In most X-ray diffraction studies reported vanadate binds as a 5-coordinate moiety within the protein.
•Interactions of vanadium compounds with proteins are reviewed.•Structural and functional ...aspects of vanadium–protein interactions are discussed.•The interactions of vanadium ions with enzymes may imply interference at distinct levels.•Phosphate–vanadate physicochemical similarities are relevant in protein binding and inhibition.•Vanadate(IV) can also mimic phosphate.
Vanadium is an element ubiquitously present in our planet's crust and thus there are several organisms that use vanadium for activity or function of proteins. Examples are the vanadium-dependent haloperoxidases and the vanadium-containing nitrogenases. Some organisms that use vanadium have extremely efficient and selective protein-dependent systems for uptake and transport of vanadium and are able to accumulate high levels of vanadium from seawater, vanabins being a unique family of vanadium binding proteins found in ascidians involved in this process. For all of the systems a discussion regarding the role of the V-containing proteins is provided, mostly centered on structural aspects of the vanadium site and, when possible or relevant, relating this to the mechanisms operating. Phosphate is very important in biological systems and is involved in an extensive number of biological recognition and bio-catalytic systems. Vanadate(V) is able to inhibit many of the enzymes involved in these processes, such as ATPases, phosphatases, ribonucleases, phosphodiesterases, phosphoglucomutase and glucose-6-phosphatase, and it appears clear that this is closely related to the analogous physicochemical properties of vanadate and phosphate. The ability of vanadium to interfere with the metabolic processes involving Ca2+ and Mg2+, connected with its versatility to undergo changes in coordination geometry, allow V to influence the function of a large variety of phosphate-metabolizing enzymes and vanadate(V) salts and compounds have been frequently used either as inhibitors of these enzymes, or as probes to study the mechanisms of their reactions and catalytic cycle. In this review we give an overview of the many examples so far reported, also disclosing that vanadate(IV) may also have an equally efficient inhibiting effect. The prospective application of vanadium compounds as therapeutics has also been an important topic of research. How vanadium may be transported in blood and up-taken by cells are particularly relevant issues, this being mainly dependent on transferrin (and albumin) present in blood plasma. The thousands of studies reported on the effects of vanadium compounds reflect the complexity of the interactions occurring. Although it is not easy to anticipate/determine if a particular effect observed in a test tube or in vitro is also going to take place in vivo, it is clear that vanadium ions may interfere with many metabolic processes at many distinct levels. Emphasis is given on structural and functional aspects of vanadium–protein interactions relevant for vanadium binding and/or for clarification of role of the metal center in the reaction mechanisms. The additional knowledge that the presence of vanadium can change the action of a protein, other than simply inhibiting it, may also be important to understand how vanadium affects biological systems. This possibility, together with the vanadate–phosphate analogy further potentiates the belief that vanadium probably has relevant functions in living beings, which may involve interaction or incorporation of the metal ion and/or its compounds with several proteins.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent methodologies for preparation and advantages of immobilized vanadium complexes for catalytic oxidations are discussed. Display omitted
•Advantages of homogeneous vs. immobilized vanadium-based ...catalytic systems.•Vanadium complexes immobilized on polymeric supports for asymmetric synthesis.•Methodologies for the immobilization of vanadium-based homogeneous catalysts.
Homogeneous catalysts have widespread technological application. However, due to advantageous features of immobilization of homogeneous catalysts on solid supports over their soluble counterparts, particularly their easy separation from the reaction mixture and their recycle ability, such systems have grown rapidly over the past few years. Amongst transition-metal compounds, vanadium-based complexes are often good catalysts for oxidation of organic compounds, e.g. by using H2O2 as primary oxidant, and have been successfully applied to a great variety of substrates. This work revises and discusses the performance of the various vanadium-based systems immobilized on polymeric supports developed since ca. 2011, with enhanced focus on applications for asymmetric synthesis. Several strategies are used to prepare immobilized vanadium-based complexes to be used as catalysts. The usual starting point is typically the selection of a homogeneous catalyst i.e. a vanadium complex that has been demonstrated to be highly active and/or highly selective. The additional constraints of the immobilized catalysts sometimes result in more effective catalysts with high turnover numbers which offer real prospect for technological developments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In aqueous media, VIV- and VV-ions and compounds undergo chemical changes such as hydrolysis, ligand exchange and redox reactions that depend on pH and concentration of the vanadium species, and on ...the nature of the several components present. In particular, the behaviour of vanadium compounds in biological fluids depends on their environment and on concentration of the many potential ligands present. However, when reporting the biological action of a particular complex, often the possibility of chemical changes occurring has been neglected, and the modifications of the complex added are not taken into account. In this work, we highlight that as soon as most vanadium(IV) and vanadium(V) compounds are dissolved in a biological media, they undergo several types of chemical transformations, and these changes are particularly extensive at the low concentrations normally used in biological experiments. We also emphasize that in case of a biochemical interaction or effect, to determine binding constants or the active species and/or propose mechanisms of action, it is essential to evaluate its speciation in the media where it is acting. This is because the vanadium complex no longer exists in its initial form.
The interpretation of in vitro cytotoxicity data of Cu(II)-1,10-phenanthroline (phen) complexes normally does not take into account the speciation that complexes undergo in cell incubation media and ...its implications in cellular uptake and mechanisms of action. We synthesize and test the activity of several distinct Cu(II)-phen compounds; up to 24 h of incubation, the cytotoxic activity differs for the Cu complexes and the corresponding free ligands, but for longer incubation times (e.g., 72 h), all compounds display similar activity. Combining the use of several spectroscopic, spectrometric, and electrochemical techniques, the speciation of Cu-phen compounds in cell incubation media is evaluated, indicating that the originally added complex almost totally decomposed and that Cu(II) and phen are mainly bound to bovine serum albumin. Several methods are used to disclose relationships between structure, activity, speciation in incubation media, cellular uptake, distribution of Cu in cells, and cytotoxicity. Contrary to what is reported in most studies, we conclude that interaction with cell components and cell death involves the separate action of Cu ions and phen molecules, not Cu(phen) n species. This conclusion should similarly apply to many other Cu-ligand systems reported to date.
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Two novel bicapped Keggin polyoxidovanadates with organic cations, (C
6
H
8
N)
5
H
4
PV
14
O
42
·5H
2
O (
1
) and (C
6
H
14
N
4
)
2
(NH
4
)H
4
PV
14
O
42
·11H
2
O (
2
), (PV
14
O
42
6−
= PV14, C
6
H
...7
N = 3-picoline and C
6
H
12
N
4
= methenamine) were synthesized. These compounds were isolated and characterized in the solid state and in solution by elemental analysis, powder X-ray diffraction, FTIR, UV-vis,
51
V,
31
P,
13
C and
1
H NMR, and fluorescence spectroscopy. Further confirmation of the PV14 structures was obtained by single-crystal X-ray diffraction studies of
1
and
2
. The Hirshfeld surface analysis was performed to confirm that within the intermolecular interactions occurring in the two crystals, the O H/H O, O O and H H interactions dominate. The protonation and one-electron reduction of the PV14 moiety were also analysed by means of DFT calculations; besides confirming the protonation sites and correctly predicting the p
K
a
values, the DFT results also indicate that molecular reduction is energetically more favourable in protonated PV14 anions. Upon the addition of PV14 anions to bovine serum albumin (BSA) up to a ratio of 1 : 1, the fluorescence decreased by 45% for both
1
and
2
, indicating that the interaction of vanadium-containing species with this protein takes place; log(
K
SV
) values of
ca.
5.5 were obtained in both systems. Upon the addition of
1
or
2
to solutions of calf-thymus DNA (ctDNA), changes were observed in the UV-vis absorption and circular dichroism spectra. The significance of the changes observed is discussed considering the several V-containing species that form in the solution.
Two new crystal structures of phosphotetradecavanadates are reported and theoretical calculations, including DFT analysis, disclose their intermolecular binding interactions.
Five copper(II) complexes, Cu(sal-Gly)(bipy)(1), Cu(sal-Gly)(phen) (2), Cu(sal-l-Ala)(phen) (3), Cu(sal-D-Ala)(phen) (4), Cu(sal-l-Phe)(phen) (5) and five oxidovanadium(IV) complexes, ...VIVO(sal-Gly)(bipy) (6), VIVO(sal-Gly)(phen) (7), VIVO(sal-l-Phe)(H2O) (8), VIVO(sal-l-Phe)(bipy) (9), VIVO(sal-l-Phe)(phen) (10) (sal=salicylaldehyde, bipy=2,2′-bipyridine, phen=1,10-phenanthroline) were synthesized and characterized, and their interaction with DNA was evaluated by different techniques: gel electrophoresis, fluorescence, UV–visible and circular dichroism spectroscopy. The complexes interact with calf-thymus DNA and efficiently cleave plasmid DNA in the absence (only 2 and 5) and/or presence of additives. The cleavage ability is concentration-dependent as well as metal and ligand-dependent. Moreover, DNA binding experiments show that the phen-containing CuII and VIVO compounds display stronger DNA interaction ability than the corresponding bipy analogues. The complexes present cytotoxic activity against human ovarian (A2780) and breast (MCF7) carcinoma cells. Cell-growth inhibition (IC50) of compounds 1, 2 and 5 in human promyelocytic leukemia (HL60) and human cervical cancer (HeLa) cells were also determined. The copper complexes show much higher cytotoxic activity than the corresponding vanadium complexes and the reference drug cisplatin (except for the sal-Gly complexes); namely, the phenanthroline copper complexes 2–5 are ca. 10-fold more cytotoxic than cisplatin and more cytotoxic than their bipyridine analogues.
VIVO and CuII ternary complexes of the type M(sal-AA)(NN) were prepared and its cytotoxicity and ability to interact and cleave DNA were evaluated by several techniques. Phen-containing CuII compounds display stronger nuclease and cytotoxicity activity than corresponding bipy and VIVO analogues. Display omitted
•VIVO and CuII ternary complexes of the type M(sal-AA)(NN), where NN are planar N-donor heterocyclic bases, were prepared.•Complexes interact with calf-thymus DNA and two CuII complexes efficiently cleave plasmid DNA in the absence of additives.•Phen-containing CuII and VIVO compounds display stronger DNA interaction ability and cytotoxicity than the corresponding bipy analogues.•The copper complexes show much higher cytotoxic activity than the corresponding vanadium complexes and the reference drug Cisplatin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The structural determination and characterization of molecules, namely proteins and enzymes, is crucial to gaining a better understanding of their role in different chemical and biological processes. ...The continuous technical developments in the experimental and computational resources of X-ray diffraction (XRD) and, more recently, cryogenic Electron Microscopy (cryo-EM) led to an enormous growth in the number of structures deposited in the Protein Data Bank (PDB). Bioinorganic chemistry arose as a relevant discipline in biology and therapeutics, with a massive number of studies reporting the effects of metal complexes on biological systems, with vanadium complexes being one of the relevant systems addressed. In this review, we focus on the interactions of vanadium compounds (VCs) with proteins. Several types of binding are established between VCs and proteins/enzymes. Considering that the V-species that bind may differ from those initially added, the mentioned structural techniques are pivotal to clarifying the nature and variety of interactions of VCs with proteins and to proposing the mechanisms involved either in enzymatic inhibition or catalysis. As such, we provide an account of the available structural information of VCs bound to proteins obtained by both XRD and/or cryo-EM, mainly exploring the more recent structures, particularly those containing organic-based vanadium complexes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We report the synthesis, characterization and biological screening of new chromone Schiff bases derived from the condensation of three 6-substituted-3-formyl-chromones with pyridoxal (HL
1−3
) and ...its Cu(II) complexes Cu(L
1−3
)Cl,
1
–
3
. For the 6-methyl derivative, HL
2
, the V
IV
O-complex VO(L
2
)Cl (
5
), as well as ternary Cu and V
IV
O complexes with 1,10-phenanthroline (phen), Cu(L
2
)(phen)Cl (
4
) and VO(L
2
)(phen)Cl (
6
), were also prepared and evaluated. Their stability in aqueous medium and radical scavenging activity toward DPPH are screened, with Cu(L
2
)(phen)Cl (
4
) showing hydrolytic stability and VO(L
2
)(phen)Cl (
6
) high radical scavenging activity. Spectroscopic studies establish bovine serum albumin (BSA), a model for HSA, as a potential reversible carrier of Cu(L
2
)(phen)Cl in blood with K
BC
≈ 10
5
M
−1
. The cytotoxic activity of a group of compounds is evaluated against a panel of human cancer cell lines of different origin (ovary, cervix, brain and breast) and compared to normal cells. Our results indicate that Cu complexes are more cytotoxic than the ligands but not selective towards cancer cells. The most potent complexes (
4
and
6
) are further evaluated for their apoptotic potential, induction of reactive oxygen species (ROS) and genotoxicity. Both complexes efficiently triggered cell death through apoptosis as evaluated by DNA morphology and TUNEL assay, increased ROS formation as determined by DCFDA (2ʹ,7ʹ-dichlorodihydrofluorescein diacetate) analysis, and induced genotoxic damage as visualized via COMET assay in all cancer cells under study. Therefore,
4
and
6
may be potential precursor anticancer molecules, yet they need to be targeted toward cancer cells.
Graphical abstract
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Schiff bases {H
3
dfmp-(smdt)
2
} (
I
), {H
3
dfmp-(sbdt)
2
} (
II
) and {H
3
dfmp-(tsc)
2
} (
III
) are synthesized by reaction of 2,6-diformyl-4-methylphenol (H
3
dfmp) and
S
...-methyldithiocarbazate (smdt),
S
-benzyldithiocarbazate (sbdt) and thiosemicarbazide (tsc), respectively. Addition of V
IV
O(acac)
2
to solutions of these compounds in methanol leads to the formation of the oxidovanadium(
iv
) complexes V
IV
O{Hdfmp-(smdt)
2
(CH
3
OH)} (
1
), V
IV
O{Hdfmp-(sbdt)
2
(CH
3
OH)} (
2
) and V
IV
O{Hdfmp-(tsc)
2
(CH
3
OH)} (
3
). All these V
IV
O-compounds can be oxidized to the corresponding dioxidovanadium(
v
) (V
V
O
2
) complexes in methanolic solution upon aerial oxidation in the presence of KOH. The isolated compounds are KV
V
O
2
{Hdfmp-(smdt)
2
} (
4
), KV
V
O
2
{Hdfmp-(sbdt)
2
} (
5
) and KV
V
O
2
{Hdfmp-(tsc)
2
} (
6
). The Cs
+
salts of these complexes
i.e.
CsV
V
O
2
{Hdfmp-(smdt)
2
} (
7
), CsV
V
O
2
{Hdfmp-(sbdt)
2
} (
8
) and CsV
V
O
2
{Hdfmp-(tsc)
2
} (
9
) are prepared similarly in the presence of CsOH. All these compounds are characterized by various spectroscopic techniques like FT-IR, UV-visible, and
1
H and
51
V NMR and thermal studies. IR spectral data confirm the coordination of ligands through the azomethine nitrogen, the sulphur and the phenolic oxygen atoms to the metal. These complexes show excellent catalytic activity and selectivity for the oxidation of benzyl alcohol and ethylbenzene in the presence of H
2
O
2
as an oxidant. Various parameters such as the amount of catalyst and oxidant, reaction time, reaction temperature and solvent were taken into consideration to optimize these catalytic oxidations. Compound
7
was also remarkably efficient and selective in the catalytic oxidation of primary and secondary alcohols to the corresponding aldehyde/ketone, as well as of several aromatic compounds such as toluene, benzene, cumene and tetralin.
The new thiosemicarbazide and dithiocarbazate based vanadium complexes show remarkable catalytic potential for oxidation of alcohols and simple arenes.
A series of mononuclear non-oxido vanadium(IV) VIV(L1–4)2 (1–4), oxidoethoxido vanadium(V) VVO(L1–4)(OEt) (5–8), and dinuclear μ-oxidodioxidodivanadium(V) VV 2O3(L1)2 (9) complexes with ...tridentate aroylazine ligands are reported H2L1 = 2-furoylazine of 2-hydroxy-1-acetonaphthone, H2L2 = 2-thiophenoylazine of 2-hydroxy-1-acetonaphthone, H2L3 = 1-naphthoylazine of 2-hydroxy-1-acetonaphthone, H2L4 = 3-hydroxy-2-naphthoylazine of 2-hydroxy-1-acetonaphthone. The complexes are characterized by elemental analysis, by various spectroscopic techniques, and by single-crystal X-ray diffraction (for 2, 3, 5, 6, 8, and 9). The non-oxido VIV complexes (1–4) are quite stable in open air as well as in solution, and DFT calculations allow predicting EPR and UV–vis spectra and the electronic structure. The solution behavior of the VVO(L1–4)(OEt) compounds (5–8) is studied confirming the formation of at least two different types of VV species in solution, monomeric corresponding to 5–8, and μ-oxidodioxidodivanadium VV 2O3(L1–4)2 compounds. The μ-oxidodioxidodivanadium compound VV 2O3(L1)2 (9), generated from the corresponding mononuclear complex VVO(L1)(OEt) (5), is characterized in solution and in the solid state. The single-crystal X-ray diffraction analyses of the non-oxido vanadium(IV) compounds (2 and 3) show a N2O4 binding set and a trigonal prismatic geometry, and those of the VVO complexes 5, 6, and 8 and the μ-oxidodioxidodivanadium(V) (9) reveal that the metal center is in a distorted square pyramidal geometry with O4N binding sets. For the μ-oxidodioxidodivanadium species in equilibrium with 5–8 in CH2Cl2, no mixed-valence complexes are detected by chronocoulometric and EPR studies. However, upon progressive transfer of two electrons, two distinct monomeric VIVO species are detected and characterized by EPR spectroscopy and DFT calculations.
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