Surface modification minimizes the toxicity of silver nanoparticles: an in vitro and in vivo study.

Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system. Ag-NPs released excess Ag+ ions leads to activation of NADPH oxidase and helps in generating the reactive oxygen species (ROS). Silver nanoparticles elicit the production of excess amount of ROS results activation of TNF-α. Ag-NPs activates caspase-3 and 9 which are the signature of mitochondrial pathway. Ag-NPs are responsible to decrease the antioxidant enzymes and imbalance the oxidative status into the cells but functionalization with BSA and PEG helps to protect the adverse effect of Ag-NPs on the cells. This study suggested that Ag-NPs are toxic to normal cells which directly lead with human health. Surface functionalization may open the gateway for further use of Ag-NPs in different area such as antimicrobial and anticancer therapy, industrial use or in biomedical sciences.

Relation between the catalytic efficiency of the synthetic analogues of catechol oxidase with their electrochemical property in the free state and substrate-bound state.

A library of 15 dicopper complexes as synthetic analogues of catechol oxidase has been synthesized with the aim to determine the relationship between the electrochemical behavior of the dicopper(II) species in the absence as well as in the presence of 3,5-di-tert-butylcatechol (3,5-DTBC) as model substrate and the catalytic activity, kcat, in DMSO medium. The complexes have been characterized by routine physicochemical techniques as well as by X-ray single-crystal structure analysis in some cases. Fifteen "end-off" compartmental ligands have been designed as 1 + 2 Schiff-base condensation product of 2,6-diformyl-4-R-phenol (R = Me, (t)Bu, and Cl) and five different amines, N-(2-aminoethyl)piperazine, N-(2-aminoethyl)pyrrolidine, N-(2-aminoethyl)morpholine, N-(3-aminopropyl)morpholine, and N-(2-aminoethyl)piperidine. Interestingly, in case of the combination of 2,6-diformyl-4-methylphenol and N-(2-aminoethyl)morpholine/N-(3-aminopropyl)morpholine/N-(2-aminoethyl)piperidine 1 + 1 condensation becomes the reality and the ligands are denoted as L2(1-3). On reaction of copper(II) nitrate with L2(1-3) in situ complexes 3, 12, and 13 are formed having general formula Cu2(L2(1-3))2(NO3)2. The remaining 12 ligands obtained as 1 + 2 condensation products are denoted as L1(1-12), which produce complexes having general formula Cu2(L1(1-12))(NO3)2. Catecholase activity of all 15 complexes has been investigated in DMSO medium using 3,5-DTBC as model substrate. Treatment on the basis of Michaelis-Menten model has been applied for kinetic study, and thereby turnover number, kcat, values have been evaluated. Cyclic voltametric (CV) and differential pulse voltametric (DPV) studies of the complexes in the presence as well as in the absence of 3,5-DTBC have been thoroughly investigated in DMSO medium. From those studies it is evident that oxidation of 3,5-DTBC catalyzed by dicopper(II) complexes proceed via two steps: first, semibenzoquinone followed by benzoquinone with concomitant reduction of Cu(II) to Cu(I). Our study reveals that apparently there is nearly no linear relationship between kcat and E° values of the complexes. However, a detailed density functional theory (DFT) calculation sheds light on this subject. A very good correlation prevails in terms of the energetics associated with the Cu(II) to Cu(I) reduction process and kcat values, as revealed from the combined theoretical and experimental approach.

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.

Biodistribution and toxickinetic variances of chemical and green Copper oxide nanoparticles in vitro and in vivo.

In this study, chemical (S1) and green (S2) Copper Oxide nanoparticles (NPs) were synthesized to determine their biodistribution and toxicokinetic variances in vitro and in vivo. Both NPs significantly released Copper ions (Cu) in lymphocytes and were primarily deposited in the mononuclear phagocyte system (MPS) such as the liver and spleen in mice. In particular, S2NPs seemed to be prominently stored in the spleen, whereas the S1NPs were widely stored in more organs including the liver, heart, lungs, kidney and intestine. The circulation in the blood and fecal excretions both showed higher S2NPs contents respectively. Measurements of cell viability, Hemolysis assay, Reactive Oxygen Species (ROS) generation, biochemical estimation and apoptotic or necrotic study in lymphocytes after 24 h and measurements of body and organ weight, serum chemistry evaluation, cytokines level, protein expressions and histopathology of Balb/C mice after 15 days indicated significant toxicity difference between the S1NPs and S2NPs. Our observations proved that the NPs physiochemical properties influence toxicity and Biodistribution profiles in vitro and in vivo.

Unveiling the effects of the in situ generated arene anion radical and imine radical on catecholase like activity: a DFT supported experimental investigation.

Two new dinuclear nickel(ii) complexes namely [Ni2(L1)2(OAc)2(H2O)2]·CH3CN (1) and [Ni2(L2)2(SCN)2(CH3OH)2]·CH3OH (2) have been synthesized from the designed Schiff-base ligand 4-bromo-2-[(2-hydroxy-1,1-dimethyl-ethylimino)-methyl]-phenol (HL1) and its reduced analogue 4-bromo-2-[(2-hydroxy-1,1-dimethyl-ethylamino)-methyl]-phenol (HL2), respectively. Both 1 and 2 have been characterised by usual physicochemical techniques (UV-Vis, FT-IR, ESI-MS study and single crystal XRD) and their variable temperature magnetic study has been performed. The nickel(ii) centres in the dinuclear complexes 1 and 2 are antiferromagnetically coupled through participation of the bridging phenoxyl oxygen. In acetonitrile solution both 1 and 2 retain their dinuclear structural integrity as is evident from the ESI-MS study. The catecholase-like activity of 1 and 2 has been performed in acetonitrile medium using 3,5-di-tert-butylcatechol (3,5-DTBC) as a model substrate. Complex 1 shows a higher catalytic activity than that of complex 2. The ESI-MS study suggests that dinuclear species undergo cleaving into a mononuclear entity in the presence of 3,5-DTBC and that mononuclear species are supposed to act as active catalysts in the catalytic cycle. The EPR study of catalytic reactions confirms that organic radicals have been generated during catalysis in both cases. However, in the case of complex 1 catalyzed reaction a single isotropic signal at g = 1.97 is obtained which is most likely due to imine radical formation. On the other hand, for complex 2 catalyzed reaction the spectrum shows a signal with hyperfine splitting (g = 2.11, 2.05 and 1.9), thereby suggesting the generation of a new radical i.e. an arene anion radical in this study on catecholase activity. Extensive DFT calculations have been performed to support the experimental observation and thus to put forward the most probable mechanistic pathways operating in the two cases. The higher efficiency of the imine radical pathway over the arene anion radical has been rationalized by DFT calculations.

Thiocyanate mediated structural diversity in phenol based "end-off" compartmental ligand complexes of group 12 metal ions: Studies on their photophysical properties and phosphatase like activity.

The reaction of a pentadentate compartmental ligand LH, namely 4-tert-Butyl-2,6-bis-[(2-pyridin-2-yl-ethylimino)-methyl]-phenol, with group 12 metal ions (ZnII, CdII, HgII) followed by addition of NaSCN afforded one discrete dinuclear complex [Zn2(L)(SCN)3](1), and two polymeric 1D species [Cd2.5(L)(SCN)3(AcO)]n (2) and [Hg2(L)(SCN)3]n (3). All the complexes have been structurally characterized by single crystal X-ray diffraction. The crystal structure of the complexes reveals different coordination modes of thiocyanate anion that affect the different topology detected in the compounds: the anions are µ1-NCS and µ1,1-NCS connected in complex 1, while µ1,3-NCS bridging mode is observed in 2, and µ1-SCN and µ1,3-NCS in 3. The polymeric Hg complex of the bicompartmental ligand system here reported is unprecedented. Detail study of their photophysical properties including the phosphorescence spectra at 77K has been done. Phosphatase like activity of all the three complexes has been performed in DMSO-H2O medium and their activity follows the order of 1>2>>3.

Unique mononuclear Mn(II) complexes of an end-off compartmental Schiff base ligand: experimental and theoretical studies on their bio-relevant catalytic promiscuity.

Three new mononuclear manganese(ii) complexes, namely [Mn(HL)2]·2ClO4 (1), [Mn(HL)(N(CN)2)(H2O)2]·ClO4 (2) and [Mn(HL)(SCN)2] (3) [LH = 4-tert-butyl-2,6-bis-[(2-pyridin-2-yl-ethylimino)-methyl]-phenol], have been synthesized and structurally characterized. An "end-off" compartmental ligand (LH) possesses two symmetrical compartments with N2O binding sites but accommodates only one manganese atom instead of two due to the protonation of the imine nitrogen of one compartment. Although all three complexes are mononuclear, complex 1 is unique as it has a 1 : 2 metal to ligand stoichiometry. The catalytic promiscuity of complexes 1-3 in terms of two different bio-relevant catalytic activities namely catecholase and phenoxazinone synthase has been thoroughly investigated. EPR and cyclic voltametric studies reveal that radical formation rather than metal centered redox participation is responsible for their catecholase-like and phenoxazinone synthase-like catalytic activity. A computational approach suggests that imine bond bound radical generation rather than phenoxo radical formation is most likely responsible for the oxidizing properties of the complexes.

Influence of para substituents in controlling photophysical behavior and different non-covalent weak interactions in zinc complexes of a phenol based "end-off" compartmental ligand.

Three dinuclear zinc(II) complexes with "end-off" compartmental ligands, namely 2,6-bis(N-ethylmorpholine-iminomethyl)-4-R-phenol (R = -CH3, Cl, (t)Bu) have been synthesized with the aim of exploring the role of the para substituent present in the ligand backbone in controlling the structural diversity, photophysical properties and different weak interactions of the complexes. All three species, with the general formula {2[Zn2L(CH3COO)2][Zn(NCS)4]}, show the complex anion Zn(NCS)4(2-) as a common structural feature decisive for crystallization. Interestingly, all of them possess several non-covalent weak interactions where the nature of the "R" group plays an essential role as exposed by DFT study. Besides exhibiting fluorescence behavior, the complexes also show para substitution controlled phosphorescence both at room and low temperature. Anisotropy studies suggest the existence of complexes 2 and 3 as dimers in solution. The origins of the unusual room temperature phosphorescence and fluorescence behavior of the complexes have been rationalized in the light of theoretical calculations.

A radical pathway in catecholase activity with nickel(II) complexes of phenol based "end-off" compartmental ligands.

Seven dinuclear and one dinuclear based dicyanamide bridged polymeric Ni(II) complexes of phenol based compartmental ligands (HL(1)-HL(4)) have been synthesized with the aim to investigate their catecholase-like 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(L(2))(SCN)3(H2O)(CH3OH)] (), [Ni2(L(4))(SCN)3(CH3OH)2] (), [Ni2(L(2))(SCN)2(AcO)(H2O)] (), [Ni2(L(4))(SCN)(AcO)2] (), [Ni2(L(2))(N3)3(H2O)2] (), [Ni2(L(4))(N3)3(H2O)2] (), [Ni2(L(1))(AcO)2(N(CN)2)]n () and [Ni2(L(3))(AcO)2(N(CN)2)] (), [SCN = isothiocyanate, AcO = acetate, N3 = azide, and N(CN)2 = dicyanamide anion; L(1-4) = 2,6-bis(R2-iminomethyl)-4-R1-phenolato, where R1 = methyl and tert-butyl, R2 = N,N-dimethyl ethylene for L(1-2) and R1 = methyl and tert-butyl, R2 = 2-(N-ethyl) pyridine for L(3-4)]. 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 Ni(II) to Ni(I) and that of the imine bond of the ligand system have been detected at ∼-1.0 V and ∼-1.5 V, respectively. Coulometric separation of the species at -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 -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.