Lanthanide(III) and group 13 metal ion complexes of tripodal amino phosphinate ligands

Article abstract of DOI:10.1039/b507905e

The tripodal amino-phosphinate ligands, tris(4-(phenylphosphinato)-3- benzyl-3-azabutyl)amine (H₃ppba·2HCl·H₂O) and tris(4-(phenylphosphinato)-3-azabutyl)amine (H ₃ppa·HCl·H₂O) were synthesized and reacted with

Full text of DOI:10.1039/b507905e

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www.rsc.org/dalton | Dalton Transactions
Lanthanide(III) and group 13 metal ion complexes of tripodal amino
phosphinate ligands†
Michael S. Kovacs, Vishakha Monga, Brian O. Patrick and Chris Orvig*
Received 24th June 2005, Accepted 6th September 2005
First published as an Advance Article on the web 25th October 2005
DOI: 10.1039/b507905e
The tripodal amino-phosphinate ligands, tris(4-(phenylphosphinato)-3-benzyl-3-azabutyl)amine
(H3ppba·2HCl·H2O) and tris(4-(phenylphosphinato)-3-azabutyl)amine (H3ppa·HCl·H2O) were
synthesized and reacted with Al3+, Ga3+, In3+ and the lanthanides (Ln3+). At 2 : 1 H3ppba to metal
ratios, complexes of the type [M(H3ppba)2]3+ (M = Al3+, Ga3+, In3+, Ho3+–Lu3+) were isolated. The
bicapped [Ga(H3ppba)2](NO3)2Cl·3CH3OH was structurally characterized and was shown indirectly by
various techniques to be isostructural with the other [M(H3ppba)2]3+ complexes. Also, at 2 : 1 H3ppba
to metal ratios, complexes of the type [M(H4ppba)2]5+ (M = La3+–Tb3+) were characterized, and the
X-ray structure of [Gd(H4ppba)2](NO3)4Cl·3CH3OH was determined. At 1 : 1 H3ppba to metal ratios,
complexes of the type [M(H4ppba)]4+ (M = La3+–Er3+) were isolated and characterized. Elemental
analysis and spectroscopic evidence supported the formation of a 1 : 1 monocapped complex. Reaction
of 1 : 1 ratios of H3ppa with Ln3+ and In3+ yielded complexes of the type [M(H3ppa)]3+ (M =
La3+–Yb3+) but with Ga3+, complex of the type [Ga(ppa)]·3H2O was obtained. Reaction of 1 : 1 ratios of
H3ppa with Ln3+ and In3+ yielded complexes of the type [M(H3ppa)]3+ (M = La3+–Yb3+) but with Ga3+
neutral complex [Ga(ppa)]·3H2O was obtained. The formation of an encapsulated 1 : 1 complex is
supported by elemental analysis and spectroscopic evidence.
a
characterized using a variety of NMR techniques.9,12–15 The DOTA
phosphinate ligands have also been modified to act as bifunctional
chelates.16
Introduction
For many years, the group 13 metals (Al, Ga, In, Tl) and the lan-
thanides (Ln) have either been employed, or have been investigated
for potential use in nuclear medicine.1 67Ga(III) and 111In(III) have
been used in diagnostic agents, the former for imaging certain types
of cancer, and the latter as pretargeting agents for cancer imaging
and therapy, e.g. the use of 111In-octreoscan.2 201Tl+ as a myocardial
imaging agent predates the use of 99mTc for this application,
although 201Tl+ imaging has been largely supplanted by Tc-based
The tripodal ligand H3ppma was found to form 2 : 1 bicapped
complexes with group 13 metals and the lanthanides.17–19 The
S6 symmetry of these bicapped complexes made unique 27Al,
71Ga and 31P NMR spectroscopic studies amenable that allowed
the determination of stability constants below the pH limit
of traditional potentiometric techniques.17 Encapsulated 1 : 1
complexes were not obtained in the tripodal amino-phosphinate
system. For application in nuclear medicine, this result was a
significant setback because 1 : 1 encapsulated complexes are ideal.
Such a complex should have higher thermodynamic stability than
would a 2 : 1 bicapped complex; the coordination sphere would
contain only donors from the ligand, unlike in the monocapped
case, where kinetically labile water molecules or counterions
are coordinated. Encapsulated 1 : 1 complexes are also much
less sensitive to entropic effects that occur at extreme dilution.
Kinetically inert complexes with high thermodynamic stability
are required to prevent demetallation of the complex in vivo.
To investigate the possibility of isolating 1 : 1 encapsulated
complexes containing group 13 metals or the lanthanides, modi-
fications to the tripodal amino-phosphinate ligands are described
herein. Attempts were made to prepare new ligands with modifi-
cations occurring at the phosphinate R group and/or the amine R
group. Although modification at the phosphinate R group proved
difficult, synthesis of the benzylated amino-phosphinate ligand
tris(4-(phenylphosphinato)-3-benzyl-3-azabutyl)amine (H3ppba)
was successful. Two distinct classes of 2 : 1 complexes, and one
class of 1 : 1 complex were prepared and characterized with the
group 13 metal ions (Al3+, Ga3+, In3+) and the lanthanides. H3ppba
R
diagnostic agents such as Cardioliteꢀ. The use of the lanthanides
as therapeutic agents has received extensive attention since the
US Food and Drug Administration approval of 153Sm(EDTMP)
for bone pain palliation in terminal cancer patients. Gd(III) has
received extensive attention due to its use in MRI contrast
agents.3,4
Efforts to explore amino-phosphinate ligands with the group 13
metals and the lanthanides have focused on DOTA-type ligands
and tren-based tripodal ligands (Scheme 1). The former have
been more thoroughly investigated, and a variety of work has
been published on their synthesis, structures of their lanthanide
complexes, solution behavior and luminescence properties.5–11
1 : 1 Complexes with the lanthanides have been obtained with
this type of ligand system and the resulting stereochemistry has
been extensively investigated.9,12–15 In addition to the clockwise and
counterclockwise wrapping isomers, six diastereomers have been
Medicinal Inorganic Chemistry Group, Department of Chemistry, University
of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada.
E-mail: orvig@chem.ubc.ca
† Electronic supplementary information (ESI) available: Experimental
section. See http://dx.doi.org/10.1039/b507905e
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Scheme 1
was also used as a synthetic precursor to obtain the unique amino-
phosphinate ligand tris(4-(phenylphosphinato)-3-azabutyl)amine
(H3ppa) by N-debenzylation. H3ppa contains a secondary amine,
a functionality that has been elusive in amino-phosphinate systems
until this report.
however, afforded the novel secondary amine tripod tris(4-(phenyl-
phosphinato)-3-azabutyl)amine (H3ppa·HCl·H2O) (Scheme 3).
The reaction is easily monitored by the loss of the methylene
resonance of the benzyl group in the 1H NMR spectrum at
4.45 ppm. Catalytic hydrogenation of N-benzyl groups is known to
be difficult because of the propensity of free amines to poison the
Pd catalyst.22 High pressure and a large excess of Pd catalyst were
required for this reaction to proceed. Hydrogenation reactions are
known to produce pure products in high yield; the products of
the reaction are H3ppa and toluene, and the problem of purifying
the zwitterionic product from the Moedritzer–Irani reaction is
avoided. H3ppa is highly water-soluble; the ligand is also soluble
in alcohols such as methanol and ethanol.
Results and discussion
The synthesis of new amino-phosphinate ligands was accom-
plished by adapting the Moedritzer–Irani reaction20 to react
phenylphosphinic acid with tris(2-benzylaminoethyl)amine in the
presence of formaldehyde (Scheme 2). The synthesis of tris(2-
benzylaminoethyl)amine (the benzylated derivative of tren) was
accomplished by standard methods.21 Recrystallization of the
product from the reaction of benzylated tren and phenylphos-
phinic acid affords pure tris(4-(phenylphosphinato)-3-benzyl-3-
azabutyl)amine (H3ppba·2HCl·H2O) in good yield. The ligand
was found to be soluble in methanol, hot ethanol, hot isopropanol,
DMSO and DMF.
The possibility of modification at the amine was also inves-
tigated. It was expected that the presence of the three bulky
benzyl groups would discourage 1 : 1 encapsulated complex
formation. Removal of these groups by catalytic hydrogenation,
Scheme 3
Scheme 2
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˚
Complexes of the ligand H3ppma were clearly shown to be 2 : 1
bicapped complexes of the type [M(H3ppma)2](NO3)3, where M =
Al3+, Ga3+, In3+ and Ln3+.17–19 Therefore, the first step of this study
was to prepare 2 : 1 ligand : metal complexes for comparison.
All complexes were prepared under similar conditions, but two
distinct classes of 2 : 1 bicapped complexes were identified.
Reaction of one equivalent of Ga(NO3)3·6H2O with two equiva-
lents of H3ppba·2HCl·H2O in methanol results in the formation of
the 2 : 1 bicapped complex [Ga(H3ppba)2](NO3)2Cl·3CH3OH (1).
Indicating that complex formation occurs in methanol solution,
the 31P NMR singlet of H3ppba shifted upfield from 23.2 to
14.4 ppm for the complex, but little other information is obtained
from NMR spectroscopy. A number of metal salts were tried,
including chloride, triflate and perchlorate, but only the mixed
nitrate/chloride product formed crystals that were amenable to X-
ray structural analysis and had consistent composition. Reactions
with Al3+, In3+, and the lanthanides Ho3+ through Lu3+ formed the
same type of tricationic complex. Isolated yields ranged from 31 to
84%. In the case of the lanthanides, the complexes appeared to have
somewhat higher solubility, and yields were difficult to improve.
Any attempt to improve the yields by removing the solvent resulted
in the formation of glassy solids with inconsistent compositions
according to their elemental analyses.
Table 1 Selected bond lengths (A) and bond angles ( ) in Ga(H3ppba)2]-
(NO3)2Cl·3CH3OH (1)
Ga(1)–O(1)
O(1)–P(1)
O(2)–P(1)
1.9501(13)
1.5051(13)
1.4923(14)
C(3)–P(1)
C(4)–P(1)
1.8355(19)
1.796(2)
P(1)–O(1)–Ga(1)
O(1)–Ga(1)–O(1*)a
O(1)–Ga(1)–O(1*)a
O(1)–Ga(1)–O(1*)a
C(4)–P(1)–C(3)
143.83(8)
88.85(6)
91.15(6)
180.00(7)
99.51(9)
O(2)–P(1)–O(1)
O(1)–P(1)–C(3)
O(1)–P(1)–C(4)
O(2)–P(1)–C(3)
O(2)–P(1)–C(4)
120.24(8)
104.05(8)
110.32(9)
110.76(9)
109.84(9)
a The O atoms are related to each other by symmetry.
ligand. The ligands are best regarded as neutral zwitterions, thus,
the complex has an overall +3 charge. The Ga3+ ion is coordinated
only by the phosphinato O atom donors with one symmetry-
˚
imposed Ga–O bond length of 1.9501(13) A. The two H3ppba
ligands are related to each other through a crystallographic
inversion center at the Ga3+ ion. Although the portion of the unit
cell containing [Ga(H3ppba)2]3+ is well established, large void
spaces exist where satisfactory modeling of mixed NO3−, Cl−
and CH3OH was not possible. Correction of the disordered data
in the void spaces resulted in R1 = 0.048 and no peak in the
−3
difference map exceeding 0.87 e− A . The elemental analyses
˚
An X-ray structural analysis was performed on a crystal of
1 isolated from the reaction of H3ppba with Ga3+ (Fig. 1,
Table 1). The Ga3+ ion is clearly bicapped by two H3ppba ligands;
examination of the bond lengths and a difference map indicate that
each of the three arm N atoms are protonated on each H3ppba
for the Ga3+ and other H3ppba complexes strongly support the
proposed composition.
Analogous to the structurally characterized [In(H3ppma)2]3+
or [Lu(H3ppma)2]3+ complexes,17,19 there is nearly perfect S6
symmetry around the Ga3+ ion. In the case of [In(H3ppma)2]3+,
the crystallographic symmetry imposed perfect 90 and 180◦ angles
between the O atoms of the phosphinato ligands.17 The 180◦
angles in [Lu(H3ppma)2]3+ are crystallographically imposed, and
the 88.72(6) and 91.28(6)◦ angles are extremely close to 90◦.19
The unique bond angles in 1 are 180.00, 91.15(6) and 88.85(6)◦,
therefore, the structure is also an octahedral complex with nearly
perfect S6 symmetry. The bond lengths in each of the three
complexes are comparable when the ionic radii are corrected for
the three different metals.
Also analogous to the two known H3ppma complexes, the
coordination of each phosphinato O atom introduces a chiral
center at each P atom.17,19 In the crystal structure of 1, only the
RRRSSS diastereomer is observed. In order to accommodate the
bulk of the phenyl rings on the phosphinate group, the only other
diastereomer that is chemically possible is the RRSSSR.17 There is
no evidence for the presence of this diastereomer in the solid state
in any of the studies to date.
Mass spectral (+LSIMS) data for the entire series of complexes
demonstrate clearly that 2 : 1 complexes are formed (see ESI†).
Peaks are seen in each case corresponding to the monocationic 2 :
1 and 1 : 1 complexes. Since the ligand peak at 879 is also observed
in every case, it is reasonable to conclude that the 1 : 1 complex is
formed by fragmentation in the mass spectrometer.
IR spectroscopy shows that complexes of H3ppba with Al3+,
Ga3+, In3+ and the lanthanides Ho3+ through Lu3+ are completely
isostructural (Fig. 2). The IR spectra have several notable features
in the region shown. The peak around 1450 cm−1 is attributed to
m(P–Ph); the sharp peak at 1383 cm−1 arises from m(NO3); the three
large peaks at ca. 1190, 1130, 1070 cm−1 are attributed to m(P–O);
and the peaks around 700 cm−1 are due to m(P–C) and m(P–Ph).
Fig. 1 ORTEP diagram of the [Ga(H3ppba)2]3+ cation with the solvent
molecules and the aromatic rings removed for clarity; 50% thermal
probability ellipsoids are shown. Symmetry labels: i: −y, x − y, z;
ii: −x + y, −y, z; iii: −x + 1/3, −y + 2/3, −z + 2/3; iv: y + 1/3,
−x + y + 2/3, −z + 2/3; v: x − y + 1/3, x + 2/3, −z + 2/3.
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Table 2 Selected bond lengths (A) and bond angles ( ) in [Gd(H4ppba)2]-
(NO3)4Cl·3CH3OH (2)
Gd–O(2)
P(1)–O(1)
P(1)–O(2)
2.2841(17)
1.500(2)
1.5104(16)
P(1)–C(1)
P(1)–C(7)
1.797(3)
1.845(3)
Gd–O(2)–P(1)
143.85(10)
87.52(6)
92.48(6)
180.00
O(1)–P(1)–C(1)
O(1)–P(1)–C(7)
O(2)–P(1)–C(1)
O(2)–P(1)–C(7)
C(1)–P(1)–C(7)
112.67(11)
108.17(10)
107.45(11)
107.94(10)
101.97(12)
O(2)–Ga–O(2*)a
O(2)–Ga–O(2*)a
O(2)–Ga–O(2*)a
O(1)–P(1)–O(2)
117.45(11)
a The O atoms are related to each other by symmetry.
Fig. 2 IR spectra of [M(H3ppba)2](NO3)2Cl, M as indicated.
The intensity and position of all of these peaks remains relatively
unchanged in all of the spectra, except in that of Dy3+, which
appears to show some additional spectral features (vide infra).
For the series of lanthanides La3+ through Dy3+, however,
the IR spectra of the complexes were found to differ greatly
from the “Ga3+ type” structures. The elemental analyses (see ESI†)
of the Eu3+, Gd3+ and Tb3+ complexes indicate that complexes of
the type [Ln(H4ppba)2]5+ are formed wherein the apical nitrogen of
each ligand is protonated to afford a +5 complex. Obtaining good
elemental data for this class of complex was difficult. Isolated
yields were quite low (10–15%), and only Eu3+, Gd3+ and Tb3+
complexes were isolated in pure form. Satisfactory elemental
analyses for the La–Sm3+ and Dy3+ complexes were never obtained.
Lying on the border between the +5 and +3 complexes, it is
possible that Dy3+ formed a mixture of both complex types. The
appearance of new features in the IR spectrum of the Dy3+ complex
supports this hypothesis.
Fig. 3 ORTEP diagram of the [Gd(H4ppba)2]5+ cation with the solvent
molecules and the aromatic rings removed for clarity; 50% thermal
probability ellipsoids are shown. Symmetry labels: i: −y, x − y, z;
ii: −x + y, −x, z; iii: −x, −y, −z; iv: y, −x + y, −z; v: x − y, x, −z.
Despite the fact that pure complexes could not be obtained for
all of the early Ln3+ series, the +LSIMS data and IR spectroscopy
indicate that these complexes have similarities to the Eu3+, Gd3+
and Tb3+ complexes. The large shift in frequency of the IR bands
associated with P and O bonding may be attributed to a change in
the intramolecular H-bonding involving the protonated N atoms.
If this is the case, the positions of the transitions in the IR spectra
are a remarkably sensitive probe of the intramolecular H-bonding.
Although the Sm3+ complex has an identical IR spectrum to those
of the Gd3+ and Tb3+ complexes, strangely the Eu3+ complex does
not, even though its elemental analysis supports its formulation
as [Eu(H4ppba)2]5+. The Nd3+ spectrum is identical to the Eu3+
spectrum. The early Ln3+ may have a propensity to form a mixture
of 2 : 1 and 1 : 1 complexes (vide infra). This may explain why
satisfactory elemental analyses could not be obtained for La3+–
Sm3+, and may also explain the presence of the 2 : 1 peaks in the
+LSIMS spectra.
found in 1. Each arm of the tripod is related to the other arms by
six-fold crystallographic symmetry. Both the pendant amines and
the apical amines are protonated to afford the product complex
as [Gd(H4ppba)2](NO3)4Cl·3CH3OH (2). The geometry around
Gd3+ is nearly octahedral, with unique bond angles of 180.00,
87.52(6) and 92.48(6)◦ between the O phosphinato donor atoms.
As in 1, the P atoms in 2 have a RRRSSS configuration and this is
the only diastereomer seen in the solid state. The presence of the
[M(H4ppba)2]5+ complex in the unit cell is very clear, but the six-
¯
fold symmetry of the R3 unit cell complicated the identification
of the five counterions and the CH3OH in the large void spaces
of the unit cell. This disorder was modeled with help from the
analytical data and was refined to R1 = 0.034.
The switch from [M(H4ppba)2]5+ (M
=
La3+–Tb3+) to
[Mꢀ(H3ppba)2]3+ (Mꢀ = Al3+, Ga3+, In3+, Ho3+–Lu3+) is an inter-
esting phenomenon that was not observed in the H3ppma system.
It is possible that the size of the metal ion and the nature of the H-
bonding network in the uncoordinated upper part of the tripodal
From the reaction mixture of Gd3+ and H3ppba, a single crystal
was obtained and was used in an X-ray structural analysis (Fig. 3,
Table 2). The complex has a bicapped structure similar to that
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ligand have some role in this behavior. It is a well-known fact that
early lanthanide trivalent metal ions are larger than late lanthanide
trivalent metal ions. The angles between the phosphinate O donors
in 1 have two unique angles of 88.88(6) and 91.12(6)◦, whereas the
unique angles in the 2 are 87.52(6) and 92.48(6)◦. It is possible
that the larger Ln3+ ions can tolerate this compression of the
bond angles better than the smaller Ln3+ and group 13 metal ions.
As a result of the compression at the bottom of the tripod, the
upper tripod can open up and a rearrangement of the H-bonding
network can occur (including the apical N proton) to produce the
observed +5 complex. This explanation is also supported by the
be obtained. The complexes only have limited solubility, even in
solvents such as DMSO; after dissolution they are unrecoverable.
Given that the elemental analysis supports the formulation
[M(H4ppba)]4+, wherein all four N atoms are protonated, it seems
highly unlikely that an encapsulated complex is formed. The
m(NO3) in the IR spectra is identical to that of the two structurally
−
characterized 2 : 1 complexes, therefore, it is unlikely that the NO3
ligands are coordinated to Ln3+ in the 1 : 1 complexes. Given this
combined evidence, the most reasonable assumption is that the
complexes are monocapped, with 3–5 H2O molecules completing
the coordination sphere.
=
dramatic change in the P O and P–O stretching frequencies in
Reaction of tris(4-(phenylphosphinato)-3-azabutyl)amine
(H3ppa·HCl·H2O) with Ga(NO3)3·6H2O in methanol at a 1 :
1 molar ratio results in the formation of a finely-divided white
precipitate after standing for 48 h. Elemental analysis of this
precipitate gives the composition [Ga(ppa)]·3H2O (6). Clearly,
this is a very interesting result because it is possible that an
encapsulated 1 : 1 complex has formed. The lack of counterions
strongly suggests that the pendant N donors are not protonated
the IR spectra of the complexes.
In order to investigate further the strange behavior of the 2 : 1
La3+–Sm3+ complexes, including the possibility of 1 : 1 complex
formation, a study of the system in 1 : 1 ratios was initiated. Under
similar conditions to those which produced the 2 : 1 complexes,
1 : 1 ratios of M(NO)3 (M = La3+–Lu3+) and H3ppba were
reacted in methanol. These reactions afforded complexes of the
type [M(H4ppba)]4+ in 14–34% yield. Upon mixing of the starting
materials, a finely-divided precipitate immediately formed for most
of the lanthanides. Towards the end of the series (Tm3+–Lu3+), no
precipitate formed and prismatic crystals appeared corresponding
to the [M(H3ppba)2]3+ complexes over a period of 48 h. This was
verified crystallographically for the Yb3+ complex (the full solution
of the structure was not completed once this was discovered).
Unlike those of the 2 : 1 complexes, the +LSIMS mass spectra
of the 1 : 1 complexes show no substantial evidence of 2 : 1 peaks.
In some of the complexes, 2 : 1 peaks were observed at trace levels
(20× gain). The possibility exists that a small excess of ligand may
have been present in these cases. Lanthanide nitrate salts are very
hygroscopic and the excess water would not have been accounted
for if it were present.
The IR spectra of the 1 : 1 complexes La3+–Er3+ are remarkably
similar. The m(NO3) peak is at 1384 cm−1, which is the same
frequency as that seen in the 2 : 1 complexes. With the exception
of complexes of La3+ Sm3+, and Er3+ which have an additional
peak at 1238 cm−1, all the other complexes share similar features
in the m(PO) region of the spectrum (1303, 1181, 1134, 1054 cm−1).
The IR spectrum of the Ho3+ complex has a peak at 1238 cm−1
which is seen as a small shoulder on the broad peak at 1181 cm−1.
The fact that this same peak is seen the 2 : 1 Nd3+ and Eu3+ IR
spectra (see electronic supplementary information) supports the
possibility that a 1 : 1 complex may be present depending on
the exact conditions of preparation of the early lanthanide 2 : 1
complexes. The IR spectra of the late lanthanide 2 : 1 complexes
(Fig. 2) demonstrate that these metals have no propensity to form
1 : 1 complexes under these conditions.
NH2 , but rather the neutral NH. Unlike the [M(H4ppba)]4+
+
complexes described previously, the formation of an encapsulated
1 : 1 complex is a distinct possibility. The +LSIMS data support
the formulation as 1 : 1; a large peak at m/z 675 corresponding
to [Ga(Hppa)]+ is seen. Only a trace peak is seen at m/z 1285
corresponding to the 2 : 1 complex [GaH4(ppa)2]+. In order to
investigate further this behavior and to compare the reactivity of
lanthanides with H3ppa, similar reactions were carried out with
indium and lanthanide (M = La3+–Yb3+) nitrate salts. A study of
the system in 1 : 1 ratios of M(NO3)3 : H3ppa in methanol was
initiated to explore the possibility of 1 : 1 complex formation.
These reactions afforded complexes of the type [M(H3ppa)]3+,
just as the lanthanide complexes with H3ppba in good yields
(50–83%). Upon mixing of the starting materials, a finely-divided
precipitate immediately formed for the indium complex and
most of the lanthanides. It was interesting to note that the
indium complex with this ligand forms complexes resembling the
lanthanides rather than gallium.
Analogous to the 1 : 1 M3+ : H3ppba complexes, the +LSIMS
and ESIMS mass spectra of the 1 : 1 M3+ H3ppa complexes show
no substantial evidence of 2 : 1 peaks (see ESI†). In some of the
complexes, 2 : 1 peaks were observed at trace levels (20× gain).
Lanthanide nitrate salts are very hygroscopic and the excess water
would not have been accounted for if it were present. With a
small variation in hydration, the elemental analyses for the 1 : 1
complexes are very consistent. All the Ln complexes appear to
have the formulation [M(H3ppa)](NO3)3Cl·xH2O whereas the In
complex was isolated as [In(H3ppa)](NO3)3Cl·2CH3OH.
Because all of the In and Ln complexes precipitate as highly
insoluble powders, crystals suitable for an X-ray structural analysis
could not be obtained. The complexes only have limited solubility,
even in solvents such as DMSO; after dissolution they are
unrecoverable. Given that the elemental analysis supports the
formulation [M(H3ppa)]3+, wherein three of the N atoms are
protonated, it seems highly unlikely that an encapsulated complex
is formed. The m(NO3) in the IR spectra is identical to that of the
two structurally characterized 2 : 1 complexes of these metal ions
With a small variation in hydration, the elemental analyses for
the 1 : 1 complexes are very consistent. All the complexes appear to
have the formulation [M(H4ppba)](NO3)3Cl·xH2O. As expected,
the carbon content is much lower than in any of the 2 : 1 complexes,
and the nitrogen content is much higher, owing to the lack of a
second carbon-rich ligand. The analyses of the Ho3+ and Er3+
complexes appear to have slightly higher levels of carbon, perhaps
because of the preference of the late Ln3+ to form 2 : 1 complexes
in this system.
−
with H3ppba, therefore, it is unlikely that the NO3 ligands are
Because all the 1 : 1 complexes precipitate as highly insoluble
powders, no crystals suitable for an X-ray structural analysis could
coordinated to In3+ and Ln3+ in the 1 : 1 complexes. Given this
combined evidence, the most reasonable assumption is that the
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complexes are monocapped, with 3–5 H2O molecules (or CH3OH
in case of In) completing the coordination sphere.
structure was not obtained, the combination of IR spectroscopic,
mass spectrometric and elemental analysis data strongly support
the formation of a monocapped complex wherein the nitrate
counterions are not coordinated to the metal centre. 1 : 1 molar
ratios of H3ppa·HCl·H2O and Ga(NO3)3·6H2O in methanol afford
The IR spectra of the H3ppa ligand and the Ga, In and Ln
complexes have several notable features. One of the m(PO) bands
shifts from 1188 to 1181 cm−1 upon complex formation. The band
at 954 cm−1 in the free ligand disappears completely. Unlike all
other complexes with H3ppa, there is no indication of a free nitrate
in the IR spectrum of the gallium complex at ca. 1385 cm−1. The
broad m(NH) peak shifts from 3414 cm−1 in the free uncomplexed
ligand to 3421 cm−1 in the complexes, which may indicate that
the N donors are involved in complex formation. The seemingly
unusual strengthening of the N–H bond upon coordination may
occur because the N atom is first deprotonated from NH2+ to NH,
then is subsequently coordinated to Ga3+. Since this is a two-step
process, it is difficult to state with absolute certainty that the N
donors are coordinated to Ga3+ on the basis of IR spectroscopy
alone. With respect to the free ligand and the gallium complex,
the IR spectra of all other complexes show more distinct features
in the fingerprint region.
The 31P NMR spectrum of 6 in methanol is complicated and
contains at least seven resonances between 23.7 and 24.9 ppm,
shifted downfield from the ligand in which it is seen as a singlet at
21.1 ppm. Unlike the gallium complex, the 31P NMR resonances
of In and La complexes shifted upfield to 16.1–19.2 ppm. The 1H
NMR spectra of the complexes and the free ligand demonstrate
significant shifts of the CH2 groups compared to the free ligand.
Although the speciation in solution is complicated, the shifts of
the pendant CH2 arms are strongly indicative of pendant N atom
coordination to the metal. It is plausible to regard the complex as
encapsulated, but in the absence of X-ray structural data, it can
not be stated for certain.
1
the 1 : 1 complex [Ga(ppa)]·3H2O. Although H and 31P NMR
spectroscopies, IR spectroscopy, +LSIMS and elemental analysis
support the formation of a 1 : 1 encapsulated complex, the exact
nature of the complex can not be ascertained without an X-ray
structural analysis. The reaction of H3ppa·HCl·H2O with various
lanthanides and In(NO3)3 in a 1 : 1 molar ratio afforded complexes
of the type [M(H3ppa)]3+ (M = In3+, La3+–Yb3.
Experimental
Materials
All solvents were of HPLC grade and were obtained from
Fisher. When anhydrous solvents were required they were dried
using conventional procedures.23 Ligand syntheses were carried
out under Ar; metal complexes were prepared in air and were
found to be completely air and moisture stable. HPLC grade
methanol (Fisher), tris(2-aminoethyl)amine (W.R. Grace & Co.),
benzaldehyde (Aldrich), NaBH4 (Fisher), 37% aqueous formalde-
hyde (Fisher), concentrated HCl (Fisher), phenylphosphinic acid
(Aldrich), 10% Pd on C (Aldrich), and prepurified H2(g) (Praxair)
were all obtained from commercial sources and were used
without further purification. Tris(2-benzylaminoethyl)amine was
synthesized by published methods.21 All hydrated metal salts were
used as received and were obtained from Johnson Matthey.
Instrumentation
Conclusions
Mass spectra were obtained with either a Kratos MS 50 (elec-
tron impact ionization, EIMS) or a Kratos Concept II H32Q
instrument (Cs+-LSIMS with positive ion detection). Infrared
(IR) spectra in the range 4000–500 cm−1 were recorded as KBr
disks with a Mattson Galaxy Series 5000 FTIR spectropho-
tometer. Microanalyses for C, H, N, and Cl were performed by
Mr P. Borda in this department. 1H NMR spectra were recorded
on Bruker AC-200E (200 MHz) or Bruker AV-300 (300 MHz)
NMR spectrometers with d referenced downfield from external
TMS. 13C(1H} NMR spectra were recorded on a Bruker AC-200E
(50 MHz) spectrometer with d referenced downfield from external
In order to obtain 1 : 1 complexes of the group 13 metals
Al3+, Ga3+, In3+ and the lanthanides, two new amino-phosphinate
tripod ligands were synthesized. H3ppba was synthesized by
the Moedritzer–Irani reaction of tris(2-benzylaminoethyl)amine,
formaldehyde and phenylphosphinic acid to afford tris(4-(phenyl-
phosphinato)-3-benzyl-3-azabutyl)amine (H3ppba·2HCl·H2O) in
good yield. The reaction of H3ppba·2HCl·H2O with H2 at 70 bar
with a 10% Pd on C catalyst yielded tris(4-(phenylphosphinato)-
3-azabutyl)amine (H3ppa), a water soluble tripodal amino-
phosphinate ligand containing three secondary amine functional
groups. H3ppba·2HCl·H2O was reacted with Al3+, Ga3+, In3+
and Ln3+ in 2 : 1 ratios and was found to form bicapped
complexes of the type [M(H3ppma)2]3+ (M = Al3+, Ga3+, In3+,
Ho3+–Lu3+) or [M(H4ppma)2]5+ (M = La3+–Tb3+). Crystal struc-
tures were obtained for [Ga(H3ppba)2]3+ and [Gd(H4ppba)2]5+,
and a combination of IR spectroscopic, mass spectrometric
and elemental analytical data were used to infer the structures
of the remaining metal complexes. The bicapped geometry is
formed by a pair of ligands coordinating to the metal centre
through its phosphinate O atoms only. Either three or four of
the nitrogen atoms on each ppba unit are protonated, and an
H-bonded network is formed in the empty space of the tripod.
1 : 1 complexes of the type [M(H4ppba)2]4+ (M = La3+–Er3+)
were obtained by the reaction of H3ppba·2HCl·H2O and the
appropriate metal salts at 1 : 1 molar ratios. Although an X-ray
1
TMS. 31P{ H} NMR spectra were recorded on a Bruker AV-300
(121.5 MHz) NMR spectrometer with d referenced to external
85% aqueous phosphoric acid. A Parr model 4753 pressure vessel
and a model 4316 gauge block assembly equipped with a 140 bar
burst plate were used for the hydrogenation reaction.
Preparation of compounds
Tris(4-(phenylphosphinato)-3-benzyl-3-azabutyl)amine, H3ppba·
2HCl·H2O. Tris(2-benzylaminoethyl)amine (2.0 g, 4.8 mmol)
was dissolved in 10 mL methanol. Concentrated HCl (20 mL)
was added dropwise, followed by phenylphosphinic acid (2.1 g,
15 mmol). The temperature was raised to reflux; 37% aqueous
formaldehyde was added dropwise over a 30 min period, and the
reaction was refluxed for a further 5 h. After cooling, acetone was
added to the creamy yellow-coloured suspension to precipitate
3 6 | Dalton Trans., 2006, 31–38
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the product completely. The product was recovered by filtration
and was recrystallized from boiling ethanol to afford the pure
white product (yield = 3.8 g, 81%). Anal. Calc. (found) for
C48H57N4O6P3·2HCl·H2O: C, 59.44 (59.44); H, 6.34 (6.18); N,
5.78 (5.95). (+)LSIMS: m/z 879 ([M + H]+). 1H NMR (CD3OD,
300 MHz) d 7.75–7.15 (overlapped multiplets, 30H), 4.45 (s, 6H),
3.63 (s, 6H), 3.39 (s, 12H). 31P NMR (CD3OD) d 23.2 (s).
and a finely-divided white powder was isolated by filtration (yield
45 mg, 80%). The insolubility of the white powder made it
impossible to obtain crystals for X-ray structural analysis.
[In(H3ppa)](NO3)3Cl·xH2O (5). To a solution of H3ppa·
HCl·H2O (47 mg, 0.069 mmol) in 5 mL CH3OH was added
a solution of In(NO3)3·H2O (22 mg, 0.069 mmol) in 0.5 mL
CH3OH. A precipitate immediately formed out of the mixture
and a finely-divided white powder was isolated by filtration (yield
46 mg, 71%). The insolubility of the white powder made it
impossible to obtain crystals for X-ray structural analysis.
Tris(4-(phenylphosphinato)-3-azabutyl)amine, H3ppa·HCl·H2O.
H3ppba·2HCl·H2O (500 mg, 0.510 mmol) was dissolved in 50 mL
methanol, to which 10% Pd on C (300 mg, 0.282 mmol) was
added as an ethanol suspension. The mixture was stirred at room
temperature and reacted with H2(g) (70 bars, 48 h). The catalyst
was removed by filtration on a fine frit, the solvent was removed,
and the hygroscopic white product was recrystallized from a hot
ethanol–acetone mixture (yield 150 mg, 44%). Anal. Calc. (found)
for C27H39N4O6P3·HCl·H2O: C, 48.91 (49.18); H, 6.38 (6.38); N,
8.45 (7.95). (+)LSIMS: m/z = 609 ([M + H]+). 1H NMR (CD3OD,
300 MHz) d 7.87 (s, 6H), 7.50 (s, 9H), 3.16 (s, 12H), 2.95 (s, 6H).
31P NMR (CD3OD, 121.5 MHz) d 21.1 (s).
[Ga(ppa)]·3H2O (6). To a solution of H3ppa·HCl·H2O (50 mg,
0.071 mmol) in 5 mL CH3OH was added a solution of
Ga(NO3)3·6H2O (25.8 mg, 0.071 mmol) in 0.5 mL CH3OH. A
fine white powder formed over 48 h at room temperature and was
isolated by filtration (yield 29 mg, 56%). Anal. Calc. (found) for
C27H36N4O6P3Ga·3H2O: C, 44.47 (44.89); H, 5.80 (5.83); N, 7.68
(7.81). (+)LSIMS: m/z 675 ([M + H]+). The IR spectrum and the
1H and 31P NMR spectra are given in the ESI.†
X-Ray crystallographic analyses of 1 and 2
Synthesis of metal complexes
Please refer to the ESI for experimental details, and for complete
tables of bond lengths and bond angles.
Detailed procedures are given for representative examples
of [M(H3ppba)2]3+ (M
=
Al3+, Ga3+, In3+, Ho3+–Lu3+),
[M(H4ppba)2]5+ (M = Ln3+–Tb3+), [M(H4ppba)]4+ (M = La3+–
Tm3+) and [M(H3ppa)]3+ (M = La3+–Yb3+, In3+) complexes.
Characterization data for all compounds prepared are listed in
the ESI.†
Compound 1. C96H114GaN8O12P6: FW = 1827.49, crystal sys-
¯
tem: trigonal, space group R3c, a = b = 23.9800(7), c = 32.5706(9)
◦
3
˚
˚
A, a = b = 90, c = 120 , V = 16220.1(8) A , T = 173 K, Z =
6, l = 0.399 mm−1, total no. of reflections collected = 46807, no.
unique reflections = 4271, Rint = 0.031, R1 (I > 2r(I)) = 0.046,
wR2 (all data) = 0.134.
General preparative method for the synthesis of M(H3ppba)2]-
(NO3)2Cl·3CH3OH (M
=
Ga3+), (1). To
a solution of
H3ppba·2HCl·H2O (100 mg, 0.103 mmol) in 5 mL CH3OH was
added a solution of Ga(NO3)3·6H2O (18.7 mg, 0.052 mmol) in
0.5 mL CH3OH. Upon standing for 48 h at room temperature,
colourless prismatic crystals formed, of which one was extracted
for X-ray structural analysis. The remaining crystals were recov-
ered by filtration (yield 90 mg, 84%).
Compound 2. C96H116GdN12O24P6Cl: FW = 2200.53, crystal
¯
system: trigonal, space group = R3, a = b = 14.9142(4), c =
◦
3
˚
˚
44.202(2) A, a = b = 90, c = 120 , V = 8514.4(5) A , T = 198 K,
Z = 3, l = 0.762 mm−1, total no. of reflections collected = 18646,
no. unique reflections = 4368, Rint = 0.045, R1 (I > 2r(I)) = 0.034,
wR2 (all data) = 0.093.
General preparative method for the synthesis of [M(H4ppba)2]-
(NO3)4Cl·3CH3OH (M
=
Gd3+), (2). To
a solution of
CCDC reference numbers 275600 and 275601.
See http://dx.doi.org/10.1039/b507905e for crystallographic
data in CIF or other electronic format.
H3ppba·2HCl·H2O (100 mg, 0.103 mmol) in 5 mL CH3OH was
added a solution of Gd(NO3)3·6H2O (23.2 mg, 0.0515 mmol)
in 0.5 mL CH3OH. During one week of standing at room
temperature, colourless hexagonal plates formed, one of which
was extracted for X-ray structural analysis. The remaining crystals
were recovered by filtration (yield 15 mg, 13%.).
Acknowledgements
We thank the Natural Sciences and Engineering Research Council
(NSERC) of Canada and DuPont Pharmaceuticals, Inc. for
financial support.
General preparative method for the synthesis of [M(H4ppba)]-
(NO3)3Cl·3H2O (M
=
Gd3+), (3). To
a
solution of
H3ppba·2HCl·H2O (100 mg, 0.103 mmol) in 5 mL CH3OH was
added a solution of Gd(NO3)3·6H2O (46.4 mg, 0.103 mmol)
in 0.5 mL CH3OH. A precipitate immediately formed out of
the mixture and a finely-divided white powder was isolated by
filtration (yield 45 mg, 33%). The insolubility of the white powder
made it impossible to obtain crystals for X-ray structural analysis.
References
1 F. Rosch and E. Forssell-Aronsson, Met. Ions Biol. Syst., 2004, 42, 77.
2 C. J. Anderson and M. J. Welch, Chem. Rev., 1999, 99, 2219.
3 P. Caravan, J. J. Ellison, T. J. McMurry and R. B. Lauffer, Chem. Rev.,
1999, 99, 2293.
4 M. J. Allen and T. J. Meade, Met. Ions Biol. Syst., 2004, 42, 1.
5 C. J. Broan, E. Cole, K. J. Jankowski, D. Parker, K. Pulukkody, B. A.
Boyce, R. A. B. Nigel, K. Millar and A. T. Millican, Synthesis, 1992,
63.
6 E. Cole, R. C. B. Copley, J. A. K. Howard, D. Parker, G. Ferguson, J. F.
Gallagher, B. Kaitner, A. Harrison and L. Royle, J. Chem. Soc., Dalton
Trans., 1994, 1619.
General preparative method for the synthesis of [M(H3ppa)]-
(NO3)3Cl·xH2O (M
=
Eu3+), (4). To
a
solution of
H3ppa·HCl·H2O (38 mg, 0.058 mmol) in 5 mL CH3OH was added
a solution of Eu(NO3)3·6H2O (25.7 mg, 0.058 mmol) in 0.5 mL
CH3OH. A precipitate immediately formed out of the mixture
This journal is
The Royal Society of Chemistry 2006
Dalton Trans., 2006, 31–38 | 3 7
©

View Article Online
7 S. Aime, M. Botta, D. Parker and J. A. G. Williams, J. Chem. Soc.,
Dalton Trans., 1996, 17.
8 E. Huskowska, C. L. Maupin, D. Parker, J. A. G. Williams and J. P.
Riehl, Enantiomer, 1997, 2, 381.
9 S. Aime, A. S. Batsanov, M. Botta, R. S. Dickins, S. Faulkner, C. E.
Foster, A. Harrison, J. A. K. Howard, J. M. Moloney, T. J. Norman, D.
Parker, L. Royle and J. A. G. Williams, J. Chem. Soc., Dalton Trans.,
1997, 3623.
10 S. Aime, M. Botta, R. S. Dickins, C. L. Maupin, D. Parker, J. P. Riehl
and J. A. G. Williams, J. Chem. Soc., Dalton Trans., 1998, 881.
11 J.-C. G. Bunzli, Metal Ions Biol. Syst., 2004, 42, 39.
12 J. P. Pulukkody, T. J. Norman, D. Parker, L. Royle and C. J. Broan,
J. Chem. Soc., Perkin Trans. 2, 1993, 605.
15 W. D. Kim, G. E. Kiefer, J. Huskens and A. D. Sherry, Inorg. Chem.,
1997, 36, 4128.
16 S. Liu and D. S. Edwards, Bioconjugate Chem., 2001, 12, 7.
17 M. P. Lowe, S. J. Rettig and C. Orvig, J. Am. Chem. Soc., 1996, 118,
10446.
18 P. Caravan, M. P. Lowe, P. W. Read, S. J. Rettig, L. W. Yang and C.
Orvig, J. Alloys Compd., 1997, 249, 49.
19 M. P. Lowe, P. Caravan, S. J. Rettig and C. Orvig, Inorg. Chem., 1998,
37, 1637.
20 K. Moedritzer and R. R. Irani, J. Org. Chem., 1966, 31, 1603.
21 A. Naiini, W. M. P. B. Menge and J. G. Verkade, Inorg. Chem., 1991,
30, 5009.
22 T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis,
13 S. Aime, A. S. Batsanov, M. Botta, J. A. K. Howard, D. Parker, K.
Senanayake and J. A. G. Williams, Inorg. Chem., 1994, 33, 4696.
14 A. D. Sherry, J. Alloys Compd., 1997, 249, 153.
John Wiley & Sons, Inc., New York, 1999.
23 D. D. Perrin, W. L. F. Armarego and D. R. Perrin, Purification of
Laboratory Chemicals, Pergamon Press, Oxford,1980.
3 8 | Dalton Trans., 2006, 31–38
This journal is
The Royal Society of Chemistry 2006
©