Complexation properties of the di-, tri-, and tetraacetate derivatives of bis(aminomethyl)phosphinic acid

Article abstract of DOI:10.1002/ejic.200600891

Four ligands, which can be considered as di- [both symmetric (L ¹) and asymmetric (L²)], tri- (L³), and tetraacetate (L⁴) derivatives of bis(aminomethyl)phosphinic acid (L⁰) have been synthesized and

Full text of DOI:10.1002/ejic.200600891

FULL PAPER
DOI: 10.1002/ejic.200600891
Complexation Properties of the Di-, Tri-, and Tetraacetate Derivatives of
Bis(aminomethyl)phosphinic Acid
Gyula Tircsó,*[a][‡] Attila Bényei,[b] Róbert Király,[a] István Lázár,[a] Róbert Pál,[a] and
[a]
˝
Erno Brücher*
Keywords: Phosphinic acid derivatives / Divalent metal ions / Synthesis / Protonation constants / Stability constants
Four ligands, which can be considered as di- [both symmetric
(L1) and asymmetric (L2)], tri- (L3), and tetraacetate (L4) de-
rivatives of bis(aminomethyl)phosphinic acid (L0) have been
synthesized and their complexation equilibria involving
derivatives. The phosphinate group is not directly coordi-
nated to the metal ions but may contribute to the stability by
increasing the electrostatic interaction, which is significant
for the complexes of L4. The 1H NMR spectra of complexes
Mg2+, Ca2+, Ni2+, Cu2+, Zn2+, Cd2+, and Pb2+ have been ZnL2, ZnL3, and ZnL4 show an AB multiplet pattern for the
studied by pH potentiometry. The first two protonation con- protons of the iminodiacetate moiety of the ligands, which
stants of the ligands are lower than those of the analogous
diaminopolycarboxylates due to the electron-withdrawing
effect of the phosphinate group. The asymmetric ligands L2
and L3 and their complexes are protonated first at the pri-
mary (NH2) and secondary (NH) amine groups, respectively.
The ligands L0, L1, L2, and L3 form the species ML, MLH,
ML2, and ML2H whereas heptadentate L4 forms very stable
ML complexes, protonated (MLH and MLH2) species and,
indicates the long half-life of the Zn2+–N bond and the rigid
structure of this segment of the complexes. The solid-state
structure of the ligand [H5L3]Cl and complex K[CuL1]·H2O
have been determined by X-ray diffraction techniques. The
arrangement of the ligand L1 is square planar around Cu2+
with two nitrogen and carboxylate oxygen donor atoms, al-
though the axial proximity of a carboxylate and a phos-
phinate oxygen atom in two neighboring molecules results
unlike the other ligands, it also forms dinuclear M2L com- in a distorted octahedral coordination.
plexes. The stability constants of the complexes of L0, L1, L2,
and L3 are generally lower, while those of the L4 are similar
or higher, than those of the analogous diaminocarboxylate
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
The successful use of some tri- and tetraacetate deriva-
tives of cyclen in medical diagnosis and therapy has drawn
attention to the tetramethylenephosphinates of cyclen, and
a number of cyclen derivatives have been synthesized with
different phosphinate functional groups. The Gd3+ com-
plexes of these ligands have been proposed as contrast en-
hancing agents in magnetic resonance imaging.[9–15] Since
Introduction
Due to their biological importance there has been a
growing interest in recent years in the coordination chemis-
try of ligands containing phosphinate functional groups.[1]
–
The charge of the phosphinate group, PO2 , is minus one,
similar to that of the carboxylate, and thus the complex-
ation properties of aminoalkylphosphinate ligands are sim-
ilar to those of aminocarboxylates in many respects. How-
ever, as phosphinate groups are less basic than carboxylates,
the stability constants of the complexes formed with amino-
alkylphosphinates are lower than those of aminocarboxyl-
ates.[2–8]
–
the methylenephosphinate groups [CH2P(R)O2 , where R is
H, alkyl, or aryl] in these cyclen derivatives are attached to
the ring nitrogens, the phosphinate groups are in terminal
position, similar to open-chain ligands. However, in con-
trast to the carboxylate and phosphonate groups, phosphin-
ate groups may also occupy an “in-chain” position and
some multidentate aminocarboxylate ligands that contain
[a] University of Debrecen, Department of Inorganic and Analyti-
cal Chemistry,
–
PO2 groups as linkers have attracted considerable interest
P. O. Box 21, Egyetem tér 1, Debrecen 4010, Hungary
Fax: +36-52-489-667
in recent years.[16–26] Phosphinic acid peptides are specific
inhibitors of peptide hydrolytic enzymes (e.g. Zn metallo-
proteinases and aspartic acid proteinases) because the non-
E-mail: gyulat@gmail.com
ebrucher@delfin.klte.hu
[b] University of Debrecen, Department of Chemistry, Laboratory
for X-ray Diffraction,
–
hydrolyzable ϾPO2 moiety resembles the transition state
P. O. Box 7, Egyetem tér 1, Debrecen 4010, Hungary
[‡] Present address of the corresponding author: Department of
Chemistry, University of Texas at Dallas,
P. O. Box 830660, Richardson, Texas 75080, USA
Fax: +1-972-883-2925
of the hydrolyzable peptides.[18,19]
The complexation properties of bis(aminomethyl)phos-
phinic acid and some of its derivatives have already been
investigated. Complex formation between the ligands bis-
(aminomethyl)-, bis(N-methylsarcozinato)-, bis(N-methyl-
Supporting information for this article is available on the
WWW under http://www.eurjic.org or from the author.
Eur. J. Inorg. Chem. 2007, 701–713
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FULL PAPER
prolinato)-, and bis(N-methyliminodiacetato)phosphinate tive steps we have successfully synthesized the ligands H3L1,
and some divalent metal (Co2+, Cu2+, Zn2+, Cd2+, Pb2+ H3L2, and H3L3 (Scheme 1). These compounds can be re-
)
and lanthanide(III) (Ln3+) ions has been studied in solution garded as fragments of the edta analog H5L4, which was
by pH potentiometry and 1H NMR and EPR spec- reported earlier.[21,22] In the present study, the stability con-
troscopy.[20–24] Although the coordination of the phosphin- stants of the complexes formed between some endogenous
ate group to M2+ ions has been detected in some cases, it (Mg2+, Ca2+, Cu2+, and Zn2+) and toxic (Ni2+, Cd2+, and
is more important in the formation of complexes with Ln3+ Pb2+) divalent metal ions and bis(aminomethyl)phosphinic
–
ions.[21,22] The PO2 group has also been incorporated into acid derivatives are examined by pH potentiometry. The
macrocyclic rings. Eight- and fourteen-membered function- structures of the ligand [H5L3]Cl and the complex K[CuL1]·
alized bis(aminomethyl)phosphinate macrocycles have re- H2O have been determined in the solid state by X-ray dif-
1
cently been synthesized by Aime et al. and Song et al., fraction methods and the Zn2+ complexes studied by H
respectively.[25,26] The stability constant of the Gd3+ com- and 31P NMR spectroscopy in solution.
plex formed with the eight-membered diphosphinate ligand
was found to be relatively high (logKGdL = 17.6).[25] The
Results and Discussion
fourteen-membered ligand does not form highly stable com-
plexes.[26]
Synthesis of the Ligands
The ligand HL0 (Scheme 1) was first synthesized by Mai-
er and somewhat later by Natchev.[27,28] More recently, Ku-
Synthesis of the symmetric bis(aminomethyl)phosphinic
bicek et al. have published a new procedure for the synthesis acid derivatives was achieved in a multi-step reaction start-
ˇ
of HL0 and they also studied its CoII, NiII, CuII, and ZnII ing from N,N-dibenzylamine according to Scheme 2. The
complexes in solution and in the solid state.[24] The ligand monohydrochloride of the intermediate 1 was obtained in
H3L1 was also prepared by Maier but its complexation was high yields by a Mannich reaction in 6  HCl. The deben-
studied only with NiII.[29] The same author prepared the zylation of this key intermediate by catalytic hydrogenolysis
ligand H5L4 from the reaction of iminodiacetic acid can be carried out in different ways depending on the sol-
(H2imda) and paraformaldehyde in the presence of hypo- vent selected. Using acetic acid/water as a solvent in the
phosphorus acid.[30] Similar conditions were used pre- presence of EtOH with slight heating to achieve complete
viously in our laboratory by Varga to obtain some bis(ami- dissolution of the starting material the bis(aminomethyl)-
nomethyl)phosphinic acid derivatives from various imino- phosphinic acid hydrochloride 2 could be prepared in very
(di)acids.[20] The experimental conditions were found to high yields. Another advantage of this synthesis is that it
have a great influence on these reactions. Thus, high con- does not use expensive materials or instrumentation and
centrations of the reactants at reflux temperature led to the can be scaled up easily. The debenzylation of 1 in MeOH
formation of a number of by-products and purification of in the presence of formic acid was found to be controlled
the final products was difficult.[20]
by solubility and the hydrochloride salt of the selectively
protected bis(benzylaminomethyl)phosphinic acid 3 crys-
tallized out quantitatively from the reaction mixture during
the reduction process. An analytical sample of 3 was ob-
tained by recrystallization of crude 3 from hot water. Com-
pound 3 proved to be a valuable intermediate for the syn-
thesis of new carboxy- or phosphonomethyl derivatives of
bis(aminomethyl)phosphinic acid. Alkylation of 3 with bro-
moacetic acid in the presence of NaOH afforded the tri-
sodium salt of 4. The monohydrochloride salt of the free
acid was prepared by crystallizing 4 from fairly acidic solu-
tions (pH Ͻ 2). Debenzylation of 4 in a water/acetic acid
mixture afforded compound 5 (H3L1).
The synthesis of the asymmetric bis(aminomethyl)phos-
phinic acid derivatives 7–10 is presented in Scheme 3. They
are all new compounds that have not been published pre-
viously. The intermediate 6 was obtained from the reaction
Scheme 1. Structure of the ligands synthesized and investigated in
this work.
One of our goals was to find a procedure which would of iminodicarboxylic acid with paraformaldehyde in a Man-
allow the large-scale preparation of bis(aminomethyl)phos- nich-type reaction in ethanol in the presence of excess hypo-
phinic acid derivatives from readily available, inexpensive phosphorus acid, which also acts as an acid catalyst. In this
starting materials without expensive instrumental purifica- particular case (when H2imda was used as starting mate-
tion methods. Similarly, the bis(aminomethyl)phosphinic rial), the reaction was found to be solubility controlled and
acid itself can be considered as a building block for the at the end of the reaction the product crystallized out from
synthesis of macrocycles containing linker phosphinate the reaction mixture. The remaining P–H bond in the mole-
group(s) when the macrocycle itself has a negative charge. cule can be reacted further in a second Mannich-type reac-
By dividing the Mannich-type synthesis into two consecu- tion in 6  HCl to replace the H with another aminomethyl
702
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Acetate Derivatives of Bis(aminomethyl)phosphinic Acid
FULL PAPER
Scheme 2. Synthesis of the symmetric bis(aminomethyl)phosphinic acid derivatives studied in this work.
segment. This process allowed us to synthesize hitherto un- mixtures yielded compounds 4 and H5L4, respectively, after
known asymmetric bis(aminomethyl)phosphinic acid deriv- the workup and separation procedure. The formation of
atives (Scheme 3). The best yields for this reaction were ob- these compounds is evidence that the phosphorus–carbon
tained when short reaction times (about 1.5 h) were used as bond [CH2P(O)(OH)H] is not stable under Mannich condi-
the number of by-products in the reaction mixture in- tions and trans-aminomethylation occurs. The deben-
creased with an increase of the reaction time while the zylation of 7 and 9 to 8 (H4L3) and 10 (H3L2), respectively,
amount of desired products (7 and 9) decreased. When was achieved by catalytic hydrogenation under similar con-
longer reaction times (up to 6 h) were used the reaction ditions to those described for compound 2.
Scheme 3. Synthesis of the asymmetric bis(aminomethyl)phosphinic acid derivatives studied in this work.
Eur. J. Inorg. Chem. 2007, 701–713
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FULL PAPER
X-ray Crystal Structure of [H5L3]Cl and K[CuL1]·H2O
The structures of [H5L3]Cl and K[CuL1]·H2O were estab-
lished by single-crystal X-ray diffraction studies (see Fig-
ures 1 and 2, Tables 1 and 2, and the Supporting Infor-
mation). The most important feature of the structure of the
protonated ligand of [H5L3]Cl is the extensive H-bonding
network (Table S1) and the related disordered position of
the chloride ions (see below). The compound crystallizes in
the noncentrosymmetric space group Pn21a (no. 33). It is
important to note that the position of the carboxylate hy-
drogen atoms as well as the protons at the nitrogen atoms
could be found in the difference electron density maps of
both structures. However, these hydrogen atoms were
placed in geometric positions in the final refinement cycle.
The C–O bond length data (Table 3) of [H5L3]Cl show C3–
O4, C6–O6, and C8–O8 bond lengths of 1.298(10),
1.316(9), and 1.310(10) Å, respectively, which also indicate
the sites of protonation. Besides the electronic and steric
factors of the phosphinate moiety, the higher values of the
P–C bond lengths compared to C–C bonds as well as the
slightly different bond angles are another tool for the fine
tuning of the ligand that could be important in applications.
Figure 2. ORTEP view of the asymmetric unit in the structure of
K[CuL1]·H2O with thermal ellipsoids at the 50% probability level,
with atom-numbering scheme.
Table 1. Selected bond lengths [Å] and angles [°] for [H5L3]Cl.[a]
P1–O1
P1–O2
1.503(6)
1.493(5)
1.204(10)
1.298(10)
1.188(9)
1.316(9)
115.7(4)
103.7(4)
112.8(6)
111.8(6)
P1–C1
P1–C4
C8–O7
C8–O8
C1–N1
C4–N2
C2–C3–O3
C5–C6–O5
C7–C8–O7
C1–N1–C2
1.821(8)
1.803(7)
1.188(10)
1.310(10)
1.477(9)
1.469(8)
123.7(7)
125.7(7)
125.5(7)
111.8(6)
For example, the water exchange rate and thereby the re- C3–O3
laxivity of GdIII complexes formed with poly(amino)car-
C3–O4
C6–O5
boxylates depends on the steric crowding in the complex.[31]
C6–O6
In our case, the significant difference between the P1–C1
O1–P1–O2
and P1–C4 distances [1.803(7) and 1.821(8) Å, respectively]
also shows the electronic and steric effects of the mono-
and bis(diacatate) arms on the N1 and N2 nitrogen atoms,
respectively as these bond lengths are the same in the analo-
gous symmetric bis(aminomethyl)phosphinate hydrochlo-
ride structure.[24]
C1–P1–C4
C5–N2–C4
C4–N2–C7
[a] See Figure 1 for numbering scheme.
Table 2. Selected bond lengths [Å] and angles [°] for [K(CuL1)]·
H2O.[a]
Cu1–N2
Cu1–N6
Cu1–O3
2.008(6)
2.013(6)
1.940(6)
1.961(5)
2.249(5)
2.945(5)
2.731(8)
2.726(8)
90.1(3)
O1–P1
O2–P1
C1–P1
C5–P1
1.504(6)
1.491(5)
1.811(8)
1.799(8)
2.648(6)
2.714(7)
3.012(7)
2.780(7)
119.8(3)
108.8(3)
107.9(2)
104.6(4)
111.2(6)
Cu1–O5
Cu1–O2i
O1–K1
Cu1–O5ii
O1w–K1
O1w–K1iii
O4–K1
O6–K1i
O6–K1
O3–Cu1–O5
O5–Cu1–N2
N2–Cu1–N6
N2–Cu1–O2i
O5–Cu1–N6
O2–P1–O1
O2–P1–C5
O1–K1–O1w
C5–P1–C1
C1–N2–C3
166.0(2)
99.4(2)
89.7(2)
83.5(2)
[a] See Figure 2 for numbering scheme. Symmetry transformations
used to generate equivalent atoms: i: 1/3 + y, 2/3 – x + y, 2/3 – z;
ii: –x, –y, –z; iii: 4/3 – x + y, 2/3 – x, z – 1/3.
Figure 1. ORTEP view of the asymmetric unit in the structure of
[H5L3]Cl with thermal ellipsoids at the 50% probability level, with
atom-numbering scheme.
polar channel. Strong N–H···Cl hydrogen bonds fix the
anion in the analogous layered structure of bis(amino-
methyl)phosphinate hydrochloride, although the long range
The packing of [H5L3]Cl is shown in Figure S1 and the Cl–Cl distances are similar in the two structures (approx.
data of the H-bonding network are listed in Table S1 (see 3.96 Å). In our case, however, the three strong hydrogen
Supporting Information). The high max/min atomic dis- bonds with the participation of carboxylate donors and P1–
placement parameter ratio of the chloride ions in the struc- O1 or P1–O2 as acceptors as well as the steric restraints
ture of [H5L3]Cl can be explained by the fact that the chlo- prevent the formation of N–H···Cl hydrogen bonds
ride ion is not fixed in the lattice but loosely occupies a (Table S1).
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Acetate Derivatives of Bis(aminomethyl)phosphinic Acid
FULL PAPER
K[CuL1]·H2O crystallizes in the trigonal centrosymmet- Protonation Constants and Protonation Sites of the Ligands
¯
ric space group R3 (no. 148). The configuration of the ni-
The protonation equilibria of the ligands, L0, L1, L2, L3,
trogen atoms N2 and N6 is mixed, and the complex exists
as a racemate with equal amounts of (R,S) and (S,R)
enantiomers present in the lattice. Selected bond lengths
and angles are summarized in Table 2. The coordination of
the Cu2+ in K[CuL1]·H2O is best described as elongated
distorted octahedral. N2, N6, O3, and O5 form the basal
square-planar coordination and the copper is positioned
out of this plane by 0.211 Å. The carboxylate oxygen atom
O5i and phosphinate oxygen atom O2ii of symmetry-related
molecules (i: –x, –y, –z; ii: y + 1/3, –x + y + 2/3, –z + 2/3)
are coordinated in the axial positions with Cu–O distances
of 2.945 and 2.249 Å, respectively. In this way, two O5
atoms serve as bridging ligands that hold together two cop-
per complexes with a Cu–Cu distance of 3.827 Å and give
rise to a supramolecular polymer structure. This bridging
role of O5 also supports an octahedral rather than a square-
pyramidal coordination. The coordination of O2 of the next
complex in the lattice can be attributed to the electron-with-
drawing properties of the phosphinate group as well as the
increase in the length of the side arm due to the P–C bonds.
The hydrogen-bond data are summarized in the Support-
ing Information (Table S2). In this web, the H2 and H6 par-
ticipate in bifurcating hydrogen bonds while O1 is a bifur-
cating acceptor. However, the N2–H2···O1 hydrogen bond
has an unfavorable angle of 107°.
Tetradentate ligands analogous to 1,3-propanediamine-
N,NЈ-diacetate can form square-pyramidal copper(II) com-
plexes.[32] However, a search in the Cambridge Structural
Database (version 5.27, November 2005; update May 2006)
revealed that octahedral coordination may also occur in
similar compounds.[33] This is especially important in the
case of a CuII complex containing a small, sterically unde-
manding ligand such as in (3-hydroxy-1,5-diazacyclohep-
tane-N,NЈ-diacetato)copper(II), where the coordination is
N2O4.[34] Here, the hydroxyl oxygen and a water molecule
complete the octahedral coordination with Cu–O distances
of 2.456 and 2.564 Å, respectively. The deposited data do
not contain hydrogen atoms, which may indicate some am-
biguity, but similar octahedral coordination has also been
observed in another case where an axial water molecule and
another axial carboxylate oxygen complete the coordina-
tion sphere of the copper ion with Cu–O distances of 2.275
and 2.780 Å, respectively.[35]
1
and L4 were studied by pH-potentiometry and H (in some
cases 31P) NMR spectroscopy (Figures S3–S7 in the Sup-
porting Information). The titrations were performed in the
pH range of about 1.8–11.5 in the presence of 1.0 
Me4NCl. The protonation constants, defined as KiH
=
[HiL]/[Hi–1L][H+], were also determined in 1.0  KNO3
since the complexation with Cd2+ and Pb2+ was studied in
KNO3 solution in order to avoid the formation of chloro
complexes. For the calculation of the protonation constants
of the ligands, the number of data points was between 160
and 250. The logKiH values obtained are presented in
Table 3, where the standard deviations are shown in paren-
theses. The protonation constants of the ligands L0 and L4,
which have been determined previously (Table 3),[22–24] are
comparable with the ones obtained in this work when the
different experimental conditions are taken into account.
As was expected, we found by 1H (and 31P) NMR studies
that the most basic donor atoms in all derivatives of L0 are
the two nitrogens, which are protonated first (Figures S4
and S5).[21,22,24] The protonation of these nitrogens is fol-
lowed by protonation of the carboxylates, while the strongly
acidic phosphinate group is protonated only in strongly
acidic solution.[22,24] The protonation constants of L0 are
H
lower than those of 1,3-diaminopropane (logK1 = 10.52
H
and logK2 = 8.74), in which the two nitrogen donors are
also separated from each other by three atoms. The behav-
ior of the derivatives of L0 is similar. The first two proton-
ation constants of L4 (Table 3) are significantly lower than
those of 1,3-diaminopropane-N,NЈ,NЈЈ,NЈЈЈ-tetraacetic acid
H
H
(10.41 and 8.02).[36] Similarly, the logK1 and logK2 val-
ues of L1 are lower than the first two protonation constants
of ethylenediamine-N,NЈ-diacetic acid (L6; 9.69 and
6.72).[36] The lower basicity of the nitrogen atoms of the
phosphinate ligands is probably due to the electron-with-
drawing effect of the phosphinate group.
Table 3. Protonation constants of the ligands L0, L1, L2, L3, and
L4 (25 °C).
H
H
H
H
L
logK1
logK2
logK3
logK4
L0 [a,f]
L0 [b]
L0 [c]
L1 [a]
L1 [b]
L2 [a]
L2 [b]
L3 [a]
L3 [b]
L4 [a]
L4 [b]
L4 [d]
L4 [e]
8.73 (0.01)
8.74 (0.01)
8.51
7.35 (0.01)
7.38 (0.01)
7.07
–
–
–
–
1.66
1.77 (0.05)
–
–
2.03 (0.04)
1.43 (0.04)
2.17
1.98 (0.01)
1.69 (0.05)
2.32
The coordination of potassium is also octahedral, with
carboxylate, phosphinate, and water oxygen atoms (O6i,
O6iii, O4, O1, O1w, and O1wiv; i: –x, –y, –z; iii: x – y +
1/3, –x + 2/3, –z + 2/3; iv: –y + 2/3, x – y + 1/3, z + 1/3)
with K···O distances in the range o2.65–3.01 Å. O6 and
O1w serve as bridges between the potassium ions and the
K···K distance is 4.046 Å. Altogether, the complicated
supramolecular structure of K[CuL1]·H2O is stabilized by
interpenetrating ionic and coordination interactions as well
as a strong hydrogen bond network. In the polymer there
are hexagonal channels with a diameter of approximately
8.5 Å (Figure S2, Supporting Information), which are filled
with disordered water molecules.
0.91 (0.08)
0.77
2.53
9.00
6.53
8.93 (0.02)
9.97 (0.01)
9.94 (0.01)
10.17 (0.01) 5.52 (0.01)
9.79 (0.01)
10.01
9.44 (0.01)
8.87 (0.01)
9.27
6.80 (0.03)
5.62 (0.02)
5.68 (0.01)
2.65 (0.05)
2.42 (0.02)
2.23 (0.01)
2.49 (0.02)
2.68 (0.03)
2.68
2.54 (0.01)
2.49 (0.01)
2.84
5.67 (0.02)
6.50
6.56 (0.01)
6.41 (0.01)
6.56
[a] 1.0  Me4NCl. [b] 1.0  KNO3. [c] 0.1  KNO3.[24] [d] 1.0 
NaCl. [e] 0.16  NaCl.[22] [f] Redetermined in the present study (I
= 1.0  Me4NCl).
Eur. J. Inorg. Chem. 2007, 701–713
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G. Tircsó, A. Bényei, R. Király, I. Lázár, R. Pál, E. Brücher
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A comparison of the data in Table 3 reveals that the dif-
In Figure 4, a decrease of the pH from about 12 to 8
H
ference between the protonation constants logK1 and leads to a significant change in the chemical shifts
H
logK2 is lower for the symmetric ligands L0, L1, and L4 of the glycinate and phosphinate methylene protons
than for asymmetric L2 and L3, which show a larger differ- (-CH2NHCH2COOH), which indicates the protonation of
ence in the basicity of the nitrogen atoms. Parallel with this the glycinate nitrogen of L3. In the pH range 4–7 a strong
finding, the question arises regarding the protonation order change can be observed in the chemical shifts of the imda
of the nitrogens in the asymmetric ligands L2 and L3. The and phosphinate methylene protons, which shows that the
1
protonation scheme of L2 and L3 was determined by H second proton is attached to the nitrogen of the imda group.
1
NMR titrations in the pH range of about 1–12. The H At a pH of around 3.5 the signal of the glycinate methylene
NMR titration curves of ligands L2 and L3 are shown in protons starts to move to higher frequencies due to the pro-
Figures 3 and 4, respectively. In Figure 3, the chemical shift tonation of the glycinate carboxylate.
H
of the -CH2NH2 methylene protons (the center of the doub-
The protonation constants logK1 determined in KNO3
let) increases with a decrease of pH from about 12 to 8.5, solution are generally lower than those obtained in Me4NCl
H
while the signals of both the phosphinate and acetate meth- solution, and the logK1 value of L4 determined in NaCl
ylene protons [-CH2N(CH2COO–)2] are practically not solution is even lower. These results indicate that at higher
shifted. This finding indicates that the first proton is at- pH values the ligands form very poorly stable complexes
tached to the NH2 group of L2. In the pH range of about with K+ and somewhat more stable complexes with Na+
4 to 7 the signals of both the phosphinate and acetate meth- ions.
ylene protons [-CH2N(CH2COO–)2] are strongly shifted to
higher frequencies due to the protonation of the imda nitro-
Stability Constants of the Complexes
gen. A further decrease of pH below about 3 results in a
shift of the signal of the acetate methylene protons to higher
frequencies, which indicates the protonation of the carbox-
ylate groups.
To characterize the complexation properties of L0, L1,
L2, L3, and L4 the formation equilibria between these li-
gands and the metal ions Mg2+, Ca2+, Ni2+, Cu2+, Zn2+
,
Cd2+, and Pb2+ were studied by pH potentiometry. The ti-
trations were performed at three or four different metal-to-
ligand concentration ratios. The number of data points for
the calculations were usually between 250 and 500. Some
typical titration curves are presented in Figure 5, which
shows the formation of complexes with L1. The equilibrium
models used for the calculation of the stability constants
were selected on the basis of the properties of the metal ions
and the ligands by taking into consideration the quality and
number of the donor atoms. The results of the EPR study
of the Cu2+ complexes with L0, L1, and L4 were also used
to assume the species formed in these systems.[23] For char-
acterizing the solution equilibria, the formation of the fol-
lowing complexes was considered: MLH2, MLH, ML,
M(OH)L, ML2H, ML2, and M2L. The stability constants
that describe the equilibria were defined as follows (the
charges of the species have been omitted for simplicity):
Figure 3. 1H NMR titration curves of ligand L2 (CL = 0.05 ,
25 °C) showing the change in the chemical shifts of the protons
indicated in the figure.
Figure 4. 1H NMR titration curves of ligand L3 (CL = 0.05 ,
25 °C) showing the change in the chemical shifts of the protons
indicated in the figure.
Figure 5. Titration curves of a 5ϫ10–3  solution of L1 in the ab-
sence of metal ions (1) and in the presence of one equivalent of
Ca2+ (2), Pb2+ (3), Cd2+ (4), Zn2+ (5), and Cu2+ (6).
706
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Eur. J. Inorg. Chem. 2007, 701–713

Acetate Derivatives of Bis(aminomethyl)phosphinic Acid
FULL PAPER
Table 4. Stability constants of the complexes formed between L0
and Ni2+, Cu2+, Zn2+ (25 °C, 1.0  Me4NCl), Cd2+, and Pb2+
(25 °C, 1.0  KNO3).
H
H
logKML
logKML
logKML
logKML
2
2
Ni2+
5.63 (0.01) 6.12 (0.06) 3.99 (0.03)
7.46 (0.05)
–
6.59
6.74
7.95 (0.05)
–
Ni2+[a] 5.58
Cu2+[b] 8.30
Cu2+[a] 7.64
5.4
5.01
5.07
3.83
6.35
5.41
Zn2+ 4.28 (0.02) 6.59 (0.04) 2.97 (0.02)
Zn2+[a] 4.12
Cd2+ 4.25 (0.04) 7.52 (0.02) 3.73 (0.02)
Pb2+
4.20 (0.04) 7.46 (0.03) 3.01 (0.04)
6.5
3.41
7.79 (0.03)
8.02 (0.08)
[a] I = 0.1  KNO3.[24] [b] I = 1.0  Me4NCl.[23]
The KMLH and KML H protonation constants of the com-
The equilibrium constants βpqr = [MpHqLr]/[M]p[H]q[L]r
were calculated with the program PSEQUAD.[37] Tables 4,
5, 6, and 7 present the stepwise stability constants related
to the formation of ML, ML2 and M2L complexes as calcu-
lated from the βpqr values. We also calculated the proton-
ation constants of the complexes, KMLH, KMHLH, and
2
plexes are relatively large (Table 4), which suggests that the
protonation occurs at one of the two NH2 groups while the
ligand L0 is coordinated only through its other NH2 group.
The negatively charged phosphinate group may contribute
to the stability of the protonated complex.
H
KML because these values give some information about
Complexes of L1 and L2
the s2ite of protonation (nitrogen or carboxylate oxygen). By
fitting the titration data to the assumed equilibrium model
The ligands L1 and L2 possess two amine nitrogens, two
we obtained the equilibrium constants βpqr and also the carboxylate oxygens, and one phosphinate oxygen as donor
standard deviation values (given in parentheses in Tables 4– atoms. The structure of L1 and the asymmetric L2 resemble
7).
the structure of ethylenediamine-N,NЈ-diacetate (L6) and
ethylenediamine-N,N-diacetate (L7), with the difference that
the latter do not contain a phosphinate moiety. For com-
Complexes of L0
The formation of complexes between the L0 and Mg2+ parison, therefore, the diacetate derivatives of 1,3-diami-
or Ca2+ could not be detected by pH potentiometry up to nopropane would be more suitable, but unfortunately these
a pH of around 10. This is probably due to the fact that ligands have not been studied to date. The titration data
the nitrogens of the two NH2 groups do not coordinate to obtained for L1 in the presence of Mg2+, Ca2+, Ni2+, and
Mg2+ or Ca2+ and the binding of the phosphinate oxygen Cu2+ can be interpreted by assuming the formation of the
is very weak. The titration curves obtained in the presence species ML only, while Zn2+, Cd2+, and Pb2+ form hydroxo
of Ni2+, Cu2+, Zn2+, Cd2+, and Pb2+ can be interpreted by complexes M(OH)L and very weak ML2 complexes as well
assuming the formation of complexes ML and ML2 and the at a pH above 9. The stability constants are shown in
protonated species MLH and ML2H. The possible forma- Table 5. Ligand L1 has been prepared earlier and the sta-
tion of hydroxo complexes was taken into consideration bility constant of its Ni2+ complex, logKNiL = 12.24, agrees
when calculating the stability constants by using the equi- well with the value found by us (Table 5).[17] The stability
librium constants known for the species M(OH)+.[38] The constants of the ML complexes formed with L1 are some-
stability constants of the complexes of Ni2+, Cu2+, and what lower than those formed with L6 (the logKML values
Zn2+ determined by Kubicek et al. and in our laboratory for the complexes of L6 formed with Mg2+, Ni2+, Zn2+, and
ˇ
are similar (Table 4). The logKML and logKML values are Cd2+ are 3.95, 13.65, 11.22, and 8.99, respectively).[36] The
2
lower than those of the complexes formed with 1,3-diami- lower logKML values of the complexes can be interpreted
nopropane (L5). The stability constants (logK) of the spe- as being due to the lower protonation constants of the li-
cies ML, ML2, and ML3 formed, for example, between Ni2+ gand L1 (the protonation constants for L6 are 9.69, 6.72,
and Cd2+ and L5 are 6.47, 4.43, and 1.2 and 4.50, 2.70, and 2.37, and 1.66).[36] Considering these findings, it is surpris-
0.8, respectively.[36] The lower stabilities of the complexes of ing that the stability constant logKML of the Cu2+ complex
L0 indicate that the phosphinate group does not play a role of L1 is higher than that of CuL6 (logKCuL = 16.2).[36] This
in the complexation. It is more probable that L0 is coordi- unexpected result can not be interpreted by assuming par-
nated to the two N donor atoms to form a six-membered ticipation of the phosphinate group in the complexation.
chelate ring.[24] However, the ligand L5 forms ML3 species It is more likely that the formation of two five-membered
and the absence of the formation of 1:3 complexes with L0 (ϾNCH2COO–) and
a
six-membered (ϾNCH2PO2–
shows that some weak interaction may exist between the CH2NϽ) chelate ring around the Cu2+ ion leads to a more
metal ion and the phosphinate group and the steric require- stable square-planar arrangement than the coordination of
ment of the L0 is larger than that of L5, which hinders the L6, which involves the formation of three five-membered
coordination of a third L0 ligand.
chelate rings. Similar results are known for the formation
Eur. J. Inorg. Chem. 2007, 701–713
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707

G. Tircsó, A. Bényei, R. Király, I. Lázár, R. Pál, E. Brücher
FULL PAPER
Table 5. Stability constants of the complexes formed between the ligands L1 and L2 and Mg2+, Ca2+, Cu2+, Zn2+ (25 °C, 1.0  Me4NCl),
Cd2+, and Pb2+ (25 °C, 0.1  KNO3).
L1
logKM(OH)L
L2
logKM(OH)L
M2+
logKML
logKML
logKML
logKML
2
H
Mg2+
Ca2+
Ni2+
2.50 (0.05)
2.61 (0.02)
12.22 (0.03)
17.40[a]
–
–
–
–
3.98 (0.06)
4.62 (0.04)
12.89 (0.05)
13.76 (0.07)
10.37 (0.04)
9.00 (0.04)
9.59 (0.03)
8.44 (0.05)
8.00 (0.03)
4.44 (0.09)
5.21 (0.01)
5.80 (0.01)
6.50 (0.03)
7.32 (0.02)
–
–
–
3.00 (0.07)
2.69 (0.08)
2.80 (0.08)
–
Cu2+
Zn2+[b]
–9.63 (0.07)
–10.80 (0.04)
–10.51 (0.05)
–11.27 (0.03)
9.82 (0.01)
–10.27 (0.02)
–11.40 (0.05)
–10.87 (0.07)
–
Cd2+[b,c] 7.82 (0.01)
3.61 (0.06)
2.87 (0.05)
Pb2+[b,c]
8.19 (0.03)
[a] Ref.[23] [b] The stability constants of ML2 complexes formed with L1 are as follows: logK
= 1.94 (0.06), logKCdL = 2.47 (0.05),
2
ZnL2
logKPbL = 2.95 (0.04). [c] The studies with Cd2+ and Pb2+ were performed in 1.0  KNO3.
2
of Cu2+ complexes with N,NЈ-bis(2-aminoethyl)dimethyl- one phosphinate oxygen donor atoms, the asymmetric L3
enediamine (logKCuL = 23.9) and triethylenetetramine contains only three carboxylate groups. Because of its hep-
(logKCuL = 20.1).[36]
tadentate nature, L4 does not form ML2 complexes, and
The structure and donor atoms of ligand L1 and those the ML2 species formed with hexadentate L3 have very low
of bis(N-methylsarcosinato)phosphinic acid, which was syn- stability (Cu2+ does not even form such a complex). The
thesized previously in our laboratory, are similar, although L3 ligands in the ML2 complexes are probably coordinated
the stability constants of the complexes formed with L1 are through their imda groups and the coordination of two
higher.[20,21] This difference is probably a result of the steric imda groups is more favorable than formation of the ML
hindrance caused by the two methyl groups attached to the complex.
The titration data obtained for the ligand L3 in the pres-
ence of metal ions can be interpreted by the formation of
the complexes MLH, ML, M(OH)L, ML2, and ML2H. The
calculated stability constants are presented in Table 6. The
logKML values are significantly lower than those of the
hexadentate edta (ethylenediamine-N,N,NЈ,NЈ-tetraacetate).
The only exception is CuL3, whose stability constant is sim-
ilar to that of Cu(edta)2– (logKCuL = 18.80).[36]
The logKML values of the complexes CuL3 and CuL1 are
practically identical, which suggests that L3 is coordinated
to Cu2+ through two nitrogen and two carboxylate oxygen
donor atoms and that the third carboxylate (and phosphin-
ate) group does not participate in the complexation. The
protonation constant of the complex CuL3 is very low,
which indicates protonation of the free carboxylate. The
protonation constants of the other complexes of L3 are
higher (particularly those of MgL3 and CaL3) as in these
species the nitrogen atom of the glycinate is most likely pro-
tonated.
In an earlier study of complexes of the ligand L4 with
some divalent metal ions the formation of ML and MLH
species was assumed.[21] The results of a recent, more de-
tailed pH potentiometric titration study were interpreted by
the formation of ML, MLH, MLH2, and M2L species. The
number of data points used for the calculations, which were
obtained at three or four metal-to-ligand ratios, are given
in parenthesis for the respective metals as follows: Mg2+
(338), Ca2+ (355), Ni2+ (347), Cu2+ (665), Zn2+ (513), Cd2+
(476), and Pb2+ (493). The calculated stability constants as
well as the data reported for the analogous propylenediam-
ine-N,N,NЈ,NЈ-tetraacetate (L8) are shown in Table 7. We
have also determined the protonation constants of L8 and
found that at 25 °C in 1.0  KCl the logKiH values are 10.50
nitrogen donor atoms of the bis(N-methylsarcosinato)phos-
phinate ligand.
The titration data obtained for L2 in the presence of the
metal ions were interpreted by assuming the formation of
the species ML, MLH, ML2, and M(OH)L. The stability
constants of ML complexes are generally higher than those
of the complexes of L1. The only exception is complex
CuL2, which exhibits much lower stability than CuL1. This
difference in the behavior of Cu2+ complexes is understand-
able if we take into account the propensity Cu2+ to form
square-planar complexes. The other metal ions studied pre-
fer octahedral (or some other) geometry. Due to its linear
structure, L1 forms a high stability square-planar complex
with Cu2+. The ligand L2 can not occupy four coordination
sites in one plane if the phosphinate is not involved in com-
plexation. For metal ions other than Cu2+, the coordination
of the two nitrogen and two carboxylate oxygen donor
atoms of L2 is possible at four apices of an octahedron,
which results in relatively high logKML values. The fourth
coordination site of CuL2 in the equatorial position is prob-
ably occupied by a water molecule as, in contrast to CuL1,
CuL2 starts to hydrolyze at about pH 8.
All the metal ions except Cu2+ and Zn2+ form ML2 com-
plexes with L2. The logKML values are much lower than
2
those for ligand L7 (the logKML values for the ML2 com-
2
plexes of Ni2+ and Cd2+ are 5.91 and 6.01, respectively).[36]
The low logKML values indicate that the first ligand prob-
ably coordinates 2in the equatorial plane and hinders the co-
ordination of the second ligand. As a result, the second
ligand is coordinated through only two donor atoms for
steric reasons.
Complexes of L3 and L4
Ligands L3 and L4 are structurally similar. While the (0.03), 8.17 (0.04), 2.78 (0.05), and 1.96 (0.05). These
symmetric L4 possesses two nitrogen, four carboxylate, and logKiH values are significantly higher than those of L4
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Eur. J. Inorg. Chem. 2007, 701–713

Acetate Derivatives of Bis(aminomethyl)phosphinic Acid
FULL PAPER
Table 6. Stability constants of the complexes formed between L3 and Mg2+, Ca2+, Cu2+, Zn2+ (25 °C, 1.0  Me4NCl), Cd2+, and Pb2+
(25 °C, 0.1  KNO3).
H
H
logKML
logKML
logKM(OH)L
logKML
logKML
2
2
Mg2+
Ca2+
Cu2+
Zn2+
Cd2+
Pb2+
4.83 (0.04)
5.35 (0.04)
18.32 (0.25)
12.66 (0.01)
10.04 (0.03)
10.34 (0.03)
7.40 (0.05)
7.66 (0.03)
1.75 (0.09)
3.47 (0.01)
5.11 (0.03)
5.60 (0.02)
–
–
–
3.63 (0.04)
3.80 (0.05)
–
1.90 (0.16)
2.44 (0.09)
2.77 (0.06)
8.97 (0.07)
9.02 (0.08)
–
–
–
–
–12.16 (0.04)
–11.47 (0.04)
–10.92 (0.04)
Table 7. Stability constants of the complexes of the ligands L4 and L8[a] formed with Mg2+, Ca2+, Ni2+, Cu2+, Zn2+, Cd2+, and Pb2+. The
data for L4 were obtained at 25 °C, in 1.0  Me4NCl[b] and for L8 at 20 °C, in 0.1  Me4NCl.
L4
logKML
L8[a]
logKML
H
H
H
logKML
logKMLH
logKM L
logKML
2
Mg2+
Ca2+
7.65 (0.03)
7.66 (0.03)
17.77 (0.05)
19.30
15.94 (0.01)
13.07 (0.01)
11.29 (0.04)
6.42 (0.04)
6.41 (0.02)
2.64 (0.07)
2.80
2.14 (0.01)
3.16 (0.01)
5.66 (0.05)
4.28 (0.02)
4.28 (0.02)
–
3.23 (0.03)
3.23 (0.03)
3.30 (0.09)
3.70
1.61 (0.05)
3.00 (0.02)
6.31 (0.04)
6.21
7.28
18.15
18.92
15.26
13.90
13.78
7.30
6.34
2.20
2.20
2.50
3.06
3.86
Ni2+
Cu2+ [b]
Zn2+
–
1.96 (0.02)
2.53 (0.02)
2.26 (0.09)
Cd2+ [c]
Pb2+ [c]
[a] Propylenediamine-N,N,NЈ,NЈ-tetraacetate.[36] [b] Ref.[23] [c] The studies with Cd2+ and Pb2+ were performed in 1.0  KNO3.
(Table 3). In spite of the lower protonation constants, the
stability constants of the complexes of L4 are very similar
or higher than those of L8. The phosphinate oxygen is not
coordinated directly to the metal ion and the high stability
constants probably result from the higher negative charge
of the ligand and the two coordinated imda groups, which
pull the phosphinate closer to the metal ion. However, the
complexes of smaller and larger metal ions (Ni2+, Cu2+, and
Zn2+ vs. Cd2+and Pb2+) behave differently, which is particu-
larly evident when the stability constants are compared with
those of the edta complexes. The logKML values for the
edta complexes of Zn2+ and Pb2+ are 16.50 and 18.04,
respectively, while ligand L4 shows an unexpectedly high
Figure 6. Titration curves of 5ϫ10–3  solutions of L4 in the pres-
ence of one (1) and two equivalents (2) of Pb2+ ions (I = 1.0 
KNO3, T = 25 °C).
selectivity for Zn2+ over Pb2+ (logKML values of 15.94 and
11.29, respectively; Table 7). These results can be interpre-
ted according to Hancock, who found that larger metal ions
prefer five-membered chelate rings while smaller metal ions
form high stability complexes with both five- and six-mem-
bered chelate rings.[39] In the dinuclear complexes formed
1H NMR Spectra of the Zn2+ Complexes
The formation of complexes between Zn2+ and the li-
with L4 both metal ions are attached to an iminodiacetate gands L1, L2, L3, and L4 results in a significant change in
group of the ligand, as was found for the Cu2+ complexes the H NMR spectra. The doublet signals of the phosphin-
1
–
by EPR spectroscopy.[23] The formation of dinuclear com- ate (–[CH2]2PO2 ) methylene protons are shifted slightly to
plexes was also unambiguously detected by pH potentiome- low field but their multiplicity does not change. The shift
try. Typical titration curves obtained in the presence of one of the signals of the methylene protons is due to the induc-
and two equivalents of Pb2+ are shown in Figure 6. Because tive effect of the Zn2+ ion. Upon formation of ZnL1 the
of the strong competition between protons and Pb2+ in the signal of the glycinate methylene protons is shifted to δ =
presence of one extra equivalent of Pb2+, the buffer region 3.48 ppm but is not split. With a decrease of temperature
observed at a 1:1 metal-to-ligand ratio disappears com- from 50 °C to close to 0 °C the signals broaden signifi-
pletely, which indicates the formation of dinuclear species cantly, however an AB multiplet pattern could not be ob-
H
in solution. The KML protonation constants imply the served even at this temperatures (Figure S8). Similarly, the
protonation of the acetate group in the complexes of Ni2+
,
signal of the glycinate methylene protons for ZnL3 is not
Cu2+, Zn2+, and Cd2+ while the protonation is more prob- split by the formation of the complex and it appears at
able at a nitrogen in the complexes of Mg2+, Ca2+, and about δ = 3.30 ppm (pH 7.05) as a broad signal (Figure 8).
Pb2+
.
The shift of the signals for the acetate methylene protons
Eur. J. Inorg. Chem. 2007, 701–713
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709

G. Tircsó, A. Bényei, R. Király, I. Lázár, R. Pál, E. Brücher
FULL PAPER
2
of the iminodiacetate groups are usually larger and often tered at δ = 2.95 and 2.93 ppm (2JP,H = 12.6 and JP,H
=
appear in the form of AB multiplets (Figures 7 and 8). The 13.3 Hz). For ZnL4 the imda methylene protons appear as
formation of an AB multiplet indicates the inequivalence of an AB multiplet (2JH,H = 17.5 Hz), which shows the rigid
the acetate methylene protons of the imda group, which is structure of the complex (Figure S9). These carboxymethyl
the result of the relatively long lifetime of the Zn2+–N bond groups may occupy equivalent positions on the coordina-
on the NMR timescale.[40] The chemical shifts of the non- tion polyhedron around Zn2+. In summary, we can state
equivalent A and B protons of ZnL2 at pH 7.02 (Figure 7) that in complexes ZnL2, ZnL3, and ZnL4 the Zn2+–N bond
are δ = 3.62 and 3.23 ppm, respectively. The exceptionally of the coordinated imda fragment has a long lifetime while
large H–C–H geminal coupling constant between these pro- the Zn2+–N bonds formed by the coordination of the
tons (2JH,H = 17.3 Hz) suggests a dihedral angle of about -NHCH2COO– group in ZnL1 and ZnL3 and the -CH2NH2
180° for the coordinated acetate arms (positions of the CH2 group in ZnL2 appear to be more labile. These findings
H atoms towards the pz orbital of the carbon atom of demonstrate that the lifetime of the Zn2+–N bond is long
COO–).[41] The signals of the phosphinate methylene pro- on the NMR timescale as the coordination of the two car-
tons give a “pseudo-triplet” consisting of two overlapping boxylate groups keeps the N atom in the vicinity of the
doublets centered at δ = 2.99 and 2.96 ppm (2JP,H = 8.6 and Zn2+ ion.
2JP,H = 11.5 Hz). Since these signals are doublets due to
coupling with phosphorus, the value of the geminal coup-
ling constants for the CH2 protons (2JH,H) can not be deter-
mined from the spectra (the values appear to be less than
Conclusions
0.8 Hz), which indicates a very weak interaction between
A new synthetic method has been developed that starts
the phosphinate oxygen and Zn2+ in these complexes (pre- from inexpensive materials and gives reasonable yields of
1
sumably of an electrostatic nature). Figure 8 shows the H bis(aminomethyl)phosphinic acid as well as its derivatives
NMR spectrum of ZnL3 recorded at pH 7.05. The AB mul- containing the phosphinate group in a linker position. In
tiplet pattern of the iminodiacetate methylene protons ap- addition, two consecutive Mannich reactions afford asym-
pears at δ = 3.57 and 3.19 ppm (the geminal coupling con- metric bis(aminomethyl)phosphinic acids. These procedures
2
stant is JH,H = 17.3 Hz), and the broad singlet at δ = can easily be scaled up and do not require inert atmosphere
3.30 ppm is due to the glycinate methylene protons, while techniques. This synthetic method will likely be applicable
the doublets of the phosphinate methylene protons are cen- to the synthesis of macrocyclic ligands that incorporate a
bis(aminomethyl)phosphinic acid moiety in the macrocycle.
The basicities of the nitrogen atoms of the symmetric and
asymmetric diacetate (L1 and L2) and tri- (L3) and tetraace-
tate (L4) derivatives of bis(aminomethyl)phosphinic acid
(L0) are lower than those of the analogous diaminopolycar-
boxylates mainly due to the electron-withdrawing effect of
the phosphinate group. For a given ligand, the basicity of
the nitrogen atoms decreases in the order primary Ͼ sec-
ondary Ͼ tertiary.
The stability constant of complexes formed between L0,
L1, L2, L3, and L4 and the metal ions Mg2+, Ca2+, Ni2+
,
Cu2+, Zn2+, Cd2+, and Pb2+ increase with an increasing
number of carboxylate groups of the ligands. The com-
plexes formed with ligands L0, L1, L2, and L3 generally have
lower stability constants than those of the analogous diami-
nopolycarboxylates, which indicates the unimportant role
of the phosphinate group in the complexation. On the other
hand, the presence of the phosphinate group has a signifi-
cant effect on the complexation properties of L4. In spite of
the lower basicities of the two nitrogen atoms of L4, it forms
complexes of similar or higher stability with the smaller
metal ions than the analogous 1,3-diaminopropane-
N,N,NЈ,NЈЈ-tetraacetate (L8). L4 also shows an unusually
high selectivity for Zn2+ over Pb2+, unlike edta or L8. Its
stability constants are higher probably because of the higher
charge of the ligand, and there is a strong electrostatic inter-
action between the phosphinate and the metal ion due to
the coordination of both imda groups. Furthermore, L4
shows a strong propensity for the formation of dinuclear
M2L complexes, which indicates that in the presence of the
Figure 7. 1H NMR spectrum of a 0.05  ZnL2 solution at 25 °C
(pH 7.02).
Figure 8. 1H NMR spectrum of a 0.05  ZnL3 solution at 25 °C
(pH 7.05).
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Eur. J. Inorg. Chem. 2007, 701–713

Acetate Derivatives of Bis(aminomethyl)phosphinic Acid
FULL PAPER
phosphinate group the two imda groups behave more inde- Table 8. X-ray crystallographic data and structure refinement for
[H5L3]Cl and [K(CuL1)]·H2O.
[H5L3]Cl
pendently than in the case of edta or L8.
Of the two diacetate derivatives the asymmetric L2 forms
complexes of higher stability with the metal ions that prefer
octahedral coordination. However, the metal ions that pre-
K[CuL1]·H2O
Chemical formula
Molecular weight
C8H16ClN2O8P
334.65
colorless block
C6H12CuKN2O7P
357.79
blue block
fer square-planar coordination, like Cu2+, form more stable Crystal color and habit
complexes with the symmetric ligand L1. The equatorial co-
Crystal size [mm]
0.45ϫ0.4ϫ0.36 0.55ϫ0.35ϫ0.27
Crystal system
ordination of L1 to Cu2+ has been confirmed by X-ray crys-
Space group
orthorhombic
Pn21a (no. 33)
7.877(3)
13.564(3)
13.837(5)
90.00
trigonal
¯
R3 (no. 148)
tallography in the solid state for K[CuL1]·H2O, which has
a [Å]
28.477(2)
28.477(2)
8.681(2)
90.00
a polymer structure with hexagonal channels.
b [Å]
c [Å]
α [°]
The ligands L2 and L3 form ML and ML2 complexes but
the stability constants of the ML2 species are relatively low,
probably due to the larger steric requirement of the phos-
phinate-containing ligands.
β [°]
90.00
90.00
1478.4(8)
4
90.00
γ [°]
120.00
6096.6(15)
18
293
1.754
2.062
3257
52
–35 Յ h Յ 30
–15 Յ k Յ 35
–10 Յ l Յ 5
4275
V [Å3]
In the 1H NMR spectra of the complexes of Zn2+ formed
with L1, L2, L3, and L4 the acetate methylene protons of
the coordinated imda groups appear as an AB multiplet,
thus indicating the long lifetime of the Zn2+–N bond on the
NMR timescale, while the signal of the glycinate methylene
protons is a singlet.
Z
Temperature [K]
Dcalcd. [gcm–3]
µ [mm–1]
F(000)
2θmax [°]
Index ranges
293
1.504
0.403
696
50.4
–4 Յ h Յ 9
–2 Յ k Յ 15
0 Յ l Յ 15
1391
Reflections collected
Unique reflections with I
Ͼ 2σ(I)
Experimental Section
1244
1731
Synthesis of the Ligands: All reagents and solvents used in this pa-
per were commercially available and used without further purifica-
tion, unless noted otherwise. The synthesis of ligands L0, L1, L2,
and L3 is outlined in Schemes 1 and 2. Ligand L4 was prepared
following a previously published procedure.[20] A detailed descrip-
tion of the synthetic procedures for compounds 1–10 is included in
the Supporting Information (SI). The purity of the ligands was
controlled by multinuclear (1H, 13C, and 31P) NMR spectroscopy;
the spectra obtained together with the results of pH potentiometric
studies indicated the suitable purity of the ligands (higher than
99%).
Completeness of data
Decay [%]
Parameters
97.5
2
181
95.4
0
169
Refinement method
Full-matrix least-squares on F2
0.053
0.154
1.292
R[a]
0.057
0.193
1.082
0.994/–0.924
Rw (all data)[b]
GOF on F2
Largest diff. peak/hole
0.583/–0.587
[eÅ–3]
[a] R = ∑|Fo – Fc|/∑Fo. [b] Rw = {∑[w(Fo – Fc ) ]/∑[w(Fo2)2]}1/2
,
2
2 2
2
2
2
where w = 1/[σ2{Fo = +(aP)2 + bP}], P = (Fo + Fc )/3; a and b
are given in the Supporting Information.
X-ray Diffraction Studies: Large crystals of approx.
1 cmϫ5 mmϫ3 mm were obtained from saturated solution after
the purification of L3. Equivalent amounts (0.3 mmol) of H3L1 and
CuCl2 stock solutions were mixed and the pH of the mixture was
increased to about pH 7.5 by addition of KOH solution. The solu-
tion was evaporated to dryness and a weighed amount (0.1 mmol)
of the dried complex was redissolved in doubly distilled water
(0.5 mL) and placed into a narrow tube. Anhydrous ethanol was
carefully layered on the aqueous phase and the tube was placed in
a refrigerator at around 4 °C. Navy blue crystals suitable for X-ray
crystallography grew in three weeks.
CCDC-616444 (for [H5L3]Cl) and -616445 (for K[CuL1]·H2O) con-
tain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Materials and Preparation of Solutions: Stock solutions of MgCl2,
CaCl2, NiCl2, CuCl2, ZnCl2, Cd(NO3)2, Pb(NO3)2, Me4NOH, and
KOH were prepared with the highest analytical grade reagents. The
concentrations of the metal-ion solutions were determined by com-
plexometric titration with standardized Na2H2edta solution using
eriochrome black T, murexide or xylenol orange indicator. Aque-
ous solutions of the ligands were prepared by weight and the con-
centrations were determined by pH potentiometric titrations.
X-ray quality crystals of [H5L3]Cl and K[CuL1]·H2O were mounted
on a glass fiber using epoxy resin. Data were collected at 293(1) K
with an Enraf Nonius MACH3 diffractometer using monochro-
mated Mo-Kα radiation (λ = 0.71073 Å) in the ω–2θ mode. The
absorption correction was made using psi scans. The structure was
solved by direct methods with the SIR-92 software and refined on
F2 by full-matrix least-squares methods with the program SHELX-
97.[42,43] All non-hydrogen atoms were refined anisotropically. Hy-
drogen atoms were included using a riding model. Some of the
water hydrogen atoms were found in the difference electron density
map while others were placed in calculated positions for strong
hydrogen bonds. For the final refinement the O–H bond lengths
were restrained at 0.85 Å but otherwise the coordinates of O–H
hydrogen atoms were refined. Publication material was prepared
with the WINGX-97 suite.[44] Some other details of data collection
and structure determination are shown in Table 8.
Equilibrium Studies: The protonation constants of the ligands and
stability constants of complexes were determined by pH potentio-
metric titration in vessels thermostatted at 25 °C. The ionic
strength of the solutions was kept constant at 1.0  Me4NCl or, in
the case of Cd2+ and Pb2+, at 1.0  KNO3. Titration experiments
were performed at two to four different metal-to-ligand ratios (1:1,
1:2, 1:3, and 2:1) by varying the ligand concentration in the range
0.0025–0.006 . The titrations were performed with a Radiometer
pHM 85 pH-meter equipped with pHG 211 glass and REF 201
Ag/AgCl electrodes and a Radiometer ABU 80 autoburette. The
Eur. J. Inorg. Chem. 2007, 701–713
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
711

G. Tircsó, A. Bényei, R. Király, I. Lázár, R. Pál, E. Brücher
FULL PAPER
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Acknowledgments
This work was supported by the Hungarian Science Foundation
(OTKA T-038364 and OTKA T-043365) and performed within the
framework of the EU COST Action D18. I. L. is grateful to the
Hungarian Academy of Sciences for an István Széchenyi Fellowhip
and A. B. is grateful for an Öveges József Fellowship from the
Hungarian Research and Technology Foundation. The helpful dis-
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2007, 701–713

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Received: September 24, 2006
Published Online: January 4, 2007
Eur. J. Inorg. Chem. 2007, 701–713
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
713