Characterization and antidiabetic activity of salicylhydrazone Schiff base vanadium(IV) and (V) complexes

Article abstract of DOI:10.1007/s11243-020-00437-1

Twenty-four oxidovanadium(IV,V) complexes with tridentate Schiff base ligands based on 5-nitrosalicylaldehyde, 5-methoxysalicylaldehyde, or 5-sulfosalicylaldehyde and respective hydrazide were isolated, and characterized using physicochemical and spectros

Full text of DOI:10.1007/s11243-020-00437-1

Transition Metal Chemistry (2021) 46:201–217
https://doi.org/10.1007/s11243-020-00437-1
Characterization and antidiabetic activity of salicylhydrazone Schif
base vanadium(IV) and (V) complexes
Janusz Szklarzewicz1 · Anna Jurowska1 · Maciej Hodorowicz1 · Grzegorz Kazek2 · Barbara Mordyl2 ·
Elżbieta Menaszek2 · Jacek Sapa2
Received: 28 September 2020 / Accepted: 31 October 2020 / Published online: 24 December 2020
© The Author(s) 2020
Abstract
Twenty-four oxidovanadium(IV,V) complexes with tridentate Schif base ligands based on 5-nitrosalicylaldehyde, 5-methox-
ysalicylaldehyde, or 5-sulfosalicylaldehyde and respective hydrazide were isolated, and characterized using physicochemical
and spectroscopic methods. Three of them were structurally characterized by single-crystal X-ray structure determination.
The biological activity studies included inhibition of human tyrosine phosphatases, studies on myocyte C2C12, adipocyte
3T3-L1, and human hepatocyte HepG2 cell lines, glucose uptake in myocytes and adipocytes, and cytotoxicity tests. The
complexes that were unstable in solutions showed biological activity typical of other V(IV) complexes, while the stable one
showed much higher, ligand-dependent, activity.
Introduction
a standard for investigation of insulin-mimetic activity [4–8].
Soon, other biological activities were recognized—such as
anticancer, antifungal or antibacterial, including activity
toward protection from anticancer chemotherapy resistance
[9–14]. Depending on the type of vanadium complex and
ligands used, vanadium compounds exhibit large diferences
in terms of their structure and properties, and thus show dif-
ferent permeability through the cell membrane.
Vanadium compounds are of great importance not only in
science but also in industry, including the very popular V2O5
used as a catalyst [1–3]. Its variety of oxidation states (typi-
cally ranging from II to V), coordination numbers, and bio-
logical activity result in frequent use of this metal in coordi-
nation chemistry, especially because vanadium in diferent
oxidation states forms a range of stable compounds, mak-
ing synthesis relatively simple. In the course of our inves-
tigation connected with the insulin-mimetic properties of
vanadium compounds, it is worth noting that both inorganic
complexes (including V2O5 and VOSO4) and those with
organic ligands are found to be active. Inorganic compounds
were studied frst, but it was soon shown (by McNeill) that
organic compounds of vanadium work much better, and
today bis(maltolato)oxidovanadium(IV) (BMOV) is used as
The best known and most widely described mechanism of
the insulin-mimetic action of vanadium and its complexes in
activation of cellular glucose uptake is inhibition of protein
tyrosine phosphatases, especially PTP1B (but also TCPTP,
PTP-MEG2, SHP-1, SHP-2, and LAR) [15–17]. Phos-
phatases are a group of enzymes that hydrolyze monoesters
of phosphoric acid to a phosphate group and molecules with
a free hydroxyl group. By removing a phosphate group, pro-
tein phosphatases can modulate the activity of cellular pro-
teins and regulate cell metabolism by afecting many signal
transduction pathways. Protein tyrosine phosphatases (PTPs)
play an important role in the pathomechanisms of numerous
diseases, thus many of them are potential pharmacological
targets. In the glucose uptake process, this leads to mainte-
nance of the phosphorylated state of the insulin receptor and
thus to upstreaming signaling, which is similar to the action
of the insulin hormone [18]. However, the list of molecu-
lar targets identifed for vanadium action is much wider.
Other enzymes (for example, kinases) in the glucose uptake
pathway are also important, but the insulin-like efects of
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s11243-020-00437-1) contains
supplementary material, which is available to authorized users.
* Janusz Szklarzewicz
szklarze@chemia.uj.edu.pl
1
Faculty of Chemistry, Jagiellonian University, Gronostajowa
2, 30-387 Kraków, Poland
2
Faculty of Pharmacy, Jagiellonian University Medical
College, Medyczna 9, 30-001 Kraków, Poland
Vol.:(0123456789)
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Transition Metal Chemistry (2021) 46:201–217
vanadium have not yet been fully clarifed [19]. All this leads
to modulation of various cellular functions and may be a
basis for understanding the therapeutic role of vanadium
compounds in metabolic, neoplastic, infammatory, neuro-
degenerative, and other diseases.
an Elementar Vario MICRO Cube elemental analyzer. IR
spectra were recorded on a Bruker EQUINOX 55 FT-IR
spectrophotometer in KBr pellets. Electronic absorp-
tion spectra were recorded with a Shimadzu UV-3600
UV–Vis–NIR spectrophotometer equipped with a CPS-240
temperature controller. Difuse refectance spectra were
measured in BaSO4 pellets with BaSO4 as reference on a
Shimadzu 2101PC equipped with an ISR-260 integrating-
sphere attachment. Magnetic susceptibility measurements
were performed on a Sherwood Scientifc magnetic suscep-
tibility balance. Cyclic voltammetry measurements were
carried out in dimethyl sulfoxide (DMSO) with [Bu4N]PF6
(0.1 M) as supporting electrolyte, using Pt working and
counter and Ag/AgCl reference electrodes on an Autolab
PGSTAT128N potentiostat/galvanostat. E1/2 values were cal-
culated from the average anodic and cathodic peak potentials
as E1/2 =0.5(Ea +Ec). Redox potentials were calibrated ver-
sus ferrocene (0.440 V versus standard hydrogen electrode
(SHE)), which was used as an internal potential standard for
measurements in organic solvents to avoid the infuence of a
liquid junction potential; the fnal values are reported versus
SHE. Thermogravimetric measurements were performed on
a Mettler Toledo TGA/SDTA 851e microthermogavimeter at
scan speed of 10°/min in the 25–755 °C range in air.
We present herein the synthesis and physicochemical
characterization of vanadium(IV,V) complex with tridentate
ONO hydrazone Schif base ligands, now extended to those
based on 5-nitrosalicylaldehyde, 5-methoxysalicylaldehyde,
and 5-sulfosalicylaldehyde with a set of hydrazides used
by us previously [20–28]. As shown earlier, for tridentate
contrary to bidentate ligands, a huge change of biological
activity is observed, indicating that complexes in unchanged
form (or at least with ONO ligand still coordinated to vana-
dium) pass into cells. Single-crystal X-ray structure analysis
of three complexes as well as elemental analysis, magnetic
susceptibility measurements, infrared (IR) and ultravio-
let–visible (UV–Vis) spectroscopies, thermogravimetric
measurements, and cyclic voltammetry are presented and
discussed. To increase the stability of the complexes and fll
the coordination sphere of V(IV/V), 2,2′-bipyridine (bpy) or
1,10-phenanthroline (phen) was used as co-ligand.
The importance of the PTPs tested in this study (PTP1B,
SHP1, SHP2, and LAR) in metabolic disorders and diabe-
tes has been discussed in literature [29, 30]. Due to the low
specifcity of vanadium compounds in inhibiting the activity
of individual PTPs and the potential adverse efects associ-
ated with this, the ability to inhibit CD45 phosphatase was
examined. This phosphatase is associated with a possible
impairment of hematopoietic cells and immune system dis-
turbances [31].
Inhibition of human tyrosine phosphatases
For this determination, the ability of the tested compounds
to inhibit tyrosine phosphatases human recombinant pro-
tein was used. To solution of the tested complexes in black
384-well microplate wells (PerkinElmer), an equal volume
of test solution of phosphatase was added in reaction bufer
[25 mM 3-(N-morpholino) propanesulfonic acid (MOPS),
50 mM NaCl, 1 mM dithiothreitol (DTT), and 0.05% Tween-
20, pH 7.0]. The fnal 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 ng/ml. After 10 min, solution
of phosphate 6,8-difuoro-4-methyl (DiFMUP) was added
to fnal concentration of 0.1 mM. After 20 min of incuba-
tion at room temperature, the fuorescence intensity (exci-
tation at 355 and emission at 560 nm) was measured on
a multifunctional PTP1B POLARstar Omega plate reader
(BMG Labtech, Germany). Assays were performed in trip-
licate. Results are expressed as the percent of inhibition of
untreated control (enzyme with solvent only) [33].
Experimental
Materials and methods
[VO(acac)2], VOSO4aq, 1,10-phenanthroline (phen),
2,2′-bipyridine (bpy), 5-nitrosalicylaldehyde, 5-methox-
ysalicylaldehyde, 5-sulfosalicylaldehyde, benzhydrazide,
nicotinic hydrazide, phenylacetic acid hydrazide, 4-chlo-
robenzhydrazide, 2-hydroxybenzhydrazide, 4-hydroxy-
benzhydrazide, 4-methoxybenzhydrazide, and 3-hydroxy-
2-naphthoic acid hydrazide were of analytical grade
(Aldrich or Alfa Aesar) and used as supplied. bis(maltolato)
oxovanadium(IV) (BMOV) was synthesized according to lit-
erature method [8]. Ethanol (98%) of pharmaceutical grade
was from Polmos and used as supplied. All other solvents
were of analytical grade (Aldrich) and used as supplied.
BaSO4 was of spectroscopic grade (Japan). Bu4NPF6 was
synthesized from Bu4NBr and KPF6 by a standard method
and recrystallized from acetone [32]. Microanalysis of car-
bon, hydrogen, nitrogen, and sulfur was performed using
Cell models
Myocyte C2C12 cell line (ATCC CRL-1772), a subclone of
myoblasts from mouse muscles, was cultured according to
standard protocol in Dulbecco’s modifed Eagle’s medium
(DMEM) supplemented with 10% fetal calf serum, 100 IU/
ml penicillin, and 100 µg/ml streptomycin at 37 °C in 5%
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Transition Metal Chemistry (2021) 46:201–217
203
CO2. Cells were plated on 96-well microplate and after
reaching confuence diferentiated in medium with 2% horse
serum. Diferentiation medium was changed every 72 h.
Adipocyte 3T3-L1 cell line (ATCC CRL-11605), derived
from fbroblasts from mouse embryo tissue, was cultured
according to standard protocol in DMEM medium supple-
mented with 10% bovine calf serum, 100 IU/ml penicillin,
and 100 µg/ml streptomycin at 37 °C in 5% CO2. Cells were
seeded in 96-well poly-d-lysine-coated plates and cultured
to reach confuence. The medium was then switched to dif-
ferentiation medium and changed every 48 h.
control. After that, cells were washed three times with cold
KRB, and cytochalasin B (10 µM fnal) was added for sev-
eral wells as “no uptake.”
For myocytes and adipocytes processed as described
above, 2-deoxy-d-[U-14C]-glucose solution in KRB with
total activity of 0.03 µCi was added to each well. After 1 h
of incubation at 37 °C and 5% CO2, uptake was blocked by
adding cytochalasin B (10 µM fnal). Radioactivity of sam-
ples was measured using a MicroBeta Trilux 1450 scintilla-
tion counter (PerkinElmer, USA). Nonspecifc radioactivity
was subtracted from each result (cpm). Two independent
experiments in triplicate were conducted. Final results are
expressed as percent of control containing solvent only
instead of tested compound.
Human hepatocyte HepG2 cell line (ATCC HB-8065)
was cultured according to standard protocol in DMEM sup-
plemented with 10% fetal bovine serum, 100 IU/ml penicil-
lin, and 100 µg/ml streptomycin at 37 °C in 5% CO2. Cells
were plated on 96-well microplate.
Viability and cytotoxicity tests
Glucose uptake in myocytes and adipocytes
After differentiation of C2C12 myocytes, medium was
changed for medium with 0.2% bovine serum albumin,
100 IU/ml penicillin, and 100 µg/ml streptomycin, and after
2 h of incubation medium was changed for fresh medium
containing vanadium complexes. After 48 h of incubation
of 3T3-L1 adipocytes, medium was changed for standard
medium with human recombinant insulin and tested vana-
dium complexes. Hepatocytes HepG2 were used for experi-
ments after seeding for 18–24 h and after medium exchange.
Vanadium complexes were tested at fnal concentration of
50 µM. After 24 h of incubation with tested compounds at
37 °C in 5% CO2, 10 μl PrestoBlue cell viability reagent
(Thermo Fisher Scientifc) was added to each microplate
well, and the microplate was placed on an orbital shaker
for content mixing. Plates were incubated for 20 min, and
the fuorescence intensity at 560 nm excitation and 590 nm
emission was determined using a POLARstar Omega mul-
timode microplate reader (BMG Labtech, Germany). The
results were normalized to untreated control (cells with sol-
vent only), whose fuorescence intensity was taken as 100%.
Incubations of vanadium complexes with cells were per-
formed in triplicate, and each compound was tested in three
to four independent experiments. Similarly, cytotoxicity
tests based on assessment of integrity of HepG2 hepatocyte
membrane were performed using ToxiLight cytotoxicity kit
(Lonza) according to manufacturer protocol.
Myocytes C2C12 after 8-day differentiation and adipo-
cytes 3T3-L after 11 days of diferentiation were cultured
and maintained as described above but plated on 96-well
microplate coated with solid-phase scintillator (ScintiPlate,
PerkinElmer, USA).
Myocytes were washed, and medium was changed for
medium with 0.5% bovine serum albumin (BSA) instead
of serum. After 24 h of incubation, tested complexes were
added at fnal concentration of 50 µM. After 2 h of incuba-
tion at 37 °C in 5% CO2, medium was changed for low-
glucose (1000 mg/l) medium, tested complexes were added
again, and further incubation for 4 h was conducted. Next,
cells were washed three times with Krebs–Ringer bufer
(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 insulin at fnal concentra-
tion 100 nM (Sigma-Aldrich) was added for 15 min. Wort-
mannin at fnal concentration of 200 nM (Sigma-Aldrich)
was used as negative control. After that, cells were washed
three times with cold KRB and cytochalasin B (10 µM fnal)
was added to several wells as “no uptake” control, proceed-
ing as described below.
Adipocytes were washed, and medium was changed for
basal medium. After 24 h of incubation, tested complexes
were added at fnal concentration of 50 µM. After 2 h of
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 h was conducted. Next, cells were washed three times
with KRB without glucose, and KRB with human recom-
binant insulin at fnal concentration of 100 nM (Sigma-
Aldrich) was added for 15 min. Wortmannin at fnal con-
centration of 200 nM (Sigma-Aldrich) was used as negative
Synthesis
Table 1 presents the Schif base ligand notation and ligand
components.
Preparation of [{VO(HL1)(H2O)2}2(SO4)]·1.5H2O (1)
5-Nitrosalicylaldehyde (500 mg, 3 mmol) and benzhydrazide
(410 mg, 3 mmol) in 25 ml EtOH were refuxed for 10 min
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Transition Metal Chemistry (2021) 46:201–217
Table 1 List of ligands and
Ligand notation
Aldehyde
Hydrazide
ligand components
H2L1
H2L2
H2L3
H2L4
H2L5
H2L6
5-Nitrosalicylaldehyde
5-Nitrosalicylaldehyde
5-Nitrosalicylaldehyde
5-Nitrosalicylaldehyde
5-Nitrosalicylaldehyde
5-Nitrosalicylaldehyde
Benzhydrazide
2-Hydroxybenzhydrazide
4-Hydroxybenzhydrazide
Phenylacetic acid hydrazide
Nicotinic hydrazide
3-Hydroxy-2-naphthoic acid
hydrazide
H2L7
H2L8
H2L9
H2L10
H2L11
H2L12
H2L13
5-Methoxysalicylaldehyde
5-Methoxysalicylaldehyde
5-Methoxysalicylaldehyde
5-Methoxysalicylaldehyde
5-Methoxysalicylaldehyde
5-Methoxysalicylaldehyde
5-Methoxysalicylaldehyde
Benzhydrazide
2-Hydroxybenzhydrazide
4-Hydroxybenzhydrazide
4-Chlorobenzhydrazide
Phenylacetic acid hydrazide
Nicotinic hydrazide
3-Hydroxy-2-naphthoic acid
hydrazide
H2L14
H2L15
H2L16
H3L17
H3L18
5-SO3-salicylaldehyde
5-SO3-salicylaldehyde
5-SO3-salicylaldehyde
5-SO3-salicylaldehyde
5-SO3-salicylaldehyde
4-Hydroxybenzhydrazide
4-Methoxybenzhydrazide
Phenylacetic acid hydrazide
Nicotinic hydrazide
3-Hydroxy-2-naphthoic acid
hydrazide
under Ar. Then, VOSO4 (657 mg, 3 mmol) was added, and
the mixture was refuxed for 40 min. At this stage, mix-
ture was fltered of and the residue removed. The fltrate
was concentrated to 50% of initial volume and cooled, and
formed crystals were filtered off. Complex was washed
three times with ethanol and dried in air. Yield 0.554 g,
42% MW= 897.50. Anal. Calc. for C28H31N6O19.5SV2: C,
37.47; H, 3.48; N, 9.36; S, 3.61%. Found: C, 37.83; H, 3.55;
N, 8.94; S~4%. The complex is paramagnetic µef =1.80µB.
FT-IR (KBr, cm−1): 3405 (w), 3299 (w), 3193 (w), 3075 (w),
1606 (vs), 1558 (s), 1489 (w), 1388 (m), 1337 (vs), 1317
(vs), 1248 (w), 1192 (w), 1131 (w), 1095 (m), 1041 (w),
959 (m), 904 (w), 837 (w), 808 (w), 751 (w), 705 (m), 659
(w), 569 (w), 514 (w), 475 (w), 451 (w). UV–Vis (DMSO):
324, 390 nm, (MeCN): 227, 290 nm, (EtOH): 317, 371 nm.
3429 (w, br), 3051 (w), 1600 (s), 1552 (w), 1511 (m), 1491
(m), 1466 (m), 1438 (m), 1357 (w), 1316 (vs), 1245 (w),
1201 (w), 1175 (w), 1101 (m), 1037 (w), 1023 (w), 957 (s),
906 (w), 828 (w), 801 (w), 767 (m), 734 (w), 717 (w), 701
(m), 653 (w), 563 (w), 524 (w), 454 (w). UV–Vis (DMSO):
284, 327, 393 nm, (MeCN): 240, 304, 324, 389 nm, (EtOH):
286, 318, 383 nm.
Preparation of [VO(L1)(phen)]·1.5H2O (3)
5-Nitrosalicylaldehyde (500 mg, 3 mmol) and benzhydrazide
(408 mg, 3 mmol) in 50 ml EtOH were refuxed for sev-
eral minutes under Ar. Then, VOSO4 (666 mg, 3 mmol)
was added, and the mixture was refuxed for 40 min. Next,
the mixture was fltered and, to the 25 ml of fltrate, phen
(272.3 mg, 1.5 mmol) was added. The complex was fltered
of, washed two times with EtOH, and dried in air. Yield
0.651 g, 40% MW=557.40. Anal. Calc. for C26H21N5O6.5 V:
C, 56.02; H, 3.62; N, 12.56%. Found: C, 56.32; H, 3.30; N,
12.30%. The complex is paramagnetic µef =1.61µB. FT-IR
(KBr, cm−1): 3452 (w, br), 3051 (w), 1614 (s), 1598 (s),
1549 (w), 1510 (m), 1491 (w), 1465 (w), 1425 (w), 1360
(w), 1336 (w), 1315 (vs), 1243 (w), 1198 (w), 1141 (w),
1102 (m), 1039 (w), 960 (m), 909 (w), 848 (w), 795 (w), 754
(w), 725 (m), 703 (m), 658 (w), 569 (w), 454 (w), 429 (w).
UV–Vis (DMSO): 326, 392 nm, (MeCN): 225, 271, 327,
386 nm, (EtOH): 225, 269, 322, 394 nm.
Preparation of [VO(L1)(bpy)]·0.5EtOH·0.5H2O (2)
5-Nitrosalicylaldehyde (249 mg, 1.5 mmol) and benzhy-
drazide (204 mg, 1.5 mmol) in 25 ml EtOH were refuxed
for 5 min under Ar. Then, VOSO4 (325 mg, 1.5 mmol)
was added and the mixture was refuxed for 50 min. Next,
the mixture was fltered, and bpy (236 mg, 1.5 mmol) was
added to the fltrate. The complex was fltered of, washed
three times with EtOH, and dried in air. Yield 0.417 g, 51%
MW=538.43. Anal. Calc. for C25H21N5O6V: C, 55.77; H,
3.93; N, 13.01%. Found: C, 55.92; H, 3.62; N, 13.28%. The
complex is paramagnetic µef =1.51µB. FT-IR (KBr, cm−1):
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Transition Metal Chemistry (2021) 46:201–217
205
for C26H22N5O8.5 V: C, 52.80; H, 3.75; N, 11.84%. Found:
C, 52.80; H, 3.34; N, 11.67%. The complex is paramagnetic
µef =1.28µB. FT-IR (KBr, cm−1): 3423 (w, br), 1606 (vs),
1554 (w), 1496 (vs), 1467 (w), 1425 (m), 1379 (m), 1361
(m), 1334 (s), 1313 (vs), 1244 (w), 1197 (w), 1166 (m), 1143
(w), 1103 (m), 1033 (w), 956 (s), 913 (w), 846 (s), 757 (m),
724 (s), 645 (m), 597 (w), 566 (w), 521 (w), 475 (w), 445
(w). UV–Vis (DMSO): 326, 395 nm, (MeCN): 223, 270,
328, 392 nm, (EtOH): 226, 266, 326, 390 nm.
Preparation of [VO(L2)(EtO)] (4)
5-Nitrosalicylaldehyde (250.7 mg, 1.5 mmol) and
2-hydroxybenzhydrazide (228.2 mg, 1.5 mmol) in 40 ml
EtOH were refluxed 15 min under Ar. Then, VOSO4
(333 mg, 1.5 mmol) was added with additional 10 ml EtOH,
and mixture was refuxed for 105 min. Next, the mixture was
fltered, washed with a small amount of EtOH, and dried
in air. Yield 0.356 g, 58% MW= 411.24. Anal. Calc. for
C16H14N3O7V: C, 46.73; H, 3.43; N, 10.22%. Found: C,
46.58; H, 3.66; N, 10.08%. The complex is diamagnetic.
FT-IR (KBr, cm−1): 3482 (w, br), 2981 (w), 1626 (vs), 1609
(vs), 1580 (w), 1560 (m), 1520 (s), 1484 (m), 1468 (m),
1381 (m), 1341 (vs), 1308 (w), 1284 (m), 1248 (m), 1218
(m), 1160 (m), 1128 (w), 1089 (m), 1065 (w), 1035 (m),
997 (s), 966 (w), 908 (m), 873 (w), 843 (m), 817 (m), 755
(s), 720 (m), 703 (m), 674 (w), 656 (w), 614 (m), 578 (w),
519 (m), 481 (w), 468 (w), 447 (w). UV–Vis (DMSO): 326,
387 nm, (MeCN): 267, 310, 324, 389 nm, (EtOH): 321 nm.
Preparation of [VO(L4)(EtO)]·H2O (7)
5-Nitrosalicylaldehyde (251.0 mg, 1.5 mmol) and phe-
nylacetic acid hydrazide (226.1 mg, 1.5 mmol) in 67 ml
EtOH were refuxed 20 min under Ar. Then, [VO(acac)2]
(399.0 mg, 1.5 mmol) was added, and the mixture was
refuxed for 42 min. This was then evaporated to ca. 20 ml
and left aside for crystallization. The next day, brown crys-
talline product was fltered of, washed with EtOH, and
dried in air. Yield 0.340 g, 53% MW=427.28. Anal. Calc.
for C17H18N3O5V: C, 47.79; H, 4.25; N, 9.83%. Found: C,
47.46; H, 4.14; N, 9.69%. The complex is diamagnetic.
FT-IR (KBr, cm−1): 3547 (m), 2974 (w), 1612 (s), 1598 (s),
1557 (w), 1526 (s), 1497 (s), 1461 (w), 1334 (vs), 1303 (s),
1201 (w), 1155 (w), 1128 (w), 1088 (m), 1031 (m), 983 (s),
941 (w), 909 (m), 841 (m), 808 (w), 781 (w), 759 (w), 723
(m), 692 (w), 660 (w), 635 (m), 582 (m), 549 (w), 513 (w),
460 (m), 429 (w). UV–Vis (DMSO): 319 nm, (MeCN): 289,
334 nm, (EtOH): 308, 364 nm.
Preparation of [VO(L2)(bpy)]·H2O (5)
5-Nitrosalicylaldehyde (250.7 mg, 1.5 mmol) and
2-hydroxybenzhydrazide (228.2 mg, 1.5 mmol) in 33 ml
EtOH were refluxed for 6 min under Ar. Then, VOSO4
(333 mg, 1.5 mmol) was added, and the mixture was refuxed
for 10 min. Then, bpy (234 mg, 1.5 mmol) in 2 ml EtOH was
added. The mixture was refuxed for an additional 5 min.
The mixture was cooled, and the product was fltered of,
washed with EtOH, and dried in air. Yield 0.656 g, 81%
MW=540.38. Anal. Calc. for C24H19N5O7V: C, 53.34; H,
3.54; N, 12.96%. Found: C, 53.57; H, 3.34; N, 13.00%. The
complex is paramagnetic µef =1.46µB. FT-IR (KBr, cm−1):
3476 (w, br), 3057 (w), 1604 (vs), 1551 (w), 1514 (m), 1491
(s), 1469 (m), 1443 (m), 1366 (m), 1315 (vs), 1248 (w),
1160 (w), 1130 (w), 1101 (m), 1060 (w), 1022 (w), 955 (s),
914 (w), 830 (w), 802 (w), 753 (s), 731 (m), 720 (m), 694
(w), 653 (m), 631 (w), 582 (w), 519 (w), 472 (m), 446 (w).
UV–Vis (DMSO): 286, 329, 390, 465 nm, (MeCN): 214,
306, 387 nm, (EtOH): 284, 375 nm.
Preparation of [VO(L4)(phen)] (8)
The synthesis was performed for 6. The hydrazide used was
phenylacetic acid hydrazide (227.1 mg, 1.5 mmol). Yield
0.649 g, 79% MW=544.41. Anal. Calc. for C27H19N5O5V:
C, 59.57; H, 3.52; N, 12.86%. Found: C, 59.20; H, 3.51; N,
12.62%. The complex is paramagnetic µef =1.47µB. FT-IR
(KBr, cm−1): 3446 (w, br), 3057 (w), 1616 (s), 1601 (s),
1551 (m), 1520 (vs), 1489 (s), 1467 (w), 1425 (s), 1365
(m), 1313 (vs), 1250 (w), 1197 (w), 1143 (w), 1102 (m),
1028 (w), 957 (s), 941 (m), 908 (w), 840 (s), 800 (w), 759
(w), 722 (s), 689 (w), 661 (w), 647 (w), 587 (w), 558 (w),
539 (w), 517 (w), 473 (m), 428 (w). UV–Vis (DMSO): 313,
380 nm, (MeCN): 270, 316, 375 nm, (EtOH): 362 nm.
Preparation of [VO(L3)(phen)]·2.5H2O (6)
5-Nitrosalicylaldehyde (250.7 mg, 1.5 mmol) and
4-hydroxybenzhydrazide (225.5 mg, 1.5 mmol) in 40 ml
EtOH were refuxed 20 min under Ar. Then, [VO(acac)2]
(395 mg, 1.5 mmol) in 10 ml EtOH was added, and the mix-
ture was refuxed for 30 min. The mixture was fltered of,
and to the fltrate, phen (273.5 mg, 1.5 mmol) in 10 ml EtOH
was added. The mixture was heated for an additional 8 min,
and formation of orange precipitate was observed. This was
fltered of, washed with a small amount of cold EtOH, and
dried in air. Yield 0.476 g, 54% MW=591.42. Anal. Calc.
Preparation of [VO(L5)(H2O)] (9)
5-Nitrosalicylaldehyde (251 mg, 1.5 mmol) and nicotinic
acid hydrazide (206 mg, 1.5 mmol) in 70 ml EtOH were
refuxed for 10 min under Ar. Then, [VO(acac)2] (398 mg,
1.5 mmol) was added, and the mixture was refuxed for
20 min. The obtaining product was fltered of, washed with
small amount of EtOH, and dried in air. Yield 0.479 g, 75%
1 3

206
Transition Metal Chemistry (2021) 46:201–217
MW=369.18. Anal. Calc. for C13H10N4O6V: C, 42.29; H,
2.73; N, 15.18%. Found: C, 42.31; H, 2.72; N, 14.85%. The
complex is paramagnetic µef =1.39µB. FT-IR (KBr, cm−1):
3417 (w, br), 3070 (w), 1605 (s), 1551 (m), 1520 (m), 1500
(w), 1465 (m), 1365 (m), 1337 (vs), 1312 (m), 1242 (w),
1197 (m), 1154 (w), 1127 (w), 1099 (m), 1056 (w), 1027
(w), 957 (w), 919 (w), 880 (vs), 834 (w), 800 (w), 755 (w),
721 (m), 694 (m), 656 (m), 579 (m), 517 (w), 454 (m).
UV–Vis (DMSO): 324, 391 nm, (MeCN): 378, 317 nm,
(EtOH): 319 nm.
Preparation of [{VO(HL7)}2(SO4)]·H2O (12)
5-Methoxysalicylaldehyde (187 µl, 1.5 mmol) and benzhy-
drazide (207 mg, 1.5 mmol) in 25 ml EtOH were refuxed
for 10 min under Ar. Then, VOSO4 (331.4 mg, 1.5 mmol)
was added, and the mixture was refuxed for the next 40 min.
After that, the solution was evaporated to ca. 10 ml and left
cooling in the refrigerator. The product was fltered of,
washed with ethanol, and dried in air. Yield 0.402 g, 68%
MW=788.51. Anal. Calcd. for C30H30N4O13SV2: C, 45.81;
H, 3.80; N, 7.12; S, 4.08%. Found: C, 45.77; H, 4.65; N,
7.10; S ~ 4%. The complex is paramagnetic, µ = 1.27µB.
FT-IR (KBr, cm−1): 3423 (w, br), 2945 (w), 2845 (w), 1617
(w), 1605 (w), 1581 (w), 1537 (s), 1490 (s), 1448 (w), 1417
(w), 1388 (s), 1346 (s), 1284 (m), 1268 (w), 1243 (s), 1171
(s), 1121 (vs), 1091 (s), 1030 (s), 1002 (m), 968 (s), 897
(m), 828 (m), 793 (w), 700 (s), 671 (w), 629 (w), 609 (w),
584 (w), 560 (w), 507 (w), 471 (w). UV–Vis (DMSO): 331,
424 nm, (MeCN): 326, 419 nm, (EtOH): 327, 416 nm.
Preparation of [VO(L6)(EtO)(EtOH)] (10)
5-Nitrosalicylaldehyde (334 mg, 2 mmol) and 3-hydroxy-
2-naphthoic acid hydrazide (404 mg, 2 mmol) in 110 ml
EtOH were heated on a magnetic stirrer for 15 min under
Ar. The temperature was raised to 100 °C. Then, VOSO4
(444 mg, 2 mmol) and 20 ml ethanol was added, and het-
erogenic mixture was refuxed for ca. 40 min. After that,
the volume of the reaction mixture was concentrated to
fnal volume of ca. 40 ml and cooled to room temperature.
The precipitate was fltered of, washed with ethanol, and
dried in air. Yield 0.652 g, 65% MW=507.37. Anal. Calc.
for C22H22N3O8V: C, 52.08; H, 4.37; N, 8.28%. Found: C,
51.58; H, 4.21; N, 8.17%. The complex is diamagnetic.
FT-IR (KBr, cm−1): 3435 (w, br), 3075 (w), 1633 (s), 1612
(s), 1555 (s), 1524 (vs), 1512 (s), 1458 (m), 1378 (m), 1341
(vs), 1302 (w), 1263 (w), 1239 (w), 1198 (w), 1175 (w),
1149 (m), 1128 (w), 1089 (m), 956 (w), 905 (s), 884 (w),
845 (w), 804 (w), 757 (m), 710 (w), 644 (m), 591 (w), 570
(w), 519 (w), 481 (m), 423 (w). UV–Vis (DMSO): 326,
391 nm, (MeCN): 358, 415 nm, (EtOH): 324, 454 nm.
Preparation of [VO(L8)(phen)]·4H2O (13)
5-Methoxysalicylaldehyde (187 µl, 1.5 mmol) and
2-hydroxybenzhydrazide (227.4 mg, 1.5 mmol) in 25 ml
EtOH were refuxed for 10 min under Ar. Then, VOSO4
(334 mg, 1.5 mmol) was added, and the mixture was refuxed
for the next 47 min. Phen (272.9 mg, 1.5 mmol) was added
to the transparent solution, and heating was continued for
10 min. This slowly started to crystallize, especially on
cooling. The brown crystalline product was fltered of,
washed with EtOH, and dried in air. Yield 0.369 g, 38%
MW=703.48. Anal. Calc. for C27H28N4O9V: C, 53.74; H,
4.68; N, 9.28%. Found: C, 53.56; H, 3.86; N, 9.31%. The
complex is paramagnetic µef =1.41µB. FT-IR (KBr, cm−1):
3429 (m, br), 3064 (w), 1623 (m), 1596 (s), 1537 (s), 1518
(s), 1491 (s), 1466 (w), 1424 (s), 1374 (m), 1340 (w), 1286
(w), 1257 (m), 1223 (m), 1166 (m), 1145 (w), 1107 (w),
1032 (s), 957 (s), 867 (w), 846 (m), 816 (w), 759 (m), 722
(s), 699 (w), 657 (w), 643 (w), 582 (w), 473 (w), 449 (w),
427 (w). UV–Vis (DMSO): 331, 429 nm, (MeCN): 297, 386,
519 nm, (EtOH): 267, 339, 439 nm.
Preparation of [VO(HL7)2]·EtOH (11)
5-Methoxysalicylaldehyde (187 µl, 1.5 mmol) and ben-
zhydrazide (207.3 mg, 1.5 mmol) in 25 ml EtOH were
refuxed for 12 min under Ar. Then, [VO(acac)2] (398.6 mg,
1.5 mmol) was added, and the mixture was refuxed for the
next 45 min. After that, the solution was evaporated to ca.
10 ml and left cooling in the refrigerator. The product was
fltered of, washed with ethanol, and dried in air. Yield
0.170 g, 35% MW=650.55. Anal. Calc. for C32H31N4O8V:
C, 59.17; H, 4.80; N, 8.63%. Found: C, 59.73; H, 4.62; N,
8.50%. The complex is paramagnetic µef = 1.27µB. FT-IR
(KBr, cm−1): 3464 (w, br), 3053 (w), 2915 (w), 2833 (w),
1603 (w), 1575 (m), 1539 (vs), 1503 (m), 1454 (m), 1440
(m), 1410 (w), 1356 (s), 1327 (m), 1275 (s), 1225 (vs), 1196
(w), 1169 (m), 1137 (w), 1119 (w), 1031 (s), 945 (w), 830
(m), 810 (m), 785 (w), 738 (w), 697 (s), 613 (w), 586 (w),
553 (w), 516 (w), 484 (w). UV–Vis (DMSO): 300, 396 nm,
(MeCN): 297, 386, 519 nm, (EtOH): 296, 399, 521 nm.
Preparation of [VO(L9)(phen)]·1.5H2O (14)
The synthesis was performed as for 6. The aldehyde used
was 5-methoxysalicylaldehyde (187 μl, 1.5 mmol), and the
hydrazide used was 4-hydroxybenzhydrazide (226.7 mg,
1.5 mmol). Yield 0.359 g, 43% MW =558.44. Anal. Calc.
for C27H23N4O6.5V: C, 58.07; H, 4.15; N, 10.03%. Found:
C, 58.25; H, 4.06; N, 9.77%. The complex is paramagnetic
µef =1.60µB. FT-IR (KBr, cm−1): 3418 (w, br), 3163 (w, br),
1 3

Transition Metal Chemistry (2021) 46:201–217
207
1598 (vs), 1545 (s), 1501 (vs), 1477 (m), 1423 (m), 1374
(w), 1360 (m), 1339 (w), 1279 (s), 1226 (s), 1169 (s), 1104
(w), 1031 (m), 954 (s), 906 (w), 845 (s), 810 (m), 787 (w),
757 (w), 724 (m), 697 (w), 642 (w), 597 (w), 562 (w), 474
(w), 441 (w). UV–Vis (DMSO): 334, 426 nm, (MeCN): 269,
334, 428 nm, (EtOH): 228, 264, 330, 421 nm.
µef = 1.59µB. FT-IR (KBr, cm−1): 3135 (w, br), 2966 (w),
1602 (s), 1550 (vs), 1531 (vs), 1476 (s), 1455 (m), 1419 (w),
1383 (w), 1330 (w), 1270 (vs), 1230 (s), 1194 (w), 1164 (m),
1088 (w), 1048 (vs), 1025 (m), 974 (vs), 920 (m), 878 (w),
836 (s), 774 (w), 736 (s), 686 (w), 663 (m), 580 (w), 564
(w), 524 (w), 473 (w), 444 (w), 425 (w). UV–Vis (DMSO):
412, 396 nm, (EtOH): 262 nm.
Preparation of [VO(L10)(phen)] (15)
Preparation of [VO(L12)(H2O)]·0.5H2O (18)
The synthesis was performed as for 14. The hydrazide
used was 4-chlorobenzhydrazide (252.1 mg, 1.5 mmol).
Yield 0.565 g, 69% MW = 549.86. Anal. Calc. for
C27H19ClN4O4V: C, 58.98; H, 3.48; N, 10.19%. Found: C,
58.91; H, 3.47; N, 10.15%. The complex is paramagnetic
µef = 1.53µB. FT-IR (KBr, cm−1): 3452 (w, br), 3051 (w),
2821 (w), 1623 (w), 1602 (s), 1543 (s), 1506 (vs), 1486
(s), 1466 (m), 1423 (s), 1375 (m), 1348 (m), 1293 (m),
1260 (s), 1222 (w), 1179 (w), 1159 (m), 1089 (w), 1053
(w), 1030 (m), 1012 (w), 955 (vs), 906 (w), 867 (w), 851
(m), 811 (m), 774 (w), 741 (w), 729 (m), 680 (w), 644
(w), 583 (w), 467 (w), 436 (w). UV–Vis (DMSO): 331,
428 nm, (MeCN): 267, 337, 447 nm, (EtOH): 228, 264,
326, 430 nm.
5-Methoxysalicylaldehyde (374 µl, 3 mmol) and nicotinic
acid hydrazide (411 mg, 3 mmol) in 45 ml EtOH were
refluxed for 15 min under Ar. Then, VOSO4 (666 mg,
3 mmol) was added, and the mixture was refuxed for the
next 40 min. The compound was fltered of, washed with
EtOH, and dried in air. Yield 0.800 g, 73% MW=363.20.
Anal. Calc. for C14H14N3O5.5 V: C, 46.26; H, 3.85; N,
11.56%. Found: C, 46.06; H, 3.22; N, 11.29%. The complex
is paramagnetic µef =1.42µB. FT-IR (KBr, cm−1): 3490 (w,
br), 3066 (w), 1625 (m), 1597 (s), 1551 (vs), 1481 (s), 1461
(m), 1420 (w), 1340 (s), 1287 (s), 1260 (w), 1219 (s), 1195
(m), 1171 (s), 1031 (s), 949 (s), 932 (m), 872 (s), 827 (s),
786 (m), 707 (s), 673 (m), 614 (s), 574 (s), 477 (m). UV–Vis
(DMSO): 333, 429 nm, (MeCN): 254 nm, (EtOH): 249 nm.
Preparation of [VO(L11)(EtO)(EtOH)] (16)
Preparation of [VO(L13)(EtO)]·0.5H2O (19)
5-Methoxysalicylaldehyde (187 µl, 1.5 mmol) and pheny-
lacetic acid hydrazide (225.2 mg, 1.5 mmol) in 50 ml EtOH
were refluxed for 11 min under Ar. Then, [VO(acac)2]
(399 mg, 1.5 mmol) was added, and the mixture was refuxed
for the next 58 min. This was evaporated in part, but pre-
cipitation was observed the next day in refrigerator. This
was fltered of, washed with EtOH, and dried in air. Yield
0.410 g, 62% MW=440.36. Anal. Calc. for C20H25N2O6V:
C, 54.67; H, 5.68; N, 6.38%. Found: C, 54.55; H, 5.72; N,
6.36%. The complex is diamagnetic. FT-IR (KBr, cm−1):
3452 (w, br), 2990 (w), 1625 (w) 1600 (s), 1546 (vs), 1514
(vs), 1468 (m), 1421 (m), 1377 (w), 1358 (m), 1326 (w),
1288 (m), 1265 (vs), 1238 (w), 1181 (w), 1160 (m), 1107
(w), 1048 (w), 1026 (m), 991 (vs), 901 (w), 844 (m), 817
(m), 766(w), 726 (vs), 690 (w), 637 (w), 587 (w), 553 (w),
524 (w), 467 (w), 425 (w). UV–Vis (DMSO): 323, 413 nm,
(MeCN): 408 nm, (EtOH): 315, 412 nm.
5-Methoxysalicylaldehyde (187 µl, 1.5 mmol) and
3-hydroxy-2-naphthoic acid hydrazide (303 mg, 1.5 mmol)
in 90 ml EtOH were heated on a magnetic stirrer for 10 min
under Ar. The temperature was raised to 100 °C. Then,
VOSO4 (333 mg, 1.5 mmol) and 10 ml of EtOH was added,
and the heterogenic mixture was refuxed for ca. 180 min.
After that, the volume of the reaction mixture was concen-
trated to a fnal volume of ca. 40 ml and cooled to room
temperature. The precipitate was fltered of, washed with
ethanol, and dried in air. Yield 0.698 g, 78% MW=446.33.
Anal. Calc. for C21H19N2O6V: C, 56.51; H, 4.29; N, 6.28%.
Found: C, 56.08; H, 4.25; N, 6.15%. The complex is dia-
magnetic. FT-IR (KBr, cm−1): 3453 (w, br), 2932 (w), 1639
(m), 1596 (m), 1572 (w), 1554 (s), 1524 (m), 1473 (m),
1386 (w), 1371 (w), 1341 (w), 1309 (m), 1274 (s), 1239 (m),
1212 (w), 1168 (w), 1145 (w), 1088 (m), 1031 (s), 991 (s),
954 (w), 904 (w), 822 (m), 765 (w), 719 (w), 683 (w), 622
(m), 597 (m), 577 (m), 527 (w), 478 (w). UV–Vis (DMSO):
333, 438 nm, (MeCN): 325, 427 nm, (EtOH): 321, 428 nm.
Preparation of [VO(L11)(phen)] (17)
Preparation of [VO(L14)(phen)]·4.5H2O (20)
The synthesis was performed as for 14. The hydrazide used
was phenylacetic acid hydrazide (225.8 mg, 1.5 mmol).
Yield 0.619 g, 78% MW = 529.44. Anal. Calc. for
C28H22N4O4V: C, 63.52; H, 4.19; N, 10.58%. Found: C,
63.26; H, 4.11; N, 10.43%. The complex is paramagnetic
Potassium salt of 5-sulfosalicylaldehyde (366 mg, 1.5 mmol)
and 4-hydroxybenzhydrazide (228 mg, 1.5 mmol) in
50 ml ethanol were refuxed for 10 min under Ar. Then,
[VO(acac)2] (397 mg, 1.5 mmol) was added. The refux
1 3

208
Transition Metal Chemistry (2021) 46:201–217
was continued for 15 min under Ar. Next, phen (273 mg,
1.5 mmol) in 10 ml of EtOH was added, and the mixture was
heated for an additional 8 min. The next day, formed crys-
tals were fltered of, washed with cold ethanol, and dried
in air. Yield: 0.312 g, 30%. MW=700.60. Anal. Calcd. for
C26H27N4O11.5KSV: C, 44.57; H, 3.74; N, 5.58; S, 4.64%.
Found: C, 44.70; H, 3.54; N, 7.85; S, 4.31%. The complex is
paramagnetic, µef =1.26µB. FT-IR (KBr, cm−1): 3436 (vs),
1606 (vs), 1501 (s), 1463 (w), 1423 (m), 1375 (m), 1356
(m), 1280 (w), 1194 (w), 1166 (s), 1112 (m), 1033 (vs), 958
(m), 903 (w), 844 (m), 723 (m), 673 (w), 648 (w), 617 (m),
565 (w), 450 (w). UV–Vis (DMSO): 327, 407 nm, (MeCN):
268, 330, 414 nm, (EtOH): 226, 264, 325, 406 nm.
423 (w). UV–Vis (DMSO): 367 nm (MeCN): 271, 387 nm,
(EtOH): 226, 266, 377 nm.
Preparation of [VO(HL17)(H2O)]∙2H2O (23)
Potassium salt of 5-sulfosalicylaldehyde (480 mg, 2.0 mmol)
and nicotinic acid hydrazide (274 mg, 2.0 mmol) in
100 ml ethanol were refuxed for 20 min under Ar. Then,
[VO(acac)2] (530 mg, 2.0 mmol) was added. The refux was
continued for 45 min under Ar. The obtained compound was
fltered of, washed several times with ethanol, and dried at
room temperature. Yield: 0.637 g, 67%. MW=479.37. Anal.
Calcd. for C13H15N3O9KSV: C, 32.54; H, 3.13; N, 8.76; S,
6.70%. Found: C, 33.04; H, 2.77; N, 8.44; S, 6.66%. The
complex is paramagnetic, µef =1.19µB. FT-IR (KBr, cm−1):
3421 (vs), 1613 (vs), 1534 (m), 1461 (m), 1414 (w), 1384
(m), 1363 (m), 1298 (w), 1193 (s), 1113 (s), 1035 (vs), 912
(m), 883 (m), 832 (w), 720 (w), 671 (w), 619 (s), 535 (w),
458 (w), 415 (w). UV–Vis (DMSO): 326, 409 nm, (MeCN):
242, 325, 405 nm, (EtOH): 320, 399 nm.
Preparation of [VO(L15)(phen)]·4H2O (21)
Potassium salt of 5-sulfosalicylaldehyde (367 mg, 1.5 mmol)
and 4-methoxybenzhydrazide (250 mg, 1.5 mmol) in
45 ml ethanol were refuxed for 20 min under Ar. Then,
[VO(acac)2] (378 mg, 1.5 mmol) was added. The refux
was continued for 20 min under Ar. Next, phen (271 mg,
1.5 mmol) was added. The mixture with precipitate
was evaporated to 50% and left for cooling. The mix-
ture was fltered of, washed with ethanol, and dried in
air. Yield: 0.599 g, 55%. MW = 705.63. Anal. Calcd. for
C27H27N4O11KSV: C, 45.96; H, 3.86; N, 7.94; S, 4.54%.
Found: C, 45.65; H, 3.70; N, 7.83; S, 4.40%. The complex
is paramagnetic, µef = 1.34µB. FT-IR (KBr, cm−1): 3436
(vs), 1609 (vs), 1535 (w), 1499 (s), 1461 (m), 1421 (m),
1371 (m), 1352 (s), 1310 (w), 1252 (s), 1175 (vs), 1116 (s),
1040 (vs), 963 (s), 905 (w), 846 (m), 751 (w), 728 (m), 675
(m), 646 (w), 617 (m), 587 (w), 469 (w), 437 (w). UV–Vis
(DMSO): 325, 406 nm, (MeCN): 224, 268, 327, 420 nm,
(EtOH): 226, 263, 325, 406 nm.
Preparation of K4[{VO(L18)}2(SO4)]·2H2O·EtOH (24)
Potassium salt of 5-sulfosalicylaldehyde (361 mg, 1.5 mmol)
and 3-hydroxy-2-naphtoic acid hydrazide (303 mg,
1.5 mmol) were dissolved in 60 ml ethanol under Ar fow
on a magnetic stirrer. The mixture was refuxed for 20 min
with constant stirring, and the temperature was raised to
100 °C. Then, VOSO4 (333 mg, 1.5 mmol) in 15 ml ethanol
was added. The refux was continued for 180 min under Ar.
After that, the volume of the reaction mixture was concen-
trated to fnal volume of ca. 20 ml and cooled to room tem-
perature. The obtained compound was fltered of, washed
several times with ethanol, and dried in air. Yield: 0.766 g,
85%. MW=1197.06. Anal. Calcd. for C38H32K4N4O21S3V2:
C, 37.01; H, 2.61; N, 4.54; S, 7.79%. Found: C, 37.35; H,
2.67; N, 4.66; S, 8.54%. The complex is diamagnetic. FT-IR
(KBr, cm−1): 3471 (w, br), 3290 (w), 3081 (w), 1629 (m),
1600 (s), 1578 (w), 1540 (vs), 1462 (w), 1375 (s), 1229 (s),
1138 (vs), 1106 (vs), 1039 (s), 977 (s), 918 (w), 886 (vs),
835 (w), 761 (w), 727 (w), 617 (s), 583 (w), 505 (w), 454
(w), 429 (w). UV–Vis (DMSO): 324, 414 nm, (EtOH): 225,
274, 326 nm.
Preparation of [VO(L16)(phen)]·phen·2H2O (22)
Potassium salt of 5-sulfosalicylaldehyde (361 mg, 1.5 mmol)
and phenylacetic acid hydrazide (225 mg, 1.5 mmol) in
30 ml ethanol were refuxed for 10 min under Ar. Then,
[VO(acac)2] (398 mg, 1.5 mmol) was added. The refux
was continued for 45 min under Ar. Then, phen (270 mg,
1.5 mmol) was added, and refux was continued for 5 min.
The formed precipitate was fltered of, washed with etha-
nol, and dried in air. Yield: 0.493 g, 42%. MW= 795.71.
Anal. Calcd. for C39H32N6O8SV: C, 58.87; H, 4.05; N,
10.56. Found: C, 59.35; H, 4.55; N, 10.75%. The complex
is paramagnetic, µef =0.93µB. FT-IR (KBr, cm−1): 3050 (w),
1586 (s), 1554 (s), 1501 (vs), 1423 (s), 1400 (s), 1369 (w),
1345 (w), 1318 (w), 1288 (w), 1217 (w), 1173 (w), 1143
(w), 1105 (w), 1073 (w), 1025 (m), 956 (vs), 846 (s), 770
(w), 722 (vs), 703 (w), 654 (w), 608 (w), 522 (w), 469 (w),
Crystallographic data collection and structure
refnement
Difraction intensity data for a single crystal of three new
compounds were collected at 293 K on an Oxford Difrac-
tion Super Nova difractometer using monochromatic Mo
Kα (10, 16) or Cu Kα (4) radiation at λ = 0.71073 Å and
λ=1.5418 Å, respectively. Cell refnement and data reduc-
tion were performed using frmware [34]. Positions of all
1 3

Transition Metal Chemistry (2021) 46:201–217
209
nonhydrogen atoms were determined by direct methods
using SIR software (4, 10: SIR92 [35], 16: SIR97 [36].
All nonhydrogen atoms were refned anisotropically using
weighted full-matrix least-squares on F2. Refnement and
further calculations were carried out using SHELXL soft-
ware [37] (4, 10: ver 2017/1, 16: ver 2016/1]. All hydrogen
atoms joined to carbon atoms were positioned with idealized
geometries and refned using a riding model with Uiso(H)
fxed at 1.2 Ueq(Carom). In structure 10, two carbon atoms
of the coordinating ethanol molecule, C31 (methylene)
and C32 (methyl), show disorder and were modeled (split)
into two sets of positions A and B with their geometries
restrained, with the refned occupancies being 0.54(5) and
0.46(5), respectively. The positions of all hydrogen atoms
were constrained for all compounds using AFIX (SHELXL)
commands. CCDC 1871461, 1871462, and 1871642 contain
the supplementary crystallographic data for 4, 10, and 16.
These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Center via www.ccdc.cam.
ac.uk/data_request/cif. The crystallographic data and
detailed information on the structure solution and refnement
are presented in Table 2. The bond distances and angles are
listed in Supplementary Tables S1–S3.
Results and discussion
General remarks on the synthesis
As a result of the syntheses, 24 oxidovanadium(IV,V)
complexes were obtained by reaction of VOSO4aq or
[VO(acac)2] with in situ formed tridentate Schif base
Table 2 Crystal data and structure refnement parameters for 4, 10, and 16
4
10
16
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
Unit cell dimensions
a (Å)
b (Å)
c (Å)
α (°)
β (°)
C16H14N3O7V
411.24
293(2)
1.5418
Triclinic
P-1
C22H22N3O8V
507.36
293(2)
0.71069
Monoclinic
P21/c
C20H25N2O6V
440.36
293(2)
0.71073
Triclinic
P-1
7.4393(4)
8.6931(5)
13.2880(8)
88.914(5)
80.414(5)
82.214(5)
839.53(8)
2
11.163(5)
28.248(5)
7.563(5)
90
94.337(5)
90
2378.0(19)
4
1.417
0.469
1048
0.460×0.340×0.140
3.416 to 26.367
10.467(5)
10.683(5)
10.991(5)
118.752(5)
94.900(5)
96.272(5)
1057.5(9)
2
1.383
0.507
460
0.630×0.190×0.100
3.722 to 26.374
γ (°)
Volume (Å3)
Z
Density, calculated (Mg/m3)
Absorption coefcient (mm−1
F(000)
1.627
5.383
420
)
Crystal size (mm3)
θ range for data collection (°)
Index ranges
0.260×0.120×0.060
3.373 to 61.167
−8≤h≤8, −9≤k≤9, −3≤l≤15
−13≤h≤13, −35≤k≤35,
−13≤h≤13, −13≤k≤13,
−7≤l≤9
−13≤l≤13
Refections collected
Independent refections
Completeness to θ (%)
Absorption correction
Refnement method
2545
15,774
4834 [R(int)=0.0207]
99.4
13,522
4316 [R(int)=0.0224]
99.7
2545 [R(int)=0.0457]
98.8
Multiscan
Multiscan
Multiscan
Full-matrix least-squares on F2
2545/14/250
Full-matrix least-squares on F2
4834/25/332
Full-matrix least-squares on F2
4316/0/269
Data/restraints/parameters
Goodness-of-ft on F2
Final R indices [I>2σ(I)]
R indices (all data)
1.163
1.087
1.082
R1 =0.0682, wR2 =0.1903
R1 =0.0795, wR2 =0.1946
0.893 and −0.477
R1 =0.0433, wR2 =0.1374
R1 =0.0577, wR2 =0.1437
0.707 and −0.247
R1 =0.0356, wR2 =0.1010
R1 =0.0469, wR2 =0.1059
0.329 and −0.322
Largest dif. peak and hole (e/Å3)
1 3

210
Transition Metal Chemistry (2021) 46:201–217
ligands. Six of these (4, 7, 10, 16, 19, and 24) are V(V)
complexes, while the others are V(IV) complexes. In
some syntheses, co-ligand in the form of 2,2′-bipyridine
or 1,10′-phenanthroline was used to precipitate the com-
pounds. As vanadium source, VOSO4aq or [VO(acac)2]
was used. In general, [VO(acac)2] was found to be more
suitable due to solubility; however, the product compo-
sition in most cases was similar, independently of the
complex used. Only in three cases (1, 12, and 24) was
SO24− group noticed to be present in the complex and could
not be removed by simple washing. The analysis indicates
that one ion per two vanadium centers is present, in all
the performed syntheses. Thus, the dimeric form of the
complex is suggested.
taking the shape of an almost perfect square pyramid. The
square base of the polyhedron is made of the atoms of a
tridentate L2 ligand and consists of phenolic oxygen O8,
imine nitrogen N4, enol oxygen O1, and an oxygen atom
O24 from deprotonated ethoxide oxygen. The apical posi-
tion of the square pyramid is occupied by the terminal oxido
(O2-) group O23. The short V1–O23 distance of 1.566(5) Å
indicates the presence of a double vanadium–oxygen bond
(V=O). The central vanadium V1 atom is located above
the basal plane of O24, O1, N4, and O8 by 0.450 Å and is
directed toward the apical oxido ligand. Both L2 aromatic
rings are slightly bent downwards in relation to the plane
they create, and the highest deviation relates to the C17 and
C11 atoms and amounts to 0.341 Å and 0.233 Å, respec-
tively (Fig. 1). The square pyramid is slightly distorted, in
which the individual angles N4–O1–O24, O1–O24–O8,
O24–O8–N4, and O8–N4–O1 are 97.16°, 85.10°, 87.69°,
and 89.96°, respectively, where the highest deviation from
the ideal 90° is 7.16°. The observed distortion is due to the
intramolecular structural tension caused by the presence
of both fve- and six-membered rings in the square plane
of the pyramid. Packing analysis of the crystal structure
reveals that the complex molecules are held together by two
π…π stacking and four weak intermolecular interactions of
C–H…O type, as summarized in Supplementary Tables S4
and S5.
Usually, in our previous investigations with vanadium
complexes based on Schif base ligands, oxidation of V(IV)
to V(V) when co-ligand (for example, phen) was not used
[22, 23, 25, 27, 28] was observed. In this part of the inves-
tigation, the oxidovanadium(IV) complexes (1, 9, 11, 12,
18, 23) were obtained, among others, for which there was
no change in the oxidation state and for which a stabilizing
ligand for the V(IV) oxidation state was not used in the syn-
thesis. It must be underlined, however, that those complexes
are not as stable in time as those with co-ligands, especially
with phen.
As the syntheses were performed under Ar atmosphere,
it was difcult to dry the samples to constant mass due to
their air sensitivity. Moreover, the samples were weighed
in air for elemental analysis. This caused the analyses not
to ft perfectly (within 0.4%) in several cases to a proposed
formula (in two cases the largest mistake was on hydrogen,
but still less than 0.9%).
The structure of 10 with atom numbering scheme and
coordination polyhedron of vanadium is presented in Fig. 2.
The vanadium atom is surrounded by ONO donor atoms of
ligand L, two oxygens from EtOH and EtO− molecules, and
O2− anion. The central vanadium atom has six-coordinated
surrounding with ethoxy and L ligand in plane and EtOH
and O2− as apexes. The vanadium atom is shifted out of
plane (constructed on N15–O13–O27 atoms) toward the
oxygen atom by 0.286 Å. Contrary to 4, in 10 aromatic rings
are shifted below this plane (hydrazide ones) and above the
plane (from aldehyde moieties) with the longest distances to
plane for C7 (0.676 Å) and C21 (0.387 Å). The octahedron
is slightly distorted, with O33–V1–O30 angle of 174.28°.
Description of the structures
Compound 4 crystallizes in the triclinic space group P-1 with
an asymmetric cell unit (Fig. 1) containing the monomeric
complex of [VO(L2)(EtO)]. The central vanadium atom has
a fve-coordinate environment with VO4N composition,
Fig. 1 Structure of 4 with marked coordination polyhedron and atom labeling scheme (left), showing the planarity of the ligand and donor atoms
with plane constructed on N4–O1–O24 atoms with 30% probability ellipsoids (right). Hydrogen atoms omitted for clarity
1 3

Transition Metal Chemistry (2021) 46:201–217
211
Fig. 2 Structure of 10 with marked coordination polyhedron and atom labeling scheme. The packing in 10 with 30% probability ellipsoids
(right). Hydrogen atoms omitted for clarity
Again, as in 4, distortion of the square-pyramidal plane
N15–O13–O27–O23, caused by the presence of fve- and
six-membered rings, is observed.
space group P-1 with the asymmetric unit cell containing
one molecule of [VO(L11)(EtO)(EtOH)] complex. Oxi-
dovanadium cation (VO2+) is coordinated with the fully
deprotonated tridentate hydrazone ligand (L11) through
phenolate oxygen (O7), azomethine nitrogen (N11), and
enolate oxygen (O21) and additionally with two oxygen
atoms, one of which is deprotonated ethoxide oxygen
(O22), while the second oxygen (O25) comes from the
ethanol molecule. Thus, the coordination environment
of the central atom V adopts the geometry of an elon-
gated octahedron with the scheme O5N. The basic plane
is defned by the atoms O7, O21, O22, and N11, while the
central vanadium atom is above this plane by 0.3037(8)
Å and is shifted toward the O28 atom (the V–O distance
equals 1.583(2) Å). In the discussed complex (16), the
lengths of V–O bonds have diferent values, the V=Ooxido
bond being the shortest and the V–Oenolate = 2.383(2) Å
(O25 of ethanol) bond being the longest. The oxygen
(O28) atom and atom O25 of the ethanol molecule occupy
the apical sites of the octahedron with a trans angle of
Similarly to 4, in the cell unit there is an equimolar mix-
ture of two isomers, but in the case of 10, four molecules are
present in the unit cell. The packing is presented in Fig. 2
(right).
In 10, both intra- and intermolecular hydrogen bonds are
present. The intramolecular one is between N14 and O11,
similarly to 4, with a distance of 2.577(2) Å, slightly shorter
than in 4. The intermolecular hydrogen bond is formed
between O11 and O30, with a distance equal to 2.784(2) Å
(Supplementary Table S6).
The structure of 10 consists of separated layers, as pre-
sented in Fig. 3. While the layers are supported by a net of
hydrogen bonds, only very weak intramolecular interactions
are present between layers.
The structure of the asymmetric parts of the unit cell of
complex 16 and the adopted atomic numbering scheme are
shown in Fig. 4. This complex crystallizes in the triclinic
Fig. 3 Packing scheme in 10; the net of hydrogen bonds and short contacts are visualized. Hydrogen atoms omitted for clarity, with 30% prob-
ability ellipsoids shown
1 3

212
Transition Metal Chemistry (2021) 46:201–217
Fig. 4 Structure of 16 with marked coordination polyhedron and atom labeling scheme (left). Packing scheme in 16, with 30% probability ellip-
soids (right). Hydrogen atoms omitted for clarity
174.7(6)°. The phenyl ring (C15–C20) of the ligand
forms a dihedral angle of 112.6(3)° with the 2-hydroxy-
5-methoxyphenyl ring. This causes intracomplex tension
and, consequently, is an additional cause of the octahedral
deformation of the geometry of the coordination environ-
ment of the central vanadium atom. Packing analysis of
the crystal structure of 16 reveals that the complex mol-
ecules are stabilized by one typical hydrogen interaction
of O–H…N type [O(25)–H(25)…N(12) [−x + 1, −y + 1,
−z + 1], d(D–H) = 0.76(2) Å, d(H…A) = 2.07(2) Å,
d(D…A) = 2.823(2) Å, and ∠(DHA) = 172(2)°] (Supple-
mentary Table S7). The long-distance packing scheme is
presented in Fig. 4 (right).
This is a direct diference from the V(V) complexes, where
weak bands in this range or intense bands at 983 cm−1 are
observed. The investigated complexes also show a band at
ca. 1600 cm−1 that can be assigned to ν(C=N) vibration
in a Schif base ligand. For complexes with phen or bpy
as ligand, the characteristic bands at ca. 1490, 1425, and
725 cm−1 are related to the vibration in these ligands and
were also observed in other d-electron metal complexes
with phen or bpy [38].
UV–Vis spectra
The positions of the bands for the compounds in three
selected solvents (DMSO, MeCN, and EtOH) were pre-
sented above. The UV–Vis spectra for all the complexes
in organic solvents [DMF, DMSO, EtOH, MeOH, MeCN,
dichloroethane (EtCl2), and n-octanol] and in solid state
as well as their stability at neutral pH and at pH 2.00 are
presented in the Supplementary Electronic Material. In the
UV part of the electronic spectra, the bands attributed to
the coordinated Schif base ligand and co-ligand (phen or
bpy) where present are observed as separate peaks. In the
visible part of the spectra, the band located at ca. 400 nm
can be assigned to a ligand-to-metal charge-transfer (LMCT)
transition between the metal center and Schif base ligand.
This band is relatively intense with molar extinction coef-
cient (mol−1 cm−1 dm3) in DMSO of 2.56 × 104 (1, 390 nm),
2.89 × 104 (2, 393 nm), 2,61 × 104 (3, 399 nm), 4.97 × 104
(4, 387 nm), and 2.55 × 104 (5, 390 nm).
A comparison of the V=O distances in 4, 10, and 16, of
1.568, 1.582, and 1.583 Å, respectively, refects the pres-
ence of EtOH ligand in 10 and 16, resulting in an increase
in the bond distance by ca. 0.014 Å compared with 4. The
V=O bond distance in 4, 10, and 16 is shorter than that
observed in V(IV) analogs (1.604, 1.606, 1.593, 1.598, and
1.594 Å), and similar shortening is observed also for the
V–OL (L = Schif base ligand) bond [21, 22]. In contrast,
the V–NL distance is longer in V(V) compared with V(IV)
complexes (bond distances 2.046, 2.058, 2.039, 2.038, and
2.031 Å) [21, 22].
IR spectra
IR spectral measurements confrmed the presence of char-
acteristic groups in the synthesized oxidovanadium com-
plexes for both V(IV) and V(V). All the vibrational bands
are listed in the “Experimental” section. The most charac-
teristic strong band located in the range of 955–965 cm−1
is associated with ν(V=O) vibration in V(IV) complexes.
The reflectance spectra of representative complexes
[oxidovanadium(IV) complexes with bpy and phen as co-
ligand and oxidovanadium(V) complex] are presented in
Fig. 5. Complexes 2 and 3 show absorption above 700 nm,
which is typical for d1 confguration of V(IV) and is in
1 3

Transition Metal Chemistry (2021) 46:201–217
213
accordance with the magnetic measurements presented
above. Due to low solubility of all complexes, the d–d tran-
sition can be observed only in refectance spectra, while in
solution it is obscured by low intensity. For 10, no band
appears in the range above 500 nm, confrming the V(V)
oxidation state and d0 confguration. This situation was also
observed for the other V(V) complexes (4, 7, 10, 16, 19,
and 24).
Due to problems with the insolubility of the obtained
compounds in water, the complexes were studied in DMSO.
This solvent was selected because of its usefulness in, e.g.,
medicine, as it supports transfer of substances through bio-
logical membranes. The stability of the selected complexes
was measured by UV–Vis spectra versus time. The com-
pounds showed stability in the solvent tested and were dis-
solved in DMSO-H2O mixture (20 µl+3 ml, respectively)
at neutral pH and at pH 2.00. The UV–Vis spectra were
measured over time for each mixture. Most of the complexes
tested were stable in natural pH but gradually decomposed in
Fig. 5 Refectance spectra of complexes 2 (black, solid line), 3 (red,
dashed line), and 10 (blue, dotted line) in the range 200–900 nm after
Kubelka–Munk transformation. BaSO4 as internal (white) reference
Fig. 6 UV–Vis spectra of complex 2 (left side) and 3 (right side) in DMSO-H2O mixture (20 µl+3 ml, respectively) at natural pH (above) and
pH 2.00 (below). T=37 °C, d=1 cm, 15 spectra measured at 340-s intervals. The arrow shows the direction of changes in spectra
1 3

214
Transition Metal Chemistry (2021) 46:201–217
Fig. 9 TG (left axis) and SDTA (right axis) curves for 2. Scan speed
Fig. 7 Cyclic voltammogram of 3 in DMSO. 0.1 M Bu4NPF6 as elec-
trolyte, Pt working and counter and Ag/AgCl reference electrodes,
potentials versus NHE. Scan speed 100 mV/s (for main curve in full
range); insets: scans in selected voltage range with scan speeds in the
range of 20–1000 mV/s
10°/min, air
Fig. 10 TG (left axis) and SDTA (right axis) curves for 3. Scan speed
10°/min, air
Fig. 8 Cyclic voltammogram of 5 in DMSO. 0.1 M Bu4NPF6 as elec-
trolyte, Pt working and counter and Ag/AgCl reference electrodes,
potentials versus NHE. Scan speed 100 mV/s (for main curve in full
range); insets: scans in selected voltage range with scan speeds in the
range of 20–1000 mV/s
Cyclic voltammetry
Cyclic voltammetry measurements were performed in
DMSO using Pt working and counter and Ag/AgCl ref-
erence electrodes in 0.1 M Bu4NPF6 as supporting elec-
trolyte. Exemplary voltammograms were selected for
oxidovanadium(IV) complexes with phen (Fig. 7) and bpy
(Fig. 8) ligands. In general, for oxido complexes of vana-
dium, irreversible redox processes are observed. Only for
complexes with phen or bpy as co-ligand were reversible
peaks, attributed to reduction of these ligands, observed in
the negative part of the voltammograms. The presence of
two reversible processes for 3 (Fig. 7) in this part is a result
of the observed instability of 3 in DMSO. Thus, we observe
“free” and coordinated phen reversible redox processes. As
pH 2.00 (1, 3, 6, 8–10, 12–15, 18–21, 23, 24). Complexes 2,
4, 17, and 22 were unstable at natural pH and pH 2.00. Only
complexes 7 and 16 were stable in natural pH as well as pH
2.00. Exemplary spectral changes for complexes 2 and 3 are
presented in Fig. 6.
1 3

Transition Metal Chemistry (2021) 46:201–217
215
coordination as ligands. The ligand release in 3 is the most
typical example. The most volatile hydrazide is released
frst, while the high-molecular-mass phen ligand is released
second. The thermograms of 2 and 5 with relatively similar
composition (the only diference in the benzhydrazide or
hydroxybenzhydrazide component of ONO ligand) are very
interesting, as they show very diferent thermal behavior, as
presented in Figs. 9 and 11.
As the thermograms were measured in air, the fnal
product is a V2O5 molecule. The formation of vanadium(V)
oxide increases the mass of the fnal product by 4.46% for
2 and by 4.31% for 3, and this should be corrected from
the fnal results presented in Table 3, for example from the
calculated 88.35% to 84.05%, which is very close to the
experimental value of 83.50%.
Fig. 11 TG (left axis) and SDTA (right axis) curves for 5. Scan speed
10°/min, air
Pharmacological activity
a result of complex stability, Fig. 8 presents the voltammo-
gram of 5 which, contrary to 3, is stable in DMSO. The pre-
sented voltammograms are very similar to those described
by us earlier [20–26].
Most of the tested complexes at concentration of 1 μM
showed similar (2, 4, 9) or weaker (12, 13, 16) activity
than BMOV used as a comparator of activity. These results
may be explained by structural diferences between these
complexes. Complex 3 (Table 4) showed signifcantly
lower ability to inhibit all the tested PTPs. This complex
is characterized by the greatest diferences between the
inhibition potency of PTPs associated with antidiabetic
activity (PTP1B, SHP1, and SHP2) and the inhibition of
CD45 phosphatase. To assess the antidiabetic activity of
3, pharmacological activity studies were performed in cell
models (Table 5). The antidiabetic activity of this com-
plex has the same cellular profle and activity as BMOV.
Radiolabeled glucose uptake by C2C12 myocytes is 126%
for 3 and 125% for BMOV. The efect on glucose uptake
in 3T3-L1 adipocytes is negligible for both complexes. In
addition, both complexes do not show signifcant changes
Thermogravimetry
Thermal decomposition studies were performed in air
atmosphere for complexes 2, 3, and 5. The TG curve
together with SDTA results are presented in Figs. 9 10, and
11. The numerical data are presented in Table 3. In general,
all the presented complexes are of V(IV) type with co-ligand
(bpy or phen). Complicated decomposition processes over-
lapping with each other were observed. Similarly, as in our
previous study, we observed that Schif base ligand decom-
posed partly, with hydrazide component released frst. A
high temperature of solvent molecules release indicates their
Table 3 TG and SDTA data for
Complex
m (mg)
Tmax, SDTA (°C)
Δmexp (%)
Δmcalc (%)
Attributed to
complexes 2, 3, and 5
2
11.0332
10.9660
10.6505
7.4592
5.1075
2.1618
109
309
441
812
0.61
4.27
0.5 EtOH
3.47
34.98
60.27
87.96
bpy, 0.5 EtOH, 0.5 H2O
bpy, 0.5 EtOH, hydrazide
bpy, 0.5 EtOH, L
32.39
53.71
80.41
3
5
10.1038
9.9643
8.1914
4.8075
1.6667
11.8891
11.81331
1.9695
321.5 (exo)
345 (exo)
364 (exo)
501 (exo)
1.38
24.83
57.16
88.35
hydrazide
18.93
52.42
83.50
phen, hydrazide
1.5 H2O, phen, L
324 (exo)
453 (exo)
0.64
87.39
H2O, bpy, L
83.43
Scan speed 10°/min
1 3

216
Transition Metal Chemistry (2021) 46:201–217
Table 4 Inhibition (%) of human tyrosine phosphatases
ligands with the same set of hydrazide component of
ligands, with one or two selected aldehydes. Very diferent
biological activity was observed with various hydrazides,
but compared with data from other publications, it is obvi-
ous that the type of aldehyde used in the synthesis is of
similar importance. Here, we present 24 new complexes
synthesized with three diferent aldehydes. In most cases,
we used phen as co-ligand to stabilize the oxidation state
of V(IV), and here we use also the more fexible bpy co-
ligand, with good stabilization efect. In general, however,
more fexible ligand complexes were found to be less sta-
ble in solutions. Comparing the biological activity of com-
plexes 2 and 3, the only diference is the co-ligand used
(bpy or phen). It was found that complex 3 with the more
rigid phen ligand shows similar activity to BMOV, while
complex 2 with fexible bpy shows greater activity. In con-
trast, ca. 32% of complex 2 remains in DMSO-H2O mix-
ture at 60 min after solution preparation, while complex 3
decomposes almost completely after this time. Similarly,
at pH 2, complex 2 is slightly more stable than 3. All this
may indicate that the biological activity of 3 is similar to
that of BMOV, as both types of complex decompose after
injection into simple VO2+ ions. Complex 2, being more
stable, is more efective due to its only partial decomposi-
tion, supporting the observed fact that the type of L ligand
infuences the biological activity and in some cases V(IV)
complexes with ONO ligands are threefold more efective
than BMOV and human insulin [23].
Complex
PTB1B
1 μM
LAR
SHP1
SHP2
CD45
0.01 μM
VOSO4
62
44
70
77
40
BMOV
77
74
24
75
58
73
52
54
50
58
77
9
75
64
62
35
46
33
76
78
46
77
75
75
67
68
68
82
83
56
83
82
81
74
71
73
55
53
5
42
33
46
29
16
38
2
3
4
5
9
12
13
16
Numerical results expressed as percent inhibition of untreated control
(enzyme with solvent only). The highest values are indicated in bold,
and the lowest in bold italics. The standard deviation did not exceed
3% in all cases
Table 5 Pharmacological activity test results for 3 and BMOV at con-
centration of 50 µM
BMOV
3
Radiolabeled glucose uptake C2C12
Radiolabeled glucose uptake 3T3-L1
Viability HepG2
Viability C2C12
Viability 3T3-L1
125
109 12
106 10
98
117
100
6
126
103
8
6
106 15
4
2
1
104
107
96
2
8
2
Cytotoxicity HepG2
Acknowledgments This work was partly fnanced by the European
Regional Development Fund under the Innovative Economy Pro-
gramme 2007–2013 (WND POIG.01.03.01-174/09).
The results are given as percent of control (solvent only) standard
deviation (SD)
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
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as you give appropriate credit to the original author(s) and the source,
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in myocyte and adipocyte viability and are not cytotoxic
to HepG2 hepatocytes.
The studies of the pharmacological activity of the vana-
dium complexes showed that they are characterized by
diverse activity in inhibiting tyrosine phosphatases. The
degree of inhibition of tyrosine phosphatases described
as the primary mechanism of action of vanadium com-
pounds need not be crucial for antidiabetic activity such as
PTP1B, SHP1, or SHP2. Due to the above, vanadium com-
pound activity studies should include tests in cell models,
not just using isolated enzymes.
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