Monomeric copper(II) complexes with unsymmetrical salen environment: Synthesis, characterization and study of biological activities.

Three new ONNO-donor tetradentate unsymmetrical salen ligands were synthesized by using o-phenyl diamine with substituted salicylaldehydes followed by a two-step reaction methodology. These three ligands by reaction with Cu(OAc)2.4H2O produced three new monomeric Cu(II) complexes, [CuII(L1-3)] (1-3). Elemental analysis, IR, UV-vis, NMR, and HR-ESI-MS techniques were used to analyze and characterize all the synthesized ligands and their corresponding metal complexes. Molecular structures of 1-3 were confirmed by the single-crystal-XRD analysis. Furthermore, the DNA binding ability of these complexes was checked through UV-vis, fluorescence spectroscopy, and also by circular dichroism studies. All the complexes were found to show an intercalation mode of binding with the Kb value in the range of 104-105 M-1. Finally, 1-3 was tested against two malignant (HeLa and A549) and non-cancerous (NIH-3T3) cell lines to check their in vitro antiproliferative activities. Among all, 1 is the most cytotoxic of the series having IC50 values of 5.7 ± 0.9 and 6.0 ± 0.3 µM against HeLa and A549 cell lines, respectively. This result is also consistent with the DNA binding order. Furthermore, the apoptotic mode of cell death of all the complexes was also evaluated by DAPI, AO/EB, and Annexin V-FITC/PI double staining assays.

Hydrolytically Stable TiIV-Hydrazone-Based Metallodrugs: Protein Interaction and Anticancer Potential.

In this work, three titanium(IV) [TiIV(L1-3)2] (1-3) complexes have been reported using three different tridentate dibasic ONO donor hydrazone ligands, pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L1), furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L2), and thiophene-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L3) tethered with heterocyclic moieties. Elemental analysis, FT-IR, UV-vis, NMR, HR-ESI-MS, and single-crystal X-ray analysis have been used to characterize H2L1-3 and 1-3. In solid structures of 1-3, two ligand molecules with N2O4 donor sets give distorted octahedral geometries to the metal center. The aqueous stability of 1-3 was investigated and well correlated to their perceived pharmacological results. During the investigation, all three complexes were found to be hydrolytically stable in a 90% DMSO-d6/10% D2O (v/v) medium up to 48 h. Furthermore, the interaction of 1-3 with bovine serum albumin (BSA) was tested using fluorescence and absorption techniques. The complexes showed static quenching with a biomolecular quenching constant of Kq ∼ 1013 proposing a high affinity of complexes for BSA. Finally, the anticancer potential of 1-3 was tested against HeLa, A549, and NIH-3T3 cell lines. Among all, 1 with an IC50 value of 11.6 ± 1.1 µM against HeLa cells was found to be the most cytotoxic in the series. Furthermore, it has been found that the compounds induce an apoptotic mode of cell death, which is confirmed by the live cell confocal microscopy and flow cytometry techniques.

Recent Advances in Mitochondria-Localized Luminescent Ruthenium(II) Metallodrugs as Anticancer Agents.

Presently, the most effective way to transport drugs specifically to mitochondria inside the cells is of pharmacophoric interest, as mitochondria are recognized as one of the most important targets for new drug design in cancer diagnosis. To date, there are many reviews covering the photophysical, photochemical, and anticancer properties of ruthenium(II) based metallodrugs owing to their high interest in biological applications. There are, however, no reviews specifically covering the mitochondria-localized luminescent Ru(II) complexes and their subsequent mitochondria-mediated anticancer activities. Therefore, this review describes the physicochemical basis for the mitochondrial accumulation of ruthenium complexes, their synthetic strategies to localize and monitor the mitochondria in living cells, and their related underlying anticancer results. Finally, we review the related areas from previous works describing the mitochondria-localized ruthenium complexes for the treatment of cancer-related diseases. Along with this, we also deliberate the perspectives and future directions for emerging more bifunctional Ru(II) complexes that can target, image, and kill tumors more efficiently in comparison with the existing mitochondria-targeted cancer therapeutics.

Recent advancements of fluorescent tin(IV) complexes in biomedical molecular imaging.

In the last few years, tin(IV) complexes have emerged as very attractive candidates in the field of molecular imaging due to their unique photophysical properties. Despite the few reviews published to date covering the chemistry of organotin and tin complexes and their cytotoxic potential, there are no reviews devoted to their live cell imaging properties. Therefore, this feature article summarizes the discussion of the fundamental photophysical properties of fluorescent tin metal complexes focusing on their recent advances in "biomedical molecular imaging". A debate on the design of tin complexes as cellular imaging agents relating to their chemical, electronic and photophysical properties is enclosed. This paper also discusses the imaging applications of tin complexes in cells, tissues, and organisms via confocal and multiphoton imaging for sensing mechanisms in cellular media, bioimaging, and therapeutic labeling. In addition, it explores and explains the current challenges and prospects associated with these tin complexes as emerging luminescent cellular agents for potential clinical use.

Kink distortion of the pseudo-S4 axis in pseudotetrahedral [N2O2] bis-chelate cobalt(II) single-ion magnets leads to increased magnetic anisotropy.

Two new mononuclear cobalt(II) complexes with the general formula [Co(L1,2)2] (1 and 2) were synthesized using bidentate Schiff base ligands with NO donor set, namely, 2-(benzothiazole-2-ylimino)methyl-5-(diethylamino)phenol (HL1) and its methyl substituted derivative 2-(6-methylbenzothiazole-2-ylimino)methyl-5-(diethylamino)phenol (HL2). X-ray structure analysis reveals a distorted pseudotetrahedral coordination sphere at the cobalt(II) ion, that cannot be described by a simple twisting of the two ligand chelate planes with respect to each other, which would imply a rotation about the pseudo-S4 axis of the complex. Such a pseudo-rotation axis would approximately be colinear with the two vectors defined by the cobalt ion and the two centroids of the chelate ligands, where the angle κ between the two vectors would be 180° in an ideal pseudotetrahedral arrangement. For complexes 1 and 2, the observed distortion can be characterized by a significant bending at the cobalt ion with angles κ of 163.2° and 167.4°, respectively. Magnetic susceptibility and FD-FT THz-EPR measurements together with ab initio calculations reveal an easy-axis type of anisotropy for both complexes 1 and 2, with a spin-reversal barrier of 58.9 and 60.5 cm-1, respectively. For both compounds, frequency-dependent ac susceptibility measurements show an out-of-phase susceptibility under applied static fields of 40 and 100 mT, which can be analyzed in terms of Orbach and Raman processes within the observed temperature range.

A Series of Non-Oxido VIV Complexes of Dibasic ONS Donor Ligands: Solution Stability, Chemical Transformations, Protein Interactions, and Antiproliferative Activity.

A series of mononuclear non-oxido vanadium(IV) complexes, [VIV(L1-4)2] (1-4), featuring tridentate bi-negative ONS chelating S-alkyl/aryl-substituted dithiocarbazate ligands H2L1-4, are reported. All the synthesized non-oxido VIV compounds are characterized by elemental analysis, spectroscopy (IR, UV-vis, and EPR), ESI-MS, as well as electrochemical techniques (cyclic voltammetry). Single-crystal X-ray diffraction studies of 1-3 reveal that the mononuclear non-oxido VIV complexes show distorted octahedral (1 and 2) or trigonal prismatic (3) arrangement around the non-oxido VIV center. EPR and DFT data indicate the coexistence of mer and fac isomers in solution, and ESI-MS results suggest a partial oxidation of [VIV(L1-4)2] to [VV(L1-4)2]+ and [VVO2(L1-4)]-; therefore, all these three complexes are plausible active species. Complexes 1-4 interact with bovine serum albumin (BSA) with a moderate binding affinity, and docking calculations reveal non-covalent interactions with different regions of BSA, particularly with Tyr, Lys, Arg, and Thr residues. In vitro cytotoxic activity of all complexes is assayed against the HT-29 (colon cancer) and HeLa (cervical cancer) cells and compared with the NIH-3T3 (mouse embryonic fibroblast) normal cell line by MTT assay and DAPI staining. The results suggest that complexes 1-4 are cytotoxic in nature and induce cell death in the cancer cell lines by apoptosis and that a mixture of VIV, VV, and VVO2 species could be responsible for the biological activity.

LVVO-Ethyl Maltol-Based Metallodrugs (L2- = Tridentate ONO Ligands): Hydrophobicity, Hydrolytic Stability, and Cytotoxicity via ROS-Mediated Apoptosis.

Four new oxidovanadium [VVOL1-4(ema)] complexes (1-4) have been synthesized using tridentate binegative ONO donor ligands H2L1-4 [H2L1: (E)-N'-(2-hydroxybenzylidene)furan-2-carbohydrazide; H2L2: (E)-N'-(4-(diethylamino)-2-hydroxybenzylidene)thiophene-2-carbohydrazide; H2L3: (E)-2-(4-(diethylamino)-2-hydroxybenzylideneamino)-4-methylphenol; H2L4: (E)-2-(3-ethoxy-2-hydroxybenzylideneamino)-4-methylphenol] and ethyl maltol (Hema) as a bidentate uninegative coligand and characterized by CHNS analysis, IR, UV-vis, NMR, and HR-ESI-MS methods. The structures of 1, 3, and 4 are confirmed by single-crystal X-ray analysis. The hydrophobicity and hydrolytic stability of the complexes are tested using NMR and HR-ESI-MS and correlated with their observed biological activities. It is observed that 1 hydrolyzed into a penta-coordinated vanadium-hydroxyl species (VVOL1-OH) with the release of ethyl maltol, whereas 2-4 are found quite stable under the investigated time period. The biomolecular interaction of 1-4 with DNA and BSA was performed using absorbance, fluorescence, and circular dichroism techniques. The in vitro cytotoxicity activities of H2L1-4 and 1-4 were tested against A549, HT-29, and NIH-3T3 cell lines. Among complexes, 2 with an IC50 value of 4.4 ± 0.1 µM displayed maximum anticancer activity against the HT-29 cell line. Complexes induce cell cycle arrest at the G2/M phase and subsequently trigger dose-dependent cell apoptosis, which is obtained by the cell apoptosis analysis via flow cytometry and confocal microscopy assays. Being fluorescence active, 1-4 were observed to target the mitochondria and exhibit disruption of the mitochondrial membrane potential, which consequently causes overproduction of intracellular reactive oxygen species and induced cell apoptosis.

Ruthenium(II)-Dithiocarbazates as Anticancer Agents: Synthesis, Solution Behavior, and Mitochondria-Targeted Apoptotic Cell Death.

The reaction of the Ru(PPh3 )3 Cl2 with HL1-3 -OH (-OH stands for the oxime hydroxyl group; HL1 -OH=diacetylmonoxime-S-benzyldithiocarbazonate; HL2 -OH=diacetylmonoxime-S-(4-methyl)benzyldithiocarbazonate; and HL3 -OH=diacetylmonoxime-S-(4-chloro)benzyl-dithiocarbazonate) gives three new ruthenium complexes [RuII (L1-3 -H)(PPh3 )2 Cl] (1-3) (-H stands for imine hydrogen) coordinated with dithiocarbazate imine as the final products. All ruthenium(II) complexes (1-3) have been characterized by elemental (CHNS) analyses, IR, UV-vis, NMR (1 H, 13 C, and 31 P) spectroscopy, HR-ESI-MS spectrometry and also, the structure of 1-2 was further confirmed by single crystal X-ray crystallography. The solution/aqueous stability, hydrophobicity, DNA interactions, and cell viability studies of 1-3 against HeLa, HT-29, and NIH-3T3 cell lines were performed. Cell viability results suggested 3 being the most cytotoxic of the series with IC50 6.9±0.2 µM against HeLa cells. Further, an apoptotic mechanism of cell death was confirmed by cell cycle analysis and Annexin V-FITC/PI double staining techniques. In this regard, the live cell confocal microscopy results revealed that compounds primarily target the mitochondria against HeLa, and HT-29 cell lines. Moreover, these ruthenium complexes elevate the ROS level by inducing mitochondria targeting apoptotic cell death.

Mitochondria-Targeted Luminescent Organotin(IV) Complexes: Synthesis, Photophysical Characterization, and Live Cell Imaging.

Five fluorescent ONO donor-based organotin(IV) complexes, [SnIV(L1-5)Ph2] (1-5), were synthesized by the one-pot reaction method and fully characterized spectroscopically including the single-crystal X-ray diffraction studies of 2-4. Detailed photophysical characterization of all compounds was performed. All the compounds exhibited high luminescent properties with a quantum yield of 17-53%. Additionally, the results of cellular permeability analysis suggest that they are lipophilic and easily absorbed by cells. Confocal microscopy was used to examine the live cell imaging capability of 1-5, and the results show that the compounds are mostly internalized in mitochondria and exhibit negligible cytotoxicity at imaging concentration. Also, 1-5 exhibited high photostability as compared to the commercial dye and can be used in long-term real-time tracking of cell organelles. Also, it is found that the probes (1-5) are highly tolerable during the changes in mitochondrial morphology. Thus, this kind of low-toxic organotin-based fluorescent probe can assist in imaging of mitochondria within living cells and tracking changes in their morphology.

Dithiocarbazate based oxidomethoxidovanadium(V) and mixed-ligand oxidovanadium(IV) complexes: Study of solution behavior, DNA binding, and anticancer activity.

In this work, one oxidomethoxidovanadium(V) [VVO(L)(OMe)] (1) and two mixed-ligand oxidovanadium(IV) [VIVO(L)(phen)] (2), and [VIVO(L)(bipy)] (3) complexes have been synthesized using a tridentate bi-negative ONS donor dithiocarbazate as main ligand, H2L [where, H2L = S-benzyl-3-(2-hydroxy-3-ethoxyphenyl)methylenedithiocarbazate] along with 1,10-phenanthroline (phen) (for 2) and 2,2'-bipyridine (bipy) (for 3) as co-ligands. The ligand and complexes have been characterised by FT-IR, UV-vis, NMR, and HR-ESI-MS techniques. Distorted square pyramidal for 1, and distorted octahedral geometry for 2 and 3 was confirmed by single crystal X-ray crystallography. The behavior of 1-3 in solution medium has been investigated through various physicochemical techniques. It is observed that 1 completely and 2-3 partially decomposes and converts into a penta-coordinated species, [VIVO(L)(DMSO/H2O)] after the release of the methoxido group (1) or breaking of the diimine based co-ligands (2 and 3) in DMSO/aqueous solution. Interestingly, in DMSO/aqueous solution, 1 gets completely reduced and converted into the corresponding oxidovanadium(IV) species. Interaction of 1-3 with calf thymus DNA (CT-DNA) was investigated and the results show, complex 2 exhibited the maximum binding constants, Kb = 7.12 × 104 M-1. The anticancer potential of 1-3 was evaluated by cell viability assay against human breast carcinoma cell, MCF-7, and noncancerous mouse embryonic cell, NIH-3T3 and 2 was found to be the most cytotoxic complex (IC50 = 6.73 ± 0.36 µM) in the series. In addition, 2 selectively inhibit colony formation compared to the rest complexes. Also, the cell cycle studies of the complexes were performed using flow cytometry analysis.

Evaluation of DNA/BSA interaction and in vitro cell cytotoxicity of µ2-oxido bridged divanadium(V) complexes containing ONO donor ligands.

Two new µ2-oxido bridged divanadium (V) complexes, [VV2O3(L1,2)2] (1 and 2) have been synthesized using bi-negative tridentate ONO-donor ligands, H2L1,2 (H2L1 = 4-tert-butyl-2-[[[3,5-di-tert-butyl-2-hydroxyphenyl]methylene]amino]phenol and H2L2 = 5-bromo-2-[[[4-(diethylamino)-2-hydroxyphenyl]methylene]amino]phenol). The synthesized ligands and complexes have been characterized through FT-IR, UV-vis, NMR, and HR-ESI-MS techniques. Single crystal X-ray crystallography data confirmed distorted square pyramidal geometry for both the complexes. The aqueous phase stability of these complexes has been evaluated through HR-ESI-MS in CH3CN:H2O (80:20) mixture. Thereafter their interaction with calf thymus DNA (CT-DNA) have been studied using electronic absorption and fluorescence spectroscopy, revealing an intercalation mode of binding, with binding constant in the order of 104 M-1. Moreover, bovine serum albumin (BSA) interaction of 1 and 2 has been evaluated via fluorescence quenching experiment, which suggests that the quenching mechanism is static (~1013 M-1) in nature. Additionally, the in vitro cytotoxicity of the complexes has been evaluated in human cervical cancer cells (HeLa) (IC50 = 13.57-16.62 µM) and normal mouse embryonic fibroblasts cells (NIH-3T3). The mechanism of cell death brought about by these complexes was studied by nuclear staining, cell cycle and Annexin V/PI double staining apoptotic assay. These studies indicate that 1 and 2 exert inhibitory effects on the S and G2M phase of cell cycle, which is an indication of apoptotic cell death. Also, a clonogenic assay was performed, which showed that the complexes could effectively inhibit colony formation.

Recent advancements on decarbonylation reactions assisted by Ru-complexes: Synthetic and mechanistic approach.

This frontier article covers the recent advancements in ruthenium complex catalysed decarbonylation reactions of different types of carbonyl compounds and provides a direction towards the mechanistic understanding. The mechanistic pathways provide new strategies for the use of appropriate ruthenium-catalysts, increase the substrate scope, and help in the synthesis of new complexes having multiple functionalities. The content of the article is categorized on the basis of the use of substrates. The new challenges of the decarbonylation reaction depend on the development of new ruthenium-catalysts and the efficiency of the catalytic cycles. Therefore, this short review will give an overall idea about the progress in the field of ruthenium-complex catalysed decarbonylation, catalytic pathways, synthetic applications, and utilities of their products and side products.

New mixed ligand oxidovanadium(IV) complexes: Solution behavior, protein interaction and cytotoxicity.

Herein we report the synthesis of five new mononuclear mixed ligand oxidovanadium(IV) complexes [VIVO(L1-3)(LNN)] (1-5) with tridentate O,N,O-donor aroylhydrazones as main ligand (H2L1-3) and N,N-chelating 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) as co-ligand (LNN). The complexes were characterized by elemental and thermogravimetric analysis (TGA), IR, UV-vis, and electron paramagnetic resonance (EPR) spectroscopy, electrospray ionization-mass spectrometry (ESI-MS) and cyclic voltammetry (CV). The structure of 1-5 was confirmed by single crystal X-ray analysis and also optimized by density functional theory (DFT) methods. At physiological pH an equilibrium [VIVO(L1-3)(LNN)] + H2O ⇄ [VIVO(L1-3)(H2O)] + LNN, shifted towards left, is established, with water molecule that could be replaced by the biomolecules of the organism. The studies on the interaction with two proteins, lysozyme (Lyz) chosen as a representative model of a small protein, and human serum albumin (HSA) show that two types of binding are possible: a non-covalent binding through the accessible residues on protein surface with [VIVO(L1-3)(LNN)] keeping its octahedral structure, and a covalent binding upon the replacement of water in [VIVO(L1-3)(H2O)] with His-N donors to form VIVO(L1-3)(HSA). In vitro cytotoxicity of ligands and complexes were screened against human cervical cancer (HeLa) (IC50 = 7.39-15.13 µM), colon cancer (HT-29) (IC50 = 11.04-28.20 µM) and mouse embryonic fibroblast (NIH-3T3) cell lines (IC50 = 62.22-87.75 µM) by MTT assay. Particularly, 5 showed higher cytotoxicity than cisplatin and cyclophosphamide, with an IC50 of 7.39 ± 1.21 µM and 11.04 ± 0.29 µM against HeLa and HT-29.

Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations.

The transport and cytotoxicity of molybdenum-based drugs have been explained with the concept of chemical transformation, a very important idea in inorganic medicinal chemistry that is often overlooked in the interpretation of the biological activity of metal-containing systems. Two monomeric, [MoO2(L1)(MeOH)] (1) and [MoO2(L2)(EtOH)] (2), and two mixed-ligand dimeric MoVIO2 species, [{MoO2(L1-2)}2(µ-4,4'-bipy)] (3-4), were synthesized and characterized. The structures of the solid complexes were solved through SC-XRD, while their transformation in water was clarified by UV-vis, ESI-MS, and DFT. In aqueous solution, 1-4 lead to the penta-coordinated [MoO2(L1-2)] active species after the release of the solvent molecule (1 and 2) or removal of the 4,4'-bipy bridge (3 and 4). [MoO2(L1-2)] are stable in solution and react with neither serum bioligand nor cellular reductants. The binding affinity of 1-4 toward HSA and DNA were evaluated through analytical and computational methods and in both cases a non-covalent interaction is expected. Furthermore, the in vitro cytotoxicity of the complexes was also determined and flow cytometry analysis showed the apoptotic death of the cancer cells. Interestingly, µ-4,4'-bipy bridged complexes 3 and 4 were found to be more active than monomeric 1 and 2, due to the mixture of species generated, that is [MoO2(L1-2)] and the cytotoxic 4,4'-bipy released after their dissociation. Since in the cytosol neither the reduction of MoVI to MoV/IV takes place nor the production of reactive oxygen species (ROS) through Fenton-like reactions of 1-4 with H2O2 occurs, the mechanism of cytotoxicity should be attributable to the direct interaction with DNA that happens with a minor-groove binding which results in cell death through an apoptotic mechanism.

Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential.

Five new anionic aqueous dioxidovanadium(V) complexes, [{VO2L1,2}A(H2O)n]α (1-5), with the aroylhydrazone ligands pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L1) and furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L2) incorporating different alkali metals (A = Na+, K+, Cs+) as countercation were synthesized and characterized by various physicochemical techniques. The solution-phase stabilities of 1-5 were determined by time-dependent NMR and UV-vis, and also the octanol/water partition coefficients were obtained by spectroscopic techniques. X-ray crystallography of 2-4 confirmed the presence of vanadium(V) centers coordinated by two cis-oxido-O atoms and the O, N, and O atoms of a dianionic tridentate ligand. To evaluate the biological behavior, all complexes were screened for their DNA/protein binding propensity through spectroscopic experiments. Finally, a cytotoxicity study of 1-5 was performed against colon (HT-29), breast (MCF-7), and cervical (HeLa) cancer cell lines and a noncancerous NIH-3T3 cell line. The cytotoxicity was cell-selective, being more active against HT-29 than against other cells. In addition, the role of hydrophobicity in the cytotoxicity was explained in that an optimal hydrophobicity is essential for high cytotoxicity. Moreover, the results of wound-healing assays indicated antimigration in case of HT-29 cells. Remarkably, 1 with an IC50 value of 5.42 ± 0.15 µM showed greater activity in comparison to cisplatin against the HT-29 cell line.

Protein binding and cytotoxic activities of monomeric and dimeric oxido-vanadium(V) salan complexes: Exploring the solution behavior of monoalkoxido-bound oxido-vanadium(V) complex.

Three ONNO donor tetradentate diamino bis(phenolato) "salan" ligands, N, N'-dimethyl-N, N'-bis-(5-chloro-2-hydroxy-3-methyl-benzyl)-1,2-diaminoethane (H2L1), N, N'-dimethyl-N, N'-bis-(5-chloro-2-hydroxy-3-isopropyl-6-methyl-benzyl)-1,2-diamino-ethane (H2L2) and N, N'-bis-(5-chloro-2-hydroxy-3-isopropyl-6-methyl-benzyl)-1,2-diaminocyclohexane (H2L3) have been synthesized by following Mannich condensation reaction. Reaction of these ligands with their corresponding vanadium metal precursors gave one oxidomethoxidovanadium(V) [VVOL1(OCH3)] (1) and two monooxido-bridged divanadium (V, V) complexes [VVOL2-3]2(µ-O) (2-3). The complexes were characterized by IR, UV-vis, NMR and ESI mass spectrometry. Also, the structure of all the complexes (1-3) was confirmed by the Single-Crystal X-ray diffraction analysis, which revealed a distorted octahedral geometry around the metal centres. The solution behavior of the [VVOL1(OCH3)] (1) reveals the formation of two different types of V(V) species in solution, the structurally characterized compound 1 and its corresponding monooxido-bridged divanadium (V, V) complex [VVOL1]2(µ-O), which was further studied by IR, and NMR spectroscopy. The electrochemical behavior of all the complexes was evaluated through cyclic voltammetry. Interaction of the salan-V(V) complexes with human serum albumin (HSA) and bovine serum albumin (BSA) were analysed through fluorescence quenching, UV-vis absorption titration, synchronous fluorescence, circular dichroism studies, and förster resonance energy transfer (FRET). Finally, the in vitro cytotoxicity of the complexes was investigated against MCF-7 and HT-29 and NIH-3T3 cell lines. Cytotoxicity value of complexes in both MCF-7 and HT-29 follows the same trend that is 3 > 1 > 2 which is in line with protein binding affinity of the complexes.

Probing CO Generation through Metal-Assisted Alcohol Dehydrogenation in Metal-2-(arylazo)phenol Complexes Using Isotopic Labeling (Metal = Ru, Ir): Synthesis, Characterization, and Cytotoxicity Studies.

The reaction of 2-{2-(benzo[1,3]dioxol-5-yl)- diazo}-4-methylphenol (HL) with [Ru(PPh3)3Cl2] in ethanol resulted in the carbonylated ruthenium complex [RuL(PPh3)2(CO)] (1), wherein metal-assisted decarbonylation via in situ ethanol dehydrogenation is observed. When the reaction was performed in acetonitrile, however, the complex [RuL(PPh3)2(CH3CN)] (2) was obtained as the main product, probably by trapping of a common intermediate through coordination of CH3CN to the Ru(II) center. The analogous reaction of HL with [Ir(PPh3)3Cl] in ethanol did not result in ethanol decarbonylation and instead gave the organoiridium hydride complex [IrL(PPh3)2(H)] (3). Unambiguous evidence for the generation of CO via ruthenium-assisted ethanol oxidation is provided by the synthesis of the 13C-labeled complex, [Ru(PPh3)2L(13CO)] (1A) using isotopically labeled ethanol, CH313CH2OH. To summarize all the evidence, a ruthenium-assisted mechanistic pathway for the decarbonylation and generation of alkane via alcohol dehydrogenation is proposed. In addition, the in vitro antiproliferative activity of complexes 1-3 was tested against human cervical (HeLa) and human colorectal adenocarcinoma (HT-29) cell lines. Complexes 1-3 showed impressive cytotoxicity against both HeLa (half-maximal inhibitory concentration (IC50) value of 3.84-4.22 µM) and HT-29 cancer cells (IC50 values between 3.3 and 4.5 µM). Moreover, the complexes were comparatively less toxic to noncancerous NIH-3T3 cells.

New VIV, VIVO, VVO, and VVO2 Systems: Exploring their Interconversion in Solution, Protein Interactions, and Cytotoxicity.

The synthesis and characterization of one oxidoethoxidovanadium(V) [VVO(L1)(OEt)] (1) and two nonoxidovanadium(IV) complexes, [VIV(L2-3)2] (2 and 3), with aroylhydrazone ligands incorporating naphthalene moieties, are reported. The synthesized oxido and nonoxido vanadium complexes are characterized by various physicochemical techniques, and their molecular structures are solved by single crystal X-ray diffraction (SC-XRD). This revealed that in 1 the geometry around the vanadium atom corresponds to a distorted square pyramid, with a O4N coordination sphere, whereas that of the two nonoxido VIV complexes 2 and 3 corresponds to a distorted trigonal prismatic arrangement with a O4N2 coordination sphere around each "bare" vanadium center. In aqueous solution, the VVO moiety of 1 undergoes a change to VVO2 species, yielding [VVO2(L1)]- (1'), while the nonoxido VIV-compounds 2 and 3 are partly converted into their corresponding VIVO complexes, [VIVO(L2-3)(H2O)] (2' and 3'). Interaction of these VVO2, VIVO, and VIV systems with two model proteins, ubiquitin (Ub) and lysozyme (Lyz), is investigated through docking approaches, which suggest the potential binding sites: the interaction is covalent for species 2' and 3', with the binding to Glu16, Glu18, and Asp21 for Ub, and His15 for Lyz, and it is noncovalent for species 1', 2, and 3, with the surface residues of the proteins. The ligand precursors and complexes are also evaluated for their in vitro antiproliferative activity against ovarian (A2780) and prostate (PC3) human cancer cells and in normal fibroblasts (V79) to check the selectivity of the compounds for cancer cells.

Polynuclear zinc(II) complexes of thiosemicarbazone: Synthesis, X-ray structure and biological evaluation.

Two new dimeric Zn(II) ([{ZnL1(DMSO2)}2]·DMSO (1), [{ZnL2Cl}2] (2)) and a novel tetrameric Zn(II) complex ([(Zn2L3)2(µ-OAc)2(µ3-O)2] (3)), where H2L1 = 4-(p-methoxyphenyl) thiosemicarbazone of o-hydroxynapthaldehyde, HL2 = 4-(p-methoxyphenyl)thiosemicarbazone of benzoyl pyridine and H2L3 = 4-(p-chlorophenyl)thiosemicarbazone of o-vanillin are reported. Ligands and their complexes were characterized by spectroscopic and single crystal X-ray diffraction techniques. In addition, the complexes exhibited good binding affinity towards HSA (1012 M-1), which is supported by their ability to quench the tryptophan fluorescence emission spectra of HSA. The complexes were also screened for their DNA binding propensity through UV-vis absorption titration, circular dichroism and fluorescence spectral studies. Results show that they effectively interact with CT-DNA through an intercalative mode of binding, with binding constants ranging from 103 to 104 M-1. Among the three complexes 1 has the highest binding affinity towards CT-DNA. Further, the phosphatase activity was evaluated using bis(2,4-dinitrophenyl)phosphate (BDNPP) as substrate, however, the complexes did not yield any measurable catalytic activity. Nevertheless the complexes showed significant cytotoxic potential against HeLa and HT-29 cancer cell lines that was assessed through MTT assay and DAPI staining. Remarkably, complex 1 showed better activity than cisplatin against HT-29 cell line.