Ternary complex formation in the system Ni(II) with picolinic acid and selected amino acids: Solution studies, isolation and computational calculations

Article abstract of DOI:10.1016/j.ica.2017.11.017

The formation of mixed ligand complexes of Ni(II) with picolinic acid (Hpic) in presence of selected amino acids (HL) (serine (Hser), threonine (Hthr), methionine (Hmet) and phenylalanine (Hphe)) has been studied by pH-metric titrations. The pH-titrations of the reaction mixtures are shown to yield the complexes Ni(pic)L, [Ni(pic)(L)(OH)]^? and [Ni(pic)(L)₂]^? in the systems studied with the amino acids ser, met and phe, while in the Ni(II)-Hpic-Hthr system only the complexes Ni(pic)L and [Ni(pic)(L)₂]^? were formed. The equilibrium and formation constants of the resulting ternary complexes have been calculated at I = 1.0 mol.dm^?3 of NaCl. The stability of the ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameters Δ log₁₀ K″. The concentration distributions of various species formed in solution were also evaluated as a function of pH. The synthesis of the ternary species Ni(II)-Hpic-HL, in which HL corresponds to the amino acids ser and phe, was performed, and the solids were characterized using a combination of FT-IR, UV–Vis, elemental analysis, TGA, powder DRX and ¹H NMR. The crystallization of the isolated ternary complexes was attempted, yielding only the corresponding binary species Ni(pic)₂. Calculations on the stability of the ternary complexes were performed, to account for the impossibility to crystallize them.

Full text of DOI:10.1016/j.ica.2017.11.017

Inorganica Chimica Acta 471 (2018) 297–304
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Inorganica Chimica Acta
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Research paper
Ternary complex formation in the system Ni(II) with picolinic acid and
selected amino acids: Solution studies, isolation and computational
calculations
Vanessa R. Landaeta a, , Yessica Barrera a, Edgar del Carpio a, Anggie Nóbrega a, Rafael E. Rodríguez-Lugo a,b
,
⇑
David S. Coll-Gómez c,d, Vito Lubes a,
⇑
a Departamento de Química, Universidad Simón Bolívar, Valle de Sartenejas, Baruta, Apartado 89000, Caracas 1080A, Venezuela
b Laboratorio de Química Bioinorgánica, Centro de Química, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020-A, Venezuela
c Laboratorio de Físico Química Teórica de Materiales, Centro de Química, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020-A, Venezuela
d Escuela Superior Politécnica del Litoral, Centro de Investigación y Desarrollo de Nanotecnología, Ecuador
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 July 2017
Received in revised form 3 November 2017
Accepted 10 November 2017
Available online 17 November 2017
The formation of mixed ligand complexes of Ni(II) with picolinic acid (Hpic) in presence of selected amino
acids (HL) (serine (Hser), threonine (Hthr), methionine (Hmet) and phenylalanine (Hphe)) has been stud-
ied by pH-metric titrations. The pH-titrations of the reaction mixtures are shown to yield the complexes
Ni(pic)L, [Ni(pic)(L)(OH)]ꢀ and [Ni(pic)(L)2]ꢀ in the systems studied with the amino acids ser, met and
phe, while in the Ni(II)-Hpic-Hthr system only the complexes Ni(pic)L and [Ni(pic)(L)2]ꢀ were formed.
The equilibrium and formation constants of the resulting ternary complexes have been calculated at I
= 1.0 mol.dmꢀ3 of NaCl. The stability of the ternary complexes was quantitatively compared with their
This contribution is dedicated to Dr. Felipe
Brito (1930–2017). A lifetime dedicated to
the study of inorganic chemistry and
solution equilibria.
corresponding binary complexes in terms of the parameters
D
log10 K00. The concentration distributions
of various species formed in solution were also evaluated as a function of pH. The synthesis of the ternary
species Ni(II)-Hpic-HL, in which HL corresponds to the amino acids ser and phe, was performed, and the
solids were characterized using a combination of FT-IR, UV–Vis, elemental analysis, TGA, powder DRX
and 1H NMR. The crystallization of the isolated ternary complexes was attempted, yielding only the cor-
responding binary species Ni(pic)2. Calculations on the stability of the ternary complexes were per-
formed, to account for the impossibility to crystallize them.
Keywords:
Nickel(II) complexes
Picolinic acid
Potentiometric studies
Speciation
Ternary complexes
Ó 2017 Elsevier B.V. All rights reserved.
1. Introduction
great importance for a more accurate understanding of their distri-
butions, mobility, toxicity, bioavailabilityß and for setting environ-
Bioavailability of metal ions depends on their being either in
their free form or in a binding or complexed state, with various
constituents present in requisite amounts during biological reac-
tions. The changes in various constraints like pH, temperature
and ionic strength cause changes in the complexation behavior of
metals and their binding state. Hence, complexation can signifi-
cantly affect the bioavailability of metal ions in various biosystems
[1]. In particular, binding studies of metal ions by amino acids, pro-
teins or peptides are fundamental to understand their role in
bioinorganic processes [2], and to mimic specific functions of
bioinorganic compounds such as metalloproteins, metalloenzymes
for catalysis [3] or metallic complexes used in medicine. Chemical
speciation studies of essential metal ion complexes are thus of
mental quality standards. Mixed-ligand complexes are
fundamental in biological chemistry, since mixed chelation com-
monly occurs in biological fluids, as millions of potential ligands
usually compete for metal ions in vivo. These create specific struc-
tures and have been implicated in the storage and transport of
active substances through membranes [1].
As a consequence, the binding of metal ions to chelating ligands
such as picolinate, has been of great interest in bioinorganic chem-
istry. For example, the bis(picolinate)oxovanadium(IV), VO(pic)2,
has shown a modest glucose-lowering activity [4]. Other metallop-
icolinate complexes have shown insulinomimetic activity as well
[5]. Sakurai et al. [6] studied in vivo coordinative structural changes
of an insulinomimetic agent, bis(picolinato)oxovanadium(IV), by
electron spin-echo envelope modulation spectroscopy, and
observed that the original binary complex is transformed into a
ternary complex of general composition VO(pic)(X), where X repre-
⇑
Corresponding authors.
E-mail addresses: vlandaeta@usb.ve (V.R. Landaeta), lubesv@usb.ve (V. Lubes).
https://doi.org/10.1016/j.ica.2017.11.017
0020-1693/Ó 2017 Elsevier B.V. All rights reserved.

298
V.R. Landaeta et al. / Inorganica Chimica Acta 471 (2018) 297–304
sents an amino acid. Substantial variations in insulinomimetic
activity were observed upon formation of the ternary species.
The importance of nickel in bioinorganic chemistry has been
recognized, among other examples, with the recent discovery of
the metalloenzyme NiSOD [7], part of the defense enzymes group
called superoxide dismutases (SODs) [8]. Considering the potential
applications of metallopicolinato complexes as insulinomimetic
agents, our group decided to study the formation of ternary com-
plexes in the Nickel(II)-Hpic-amino acid systems (serine (Hser),
threonine (Hthr), methionine (Hmet) and phenylalanine (Hphe)).
Potentiometric studies on the solution chemistry of Ni(II)-pep-
tide systems have been reported [9]. Also, investigations on the
mixed-ligand complex formation equilibria for the systems Ni(II)-
gen atmosphere inlet with outlet tubes. The temperature was kept
at (25.0 0.1) °C by constant circulation of water from the ther-
mostat bath.
UV–Vis absorption spectra were recorded on an Agilent 8453
spectrophotometer in water or dimethyl sulfoxide (DMSO) solu-
tion. FT-IR spectra were recorded on a Nicolet I.S10 spectrometer
in KBr discs. The absorption bands are described as follows: strong
(s), very strong (vs), middle (m), weak (w), or broad (br). 1H NMR
spectra were recorded on a Bruker Avance 300 spectrometer. The
chemical shifts (d) were measured according to IUPAC [16] and
expressed in parts per million (ppm) relative to TMS for 1H.
Deuterated solvents (D2O and DMSO d6) were purchased from
Armar Chemicals. The abbreviation br. is given for broadened sig-
nals. X-ray powder diffraction (XRD) analysis was carried out at
ambient temperature using a Siemens D-5005 diffractometer.
The instrument is equipped with a copper anode generating Ni-fil-
tered CuK_ radiation (k = 1.54056A°, 40 kV, 30 mA). Diffractograms
were recorded in the 2h range between 5.0° and 89.96° with a step
size (2h) of 0.020° and a step time of 0.42 s. Thermogravimetric
analysis (TG) of the complexes were carried out in a dynamic nitro-
gen atmosphere (20 ml/min) with a heating rate of 10 °C/min using
a Mettler Toledo TGA/DSC STARe System analyzer. Temperature
range: 25–500 °C.
Hpic and the amino acids glycine, a-alanine, b-alanine and proline
have also been carried out in our group [10]. The binary and tern-
ary complexes of Ni(II) with dipicolinic acid and the amino acids of
interest in the present study were recently investigated as well
[11]. However, to the best of our knowledge, there are no reports
on the aqueous-solution speciation of ternary complexes of Ni
(II)–Hpic with the amino acids selected for this study, up to date
[12,13]. In view of the above facts, it therefore seems to be of con-
siderable interest to conduct investigations of the ternary com-
plexes of nickel(II) with picolinic acid (Hpic) and some selected
amino acids (serine (Hser), threonine (Hthr), methionine (Hmet)
and phenylalanine (Hphe)) as ligands. In addition, attempts to iso-
late and crystallize the ternary complexes for the systems in which
a major species was identified were performed, to obtain further
insights on the behavior of these species in the solid state and com-
pare them with the data in solution.
2.3. Methods
The emf (H) measurements were carried out by means of the
REF//S/GE cell, where REF = Ag/AgCl/3.0 mol.dmꢀ3 KCl; S = equilib-
rium solution and GE = glass electrode. At 25 °C the emf (mV) of
this cell follows the Nernst equation, E = E0 + jh + 59.16 log h,
where h represents the free hydrogen ion concentration, E0 is the
standard potential and j is a constant which takes into account
the liquid junction potential [17]. The experiments were carried
out as follows: a fixed volume of 0.100 mol.dmꢀ3 HCl was titrated
with successive additions of 0.100 mol.dmꢀ3 NaOH until near neu-
trality in order to get the parameters E0 and j. Then, aliquots of the
HPic and the amino acid under study were added and finally an ali-
quot of the Nickel(II) stock solution was added sequentially. The
titration was continued with 0.100 mol.dmꢀ3 NaOH. The measure-
ments were done using a total metal concentration, MT = 2–3
mmol.dmꢀ3 and Nickel(II):HPic:amino acid molar ratios R = 1:1:1,
1:1:2 and 1:2:1.
2. Experimental
2.1. Reagents
NiCl26H2O, Ni(OOCCH3)24H2O and the amino acids serine
(Hser), threonine (Hthr), methionine (Hmet) and phenylalanine
(Hphe) were obtained from commercial sources (Merck p.a.) and
used without further purification. Na2EDTAꢁ2H2O and bromopyro-
gallol Red (Merck p.a.) as indicator were used to standardize the
nickel(II) stock solution. The HCl and NaOH solutions were pre-
pared using 100.0 mmol.dmꢀ3 Titrisol Merck ampoules. The NaOH
solution was standardized against potassium hydrogen phthalate
(Merck p.a., recrystallized and dried at 120 °C) using phenolph-
thalein as indicator. The HCl solution was standardized with NaOH
solution of known concentration [14]. The solutions were prepared
using triply glass-distilled water, which was boiled before prepara-
tion of the solutions to remove dissolved CO2. 100 mmol.dmꢀ3 HCl
was added to the NiCl2 stock solution to prevent its hydrolysis.
NiCl2 is hygroscopic and must be weighed on a very short time-
scale. In light of this observation, it becomes necessary to standard-
ize the NiCl2 stock solution using a Na2EDTAꢁ2H2O solution (0.01
mol.dmꢀ3) in a buffer media (pH = 10) using bromopyrogallol red
as indicator [14]. The acidity of the NiCl2 stock solution was deter-
mined by the Gran method [15]. Potentiometric measurements
were carried out in aqueous solution using 1.0 mol.dmꢀ3 NaCl as
ionic medium. Nitrogen free of O2 and CO2 was used.
The systems Ni2+- picꢀ - Amino Acids (Bꢀ) were studied accord-
ing to the reaction scheme:
pHþ þ qNi2þ þ rpicꢀ þ sBꢀ ꢀ ½NiqðHÞ ðpicÞ ðBÞ ꢂ; b
p;q;r;s
p
r
s
where Bꢀ represents the amino acids: serꢀ, thrꢀ, metꢀ and pheꢀ and
[Niq(H)p(Pic)r(B)s] is the ternary (p, q, r, s) complex (the charges
were omitted) and bpqrs is the respective stability constant.
The potentiometric data was analyzed using the program LETA-
GROP [18,19], in order to minimize the function ZC = (H ꢀ h)/[li-
gand] and ZB = (H ꢀ h)/MT, where ZC and ZB are the average
number of mole of H+ associates per mole of ligand and metal
respectively. H is the total (analytical) concentration of H+, h repre-
sents the concentration in equilibrium of H+, and MT represents the
total (analytical) concentration of Nickel (II).The pKw of water was
calculated at the ionic strength of 1.0 molꢁdmꢀ3 NaCl to be 13.69
( 0.01). Equilibria corresponding to the formation of the hydroxo
complexes of Nickel (II) were considered in the calculation of the
stability constants of the ternary complexes. The following species
2.2. Equipments
The potentiometric measurements were performed using the
following instruments: Thermo Orion model 520A pH meter,
Metrohm EA 876–20 titration vessel, Lauda Brikmann RM6 ther-
mostat bath. The sealed 100 mL thermostated double-walled glass
titration vessel was fitted with a combined Orion Ross 8102BN pH
electrode with a titrant inlet, magnetic stirrer, and an inert nitro-
were assumed: [Ni(OH)]+, log b1,-1 = ꢀ9.4(1); Ni(OH)2, log b1,-2
=
ꢀ16.94(4); and [Ni4(OH)4]4+, log b4,-4 = ꢀ27.73(3) [20]. The binary
Nickel (II)-Hpic [20] and the Nickel (II)-H2dipic-Amino Acid sys-
tems (amino acid = ser, met, thr, phe) [11,21] were previously
studied in our group. The stability constants of the Nickel (II)

V.R. Landaeta et al. / Inorganica Chimica Acta 471 (2018) 297–304
299
hydroxo complexes, the acidity constants of the ligands and the
stability constants of the binary complexes were kept fix during
the analysis. The aim was to find a complex or complexes giving
crystallization of the compound. After a few days, dark blue rectan-
gular crystals were obtained. Yield of the solid: 291.3 mg, 84%.
Anal. Calc. for C15H14N2NiO4ꢁC3H6Oꢁ2H2O: C, 49.24; H, 5.51; N,
6.38. Found: C, 51.05; H, 5.42; N, 6.49. 1H NMR (300.2 MHz,
DMSO d6, 25 °C): d [ppm] = 54.23 (br), 51.51 (br), 44.19 (br),
P
the lowest sum of the errors squared, U ¼ ðZeCxp ꢀ ZCcalcÞ2 and
P
U ¼ ðZBexp ꢀ ZBcalcÞ2,the fittings were done by testing different (p,
15.48 (br), 6.94 (br). IR (KBr disk,
m
in cmꢀ1): 3355 br, 3087 m,
q) and (p, q, r, s) combinations.
3064 m, 3029 m, 2929 m, 1592 s, 1497 m, 1453 m, 1406 s, 1349
m, 1102 m, 1067 m, 752 m, 728 m, 698 s, 656 m, 601 m, 576 m,
547 m. UV–Vis (DMSO, kmax in nm): 617.
The species distribution diagram were done with the computer
program HYSS [22], yielding the bpq and bpqrs values, which are
summarized in Tables 1 and 2.
2.5. Computational details
2.4. Isolation of the ternary complexes from the systems Ni (II)-Hpic-L
(L = ser, phe)
All structures were optimized using DMol3 [23,24]. This DFT
based program allows for the determination of the relative stability
of all studied species based on their electronic structure. The calcu-
lations were performed using the Kohn–Sham Hamiltonian with
the PBE gradient correction [25] and the double-zeta plus (DNP)
numerical basic set [23,24,26]. The All Electron core treatment
was used for all the atoms. Frequency calculations of all structures
showed that the values were positive indicating that all structures
are real minima. The presence of chemical bonds, has been ana-
lyzed using the quantum theory of atoms in molecules (QTAIM)
[27] and the AIM-UC code [28]. The solvent was considered explic-
itly by the addition of molecules of water and DMSO to the com-
plexes. The Lewis acid and basic sites could be identified, and
their strength quantified, by means of the electrostatic potential
(V(r)). Mapping V(r) values onto colors over an isosurface of the
electron density (0.001 a.u.), allowed for the identification of the
acid sites (zones were the nuclear contribution dominates) and
the basic sites (zones were the electronic contribution dominates)
[29,30].
2.4.1. System Ni(II)-Hpic-Ser
Nickel acetate tetrahydrate (252.1 mg; 1.01 mmol) and serine
(106.1 mg; 1.01 mmol) were dissolved in water (5 mL) and the
mixture was magnetically stirred for 30 min. Picolinic acid
(124.3 mg; 1.01 mmol) was added to the previous solution, upon
which the green solution turned light blue. A solution of NaOH
(5%) was added dropwise, to adjust the pH of the Ni(II)-Hpic-ser
system to approximately 5.7, thus observing the precipitation of
a light blue solid. The mixture was stirred for 30 min. The solid
was filtered off, washed with cold water (3 portions of 2 mL each),
acetone (5 mL) and diethyl ether (5 mL), and dried on air. Charac-
terization was performed on this solid. The mother liquor was
reserved on a Petri dish, to allow for the slow crystallization of
the compound. After a few days, dark blue rectangular crystals
were obtained. Yield of the solid: 122.5 mg, 43%. Anal. Calc. for C9-
H
10N2NiO5ꢁC2H4O2ꢁ2H2O: C, 34.68; H, 4.76; N, 7.35. Found: C,
33.68; H, 4.62; N, 7.46. 1H NMR (300.2 MHz, D2O, 25 °C): d
[ppm] = 54.48 (br), 46.01 (br), 41.98 (br), 34.35 (br), 20.33 (br),
15.99 (br), 2.53 (br, acetic acid solvate). IR (KBr disk,
3166 br, 1701 m, 1636 s, 1597 s, 1570 s, 1481 m, 1447 m, 1378 s,
m
in cmꢀ1):
3. Results and discussion
1300 m, 1247 m, 1052 m, 1026 m, 862 w, 767 s, 705 s, 647 m, 451
m. UV–Vis (DMSO, kmax in nm): 619,
3.1. Speciation studies for the studied ligands and the ternary systems
Ni(II)-HPic-L (L = serine, threonine, methionine, phenylalanine)
e .
= 5.95 L molꢀ1 cmꢀ1
2.4.2. System Ni(II)-Hpic-phe
The ionization constants of the studied ligands were deter-
mined potentiometrically. Fig. 1 shows, as an example, the ZC vs
pH data of the H+ - ser system and the protonation constants
(Table 1) in 1.0 mol.dmꢀ3 NaCl ionic medium. These results are
in good agreement with the literature values, considering the dif-
ferences in ionic strength and ionic medium [12,13]. In Fig. 2, the
species distribution diagram for this system is shown. The ZC vs
pH graphics and speciation diagrams for the other ligands studied
are provided as Supporting information.
The protonation constants of the ligand were studied using the
same experimental conditions set for the ternary systems. In Fig. 1,
the ZC(pH) data is given for the H+-Hser system. A good agreement
between the experimental data (points) and the theoretical curve
(the line) can be observed. The species distribution diagram given
Nickel chloride (237.4 mg; 1.00 mmol) and phenylalanine
(165.0 mg; 1.00 mmol) were added to water (5 mL). To allow for
the complete dissolution of the amino acid, NaOH was added
(80.0 mg; 2.00 mmol). The solution was magnetically stirred for
30 min. Picolinic acid (123.0 mg; 1.00 mmol) was added to the Ni
(II)-phe mixture, upon which the green solution turned light blue.
A solution of NaOH (5%) was added dropwise, to adjust the pH of
the Ni(II)-Hpic-ser system to approximately 6.2, thus observing
the precipitation of a light blue solid. The mixture was stirred for
30 min. The solid was filtered off, washed with cold water (3 por-
tions of 2 mL each) acetone (5 mL) and diethyl ether (5 mL), and
dried on air. Characterization was performed on this solid. The
mother liquor was reserved on a Petri dish, to allow for the slow
Table 1
Values of log10 bpr and pKi for the ligands studied (25 °C, I = 1.0 mol.dmꢀ3 NaCl ionic medium).
Equilibrium
pic
ser
log10 bpr
met
phe
thr
L
ꢀ + H+ ꢀ HL
Lꢀ + 2H+ ꢀ H2L+
5.22 (1)
5.32a
6.83(2)
6.22a
0.015
1.69
8.952(9)
9.04a
11.16(2)
11.17a
0.014
8.81(2)
8.91a
10.97(2)
11.06a
0.017
2.16
9.04(1)
9.12a
11.19(2)
11.34a
0.018
2.15
8.95(2)
9.21a
11.23(4)
11.13a
0.032
2.31
Dispersion (
pKa1
r)
2.21
pKa2
5.34
8.952
8.81
9.04
8.95
Values in parentheses are standard deviations [3
r
(log10b)] on the last significant figure.
a
Reported values of log10 bpr can be found in Ref. [13] and were studied under the following conditions: pic: NaNO3 1.0 mol.dmꢀ3, 20 °C; ser, thr and met: KCl 0.2 mol.
dmꢀ3, 25 °C; phe: NaClO4 0.2 mol.dmꢀ3, 25 °C.

300
V.R. Landaeta et al. / Inorganica Chimica Acta 471 (2018) 297–304
Table 2
Equilibrium constants (log10 bpqrs) for the Nickel(II) – picꢀ – Lꢀ systems (L = ser, thr, met, phe; 25 °C, I = 1.0 mol.dmꢀ3 NaCl ionic medium).
Equilibrium
log10 bpr
ser
thr
met
phe
Ni2+ + picꢀ + Lꢀ ꢀ Ni(pic)(L)
Ni2+ + picꢀ + Lꢀ + H2O ꢀ [Ni(pic)(L)(OH)]ꢀ + H+
Ni2+ + picꢀ + 2Lꢀ ꢀ [Ni(pic)(L)2]ꢀ
Dispersion
15.94(5)
8.5(1)
20.8(2)
0.073
15.50(3)
–
20.68(6)
0.035
15.37(4)
7.5(1)
19.9(2)
0.061
15.11(8)
7.2(1)
18.7(4)
0.090
Values in parentheses are standard deviations [3
r
(log10 bpqrs)] on the last significant figure.
Fig. 1. ZC, average number of mole of H+ associate per mole of Serine vs. pH, in 1.0
mol.dmꢀ3 NaCl at 25 °C. The line represents the theoretical curve calculated with
the equilibrium constants of Table 1.
Fig. 3. ZB, average number of mole of H+ associate per mole of Nickel(II) vs. pH of
the Nickel(II) – Hpic – Hser system, in 1.0 mol.dmꢀ3 NaCl at 25 °C. The lines
represent theoretical curves calculated with the equilibrium constants of Table 2.
Fig. 4. Species distribution diagram as a function of pH for the Nickel(II) – Hpic –
Hser system in 1.0 mol.dmꢀ3 NaCl at 25 °C considering the conditions MT = 2 mmol.
dmꢀ3 and molar ratio R = 1:1:2.
Fig. 2. Species distribution diagram as a function of pH for the Serine system in 1.0
mol.dmꢀ3 NaCl at 25 °C considering the conditions Serine = 2 mmol.dmꢀ3
.
constants summarized in Table 2. The data for the other ternary
systems (ZB(pH) and speciation diagrams for the other molar
ratios) studied are provided as Supporting information.
in Fig. 2 shows that the anionic (Lꢀ) form of this amino acid pre-
dominates at pH > 9, the zwitterionic form (HL) is very important
in the range 2.2 < pH < 8.95 and the protonated form of the serine
(H2L+) is the major species formed at pH > 2.2.
The formation of the ternary Nickel (II) complexes was also
studied. Fig. 3 shows the ZB(pH) data, which is given as an example
of the ternary complexes studied in this work. In this case, the Ni
(II) – Hpic – Hser system is presented, and in Fig. 4 the species dis-
tribution diagram is shown. For this system the conditions are: MT
= 2 mmol.dmꢀ3 and molar ratio R = 1:1:2, considering the stability
As an example of the ternary systems, the potentiometric data
analysis for the Nickel(II)-Hpic-Hser system performed with the
program LETAGROP [18,19] is given. The analysis indicates the for-
mation of the mononuclear complexes Ni(pic)(ser), [Ni(pic)(ser)
(OH)]ꢀ and [Ni(pic)(ser)2]ꢀ. The same speciation was obtained for
the Nickel(II)-Hpic-Hmet and Nickel(II)-Hpic-Hphe systems. In
the case of the Nickel(II)-Hpic-Hthr only two complexes Ni(pic)
(thr) and [Ni(Pic)(thr)2]ꢀ were considered. The behavior observed
for the Ni(II)-Hpic-Hthr system was mainly due to the fact that
at pH > 8 the nickel species precipitates. The species distribution

V.R. Landaeta et al. / Inorganica Chimica Acta 471 (2018) 297–304
301
diagram for the system Nickel(II) – Hpic – Hser at a molar ratio of
1:1:2, is given in Fig. 4. It can be observed that in the range 2.5 <
pH < 7 the most important species is the ternary complex Ni(pic)
(ser), while between 7 < pH < 9 the major species is the complex
[Ni(pic)(ser)2]ꢀ and at pH > 9 the species [Ni(pic)(ser)(OH)]ꢀ
predominates.
The solubility of the isolated light blue solids was studied in
water (Ni(pic)(ser) slightly soluble, Ni(pic)(phe) sparingly soluble),
dimethylformamide (both solids are insoluble) and dimethyl sul-
foxide (Ni(pic)(ser) and Ni(pic)(phe) slightly soluble). These com-
pounds are insoluble in most of the other common organic
solvents. The poor solubility of the complexes made their charac-
terization in solution quite difficult. Since DMSO gave the best sol-
ubility for both compounds, the UV–vis and NMR studies were
performed in this solvent.
The relative stability of the ternary complexes, in comparison
with the binary ones, can be obtained from the
D
log K00 value,
where
D
log K00 is calculated considering the reactions:
The UV–Vis absorption spectra of Ni(pic)(phe) in DMSO shows a
maximum at 617 nm in the visible range of the spectrum (see Sup-
porting information). For the Ni(pic)(ser) compound in DMSO a
maximum at 619 nm was observed (see Supporting information).
½NiðpicÞꢂþ þ ½NiðserÞꢂþ ꢀ ½NiðpicÞðserÞꢂ þ Ni2þ
½NiðpicÞꢂþ þ ½NiðthrÞꢂþ ꢀ ½NiðpicÞðthrÞꢂ þ Ni2þ
;
;
D
D
log K00 ¼ þ0:76
log K00 ¼ þ0:18
For this compound the molar attenuation coefficient,
molꢀ1 cmꢀ1, was measured according to the Beer-Lambert Law
(see Supporting information). The magnitude of is consistent
with a d-d transition in a relatively centro-symmetric compound.
Unfortunately, for the complex Ni(pic)(phe) could not be reliably
e = 5.95 L
½NiðpicÞꢂþ þ ½NiðmetÞꢂþ ꢀ ½NiðpicÞðmetÞꢂ þ Ni2þ
;
D
log K00 ¼ þ0:74
e
½NiðpicÞꢂþ þ ½NiðpheÞꢂþ ꢀ ½NiðpicÞðpheÞꢂ þ Ni2þ
;
D
log K00 ¼ ꢀ0:39
e
which means that the ternary complexes formed with the amino
acids ser, thr and met are more stable than their binary analogues,
while in the case of the ternary complex formed with phe, the spe-
cies formed is less stable than the binary complexes [31]. These
studies do not provide information on the coordination modes of
the amino acids or the picolinate on the studied systems, although
from the stability constants it might be proposed that these are
bonded in a chelating fashion. Previous reports on the coordination
mode of picolinic acid support this proposal, given the fact this
ligand usually coordinates as an N,O-chelate [3,5,32], although
other coordination modes have been identified [32].
measured due to its poor solubility in common solvents. The max-
imum of absorption in the visible range (orange) is in agreement
with the observed color (light blue) of the isolated compounds.
The 1H NMR spectrum of Ni(pic)(ser) in a ‘‘classical” spectral
width (SW = 16 to ꢀ4) returned only the solvent residual reso-
nance (D2O) and a broad signal at 2.53 ppm. The spectrum was
recorded again in a wider window (SW = 200 to ꢀ200, see Support-
ing information) and changing the relaxation delay (d1). The best
spectrum (better signal/noise ratio and resolution) was obtained
with a relatively short d1 (0.500 s vs. default d1 = 1.000 s). A new
set of six broadened resonances were observed in the range of 55
to 14 ppm. As expected, 13C{1H} resonances were not properly
resolved. This behavior in solution indicates that the complex Ni
(pic)(ser) has an important paramagnetic character. For Ni(pic)
(phe) the 1H NMR spectrum in DMSO d6 features a set of five
broadened resonances between 55 and 6 ppm. The experimental
conditions were the same than those for Ni(pic)(ser) (SW = 400
ppm, O1P = 0 ppm, d1 = 0.500 s). For comparison, the binary com-
plexes Ni(pic)2, Ni(ser)2 and Ni(phe)2 were intentionally prepared
based on reported protocols [33] and their 1H NMR spectra in
DMSO d6 were recorded (see Supporting information). The species
Ni(pic)2, exhibits four broad signals, while the NiL2 (L = ser, phe)
systems only show two resonances. Details about the spectra as
well as their qualitative comparison can be found in the Supporting
information.
3.2. Isolation of the ternary complexes Ni(pic)(L) (L = ser, phe)
The wide pH range in which the ternary complex Ni(pic)(ser) is
the major species in solution (2.5 < pH < 7, 94% of total nickel) sug-
gests that, under the appropriate conditions, attempts of isolation
of this species could be performed. A similar situation was
observed for the Ni(II)-pic-phe system (at pH = 6.2 87% of total
nickel was the ternary species) and, thus, these were the com-
plexes of choice to study their synthesis and isolation in the solid
state. The Ni(pic)(L) complexes were prepared from Nickel(II) acet-
ate or Nickel(II) chloride in two consecutive steps as depicted in
Scheme 1. In the first step, one equivalent of the corresponding
amino acid is added and the picolinic acid is incorporated after-
wards. With this protocol, light blue solids were obtained in mod-
erate yields.
Thermogravimetric analysis of the Ni(pic)(L) (L = ser, phe) com-
plexes were performed (plots of TGA can be consulted in the Sup-
porting information). The assignment of the different
decomposition steps is given in Table 3.
Ni(pic)(ser) was thermally decomposed in four successive
decomposition steps within the studied temperature range (25–
500 °C). The first decomposition step corresponds to an estimated
mass loss of 9.72% (37.03 uma) within the temperature range 77–
115 °C and might be attributed to the liberation of the two water
molecules (hydrate). The second decomposition steps takes place
within the temperature range 122–322 °C with an estimated mass
loss of 11.29% (43.02 uma), which can be accounted for the
removal of one CO2. The picolinate ligand (pic) and the acetic acid
solvate were removed in the third step within the temperature
range 388–442 °C (mass loss of 48.31%. 184.05 uma). The remain-
ing residue consists of decarboxylated serine (1,2-ethanolamine)
bonded to Ni(II) as XX ligand (residue of 30.68%, 116.86 uma).
The compound Ni(pic)(phe) decomposes in two consecutive steps
within the measured temperature range (25–500 °C). The first
decomposition occurs within 115–141 °C, with a mass loss of
7.99% (35.09 uma), possible due to the release of two water mole-
cules. During the next step, in the range 308–405 °C, the concomi-
tant elimination of the acetone solvate with the ligands (mass loss
Scheme 1. Synthesis of Ni(pic)(ser) (top) and Ni(pic)(phe) (bottom). Stereochem-
istry is omitted for clarity purposes.

302
V.R. Landaeta et al. / Inorganica Chimica Acta 471 (2018) 297–304
Table 3
Thermal analytical data for the ternary complexes Ni(pic)(L) (L = ser, phe).
Molec. Formula
Decomp. Temp. (°C)
Mass Loss (%)
Molec. Mass Found
Eliminated Species
Solid Residue (%)
Ni(pic)(ser)ꢁC2H4O2ꢁ2H2O
77–115
9.72
37.03
43.02
184.05
116.86
2 H2O
CO2
C8H9NO4
C
11H18N2NiO9
122–322
338–442
450–500
11.29
48.31
30.68
M. W. 380.96 g/mol
C2H5NNiO (30.68)
NiO (16.85)
Ni(pic)(phe)ꢁC3H6Oꢁ2H2O
115–141
308–405
420–500
7.99
75.16
16.85
35.09
330.02
73.98
2 H2O
C18H22N2O4
C
18H24N2NiO7
M. W. 439.09 g/mol
of 75.16%, 330.02 uma) takes place, leaving only NiO as the residue
(residue of 16.85%, 73.98 uma).
added. This procedure was done to complete the octahedral con-
formation with another water molecule, which could be located
in an antisymmetric position to the other water ligand in the upper
vortex of the pyramid. Despite several calculations changing the
number and conformation of the water molecules, this octahedral
geometry could not be reached.
Finally, the pale blue solid isolated from the synthesis of the
compound Ni(pic)(phe) was finely grounded and subjected to
XRD analysis. Also, the binary complexes Ni(pic)2 and Ni(phe)2
were studied by this technique. The qualitative comparison of
the diffractograms (see Supporting information) further proves
the isolation of the ternary complexes under the specified reaction
conditions.
In Fig. 6, the mapping of the electrostatic potential over an iso-
surface of electronic density for the dehydrated complex, is pre-
sented. The geometry of Fig. 5 was kept in order to localize the
most acid and basic zones surrounding the complex. A color scale
which increases in acidity from red (most basic zones), following
green and yellow, to reach blue (most acid zones) was established.
This figure has two images, which correspond to both faces, above
and below, of the Ni (II) square planar geometry. It can be clearly
observed that the most acidic zone is located over the hydrogen
atom bonded to the phenylalanine nitrogen atom. On the other
face the proton acidity of the ligand is still stronger than that of
the Ni atom. This explains why this hydrogen atom is the preferred
site of interaction with an oxygen atom of an additional water
molecule, instead of the less acid Ni atom. In this sense, a water
molecule reacts first with this proton, thus making the Ni atom
accessible for a second water molecule.
It has been shown that Ni(II) species have a strong preference to
form distorted octahedral complexes [3,9]. Also, the relative stabil-
ity between octahedral and square pyramidal conformations has
been studied [3]. In this sense, to investigate on the possibility of
stabilizing an octahedral Ni(II) complex, preliminary calculations
were performed for the Ni(II) system with picolinic acid and ala-
nine as model amino acid. This resulted in an octahedral coordina-
tion for the ternary complex. In this conformation the picolinic acid
and the amino acid are not in the same plane, as they are in the
square planar conformation. For the octahedral conformation, the
oxygen atom from the picolinic acid ligand is twisted in 90 degrees
(thus coordinating in an axial position), and two water molecules
complete the coordination sphere. In Fig. 7, the analogous opti-
mized geometry for this type of coordination for the Ni(pic)(phe)
complex is presented, showing the six bonds of the Ni atom with
the picolinic acid ligand, the phenylalanine and two water mole-
cules. The topological analysis of the electron density was also
applied to this complex, in order to corroborate the existence of
these interactions. Results are displayed in Fig. S34 (Supporting
information). Even when this conformation can be adopted by
the complex Ni(pic)(phe), it is less stable than the pentacoordi-
nated one by 21 kcal/mol due to the internal stress induced by
the presence of the phenyl ring. For the calculations of the energy
differences, water molecules were only considered if they were
interacting with the Ni atom, taking care of always keeping the
mass balance. In the case of structures presented in Figs. 5 and 7,
six water molecules were considered for the optimization of the
tetrahedral structure and only two water molecules were consid-
ered for the octahedral type (the energy of 4 water molecules
was added). For the formation of the square pyramidal conforma-
tion at least 6 water molecules were needed, because the acidity of
3.3. Theoretical studies
Due to the difficulties of crystallizing the Ni(pic)(phe) ternary
complex, theoretical calculations were performed in order to pro-
pose its possible structure, including the constitution in water
and DMSO. These types of studies have been previously performed
by other authors to assess on the stabilities and geometries of tern-
ary Ni(II) complexes [3,34].
In this case, several conformations were considered, but only
the most stable ones will be displayed below. In Fig. 5, the most
stable conformation for the Ni(pic)(phe) complex in water is pre-
sented. In addition to the intrinsic bonds of the complex, interac-
tions between this compound and the solvent water molecules
are also presented. These interactions are corroborated by the
topological analysis of the electron density (QTAIM). Results and
theoretical support of this methodology, as well as the EDD tech-
nique, are presented in the Supporting information. In this figure
the square pyramidal conformation around the Ni atom can be
seen. In the base of the pyramid, two O and two N atoms from
the picolinic acid and the phenylalanine are coordinated forming
a square base with the Ni, and in the upper vortex a water mole-
cule completes the pyramidal conformation. In a previous work
from Sankaralingam et al. [3] a distorted octahedral coordination
geometry which could be in equilibrium with a square pyramidal
conformation was proposed for a Ni (II) complex. Starting from
the square pyramidal conformation, 12 water molecules were
Fig. 5. Most stable conformation for the penta-coordinated mode of the Ni atom in
the Ni(pic)(phe) complex. Light blue, dark blue, red, gray and white spheres
represent the Ni, N, O, C and H atoms, respectively. (For interpretation of the
references to color in this figure legend, the reader is referred to the web version of
this article.)

V.R. Landaeta et al. / Inorganica Chimica Acta 471 (2018) 297–304
303
Fig. 6. Electrostatic potential mapping over an isosurface of electron density for the dehydrated penta-coordinated mode presented in Fig. 5. Light blue, dark blue, red, gray
and white spheres represent the Ni, N, O, C and H atoms, respectively. (For interpretation of the references to color in this figure legend, the reader is referred to the web
version of this article.)
Fig. 7. Most stable conformation for the hexa-coordinated mode of the Ni atom in
Fig. 8. Octahedral coordination for the Ni(pic)(phe) complex when the solvent is
DMSO. Light blue, dark blue, red, yellow, gray and white spheres represent the Ni, N,
O, S, C and H atoms, respectively. (For interpretation of the references to color in
this figure legend, the reader is referred to the web version of this article.)
the Ni(pic)(phe) complex. Light blue, dark blue, red, gray and white spheres
represent the Ni, N, O, C and H atoms, respectively. (For interpretation of the
references to color in this figure legend, the reader is referred to the web version of
this article.)
4. Conclusions
the Ni atom is not sufficiently attractive for the first five water
molecules.
The analysis of the potentiometric data by means of the compu-
tational least-squares program LETAGROP, indicates that in the
Nickel(II)-Hpic-Hser, Nickel(II)-Hpic-Hmet and Nickel(II)-Hpic-
Hphe systems the complexes Ni(pic)(L), [Ni(pic)(L)(OH)]ꢀ and [Ni
(pic)(L)2]ꢀ are formed. In the Nickel (II)-Hpic-Hthr system, only
the complexes Ni(pic)(L) and [Ni(pic)(L)2]ꢀ were identified. The
analysis of the ternary complexes stability compared to the binary
The relative stability of the binary and ternary complexes was
also investigated by means of computational calculations. In the
gas phase, the binary species Ni(phe)2 is the most stable compared
to the other two compounds Ni(pic)(phe) and Ni(pic)2. The ternary
complex Ni(pic)(phe) is only 2.5 kcal/mol less stable than Ni(phe)2.
However, this value is very close to the experimental error and,
then, almost non significant. The binary compound Ni(pic)2 is 27
kcal/mol less stable than Ni(phe)2. In solution, the potentiometric
data analysis for this particular system (amino acid phenylalanine)
indicates that the ternary species is less stable than the binary
complexes. Further theoretical studies on the ternary system Ni
(II)-picolinic acid-amino acid will be discussed in future reports.
In DMSO, the octahedral conformation is also possible. In Fig. 8,
this geometrical arrangement is displayed. O atoms of both solvent
molecules, are pointing towards the most acid zones of the com-
plex, allowing the S atoms to be located over the Ni atom. The
topological analysis of the electron density was also applied to this
complex, in order to corroborate the presence of these interactions.
Results are displayed in Fig. S35 of the Supporting information.
ones using the
D
log K00 value indicates that the ternary complex
formed with the amino acids ser, thr and met are more stable. In
the case of the ternary complex with phe, it is less stable than
the binary complexes. The synthesis of two of the Ni(pic)(L) (L =
ser, phe) complexes was achieved and both elemental analysis
and TGA show that the solids are obtained as hydrates. Crystalliza-
tion of these solids was attempted, revealing differences in stabil-
ity which seem to favor the binary picolinate complex rather than
the ternary species. Theoretical calculations indicate that it is pos-
sible to obtain two conformations for the Ni(pic)(phe) ternary
complex in water, the most stable one which is pentacoordinated,
and the octahedral one. In DMSO it is also possible to obtain an
octahedral arrangement.

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V.R. Landaeta et al. / Inorganica Chimica Acta 471 (2018) 297–304
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The authors thank Dr. Felipe Brito for valuable discussions. The
authors are grateful for the financial aid provided by the Decanato
de Investigación y Desarrollo (Universidad Simón Bolívar) to sup-
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characterization of the compounds: Pedro Moncada (IR spectra,
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