Tridentate ONO ligands in vanadium(III-V) complexes - synthesis, characterization and biological activity

Article abstract of DOI:10.1016/j.molstruc.2020.129205

The synthesis, properties, including single crystal structures and biological activity of 16 new vanadium complexes with tridentate ONO Schiff base ligands L based on 5-chloro- and 5-hydroxy-salicylaldehyde and selected hydrazides are presented. Several t

Full text of DOI:10.1016/j.molstruc.2020.129205

Journal of Molecular Structure 1224 (2021) 129205
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Tridentate ONO ligands in vanadium(III-V) complexes - synthesis,
characterization and biological activity
Janusz Szklarzewicza,∗, Anna Jurowskaa, Maciej Hodorowicza, Grzegorz Kazekb,
b
Monika Głuch-Lutwinb, Jacek Sapab, Monika Papiez˙
a Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland
b Jagiellonian University Medical College, Faculty of Pharmacy, 30-001 Kraków, Medyczna 9, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis, properties, including single crystal structures and biological activity of 16 new vanadium
complexes with tridentate ONO Schiff base ligands L based on 5-chloro- and 5-hydroxy-salicylaldehyde
and selected hydrazides are presented. Several types of complexes were synthesized at different oxida-
tion state of vanadium: [VO(L)(phen)] (where phen denote 1,10-phenanthroline) with V(IV), [VO(L)(solv)]
(where solv denote solvent molecule H2O or EtO−) with V(IV or V), [VO2L] and [VOL(H2O)2] with V(V)
and [VL2] with V(III). All complexes were characterized by elemental analysis, IR, UV-Vis, EPR spec-
troscopy, cyclic voltammetry and thermogravimetric measurements. The molecular structures of two V(V)
complexes were confirmed by single-crystal X-ray diffraction. The stability of complexes in solution as
well as the biological activity - inhibition of human tyrosine phosphatases, were investigated and dis-
cussed.
Received 6 May 2020
Revised 28 August 2020
Accepted 2 September 2020
Available online 3 September 2020
Keywords:
Vanadium
Schiff base
Structure
Spectroscopy
Biological activity
© 2020 Published by Elsevier B.V.
1. Introduction
dium complexes with tridentate ligands show specific effect on in-
sulin mimetic properties, which could not be explained in such
Almost up to the 1980s vanadium compounds was studied in
the toxicological influence on living organisms [1,2]. Since this time
vanadium was recognized as a bio element causing a growing in-
terest in vanadium compounds role in biological systems, mainly
in glycemic normalization activity [3]. The positive effect on glu-
cose regulation [4–6], anticancer activity [7–9] including recovery
of sensitivity to oncological immunotherapy [10], antioxidant ac-
tivity [11], in collagen synthesis [12], replacement of phosphates
in ATP dependent processes [13] serum lipid lowering [14] was
found. As in case of many other elements, it has been shown that
organic compounds of this element are more bioavailable than in-
organic compounds [15–16]. In case of vanadium insulin mimetic
properties different organic ligands were investigated, maltol and
its derivatives were found to be especially active and now are
commonly used as references {as BMOV, bismaltolatooxidovana-
dium(IV)} [17]. The main problem is that the bidentate ligands (as
maltol) were found to be released in organisms digestion system,
resulting also in redox reactions leading to V(V) or V(IV) moieties
and the role of vanadium complexes could be reduced to activity
of simple VO2+ ions [18]. In last years it was shown, that the vana-
a simple way. Our previous studies showed, that such complexes
can survive passage through digestion system and are much more
active toward glucose uptake (even several times) than rosiglita-
zone or BMOV possessing lower toxicity [19–21]. We show also
the influence of chronic supply of vanadium compounds on organ
weights and body mass in animal diabetes model (NZO, New Ze-
land Obese mice) [22].
In present paper we present more detailed part of our investi-
gations extended now on 5-substituted salicylaldehyde based ONO
donating Schiff bases. The substituents we used are the chloro- or
hydoxo- derivatives of salicylaldehyde. As amine components we
used hydrazides. Such a composition of Schiff base ligands makes
them flexible, thus they do not influence on the vanadium ge-
ometry, which can vary from distorted square pyramid to octahe-
dron. Presence of hydrazone part allow the ligand to change its
charge and in general this was result in formation of neutral com-
plexes. As the charge of complexes was identical, independent on
oxidation state of vanadium (which range in this paper from III
to V), the influence of complex charge on its biological activity
could be neglected. The X-ray structure measurement as well as
the elemental analysis, magnetic susceptibility, IR, UV-Vis spectra
and cyclic voltammetry are presented and indicate the coordina-
tion of the oxido, Schiff base and/or 1,10-phenanthroline ligands to
∗
Corresponding author.
E-mail address: szklarze@chemia.uj.edu.pl (J. Szklarzewicz).
https://doi.org/10.1016/j.molstruc.2020.129205
0022-2860/© 2020 Published by Elsevier B.V.

2
J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
the vanadium centre. The 1,10-phenanthroline was used in some
synthesis as a co-ligand to increase the complex stability and to
fill the coordination sphere of V(IV). The biological activity towards
inhibition of human tyrosine phosphatases (PTP1B, SHP2, LAR and
CD45) on selected myocytes C2C12, adipocytes 3T3-L1 and human
hepatocytes HepG2 cell lines was investigated and discussed.
ng/ml. After 10 minutes, a solution of phosphate 6,8-difluoro-
4-methyl (DiFMUP) was added until its final concentration was
0.1 mM. After 20 minutes of incubation at room temperature,
the fluorescence intensity (excitation 355 and emission 560 nm)
was measured on a multifunctional plate reader PTP1B POLARstar
Omega (BMG Labtech, Germany). Assays were performed in tripli-
cates. The results were expressed as per cent of inhibition of un-
treated control (enzyme with solvent only). Similarly, inhibition as-
say of PPA2 serine-threonine phosphatase, dual specificity CDC25A
phosphatase and PTPRA1 receptor tyrosine phosphatase were per-
formed according to the method described in [24].
2. Experimental
2.1. Materials and methods
[VO(acac)2], [V(acac)3], VOSO4aq, 1,10-phenanthroline (phen),
5-chlorosalicylaldehyde, 5-hydroxysalicylaldehyde, benzhydrazide,
2.2.2. Cell models
Myocytes C2C12 cell line (ATCC CRL-1772), subclone of my-
oblasts from mouse muscles were cultured according to standard
protocol in DMEM supplemented with 10% fetal calf serum, 100
IU/ml penicillin and 100 μg/ml streptomycin at 37°C in 5% CO2.
Cells were pleated on 96 well microplate and after reach conflu-
ency were differentiated in medium with 2% horse serum. Differ-
entiation medium was changed every 72 hours.
nicotinic
hydrazide,
phenylacetic
hydrazide,
4-chloro
benzhydrazide, 2-hydroxybenzhydrazide, 4-hydroxybenzhydrazide
and 3-hydroxy-2-naphthoic acid hydrazide were of analytical
grade (Aldrich or Alfa Aesar) and were used as supplied. Ethanol
(98%) of pharmaceutical grade was from Polmos and used as
supplied. All other solvents were of analytical grade (Aldrich) and
were used as supplied. BaSO4 were of spectroscopic grade (Japan).
Bu4NPF6 was synthesized from Bu4NBr and KPF6 by a standard
method and recrystallized from acetone [23]. Microanalysis of
carbon, hydrogen and nitrogen were performed using Elementar
Vario MICRO Cube elemental analyzer. IR spectra were recorded
on a Bruker EQUINOX 55 FT-IR spectrophotometer in KBr pellets.
The electronic absorption spectra were recorded with Shimadzu
UV-3600 UV-Vis-NIR spectrophotometer equipped with a CPS-240
temperature controller. Diffuse reflectance spectra were mea-
sured in BaSO4 pellets with BaSO4 as a reference on Shimadzu
2101PC equipped with an ISR-260 integrating sphere attachment.
The magnetic susceptibility measurements were performed on a
SHERWOOD SCIENTIFIC magnetic susceptibility balance. The mag-
netic moment was estimated within 0.09 μB. EPR spectra were
recorded on a BRUKER ELEXSYS 500 using 9.419 GHz microwave
frequency. Cyclic voltammetry measurements were carried out in
DMSO with [Bu4N]PF6 (0.1 M) as the supporting electrolyte, using
Pt working and counter and Ag/AgCl as reference electrodes on an
AUTOLAB/PGSTAT 128 N Potentiostat/Galvanostat. E1/2 values were
calculated from the average anodic and cathodic peak potentials,
E1/2 = 0.5(Epa + Epc). The redox potentials were calibrated versus
ferrocene (0.440 V versus SHE), which was used as an internal
potential standard for measurements in organic solvents to avoid
the influence of a liquid junction potential; the final values are
reported versus the standard hydrogen electrode (SHE). Thermo-
gravimetric measurements were performed on a TGA/SDTA 851e
Mettler Toledo Microthermogavimeter at scan speed 10 o/min in
the 25 – 755 °C range in air or under Ar atmosphere .
Adipocytes 3T3-L1 cell line (ATCC CRL-11605) derived from
fibroblasts from mouse embryo tissue were cultured according
to standard protocol in DMEM medium supplemented with 10%
bovine calf serum, 100 IU/ml penicillin and 100 μg/ml strepto-
mycin at 37°C in 5% CO2. Cells were seeded in 96-well poly-D-
lysine coated plates and cultured to reach confluency. The medium
was then switched to differentiation medium and changed every
48 hours.
Human hepatocytes HepG2 cell line (ATCC HB-8065) were cul-
tured according to standard protocol in DMEM supplemented with
10% fetal bovine serum, 100 IU/ml penicillin and 100 μg/ml strep-
tomycin at 37°C in 5% CO2. Cells were pleated on 96 well mi-
croplate.
2.2.3. Glucose uptake in myocytes and adipocytes
Myocytes C2C12 after 8 days differentiation and adipocytes
3T3-L after 11 days of differentiation were cultured and maintained
as described above but pleated on 96 well microplate coated with
solid phase scintillator (ScintiPlate, PerkinElmer, USA).
Myocytes were washed and medium was changed for medium
with 0.5% BSA instead serum. After 24 hours incubation tested
complexes were added at final concentration 50, 10 and 1 μM. Af-
ter 2 hours incubation at 37°C in 5% CO2 medium was changed
for low glucose medium (1000 mg/l), tested complexes were added
again and further incubation for 4 hours was conducted. Next, cells
were washed three times with Krebs-Ringer buffer (KRB) without
glucose (1 mM MgSO4, 1 mM CaCl2, 136 mM NaCl, 4,7 mM KCl
and 10 mM HEPES; pH 7.4) and KRB with human recombinant in-
sulin at final concentration 100 nM (Sigma-Aldrich) was added for
15 minutes. Wortmannin at final concentration 200 nM (Sigma-
Aldrich) was used as negative control. After that, cells were washed
three times with cold KRB and cytochalasin B (10 μM final) was
added for several wells as “no uptake” control and proceeded as
shown below.
2.2. Biological activity
The biological activity was studied on selected complexes. The
inhibition of human tyrosine phosphatases were studied for 1, 3-5,
8, 9-11, 15 and 16, while more extended studies were performed
for 11.
Adipocytes were washed and medium was changed for basal
medium. After 24 hours incubation tested complexes were added
at final concentration 50, 10 and 1 μM. After 2 hours incubation at
37°C in 5% CO2 medium was changed for DMEM medium without
glucose, with 0.1% BSA free from fatty acid, 200 mM L-glutamine
and 100 mM pyruvate. Tested complexes were added again and
further incubation for 4 hours was conducted. Next, cells were
washed three times with Krebs-Ringer buffer (KRB) without glu-
cose and KRB with human recombinant insulin at final concen-
tration 100 nM (Sigma-Aldrich) was added for 15 minutes. Wort-
mannin at final concentration 200 nM (Sigma-Aldrich) was used
as negative control. After that, cells were washed three times with
2.2.1. Inhibition of human tyrosine phosphatases
For determination the ability of tested compounds to inhibi-
tion of tyrosine phosphatases human recombinant protein were
used. To the solution of the tested complexes on black 384-well
microplate wells (PerkinElmer) an equal volume of a test solu-
tion of phosphatase was added in a reaction buffer (25 mM of
3-(N-morpholino) propanesulfonic acid (MOPS), 50 mM NaCl, 1
mM dithiothreitol (DTT) and 0.05% Tween-20, pH 7.0). The final
concentration of each of phosphatase was as follows: 50 ng/ml,
SHP1 400 ng/ml, SHP2 50 ng/ml, LAR 5 ng/ml and CD45 100

J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
3
cold KRB and cytochalasin B (10 μM final) was added for several
2.3. Synthesis
wells as “no uptake”.
For myocytes and adipocytes proceeded as above 2-deoxy-D-[U-
14C]-glucose solution in KRB with total activity 0,03 μCi was added
to each well. After 1 hour incubation at 37°C and 5%CO2 uptake
was blocked by adding cytochalasin B (10 μM final). Radioactivity
of samples was measured in scintillation counter MicroBeta Trilux
1450 (PerkinElmer, USA). Non-specific radioactivity was subtracted
from each result (cpm). Two independent experiments with tripli-
cates were conducted. Final results were expressed as per cent of
control contained solvent only instead tested compound.
The general synthetic procedure consists of Schiff base lig-
and formation, by reaction of aldehyde with hydrazide in ethanol
under anaerobic conditions, addition of proper vanadium salt
([VO(acac)2], VOSO4aq or [V(acac)3)]) and in some cases addition
of the co-ligand (1,10-phenanthroline) was used to precipitate the
product. The ligands formed in situ during synthetic procedures are
collected in Table 1. The scheme of the syntheses is presented in
Scheme 1.
2.3.1. Synthesis of [VO(L1)(phen)], 1
5-chlorosalicylaldehyde (236.5 mg, 1.5 mmol) and phenylacetic
hydrazide (227.5 mg, 1.5 mmol) in 50 ml of EtOH were refluxed for
10 min under Ar yielding a colorless transparent suspension. Then
[VO(acac)2] (397.9 mg, 1.5 mmol) was added and mixture was re-
fluxed for 42 min giving green-brown transparent solution. Next
phen (271.9 mg, 1.5 mmol) was added and mixture was refluxed
for next 15 min giving claret-red solution with crystals. It was left
cooling and the claret crystalline product was filtered off, washed
with EtOH and dried in air. Yield 0.621 g, 78 % MW = 533.86. Anal.
Calc. for C27H19ClN4O3V: C, 60.74; H, 3.59; N, 10.49 %. Found: C,
60.59; H, 3.54; N, 10.38 %. The complex is paramagnetic μeff = 1.53
μB. FT-IR (KBr, cm−1): 3452 (w,br), 3015 (w), 1610 (s), 1526 (vs),
1492 (w), 1460 (m), 1426 (s), 1354 (s), 1326 (w), 1294 (m), 1177
(s), 1141 (w), 1090 (w), 1030 (w), 1000 (w), 951 (vs), 870 (w), 843
(vs), 807 (w), 724 (vs), 692 (m), 666 (w), 645 (w), 583 (m), 556
(w), 507 (w), 473 (m). UV-Vis (DMSO): 394 nm, (MeCN): 308, 390
nm, (EtOH): 261, 320, 386 nm.
2.2.4. Glucose utilisation in myocytes and adipocytes
After differentiation of C2C12 myocytes and 3T3-L1 adipocytes
(as described above) medium was changed for medium with 0,2%
bovine serum albumin, 100 IU/ml penicillin, 100 μg/ml strepto-
mycin and after 2 hours incubation medium was changed for fresh
medium containing vanadium complexes. After 24 hours incuba-
tion supernatants were collected. Incubations vanadium complexes
with cells were performed in triplicates and each compound was
tested in three to four independent experiments.
Glucose concentration was determined based on enzymatic re-
action with glucose oxidase and final fluorometrically detection re-
action end product using Amplex Red Glucose/Glucose Oxidase Kit
(Invitrogen) according to manufacturer protocol. 10 μl supernatant
diluted in 50 mM PBS pH 7.4 and 10 μl reagents contained 4 U/ml
glucose oxidase, 0.4 U/ml horseradish peroxidase and 200 μM 10-
acetyl-3,7-dihydroxyphenoxazine in 50 mM PBS pH 7.4 was added
to 384-well black microplate and incubated for 30 minutes at 37°C.
All assays were conducted in triplicates. Fluorescence signal was
measured at excitation in 530 nm and emission in 580 nm using
multimodal microplate reader POLARStar Omega (BMG Labtech)
and glucose concentration in samples was calculated in MARS Data
Analysis Software based on glucose standards. Glucose utilisation
was calculated as differences between incubation medium with-
out cells and medium with cells after incubation with tested com-
pound. Final results were expressed as percent of control contained
cells and solvent only.
2.3.2. Synthesis of [VO(L2)(phen)], 2
5-chlorosalicylaldehyde (235.7 mg, 1.5 mmol), benzhydrazide
(208.7 mg, 1.5 mmol) and EtOH (20 ml) were refluxed under Ar
for 12 min yielding yellow solution. Then [VO(acac)2] (358.7 mg,
1.5 mmol) was added and reflux was continued for 30 min. The
formation of dark brown solution was observed. Then phen (270.1
mg, 1.5 mml) was added and immediate formation of fine brown
crystals was observed. The product was filtered while hot and
dried in air. Yield 0.440 g, 56 % MW = 519.83. Anal. Calc. for
C26H17 ClN4O3V: C, 60.07; H, 3.30; N, 10.78 %. Found: C, 59.67; H,
3.46; N, 10.51 %. The complex is paramagnetic μeff = 1.48 μB. FT-
IR (KBr, cm−1): 3452 (w,br), 3045 (w), 1601 (s), 1530 (s), 1508 (s),
1457 (m), 1422 (s), 1371 (m), 1354 (vs), 1299 (m), 1246 (w), 1179
(m), 1144 (w), 1109 (w), 1093 (w), 1032 (w), 956 (vs), 905 (w), 871
(w), 850 (m), 817 (w), 727 (s), 702 (m), 685 (w), 662 (w), 640 (w),
570 (w), 460 (w), 428 (w). UV-Vis (DMSO): 324, 411 nm, (MeCN):
224, 267, 330, 421 nm, (EtOH): 227, 263, 322, 413 nm.
2.2.5. Viability and cytotoxicity tests
After differentiation of C2C12 myocytes medium was changed
for medium with 0,2% bovine serum albumin, 100 IU/ml penicillin,
100 μg/ml streptomycin and after 2 hours incubation medium was
changed for fresh medium containing vanadium complexes. After
48 hours incubation of 3T3-L1 adipocytes medium was changed
for standard medium with human recombinant insulin and tested
vanadium complexes. Hepatocytes HepG2 was used for experi-
ments after seeding for 18-24 hours and after medium exchange.
Vanadium complexes was tested at final concentration 50, 10 and
1 μM. After 24 hours incubation with tested compounds at 37°C
in 5% CO2 10 μl of PrestoBlue Cell Viability Reagent (Thermo
Fisher Scientific) was added to each microplate well, and the mi-
croplate was placed on an orbital shaker for content mixing. Plates
were incubated for 20 minutes, and the fluorescence intensity at
560 nm excitation and 590 nm emission was determined using
a multi-mode microplate reader POLARstar Omega (BMG Labtech,
Germany). The results were normalized to the untreated control
(cells with solvent only), wherein the intensity of fluorescence
was taken as 100%. Incubations vanadium complexes with cells
were performed in triplicates and each compound was tested in
three to four independent experiments. Similarly, cytotoxicity tests
based on assessment of integration HepG2 hepatocytes membranes
were performed using ToxiLight Cyotoxicity Kit (Lonza) according
to manufacturer protocol.
2.3.3. Synthesis of [VO(L3)(phen)], 3
5-chlorosalicylaldehyde (233.5 mg, 1.5 mmol) and 4-
chlorobenzhydrazide (255.4 mg, 1.5 mmol) and EtOH (50 ml)
were refluxed for 10 min under Ar. The formation of light yellow
transparent solution was observed. Then [VO(acac)2] (393.9 mg,
1.5 mmol) was added. The immediate change of solution colour
to dark brown is observed. The mixture was refluxed for 20 min
and then phen (273.6 mg, 1.5 mmol in 10ml of EtOH) was added.
The solution turns blooded-red. The solution was left for one day
for crystallization. The formed crystals were filtered off, washed
with cold EtOH and dried in air. Yield 0.597 g, 72 % MW = 554.28.
Anal. Calcd. for C26H16 Cl2N4O3V: C, 56.34; H, 2.91; N, 10.11 %.
Found: C, 56.31; H, 2.92; N, 9.96 %. The complex is paramagnetic
μeff = 1.44 μB. FT-IR (KBr, cm−1): 3452 (w,br), 3051 (w), 1604 (s),
1527 (m), 1506 (vs), 1489 (s), 1455 (s), 1425 (s), 1371 (m), 1355
(s), 1297 (m), 1243 (w), 1181 (s), 1143 (w), 1090 (m), 1037 (w),
1011 (w), 957 (vs), 904 (w), 867 (w), 848 (m), 814 (m), 744 (m),
727 (m), 659 (w), 643 (w), 577 (m), 500 (w), 466 (w), 432 (m).

4
J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
Table 1
List of ligands and ligand components.
Ligand notation
aldehyde
hydrazide
H2L1
H2L2
H2L3
H2L4
H2L5
H2L6
H2L7
H2L8
H2L9
H2L10
H2L11
5-chlorosalicylaldehyde
5-chlorosalicylaldehyde
5-chlorosalicylaldehyde
5-chlorosalicylaldehyde
5-chlorosalicylaldehyde
5-chlorosalicylaldehyde
5-hydroxysalicylaldehyde
5-hydroxysalicylaldehyde
5-hydroxysalicylaldehyde
5-chlorosalicylaldehyde
5-hydroxysalicylaldehyde
phenylacetic hydrazide
benzhydrazide
4-chlorobenzhydrazide
4-hydroxybenzhydrazide
nicotinic hydrazide
2-hydroxybenzhydrazide
phenylacetic hydrazide
benzhydrazide
nicotinic hydrazide
3-hydroxy-2-naphthoic acid hydrazide
3-hydroxy-2-naphthoic acid hydrazide
Scheme 1. Scheme of the synthesis of 1-16 complexes.
μB. FT-IR (KBr, cm−1): 3411 (m,br), 1609 (vs), 1492 (vs), 1460 (m),
1426 (s), 1370 (s), 1352 (s), 1280 (m), 1243 (w), 1183 (m), 1168 (w),
1140 (w), 1097 (w), 1034 (w), 957 (s), 907 (w), 866 (w), 845 (s),
759 (w), 724 (s), 664 (w), 643 (w), 586 (w), 558 (w), 511 (w), 477
(w), 449 (w), 429 (w). UV-Vis (DMSO): 326, 341, 413 nm, (MeCN):
225, 268, 332, 419 nm, (EtOH): 226, 265, 328, 415 nm.
UV-Vis (DMSO): 328, 344, 417 nm, (MeCN): 225, 264, 325, 416 nm,
(EtOH): 229, 263, 322, 410 nm.
2.3.4. Synthesis of [VO(L4)(phen)]·2H2O, 4
5-chlorosalicylaldehyde (234.8 mg, 1.5 mmol), 4-hydroxy
benzhydrazide (224.5 mg, 1.5 mmol) and EtOH (20 ml) were re-
fluxed under Ar for 10 minutes. The light yellow solution was
formed and then solid [VO(acac)2] (400.0 mg, 1.5 mmol) was
added and the mixture was refluxed for additional 20 min. The
mixture becomes brown and no crystal formation was observed.
Then phen (278.3 mg, 1.5 mmol) was added. The solution becomes
blooded-red and it was boiled in open flask to beginning of the
crystallization. This was filtered off, washed with small amount of
cold EtOH and dried in air. Yield 0.644 g, 75 % MW = 571.86. Anal.
Calcd. for C26H21ClN4O6V: C, 54.61; H, 3.70; N, 9.80 %. Found: C,
54.54; H, 3.57; N, 9.58 %. The complex is paramagnetic μeff = 1.52
2.3.5. Synthesis of [VO(L5)(phen)]·2H2O·EtOH, 5
5-chlorosalicylaldehyde (236 mg, 1.5 mmol), nicotinic hydrazide
(205 mg, 1.5 mmol) in 75 ml of EtOH were refluxed under Ar for
15 minutes. To the yellow transparent solution [VO(acac)2] (387
mg, 1.5 mmol) was added and reflux was continued for 5 minutes.
Then phen (286 mg, 1.6) was added and ethanol was removed by
distillation to reduce the mixture volume to ½ of initial amount.
Formed red precipitate was filtered off, washed with cold EtOH
and dried in air. Yield 0.518 g, 64 % MW = 602.92. Anal. Calcd.

J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
5
for C27H26ClN5O6V: C, 53.79; H, 4.35; N, 11.62 %. Found: C, 54.15;
2.3.9. Synthesis of [VO(L5)(H2O)], 9
H, 4.06; N, 11.89 %. The complex is paramagnetic μeff = 1.88 μB.
FT-IR (KBr, cm−1): 3441 (s,br), 1605 (vs), 1517 (vs), 1473 (m), 1455
(s), 1425 (s), 1371 (w) 1352 (s), 1318 (w), 1290 (m), 1244 (w), 1178
(m), 1142 (m), 1090 (w), 1046 (w), 1029 (m), 956 (vs), 903 (w), 871
(w), 849 (m), 819 (m), 804 (w), 725 (s), 703 (m), 661 (w), 645 (w),
570 (w), 490 (w), 460 (w), 426 (w). UV-Vis (DMSO): 324, 411, 440
nm, (MeCN): 218, 270, 325, 419 nm, (EtOH): 227, 266, 324, 417 nm.
The 5-chlorosalicylaldehyde (470 mg, 3 mmol) and the nicotinic
hydrazide (411 mg, 3 mmol) in 45 ml of ethanol were refluxed
for 15 minutes under Ar (yellow solution was observed). Then the
[VO(acac)2] (795 mg, 3 mmol) was added and the formation of or-
ange transparent solution was observed. The reflux was continued
for 20 minutes under Ar. Within 20 minutes the gradual mixture
colour change to green was observed with formation of precipita-
tion. The green compound was filtered off, washed several times
with ethanol and dried in room temperature. Yield: 0.839 g, 80 %
MW = 358.62. Anal. Calc. for C13H10ClN3O4V: C, 43.54; H, 2.81; N,
11.72 %. Found C, 43.12; H, 2.72; N, 11.83 %. The complex is para-
magnetic μeff = 1.56 μB. FT-IR (KBr, cm−1): 3423 (m,br), 1613 (vs),
1582 (w), 1535 (vs), 1481 (w), 1459 (s), 1424 (w), 1369 (m), 1346
(s), 1317 (w), 1287 (s), 1184 (s), 1147 (w), 1121 (w), 1090 (w), 1055
(w), 996 (s), 948 (w), 909 (w), 821 (m), 747 (w), 727 (m), 706 (m),
692 (w), 659 (m), 585 (m), 526 (w), 502 (w), 462 (w), 438 (w).
UV-Vis (DMSO): 326, 339, 412 nm, (MeCN): 249, 327 nm, (EtOH):
245, 323 nm.
2.3.6. Synthesis of [VO(L6)(phen)]·EtOH, 6
5-hydroxysalicylaldehyde (417.5 mg,
3
mmol), 2-hydroxy
benzhydrazide (456.7 mg, 3 mmol) and EtOH (45ml) were re-
fluxed under Ar for 12 min yielding transparent brownish-yellow
solution. Then [VO(acac)2] (796.6 mg, 3 mmol) was added and
reflux was continued for 40 min. The solution becomes very dark,
almost black. Then phen (547.4 mg, 3 mmol) was added and the
solution colour change to dark-red was observed, the reflux was
continued for next 10 min. The fine, brown crystals were formed
on cooling. This was filtered off, washed with small amounts of
EtOH and dried in air. Yield 1.12 g, 66 % MW = 563.46. Anal. Calcd.
for C28H24N4O6V: C, 59.69; H, 4.29; N, 9.94 %. Found: C, 59.18; H,
3.94; N, 10.23 %. The complex is paramagnetic μeff = 1.51 μB. FT-IR
(KBr, cm−1): 3394 (w,br), 1626 (s), 1600 (s), 1551 (s), 1515 (vs),
1493 (vs), 1449 (w), 1425 (s), 1382 (w), 1357 (m), 1284 (s), 1252
(s), 1221 (m), 1166 (s), 1105 (w), 1064 (w), 970 (vs), 867 (w), 846
(m), 819 (s), 751 (m), 725 (s), 696 (w), 661 (w), 641 (w), 577 (w),
543 (w), 493 (w), 449 (m), 425 (w). UV-Vis (DMSO): 382, 421 nm,
(MeCN): 281, 372, 480 nm, (EtOH): 225, 264, 339, 434 nm.
2.3.10. Synthesis of [VO(L9)(H2O)], 10
5-hydroxysalicylaldehyde (207 mg, 1.499 mmol) and the nico-
tinic hydrazide (206 mg, 1.5 mmol) in 50 ml of ethanol were re-
fluxed for 10 minutes under Ar (green solution was observed).
Then the [VO(acac)2] (392 mg, 1.5 mmol) was added. The reflux
was continued for 30 minutes under Ar. The brown compound was
filtered off, washed several times with ethanol and dried in room
temperature. Yield: 0.323 g, 63 %, MW = 340.19. Anal. Calc. for
C13H11 N3O5V: C = 45.90; H = 3.26; N, 12.35 %. Found: C, 46.19; H
3.23; N, 12.50 %. The complex is paramagnetic μeff = 1.60 μB. FT-
IR (KBr, cm−1): 3411 (w,br), 1603 (s), 1545 (vs), 1471 (s), 1385 (w),
1345 (m), 1279 (s), 1222 (w), 1196 (w), 1161 (s), 1123 (w), 1103
(w), 1056 (w), 969 (s), 826 (vs), 725 (w), 694 (w), 659 (w), 599
(m), 483 (w), 457 (w), 413 (w). UV-Vis (DMSO): 320, 335, 434 nm,
(MeCN): 248, 326 nm, (EtOH): 240, 329, 420 nm.
2.3.7. Synthesis of [VO(L7)(phen)], 7
5-hydroxysalicylaldehyde (207.9 mg, 1.5 mmol) and pheny-
lacetic hydrazide (226.1 mg, 1.5 mmol) in 50 ml of EtOH were
refluxed for 8 min under Ar yielding a transparent light yellow
solution. Then [VO(acac)2] (399.7 mg, 1.5 mmol) was added and
mixture was refluxed for 47 min giving dark-brown transparent so-
lution. Then phen (273 mg, 1.5 mmol) was added and reflux was
continued for 14 min. The mixture with formed crystals was left
aside for cooling and claret crystals were filtered off, washed with
EtOH and dried in air. Yield 0.585 g, 76 % MW = 515.41. Anal.
Calcd. for C27H20N4O4V: C, 62.92; H, 3.91; N, 10.87 %. Found: C,
62.55; H, 3.87; N, 10.63 %. The complex is paramagnetic μeff = 1.50
μB. FT-IR (KBr, cm−1): 3270 (w,br), 1604 (s), 1538 (m), 1517 (vs),
1468 (m), 1424 (m), 1379 (w), 1360 (m), 1289 (s), 1227 (w), 1153
(m), 993 (w), 967 (w), 936 (vs), 906 (w), 870 (w), 849 (m), 826
(m), 771 (w), 739 (m), 724 (m), 646 (w), 582 (w), 546 (w), 527
(w), 453 (w), 430 (w). UV-Vis (DMSO): 324, 411, 440 nm, (MeCN):
252, 374 nm, (EtOH): 423 nm.
2.3.11. Synthesis of [VO(L6)(EtO)], 11
5-chlorosalicylaldehyde
(235.3
mg,
1.5mmol),
2-
hydroxybenzhydrazide (229.9 mg; 1.5 mmol) and EtOH (25
ml) were refluxed for 15 min under Ar. The insoluble Schiff base
was formed and solution becomes light yellow. Then VOSO4 aq
(333.4 mg; 1.5 mmol) was added and reflux was continued for 55
min. The solution becomes transparent, very dark yellow without
any precipitation. The reflux was removed and solvent was evap-
orated but no precipitation was observed. Addition of bpy did not
yield formation of the product (on a small sample). Thus water
was added and the mixture was sonicated for several minutes. The
complex was filtered off, washed with water 3 times and dried.
Yield 0.574 g, 95 % MW = 400.68. Anal. Calc. for C16 H14 ClN2O5V:
C, 47.96; H, 3.52; N, 6.99 %. Found: C, 48.34; H, 3.49; N, 7.05 %.
The complex is diamagnetic. FT-IR (KBr, cm−1): 2981 (w), 2921
(w), 2863 (w), 1621 (vs), 1607 (w), 1586 (w), 1545 (vs), 1518 (w),
1487 (s), 1467 (m), 1417 (w), 1377 (m), 1344 (s), 1307 (m), 1270
(s), 1251 (m), 1225 (m), 1204 (s), 1151 (w), 1091 (s), 1052 (m),
1034 (m), 992 (vs), 964 (w), 913 (m), 866 (w), 831 (s), 755 (s),
733 (m), 704 (m), 682 (w), 659 (w), 638 (w), 612 (s), 575 (m), 538
(w), 481 (w), 466 (m), 446 (w). UV-Vis (DMSO): 323, 340, 410 nm,
(MeCN): 292, 337, 406 nm, (EtOH): 290, 337, 412 nm.
2.3.8. Synthesis of [VO(L8)(phen)]·H2O, 8
5-hydroxysalicylaldehyde (208.8 mg; 1.5 mmol), benzhydrazide
(207.9 mg; 1.5 mmol) and EtOH (22 ml) were refluxed under Ar
for 10 min giving clear yellow solution. Then [VO(acac)2] (399.2
mg; 1.5 mmol) was added and mixture was refluxed for 30 min.
The solution changes the colour from dark yellow to almost red.
Then phen (278.1 mg; 1.5 mmol) was added and mixture was re-
fluxed for additional 10 min. The mixture was evaporated under
Ar to ca 10 ml, cooled and the complex was filtered off, washed
2 times with small amounts of EtOH and dried in air. Yield 0.300
g, 38% MW = 519.40. Anal. Calcd. for C26H20N4O5V: C, 60.12; H,
3.88; N, 10.79 %. Found: C, 59.96; H, 4.08; N, 10.21 %. The com-
plex is paramagnetic μeff = 1.57 μB. FT-IR (KBr, cm−1): 3255 (m,br),
1604 (m), 1586 (m), 1544 (s), 1508 (vs), 1494 (s), 1439 (w), 1427
(s), 1357 (m), 1287 (m), 1220 (m), 1164 (m), 1105 (w), 1038 (w),
957 (s), 869 (w), 847 (m), 821 (s), 791 (w), 724 (s), 710 (m), 643
(w), 579 (w). UV-Vis (DMSO): 336, 437 nm, (MeCN): 289, 362, 439
nm, (EtOH): 225, 287, 351, 421 nm.
2.3.12. Synthesis of [VO(L10)(EtO)], 12
5-chlorosalicylaldehyde (313 mg, 2 mmol) and 3-hydroxy-2-
naphthoic acid hydrazide (405 mg, 2 mmol) were dissolved in
100 ml of ethanol under Ar flow on a magnetic stirrer. The mixture
was refluxed for 10 minutes with constant stirring and the temper-
ature was raised to 100 °C. Then VOSO4 aq (444 mg, 2 mmol) and
30 ml of ethanol was added and heterogenic mixture was refluxed

6
J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
for ca 40 minutes. After that, the volume of the reaction mixture
was concentrated to final volume of ca 40 ml and cooled to the
room temperature. The brown powder started to precipitate form-
ing red-brown solution. The precipitate was filtered off, washed
with ethanol and dried in air. Yield: 0.658 g, 73 % MW = 450.75.
Anal. Calcd. for C20H16 ClN2O5V: C, 53.29; H, 3.58; N, 6.21 %. Found:
C, 53.31; H, 3.51; N, 6.22 %. The complex is diamagnetic. FT-IR (KBr,
cm−1): 3471 (w,br), 2974 (w), 2927 (w), 2869 (w), 1637 (s), 1598
(s), 1572 (w), 1541 (vs), 1518 (vs), 1464 (vs), 1377 (w), 1361 (w),
1336 (m), 1299 (vs), 1268 (vs), 1237 (w), 1219 (w), 1198 (w), 1170
(w), 1148 (m), 1085 (vs), 1058 (w), 1027 (s), 1000 (vs), 951 (w),
903 (s), 877 (m), 833 (s), 819 (s), 798 (w), 763 (m), 743 (s), 706
(m), 671 (m), 629 (s), 582 (m), 516 (w), 471 (m), 436 (w). UV-Vis
(DMSO): 326, 416 nm, (MeCN): 260, 323, 411 nm, (EtOH): 324, 410
nm.
(m), 822 (m), 751 (w), 729 (m), 689 (w), 666 (w), 631 (w), 586
(m), 556 (w), 507 (w), 473 (w), 445 (w). UV-Vis (DMSO): 302, 329,
388 nm, (MeCN): 284, 298, 326, 393 nm, (EtOH): 301, 330, 392
nm.
2.3.16. Synthesis of [V(L7)2]·0.5H2O, 16
5-hydroxysalicylaldehyde (277.6 mg, 2 mmol), phenylacetic hy-
drazide (301.1 mg, 2 mmol) and EtOH (21ml) were refluxed un-
der Ar for 13 min with formation of yellow transparent solution.
Then [V(acac)3] (348.5 mg, 1 mmol) was added and reflux was
continued for 28 min. The solution immediately turns to brown. In
two minutes later, after addition of vanadium complex, the brown
product started to precipitate. This was filtered off, washed with
EtOH and dried in air. Yield 0.267 g, 45 % MW = 596.48. Anal.
Calcd. for C30H25N4O6.5V: C, 60.41; H, 4.22; N, 9.39 %. Found: C,
60.52; H, 4.18; N, 9.47 %. The complex is paramagnetic μeff = 2.48
μB. FT-IR (KBr, cm−1): 3022 (w), 1575 (w), 1554 (vs), 1523 (s), 1480
(w), 1435 (s), 1391 (w), 1366 (w), 1331 (w), 1270 (m), 1243 (m),
1229 (s), 1172 (vs), 1119 (w), 1008 (w), 949 (w), 827 (vs), 792
(w), 725 (s), 692 (m), 651 (w), 569 (w), 488 (w), 449 (w). UV-Vis
(DMSO): 386 nm, (MeCN): 251, 372 nm, (EtOH): 281, 366 nm.
2.3.13. Synthesis of [VO2(L7)]·H2O, 13
5-hydroxysalicylaldehyde (208.3 mg, 1.5 mmol) and pheny-
lacetic hydrazide (226.5 mg, 1.5 mmol) in 50 ml of EtOH were re-
fluxed for 15 min under Ar yielding a transparent light yellow solu-
tion. Then [VO(acac)2] (399 mg, 1.5 mmol) was added and mixture
was refluxed for 40 min giving yellow-black transparent solution.
This was evaporated in part yielding a dark-green oil liquid. Af-
ter three days black muddy-like product was filtered off, washed
with EtOH and dried in air. Yield: 0.200 g, 36 % MW = 370.23.
Anal. Calcd. for C15H15N2O6V: C, 48.66; H, 4.08; N, 7.57 %. Found:
C, 48.14; H, 3.83; N, 6.31 %. The complex is diamagnetic. FT-IR (KBr,
cm−1): 3260 (w,br), 3043 (w,br), 1658 (w), 1523 (vs), 1445 (w),
1370 (w), 1280 (w), 1190 (w), 1115 (w), 1076 (w), 1029 (w), 978
(s,br), 835 (w), 725 (w), 697 (w), 595 (w). UV-Vis (DMSO): 296
nm, (MeCN): 311 nm, (EtOH): 259 nm.
2.4. Crystallographic data collection and structure refinement
Diffraction intensity data for single crystal of 11 were col-
lected at room temperature on a KappaCCD (Nonius) diffractome-
ter with graphite-monochromated Mo Kα radiation (λ = 0.71073
˚
A) and for 12 were collected at 293 K on the Oxford Diffrac-
tion Super Nova diffractometer using monochromatic Mo Kα ra-
˚
diation, λ = 0.71073 A. Cell refinement and data reduction were
performed using firmware [25]. Positions of all of non-hydrogen
atoms in 11 were determined by direct methods using SHELXL-
2017/1 [26,27] and in 12 were determined by heavy atom method
using SIR92 software [28]. All non-hydrogen atoms for 11 and
12 were refined anisotropically using weighted full-matrix least-
squares on F2. Refinement and further calculations were carried
out using SHELXL-2017/1 [26,27]. All hydrogen atoms joined to car-
bon atoms were positioned with an idealized geometries and re-
fined using a riding model with Uiso(H) fixed at 1.5 Ueq of C for
methyl groups and 1.2 Ueq of C for other groups (for 11) and at
1.2 Ueq (Carom) (for 12). The position of the hydrogen atom of the
-OH group in 11 and 12 was determined from the Fourier differ-
ential map. The figures were made using DIAMOND software [29].
CCDC 1883287 and 966197 contain the supplementary crystallo-
graphic data for 11 and 12 respectively. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
2.3.14. Synthesis of [VO(L11 )(H2O)]·1.5H2O, 14
5-hydroxysalicylaldehyde (207 mg, 1.5 mmol) and 3-hydroxy-2-
naphthoic acid hydrazide (303 mg, 1.5 mmol) were dissolved in
90 ml of ethanol under Ar flow on a magnetic stirrer. The mixture
was refluxed for 20 minutes with constant stirring and the tem-
perature was raised to 100 °C. Then VOSO4 aq (333 mg, 1.5 mmol)
and 10 ml of ethanol was added and the heterogenic mixture was
refluxed for ca 20 minutes. After that, the volume of the reac-
tion mixture was concentrated to final volume of ca 40 ml and
cooled to the room temperature. The orange powder started to
precipitate forming dark brown solution. The precipitate was fil-
tered off, washed with ethanol and dried in air. Yield: 0.482 g, 76 %
MW = 434.29. Anal. Calcd. for C18 H17 N2O7.5 V: C, 50.13; H, 3.74; N,
6.50 %. Found: C, 50.12; H, 3.50; N, 6.19 %. The complex is diamag-
netic. FT-IR (KBr, cm−1): 3328 (s,br), 1630 (w), 1593 (m), 1534 (s),
1456 (w), 1383 (w), 1342 (w), 1309 (w), 1260 (w), 1219 (m), 1146
(w), 1086 (w), 970 (s), 898 (w), 829 (w), 763 (m), 640 (w), 573
(w), 550 (w), 471 (w), 440 (w). UV-Vis (DMSO): 339 nm, (EtOH):
317 nm.
3. Results and discussion
3.1. General remarks to the synthesis
2.3.15. Synthesis of [V(L4)2]·H2O·EtOH, 15
The in situ generated in ethanol Schiff base ligand, under anaer-
obic conditions, reacts with respective vanadium substrate yield-
ing the respective products 1-16. For V(IV) complexes two sub-
strates were used: [VO(acac)2] or VOSO4aq. This last was found to
give mixtures with unreacted substrate thus very rigid procedure
have to be applied, especially connected with the time of the reac-
tion. Generally two synthetic schemes were applied: a) phen was
used as a co-ligand, resulting in [VO(Lx)(phen)] type complexes
(where Lx denote ligands L1-L8) and b) co-ligand was not added,
resulting in [VO(Ly)(solv)] (where y = 5, 6, 9-11) or [VO2(L7)] type
complexes. In general phen could not be used for VOSO4aq as a
substrate due to the formation of [VO(phen)2] as the impurities.
The use of a co-ligand stabilizes the V(IV) oxidation state, and
the formed complexes were found to be stable in air. When phen
5-chlorosalicylaldehyde (469.3 mg,
3
mmol), 4-hydroxy
benzhydrazide (456.4 mg,
3 mmol) and EtOH (25 ml) were
refluxed under Ar for 15 min yielding a colorless transparent
solution. Then [V(acac)3] (590.0 mg, 1.7 mmol) was added and the
reflux was continued for next 12 min. After 10 min the product
started to precipitate. The mixture was cooled and dark brown
product was filtered off, washed with EtOH and dried. Yield: 0.654
g, 67 % MW = 692.40. Anal. Calcd. for C30H26Cl2N4O8V: C, 52.04;
H, 3.78; N, 8.09 %. Found: C, 52.23; H, 3.99; N, 7.94 %. The complex
is paramagnetic μeff = 2.44 μB. FT-IR (KBr, cm−1): 3429 (w,br),
3163 (w,br), 1612 (vs), 1567 (w), 1542 (m), 1512 (m), 1491 (w),
1469 (s), 1407 (w), 1367 (vs), 1341 (w), 1315 (w), 1268 (vs), 1240
(w), 1176 (m), 1137 (w), 1101 (w), 1037 (w), 943 (w), 901 (w), 841

J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
7
Fig. 1. The molecular structures of complexes 11 (left) and 12 (right) together with the atom labelling scheme. The hydrogen atoms were omitted for clarity. Thermal
ellipsoids represent 30% of displacement probability.
Table 2
Crystal data and structure refinement for 11 and 12.
11
12
Empirical formula
Formula weight
Temperature
C
16H14ClN2O5V
C20H16ClN2O5V
450.74
400.68
293(2) K
293(2) K
˚
˚
Wavelength
0.71073 A
Triclinic
P -1
0.71073 A
Crystal system
Space group
Triclinic
P -1
˚
˚
Unit cell dimensions
a = 7.5605(6) A
a = 6.8016(7) A
˚
˚
b = 8.6791(7) A
b = 11.7621(14) A
˚
˚
c = 12.9344(8) A
α = 90.196(4)°
β = 99.341(4)°
c = 12.1871(11) A
α = 91.498(5)°
β = 95.372(5)°
γ = 98.891(4)°
γ = 100.276(6)°
3
3
˚
˚
Volume
827.06(11) A
954.21(17) A
Z
2
2
Density (calculated)
Absorption coefficient
F(000)
1.609 Mg/m3
0.791 mm−1
1.569 Mg/m3
0.696 mm−1
408
460
Crystal size
0.350 × 0.180 × 0.060 mm3
2.376 to 27.612°
-9≤h≤9, -11≤k≤=11,
-5≤l≤16
0.440 × 0.150 × 0.050 mm3
1.680 to 27.015°
-8≤h≤8, -14<≤k≤14,
-2≤l≤15
Theta range for data collection
Index
ranges
Reflections collected
Independent reflections
Completeness to theta = 25.242°
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
3734
4081
3734 [R(int) = 0.0706]
4081 [R(int) = 0.0409]
98.9 %
99.4 %
Full-matrix least-squares on F2
3734 / 4 / 252
1.035
Full-matrix least-squares on F2
4081 / 0 / 268
1.181
R1 = 0.0786, wR2 = 0.1923
R1 = 0.0743, wR2 = 0.2024
R1 = 0.1157, wR2 = 0.2106
R1 = 0.0914, wR2 = 0.2106
3
3
˚
˚
0.666 and -0.647 e/A
0.696 and -0.464 e/A
Table 3
was not used, in air oxidation of vanadium to V(V) was observed,
V(IV) relatively stable complexes were obtained only if the prod-
uct was of a low solubility. Nevertheless, such complexes had to
be stored under inner atmosphere. When V(III) was used as a sub-
strate, nonoxido complexes 15 and 16 of formula [V(L)2] were iso-
lated.
˚
Selected bond distances [A] and angles [°] in complexes 11 and 12.
11
12
V(1)-O20
1.577(4)
V(1)-O28
1.581(4)
1.826(4)
1.918(4)
1.755(4)
2.136(4)
106.1(2)
107.8(2)
99.17(18)
104.7(2)
91.24(18)
141.38(19)
95.5(2)
V(1)-O7
1.830(3)
V(1)-O23
V(1)-O12
1.929(4)
V(1)-O13
V(1)-O21
1.758(3)
V(1)-O27
V(1)-N9
2.115(4)
V(1)-N15
O(20)-V(1)-O(21)
O(20)-V(1)-O(7)
O(21)-V(1)-O(7)
O(20)-V(1)-O(12)
O(21)-V(1)-O(12)
O(7)-V(1)-O(12)
O(20)-V(1)-N(9)
O(21)-V(1)-N(9)
O(7)-V(1)-N(9)
O(12)-V(1)-N(9)
107.5(2)
O(28)-V(1)-O(27)
O(28)-V(1)-O(23)
O(27)-V(1)-O(23)
O(28)-V(1)-O(13)
O(27)-V(1)-O(13)
O(23)-V(1)-O(13)
O(28)-V(1)-N(15)
O(27)-V(1)-N(15)
O(23)-V(1)-N(15)
O(13)-V(1)-N(15)
3.2. Description of structure 11 and 12
107.56(19)
99.62(15)
103.89(18)
88.94(16)
142.95(16)
96.87(17)
153.19(18)
82.92(14)
74.29(14)
The asymmetric parts of the units cells of the complexes 11
and 12 are shown in Fig. 1. The crystallographic data and detailed
information on the structure solution and refinement are given
in Table 2. Selected bond distances and bond angles are listed
in Table 3. The complexes crystallize in the triclinic space group
P -1 with the asymmetric cell unit, containing one molecule of
[VO(L)(EtO)] complex, where L = L6 (for 11) or L10 (for 12). The
crystal packing for 11 and 12 are presented in the Supplementary
materials.
156.41(19)
82.57(17)
74.00(16)

8
J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
Fig. 2. The π···π stacking in 11 (left) and 12 (right).
Table 4
In the structure of 11 the coordination environment of the
˚
The π···π interactions in 11 and 12 [A].
vanadium atom approximates a square pyramid with the O20 ox-
ido ligand occupying the apical position and the donor atoms of
the L ligand occupying three (ONO tridentate mode) of the po-
sitions in the basal plane, O7, N9, O12. The fourth position, O21
is linked to the ethoxy group, whose carbon atoms C22 and C23
show the disorder and have been modeled in two positions (A
and B) with a ratio of 60/40. The terminal oxido groups show
the short bond distances characteristic of a V=O double bond and
are in agreement with the vanadyl group in other V(V) complexes
[30]. The shortest V-O distance is to the ethoxy oxygen atom in
agreement with the V-O distance to the terminal OCH3 group in
[VO(OCH3)3]2 [31]. The V-N distance is appreciably longer than
the V-O distances, a fact which seems to be characteristic of sev-
eral chelating ligands containing oxygen and nitrogen donors [32].
This suggests that some π-donation, leading to a partial multiple
bond, is a feature of oxygen coordination in vanadium(V) com-
plexes. Least-squares calculations show the vanadium atom to be
11
12
π···π
Cg(1)···Cg(2) [1-x,1-y,1-z] 3.9518(3)
Cg(2)···Cg(1) [1-x,1-y,1-z] 3.9518(3)
Cg(2)···Cg(3) [1-x,-y,1-z]
shift
π···π
shift
1.689 3.7856(5)
1.871 3.7856(5)
3.8151(5)
1.507
1.496
1.571
1.359
Cg(3)···Cg(2) [1-x,-y,1-z]
3.8151(5)
Cg1: C(1)-C(2)-C(3)-
Cg(1): C(1)-C(2)-C(3)-
C(4)-C(5)-C(6)
Cg2:
C(8)-C(9)-C(10)
Cg(2): C(3)-C(4)-C(5)-
C(6)-C(7)-C(8)
C(13)-C(14)-C(15)-
C(16)-C(17)-C(18)
Cg(3): C(17)-C(18)-
C(19)-C(20)-C(21)-C(22)
Table 5
˚
Hydrogen bonds for 11 and 12 [A and °].
D-H···A
d(D-H) d(H···A) d(D···A) <(DHA)
11 C(8)-H(8)···O(20) [1-x,1-y,-z]
0.93
2.59
2.50
3.355(6) 139.7
3.394(6) 161.3
2.614(5) 148(7)
3.607(6) 125.9
2.638(6) 144(7)
C(2)-H(2)···O(19) [-1+x,-1+y,z] 0.93
˚
0.470 A above the basal plane. The square pyramid is slightly
O(19)-H(19O)···N(10)
12 C(21)-H(21)···Cl(24) [x,-1+y,z]
O(11)-H(11O)···N(14)
0.95(2) 1.76(5)
0.93 2.98
0.77(8) 1.97(8)
distorted so as to raise the nitrogen atom above the plane formed
by the three donor atoms of the tridentate ligand. This is also
evident from the apical Ooxo-V-N angles which are significantly
less than the apical angles involving the oxygen atoms in the
basal plane. This effect has also been observed in the (VOL)2O
unit [33] and attributed to a greater repulsion between the non-
bonding electrons on the oxygen donors. The value of the angle
defined by the oxygen of the coordinated ethoxy group is much
larger than that of the tetrahedron (109.5°), which is consistent
with the relatively short V-O bond, which means some π donation
and the nature of the partial multiple bond. The vanadium atom
square pyramidal coordination polyhedron geometry is confirmed
by the general descriptor τ = (β − α)/60 = 0.005, where α and β
are the two largest angles at the metal center for five-coordinated
complexes. For a perfect square-pyramidal geometry τ equals to
zero, and it becomes unity for the perfect trigonal-bipyramidal ge-
ometry [34]. In the complex molecule, the aromatic ring of sali-
cylaldehyde component of the L ligand, forms a plane twisted to
the phenyl plane by angle 6.73°. Packing analysis of the crystal
structure reveals that the complex molecules are held together
by several C-H···π, π···π stacking, and intermolecular hydrogen
bonding interactions which are summarized in the Table 4 and
Table 5 and presented in Figs 2 and 3, respectively.
Fig. 3. Intermolecular hydrogen interactions of O-H ... N, C-H ... O and C-H ... π types in the structures of compounds 11 (left) and 12 (right).

J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
9
In the monomeric complex 12 the central vanadium atom has a
five-coordinate sphere with VO4N composition, taking the shape of
a slightly deformed square pyramid. The planar base of this solid
is made of the atoms of a tridentate and it consists of phenolic
oxygen O23, imine nitrogen N15, enol oxygen O13, and an oxygen
atom O27 from deprotonated ethoxide oxygen. The apical position
of the square pyramid is occupied by the terminal oxido-group
˚
O28. The short distance V1-O28 of 1.581(4) A indicates the pres-
ence of double vanadium-oxygen bond (V=O), which is common
in five- and six-coordinated complexes [35,36] of vanadium(IV) and
vanadium(V). The central vanadium V1 atom is located above the
˚
basal plane of O13, O27, N15, O23 by 0.455 A and is directed to-
wards the apical oxido ligand. Four bonds V-O type have differ-
ent lengths, where the bond V=Ooxo is the shortest, and V-Oenolate
[oxygen O28] is the longest. Similarly to other vanadium(V) com-
plexes of related ligands [35,36], the bond lengths V-O are in the
order V=Ooxo < V-Ophenoxide < V-Oenolate, which clearly indicates a
stronger binding of the alkoxy group as compared to oxygen atoms
of phenoxide or enolate. The tridentate ligand L10, which is the
Schiff’s base, coordinating to the acceptor center V(V), forms two
chelate rings, one six- and the other five-membered with the cor-
responding bite angles being 82.56° and 73.98°. The shortest inter-
Fig. 4. The UV-Vis spectra of 2 (black, solid line), 11 (red, dashed line) and 15 (blue,
dotted line) in MeCN, d = 1 cm.
˚
molecular V1...V1[1-x,-y,-z] distance is 5.945(1) A. Packing analy-
sis of the crystal structure reveals that the complex molecules are
held together by several π···π stacking and two hydrogen bond-
ing interactions (one intramolecular) which are summarised in the
Table 4 and Table 5 and presented in Figs 2 and 3 respectively.
3.3. IR spectra
The IR spectra of complexes were measured in the 400 – 4000
cm−1 range. All bands were collected in the synthetic part of the
paper. The most interesting for the vanadium complexes is the
900–1000 cm−1 range, in which the vanadyl group bands are ob-
served. They are clearly visible for complexes 1–14. In spectra of 11
and 12 characteristic bands at 2863–2981 cm−1 are related to the
coordinated EtO− molecule. For complexes of the [VO(Lx)(phen)]
type (1–8) there are bands at ca 744, 1438, and 1505 cm−1, charac-
teristic for coordinated 1,10-phenantroline. For all of the complexes
the intensive band at ca 1600 cm−1 can be assigned to C=N group
in the Schiff base ligand.
3.4. UV-Vis spectra
Fig. 5. The UV-Vis reflection spectra of 3 (black, solid line), 11 (red, dashed line)
and 16 (blue, dotted line) after Kubelka-Munk transformation [37]. BaSO4 as inter-
nal white standard.
The example UV-Vis spectra in MeCN (for 2, 11 and 15) and the
reflectance spectra (for 3, 11 and 16) are presented in Figs 4 and
5 respectively. Data for all other complexes as well as in other sol-
vents (such as MeOH, EtOH, DMSO, DMF, dichloroethane and 1-
octanol) are presented in the Supplementary materials. The band
positions for DMSO, MeCN and EtOH were posted in the Experi-
mental part. The bands of Schiff base ligand and co-ligands (for 2
and 3) are observed in the UV part of the spectra. The band above
400 nm is assigned to metal-to-ligand charge-transfer (MLCT) con-
nected with the presence of Schiff base ligand. The character of
this band is confirmed by its solvatochromism, as it was shown
in the Supplementary materials. The molar absorption coefficients
in DMSO for 11 are 10900 mol−1cm−1dm3 (at 323 nm), 11200
mol−1cm−1dm3 (at 340 nm) and 6120 mol−1cm−1dm3 (at 410 nm).
All others are presented in the Supplementary materials. Due to
relatively low intensity of the d-d band in a solution, this band can
be better seen in a solid state (Fig. 5). The complex 3 has band at
720 nm, underlying +4 formal oxidation stated of vanadium and
d1 configuration. For complex 11 no d-d band is observed as it
is typical for V(V) with d0 configuration. The complex 16, where
vanadium is on the +3 oxidation state, has d-d band at 540 nm.
The results of the UV-Vis reflectance spectra are consist with the
magnetic susceptibility measurements.
The stability of the complexes was measured in all sol-
vents studied (see Supplementary materials) and generally the
complexes are stable. The most interesting is the stability in
DMSO/H2O (20 μl + 3 ml) mixture both in pH = 7 and 2 (as in
human stomach) conditions (each complex was measured in 340 s
intervals 15 times). This DMSO/H2O ratio was used later in biolog-
ical activity studies. These data for all complexes are included in
the Supplementary materials. For complexes 1, 2, 4-8 and 11-16 at
pH = 2 the band above 400 nm (attributed to coordinated Schiff
base ligand) is not present or with a very low intensity which is
associated with the complex decomposition. The bands marked in
black, named as spectrum in DMSO (Supplementary materials), is
a spectrum of complexes in DMSO with the same concentration
as in DMSO/H2O mixture measured to see rapid changes, before
first spectrum could be measured. In, for example, spectra of S9
and S10 it can be seen, that at pH = 7 MLCT bands shift to lower

10
J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
Fig. 6. UV–Vis spectra of complexes 9 in DMSO-H2O mixture (20 μl + 3 ml re-
spectively) mixture at pH = 2.00. T = 37°C, d = 1 cm, 15 spectra measured in 340
s intervals. Black line in spectra represents the spectrum of each complex in DMSO.
The arrows show direction of changes in spectra.
Fig. 8. X-band EPR spectrum of complex 16 registered at RT.
Fig. 9. Cyclic voltammogram of 5 in DMSO. Pt working and counting and Ag/AgCl
electrodes, 0.1 M Bu4NPF6 as electrolyte. Scan speeds 100 mV/s (full scan), insets
20, 50, 100, 200, 500, 1000 mV/s.
Fig. 7. X-band EPR spectrum of complex 3 registered at RT.
energy and diminishes in time, while at pH = 2 this band could
not be detected even for the first spectrum measured. This indi-
cates that complex released ligand L so fast that it was not caught
by spectral measurements. In case of 3 (spectra S28 and S29) slow
diminish of MLCT band is observed both at pH = 7 and pH = 2.
The most stable at pH = 2 are complexes 3, 8, 9, 10, 14 and 16
(see for example Fig. 6).
tributed to the small quantities of V(IV) formed by oxidation of
complex 16, but the low intensity of the signals indicates that the
amount of V(IV) is less than 1%. Similar behavior was earlier de-
tected by us in other V(III) nonoxido complexes with Schiff base
ligands and observed signal was typical for octahedral geometry of
central atom [38].
3.5. EPR spectra
3.6. Cyclic voltamperommetry
The EPR spectra of V(IV) complexes in a solid state show only
one symmetrical peak, as exemplified in Fig. 7 for complex 3.
The lack of hyperfine structure indicates on strong interactions be-
tween vanadium centers. The EPR spectra for other V(IV) as well
as for V(III) are attached in the Supplementary materials.
In general three types of cyclic voltammograms are observed.
For V(IV) and V(V) irreversible redox processes are observed in po-
tential range studied as presented in Fig. 9. If those complexes had
phen as a co-ligand the reversible process at ca. -1.3 V, connected
with phen redox processes, is observed in negative part of the
voltammogram. In our previous studies we also observed such pro-
cess in a range -1.2 V to -1.4 V [19,20,30]. For nonoxido complexes
of V(III) (15, 16), the reversible redox process, connected with ox-
idation to nonoxido V(IV) (e.g. at +0.142 V for 15), is observed
(Fig. 10). Such a behavior for non-oxido vanadium complexes was
earlier noticed in literature and is attributed to the V(IV/III) redox
The g value (1.981) is typical for V(IV). For V(III) complexes (15
and 16), the spectrum is more complicated. Typically in the X-band
the EPR spectrum of V(III) cannot be detected as V(III) is EPR silent.
Due to the measured magnetic moment equal 2.57 μB (calculated
for V(III) 2.83 μB, for V(IV) 1.73 μB), it must be stressed, that 16
contains V(III) (not visible in the EPR X-band) and only very small
amounts of V(IV). The presence of this signal (Fig. 8) can be at-

J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
11
Table 6
The TG and SDTA data for complexes 4, 5, 11, 13, 15 and 16. Scan speed 10o /min. Tplat = temperature at which ꢀmex was read from
experimental data.
Tplat
ꢀmexp
ꢀmcalc
Complex
Conditions
air
[°C]
[%]
[%]
Attributed to
4
442
605
230
300
458
600
274
480
1000
112
197
262
363
500
113
202
276
425
652
148
461
810
1000
255
300
387
500
203
389
500
35.0833
87.7460
4.7678
37.77
88.57
5.97
phen + 2 H2O
phen + 2 H2O + L
5
air
Ar
2 H2O
14.3462
48.1769
83.8854
5.0722
-
-
46.61
88.82
5.97
nicotinic acid hydrazide + 2 H2O + 0.6 phen
phen + L + EtOH + 2 H2O
2 H2O
51.6913
77.8713
3.0666
58.55
81.19
-
nicotinic acid hydrazide + 2 H2O + phen
phen + L + 2 H2O
11
air
Ar
18.5106
30.1294
76.6868
86.6982
3.4420
18.97
30.45
69.51
88.47
-
0.5 2-hydroxybenzhydrazide
0.5 2-hydroxybenzhydrazide + EtOH
0.5 2-hydroxybenzhydrazide + EtOH + 5-chlorosalicylaldehyde
L + EtOH
-
22.3187
37.3920
66.3053
87.5071
2.1107
18.97
30.45
69.51
88.47
2.43
0.5 2-hydroxybenzhydrazide
0.5 2-hydroxybenzhydrazide + EtOH
0.5 2-hydroxybenzhydrazide + EtOH + 5-chlorosalicylaldehyde
L + EtOH
13
15
16
Ar
0.5 H2O
46.3617
68.7816
77.9777
2.1173
47.13
71.39
77.52
2.60
5-chlorosalicylaldehyde + H2O
5-chlorosalicylaldehyde + H2O + 0.5 phenylacetic hydrazide
L + H2O
air
air
H2O
7.2495
9.24
H2O + EtOH
H2O + EtOH + L
H2O + EtOH + 2 L
0.5 H2O
57.1572
87.7279
1.3060
50.91
92.58
1.51
32.5050
52.8532
32.96
50.93
0.7 L + 0.5 H2O
1.1 L + 0.5 H2O
92.4 kJ/mol, while the second peak -196.4 kJ/mol. The Tmax for
the air measurements were observed at 361 and 507 °C (for 4),
341 and 425 (for 11), 302, 364, 430 and 515 °C (for 13), 285, 334,
412 and 434 °C (for 15). The decomposition processes lead to step-
wise release of violate complex components and were attributed
to: H2O, phen and L4+H2O release (calcd.: 3.15, 31.9 and 54,0, sum
89.0 %, found: 2.37, 32.5 and 52.9, sum 87.7 % respectively) for 4;
L6+EtOH (not well resolved three steps od decomposition) (calc.:
86.9 %, found: 83.8 %) for 11; H2O and L7 (calcd.: 4.86 and 73.0,
sum 77.9 %, found: 3.30, 73.6, sum 77.9 %) for 13 and H2O and 2L4
(calcd.: 2.78 and 89.8, sum 92.6 %, found: 2.19 and 85.5, sum 87.7
%) for 15. In general water of hydration are released at very begin-
ning, but in case of 5 it can be seen that it is released at two dis-
tinguishable processes. As complex is already 6-coordinating such
a behavior must be interpreted as very strong hydrogen bonds for
one water molecule present in 5 resulting in increase of water re-
lease temperature.
Fig. 10. Cyclic voltammogram of 15 in DMSO. Pt working and counting and Ag/AgCl
electrodes, 0.1 M Bu4NPF6 as electrolyte. Scan speeds 100 mV/s (full scan), insets
20, 50, 100, 200, 500, 1000 mV/s.
3.8. Pharmacological activity of selected complexes
Complexes 8, 10 and 16 at a concentration of 1 μM showed the
greatest activity in inhibition of phosphatases PTP1B, LAR, SHP1
and SHP2, which are associated with the anti-diabetic activity of
vanadium compounds. The activity of these complexes was similar
or greater than the VOSO4 and BMOV used as comparators (Figs
11 and 12). The remaining tested complexes (1, 3, 4, 5, 9, 11 and
15) showed slightly weaker activity in the case of SHP1 and SHP2
inhibition, while their ability to inhibition of PTP1B and LAR activ-
ity was distinctly lower. These results may be explained structural
similarities in these phosphatases.
couple [20,39]. The cyclic voltammograms for all other complexes
are included in the Supplementary materials.
3.7. Thermogravimetric analysis
The thermogravimetric analysis was performed for complexes 4,
5, 11, 13, 15 and 16 both in air and under Ar atmosphere (for 5, 11
and 13). All figures are included in the Supplementary materials.
The numerical data are collected in Table 6.
For complex 11, more extensive pharmacological activity stud-
ies were performed. The complex 11 was selected to compare the
biological activity of 5-chloro substituted salicylaldehyde with 5-
nitro, 5-bromo, 5-methoxy relatives investigated earlier. The most
For all complexes exothermic decomposition processes in air
are observed, while under argon atmosphere only endothermic
ones are visible. For 5, the first SDTA peak gave the energy of -

12
J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
Fig. 11. Inhibition of human tyrosine phosphatases, where A - VOSO4, B – BMOV, C - (NH4)6Mo7O24, numbers denote complex number (concentration equal to 1 μM).
Fig. 12. Inhibition of human tyrosine phosphatases, where A - VOSO4, B – BMOV, C - (NH4)6Mo7O24, numbers denote complex number (concentration equal to 10 μM).

J. Szklarzewicz, A. Jurowska and M. Hodorowicz et al. / Journal of Molecular Structure 1224 (2021) 129205
13
Table 7
remain coordinated to vanadium centre in their passage through
digestion systems and probably act in different manner than with
bidentate ligands as BMOV.
Pharmacological activity tests results for 11 and BMOV.
BMOV
11
PTP1B inhibition (IC50 μM)
LAR inhibition (IC50 μM)
SHP1 inhibition (IC50 μM)
SHP2 inhibition (IC50 μM)
CD45 inhibition (IC50 μM)
PTPRA inhibition (% in 50 μM)
PPA2 inhibition (% in 50 μM)
CDC25A inhibition (% in 50 μM)
Viability HepG2
149
140
8
12140
2687
329
Credit Author Statement
14
1103
21
Janusz Szklarzewicz: Supervision. Oversight and leadership re-
sponsibility for the research activity planning and execution, in-
cluding mentorship external to the core team. Writing - Review &
Editing.Preparation, creation and/or presentation of the published
work by those from the original research group, specifically critical
review, commentary or revision – including pre- or postpublication
stages; Anna Jurowska: Visualization. Preparation, creation and/or
presentation of the published work, specifically visualization/data
presentation - preparation of the figures. Investigations, conduct-
ing a research and investigation process, (synthesis of complexes,
spectral analysis) and writing (preparation of the manuscript parts
connected with the synthesis and spectral analysis). Preparation
of the tables; Maciej Hodorowicz: Specifically performing the ex-
periments, or data/evidence collection, responsibility for the X-ray
crystal structure measurements and crystal structure description;
Grzegorz Kazek: Investigations - in vitro studies. Writing - prepa-
ration of the biological part of the manuscript; Monika Głuch-
Lutwin: Investigation, biological part of the manuscript, responsi-
bilility for the formal analysis of biological data; Jacek Sapa: Super-
vision of the biological investigations, responibility for the method-
ology of biological studies; Monika Papiez˙ : Responsibility for the
cell cultures for in vitro studies. Investigations and preparation of
the samples for biological studies. Preparation of rough data for
further analysis.
9
96
4
4
1
64
5
86
56
5
3
4
8
62
43
106
98
10
92
Viability C2C12
4
96
Viability 3T3-L1
117
100
125
109
98
2
103
102
179
171
150
116
3
Cytotoxicity HepG2
1
1
Radiolabelled glucose uptake C2C12
Radiolabelled glucose uptake 3T3-L1
Glucose utilisation C2C12
Glucose utilisation 3T3-L1
6
17
9
12
2
9
122
16
5
Unless otherwise stated in the parenthesis, the result is given as a
percent of the control (solvent only)
was 50 μM.
SD and tested concentration
important in choosing 11 was its highest solubility in 1-octanol,
solvent closest to the properties of fats. Complex 11 showed sig-
nificantly lower tyrosine phosphatase inhibiting ability, expressed
as IC50, than BMOV but higher glucose uptake, glucose utilisation
and no cytotoxic effects (Table 7). Complex 11 also showed the
ability to inhibition other types of phosphatases: receptor tyrosine
phosphatase PTPRA, serine-threonine phosphatase PPA2, and dual
specificity phosphatase CDC25A.
4. Conclusions
Declaration of Competing Interest
Sixteen complexes of vanadium at different oxidation state (III-
V) were investigated. The complexes with tridentate Schiff bases
in case of V(IV) and (V) contain only one ligand, due to presence
of V=O bond, blocking the possibility of second ligand coordina-
tion. These additional ligands to fill coordination sphere were thus
coordinated to vanadium, the use of phen allowed us to stabilize
the V(IV). When [V(acac)3] was used as starting material, nonox-
ido complexes with two ONO ligand were formed. These com-
plexes were found to be unstable in time and slow oxidation to
V(IV) was observed, with partial preservation of nonoxido charac-
ter of the metal center. This was proved by the magnetic moment
measurements indicating on high V(IV) content, while EPR spectra
show only very weak signal, typical for oxido V(IV) complexes. In
general, the complexes show relatively low stability in solutions at
pH = 2.0, thus their biological activity was similar to that of BMOV
as a reference. The studies of the biological activity of selected
complexes showed that they are characterized by diverse activity
in inhibiting activity of tyrosine phosphatases, and some of them
are as effective as BMOV, which has been studied in clinical trials.
On the other hand, strong inhibition of tyrosine phosphatase ac-
tivity is not necessary to achieve high anti-diabetic efficacy in the
absence of cytotoxic effects, which requires further research into
cellular mechanisms of vanadium complexes action. The ability to
inhibition other types of phosphatases indicates the potential for
applications in other areas of therapeutic use, such as neoplastic
diseases, but the lack of selectivity can be an obstacle.
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper.
Acknowledgements
This work was partly financed by the European Regional De-
velopment Fund under the Innovative Economy Programme 2007-
2013 (WND POIG.01.03.01-174/09). The complexes are protected by
the patent P.401493.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.molstruc.2020.129205.
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