Comparative analysis of Zn(II)-complexes as model metalloenzymes for mimicking Jack bean urease.

The inhibitory action of Schiff base complexes of 3d metals against the urease enzyme is well explored in the scientific community. However, the ability of such complexes in mimicking active metallobiosites of urease enzymes, possessing ureolytic behavior, still remains unexplored. With this aim firstly, two Zn(II)-complexes (PPR-HMB-Zn and PZ-HMB-Zn) have been developed from two different Schiff base ligands (HL1 = 2-((E)-(2-(piperidin-1-yl)ethylimino)methyl)-5-methylphenol and HL2 = 2-((E)-(2-(piperizin-1-yl)ethylimino)methyl)-5-methylphenol) and structurally characterized using single crystal XRD. The hydrolytic enzymatic activity of both complexes was demonstrated by the gradual increase in the absorption maxima at 425 nm for the formation of the p-nitrophenolate ion from catalytic hydrolysis mediated by the Zn(II) complexes with a disodium salt of p-nitrophenyl phosphate as a model substrate. Associated kinetic parameters, pH dependency and a relevant hydrolysis mechanism have also been explored. After confirming the hydrolytic ability, the complexes were exploited to mimic the hydrolytic activity of Jack bean urease that catalytically hydrolyses urea into ammonia and CO2. The change in the pH of the solution owing to the formation of ammonia under the complex catalysed hydrolytic action of urea has been monitored spectrophotometrically using the pH dependent structural change of phenol red. The amount of ammonia has been quantified using the Nessler's reagent spectrophotometric method. The ureolytic reaction mechanism has been investigated using density functional theory (DFT) calculations using the B3LYP and TPSSH methods for the systematic calculation of the interaction energy. In contrast to PZ-HMB-Zn, PPR-HMB-Zn functions more effectively as a catalyst due to the existence of a lattice-occluded water molecule in its crystal structure and the protonation of the non-terminal N to attract urea by H-bonding, which was further confirmed by AIM analysis.

Biochemical Resistivity against Free Radicals and Microbes: Cooperative Action of Zn(II)/Imidazole in Phosphoesterase-Mediated Cell Death.

This work delivers a targeted synthesis of four isostructural O-substituted imidazole-based zinc(II) complexes, namely, [Zn2(L1)2(I)2](DMF) (1), [Zn2(L2)2(I)2](DMF) (2), [Zn2(L1)2(Br)2] (3), and [Zn2(L2)2(Br)2] (4), derived from homologous Schiff-base ligands HL1 and HL2 to explore their impact on free radicals, microbes, and dephosphorylation of phosphoesters. The antioxidant activity of all complexes was checked by various radical scavenging assays (ABTS+•, DPPH•, and H2O2 radical quenching). Among them, complex 2 showed superior radical quenching activity, as indicated by its lowest EC50 value and thus maximum antioxidative capability. Again, antibacterial assays against several Gram-positive and Gram-negative bacteria were conducted to evaluate the zone of inhibition. The minimum bactericidal concentration and minimum inhibitory concentration values from the microdilution method for all complexes revealed complex 3 to have maximum potency against Gram-positive bacteria. The P-O bond hydrolysis in the phospholipid chain caused by the hydrolytic phosphoesterase activity of the Zn(II)-complexes plays a crucial role in cell membrane rupture. A model substrate 4-PNPP was used to explain the potency of monomeric Zn(II) complex (3) for cell penetration over dimeric one (2) with a proper mechanism. Furthermore, a heme model substrate, Fe(TPP)Cl, has been introduced with the most potent complex 3 and has spectrophotometric evidence for covalent interaction with imidazole and Fe(III) that can disrupt the nitric oxide dioxygenase function of flavohemoglobin, leading to bacterial cell death. To our knowledge, this is the first case to report a novel mechanism of antimicrobial action where both the metal and the ligand are cooperatively involved in bacterial cell death. The main goal of this work is to invent multifunctional therapeutics as well as the proper chemical rationalization of biological processes using mechanistic approaches, which includes investigating the roles of halides, imidazoles, and solution-phase structural variations of complexes..

ZnAl2O4 Nanomaterial as a Naked-Eye Arsenate Sensor: A Combined Experimental and Computational Mechanistic Approach.

Raising public awareness over the emerging health risk due to intake of arsenic-contaminated potable water is a matter of great concern. Exploration of cost-effective, self-testing kits is a substantial way to reach out to the masses and detect the presence of arsenate in water. With this agenda, a photoluminescent Mannich base Zn(II) complex (ZnMC = [Zn2(ML)2]·(ClO4)2·(H2O); HML = Mannich base ligand) has been synthesized, and its dinuclearity was verified with single-crystal X-ray diffraction structural analysis. Among a range of anions, ZnMC was found to detect arsenate selectively by showing a turn-off emission with a color change from bright green to dark under UV light. The real-life applicability of the ZnMC probe is somewhat restricted to only sensing of arsenate, but not its removal owing to the fact of its homogeneity. Considering the efficacy of ZnMC as well as a need for its easy removal from water, slight modification has been done with chloride ions in the form of ZnMC″ (=[Zn2(ML)2(Cl)2]), and finally, an interface between homogeneous and heterogeneous solid support has been explored with a strategic fabrication of ZnMC″ grafted ZnAl2O4, named as ZAZ nanomaterial. This not only imparts successful segregation of arsenate from drinking water but also provides naked-eye detection under ambient light as well as UV light. Thermodynamic parameters associated with the binding of arsenate to ZnMC and ZAZ have been evaluated through isothermal calorimetric (ITC) measurements. Steady-state and time-resolved fluorescence titration study, absorption titration study, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and computational calculations have been performed to get deep insights into the sensing properties. Proper justification of the sensing mechanism is the highlight of this work. ZAZ nanomaterial has been exploited to produce a self-test paper kit for arsenate detection with a limit of 9.86 ppb, which potentially enables applications in environmental monitoring.

Effect of O-substitution in imidazole based Zn(II) dual fluorescent probes in the light of arsenate detection in potable water: a combined experimental and theoretical approach.

Efficient detection of arsenate (AsO43-) from contaminated drinking water extracted from underground has become a matter of utmost necessity and an exquisite challenge owing to the growing public health issue due to arsenicosis. In order to combat this we planned to detect arsenate with the naked eye under UV light using a novel chemosensor material whose structure and functioning as a sensor could be certified mechanistically. Hence we were encouraged to synthesize two differently O-substituted imidazole based homologous ligands: C1 (HL1 = 2-((E)-(3-(1H-imidazole-1-yl)propylimino)methyl)-6-ethoxyphenol) and C2 (HL2 = 2-((E)-(3-(1H-imidazole-1-yl)propylimino)methyl)-6-methoxyphenol). To accomplish the purposeful exploration of the luminescent sensor, we considered Chelation Enhanced Fluorescence (CHEF) and kept on searching for a metal cation that would be able to turn on the fluorescence of the ligands. Considering Zn(II) as the most suitable candidate, luminescent complexes D1 and D2 ({[Zn2(L1)2(I)2](DMF)} and [Zn2(L2)2(I)2](DMF), respectively) were synthesized and characterized by SXRD, UV-Vis, FT-IR, and photoluminescence spectroscopy. In spite of the resemblance in the solid state structures of D1 and D2, the selective response of D1 towards arsenate with high quenching constants (2.13 × 106), unlike D2, has been demonstrated mechanistically with steady state and time resolved fluorescence titration, solution phase ESI-MS spectral analysis and DFT studies. The selectivity and sensitivity of the sensor D1 explicitly make this material a potent candidate for arsenate detection due to its very low detection limit (8.2 ppb), low cost and user friendly characteristics. Real life implementation of this work in a test strip is expected to prove beneficial for public health to identify arsenate polluted water.

Iron Complexes Anchored onto Magnetically Separable Graphene Oxide Sheets: An Excellent Catalyst for the Synthesis of Dihydroquinazoline-Based Compounds.

In this work, a green, sustainable, and efficient protocol for the syntheses of dihydroquinazoline derivatives is proposed. Initially, three Schiff base complexes of iron containing the ligand (2,2-dimethylpropane-1,3-diyl)bis(azanylylidene)bis(methanylylidene)bis(2,4-Xphenol), where X = Cl (complex 1)/Br (complex 2)/I (complex 3), were synthesized, fully characterized, and used in the desired syntheses. Complex 1 excelled as a catalyst, closely followed by complexes 2 and 3. DFT calculations helped in rationalizing the role of the halide substituent in the ligand backbone as a relevant factor in the catalytic superiority of complex 1 over complexes 2 and 3 for the synthesis of the dihydroquinazoline derivatives. Finally, to facilitate catalyst recoverability and reusability, complex 1 was immobilized on GO@Fe3O4@APTES (GO, graphene oxide; APTES, 3-aminopropyltriethoxysilane) to generate GO@Fe3O4@APTES@FeL1 (GOTESFe). GOTESFe was thoroughly characterized through scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy and efficiently used for the synthesis of dihydroquinazoline derivatives. GOTESFe could be magnetically recovered and reused up to five cycles without compromising its catalytic efficiency. Therefore, immobilization of the chosen iron complex onto magnetic GO sheets offers an extremely competent route in providing a blueprint of a readily recoverable, reusable, robust, and potent catalyst for the synthesis of dihydroquinazoline-based compounds.

Executing a Series of Zinc(II) Complexes of Homologous Schiff Base Ligands for a Comparative Analysis on Hydrolytic, Antioxidant, and Antibacterial Activities.

Six zinc(II) complexes, namely, [Zn(HL1H)Cl2] (1), [Zn(HL1H)Br2] (2), [Zn2(HL1H)2(OH)I2]·I (3), [Zn(HL2)Cl] (4), [Zn2(HL2)Br3] (5), and [Zn(HL2)I] (6) have been manufactured by using two homologous Schiff base ligands H2L1 and H2L2 for the purpose of perlustrating their phosphatase-like activity, antioxidant activity, and antibacterial activity. Complexes 1, 2, 4, and 5 have been reported earlier by us, whereas complexes 3 and 6 have been synthesized and structurally characterized by regular physicochemical methods The hydrolytic property of the six complexes has been evaluated by checking the hydrolysis of the P-O bond of a widely used substrate, namely, disodium salt of (para-nitrophenyl)phosphate (PNPP) in 97.5% (v/v) mixture of N,N-dimethylformamide and water (DMF-water). Complexes 2-5 have profound efficiency toward hydrolysis of phosphate ester bonds, and complexes 1 and 6 were noted to be inactive toward hydrolysis. Complex 3 displayed the highest efficacy among the six complexes. Additionally, antioxidant and antibacterial activities of the complexes were studied thoroughly. A detailed study of their antioxidant property revealed that complex 3 manifested superior radical scavenging activity, thus exhibiting the highest antioxidant property. The antibacterial activity was tested using four investigating bacteria, specifically Listeria monocytogenes ATCC19111, Staphylococcus aureus ATCC 700699, Salmonella typhimurium ATCC 23564, and Escherichia coli ATCC 25922 by determining minimum inhibitory concentration (MIC) values using the microdilution method. Here as well, complex 3 exhibited the highest activity to both Gram positive and Gram negative bacteria. The chemistry behind these experimental findings has been manifested by shedding light upon the structural features of the complexes. The suitable choice of ligand H2L1 where one methylene group is less than its homologous ligand and metal precursor (ZnI2) imparts a unique hydroxo-bridged molecular geometry and 2D hydrogen bonding network which in turn probably enhances the hydrolytic and biological activities of complex 3.

Association between oral nutritional supplementation and clinical outcomes among patients with ESRD.

BACKGROUND AND OBJECTIVES: Oral nutritional supplementation (ONS) was provided to ESRD patients with hypoalbuminemia as part of Fresenius Medical Care Health Plan's (FMCHP) disease management. This study evaluated the association between FMCHP's ONS program and clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Analyses included FMCHP patients with ONS indication (n=470) defined as 2-month mean albumin <3.8 g/dl until reaching a 3-month mean ≥3.8 g/dl from February 1, 2006 to December 31, 2008. Patients did not receive ONS if deemed inappropriate or refused. Patients on ONS were compared with patients who were not, despite meeting ONS indication. Patients with ONS indication regardless of use were compared with Medicare patients with similar serum albumin levels from the 2007 Centers for Medicare and Medicaid Services Clinical Performance Measures Project (CPM). Cox models calculated adjusted hospitalization and mortality risks at 1 year. RESULTS: Among patients with indication for ONS, 276 received supplements and 194 did not. ONS use was associated with 0.058 g/dl higher serum albumin overall (P=0.02); this difference decreased by 0.001 g/dl each month (P=0.05) such that the difference was 0.052 g/dl (P=0.04) in month 6 and the difference was no longer significant in month 12 . In analyses based on ONS use, ONS patients had lower hospitalization at 1 year (68.4%; P<0.01) versus patients without ONS (88.7%), but there was no significant reduction in mortality risk (P=0.29). In analyses based on ONS indication, patients with indication had lower mortality at 1 year (16.2%) compared with CPM patients (23.4%; P<0.01). CONCLUSIONS: These findings suggest that ONS use was associated with significantly lower hospitalization rates but had no significant effect on mortality in a disease management setting.