Sudhanshu Das

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

Three new mononuclear nickel(II) complexes, namely, [NiL(1)(H2O)3]I2·H2O (1), [NiL(1)(H2O)3]Br2·H2O (2), and [NiL(1)(H2O)3]Cl2·2H2O (3) [HL(1) = 2-[(2-piperazin-1-ylethylimino)methyl]phenol], have been synthesized and structurally characterized. Structural characterization reveals that they possess similar structure: [NiL(1)(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 spectrophotometric 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.

Solvent dependent ligand transformation in a dinuclear copper(II) complex of a compartmental Mannich-base ligand: synthesis, characterization, bio-relevant catalytic promiscuity and magnetic study

An “end-off” pentadentate compartmental ligand HL has been synthesized by Mannich base condensation using p-cresol and 2-benzyl amino ethanol and structurally characterized. A dinuclear copper(II) complex, namely [Cu2(L)(μ-OH)(H2O)(ClO4)2], has been prepared by treating HL with Cu(ClO4)2·6H2O in methanolic solution with the aim of investigating its catalytic promiscuity. Single crystal structural analysis reveals that the Cu–Cu separation is 2.9 A. Catecholase activity of the complex has been investigated in anhydrous DMSO as well as in a DMSO–water mixture with progressively increasing the quantity of water up to a 1 : 1 volume ratio in order to assess the bio compatibility of the catalyst using 3,5-DTBC as a model substrate. In anhydrous DMSO the catalytic activity reaches its peak and decreases with increasing water concentration, a feature most likely due to insolubility of 3,5-DTBQ, the product formed in the catalysis, in water. The complex also shows excellent phosphatase-like activity by exploiting the Lewis acidity, the necessary requirement for that activity, under different pH. Thorough investigation reveals that no activity is observed at pH 6 but the activity increases with increasing pH and attains a maximum at pH 9. A variable temperature magnetic study shows that the two Cu centers are antiferromagnetically coupled at low temperature with a J value of −78.63 ± 1.30 cm−1. In acetonitrile medium the complex shows very exciting behavior. A new transformed ligand is generated that has been assigned as a Schiff-base ligand, 2,6-bis-[(2-hydroxy-ethylimino)-methyl]-4-methylphenol. The genesis of the new ligand is a consequence of dealkylation from HL followed by oxidation. This oxidation is counterbalanced by reduction of Cu(II) to Cu(I) as is evidenced from isolation of [Cu(MeCN)4](ClO4) from the mixture followed by X-ray structural characterization of the species.

Dinuclear zinc(II) complexes with compartmental ligands: syntheses, structures, and bioactivities as artificial nuclease

Four water-soluble dinuclear Zn(II) complexes (1–4) of compartmental ligand L = 2,6-bis(R-iminomethyl)-4-R′-phenolate (where R = N-ethylpiperidine or R = N-ethylpyrrolidine, R′ = methyl or tert-butyl) have been synthesized, characterized, and their DNA cleavage activity and cytotoxicity toward HepG2 cancerous cells are evaluated. The dinuclear complexes are formed by a pentadentate-substituted phenolate ligand chelating the metal ions separated by ca 3.27 Å. Each metal is a distorted trigonal bipyramid, completing the coordination sphere through acetate. The X-ray structural determination of 2 shows that the complex is counterbalanced by half (formulation [Zn2L2(CH3CO2)2][(Zn(SCN)4]0.5), while in 1 and 3 two crystallographically-independent complexes are present in the unit cell with a . Among the four complexes only the 4-tert-butyl-phenolato derivatives (3 and 4) show DNA cleavage activity in in-vivo conditions and appear to be promising toward metal complexes to be used as anticancer agents. The cytotoxicity of the complexes, investigated through MTT assay, suggests that 4 is a better choice as artificial nuclease.

Macrocyclization of N,N′-propylenebis(3-formyl-5-tert-butylsalicylaldimine): a ratiometric fluorescence chemodosimeter for ZnII

Addition of 1,3-propane diamine to 2,6-diformyl-4-tert-butyl phenol in ethanol produces a site-selective imination product N,N′-propylenebis(3-formyl-5-tert-butylsalicylaldimine), an acyclic side-off compartmental ligand (H2L). In the presence of zinc nitrate the ligand goes on hydrolysis in 50 : 50 water–acetonitrile medium and forms a partially hydrolyzed ligand (H2L′) which slowly metallates to generate a macrocyclic dinuclear zinc(II) complex (1), as characterized by single crystal X-ray analyses. The formation of H2L′ is believed to occur through the cleavage of an imine bond of the acyclic compartmental ligand (H2L) in the presence of zinc nitrate which acts as a Lewis acid. The formation of H2L′ has been monitored by means of 1H NMR and further confirmed by HRMS spectroscopic studies. The interactions of H2L with nickel(II) and copper(II) nitrate produce dinuclear complexes 2 and 3 (reported in Inorg. Chem. Commun. 2012, 15, 266–268) respectively, which are formed with unchanged ligand. Various spectroscopic techniques have been used to further characterize the complexes. H2L hardly exhibits yellowish green fluorescence emission at 523 nm when excited at 437 nm in 1 : 1 water–acetonitrile. Upon addition of Zn2+, a new fluorescence emission band at 481 nm appears, the intensity of which slowly enhances. Thus, the ligand H2L is a ratiometric fluorescence chemodosimeter for the selective detection of Zn2+ ions. On addition of CaII, MgII, NaI and KI in the same concentrations as that of Zn2+, the emission band at 523 nm is slightly enhanced, whereas the addition of paramagnetic metal cations like CuII, FeII, NiII, CoII, and MnII resulted in quenching of fluorescence. The quenching effect is also observed in the presence of CdII, a d10 metal cation exhibiting similar coordination properties to ZnII. The ZnII ion selectivity has also been studied in the presence of other biologically relevant metal ions in 50 : 50 water–acetonitrile.