Glutathione Depleting a Chemoselective Novel Pro-oxidant Nano Metal-Organic Framework Induced G2/M Arrest and ROS-Mediated Apoptotic Cell Death in a Human Triple-Negative Breast Cancer Cell Line.

The progression of a new class of compounds to inhibit the uncontrolled proliferation of carcinoma cells has become one of the most powerful weapons to combat "cancer". To this end, a new Mn(II)-based metal-organic framework, namely, [{Mn(5N3-IPA)(3-pmh)}(H2O)]α (5N3H2-IPA = 5-azidoisophthalic acid and 3-pmh = (3-pyridylmethylene)hydrazone), has been synthesized adopting a mixed ligand approach and exploited as a successful anticancer agent via systematic in vitro and in vivo studies. Single-crystal X-ray diffraction analyses depict that MOF 1 exhibits a 2D pillar-layer structure consisting of water molecules in each 2D void space. Due to the insolubility of the as-synthesized MOF 1, a green hand grinding methodology has been adopted to scale down the particle size to the nanoregime keeping its structural integrity intact. The nanoscale metal-organic framework (NMOF 1) adopts a discrete spherical morphology as affirmed by scanning electron microscopic analysis. The photoluminescence studies revealed that NMOF 1 is highly luminescent, enhancing its biomedical proficiency. Initially, the affinity of the synthesized NMOF 1 for GSH-reduced has been evaluated by various physicochemical techniques. NMOF 1 constrains the proliferation of cancer cells in vitro by inducing G2/M seizure and accordingly leads to apoptotic cell death. More significantly, compared to cancer cells, NMOF 1 exhibits less cytotoxicity against normal cells. It has been demonstrated that NMOF 1 interacts with GSH, causing a drop in cellular GSH levels and the production of intercellular ROS. It is quite intriguing that we discovered that NMOF 1-mediated ROS generation aids in significantly modifying the mitochondrial redox status, which is a crucial factor in apoptosis. According to mechanistic research, NMOF 1 increases the production of proapoptotic proteins and lowers the expression of antiapoptotic proteins, which significantly aids in activating caspase 3 and the subsequent cleavage of PARP1 and cell death via intrinsic apoptotic pathways. Finally, an in vivo investigation using immuno-competent syngeneic mice demonstrates that NMOF 1 can stop tumor growth without causing adverse side effects.

Response of Ancillary Azide Ligand in Designing a 1D Copper(II) Polymeric Complex along with the Introduction of High DNA- and HAS-Binding Efficacy, Leading to Impressive Anticancer Activity: A Compact Experimental and Theoretical Approach.

A new versatile azide-bridged polymeric Cu(II) complex, namely, [Cu(L)(µ1,3-N3)]∞ (1), was synthesized utilizing an N,N,O-donor piperidine-based Schiff base ligand (E)-4-bromo-2-((2-(-1-yl)imino)methyl)phenol (HL), obtained via the condensation reaction of 1-(2-aminoethyl) piperidine and 5-bromo salicylaldehyde. The single-crystal X-ray diffraction analysis reveals that complex 1 consists of an end-to-end azido-bridged polymeric network, which is further rationalized with the help of a density functional theory (DFT) study. After routine characterization with a range of physicochemical studies, complex 1 is exploited to evaluate its biomedical potential. Initially, theoretical inspection with the help of a molecular docking study indicated the ability of complex 1 to effectively bind with macromolecules such as DNA and the human serum albumin (HSA) protein. The theoretical aspect was further verified by adopting several spectroscopic techniques. The electronic absorption spectroscopic analysis indicates a remarkable binding efficiency of Complex 1 with both DNA and HSA. The notable fluorescence intensity reduction of the ethidium bromide (EtBr)-DNA adduct, 4',6-diamidino-2-phenylindole (DAPI)-DNA adduct, and HSA after the gradual addition of complex 1 authenticates its promising binding potential with the macromolecules. The retention of the canonical B form of DNA and α form of HSA during the association of complex 1 was confirmed by implementing a circular dichroism spectral study. The association ability of complex 1 with macromolecules further inspired us to inspect its impact on different cell lines such as HeLa (cervical cancer cell), PA1 (ovarian cancer cell), and HEK (normal cell). The dose-dependent and time-dependent in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay suggests an effective antiproliferative property of complex 1 with low toxicity toward the normal cell line. Finally, the anticancer activity of complex 1 toward carcinoma cell lines was analyzed by nuclear and cellular staining techniques, unveiling the cell death mechanism.

Azide-mediated unusual in situ transformation of Mannich base to Schiff-Mannich base and isolation of their Cu(II) complexes: crystal structure, theoretical inspection and anticancer activities.

A new "end-off" compartmental Mannich ligand (HL1) namely 3-((bis(2-methoxyethyl)amino)methyl)-5-bromo-2-hydroxybenzaldehyde containing two methoxyethyl pendant arms and one-CHO functionality has been synthesized through conventional C-C and C-N coupling reactions. On treatment with Cu(ClO4)2, HL1 yields a dinuclear µ-phenolatocopper(II) complex having the molecular formula [Cu2(L1)2](ClO4)2(H2O)1.5 (1). Surprisingly, the ligand HL1 is radically transformed into a new asymmetric Schiff-Mannich base ligand (HLF) in the presence of NaN3 and Cu(ClO4)2 forming a unique dinuclear centro-symmetric Cu(II) complex [Cu(LF)]2 (2) as evident from single-crystal X-ray diffraction (SCXRD) analysis. A probable mechanistic rationalization has been proposed on the basis of theoretical calculations, which suggests systematic fragmentation of HL1 in the presence of azide residue and re-condensation of the fragmented units to yield the final Cu-HLF complex (2). SCXRD analysis portrays a large inter-metallic distance in complex 2 in comparison with complex 1 (5.493 vs. 2.989 Å, respectively) along with other distinct structural features. After physicochemical characterization both the complexes have been exploited to evaluate their possible anticancer proficiency on lung adenocarcinoma cell line (A549). Complex 1 distinctly impeded the proliferation of lung adenocarcinoma cells in a dose-dependent manner more efficiently than complex 2. Due to the behavior of complex 1 as potential therapeutics, cellular transformations of A549 cells have been systematically investigated. As evidenced from various in vitro experiments, the cell death mechanism triggered by complex 1 turned out to be apoptosis, as indicated by the DNA fragmentation, chromatin condensation, membrane blebbing and imbalanced cell cycle distribution as well as retard migration in A549 cells.

Active Bromoaniline-Aldehyde Conjugate Systems and Their Complexes as Versatile Sensors of Multiple Cations with Logic Formulation and Efficient DNA/HSA-Binding Efficacy: Combined Experimental and Theoretical Approach.

Two fluorescence active bromoaniline-based Schiff base chemosensors, namely, (E)-4-bromo-2-(((4-bromophenyl)imino)methyl)phenol (HL1 ) and (E)-2-(((4-bromophenyl)imino)methyl)phenol (HL2 ), have been employed for the selective and notable detection of Cu2+ and Zn2+ ions, respectively, with the simultaneous formation of two new metal complexes [Cu(L1)2] (1) and [Zn(L2)2] (2). X-ray single crystal analyses indicate that complexes 1 and 2 are tetra-coordinated systems with substantial CH...π/π...π stacking interactions in the solid-state crystal structures. These two complexes are exploited for the next step detection of Al3+ and Hg2+ where complex 2 exhibits impressive results via turn-off fluorescence quenching in (DMSO/H2O) HEPES buffer medium. The sensing phenomena are optimized by UV-vis spectral analyses as well as theoretical calculations (density functional theory and time-dependent density functional theory). The combined detection phenomena of the ligand (HL2 ) and complex 2 are exclusively utilized for the first time to construct a molecular memory device, intensifying their multisensoric properties. Furthermore, the DNA- and human serum albumin (HSA)-binding efficacies of these two complexes are examined by adopting electronic and fluorometric titration methods. Complex 2 shows a higher DNA-binding ability in comparison with complex 1, whereas in the case of HSA, the reverse situation is observed. Finally, the binding modes of both the complexes with DNA and HSA have been investigated through molecular docking studies, suggesting good agreement with the experimental results.

Green facile synthesis to develop nanoscale coordination polymers as lysosome-targetable luminescent bioprobes.

Three new coordination polymers (CPs), namely [{M(HL)(L)(H2O)}(ClO4)(H2O)]∞ (M = Zn for CP 1, Mn for CP 2, Cu for CP 3) were synthesized to explore their efficacy as lysosome-targetable luminescent bioprobes. The synthesized CPs were characterized by techniques including single-crystal X-ray analysis, FTIR spectroscopy and elemental analysis. Single-crystal analysis revealed the formation of iso-structural CPs displaying distorted adamantoid topology developed by bridging ligands and H-bonds connections and metals at the nodes. A green hand-grinding technique with a mortar and pestle resulted in nanoscale coordination polymers (NCPs) suitable for cell permeability and was further confirmed by SEM and DLS analyses. Two of these hand-ground nanoscale coordination polymers NCP 1 and NCP 2 showed excellent green luminescence and were explored as potential and selective long-time biotrackers towards lysosome using the human lung carcinoma cell line (A549). Strikingly, the developed bioprobe displayed excellent bio-availability, photostability and excellent selectivity towards lysosomes sustained by various in vitro cell imaging experiments. Moreover, the long-term probing ability of these NCPs turned out to be better than the commercially available lysosome tracker i.e. LysoTracker Red, indicating their potential real-life application in bio-imaging. To the best ofour knowledge, this is the first example of nonexpensive and less toxic essential transition metal-based nanoscale coordination polymers that can behave as effective lysosome-targetable luminescent bioprobes.

Organically Functionalized Mesoporous SBA-15 Type Material Bearing Fluorescent Sites for Selective Detection of HgII from Aqueous Medium.

Hg(II) contamination in water resources is one of the major health issues in keeping the purity standard of the municipal water supply. Herein, we report a new mesoporous sensor probe material SBA-ABZ-PEA having a 2D-hexagonally ordered mesoporous framework bearing covalently bonded fluorescent sites, and this has been synthesized through a two-step post-synthesis grafting route. A pure silica mesoporous SBA-15 material has been functionalized with (3-chloropropyl)triethoxysilane (ClPTES) to obtain chloro-functionalized SBA-15, which was further reacted with 4-aminobenzaldehyde followed by treatment with 2-(2-pyridyl)-ethylamine resulting in functionalized 2D-hexagonal mesoporous sensor probe SBA-ABZ-PEA. Small angle PXRD, N2 adsorption/desorption, HRTEM, TGA, and FT-IR studies have been carried out to characterize these materials. Our experimental results suggested successful grafting of the organic moiety on the SBA-15 surface along with preservation of mesoporosity throughout the grafting process. Photoluminescence measurements were carried out in the aqueous suspension of SBA-ABZ-PEA in the presence of different metal cations, like NaI, MgII, AlIII, KI, CaII, MnII, CoII, CuII, ZnII, CdII, PbII, and HgII. This result revealed that, among the various metal-ions, the emission intensity of the mesoporous sensing probe material SBA-ABZ-PEA has been dramatically quenched in the presence of the HgII ion. To check the sensitivity of the sensor probe, the fluorescence emission was also studied in the presence of different concentrations of HgII ions. A perfect linear plot between the concentrations of HgII ions in the aqueous medium with their corresponding fluorescence intensities with a detection limit of 1.2 × 10-6 M has been observed.

Green synthesis of nanoscale cobalt(ii)-based MOFs: highly efficient photo-induced green catalysts for the degradation of industrially used dyes.

Two new metal-organic frameworks (MOFs) based on cobalt metal, namely, [{Co0.5(5N3-IPA)0.5(1,2-bpe)1.25}]∞ (1) and [{Co(5NH2-IPA)(1,2-bpe)}]∞ (2) (5N3-IPA = 5-azidoisophthalic acid, 5NH2-IPA = 5-aminoisophthalic acid, 1,2-bpe = 1,2-bis(4-pyridyl)ethylene) were synthesized under a solvothermal condition and characterized. MOF 1 has a rare three-dimensional structure with 3-fold interpenetration, while MOF 2 has a 2D "pillar-layered" structure. The particle size of the as-synthesized MOFs was reduced to produce nanoscale MOFs (NMOFs) by a hand grinding technique while retaining the composition and structural regularity of the as-synthesized MOFs. SEM studies revealed that NMOFs 1 and 2 were hexagonal and square shaped, respectively. Since the band gap energy for MOFs 1 and 2 (2.81 eV and 2.65 eV, respectively) falls in the visible region, heterogeneous catalytic activities of NMOFs 1 and 2 in aqueous medium towards Reactive Yellow HE4R (RY84), Reactive Black HFGR (RBH), Rhodamine B (RhB) and methylene blue (MEB) were investigated under visible light irradiation. The introduction of hydrogen peroxide was observed to significantly increase the photocatalytic efficiency via dye degradation. Hydroxyl radical (OH˙) is supposed to act as the main active species during oxidation, which was further verified by performing the degradation experiment in the presence of tert-butyl alcohol, which can act as a radical trapper for hydroxide radicals in the reaction.

Anion-mediated bio-relevant catalytic activity of dinuclear nickel(ii) complexes derived from an end-off compartmental ligand.

Four dinuclear nickel(ii) complexes, namely [Ni4(L)2(H2O)8(µ2-H2O)2](NO3)6(H2O)6 (1), [Ni2(L)Cl2(µ-Cl)(CH3OH)] (2), [Ni2(L)(OAc)2(H2O)2]Br (3) and [Ni2(L)(H2O)4(µ2-OH)] (H2O)X(I)X (4), have been synthesized using a template synthesis technique by adding nickel(ii) salts (nitrate/chloride/bromide/iodide) to the N4O donor end-off compartmental ligand (HL) obtained via the condensation of 2-(2-pyridyl)ethylamine and 2,6-diformyl-4-isopropyl phenol in methanol. All complexes were characterized with the help of typical physicochemical techniques, and their solid-state structures were assigned from single crystal X-ray analysis. The variable temperature magnetic study reveals that the two nickel centers are antiferromagnetically coupled with J values ranging from -5 to -15 cm-1 in the complexes. The catecholase-like activity of complexes 1-4 was studied using 3,5-di-tert-butylcatechol (3,5-DTBC) as the model substrate in N,N-dimethylformamide (DMF) medium. Complex 1 shows the catecholase activity, while the other complexes were found to be inactive. The phosphatase-like activity of the complexes was also investigated in a 97.5% (v/v) DMF-water mixture using the disodium salt of 4-nitrophenylphosphate (4-NPP) as the model substrate and the reactivity trend was 4 > 1 > 3 > 2. The reasons behind the activity, inactivity and activity trend have been explored. It has been assumed that the anions associated with the complexes are supposed to play a crucial role in the whole event. Complex 1 showed catalytic promiscuity, whereas complexes 2, 3 and 4 should be considered only as the potential hydrolytic catalyst.

Green Approach To Synthesize Crystalline Nanoscale ZnII-Coordination Polymers: Cell Growth Inhibition and Immunofluorescence Study.

Five new coordination polymers (CPs) namely, [{Zn(µ2-H2O)0.5(5N3-IPA)(2,2'-bpe)}]∞ (1), [{Zn(µ2-H2O)0.5(5N3-IPA)(1,10-phen)}]∞ (2), [{Zn(5N3-IPA)(1,2-bpe)}]∞ (3), [{Zn(5N3-IPA)(1,2-bpey)}]∞ (4), and [{Zn(H2O)(5N3-IPA)(4,4'-tme)}(H2O)0.5]∞ (5) (5N3-H2IPA = 5-azidoisophthalic acid, 2,2'-bpe= 2,2'-bipyridine, 1,10-phen = 1,10-phenanthroline, 1,2-bpe = 1,2-bis(4-pyridyl)ethane, 1,2-bpey = 1,2-bis(4-pyridyl)ethylene, 4,4'-tme = 4,4'-trimethylenedipyridine), have been synthesized based on a mixed ligand approach adopting a solvothermal technique. Depending upon the intrinsic structural flexibility of the bis-pyridyl coligands, interesting structural topologies have also been observed in the resulting CPs: Sra SrAl2 type topology for 3 and a 3-fold interpenetrated dmp topology for 4. A green hand grinding technique has been implemented to reduce the particle size of the CPs to generate nanoscale CPs (NCPs). SEM studies of NCPs reveal the formation of square and spherical particles for NCP 1 and 2, respectively, and nano rod for NCP 3, 4, and 5. Remarkably, when scaled down to nano range all the NCPs retain their crystalline nature. The cytotoxic activity of the NCPs (1-5) has been studied using human colorectal carcinoma cells (HCT 116). Significant cell death is observed for NCP 2, which is further corroborated by cell growth inhibition study. The observed cell death is likely to be due to mitochondrial-assisted apoptosis as is evident from immunofluorescence study.