Synthesis, structure, solution behaviour and biological evaluation of oxidovanadium(IV/V) complexes: Substrate specific DMSO assisted methylation of a thiosemicarbazone

The synthesis and characterization of an oxidovanadium(IV) [VIVO(L)(acac)] (1) and of two dioxidovanadium(V) [VVO2(L')] (2) and [VVO2(L)] (2a) complexes of the Schiff base formed from the reaction of 4-(p-fluorophenyl) thiosemicarbazone with pyridine-2-aldehyde (HL) is described.The oxidovanadium(IV) species [VIVO(L)(acac)] (1) was synthesized by the reaction of VIVO(acac)2 with the thiosemicarbazone HL in refluxing ethanol. The recrystallization of [VIVO(L)(acac)] (1) in DMF, CH3CN or EtOH gave the same product i.e. the dioxidovanadium(V) complex [VVO2(L)] (2a); however, upon recrystallization of 1 in DMSO a distinct compound [VVO2(L')] (2) was formed, wherein the original ligand L- is transformed to a rearranged one, L’-. In the presence of DMSO the ligand in complex 1 is found to undergo methylation at the carbon centre attached to imine nitrogen (aldimine) and transformed to the corresponding V VO2- species through in situ reaction. The synthesized HL and the metal 2 complexes were characterized by elemental analysis, IR, UV–Vis, NMR and EPR spectroscopy. The molecular structure of [VVO2(L')] (2) was determined by single crystal X–ray crystallography.The methylation of various other ligands and complexes prepared from different vanadium precursors under similar reaction conditions was also attempted and it was confirmed that the imine methylation observed is both ligand and metal precursor specific. Complexes 1 and 2 show in vitro insulin-like activity against insulin responsive L6 myoblast cells, with complex 1 being more potent. In addition, the in vitro cytotoxicity studies of HL, and of complexes 1 and 2 against the MCF–7 and Vero cell lines were also done. The ligand is not cytotoxic and complex 2 is significantly more cytotoxic than 1. DAPI staining experiments indicate that increase in time of incubation as well as increase of concentration of the complexes lead to increase in cell death

Monomeric and dimeric oxidomolybdenum(V and VI) complexes, cytotoxicity, and DNA interaction studies: molybdenum assisted C═N bond cleavage of salophen ligands

Four novel dimeric bis-μ-imido bridged metal–metal bonded oxidomolybdenum(V) complexes [MoV2O2L′21–4] (1–4) (where L′1–4 are rearranged ligands formed in situ from H2L1–4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido- bridged complexes (1–4) have been furnished from rearranged H3L′1–4 ligands, containing an aromatic diimine (o-phenylenediamine) “linker”, where Mo assisted hydrolysis followed by −C═N bond cleavage of one of the arms of the ligand H2L1–4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL′1–4)(OEt)] (Id1–4) was generated in situ. The concomitant deprotonation and dimerization of two molybdenum(V) intermediate species (Id1–4) ultimately resulted in the formation of a bis-μ-imido bridge between the two molybdenum centers of [MoV2O2L′21–4] (1–4). The mechanism of formation of 1–4 has been discussed, and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 where the aromatic “linker” was replaced by an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV–vis spectroscopy, NMR, ESI- MS, and cyclic voltammetry, and the structural features of 1, 2, 4, and 5 have been solved by X-ray crystallography. The DNA binding and cleavage activity of 1–5 have been explored. The complexes interact with CT-DNA by the groove binding mode, and the binding constants range between 103 and 104 M–1. Fairly good photoinduced cleavage of pUC19 supercoiled plasmid DNA was exhibited by all the complexes, with 4 showing the most promising photoinduced DNA cleavage activity of ∼93%. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals that the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines

Oxidomolybdenum Complexes of Mono- and Dibasic Polydentate Ligands: Characterization, Biological and Catalytic Evaluation

Chapter 1: In this chapter the scope of the present investigation is portrayed briefly along with the aim of the work. Chapter 2: Four novel dimeric bis-μ-imido bridged metal-metal bonded oxidomolybdenum(V) complexes [MoV2O2L21-4] (14) (where L1-4 are rearranged ligands formed in situ from H2L1-4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido-bridged complexes (14) have been furnished from rearranged H3Lʹ1-4 ligands, containing an aromatic diimine (o-phenylenediamine) „linker‟, where Mo assisted hydrolysis followed by −C=N bond cleavage of one of the arms of the ligand H2L1-4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL1-4)(OEt)] (Id1-4) was generated in situ and finally formation of bis-μ-imido bridge between the two molybdenum centers of [MoV2O2L21-4] (14) took place. The mechanism of formation of 14 has been discussed and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 containing an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV–Vis spectroscopy, NMR, ESI–MS and cyclic voltammetry, and the structural features of 1, 2, 4 and 5 have been solved by X-ray crystallography. All the complexes (1–5) were tested for their ability to exhibit DNA binding and cleavage activity. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines. Chapter 3: Seven new dioxidomolybdenum(VI) complexes [MoO2L17(X)] (1–7) [Where X= EtOH in case of 1 and 5 and X=DMSO in case of 24 and 6, 7] of aroylazines containing a bulky 3-hydroxy-2-naphthoic substituent, were isolated and structurally characterized. The aroylazine ligands H2L1-7 were derived from the condensation of 3-hydroxy-2-naphthoic acid hydrazide with several substituted aromatic aldehydes/ketones. All the synthesized ligands and metal complexes were successfully characterized by elemental analysis, IR, UV–Vis and NMR spectroscopy. X-ray structures of 16 revealed that the ligands coordinate to the metal center as a dibasic tridentate ligand. Cyclic voltammetry of the complexes shows two irreversible reductive responses within the potential window 0.50 to 1.36 V, due to MoVI/MoV and MoV/MoIV processes. The synthesized complexes 1–7 were used as catalysts for the oxidation of benzoin, and for the oxidative bromination of salicylaldehyde, as a functional mimic of haloperoxidase. It was found that the percentage of conversion increased significantly in the presence of catalysts 1–7 which contained bulky substituents, and showed high percentage of conversion (>90%) with high turnover frequency (>1100 h-1) than previously reported catalysts. Benzil, benzoic acid and benzaldehyde-dimethylacetal were formed selectively for the oxidation of benzoin. Formation of 5-bromosalicylaldehyde and 3,5-dibromosalicylaldehyde took place during the oxidative bromination of salicylaldehyde in presence of H2O2 as an oxidant and therefore 1–7 act as functional models of vanadium dependent haloperoxidases. Chapter 4: Four novel mononuclear oxido-imido molybdenum(VI) complexes [MoVIOL′1-4L′′] (1−4), and a dimeric oxidomolybdenum(V) complex [Mo2VO3L′′2] (5) containing rearranged ligand fragments L′1−4 and L′′, are reported. H2L1−4′ and H2L′′, were formed by in situ ligand rearrangement of the ligands HL1-4 which gave rise to the complexes 1−4 during the first 15 mins of the reaction while complex 5 was obtained from the same reaction mixture after 24 h. All the complexes as well as the ligands were characterized by various spectroscopic techniques (IR, UV-Vis, NMR) and ESI-MS. The structures of 1, 3 and 4 were solved by single crystal X-ray crystallography. The complexes 1−4 underwent changes in solution, and time dependent UV-Vis and EPR spectroscopy studies revealed that 1−4 formed a mixed valence molybdenum(V,VI) species [MoVMoVIO3L′′2] (6) in solution. Chapter 5: The synthesis of three new dioxidomolybdenum(VI) complexes [MoO2L1-3(X)] (1−3) {where X=EtOH / DMSO} of aroylhydrazone ligands (H2L1-3) containing azobenzene moiety have been reported. The ligands H2L1-3 have been synthesized from the condensation of 5-(Arylazo) salicylaldehyde derivatives with corresponding aroyl hydrazides. The azobenzene functionality was incorporated in the aroylhydrazone systems containing benzoyl, naphthyl and furyl moieties in order to explore their influence if any, on the DNA/BSA interactions of the corresponding molybdenum complexes. All the synthesized ligands and metal complexes were successfully characterized by elemental analysis, IR, UV–Vis and NMR spectroscopy. The redox properties of the complexes were studied by cyclic voltammetry. Molecular structures of all the complexes (1−3) have been determined by X‒ray crystallography. The complexes interact with calf-thymus DNA (CT-DNA) with binding constants ~104 M-1. The cytotoxicity of the complexes against A-549 cell line has also been explored. Chapter 6: The synthesis of four new dioxidomolybdenum(VI) complexes [MoO2L1-4(S)] (1−4) {where S=DMSO for 1, 2 and 4; DMF for 3}of Schiff base ligands (H2L1-4) containing substituted azobenzene derivatives have been reported. The ligands H2L1-4 have been synthesized from the condensation of substituted 5-(Arylazo) salicylaldehyde derivatives with 2-aminophenol. The substituted azobenzene functionalities were incorporated in order to explore their influence if any, on the biological activities of the corresponding molybdenum complexes. All the synthesized ligands and metal complexes were successfully characterized by elemental analysis, IR, UV–Vis and NMR spectroscopy. The redox properties of the complexes were studied by cyclic voltammetry. Molecular structures of all the complexes (1−4) have been determined by X‒ray crystallography. The complexes have also been tested for their antibacterial activity against Pseudomonas aeruginosa , Vibrio cholerae, Escherichia Coli and Bacillus. Chapter 7: Summary of the work embodied in the research work and the scope of further research study has been discusse

Chemistry of Monomeric and Dinuclear Non-Oxido Vanadium(IV) and Oxidovanadium(V) Aroylazine Complexes: Exploring Solution Behavior

A series of mononuclear non-oxido vanadium­(IV) [V^IV(L^1–4)₂] (<b>1</b>–<b>4</b>), oxidoethoxido vanadium­(V) [V^VO­(L^1–4)­(OEt)] (<b>5</b>–<b>8</b>), and dinuclear μ-oxidodioxidodivanadium­(V) [V^V₂O₃(L¹)₂] (<b>9</b>) 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 <b>2</b>, <b>3</b>, <b>5</b>, <b>6</b>, <b>8</b>, and <b>9</b>). The non-oxido V^IV complexes (<b>1</b>–<b>4</b>) 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 [V^VO­(L^1–4)­(OEt)] compounds (<b>5</b>–<b>8</b>) is studied confirming the formation of at least two different types of V^V species in solution, monomeric corresponding to <b>5</b>–<b>8</b>, and μ-oxidodioxidodivanadium [V^V₂O₃(L^1–4)₂] compounds. The μ-oxidodioxidodivanadium compound [V^V₂O₃(L¹)₂] (<b>9</b>), generated from the corresponding mononuclear complex [V^VO­(L¹)­(OEt)] (<b>5</b>), is characterized in solution and in the solid state. The single-crystal X-ray diffraction analyses of the non-oxido vanadium­(IV) compounds (<b>2</b> and <b>3</b>) show a N₂O₄ binding set and a trigonal prismatic geometry, and those of the V^VO complexes <b>5</b>, <b>6</b>, and <b>8</b> and the μ-oxidodioxidodivanadium­(V) (<b>9</b>) reveal that the metal center is in a distorted square pyramidal geometry with O₄N binding sets. For the μ-oxidodioxidodivanadium species in equilibrium with <b>5</b>–<b>8</b> in CH₂Cl₂, no mixed-valence complexes are detected by chronocoulometric and EPR studies. However, upon progressive transfer of two electrons, two distinct monomeric V^IVO species are detected and characterized by EPR spectroscopy and DFT calculations

Chemistry of Monomeric and Dinuclear Non-Oxido Vanadium(IV) and Oxidovanadium(V) Aroylazine Complexes: Exploring Solution Behavior

A series of mononuclear non-oxido vanadium­(IV) [V^IV(L^1–4)₂] (<b>1</b>–<b>4</b>), oxidoethoxido vanadium­(V) [V^VO­(L^1–4)­(OEt)] (<b>5</b>–<b>8</b>), and dinuclear μ-oxidodioxidodivanadium­(V) [V^V₂O₃(L¹)₂] (<b>9</b>) 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 <b>2</b>, <b>3</b>, <b>5</b>, <b>6</b>, <b>8</b>, and <b>9</b>). The non-oxido V^IV complexes (<b>1</b>–<b>4</b>) 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 [V^VO­(L^1–4)­(OEt)] compounds (<b>5</b>–<b>8</b>) is studied confirming the formation of at least two different types of V^V species in solution, monomeric corresponding to <b>5</b>–<b>8</b>, and μ-oxidodioxidodivanadium [V^V₂O₃(L^1–4)₂] compounds. The μ-oxidodioxidodivanadium compound [V^V₂O₃(L¹)₂] (<b>9</b>), generated from the corresponding mononuclear complex [V^VO­(L¹)­(OEt)] (<b>5</b>), is characterized in solution and in the solid state. The single-crystal X-ray diffraction analyses of the non-oxido vanadium­(IV) compounds (<b>2</b> and <b>3</b>) show a N₂O₄ binding set and a trigonal prismatic geometry, and those of the V^VO complexes <b>5</b>, <b>6</b>, and <b>8</b> and the μ-oxidodioxidodivanadium­(V) (<b>9</b>) reveal that the metal center is in a distorted square pyramidal geometry with O₄N binding sets. For the μ-oxidodioxidodivanadium species in equilibrium with <b>5</b>–<b>8</b> in CH₂Cl₂, no mixed-valence complexes are detected by chronocoulometric and EPR studies. However, upon progressive transfer of two electrons, two distinct monomeric V^IVO species are detected and characterized by EPR spectroscopy and DFT calculations

Anionic Dinuclear Oxidovanadium(IV) Complexes with Azo Functionalized Tridentate Ligands and μ‑Ethoxido Bridge Leading to an Unsymmetric Twisted Arrangement: Synthesis, X‑ray Structure, Magnetic Properties, and Cytotoxicity

The synthesis of ethoxido-bridged dinuclear oxidovanadium­(IV) complexes of the general formula (HNEt₃)­[(VOL^1–3)₂(μ-OEt)] (<b>1</b>–<b>3</b>) with the azo dyes 2-(2′-carboxy-5′-X-phenylazo)-4-methylphenol (H₂L¹, X = H; H₂L², X = NO₂) and 2-(2′-carboxy-5′-Br-phenylazo)-2-naphthol (H₂L³) as ligands is reported. The ligands differ in the substituents at the phenyl ring to probe their influence on the redox behavior, biological activity, and magnetochemistry of the complexes, for which the results are presented and discussed. All synthesized ligands and vanadium­(IV) complexes have been characterized by various physicochemical techniques, namely, elemental analysis, electrospray ionization mass spectrometry, spectroscopic methods (UV/vis and IR), and cyclic voltammetry. X-ray crystallography of <b>1</b> and <b>3</b> revealed the presence of a twisted arrangement of the edged-shared bridging core unit. In agreement with the distorted nature of the twisted core, antiferromagnetic exchange interactions were observed between the vanadium­(IV) centers of the dinuclear complexes with a superexchange mechanism operative. These results have been verified by DFT calculations. The complexes were also screened for their <i>in vitro</i> cytotoxicity against HeLa and HT-29 cancer cell lines. The results indicated that all the synthesized vanadium­(IV) complexes (<b>1</b>–<b>3</b>) were cytotoxic in nature and were specific to a particular cell type. Complex <b>1</b> was found to be the most potent against HeLa cells (IC₅₀ value 1.92 μM)