Influence of conventional hydrogen bonds in the intercalation of phenanthroline derivatives with DNA: The important role of the sugar and phosphate backbone.

The influence of hydrogen bonds in model intercalated systems between guanine-cytosine and adenine-thymine DNA base pairs (bps) was analyzed with the popular intercalator 1,10-phenanthroline (phen) and derivatives obtained by substitution with OH and NH2 groups in positions 4 and 7. Semiempirical and Density Functional Theory (DFT) methods were used both including dispersion effects: PM6-DH2, M06-2X and B3LYP-D3 along with the recently developed near linear-scaling coupled cluster method DLPNO-CCSD(T) for benchmark calculations. Our results given by QTAIM and non-covalent interaction analysis confirmed the existence of hydrogen bonds created by OH and NH2 . The trends in the energy decomposition analysis for the interaction energy, ΔEint , showed that the ΔEelstat contributions are equal or even a little bit higher than the values for ΔEdisp . Such important ΔEelstat attractive contribution comes mainly from the conventional hydrogen bonds formed by OH and NH2 functional groups with DNA not only with bps but specially with the sugar and phosphate backbone. This behavior is very different from that of phen and other classical intercalators that cannot form conventional hydrogen bonds, where the ΔEdisp is the most important attractive contribution to the ΔEint . The inclusion of explicit water molecules in molecular dynamics simulations showed, as a general trend, that the hydrogen bonds with the bps disappear during the simulations but those with the sugar and phosphate backbone remain in time, which highlights the important role of the sugar and phosphate backbone in the stabilization of these systems.

Unravelling the binding affinity and selectivity of molybdenum(II) phenanthroline complexes with DNA G-quadruplexes by using linear-scaling DFT studies. The important role of ancillary ligands.

We have used near linear-scaling density functional theory (LS-DFT) methods including dispersion, for the first time, to study the interaction of two isomers, equatorial (Eq) and axial (Ax), of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with the DNA G-quadruplexes (GQ) to gain insight into its cytotoxicity. The LMKLL/DZDP level of calculation, which includes van der Waals contributions, with the SIESTA software was used to treat by means of first-principles computations the whole biological studied model system with ∼1000 atoms. Computed formation energies point to systems containing the Ax isomer as the most stable although the nearest system in energy containing the Eq isomer is only 7.5 kcal mol-1 above. On the other hand, the energy decomposition analysis (EDA) favours interaction energies for the systems containing the Eq isomer. However, when solvent effects are taken into account the systems containing the Ax isomer are again the most stable. This Ax isomer was found interacting by means of end-stacking with the GQ and surprisingly totally inside the non-canonical secondary structure, where all the ligands of the metal complex produce several weak interactions with the DNA structure. On the other hand, the Eq isomer prefers to interact from outside by means of intercalation in which the ancillary ligands also have some role in the interaction. Such features and comparison with the results regarding the interaction of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with duplex DNA suggest that the [Mo(η3-C3H5)Br(CO)2(phen)] would have a higher affinity and eventual selectivity for non-canonical DNA GQ structures.

Semi-empirical and linear-scaling DFT methods to characterize duplex DNA and G-quadruplexes in the presence of interacting small molecules.

The computational study of DNA and its interaction with ligands is a highly relevant area of research, with significant consequences for developing new therapeutic strategies. However, the computational description of such large and complex systems requires considering interactions of different types simultaneously in a balanced way, such as non-covalent weak interactions (namely hydrogen bonds and stacking), metal-ligand interactions, polarisation and charge transfer effects. All these considerations imply a real challenge for computational chemistry. The possibility of studying large biological systems using quantum methods for the entire system requires significant computational resources, with improvements in parallelisation and optimisation of theoretical strategies. Computational methods, such as Linear-Scaling Density Functional Theory (LS-DFT) and DLPNO-CCSD(T), may allow performing ab initio quantum mechanics calculations, including the electronic structure for large biological systems, in a reasonable computing time. In this work, we study the interaction of small molecules and cations with DNA (both duplex DNA and G-quadruplexes), comparing different computational methods: a LS-DFT method at the LMKLL/DZDP level of theory, semi-empirical methods (PM6-DH2 and PM7), mixed QM/MM, and DLPNO-CCSD(T). Our goal is to demonstrate the adequacy of LS-DFT to treat the different types of interactions present in DNA-dependent systems. We show that LMKLL/DZDP using SIESTA can yield very accurate geometries and energetics in all the different systems considered in this work: duplex DNA (dDNA), phenanthroline intercalating dDNA, G-quadruplexes, and metal-G-tetrads considering alkaline metals of different sizes. As far as we know, this is the first time that full G-quadruplex geometry optimisations have been carried out using a DFT method thanks to its linear-scaling capabilities. Moreover, we show that LS-DFT provides high-quality structures, and some semi-empirical Hamiltonians can also yield suitable geometries. However, DLPNO-CCSD(T) and LS-DFT are the only methods that accurately describe interaction energies for all the systems considered in our study.

Probing the Catalytically Active Species in POM-Catalysed DNA-Model Hydrolysis*.

Phosphoester hydrolysis is an important chemical step in DNA repair. One archetypal molecular model of phosphoesters is para-nitrophenylphosphate (pNPP). It has been shown previously that the presence of molecular metal oxide [Mo7 O24 ]6- may catalyse the hydrolysis of pNPP through the partial decomposition of polyoxomolybdate framework resulting in a [(PO4 )2 Mo5 O15 ]6- product. Real-time monitoring of the catalytic system using electrospray ionisation mass spectrometry (ESI-MS) provided a glance into the species present in the reaction mixture and identification of potential catalytic candidates. Following up on the obtained spectrometric data, Density Functional Theory (DFT) calculations were carried out to characterise the hypothetical intermediate [Mo5 O15 (pNPP)2 (H2 O)6 ]6- that would be required to form under the hypothesised transformation. Surprisingly, our results point to the dimeric [Mo2 O8 ]4- anion resulting from the decomposition of [Mo7 O24 ]6- as the active catalytic species involved in the hydrolysis of pNPP rather than the originally assumed {Mo5 O15 } species. A similar study was carried out involving the same species but substituting Mo by W. The mechanism involving W species showed a higher barrier and less stable products in agreement with the non-catalytic effect found in experimental results.

Mechanistic Insights into Promoted Hydrolysis of Phosphoester Bonds by MoO2Cl2(DMF)2.

A phosphoester bond is a crucial structural block in biological systems, whose occurrence is regulated by phosphatases. Molybdenum compounds have been reported to be active in phosphate ester hydrolysis of model phosphates. Specifically, MoO2Cl2(DMF)2 is active in the hydrolysis of para-nitrophenyl phosphate (pNPP), leading to heteropolyoxometalate structures. We use density functional theory (DFT) to clarify the mechanism by which these species promote the hydrolysis of the phosphoester bond. The present calculations give insight into several key aspects of this reaction: (i) the speciation of this complex prior to interaction with the phosphate (DMF release, Mo-Cl hydrolysis, and pH influence on the speciation), (ii) the competition between phosphate addition and the molybdate nucleation process, (iii) and the mechanisms by which some plausible active species promote this hydrolysis in different conditions. We described thoroughly two different pathways depending on the nucleation possibilities of the molybdenum complex: one mononuclear mechanism, which is preferred in conditions in which very low complex concentrations are used, and another dinuclear mechanism, which is preferred at higher concentrations.

From groove binding to intercalation: unravelling the weak interactions and other factors modulating the modes of interaction between methylated phenanthroline-based drugs and duplex DNA.

Several antitumor drugs base their cytotoxicity on their capacity to intercalate between base pairs of DNA. Nevertheless, it has been established that the mechanism of intercalation of drugs in DNA starts with the prior groove binding mode of interaction of the drug with DNA. Sometimes, for some kind of flat small molecules, groove binding does not produce any cytotoxic effect and the fast transition of such flat small molecules to the cytotoxic intercalation mode is desirable. This is the case of methylated phenanthroline (phen) derivatives, where, changes in the substitution in the position and number of methyl groups determine their capability as cytotoxic compounds and, therefore, it is a way for the modulation of cytotoxic effects. In this work, we studied this modulation by means of the interaction of the [Pt(en)(phen)]2+ complex and several derivatives by methylation of phen in different number and position and the d(GTCGAC)2 DNA hexamer via groove binding using PM6-DH2 and DFT-D methods. The analysis of the geometries, electronic structure and energetics of the studied systems was compared to experimental works to gain insight into the relation structure-interaction for the studied systems with cytotoxicity. The trends are explained by means of the Non-Covalent Interaction (NCI) index, the Energy Decomposition Analysis (EDA) and solvation contributions. Our results are in agreement with the experiments, in which the methylation of position 4 of phen seems to favour the interaction via groove binding thus making the transition to the intercalation cytotoxic mode difficult. Looking at the NCI results, these interactions come not only from the CH/π and CH/n interactions of the methyl group in position 4 but also from the ethylenediamine (en) ligand, whose orientation in the Pt complex was found in such a way that it produces a high number of weak interactions with DNA, especially with the sugar and phosphate backbone.

Electron-Transfer-Induced Side-Chain Cleavage in Tryptophan Facilitated through Potassium-Induced Transition-State Stabilization in the Gas Phase.

Fragmentation of transient negative ions of tryptophan molecules formed through electron transfer in collisions with potassium atoms is presented for the first time in the laboratory collision energy range of 20 up to 100 eV. In the unimolecular decomposition process, the dominating side-chain fragmentation channel is assigned to the dehydrogenated indoline anion, in contrast to dissociative electron attachment of free low-energy electrons to tryptophan. The role of the collision complex formed by the potassium cation and tryptophan negative ion in the electron transfer process is significant for the mechanisms that operate at lower collision energies. At those collision times, on the order of a few tens of fs, the collision complex may not only influence the lifetime of the anion but also stabilize specific transition states and thus alter the fragmentation patterns considerably. DFT calculations, at the BHandHLYP/6-311++G(3df,2pd) level of theory, are used to explore potential reaction pathways and the evolvement of the charge distribution along those.

New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes.

This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose.

Computational Studies on the Binding Preferences of Molybdenum(II) Phenanthroline Complexes with Duplex DNA. The Important Role of the Ancillary Ligands.

The interaction of two isomers, equatorial (Eq) and axial (Ax), of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with DNA was studied by using large-scaling density functional theory methods including dispersion for the whole system, represented as a d(AGACGTCT)2 DNA octamer, to gain insight into its experimentally found cytotoxicity. Three different modes of interaction were considered: (1) minor groove (mg) binding, (2) intercalation through the major groove (MG), and (3) the apparently unexpected intercalation via the mg. Computed formation energies, energy decomposition analysis, solvation energies, and noncovalent interaction analysis explain the preference for Eq and Ax isomers of the complex for intercalation via the mg. π-π interactions of the phenanthroline (phen) flat ligand that appear in the intercalation mode and do not exist for the mg binding mode suggest the preference of [Mo(η3-C3H5)Br(CO)2(phen)] for intercalation. On the other hand, the role of the ancillary ligands is crucial for better interaction of the metal complex including phen than when the phen ligand alone is considered because of their additional interactions with base pairs (bps). The role of the ancillary ligands is enhanced when intercalation takes place through the mg because such ligands are able to interact not only with bps but also with the sugar and phosphate backbone, whereas for intercalation through the MG, the interaction of these ligands is only with bps. This feature explains the preference of [Mo(η3-C3H5)Br(CO)2(phen)] for intercalation via the mg in crystal structures. Finally, the solvation penalty is more important for intercalation through the mg than via the MG, which suggests a subtle mechanism involving weak interactions with solvent molecules to explain the selectivity for intercalation in solution to answer the MG versus mg question.

Unraveling the Modulation of the Activity in Drugs Based on Methylated Phenanthroline When Intercalating between DNA Base Pairs.

Phenanthroline derivatives intercalate between base pairs of DNA and produce cytotoxic effects against tumoral cells. Nevertheless, modulation of their efficiency by substitution remains unclear in bibliography. In this work, the effects of methylation of phenanthroline, in number and position, when it intercalates between guanine-cytosine base pairs (GC/CG), were studied with PM6-DH2 and DFT-D methods including dispersion corrections. An analysis of the geometries, electronic structure, and energetics in the interaction was carried out for the studied systems. Our results were compared to experimental works to gain insight on the relation structure-interaction for the intercalated system with cytotoxicity. The trends are explained including not only intrinsic contributions to energy, ΔEPauli, ΔEdisp, ΔEorb, and ΔEelstat, but also the solvation energy, ΔESolv. A subtle balance between the number of stabilizing weak interactions (CH/π, CH/n, etc.) and steric hindrance seems to be related to the efficiency of such drugs.

On the H2 interactions with transition metal adatoms supported on graphene: a systematic density functional study.

The attachment of H2 to the full set of transition metal (TM) adatoms supported on graphene is studied by using density functional theory. Methodology validation calculations on the interactions of H2 with benzene and graphene show that any of the vdW corrections under study, the Grimme D2, D3, D3 with Becke-Jonson damping (D3BJ), and Tkatchenko-Scheffler methods, applied on the PBE functional, are similarly accurate in describing such subtle interactions, with an accuracy of almost 2 kJ mol-1 compared to experiments. The PBE-D3 results show that H2 physisorbs on especially stable d5 or d10 TMs. In other 5d metals, and the rightmost 3d and 4d ones, H2 dissociates, and only for Y, Mn, Fe, and Zr the H2 binds strongly enough for its storage in the so-called Kubas mode, where the H2 bond is sensibly elongated. Other metals (Co, Ni, Ru, Rh and Pd) feature also an elongated Kubas mode, interesting as well for H2 storage. Sc and Ti display a Kubas modes especially suited, given their lightness, for meeting the gravimetric requirements. The H2 interactions with TM adatoms imply a TM → H2 charge transfer, although the magnetic moment of the system tends to remain intact, except for the early 5d TMs, where the unpaired electron transfer seems to be associated with the H2 bond breakage.

Effects of oxygenation on the intercalation of 1,10-phenanthroline-5,6/4,7-dione between DNA base pairs: a computational study.

The effects of oxygen in positions 4,7 and 5,6 of phenanthroline when this ligand intercalates between guanine-cytosine and adenine-thymine DNA base pairs (GC/CG and AT/TA) have been studied at the M06-2X/6-31+G(d,p) level of calculation. We focused on the changes in the structure, stabilization and energy contributions in the analysis of the interaction. The obtained trends in stabilization are explained by a model including repulsive Pauli (ΔEPauli) contributions, and attractive dispersion (ΔEdisp), orbital (ΔEorb) and electrostatic (ΔEelstat) contributions to energy. When no solvation is considered, the intrinsic ΔEelstat contribution results are crucial for the stabilization of the system. However, the inclusion of the solvation energy ΔEsolv can reverse the final stability trend of the systems becoming, thus, the driving force of the process. Therefore, the solvent will have a relevant influence in the potential cytotoxicity of the intercalation drugs.

Self-Assembly of Uranyl-Peroxide Nanocapsules in Basic Peroxidic Environments.

A wide range of uranyl-peroxide nanocapsules have been synthesized using very simple reactants in basic media; however, little is known about the process to form these species. We have performed a density functional theory study of the speciation of the uranyl ions under different experimental conditions and explored the formation of dimeric species via a ligand exchange mechanism. We shed some light onto the importance of the excess of peroxide and alkali counterions as a thermodynamic driving force towards the formation of larger uranyl-peroxide species.

The energy landscape of uranyl-peroxide species.

Nanoscale uranyl peroxide clusters containing UO2(2+) groups bonded through peroxide bridges to form polynuclear molecular species (polyoxometalates) exist both in solution and in the solid state. There is an extensive family of clusters containing 28 uranium atoms (U28 clusters), with an encapsulated anion in the center, for example, [UO2(O2)(3-x)(OH)(x)(4-)], [Nb(O2)4(3-)], or [Ta(O2)4(3-)]. The negative charge of these clusters is balanced by alkali ions, both encapsulated, and located exterior to the cluster. The present study reports measurement of enthalpy of formation for two such U28 compounds, one of which is uranyl centered and the other is peroxotantalate centered. The [(Ta(O2)4]-centered U28 capsule is energetically more stable than the [(UO2)(O2)3]-centered capsule. These data, along with our prior studies on other uranyl-peroxide solids, are used to explore the energy landscape and define thermochemical trends in alkali-uranyl-peroxide systems. It was suggested that the energetic role of charge-balancing alkali ions and their electrostatic interactions with the negatively charged uranyl-peroxide species is the dominant factor in defining energetic stability. These experimental data were supported by DFT calculations, which agree that the [(Ta(O2)4]-centered U28 capsule is more stable than the uranyl-centered capsule. Moreover, the relative stability is controlled by the interactions of the encapsulated alkalis with the encapsulated anion. Thus, the role of alkali-anion interactions was shown to be important at all length scales of uranyl-peroxide species: in both comparing clusters to clusters; and clusters to monomers or extended solids.

The role of intermolecular interactions in [Fe(X-salEen)2]ClO4 spin crossover complexes.

Two new spin crossover (SCO) Fe(III) compounds were prepared, their structures were analysed and their magnetic properties were investigated. An exhaustive analysis of the effects of halogen substitution and aromatic ring functionalisation on the magnetic properties of non-solvated Fe(III) perchlorate complexes has been performed. Through comparative analysis, different magnetic profiles were found for the compounds studied, namely F (1), Cl (2), H (3), Br (4a, 4b), and I (5). Using tools like Hirshfeld analysis, the study revealed patterns in octahedral distortions and deviations from the ideal octahedral geometry. The SCO phenomenon as the conducting wire in this study, emphasises the influence of intermolecular interactions on the low spin (LS) to high spin (HS) transitions in these halogen-substituted complexes. The prevalence of H⋯H contributions has been demonstrated, albeit being the weakest and an inverse strength relationship in H⋯X interactions ranging from F to I. The findings not only interpret the intricate balance between halogen substitution, functionalisation, and intermolecular interactions in modulating magnetic properties but also direct future works in designing similar molecular systems.

Modulation of lipid-induced ER stress by fatty acid shape.

Exposure of pancreatic ß cells to long-chain saturated fatty acids (SFA) induces a so-called endoplasmic reticulum (ER) stress that can ultimately lead to cell death. This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in ß-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER stress. In the present study, we took advantage of a simple yeast-based model, which brings together most of the trademarks of lipotoxicity in human cells, to screen fatty acids of various structures for their capacity to counter ER stress. Here we demonstrate that the tendency of a free fatty acid (FFA) to reduce SFA toxicity depends on a complex conjunction of parameters, including chain length, level of unsaturation, position of the double bonds and nature of the isomers (cis or trans). Interestingly, potent FFA act as building blocks for phospholipid synthesis and help to restore an optimal membrane organization, compatible with ER function and normal protein trafficking.

Catalysis in a porous molecular capsule: activation by regulated access to sixty metal centers spanning a truncated icosahedron.

The 30 cationic {Mo(V)2O4(acetate)}(+) units linking 12 negatively charged pentagonal "ligands," {(Mo(VI))Mo(VI)5O21(H2O)6}(6-) of the porous metal-oxide capsule, [{Mo(VI)6O21(H2O)6}12{Mo(V)2O4(acetate)}30](42-) provide active sites for catalytic transformations of organic "guests". This is demonstrated using a well-behaved model reaction, the fully reversible cleavage and formation of methyl tert-butyl ether (MTBE) under mild conditions in water. Five independent lines of evidence demonstrate that reactions of the MTBE guests occur in the ca. 6 × 10(3) Å(3) interior of the spherical capsule. The Mo atoms of the {Mo(V)2O4(acetate)}(+) linkers--spanning an ca. 3-nm truncated icosahedron--are sterically accessible to substrate, and controlled removal of their internally bound acetate ligands generates catalytically active {Mo(V)2O4(H2O)2}(2+) units with labile water ligands, and Lewis- and Brønsted-acid properties. The activity of these units is demonstrating by kinetic data that reveal a first-order dependence of MTBE cleavage rates on the number of acetate-free {Mo(V)2O4(H2O)2}(2+) linkers. DFT calculations point to a pathway involving both Mo(V) centers, and the intermediacy of isobutene in both forward and reverse reactions. A plausible catalytic cycle--satisfying microscopic reversibility--is supported by activation parameters for MTBE cleavage, deuterium and oxygen-18 labeling studies, and by reactions of deliberately added isobutene and of a water-soluble isobutene analog. More generally, pore-restricted encapsulation, ligand-regulated access to multiple structurally integral metal-centers, and options for modifying the microenvironment within this new type of nanoreactor, suggest numerous additional transformations of organic substrates by this and related molybdenum-oxide based capsules.

A journey inside the U28 nanocapsule.

Anionic uranyl-peroxide U(28) nanocapsules trap cations and other anions inside, whose structures cannot be resolved by X-ray diffraction, owing to crystallographic disorder. DFT calculations enabled the complete characterization of the geometry of these complex systems and also explained the origin of the disorder. The stability of the capsules was strongly influenced by the entrapped cations. Excellent agreement between experiment and theory was also obtained for the electronic character and redox properties.

Computational Modelling of the Interactions Between Polyoxometalates and Biological Systems.

Polyoxometalates (POMs) structures have raised considerable interest for the last years in their application to biological processes and medicine. Within this area, our mini-review shows that computational modelling is an emerging tool, which can play an important role in understanding the interaction of POMs with biological systems and the mechanisms responsible of their activity, otherwise difficult to achieve experimentally. During recent years, computational studies have mainly focused on the analysis of POM binding to proteins and other systems such as lipid bilayers and nucleic acids, and on the characterization of reaction mechanisms of POMs acting as artificial metalloproteases and phosphoesterases. From early docking studies locating binding sites, molecular dynamics (MD) simulations have allowed to characterize the nature of POM···protein interactions, and to evaluate the effect of the charge, size, and shape of the POM on protein affinity, including also, the atomistic description of chaotropic character of POM anions. Although these studies rely on the interaction with proteins and nucleic acid models, the results could be extrapolated to other biomolecules such as carbohydrates, triglycerides, steroids, terpenes, etc. Combining MD simulations with quantum mechanics/molecular mechanics (QM/MM) methods and DFT calculations on cluster models, computational studies are starting to shed light on the factors governing the activity and selectivity for the hydrolysis of peptide and phosphoester bonds catalysed by POMs.

Relationship between structure and cytotoxicity of vanadium and molybdenum complexes with pyridoxal derived ligands.

In this work four vanadium complexes (compounds 1, 2, 3 and 4) and one molybdenum complex (compound 5) with hydrazone ligands derived from pyridoxal were synthesized and characterized. All compounds are mononuclear species, two of them (compounds 3 and 5) are dioxide complexes and the other three (compounds 1, 2 and 4) monoxide complexes. The vanadium atom of the compound 3 is five-coordinated and all the other compounds have a six coordinated environment polyhedron. The poses for the potential intercalation of the compounds 2 and 3 with DNA were obtained by using AutoDock software. Optimizations were also performed at PM6-D3H4 semi-empirical level whereas the study of the nature of the interaction was carried out by means of the Energy Decomposition Analysis and the Non-Covalent Interaction index by using in both cases Density Functional Theory computations. The cytotoxicity in lung cancer cells (A549 cell line) of all the compounds was also evaluated. After 24 h of treatment, vanadium complexes showed high values of IC50, between 419.93 ± 22.58 and 685.88 ± 46.55 µM. After 48 h, the results showed that the compound 3 had the lowest IC50 value, 65.32 ± 9.95 µM, and the compound 2 the highest value, 375.28 ± 32.09 µM. The molybdenum complex showed the lowest IC50 value at 48 h (11.22 ± 1.34 µM). The toxicity of the compounds 3, 4 and 5 was tested in vivo, using zebrafish model, and the molybdenum complex showed higher toxic effects than the studied vanadium complexes.