Six zinc(II) complexes have been synthesized from two designed Mannich-base ligands which consist of three dinuclear complex [Zn2(L1)2X2] (1-3) and three mononuclear complex [ZnH(L2)X2] (4-6), respectively, where X = Cl- (1,4), Br- (2,5), I- (3,6), as reported earlier by us (Sanyal et al., Inorg Chem 53:85-96, 2014). The catecholase activity of the complexes has been investigated under completely aerobic conditions in DMF-water medium (9:1) at pH 8.5 against the model substrate 3,5-di-tert-butylcatechol (3,5-DTBC). Saturation kinetic studies show that the order of conversion of substrate to product (quinone) follows the trend 5 &gt; 4 &gt; 2 &gt; 1 while 3 and 6 are inactive. The generation of phenoxyl radicals, confirmed by UV-vis and EPR spectral studies, is supposed to be responsible for the oxidation of 3,5-DTBC. The in vitro evaluation of 1-6 comprises the study of their DNA-cleaving ability using plasmid DNA and the assessment of their cytotoxic activity against Jurkat (T cell lymphoma) cell line by MTT assay. The mechanisms of toxicity appeared to be predominantly by reactive oxygen species (ROS). The comparative analysis helps to arrive at the following facts under experimental conditions: (1) mononuclear species prevail over the dinuclear ones, unlike the behavior in phosphatase activity as reported in Inorganic Chemistry; (2) the halide substituents at the active site control the overall activity in the order: (a) In catecholase activity, Cl- &lt; Br- (dinuclear) and Cl- &gt; Br- (mononuclear) and (b) in biological activity, Cl- &gt; Br- &gt; I- regardless of nuclearity. Graphical Abstract: [Figure not available: see fulltext.] © 2014 SBIC.

Debasis Das

Chemistry

R SANYAL

S K DASH

S DAS

S CHATTOPADHYAY

S ROY

D DAS

University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

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The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

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It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

Journal of Biological Inorganic Chemistry

A mononuclear tetrahedral Zn(II) complex [Zn(L)2](1)[HL = 2-(benzylimino)methyl)phenol] with phenol based bi-dentate N,O donor ligand have been prepared. The compound is characterized by various spectroscopic tools and the structure of the complex is solved by single crystal X-ray diffractometer. The tetrahedral Zn(II) complex crystallized in monoclinic space group I2/awith a = 12.2908(3) (Å), b = 9.1041(2) (Å), c = 19.9812(7) and β = 96.1466(10)°.Cyclic voltametric study of the complex 1 gives an irreversible oxidation peak due to ligand based oxidation of the phenol moiety to the phenoxyl radical. This compound also shows a strong emission band at 455 nm. The reported Zn(II) complex exhibits catecholase activity in methanol solvent under aerobic condition.The Kcatvalue for 1 in methanol is 8.411 × 103 h−1. The conversion of 3,5-di-tert-butyl catechol (3,5 DTBC) to 3,5-di-tert-butyl quinone (3,5 DTBQ) is catalysed by mono nuclear Zn(II) complex and the reaction proceeds through the generation of ligand centered phenoxyl radical. © 2020 Elsevier B.V.

Journal of Molecular Structure

Synthesis, structure, luminescent properties and catecholase activity of Zn(II) complex with N, O chelating agent

The aim of the present study was to develop zinc sulfide nanoparticles (ZnS NPs) and to study their cytotoxicity against the KG-1A (human acute myeloid leukemia) cell line. ZnS NPs were synthesized using the pyrolytic method and characterized by X-ray diffraction, dynamic light scattering, surface zeta potential, scanning electron microscopy and atomic force microscopy. Cell viability study and flow cytometric analysis confirmed the potent cytotoxic effects of ZnS NPs on cancer cells in a dose-dependent fashion. Successful uptakes of ZnS NPs by leukemic cells were confirmed by phase contrast fluorescence microscopy. pH-dependent dissolution of ZnS NPs was done using atomic absorption microscopy to understand the cell-specific internalization of Zn + . This internalization of NPs facilitated the generation of excess reactive oxygen species (ROS), followed by tumor necrosis factor alpha (TNF-α) secretion which caused severe DNA damage as observed in the comet assay and altered the mitochondrial membrane potential (MMP) in leukemic cells. Surprisingly ZnS NPs had no toxic effects on normal lymphocytes at doses up to 50 μg ml -1 . Pre-treatment with ROS and TNF-α inhibitor confirmed that these nanoparticles were able to kill leukemic cells by generating an excess amount of ROS and thereby initiated TNF-α mediated apoptosis pathway. These findings clarify the mechanism with which ZnS NPs induced anticancer activities in vitro. To elicit its utilities and its application to cancer treatment in vivo is under investigation. © 2014 John Wiley & Sons, Ltd.

Journal of Applied Toxicology

Zinc sulfide nanoparticles selectively induce cytotoxic and genotoxic effects on leukemic cells: Involvement of reactive oxygen species and tumor necrosis factor alpha

A mononucleating (HL1) and a dinucleating (HL2) "end-off" compartmental ligand have been designed and synthesized by controlled Mannich reaction using p-cresol and bis(2-methoxyethyl)amine, and their formation has been rationalized. Six complexes have been prepared on treating HL1 and HL2 with ZnIIX2 (X = Cl-, Br-, I-) with the aim to investigate their hydrolytic activity on phosphoester bond cleavage. Interestingly, the mononucleating ligand was observed to yield dinuclear complexes, [Zn 2(L1)2X2] (1-3), while the potential dinucleating ligand generated mononuclear complexes, [Zn(HL2)X 2] (4-6). Four (1-4), out of six complexes studied, were characterized by single-crystal X-ray diffraction (XRD): the Zn ion exhibits trigonal bipyramidal and tetrahedral coordination spheres in the di- and mononuclear complex, respectively. The hydrolytic kinetics, followed spectrophotometrically with 4-nitrophenylphosphate (4-NPP) in buffered dimethylformamide (DMF) (97.5% DMF, v/v) because of solubility reasons, under excess substrate conditions (substrate:complex = 20:1), indicated that the complexes enormously accelerate the rate of phosphomonoester hydrolysis with first order rate constants (kcat) in the range 2-10 s-1 at 25 °C. In each case kinetic data analyses have been run by Michaelis-Menten treatment. The efficacy in the order of conversion of substrate to product (p-nitrophenolate ion) follows the trend 1 &gt; 2 &gt; 3 &gt; 4 &gt; 5 &gt; 6, and the ratio of kcat of an analogous dinuclear to mononuclear complex is ≃2. An electrospray ionization-mass spectrometry (ESI-MS) study has revealed the dissociation of the centrosymmetric dinuclear complex to two mononuclear species instead of a syn-cooperative catalysis. Density functional theory (DFT) calculations have been performed to rationalize our proposed mechanistic pathway for phosphatase activity. The comparative analysis concludes the following facts under experimental conditions: (1) the halide bound to the active site affects the overall rate in the order: Cl- &gt; Br - &gt; I- regardless of nuclearity; (2) dinuclear complexes prevail over the mononuclear ones. © 2013 American Chemical Society.

Inorganic Chemistry

Influence of the coordination environment of zinc(II) complexes of designed mannich ligands on phosphatase activity: A combined experimental and theoretical study

Seven dinuclear and one dinuclear based dicyanamide bridged polymeric NiII complexes of phenol based compartmental ligands (HL1 &ndash;HL4 ) have been synthesized with the aim to investigate their catecholaselike activity and to evaluate the most probable mechanistic pathway involved in this process. The complexes have been characterized by routine physicochemical studies as well as by X-ray single crystal structure analyses namely [Ni2(L2 )(SCN)3(H2O)(CH3OH)] (1), [Ni2(L4 )(SCN)3(CH3OH)2] (2), [Ni2(L2 )(SCN)2(AcO)- (H2O)] (3), [Ni2(L4 )(SCN)(AcO)2] (4), [Ni2(L2 )(N3)3(H2O)2] (5), [Ni2(L4 )(N3)3(H2O)2] (6), [Ni2(L1 )(AcO)2- (N(CN)2)]n (7) and [Ni2(L3 )(AcO)2(N(CN)2)] (8), [SCN = isothiocyanate, AcO = acetate, N3 = azide, and N(CN)2 = dicyanamide anion; L1&ndash;4 = 2,6-bis(R2-iminomethyl)-4-R1-phenolato, where R1 = methyl and tert-butyl, R2 = N,N-dimethyl ethylene for L1&ndash;2 and R1 = methyl and tert-butyl, R2 = 2-(N-ethyl) pyridine for L3&ndash;4 ]. A UV-vis spectrophotometric study using 3,5-di-tert butylcatechol (3,5-DTBC) reveals that all the complexes are highly active in catalyzing the aerobic oxidation of (3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ) in methanol medium with the formation of hydrogen peroxide. An EPR study confirms the generation of radicals during the catalysis. Cyclic voltammetric studies of the complexes in the presence and absence of 3,5-DTBC have been performed. Reduction of NiII to NiI and that of the imine bond of the ligand system have been detected at &sim;&minus;1.0 V and &sim;&minus;1.5 V, respectively. Coulometric separation of the species at &minus;1.5 V followed by the EPR study at 77 K confirms the species as an organic radical and thus most probably reduced imine species. Spectroelectrochemical analysis at &minus;1.5 V clearly indicates the oxidation of 3,5-DTBC and thus suggests that the radical pathway is supposed to be responsible for the catecholase-like activity exhibited by the nickel complexes. The ligand centred radical generation has further been verified by density functional theory calculation

Dalton Trans.

A radical pathway in catecholase activity with nickel(ii) complexes of phenol based “end-off” compartmental ligands

ABSTRACT: Three new mononuclear nickel(II) complexes, namely, [NiL1 (H2O)3]I2·H2O (1), [NiL1 (H2O)3]Br2·H2O (2), and [NiL1 (H2O)3]Cl2·2H2O (3) [HL1 = 2-[(2-piperazin-1- ylethylimino)methyl]phenol], have been synthesized and structurally characterized. Structural characterization reveals that they possess similar structure: [NiL1 (H2O)3] 2+ complex cations, two halide counteranions, and lattice water molecules. One of the nitrogen atoms of the piperazine moiety is protonated to provide electrical neutrality to the system, a consequence observed in earlier studies (Inorg. Chem. 2010, 49, 3121; Polyhedron 2013, 52, 669). Catecholase-like activity has been investigated in methanol by a UV−vis spectrophoto- metric study using 3,5-di-tert-butylcatechol (3,5-DTBC) as the model substrate. Complexes 1 and 2 are highly active, but surprisingly 3 is totally inactive. The coordination chemistries of 1 and 2 remain unchanged in solution, whereas 3 behaves as a 1:1 electrolyte, as is evident from the conductivity study. Because of coordination of the chloride ligand to the metal in solution, it is proposed that 3,5-DTBC is not able to effectively approach an electrically neutral metal, and consequently complex 3 in solution does not show catecholase-like activity. Density functional theory (DFT) calculations corroborate well with the experimental observations and thus, in turn, support the proposed hypothesis of inactivity of 3. The cyclic voltametric study as well as DFT calculations suggests the possibility of a ligand-centered reduction at −1.1 V vs Ag/AgCl electrode. An electron paramagnetic resonance (EPR) experiment unambiguously hints at the generation of a radical from EPR-inactive 1 and 2 in the presence of 3,5-DTBC. Generation of H2O2 during catalysis has also been confirmed. DFT calculations support the ligand- centered radical generation, and thus a radical mechanism has been proposed for the catecholase-like activity exhibited by 1 and 2. Upon heating, 2 and 3 lose water molecules in two steps (first lattice waters, followed by coordinating water molecules), whereas 3 loses four water molecules in a single step, as revealed from thermogravimetric analysis. The totally dehydrated species are red, in all cases having square-planar geometry, and have amorphous nature, as is evident from a variable-temperature powder X-ray diffraction study.

A Combined Experimental and Theoretical Investigation on the Role of Halide Ligands on the Catecholase-like Activity of Mononuclear Nickel(II) Complexes with a Phenol-Based Tridentate Ligand

Radical Pathway in Catecholase Activity with Zinc-Based Model Complexes of Compartmental Ligands

Catecholase activity, DNA cleavage and cytotoxicity of six Zn(II) complexes synthesized from designed Mannich ligands: Higher reactivity of mononuclear over dinuclear

Journal	Data powered by TypesetJournal of Biological Inorganic Chemistry
Publisher	Data powered by TypesetSpringer Verlag
ISSN	0949-8257