratio.
–1
–1
–1
two negative Cotton effects at 603 (∆ε = –1.2 mol·L cm )
and 733 nm (∆ε = –1.08 mol·L–1 cm ). If (R)-MHA was
used as the ligand, the CD spectrum of the resulting com-
plex was the mirror image of the spectrum of the complex
of (S)-MHA. As expected, the 15-metallacrown-5 complex
made from the racemic MHA showed no signal in the CD
spectrum (Figure 6).
–1
Figure 5. Change of molar absorptivity at 330 nm (squares) and
III
II
6
38 nm (circles) of the Nd /MHA/Cu solution as a function of
number of copper() equivalents.
The complex formation of lanthanide() with mande-
lohydroxamic acid has not been reported before, and no
information about the stability of such complexes is avail-
able. The X-ray single-crystal structure of the complex
formed between europium() and analogous α-alaninehy-
droxamic acid has shown that the hydroxamate group of
Figure 6. CD absorption spectra of Nd[15-MC II
-5]
Cu N[(S)-MHA]
α-alaninehydroxamate ligands forms a bridge between two (full line), Nd[15-MCCuIIN[(R)-MHA)-5] (dotted line) and Nd[15-
[
41]
europium() ions, so that a binuclear complex is formed.
MCCuIIN(-MHA)-5] (dashed line) in methanol.
However, it has been shown that the addition of copper()
to solutions of lanthanide() and α-aminohydroxamic acid
The chirality of the 15-metallacrown-5 complex implies
leads to the formation of the 15-metallacrown-5 struc- that all five phenyl groups of the MHA ligand have to be
[
37]
ture. Obviously, the high lability of the lanthanide() li- positioned upon the same face of the metallacrown. This
gand bonds may allow for the initially formed products to side-chain orientation is enforced by the directionality of
rearrange into the 15-metallacrown-5 structure upon ad- the metal–nitrogen–oxygen bonds, as it was previously re-
ported in other chiral 15-metallacrown-5 complexes.[
22,24]
dition of copper() ion.
Eur. J. Inorg. Chem. 2006, 1466–1474
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
1471

T. N. Parac-Vogt et al.
FULL PAPER
Proton NMR of of 15-Metallacrown-5 Complexes
mandelohydroxamic ligand. The results of ESI-MS, UV/
Vis, CD, and NMR studies are consistent with the forma-
tion of 15-metallacrown-5 complexes. The mandelohydrox-
amic ligand as novel scaffold for the 15-metallacrown-5
complex fulfils the geometric requirements which bring five
metal ions into a plane, enforcing an angle of 108° between
adjacent metal ions, and thus enforcing the formation of a
planar, pentagonal ring. Our study shows that for the self-
assembly of the 15-metallacrown-5, the presence of lantha-
nide() or uranyl ions is essential, as it has been demon-
strated before. As it has been suggested before that lantha-
nide() ions are being recognized and encapsulated by 15-
metallacrown-5 complexes, this study shows that lantha-
nide() ions may have a templating effect and could play a
crucial role in the early stages of 15-metallacrown-5 forma-
tion.
Proton NMR signals of nuclei close to paramagnetic me-
tal ions are usually very broad and the extent of paramag-
netically induced line broadening depends on the electronic
relaxation time of the metal centers.[
42]
Complexes with
paramagnetic copper() ions usually exhibit broad NMR
signals because of the relatively long electronic relaxation
–
9
–9
times of copper() (τ = 1·10 s to 5·10 s). However, a
s
shortening of the electronic relaxation times can occur be-
cause of the magnetic coupling between the metal ions.
Previous studies have shown that the copper() ions in the
[
42]
[
22,24]
15-metallacrown-5 are antiferromagnetically coupled,
so that the τ value of those metallacrowns is shorter than
s
it would be in the absence of magnetic coupling. This could
allow the detection of relatively narrow peaks in high-reso-
lution NMR experiments.
1
The H NMR spectrum of the Nd[15-MC II
-5]
Cu N[(R)-MHA
complex in [D ]MeOH showed three peaks at δ = 5.85, 6.58,
and 7.75 ppm (Figure 7). The α-proton of the ligand could
4
Experimental Section
not be observed, most likely because it was too broad. It Synthesis of the Ligands: The ligands, (R)-(–)-mandelohydroxamic
acid, (S)-(+)-mandelohydroxamic acid and -mandelohydroxamic
acid were synthesized from the corresponding ethyl ester. The prep-
aration method for (S)-(+)-mandelohydroxamic acid and -mand-
elohydroxamic acid is identical to that of the synthesis of (R)-(–)-
mandelohydroxamic acid that is described below.
has been shown that the protons to the closest proximity to
the paramagnetic center are showing the greatest line
[
43]
broadening. The assignment of the peaks was done with
the help of two-dimensional proton correlation spec-
troscopy (COSY). The comparison with the proton NMR
spectrum of the previously reported Nd[15-MCCuIIN(-tyrha)-
Synthesis of Ethyl (R)-(–)-Mandelate: To a solution of (R)-(–)-man-
delic acid (100 mmol, 15.2 g) in ethanol (170 mL) was added
H SO (5 mL) as the catalyst. The reaction mixture was heated at
2 4
reflux temperature for 4 h. After the reaction mixture was cooled
to room temperature, the solvent was evaporated under reduced
pressure. Then, after addition of dichloromethane, the organic layer
5] complex revealed that the aromatic protons of the mand-
elohydroxamate ligand appear in the same region as the sig-
nals of the aromatic protons of the tyrosinehydroxamate
ligand. The simplicity of the spectra, i.e. the presence of
only one set of resonances indicates the fivefold pseudosym-
3
was neutralized by a saturated NaHCO solution and dried with
metry of the molecule. The NMR results are consistent with MgSO . Dichloromethane was removed under reduced pressure.
4
1
those of the previously studied lanthanide() containing Yield: 91% (16.41 g). H NMR ([D
6
]DMSO, 300 MHz, ppm): δ =
), 5.11 (d, 1 H, CH), 6.04
1
5-metallacrown-5 copper() complexes, which also showed 1.13 (t, 3 H, CH
3
), 4.07 (t, 2 H, OCH
2
[24]
(d, 1 H, OH), 7.40 (m, 5 H, H-aromatic).
only one set of ligand resonances.
Synthesis of (R)-(–)-Mandelohydroxamic Acid: To a solution of
NH OH·HCl (2 equiv., 182 mmol, 12.65 g) in methanol (110 mL),
2
potassium hydroxide (3 equiv., 273 mmol, 15.29 g) dissolved in
methanol (42 mL) was added under nitrogen. The hydroxylamine
solution was cooled to 0 °C and KCl was removed by filtration.
The solution was added to (R)-(–)-mandelic ethyl ester (1 equiv.,
9
1 mmol, 16.41 g) and stirred at room temperature during 12 h.
Figure 7. Proton NMR spectrum of Nd[15-MC II
complex in [D ]MeOH solution.
4
-5]
Cu N[(R)-MHA]
The white precipitate of the potassium salt was filtered off and
dried (10.53 g, 51 mmol, 56% yield). To a suspension of the potas-
sium salt in methanol was added 12  HCl (51 mmol, 4.25 mL).
Potassium chloride precipitated and was filtered off. The solvent of
It is noteworthy to emphasize the fact that whereas the
NMR signals were observable for the 15-metallacrown-5
complex in which several highly paramagnetic ions are pres- the filtrate was partially removed under reduced pressure and water
ent, no NMR spectrum could be obtained for the com- was added to the solution. The solution was left to stand at 4 °C
1
to allow the final product to crystallize. Yield: 51% (4.35 g).
NMR ([D
H
plexes formed in the absence of lanthanide() ions. Obvi-
ously, there are significant differences in the relaxation
times of copper() ions in these two types of complexes.
The absence of any protons in the NMR spectrum recorded
in the absence of lanthanide() is consistent with the pres-
ence of mononuclear copper() complexes.
6
]DMSO, 300 MHz, ppm): δ = 4.89 (d, 1 H, CH), 5.95
d, 1 H, OH), 7.40 (m, 5 H, H-aromatic), 8.77 (s, 1 H, NH), 10.72
s, 1 H, OHhydr.). C NO (167 g/mol): calcd. C 57.48, H 5.43, N
.38; found C 57.16, H 5.49, N 8.32.
(
(
8
H
9
3
8
Synthesis of the Metallacrowns
1) Nd[15-MC-5]·3(HCOO)·3(H
.25 mmol) was dissolved into methanol (50 mL) and (R)-MHA
167 mg, 1 mmol) was added. The solution was stirred for 10 min,
(
0
(
2 3 3 2
O): Nd(NO ) ·6H O (109 mg,
Conclusions
In this paper we explore the strategy that leads to the then sodium methoxide (108 mg, 2 mmol) was added to the reac-
formation of pentanuclear copper() complexes with the tion mixture. After another 10 min, anhydrous copper() chloride
1472
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Eur. J. Inorg. Chem. 2006, 1466–1474

MHa as Ligand for CuII 15-Metallacrown-5 Lanthanide() and Uranyl Complexes
FULL PAPER
(
170 mg, 1 mmol) was added. The mixture was stirred for 2 h until
the solution became green. Finally sodium formate (68 mg,
mmol) was added, and the blue-green precipitate was filtered,
washed with water to remove sodium chloride and dried under vac-
uum. C43 NdO24 (1476.8 g/mol): calcd. C 34.97, H 3.00,
N 4.74; found C 35.15, H 3.57, N 4.81.
[4] M. Arnold, D. A. Brown, O. Degg, W. Errington, W. Haase,
K. Herlihy, T. J. Kemp, H. Nimir, R. Werner, Inorg. Chem.
1
998, 37, 2920–2925.
1
[
[
[
[
[
5] I. Botos, L. Scapozza, D. Zhang, L. A. Liotta, E. F. Meyer,
Proc. Natl. Acad. Sci. USA 1996, 93, 2749–2754.
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H44Cu N
1
995, 312, 333–339.
7] M. J. Miller, Chem. Rev. 1989, 89, 1563–1579, and references
(
0
(
2) Nd[15-MC-5]·3(CH COO)·(H O): Nd(NO
.25 mmol) was dissolved into methanol (50 mL) and (R)-MHA
167 mg, 1 mmol) was added. The solution was stirred for 10 min,
3
2
3 3 2
) ·6H O (109 mg,
therein.
8] C. J. Marmion, D. Griffith, K. B. Nolan, Eur. J. Inorg. Chem.
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then sodium methoxide (108 mg, 2 mmol) was added to the reac-
tion mixture. After another 10 min, anhydrous copper() chloride
1
(
170 mg, 1 mmol) was added. The mixture was stirred for 2 h until
the solution became green. Finally the sodium acetate (82 mg,
mmol) was added, and the blue-green precipitate was filtered,
washed with water to remove sodium chloride and dried under vac-
uum. C46 NdO22 (1518.9 g/mol): calcd. C 37.26, H 3.13,
[
[
10] B. Chatterjee, Coord. Chem. Rev. 1978, 26, 281–303.
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1
[12] M. Careri, F. Dallavalle, M. Tegoni, I. Zagoni, J. Inorg. Bi-
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5 5
H46Cu N
[
13] J. A. Halfen, J. J. Bodwin, V. L. Pecoraro, Inorg. Chem. 1998,
N 4.72; found C 37.41, H 3.13, N 4.69.
37, 5416–5417.
UV/Vis and CD Spectrophotometry: UV/Vis absorption spectra
were recorded with a Shimadzu UV-1601PC spectrophotometer
using quartz cells of 1-cm path length. Circular dichroism spectra
were recorded with a JASCO J-810 spectropolarimeter using quartz
cells of 2-cm path length. The spectra were measured between
[
14] B. R. Gibney, D. P. Kessissoglou, J. W. Kampf, V. L. Pecoraro,
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[
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200 nm and 900 nm. The concentration of the copper() and mand-
7259.
elohydroxamic acid in methanol was always 0.5 m. A neodym-
ium() nitrate stock solution (0.25 m). was prepared in methanol
for the UV/Vis titration experiment. Different amounts of this solu-
tion were added to the copper()/mandelohydroxamic solution in
[
[
18] V. L. Pecoraro, Inorg. Chim. Acta 1989,155, 171–173.
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[
III
II
order to obtain different ratios of Nd /Cu . The solutions were
III
II
left to stir overnight before measurement. The Nd /Cu ratio was
varied in steps of 0.04 from 0 to 0.28.
[21] V. L. Pecoraro, A. J. Stemmler, B. R. Gibney, J. J. Bodwin, H.
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ESI-MS Method: Electrospray ionization mass spectra were re-
corded with a Q-TOF 2 mass spectrometer (Micromass, Manches-
ter, UK). Some of a ethanolic metallacrown solution, prepared with
[
[
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1
0
mmol of the copper() and mandelohydroxamic acid and
.2 mmol of the central metal ion, was injected in the apparatus at
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[
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MeOH containing equimolar amounts of Cu(OAc) and (R)-(–)-
mandelohydroxamic acid (0.1 ) was added 1.0 equiv. of
Nd(NO . This was achieved by adding 60 µL of a neodymium()
nitrate [D ]MeOH solution (0.166 ).
4
]
2
[
[
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gium) (project G.01117.03) for financial support. T. N. P.-V. ac-
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Financial support by the IWT-Vlaanderen to A. P. is gratefully ac-
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www.eurjic.org
1473

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FULL PAPER
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Published Online: February 9, 2006
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Eur. J. Inorg. Chem. 2006, 1466–1474