Binding ability of aminophosphonates containing imidazole and pyridine as additional donor systems

Article abstract of DOI:10.1016/j.ica.2011.09.024

The paper describes solution studies of Cu(II) and Ni(II) complexes of new N-substituted imidazole-2-yl(amino)methylphosphonates. The presence of the 2-imidazole ring makes studied phosphonates very efficient ligands, with nickel(II) ions chelation much more effective than by the previously designed 4-imidazole analogs. Introduction of ortho-pyridine as additional donor in the side chain further increases the binding ability. The effectiveness of this compound is due to chelation of metal ions through imidazol, imino and pyridine nitrogen donors.

Full text of DOI:10.1016/j.ica.2011.09.024

Inorganica Chimica Acta 380 (2012) 223–229
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Inorganica Chimica Acta
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Binding ability of aminophosphonates containing imidazole and pyridine
as additional donor systems
Monika Pyrkosz a, Waldemar Goldeman b, Elzbieta Gumienna-Kontecka a,
⇑
a Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland
b Department of Organic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 24 September 2011
The paper describes solution studies of Cu(II) and Ni(II) complexes of new N-substituted imidazole-2-
yl(amino)methylphosphonates. The presence of the 2-imidazole ring makes studied phosphonates very
efficient ligands, with nickel(II) ions chelation much more effective than by the previously designed 4-
imidazole analogs. Introduction of ortho-pyridine as additional donor in the side chain further increases
the binding ability. The effectiveness of this compound is due to chelation of metal ions through imidazol,
imino and pyridine nitrogen donors.
Young Investigator Award Special Issue
Keywords:
Aminomethylphosphonate ligands
Imidazole
Ó 2011 Elsevier B.V. All rights reserved.
Pyridine
Cu(II) and Ni(II) ions
1. Introduction
massive number and diversity of ligands were designed, synthe-
sized and studied. Recent works carried in our group on
Phosphonates have been widely recognized as ligands that are
able to form stable complexes with a wide variety of metal ions
[1]. Their chelating properties were intensively studied with regard
to applications as chelating agents used in analytical chemistry, for
the industrial cleaning, removal of toxic metal ions from environ-
ment or as corrosion inhibitors, to give only few examples. The
beginning of biological career of phosphonates is strongly con-
nected to the discovery in the 1940s of aminophosphonic acids
in living organisms [2]. Later on the potential of phosphonates as
natural phosphate mimics was recognized [3]. The strong struc-
tural relation to natural compounds, together with high stability
and low toxicity, caused their possible activity as antimetabolites
and competitors for various cellular receptors and molecules. Ami-
nophosphonates, for example, are able to recognize the active cen-
ters of enzymes, and by creating appropriate complexes with the
metal ions within perform their inhibition [4–6]. Moreover recent
papers demonstrate that the chemistry of phosphonates and their
complexes show potential power for the design and preparation of
nanomaterials [5]. The phosphonic group can be used as the molec-
ular tool in recognition and sensing of biologically relevant mole-
aminophosphonate ligands showed that introduction of additional
binding groups, like heterocyclic side chains drastically changes
ligands chelating ability [7–10]. We report here an extension of
these studies and present binding ability towards Cu(II) and Ni(II)
of new aminophosphonates bearing imidazole and pyridine as
additional donor groups.
2. Experimental
2.1. Synthesis of ligands
The N-substituted imidazole-2-yl(amino)methylphosphonic
acids (ligands L1–L5, Scheme 1) were prepared by the methodol-
ogy described earlier for the appropriate pyridine [11] and
4(5)-imidazole [12] derivatives. Thus, the ligands were synthe-
sized in reaction of imines (prepared from imidazole-2-carboxal-
dehyde and amines) and tris(trimethylsilyl) phosphite (generated
in situ from triethyl or trimethyl phosphite and bromotrimeth-
ylsilane) to give the silylated intermediates which after treating
with methanol gave the title compounds (Scheme 2) [13].
cules, drug delivery and treatment or as
inorganic and organic part of the bio-device.
a linker between
2.2. Physico-chemical measurements
Stimulated by their applications, and because of the ease of
attaching the phosphonic acid group to the organic moiety, the
Starting materials and solvents: The solution studies were carried
out in bidistilled water. All the chemicals were commercial prod-
ucts of reagent grade and were used without further purification.
Copper(II) solutions were prepared from Cu(ClO4)2Á6H2O (Aldrich)
and nickel(II) solutions from Ni(ClO4)2Á6H2O (Aldrich).
⇑
Corresponding author. Fax: +48 71 3757342.
E-mail address: elzbieta.gumienna-kontecka@chem.uni.wroc.pl(E. Gumienna
-Kontecka).
0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2011.09.024

224
M. Pyrkosz et al. / Inorganica Chimica Acta 380 (2012) 223–229
N
N
the pH range 2.2–11.0) were refined with the SUPERQUAD [15] pro-
gram which uses non-linear least-squares methods [16]. Potentio-
metric data points were weighted by a formula allowing greater pH
errors in the region of an end-point than elsewhere. The weighting
factor Wi is defined as the reciprocal of the estimated variance of
measurements: Wi = 1/r2i = 1/[rE2 + (dE/dV)2rV2] where rE2 and r2V
are the estimated variances of the potential and volume readings,
respectively. The constants were refined by minimizing the error-
square sum, U, of the potentials. The quality of fit was judged by
the values of the sample standard deviation, S, and the goodness
of fit, v2. The scatter of residuals versus pH was reasonably ran-
dom, without any significant systematic trends, thus indicating a
good fit of the experimental data. The successive protonation con-
stants were calculated from the cumulative constants determined
with the program. The uncertainties in the logK values correspond
to the added standard deviations in the cumulative constants. The
distribution curves of the complexes as a function of pH were cal-
culated using the HYSS2006 program [17].
H
N
[L1]2-
[L2]2-
N
H
PO3H2
H
N
N
H
PO3H2
N
[L3]2-
[L4]2-
H
N
N
N
H
PO3H2
N
Additionally, a combined potentiometric and 1H/31P NMR titra-
tions were carried out. 31P NMR spectra were recorded at 25 °C, at
202.4 and 242.9 MHz, respectively, on a Bruker Avance 500 and
Bruker Avance III 600 MHz spectrometers. All measurements were
made in D2O, with concentration of ligands of 3 Â 10À2 M and
(40%) H3PO4 used as an external reference for 31P. Measured pH⁄
was not corrected for the isotopic effect and was adjusted by addi-
tion of concentrated NaOD or DCl solutions.
H
N
N
N
H
PO3H2
N
[L5]2-
N
N
To probe the coordination properties of the new ligands with
Cu(II) and Ni(II), a UV–Vis spectrophotometric titrations in the range
of d–d bands (400–800 nm) were recorded on a Varian CARY 300
spectrophotometer in a Hellma quartz optical cell (1 cm). Electron
paramagnetic resonance spectra were collected on a Bruker ESP
300E spectrometer at X-band frequency (9.4 GHz) at 77 K. EPR spec-
tra were performed in the ethylene glycol–water (1:2 v/v) solution.
The metal ions concentrations were 2 Â 10À3 M and metal-to-ligand
molar ratio varied from 1:1 to 1:4. The spectroscopic parameters
were obtained at the maximum concentration of the particular spe-
cies as indicated by the potentiometric calculations. For Cu(II)/
Ni(II)–L3 systems, the combined potentiometric and UV–Vis titra-
tions were recorded using a Varian CARY 50 UV/Vis spectrophotom-
eter fitted with Varian optical fibers (Technologies, Inc.
908.707.1009, Stainless Steel) and immersion probe made of quartz
suprazil (Varian, Technologies Inc., 973.984.9092, 10 mm path). The
initial pH of 15 mL complex samples was adjusted to be about 2, and
the titration of the solution was then carried out by addition of
known volumes of HClO4 or NaOH. The acid titration was carried
out till the disappearance of the complex band and pH was
calculated from acid concentration. The spectrophotometric data
were analysed with Specfit [18–21] program which adjust the
absorptivities and the stability constants of the species formed at
equilibrium. Specfit uses factor analysis to reduce the absorbance
H
N
N
H
PO3H2
Scheme 1. The chemical structures of studied aminophosponates.
The potentiometric titrations were performed using an auto-
matic titrator system Titrando 809 (Metrohm) with a combined
glass electrode (Mettler Toledo InLab Semi-Micro) filled with 3 M
KCl (Mettler Toledo) in water. The electrode was calibrated daily
in hydrogen ion concentration using HClO4 (Applichem) [14].
Carbonate-free NaOH solution (0.1 M Aldrich) was standardized
by titration with potassium hydrogen phthalate (Fluka, Puriss,
PA). The ionic strength was fixed at I = 0.1 M with NaClO4 (Fluka,
Puriss, PA). The experiments were carried out at constant temper-
ature of 25 0.2 °C. A stream of argon, pre-saturated with water
vapor, was passed over the surface of the solution. The ionic prod-
uct of water for these conditions was 10À13.77 mol2 dmÀ6. All the
titrations were carried out on a 3 mL samples. Metal–ligand system
titrations were performed on solutions of ligand concentrations of
2–4.2 Â 10À3 M and metal-to-ligand molar ratios of 1:1, 1:2, 1:3
and 1:4. The potentiometric data (about 140 points collected over
N
N
CH2Cl2 room temp.24h
+
H2N-R1
O
N
or MeOH 1h reflux
R1
N
H
N
H
N
N
1)P(OAlk)3+5TMSBr
H
N
N
2)MeOH
R1
N
H
R1
N
H
PO3H2
R1=2-PyCH2-, 3-PyCH2-, 1-imidazole(CH2)3-, n-Bu-, PhCH2-
Alk=Et or Me
Scheme 2. Synthesis of N-substituted imidazole-2-yl-(amino)methylphosphonic acids.

M. Pyrkosz et al. / Inorganica Chimica Acta 380 (2012) 223–229
225
Table 1
Protonation (logbH) and stability constants (logb) of copper(II) and nickel(II) complexes with the N-substituted imidazole-2-yl(amino)methylphosphonates L1–L5 in aqueous
solution.a
Assignments
Compounds
L1
L2
8.82(1)
L3
8.41(1)
L4
8.50(1)
L5
8.70(2)
logbH1
log bH2
logbH3
9.21 (9)
14.71 (1)
18.12 (2)
–
14.42(2)
17.39 (3)
–
15.12(2)
19.64 (3)
21.23(4)
14.17(2)
18.92 (3)
20.90 (5)
15.80(2)
21.19(3)
23.95(3)
logbH4
logKH (NH2
)
9.21
5.50
–
–
3.40
–
16.86(2)
8.82
5.60
–
–
2.97
–
16.08(2)
8.41
6.71
–
4.52
1.59
–
–
8.50
5.67
–
4.76
1.98
18.81(5)
–
8.70
7.10
5.39
–
2.76
21.56(10)
–
+
+
+
logKH (NHimid
)
)
logKH (NHimid
logKH (NHPyr
)
+
logKH (PO3HÀ)
logb [CuH2L]2+
logb [CuHL]+
logb [CuL]
19.2(5)
–
–
–
34.4 (5)
28.2 (5)
–
–
–
–
6.2
–
–
–
logb [CuH4L2]2+
logb [CuH3L2]+
logb [CuH2L2]
logb [CuHL2]À
logb [CuL2]2À
logb [CuL2(OH)]3À
pK [CuH4L2]2+
pK [CuH3L2]+
pK [CuH2L2]
–
–
–
–
37.30(7)
33.66(6)
29.30(6)
24.24(7)
17.87(10)
–
44.93(1)
40.78(4)
34.64(6)
27.88(5)
20.57(7)
–
32.32 (3)
26.32(6)
19.01(8)
8.14(12)
–
–
6.00
7.19
10.87
–
31.36 (2)
26.97 (5)
20.41 (9)
9.90(12)
–
–
4.39
6.56
10.51
–
3.64
4.15
4.36
6.14
5.06
6.78
pK [CuHL2]À
6.37
7.31
pK [CuL2]2À
–
–
logb [NiH2L]2+
logb [NiHL]+
logb [NiL]
–
–
22.03(5)
–
15.64(2)
15.76(3)
21.9(4)
logb [NiH4L2]2+
logb [NiH3L2]+
logb [NiH2L2]
logb [NiHL2]À
logb [NiL2]2À
logb [NiL2(OH)]3À
pK [NiH4L2]2+
pK [NiH3L2]+
pK [NiH2L2]À
pK [NiHL2]
–
–
–
–
–
–
–
40.33(3)
–
43.78(2)
40.54(2)
34.56(11)
27.94(9)
20.90(12)
12.66(16)
3.24
5.98
6.62
7.04
8.24
30.22(4)
27.29(3)
19.45(6)
10.98(7)
–
–
2.93
7.84
8.47
28.73 (12)
26.06(5)
19.74(8)
12.12(10)
–
–
2.67
6.32
7.62
31.95(6)
27.41(5)
22.70(6)
15.77(9)
–
–
4.54
5.34
6.93
39.7(3)
35.1(4)
–
–
–
–
4.6
–
pK [NiL2]2À
a
I = 0.1 M (NaClO4), T = 25.0(2) °C. The reported errors on logb are given as 1r.
matrix and to extract the eigen values prior to the multiwavelength
fit of the reduced data set according to the Marquardt algorithm
[22,23].
shows that the shifts of 31P phosphorus reflect protonation process
of almost all groups, especially in L3 (Fig. 1a–c). The shifts of 1H pro-
tons of the pyridine moiety in L4 (Fig. 1f) mirror the protonation of
its own nitrogen (logK ꢀ4.7) and of the phosphonate function (logK
ꢀ2). For the analog with the pyridine in ortho- position, L3, 1H shifts
of the protons from the pyridine moiety, as well as from the imidaz-
ole function, indicate two not well separated logKs: of about 4.5 and
6.5 (Fig. 1e and f). pH⁄ dependent shifts of 1H of imidazole of L1 and
3. Results and discussion
3.1. Protonation constants
L
4 ligands reproduce three steps corresponding to protonation of the
To evaluate the coordination properties of the studied ligands
(Scheme 1) towards metal ions, first it was necessary to determine
their acid-base properties. The fully protonated forms of the
ligands possess four L1–L2 or five L3–L5 dissociable protons, respec-
tively. All studied ligands have one dissociable proton at the imino
nitrogen, one at the imidazole moiety and two at the phosphonic
function. Additional proton in L3–L5 derives from the pyridine or
additional imidazole ring. Under our experimental conditions, pH
imino, imidazole and phosphonate functions (Fig. 1g for L1 and 1i for
L4). Analysis of the last two spectra in addition to 31P–pH⁄ profile
was especially valuable to confirm the difference between the pro-
tonation constant of the phosphonate function (logK = 3.40 for L1
versus 1.98 for L4). Therefore, based on previous examples
[10,12,24,25] and taking into account current pH⁄–NMR study, we
can conclude that for all five ligands, the most basic constant corre-
sponds to the protonation of the nitrogen of the secondary amino
group (Table 1). Substitution of the butyl group (L1, log K ꢀ9.2) by
aromatic ring (L2), pyridine (L3 and L4) or imidazole moiety (L5)
decreases this constant of about 0.4–0.6 log units. This effect comes
from an electron-withdrawing effect of the aromatic ring. The sec-
ond protonation constant, assigned to the imidazole moiety, was
increased from logK ꢀ5.6 for L1, L2, L4 and L5 to logK of 6.71 for L3
due to possible interactions with the pyridine ring. Further constant,
with logK ꢀ3–3.4 for L1 and L2 corresponds to stepwise protonation
of the PO23À group. The possibility of the formation of an intramolec-
ular hydrogen bonding between the 2-imidazole nitrogen and
2–11, we could determine three (H3L+, L1–L2) or four (H4L2+
L3–L5) protonation constants (Table 1).
,
In order to assign the successive protonation constants to par-
ticular protonation sites we have used a combination of potenti-
ometry and NMR spectroscopy, pH⁄–NMR titrations (pH⁄ means
pH not corrected for the isotopic effect). Chosen examples showing
the chemical shifts of particular nuclei (1H or 31P) of ligands L1, L3
and L4 as a function of pH⁄ are shown in Fig. 1. Detailed analysis1
1
The analysis was based on a complete set of 1H/31P shifts as a function of pH⁄,
performed for all ligands (data not shown).

226
M. Pyrkosz et al. / Inorganica Chimica Acta 380 (2012) 223–229
L1
L3
L4
N
N
N
H
H
N
H
N
N
N
N
N
H
N
H
N
H
2-
2-
PO3
PO3
2-
PO3
14.5
14.0
13.5
13.0
12.5
12.0
11.5
11.0
10.5
14
12
10
8
13.0
12.5
12.0
11.5
11.0
10.5
10.0
9.5
6
4
2
9.0
2
4
6
8
10
12
2
4
6
8
10
12
2
4
6
pH
8
10
12
*
*
*
pH
pH
(a)
(b)
(c)
8.55
8.50
8.45
8.40
8.35
8.30
8.25
8.20
8.15
8.10
0.71
0.70
0.69
0.68
0.67
0.66
0.65
0.64
7.8
7.7
7.6
7.5
7.4
7.3
7.2
7.1
2
4
6
8
10
12
2
4
6
8
10
12
2
4
6
8
10
12
*
*
*
pH
pH
pH
(d)
(e)
(f)
7.2
7.1
7.0
6.9
6.8
7.5
7.4
7.3
7.2
7.1
7.0
6.9
6.8
7.3
7.2
7.1
7.0
6.9
6.8
2
4
6
8
10
12
2
4
6
8
10
12
2
4
6
pH
8
10
12
*
*
*
pH
pH
(g)
(h)
(i)
Fig. 1. 31P and 1H NMR titration curves as a function of pH⁄ (pH not corrected for the isotopic effect) performed for L1, L3 and L4 ligands.
phosphonate moiety explains its higher acidity in comparison to
simple monophosphonic acids, e.g. methylphosphonic acid, with
logKHL ꢀ7.5 [1]. Its value was further decreased by interactions with
pyridine moiety in ortho- position (logK = 1.59 for L3). The proton-
ation of the PO3HÀ group occurs much below pH 2 and constants
corresponding to these processes were not determined under our
experimental conditions. The value of protonation constant of the
pyridine nitrogen was 4.52 for 2-Py analog and 4.76 for 3-Py deriv-
ative. Additional imidazole moiety was showing logK typical for this
group (logK = 7.1) [26].
3.2. Cu(II) and Ni(II) complexes
All ligands studied in this work have three major binding sites
centered at the oxygen atom of phosphonic group, imidazole and
amino nitrogen donors. There is also an alternative binding site
at the imidazole nitrogen for L5 and pyridine nitrogen for L3 and
L4, however it might be competitive only in 2-Py analog L3. In 3-
Py derivative this nitrogen is rather not able to bind to metal ion
sitting at the amino-phosphonate binding site of the same ligand
molecule, yet it can become a bridging moiety in the dimeric

M. Pyrkosz et al. / Inorganica Chimica Acta 380 (2012) 223–229
227
Table 2
species [8]. So as to define the solution equilibria between Cu(II)
Spectroscopic characteristics of Cu(II) and Ni(II) complexes.
and Ni(II) and the studied ligands and to characterize species
formed in solution we have performed potentiometric titrations
supported by spectroscopic (UV–Vis and EPR) characterization.
For all ligands, calculations based on potentiometric titrations
suggest formation of variously protonated mono- and bis-
complexes. Neither dimeric, nor other polynuclear species were
detected. The respective stability constants (logb) are reported in
Table 1 together with the constants corresponding to the succes-
sive deprotonation of the complexes. According to the calculations
and spectroscopic data, ligands L1, L2, L4 and L5 form with Cu(II)
ions analogous chemical species, with the same coordination pat-
tern. The L1/L2 species differ from L4/L5 ones by proton coming
from the pyridine/imidazole rings not participating in metal ion
coordination. Therefore to simplify the discussion of the evolution
of the species coordination modes’ with pH we will present it on an
example of Cu(II)–L2 system. From the species distribution profile
shown in Fig. 2 we can see that metal ion complexation starts
below pH 2 with the formation of a protonated complex [CuHL]+.
The UV–Vis absorption d–d bands centered around 730 nm with
a
UV–Vis
L1
k
L2
k
L3
L4
L5
e
e
k
e
k
e
k
e
[CuH2L]2+
[CuHL]+
[CuL]
–
–
–
–
–
–
–
–
730 25
–
–
660 50
660 50
660 50
645 60
620 85
–
–
665
–
–
730 25
–
–
740 20
730 25
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
650 80
[CuH4L2]2+
[CuH3L2]+
[CuH2L2]
[CuHL2]À
[CuL2]2À
[NiH2L]2+
[NiHL]+
–
–
–
–
–
–
680 30
645 55
b
680 30
620 65
585 90
–
650
–
685 35
645 60
610 85
–
660
–
–
–
–
640 70
610 85
–
–
–
635 65
610 85
650 10
–
5
–
–
–
4
–
–
–
–
5
7
gII
–
–
–
2
–
–
–
3
–
–
4
6
9
gII
–
–
[NiH4L2]2+
[NiL]
640 12
–
630 12
–
620
–
–
[NiH3L2]+
[NiH2L2]
[NiHL2]À
[NiL2]2À
EPR
–
–
b
b
640
635
625
AII
625 15
b
646
640
AII
5
8
gII
655
630
AII
603
581
AII
3
6
gII
610 15
AII
gII
[CuH2L]2+
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
123 2.24 121 2.25
–
–
126 2.33 126 2.34
126 2.33 165 2.27
126 2.33 167 2.16
b
b
[CuHL]+
–
–
e
of about 25 MÀ1 cmÀ1 (Table 2) indicate that in this species one
[CuL]
–
–
–
–
–
–
175 2.12
–
–
[CuH4L2]2+
[CuH3L2]+
[CuH2L2]
[CuHL2]À
[CuL2]2À
–
–
–
–
–
–
nitrogen donor besides oxygen atom is bound to the copper ion,
[Cu{N(imid)O(PO32À)}]. The first monomeric complex is followed
by protonated bis-complex [CuH2L2], for which the distinct
increase of the d–d transitions energy to 685 nm, as well as EPR
parameters (A|| = 130 and g|| = 2.34, Table 2) indicate copper
coordination via 2 Â {N(imid)O(PO32À)} donor system. The step-
wise deprotonation of the [CuH2L2] to [CuHL2]À and [CuL2]2À (Ta-
ble 1) is accompanied by further blue-shift of the d–d bands, as
well as increase of A|| and decrease of g|| (Table 2). These
parameters correspond well to three- and four-nitrogens species
132 2.33 130 2.34
167 2.27 163 2.28 177 2.12 165 2.28 167 2.16
185 2.09 177 2.10 189 2.10 183 2.09 180 2.09
a
d–d bands. k is given in nm,
errors on kmax = 2 nm and
e
in dm3 molÀ1 cmÀ1, and AII in Gauss. Experimental
5%.
The spectral parameters were not determined due overlapping of various
species.
e
b
with
[Cu{N(imid)N(imino)O(PO32À)}{N(imid)O(PO32À)}]
and
showed the formation of first copper(II) complexes already at very
acidic solutions (pH ꢀ0.5). Therefore to evaluate their stoichiome-
try and stability constants we had to use a pH dependent spectro-
scopic titration based on d–d bands. From the first set of
experiments performed in acidic conditions (pH 0.44–2.40,
Cu(II)/L = 1, Fig. 3a) we could calculate the stability constant of
the [CuL] complex (Table 1). The UV–Vis absorption d–d band cen-
[Cu{N(imid)N(imino)O(PO32À)}2] binding modes for [CuHL2]À and
[CuL2]2À, respectively. The last species is the major complex pre-
dominating over a wide range of pH and its proposed structure is
given in Scheme 3. Above pH 9 the hydrolytic [CuL2(OH)]3À com-
plex starts to be formed, where the deprotonation of equatorially
metal-bound water occurs.
e
of about 80 MÀ1 cmÀ1 (Table 2,
The values of stepwise dissociation constants of side chain pyr-
idine and imidazole protons in Cu(II) complexes of L4 and L5 (3.64/
4.36 and 6.78/7.31, respectively) are very close to dissociation con-
stants of free ligands indicating no involvement of these groups in
copper(II) chelation.
tered at around 650 nm with
Fig. 4) can indicate that in this species three nitrogen atoms are
bound to copper ion, {CuN(imid)N(imino)N(pyr)O(PO3HÀ)}
(Scheme 4). Also EPR parameters of A|| = 175 and g|| = 2.12 corre-
spond well to the three nitrogen donors system. Further titration
showed a decrease of absorbance intensities with slight blue shift
up to pH 5.2 followed by an increase of intensity with concomitant
shift to 610 nm at pH 10.5 (Cu(II)/L = 0.5, Fig. 3b). These changes
were not observed when the titration was performed for
Due to the presence of the 2-pyridine in the molecule of ligand
L3, it behaves differently to all other ligands. Preliminary studies
[CuL2]2-
100
[CuH2L2]
[CuHL2]-
80
-O
O
P
O
H
60
N
NH
[CuL2(OH)]3-
[CuHL]+
40
N
Cu
N
20
Cu(II)free
NH
N
H
O
P
0
2
3
4
5
6
pH
7
8
9
10
O
O-
Fig. 2. Species distribution diagram for the Cu(II)–L2 system. [Cu(II)] = 2 Â 10À3 M,
Scheme 3. Schematic representation of the proposed structure of the [CuL2]2À
complex of L2.
metal-to-ligand molar ratio 1:3.

228
M. Pyrkosz et al. / Inorganica Chimica Acta 380 (2012) 223–229
[CuL2]2-
90
80
70
60
50
40
30
20
10
0
metal-to-ligand molar ratio of 1:1. Fixing the value of the [CuL] sta-
bility constant and its spectral parameters we could calculate con-
stants for two further complexes: [CuHL2]À and [CuL2]2À (Table 1).
[CuL]
The absorption d–d band centered at 640 nm with
e of
70 MÀ1 cmÀ1 may suggest that in the [CuHL2]À complex the bind-
ing mode is also realized through three nitrogens, but different
ones: [Cu{N(imid)N(imino)O(PO32À)}{N(imid)O(PO32À)}]. In the
[CuL2]2À species UV–Vis and EPR parameters confirm participation
of four nitrogen atoms in the chelate ring. Although the spectro-
scopic parameters are similar to the previous four ligands, the par-
ticipation of the pyridine nitrogen, instead of the phosphonate
oxygen, in copper chelation cannot be excluded. The pyridine
involvement would explain higher stability of the Cu(II) complexes
of L3 ligand. The species distribution diagram for the Cu(II)–L3 sys-
tem is shown in Fig. 5.
[CuHL2]-
400
450
500
550
600
650
700
750
800
Ni(II) ions form with L1, L2, L4 and L5 ligands mono- and bis-
complexes with various protonation degree (Table 1). Again, the
L1/L2 species differ from L4/L5 ones by protons coming from the
pyridine/imidazole rings not participating in metal ion coordina-
tion. According to the potentiometric calculations, ligands L1, L2,
L4 and L5 form with Ni(II) ions chemical species analogous to Cu(II)
complexes. Absorption spectra (Table 2) show that all Ni(II) com-
plexes are of octahedral or pseudo-octahedral geometry. The coor-
dination modes in Ni(II) complexes seem to be the same as in the
case of Cu(II) (vide supra). Taking ligand L2 as an example we can
see that the stepwise pK value of the [NiH2L2] ? [NiHL2]À + H+
reaction is of 2.7 in comparison to 4.39 for copper(II) (Table 1). Fur-
ther deprotonation leading to [NiHL2]À species is equal to 6.32 for
Ni(II) versus 6.56 for Cu(II). These two steps correspond to the
deprotonation of the imino moiety from two bound ligands. For
all ligands the hydrolysis of Ni(II) complex occurs at lower pH
(pH above 6) than for Cu(II) complex (pH above 9). The species dis-
tribution diagram for this system is shown in Fig. 6 together with
the plot of Ni(II) complexes of its 4-imidazole analog L3 (imidazole-
4-methyl(N-benzylamino)phosphonic acid) and is presented in
this way for purpose of other comparison [12]]. Analysis of these
speciations shows that the corresponding Ni(II)–L2 complexes
appear at lower pH indicating stronger binding ability of this
compound.
Wavelength [nm]
Fig. 4. Electronic spectra of the species calculated for Cu(II)–L3 system.
HN
H2O
N
N
Cu
O
P
NH
-O
O
Scheme 4. Schematic representation of the proposed structure of the [CuL]
complex of L3.
In order to discuss the stability of the studied Cu(II) and Ni(II)
complexes in comparison to complexes of other ligands, we pro-
pose to use the pM(II) value (Table 3), calculated at pH 7.4 for
[L] = 10À5 M and [M(II)] = 10À6 M, which eliminates the differences
in ligand protonation constants [27].
The pCu(II) values presented in Table 3 show that the methyl-
phosphonate ligands L1, L2, L4 and L5 discussed in this paper have
similar affinities for Cu(II) and all of them appear to be good
complexing agents. Introduction of the 2-imidazole instead of
4(5)-imidazole moiety, L1–L3 [12], does not affect copper(II) bind-
ing. Nonetheless, this replacement has a dramatic influence on
nickel binding. pNi(II) values of studied 2-imidazole ligands are
few orders of magnitude greater than their 4(5)-imidazole analogs
(Table 3) and therefore the ligands can be used as powerful chelat-
ing agents for Ni(II) ions which may compete with the low
molecular weight bioligands such a histidine. Introduction of
pH dependent UV–Vis spectroscopic titration based on d-d
bands carried out for Ni(II)–L3 allow to evaluate stability constants
for three complexes: [NiL] logb = 21.9(4), [NiHL2]À logb = 39.7(3)
and [NiL2]2À logb = 35.1(4). Spectroscopic parameters correspond-
ing to these species (Table 2) point toward the metal ion binding
through three and four nitrogen atoms, like it was in copper(II)
complexes (vide supra).
0.20
0.16
(1)
(3)
(1)
0.14
0.12
0.10
0.08
0.06
0.04
0.15
(2)
0.10
0.05
0.02
(2)
0.00
0.00
400 450 500 550 600 650 700 750 800
400 450 500 550 600 650 700 750 800 850 900
Wavelength [nm]
Wavelength [nm]
(a)
(b)
Fig. 3. (a) Absorption spectra collected during the acid titration of the 1:1 Cu(II)–L3 system; (1) pH 2.24, (2) pH 0.44; (b) absorption spectra collected during pH titration of the
1:2 Cu(II)–L3 system from pH 1.88 (1) through pH 5.20 (2) and up to pH 10.58 (3). I = 1 M (NaClO4), T = 25.0(2) °C; [Cu(II)] = 2 Â 10À3 M.

M. Pyrkosz et al. / Inorganica Chimica Acta 380 (2012) 223–229
229
[CuL2]2-
4. Conclusions
100
80
60
40
20
0
[CuL]
[CuHL2]-
The obtained compounds (as ligands L1–L5) were evaluated for
coordination of Cu(II) and Ni(II) ions. For all ligands, solution stud-
ies suggest formation of variously protonated mono- and bis-
complexes, where copper and nickel coordination is realized
through the nitrogen atoms of the imidazole and amino groups,
supported by an oxygen from the phosphonate unit.
A series of new 2-imidazole ligands can be used as powerful
chelating agents especially for Ni(II) ions. The presence of the
2-imidazole ring increases the binding ability of studied
aminophosphonates when compared to the previously designed
4(5)-imidazole analogs. pNi(II) values of 2-imidazole ligands are
few orders of magnitude greater than their 4(5)-imidazole deriva-
tives. The present data clearly indicate the impact of imidazole
moiety on the binding ability of aminophosphonate ligands.
Moreover, the introduction of ortho-pyridine as additional
donor in the side chain significantly increases the binding ability
towards both, Cu(II) and Ni(II) ions. The effectiveness of this com-
pound may be due to concomitant chelation of metal ion through
the imidazole, imino and pyridine nitrogen donors.
2
3
4
5
6
pH
7
8
9
10
Fig. 5. Species distribution diagram for the Cu(II)–L3 system ([Cu(II)] = 2 Â 10À3 M,
metal-to-ligand molar ratio 1:2).
[NiHL]+
100
Acknowledgments
[NiHL2]-
[NiL2]2-
Ni(II)free
The authors thank Professor Bogdan Boduszek (Wroclaw
University of Technology) for L1 and L2 ligands used in this study
and Professor Henryk Kozlowski (University of Wroclaw) for help-
ful discussions. This research was supported by the Polish Ministry
of Science and Higher Education and Faculty of Chemistry, Univer-
sity of Wroclaw (105/10/E-344/M/2011) and by internal grant
from the Faculty of Chemistry, Wroclaw University of Technology.
80
60
[NiL2(OH)]3-
40
[NiH2L2]
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21.9
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pM(II) = Àlog[M(II)]free at pH 7.4 for [M(II)] = 10À6
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Abbreviations used: L1
– (amino)(1H-imidazol-4-yl)methyl phosphonic acid;
L2 – imidazole-4-methyl(N-butyloamino) phosphonic acid; and L3 – imidazole-4-
methyl(N-benzylamino) phosphonic acid.
ortho-pyridine as additional donor in the side chain significantly
enhances the binding ability towards both, Cu(II) and Ni(II) ions
(Table 3). The corresponding pCu(II) and pNi(II) values are
increased by 8–16 orders of magnitude. The effectiveness of this
compound may come from concomitant chelation of metal ions
through the pyridine nitrogen donor together with imidazole and
imino ones.