Spectroscopic and pH-metric studies on the complexation of a novel tripodal amine-phenol ligand towards Al(III), Ga(III) and In(III)

Article abstract of DOI:10.1016/j.saa.2011.12.049

The aqueous coordination chemistry of a newly synthesized tripodal amine-phenol ligand, cis,cis-1,3,5-tris{(2-hydroxybenzyl)aminomethyl}cyclohexane (THAC) towards H⁺, Al³⁺, Ga³⁺ and In ³⁺ ions have been investig

Full text of DOI:10.1016/j.saa.2011.12.049

Spectrochimica Acta Part A 89 (2012) 322–328
Contents lists available at SciVerse ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Spectroscopic and pH-metric studies on the complexation of a novel tripodal
amine-phenol ligand towards Al(III), Ga(III) and In(III)
Suban K. Sahooa,∗, Rati kanta Berab, B.K. Kanungob, Minati Baralc
a Department of Applied Chemistry, S. V. National Institute of Technology, Surat 395 007, Gujarat, India
b Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal 148 106, Punjab, India
c Department of Chemistry, National Institute of Technology, Kurukshetra, Haryana, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The aqueous coordination chemistry of a newly synthesized tripodal amine-phenol ligand, cis,cis-1,3,5-
tris{(2-hydroxybenzyl)aminomethyl}cyclohexane (THAC) towards H+, Al3+, Ga3+ and In3+ ions have
been investigated in aqueous medium of 0.1 M KCl ionic strength and 25 1 ◦C by potentiometric and
spectrophotometric methods. Three protonation constants assigned to phenolic hydroxyl groups were
determined and were used as input data to evaluate the formation constants of the metal complexes.
The ligand formed various monomeric metal complex species MLH3, MLH2, MLH, ML and MLH-1 with
Ga(III) and In(III); MLH3, ML and MLH−1 with Al(III). The calculated stability constants followed the order
Ga(III) > In(III) > Al(III), and their pM values at physiological condition were found to be higher than the
corresponding transferrin complexes.
Received 2 September 2011
Received in revised form 9 December 2011
Accepted 21 December 2011
Keywords:
Tripodal amine-phenol ligand
Al(III)
Ga(III)
In(III)
Stability constants
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
In(III) ions with tripodal amine-phenol ligands have been explored
with respect to their potential application (67Ga, 68Ga and 111In
There is considerable clinical need for the design of new chela-
tors that can be used to reduce metal ions overload diseases and the
health effects associated with it. The factors to be considered while
designing such chelators are mainly their ability to form neutral
complex with high chelating ability towards the target metal ion.
Tripodal amine-phenol chelates have attracted people’s attention
because of their ability to form uncharged complexes with many
trivalent metal ions along with high thermodynamic stability and
kinetic inertness [1–4]. The unusual behaviour can be ascribed on
the basis of their (i) ideal donor sites for both soft and hard metal
ions, where amine nitrogen atoms for softer and phenolate oxy-
gens will preferentially for hard metal ions and (ii) preorganization
of the tripodal framework for encapsulation of metal ion, which can
offer intermediate chelation between open chain ligands and those
based on macrocycles.
complexes) as diagnostic radiopharmaceuticals [12–16] whereas
complexation of such ligands with Al(III) ion have been studied
for the development of new chelators for aluminium intoxication
[17–20]. Orvig and co-workers have investigated the aqueous
coordination chemistry of some tripodal aminophenolate ligands
tris(((2-hydroxy-5-sulfobenzyl)amino)ethyl)amine
1,1,1-tris(((2-hydroxy-5-sulfobenzyl)amino)methyl)ethane
(H6TAMS), 1,2,3-tris((2-hydroxy-5-sulfobenzyl)amino)propane
(H6TRNS),
(H6TAPS), and cis,cis-1,3,5-tris((2-hydroxy-5-sulfobenzyl)amino)
cyclohexane (H6TACS) with Al(III), Ga(III) and In(III) [2]; and found
that all these ligands except H6TACS form thermodynamically
and kinetically stable complexes. The ligand H6TACS derived from
triamine cis,cis-1,3,5-trisaminocyclohexane (TACH), exists in such
a conformation that metal ion complexation is not favourable and
exhibits exceedingly slow complexation kinetics and weaker bind-
ing, and no stability constants were reported [2]. Recently, we have
reported a tripodal amine-catechol ligand cis,cis-1,3,5-tris[(2,3-
dihydroxybenzylamino)aminomethyl]cyclohexane (TMACHCAT)
having three catechol units linked through methylene moieties
to the backbone of cis,cis-1,3,5-tris(methylamino)cyclohexane
(TMACH, i.e., the higher homolog of TACH) showed high
complexing ability towards lanthanide metal ions and Al(III)
[21].
The coordination chemistry of many tripodal hexadentate
amine-phenol ligands with the group-13 metal ions has been
investigated both in solid and solution state owing to their differ-
ent practical applications [1–11]. The compounds of Ga(III) and
∗
Corresponding author. Tel.: +91 9662620556.
E-mail address: suban sahoo@rediffmail.com (S.K. Sahoo).
1386-1425/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2011.12.049

S.K. Sahoo et al. / Spectrochimica Acta Part A 89 (2012) 322–328
323
+H2N
NH
OH
+H2N
HO
+
HN
NH2
NH
OH
OH
OH
OH
-
SO3
-
SO3
-
SO3
H6TACS
THAC
In this communication, we have introduced a new tripo-
dal amine-phenol ligand cis,cis-1,3,5-tris{(2-hydroxybenzyl)
aminomethyl}cyclohexane (THAC), the non-sulfonated higher
analog of H6TACS, as chelator for group-13 metal ions viz., Al(III),
Ga(III) and In(III). The chelating ability of the ligand and the stability
constants of the various metal complexes formed in solution have
been determined by potentiometric and spectrometric methods.
Also, some complementary information related to the structure
and electronic properties of the ligand and its metal complexes
has been obtained through molecular modeling calculations and
compared with the experimental evidences.
2.3. Titration procedure
The experimental details, calibration techniques, apparatus
used and the titration procedures were as described before [22–24].
All the solutions were prepared prior to the experiments in double
distilled deoxygenated water. KOH solution of 0.1 M was prepared
and standardized against potassium hydrogen phthalate. HCl solu-
tion (0.1 M) was prepared and standardized against standard KOH.
The ionic strength was maintained by adding appropriate amount
of 1 M KCl. Solutions of 0.01 M ligand and 0.01 M metal ions were
prepared in water. Following titrations with metal-to-ligand molar
ratios: CM/CL = 0:1 and CM/CL = 1:1 (M = Al+3, Ga+3 and In+3) were
carried out. The protonation constants of the ligand and the for-
mation constants of the metal complexes were determined using
computer program Hyperquad 2000 [25].
2. Experimental
2.1. Materials and measurements
Spectrophotometric titrations were carried out by taking dilute
solutions of the ligand (4.02 or 5 × 10−5 M) and the metal ions
(5 × 10−5 M) at CL/CM = 1:0 and 1:1 ratios keeping ionic strength
0.1 M KCl and 25 1 ◦C in aqueous medium. After each adjustment
of pH, an aliquot was removed and spectra were recorded. The pro-
tonation constants and formation constants from the spectral data
were calculated by global fitting of the whole spectral data using a
non-linear least-square fitting program, pHAb [26].
The chemicals salicylaldehyde, sodiumborohydride and
methanol used for the synthesis of the ligand, and nitrate salts
of Al(III), Ga(III) and In(III) were obtained from Sigma–Aldrich.
The required chemicals KOH, HCl and KCl for potentiometric
and spectrophotometric studies were obtained from Ranbaxy
Chemicals Ltd., India.
Proton and 13C NMR spectra were recorded on a Brucker DPX-
300 spectrometer in CDCl3 and chemical shifts were reported
relative to Me4Si. IR spectra (KBr pellets, 450–4000 cm−1) were
recorded on Perkin-Elmer RX I FT-IR spectrometer. The electronic
spectra were recorded on an Agilent-8453 diode array spectrome-
ter. Elemental analyses were determined for C, H and N using the
Exeter Analytical CE-440.
2.4. Computational methods
All computations were performed by using computer programs
CAChe Version 6.1.1 [27]. The initial geometry optimization of
THAC leading to energy minimum was achieved by using the MM3
force field and then re-optimized by applying the semi-empirical
PM3 self-consistent field molecular orbital (SCF-MO) method at the
restricted Hartree–Fock (RHF) level. The PM3 geometry optimiza-
tions were obtained by the application of the Polak–Ribiere method
with a convergence limit of 0.0001 kcal/mol and an RMS gradient of
0.001 kcal/mol. The electronic and infrared spectra of THAC were
calculated by semi-empirical method using the ZINDO and PM3
force field, respectively.
2.2. Synthesis of cis,cis-1,3,5-tris[(2-
hydroxybenzylamine)aminomethyl]cyclohexane
(L)
The
initial
compound
cis,cis-1,3,5-tris(methylamino)
cyclohexane (TMACH) [22] and its Schiff base derivative cis,cis-
1,3,5-tris{(2-hydroxybenzilidene)aminomethyl}cyclohexane
(TMACHSAL) [23] was synthesized as per the available procedures.
Further, the ligand TMACHSAL was reduced to get THAC. To
a suspension of Schiff base TMACHSAL (0.20 g, 0.41 mmol) in
methanol (50 ml) was added NaBH4 (0.09 g, 2.38 mmol) in small
portions over 30 min. After the addition, the reaction mixture
was stirred at room temperature for an additional 2 h. The yellow
suspension of Schiff base was dissolved, and solution became
colorless. The solvent was removed under reduced pressure. To
the residue, was added NH4Cl (5 g) in 75 ml water, and the mixture
was extracted with chloroform (3× 100 ml). The organic fractions
were combined, washed with water, and dried over anhydrous
MgSO4. The solution was filtered, and chloroform was removed on
a rotary evaporator to afford a pale white solid. The solid was dried
overnight under vacuum. The structure of the compound was
assigned on the basis of different spectral data (Supplementary
data).
3. Results and discussion
3.1. Ligand synthesis
The tripodal amine, TMACH, was synthesized by the method
reported earlier [22] and condensed with three moles of salicy-
laldehyde in ethanolic medium, and then reduced to get THAC, a
pale white color compound with 90% yield. This compound is solu-
ble in common organic solvents like chloroform, dichloromethane,
methanol, ethanol but insoluble in water. The compound was char-
acterized through elemental analyses and various spectral (UV–Vis,
IR, 1H NMR and 13C NMR) data.
In the 1H NMR spectra of THAC (Fig. 1S), the characteristic imine
band of TMACHSAL [23] at ı = 8.25 ppm disappeared and the ben-
zylic signal at ı = 3.97 ppm appeared indicating complete reduction

324
S.K. Sahoo et al. / Spectrochimica Acta Part A 89 (2012) 322–328
Fig. 1. (a) The HOMO diagram at ꢀmax 277 nm (calculated applying semi-empirical PM3/ZINDO method) and (b) experimental and theoretical electronic spectra of THAC.
of C N to –CH2–NH–. The spectrum showed three distinct peaks
for the three different kinds of protons found in cyclohexane ring.
A quartet and a broad band were obtained at ı = 0.67 and 1.68 ppm
for the axial and equatorial protons of the three methylene groups
respectively, whereas a doublet at 1.76 ppm was observed for the
three axial protons attached with the appended groups in the
cyclohexane ring, confirm the cis,cis-configuration. Further, the
equatorial conformation for ligand THAC was clearly delineated
from the coupling constants obtained for the methine proton in
the cyclohexane ring. It was reported that in case of equatorial
conformer, the methine proton should exhibit a large (8–12 Hz)
vicinal coupling whereas intermediate (2–4 Hz) vicinal coupling
is observed for an axial conformer [28]. The observed constants
J = 12.3 Hz for the methine protons of the ligand THAC confirm-
ing the formation of cis,cis-equatorial conformation. The peaks due
to aromatic protons were observed at 6.80, 6.99 and 7.16 ppm.
The peaks at 2.54 and 3.97 ppm were respectively assigned for the
methylene protons attached to the cyclohexane and aromatic ring.
The 13C NMR spectrum of ligand THAC showed peaks at 35.46 and
36.94 ppm for CH2 and CH groups in the cyclohexane ring, respec-
tively. The peaks at 52.96 and 55.07 ppm correspond to CH2 groups
attached to the cyclohexane and benzene ring respectively. The
peaks at 116.30, 119.04, 122.40, 128.32 and 128.72 ppm attributed
to the CH groups of the aromatic ring, whereas peak at 158.12 ppm
corresponds to C–OH present in the aromatic ring.
ZINDO calculation showed peaks with ꢀmax at 277 nm. The opti-
mized structure along with the HOMO at 277 nm is shown in Fig. 1a
and the experimental and theoretical spectra are shown in Fig. 1b.
3.2. Ligand protonation constants
The tripodal ligand THAC contains three pendant amino-phenol
groups on a cis,cis-1,3,5-tris(methylamino)cyclohexane ring as the
anchor at 1, 3 and 5 positions. Because of the insolubility of the
ligand in water under normal condition, weighed quantity of stan-
dardized 0.1 M HCl was added to make it water-soluble, and then
was titrated with standard 0.1 M KOH. The potentiometric curve
for the ligand is shown in Fig. 2, where the solid symbols repre-
sent equilibrium points collected when no solid phase was present
in the solution while dotted lines represent points collected when
turbidity or precipitation appeared. Analysis of the potentiometric
curve using the program Hyperquad 2000 gave best fit for three
protonation constants for the ligand (Table 1). The protonation
10
(a)
(b)
(c)
(d)
9
8
7
6
5
4
3
The infrared spectrum of THAC showed the absence of the
characteristic imine ꢁC
band of TMACHSAL [23] at 1632 cm−1
N
and appearance of new bands at 3268 and 1474 cm−1 due to
N–H stretching and bending vibrations, respectively. These obser-
vations confirmed the reduction of C N bond to –CH2–NH–.
The broad ꢂO–H band at 3418 cm−1 indicated the presence of
intramolecular hydrogen bonding, because the normal position
for stretching vibration of non-hydrogen bonded or free hydroxyl
group absorbs strongly in the range of 3700–3584 cm−1 [29]. The
deformation ıO–H peaks were observed at 1384 and 1354 cm−1
.
The band observed at 1258 cm−1 was attributed to ꢂC–O. Aromatic
carbon–carbon stretching vibrations were observed at 1592 and
1454 cm−1, whereas two bands at 842 and 766 cm−1 were assigned
for ring substituted bending vibrations.
-4
-3
-2
-1
0
1
2
3
4
5
6
7
8
The recorded UV–Visible spectra of THAC exhibited a broad band
between 270 nm and 280 nm with maximum absorbance (ꢀmax) at
274 nm attributed to ␲ → ␲* transitions associated with the chro-
mophoric phenyl ring. The theoretical electronic spectrum of THAC
obtained from PM3 (RHF) optimized structure by semi-empirical
a
Fig. 2. Potentiometric titration curves of ligand THAC in absence (a) and presence
of metal ions (b) Al(III), (c) Ga(III) and (d) In(III) in 1:1 M:L molar ratio, where ‘a’ is
the moles of base added per mole of the ligand present.

S.K. Sahoo et al. / Spectrochimica Acta Part A 89 (2012) 322–328
325
Table 1
15.0
12.5
10.0
7.5
Protonation constants (log K) of ligand THAC obtained through (A) potentiometric
and (B) spectrophotometric methods.
a
Equilibrium
A
B
L + H ꢀ LH
LH + H ꢀ LH2
LH2+ H ꢀ LH3
8.29 0.08
7.96 0.09
6.56 0.10
8.30 0.10
7.93 0.20
6.52 0.16
L
reaction can be proposed by the following equation (charges are
omitted for clarity):
5.0
LH
[LHn]
LHn−1 + H ꢁ LHn Kn
=
(1)
LH2
2.5
[LHn−1][H]
LH3
The pH dependent species distribution diagram (Fig. 2S) of the
ligand obtained from their calculated protonation constants indi-
cate that initially the ligand existed in fully protonated form as LH3
at pH < ∼5.0. As pH increases, stepwise deprotonation occurred and
led to the formation of species LH2, LH and L. Formation of the fully
deprotonated form L, of the ligand starts from pH ∼7.0 and becomes
predominant after pH ∼8.5.
220
240
260
280
300
320
wavelength, nm
b
The spectrophotometric titration of the ligand (L = 4.02 × 10−5 M
in ∼4 × 10−4 M HCl) was carried out in aqueous medium at an
ionic strength of 0.1 M KCl and 25 1 ◦C within the pH range
3.92–8.75. The experimental electronic spectra of the ligand THAC
at different pH is shown in Fig. 3. At low pH, the ligand exhibits
peak at 274 nm is attributed to the ␲ → ␲* transition associated
with the phenol group. With the rise in pH, the peak at 274 nm
shifted to higher wavelength (294 nm) with the concomitant rise
in absorbance forming isosbestic points, from which the state of
equilibrium between protonated and deprotonated species was
examined. Analysis of the experimental spectral data with the non-
linear least-square fitting program pHAb gave three protonation
constants, which corroborates well with the potentiometric results
(Table 1).
80
40
0
L
LH
LH 2
LH 3
240
260
280
300
320
340
wavelength, nm
The pH-dependent predicted spectra for the species LH3, LH2,
LH and L obtained from pHAb program are shown in Fig. 4a. It has
been observed that stepwise deprotonation of the fully protonated
species LH3 resulted in shifting of ꢀmax to a higher wavelength with
the concomitant rise in absorbance. The absorption band assigned
Fig. 4. (a) Predicted spectra of different species of ligand THAC (L) obtained
from pHAb and (b) calculated electronic spectra (using semi-empirical PM3/ZINDO
method) of the different species (LH3, LH2, LH and L) of ligand.
*
for the ␲ → ␲ transition at 274 nm for LH3 shifted to the extent of
absorption bands and a simultaneous increase in the absorbance.
This change in experimental electronic spectra with respect to the
various species corroborates well with their corresponding theoret-
ical electronic spectra obtained by the semi-empirical PM3/ZINDO
method (Fig. 4b). The calculated spectra for the deprotonated
species LH2, LH and L of the ligand THAC were obtained by stepwise
deprotonation of the phenolic groups of neutral species, LH3. Thus,
the three protonation constants can be characterized for the three
phenolic hydroxyl groups. Again, the low values of protonation
constants of the molecule as compared to the phenol (pKa = ∼10)
indicate the formation of intramolecular hydrogen bonds between
the amine N-atom and the closest phenolic group, which can also
be verified from the PM3 optimized structure of the ligand THAC
(Fig. 1a).
∼20 nm upon the formation of deprotonated species LH2, LH and
L. Since the phenolic group is the only significant chromophore in
the molecule, any change in the UV spectrum is attributed to the
phenol deprotonation, which causes a bathochromic shift in the
0.18
0.15
0.12
0.09
pH = 8.75
3.3. Metal complex formations
0.06
0.03
The potentiometric titration curves for all the metal–ligand sys-
tems at M:L::1:1 ratio are given in Fig. 2. The deviation in the
metal–ligand titration curves from the free ligand titration curve
implies the formation of metal complexes. Formation of turbidity
or precipitate occurred from a = ∼6 (where, a = moles of OH−/mole
of ligand), which implies that six protons may be displaced pos-
sibly three from the phenolic hydroxyl groups and the remaining
three from the protonated sec-amine groups whose protonation
pH = 3.92
0.00
220
240
260
280
300
320
wavelength, nm
Fig. 3. Experimental electronic spectra of the ligand THAC at different pH.

326
S.K. Sahoo et al. / Spectrochimica Acta Part A 89 (2012) 322–328
0.21
0.18
0.15
0.12
0.09
0.06
0.03
0.00
a
b
0.20
9.43
0.15
0.10
0.05
8.70
8.05
pH = 7.82
pH = 3.26
4.24
240
220
260
280
300
320
220
240
260
280
300
wavelength, nm
wavelength, nm
24
20
16
12
8
c
d
0.20
0.15
0.10
0.05
GaLH3
GaLH2
GaLH
GaL
GaLH-1
pH = 7.56
4
pH = 3.23
280
0
220
240
260
280
300
320
220
240
260
300
320
wavelength, nm
wavelength, nm
Fig. 5. Experimental electronic spectra of 1:1 metal-to-ligand ratio for M(III)-THAC systems: (a) Al(III), (b) Ga(III), (c) In(III) with increasing pH and (d) predicated electronic
spectra of the species for Ga(III)–L system obtained from pHAb.
Table 2
constants could not be evaluated due to the precipitation of free
Overall stability constant (log ˇ) of the metal complexes formed by the ligand THAC,
ligand solution at the moderate basic pH. Keeping in view these
preliminary observations many sets of possible complexes were
tested in the minimization programme and the best-fit models
were obtained when formation of species MLH3, MLH2, MLH, ML
(A = potentiometry and B = spectrophotometry).a
Species
Al(III)
A
Ga(III)
A
In(III)
A
B
B
B
and MLH were considered for Ga(III) and In(III); and MLH3, ML
−1
MLH3
MLH2
MLH
ML
32.53
–
–
17.54
11.21
32.49
–
–
17.52
11.19
34.06
29.66
25.94
21.78
15.02
34.09
29.67
25.92
21.75
15.12
33.27
29.72
24.92
20.11
14.20
33.26
29.69
24.89
20.07
14.18
and MLH−1 for Al(III). The overall formation constants (log ˇ) of the
species obtained from the program Hyperquad 2000 are summa-
rized in Table 2, and their equilibrium reactions can be defined by
the following equations (charges are omitted for clarity):
MLH
−1
a
Standard deviation ranges from 0.01 to 0.10.
[MLH3]
[M][L][H]3
M + L + 3H ꢁ MLH3, log ˇ1 1 3
M + L + 2H ꢁ MLH2, log ˇ1 1 2
=
=
(2)
(3)
[MLH−1][H]
[ML]
ML ꢁ MLH−1 + H, log ˇ1 1 −1
=
(6)
[MLH2]
[M][L][H]2
Spectrometric titrations of THAC was carried out at dif-
ferent pH in 1:1 metal-to-ligand ratio with the ligand con-
centration [L] = 5 × 10−5 M and the metal ion concentration
[M(III)] = 5 × 10−5 M in aqueous medium in order to comple-
ment the potentiometric results and to explain the possible
modes of coordination in the species formed in the solution. The
[MLH]
[M][L][H]
M + L + H ꢁ MLH, log ˇ1 1 1
=
(4)
(5)
[ML]
M + L ꢁ ML, log ˇ11
=
[M][L]

S.K. Sahoo et al. / Spectrochimica Acta Part A 89 (2012) 322–328
327
H
H
experimental electronic spectra of THAC–M(III) systems are given
in Fig. 5a–c. The spectral changes indicate the formation of metal
complexes. The ligand peak at 274 nm at low pH was shifted
towards higher wavelength with the formation of isosbestic points
and concomitant rise in absorbance due to the deprotonation and
complexation of phenolic hydroxy groups. The variations in the
electronic spectra for all the systems containing metal ions at differ-
ent pH are similar with respect to the ligand THAC, which indicate
similar mode of complexation. Processing of the spectral data with
the program pHAb gave best-fit for a set of formation constants
(Table 2) that are well-accorded with that obtained from the poten-
tiometric study.
The pH dependent species distribution curves (Fig. 3S) indi-
cate that complexation started from pH ∼2.0 with the formation of
MLH3 in Ga(III)/In(III)–L systems, but in case Al(III)–L system for-
mation of MLH3 was observed from pH ∼4.0. This is presumably due
to the weak complexing ability of Al(III) ion towards the N-donors
of the ligand [30]. All the protonated metal complex species MLH3,
MLH2 and MLH are predominant below pH ∼5.0. The formations
of monomeric ML species started from pH ∼4.5 and exist in max-
imum percentage at pH ∼5.5. As the formation percentage of ML
species decreases, simultaneously formation of hydroxo complex
H
H
H
L = THAC
H
H
H
M = Al(III), Ga(III) and In(III)
H
N
N
N
M
O
O
O
(a) ML
H
H
H
H
H
H
H
H
H
H
H
H
N
H
N
H
H
H
H
H
-H+
N
N
N
N
M
O
M
O
HO
H2O
O
O
O
O
(b) MLH-1
(a') ML
Fig. 6. Proposed coordination modes for the species ML (a and aꢀ) and MLH (b).
−1
species MLH was observed in all the systems that predominate
after neutral pH.
−1
Table 3
Comparative pM (pM = −log[Mn+], where Mn+ = Al3+, Ga3+ and In3+) values calculated
Interpreting the results obtained from the potentiometric and
spectrophotometric experiments, it can be inferred that the lig-
and THAC releases six protons from it fully protonated form on
interactions with the metal ions to give monomeric ML species.
With the rise in pH, the species ML has releases a proton to form
at pH 7.4 (L:M = 10:1, [L] = 5 × 10−4 M).
Ligands
pM
References
Al(III)
Ga(III)
In(III)
THAC (L)
Transferrin
H6TRNS
H6TAMS
H6TAPS
DTPA
17.98
14.50
–
15.20
15.8
21.90
20.90
22.40
25.10
24.4
20.95
18.70
22.10
21.00
20.4
Present work
[33–35]
[2]
[2]
[2]
MLH that predominant after neutral pH in all metal–ligand sys-
−1
tems. According to the equilibrium reaction (6), this proton may
come from a water molecule attached to the metal, leaving behind
a hydroxide group, or it may come from the coordinated ligand in
ML species. The previous reports by Orvig and his coworker [31]
on the coordination behaviour of similar tripodal aminophenolate
ligands suggested that such monomeric ML complex (M = Cu(II);
L = H6TAMS and H6TAPS) in solution exist as a mixture of species:
one in which the ligand coordinated through N3O3-donor sets
and secondly, of the type ML(H2O), where the ligand binds metal
ion through N3O2 or N2O3-donor sets and one water molecule
coordinated to central metal ion to complete the octahedron. Sub-
sequently, the coordinated water molecules releases a proton to
give the species ML(OH−). Accordingly, it may be suggested that
the ligand THAC coordinated by N3O3 to give tris(aminophenolate)
type metal complex, and either by N2O3 or N3O2 donor sets to give
different mixture species [M(THAC)] and [M(THAC)(H2O)]. Coordi-
nation by N3O2 donor sets for ligand THAC in [M(THAC)(H2O)] can
be ruled out from the bathochromic shifting of ligand peak from
low to high pH (indicating coordination of phenol as phenolate ion,
15.55
15.89
22.58
20.04
25.55
23.40
[36]
[36]
EDTA
the group-13 metals [30], and these estimates show log K trend as
In(III) ∼Ga(III) ꢁ Al(III) for M(NH3)3+ formation. Thus, the prefer-
ence of aminophenol ligand THAC binding to Ga(III) over In(III) can
be rationalized due to the presence of the oxybenzyl donors.
In solution, the metal ion competes with the proton during com-
plexation. The proton competition mainly depends on the pH and
pKa of the ligand and thus, the pM (pM = −log[Mn+]) is a better value
of the relative complexation efficiency of the ligand under given
conditions of pH, Mn+ and L concentrations. The pM (M3+ = Al3+
,
Ga3+ and In3+) values were calculated at pH 7.4, [L]total = 5 × 10−4 M
and [M3+
]
total = 5 × 10−5 M, and summarized in Table 3 along with
some related ligands. It is evident from Table 3 that at physiological
pH, the ligand binds Ga(III) more selectively than In(III) followed by
Al(III). Also, the pM values calculated for the M(THAC) complexes
are found to be higher than transferrin. This is very important for
Ga(III) and In(III) complexes to be considered as potential radio-
phamaceuticals, because the metal complex must be more stable
with respect to demetalation by the blood serum protein transfer-
rin. The pH dependence of the selectivity was also examined owing
to the fact that in particular biological compartments or circum-
stances, pH values far from 7 can be observed. Hence, it is important
to see whether the selectivity of the ligand still remains in a bio-
logical relevant pH range. The plots of pM as a function of the pH
(Fig. 4S) inferred that the selectivity of the ligand for all the three
metal ions is maintained over the pH range 4–8.
Fig. 5) and also from the higher preference of these metal ions (Al3+
,
Ga3+ and In3+) for phenolate O-atom than the neutral N-atom. Thus,
the coordination modes in two possible species for ML are shown in
Fig. 6 and the formation of MLH−1 (Fig. 6b) can now be represented
by the following equilibrium reactions:
M(III) + LH33+ + H2O ꢁ [ML(H2O)]+ + 2H+
[ML(H2O)]+ ꢁ [ML(HO−)] + H+
(7)
(8)
3.4. Selectivity and binding ability of the ligand
Table 2 reveals that Ga(III) forms stronger complexes than In(III)
followed by Al(III). This stability order agrees with the literature
for the similar complexes [32]. Martell and coworkers have shown
that the oxybenzyl donor displays a large preference for coordina-
tion to gallium(III) over indium(III) [32]. Hancock and co-workers
have given estimates for the formation constant of ammonia with
Further, the 3D model geometry of the monomeric complex
species ML was drawn through molecular modeling calcula-
tions. With MM3 force field calculations, it was observed that
the ligand preferred to exist in the equatorial form in the
uncomplexed form. However, the ligand preferred to flip its

328
S.K. Sahoo et al. / Spectrochimica Acta Part A 89 (2012) 322–328
conformation from equatorial to axial in order to encapsulate the
metal ion. Similar ring-flipping upon chelation has been reported
for many tripodal amine-phenol ligands derived from cyclohex-
ane based tripodal triamine TACH [6–8]. The least strain structures
for all the complexes were further re-optimized by applying
PM3 Hamiltonian. The order of calculated total energies for the
ML species is GaL (ET = −5541.51 eV) < InL (ET = −5529.71 eV) < AlL
(ET = −5529.69 eV), which correlates well with the stability order.
The complexes were preferred to exist in a distorted octahedral
geometry in which each coordinated oxygen moiety was observed
trans to the amine nitrogen of a neighboring pendant arm (the
model optimized structure for InL complex is shown in Fig. 5S).
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4. Conclusions
The flexible C3-symmetrical tripodal amine-phenol ligand THAC
showed the potential to encapsulate metal ions viz., Al(III), Ga(III)
and In(III) in solution to form a tris(aminophenolate) type metal
complexes. The stability order: Ga(III) > In(III) > Al(III) correlates
with the total energy calculated for their ML metal complex species
by the PM3 method as well as with their calculated pM values at
pH 7.4, pGa (21.90) > pIn (20.95) > pAl (17.98). The pM values for
the metal complexes were higher than their corresponding trans-
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the ligand THAC or its related derivatives can be implemented as
potential chelators for many practical applications related with the
group-13 metal ions.
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Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.saa.2011.12.049.
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