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

Abstract

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⁺ a neutral complex [Ga(ppa)]·3H₂O was obtained. The formation of an encapsulated 1 : 1 complex is supported by elemental analysis and spectroscopic evidence.

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Introduction

For many years, the group 13 metals (Al, Ga, In, Tl) and the lanthanides (Ln) have either been employed, or have been investigated for potential use in nuclear medicine.¹⁶⁷Ga(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.²²⁰¹Tl⁺ as a myocardial imaging agent predates the use of ^99mTc for this application, although ²⁰¹Tl⁺ imaging has been largely supplanted by Tc-based diagnostic agents such as Cardiolite®. 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 characterized using a variety of NMR techniques.^9,12–15 The DOTA phosphinate ligands have also been modified to act as bifunctional chelates.¹⁶

Scheme 1

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, modifications to the tripodal amino-phosphinate ligands are described herein. Attempts were made to prepare new ligands with modifications 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 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.

Results and discussion

The synthesis of new amino-phosphinate ligands was accomplished 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 phenylphosphinic 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.

Scheme 2

The possibility of modification at the amine was also investigated. 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, however, afforded the novel secondary amine tripod tris(4-(phenylphosphinato)-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.

Scheme 3

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 equivalents 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.

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 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) Å. 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 difference map exceeding 0.87 e⁻ Å⁻³. The elemental analyses for the Ga³⁺ and other H₃ppba complexes strongly support the proposed composition.

Table 1 Selected bond lengths (Å) and bond angles (°) in Ga(H₃ppba)₂](NO₃)₂Cl·3CH₃OH (1)

a The O atoms are related to each other by symmetry.
Ga(1)–O(1)	1.9501(13)	C(3)–P(1)	1.8355(19)
O(1)–P(1)	1.5051(13)	C(4)–P(1)	1.796(2)
O(2)–P(1)	1.4923(14)
P(1)–O(1)–Ga(1)	143.83(8)	O(2)–P(1)–O(1)	120.24(8)
O(1)–Ga(1)–O(1*)^a	88.85(6)	O(1)–P(1)–C(3)	104.05(8)
O(1)–Ga(1)–O(1*)^a 91.15(6)		O(1)–P(1)–C(4)	110.32(9)
O(1)–Ga(1)–O(1*)^a	180.00(7)	O(2)–P(1)–C(3)	110.76(9)
C(4)–P(1)–C(3)	99.51(9)	O(2)–P(1)–C(4)	109.84(9)

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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.

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 ν(P–Ph); the sharp peak at 1383 cm⁻¹ arises from ν(NO₃); the three large peaks at ca. 1190, 1130, 1070 cm⁻¹ are attributed to ν(P–O); and the peaks around 700 cm⁻¹ are due to ν(P–C) and ν(P–Ph). 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).

Fig. 2 IR spectra of [M(H₃ppba)₂](NO₃)₂Cl, M as indicated.

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.

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.

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 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 R3̄ 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.

Table 2 Selected bond lengths (Å) and bond angles (°) in [Gd(H₄ppba)₂](NO₃)₄Cl·3CH₃OH (2)

a The O atoms are related to each other by symmetry.
Gd–O(2)	2.2841(17)	P(1)–C(1)	1.797(3)
P(1)–O(1)	1.500(2)	P(1)–C(7)	1.845(3)
P(1)–O(2)	1.5104(16)
Gd–O(2)–P(1)	143.85(10)	O(1)–P(1)–C(1)	112.67(11)
O(2)–Ga–O(2*)^a	87.52(6)	O(1)–P(1)–C(7)	108.17(10)
O(2)–Ga–O(2*)^a	92.48(6)	O(2)–P(1)–C(1)	107.45(11)
O(2)–Ga–O(2*)^a	180.00	O(2)–P(1)–C(7)	107.94(10)
O(1)–P(1)–O(2)	117.45(11)	C(1)–P(1)–C(7)	101.97(12)

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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.

The switch from [M(H₄ppba)₂]⁵⁺ (M = La³⁺–Tb³⁺) to [M′(H₃ppba)₂]³⁺ (M′ = Al³⁺, Ga³⁺, In³⁺, Ho³⁺–Lu³⁺) is an interesting 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 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 dramatic change in the P=O and P–O stretching frequencies in 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 ν(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 ν(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.

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.

Because all the 1 : 1 complexes precipitate as highly insoluble powders, no crystals suitable for an X-ray structural analysis could 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 ν(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.

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 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 ν(NO₃) in the IR spectra is identical to that of the two structurally characterized 2 : 1 complexes of these metal ions with H₃ppba, therefore, it is unlikely that the NO₃⁻ ligands are coordinated to In³⁺ and 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 (or CH₃OH in case of In) completing the coordination sphere.

The IR spectra of the H₃ppa ligand and the Ga, In and Ln complexes have several notable features. One of the ν(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 ν(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.

Conclusions

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-(phenylphosphinato)-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 structures 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 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 1 : 1 complex [Ga(ppa)]·3H₂O. Although ¹H 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 formaldehyde (Fisher), concentrated HCl (Fisher), phenylphosphinic acid (Aldrich), 10% Pd on C (Aldrich), and prepurified H_2(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

Mass spectra were obtained with either a Kratos MS 50 (electron 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 spectrophotometer. 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 δ referenced downfield from external TMS. ¹³C(¹H} NMR spectra were recorded on a Bruker AC-200E (50 MHz) spectrometer with δ referenced downfield from external TMS. ³¹P{¹H} NMR spectra were recorded on a Bruker AV-300 (121.5 MHz) NMR spectrometer with δ 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 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) δ 7.75–7.15 (overlapped multiplets, 30H), 4.45 (s, 6H), 3.63 (s, 6H), 3.39 (s, 12H). ³¹P NMR (CD₃OD) δ 23.2 (s).

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 H_2(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) δ 7.87 (s, 6H), 7.50 (s, 9H), 3.16 (s, 12H), 2.95 (s, 6H). ³¹P NMR (CD₃OD, 121.5 MHz) δ 21.1 (s).

Synthesis of metal complexes

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.†

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 recovered by filtration (yield 90 mg, 84%).

General preparative method for the synthesis of [M(H₄ppba)₂](NO₃)₄Cl·3CH₃OH (M = Gd³⁺), (2). 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 (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%.).

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.

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 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.

[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

Please refer to the ESI for experimental details, and for complete tables of bond lengths and bond angles.

Compound 1. C₉₆H₁₁₄GaN₈O₁₂P₆: FW = 1827.49, crystal system: trigonal, space group R3̄c, a = b = 23.9800(7), c = 32.5706(9) Å, α = β = 90, γ = 120°, V = 16220.1(8) ų, T = 173 K, Z = 6, µ = 0.399 mm⁻¹, total no. of reflections collected = 46807, no. unique reflections = 4271, R_int = 0.031, R₁ (I > 2σ(I)) = 0.046, wR₂ (all data) = 0.134.

Compound 2. C₉₆H₁₁₆GdN₁₂O₂₄P₆Cl: FW = 2200.53, crystal system: trigonal, space group = R3̄, a = b = 14.9142(4), c = 44.202(2) Å, α = β = 90, γ = 120°, V = 8514.4(5) ų, T = 198 K, Z = 3, µ = 0.762 mm⁻¹, total no. of reflections collected = 18646, no. unique reflections = 4368, R_int = 0.045, R₁ (I > 2σ(I)) = 0.034, wR₂ (all data) = 0.093.

 

CCDC reference numbers 275600 and 275601.

See http://dx.doi.org/10.1039/b507905e for crystallographic data in CIF or other electronic format.

Acknowledgements

We thank the Natural Sciences and Engineering Research Council (NSERC) of Canada and DuPont Pharmaceuticals, Inc. for financial support.

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Footnote

† Electronic supplementary information (ESI) available: Experimental section. See http://dx.doi.org/10.1039/b507905e

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