In Silico and In Vitro Studies of 4-Hydroxycoumarin-Based Heterocyclic Enamines as Potential Anti-Tumor Agents.

The present study reports the one-step synthesis of several 3-formyl-4-hydroxycouramin-derived enamines (4a-4i) in good yields (65-94%). The characterization of the synthesized compounds was carried out via advanced analytical and spectroscopic techniques, such as melting point, electron impact mass spectrometry (EI-MS), 1H-NMR, 13C-NMR, elemental analysis, FTIR, and UV-Visible spectroscopy. The reaction conditions were optimized, and the maximum yield was obtained at 3-4 h of reflux of the reactants, using 2-butanol as a solvent. The potato disc tumor assay was used to assess Agrobacterium tumefaciens-induced tumors to evaluate the anti-tumor activities of compounds (4a-4i), using Vinblastine as a standard drug. The compound 4g showed the lowest IC50 value (1.12 ± 0.2), which is even better than standard Vinblastine (IC50 7.5 ± 0.6). For further insight into their drug actions, an in silico docking of the compounds was also carried out against the CDK-8 protein. The binding energy values of compounds were found to agree with the experimental results. The compounds 4g and 4h showed the best affinities toward protein, with a binding energy value of -6.8 kcal/mol.

Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester.

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus.

Metal-Based Scaffolds of Schiff Bases Derived from Naproxen: Synthesis, Antibacterial Activities, and Molecular Docking Studies.

We report here the synthesis, characterization, and antibacterial evaluation of transition metal complexes of Ni, Cu, Co, Mn, Zn, and Cd (6a⁻f), using a Schiff base ligand (5) derived from naproxen (an anti-inflammatory drug) and 5-bromosalicylaldehyde by a series of reactions. The ligand and the synthesized complexes were characterized by elemental analysis, UV-Visible, FTIR, and XRD techniques. The ligand 5 behaves as a bidentate donor and coordinates with metals in square planar or tetrahedral fashion. In order to evaluate its bioactivity profile, we screened the Schiff base ligand and its metal complexes (6a⁻f) against different species of bacteria and the complexes were found to exhibit significant antibacterial activity. The complexes showed more potency against Bacillus subtilis as compared to the other species. Moreover, we modeled these complexes' binding affinity against COX1 protein using computational docking.

A Brief Review on Fluorescent Copper Sensor Based on Conjugated Organic Dyes.

The design and development of the fluorescence reporting molecules for the trace recognition of the metallic ions in the aqueous, mixed organic aqueous media, environmental specimen, living things e.g., body fluids, serum, urine etc is the evergreen research area. Among several methodologies utilized for these purposes, the fluorescent techniques have wonderful impact in the era of metal sensor development due to their acclamatory features of non-invasive detection process and appreciable sensitivity. The utilization of small organic molecules for the sensation of metallic ions through the fluorescent techniques harvested the wonderful results having some interesting features of chromogenic response on metal binding, robustness in the preparation and applicability to establish the metallic accumulation level inside the live cells via bioimaging studies. The detailed knowledge and background about the several reported chemosening strategies have the utmost importance in order to understand or to design the novel molecules for metal sensing purposes. The objective of the presents review was to compile the best ever used copper sensing strategies via fluorescent means in the running decade. We have summarized the values of optical positions of the spectral lines, spectral shifting upon metal binding, binding/association/dissociation constants, chromogenic changes in the reaction mixture, proposed complexation mechanism of the ligand with the copper, ligand sensitivities toward the copper recognition, binding stoichiometries and the detailed bioimaging results where applicable.

Anticancer Ru and Os complexes of N-(4-chlorophenyl)pyridine-2-carbothioamide: Substitution of the labile chlorido ligand with phosphines.

Half-sandwich MII(cym)Cl (cym = Î·6-p-cymene; M = Ru, Os) complexes of pyridinecarbothioamide (PCA) ligands have demonstrated potential as orally active anticancer agents. In order to investigate the impact of the substitution of the labile chlorido ligand with phosphorous donor ligands on the antiproliferative properties, the triphenylphosphine (PPh3) and 1,3,5-triaza-7-phophaadamantane (pta) analogues were prepared and characterized by spectroscopic techniques and the molecular structures of several complexes were determined by X-diffraction analysis. Interestingly, the molecular structures contained the PCA ligand deprotonated, presumably driven by the reduction in overall charge of the complex. Density Functional Theory (DFT) calculations suggested minor energy differences between the protonated and deprotonated forms. The aqueous stability and the reactivity with the amino acids l-histidine and l-cysteine were investigated by 1H NMR spectroscopy of representative examples. The most potent anticancer agents featured Ru or Os centers and a PPh3 ligand and showed IC50 values in the submicromolar range against four cancer cell lines. This suggests that the antiproliferative activity was mainly dependent on the lipophilic properties of the phosphine ligand with PPh3 having a significantly higher clog P value than pta.

Synthesis of an amantadine-based novel Schiff base and its transition metal complexes as potential ALP, α-amylase, and α-glucosidase inhibitors.

A Schiff base ligand HL, (E)-2-((adamantan-1-ylimino)methyl)-6-allylphenol, was synthesized by condensation of amantadine with 3-allyl-2-hydroxybenzaldehyde, followed by the synthesis of its Zn(ii), Co(ii), Cr(iii), and VO(iv) complexes under reflux conditions. The synthesized compounds were comprehensively elucidated by using different spectroscopic and analytical techniques: UV-Vis, 1H and 13C-NMR, FT-IR, ESI-MS, thermal, and single-crystal XRD analysis. The chemical composition of the synthesized compounds was also verified by molar conductance and elemental analysis. An octahedral geometry for Cr(iii) and Co(ii) complexes, tetrahedral for Zn(ii) complex, and square pyramidal geometry have been proposed for VO(iv) complexes. The antidiabetic activities of the synthesized compounds were also evaluated by performing in vitro α-amylase and α-glucosidase inhibition studies. The Co(ii) complex exhibited the highest α-glucosidase inhibitory activity, whereas oxovanadium(iv) and zinc(ii) complexes were also found to be effective against α-amylase. In alkaline phosphatase (ALP) inhibition studies, the HL was found to be inactive, while the complexes showed remarkable enzyme inhibition in the following order: VO > Zn > Co, in a concentration-dependent manner.

Correction: Synthesis of an amantadine-based novel Schiff base and its transition metal complexes as potential ALP, α-amylase, and α-glucosidase inhibitors.

[This corrects the article DOI: 10.1039/D2RA07051K.].

Synthesis, antioxidant activity, antimicrobial efficacy and molecular docking studies of 4-chloro-2-(1-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazol-2-yl)phenol and its transition metal complexes.

Herein, a one-pot synthesis of tetra-substituted imidazole, 4-chloro-2-(1-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazol-2-yl)phenol (HL), is reported by the reaction of benzil, 5-bromosalicylaldehyde, ammonium acetate and anisidine. The synthesized imidazole was reacted with salts of 1st row transition metals (Co(ii), Ni(ii), Cu(ii), Mn(ii) and Zn(ii)) to obtain metal complexes. The structure of the compounds was confirmed using various spectroscopic and analytical techniques. HL, which is crystalline, was characterized by SC-XRD. Subsequently, the synthesized compounds were evaluated for their antioxidant and antimicrobial activities. Antimicrobial studies revealed the more noxious nature of metal complexes compared to ligand against various strains of bacteria and fungi. Molecular docking results based on the binding energy values also supported the experimental results of the antioxidant activities of the compounds. HL was found to be a better antioxidant than metal complexes. For a better insight into the structure, computational studies of the compounds were also carried out. A clear intra-molecular charge transfer was perceived in the ligand and its metal complexes. The transfer integral values for holes (36.48 meV) were found to be higher than the electron transfer integrals (24.76 meV), which indicated that the ligand would be a better hole transporter. According to the frontier molecular orbitals of the dimer, the charge transfer within the molecule is found from monomer 1 to 2.

2-Eth-oxy-6-{(E)-[(4-methyl-phen-yl)imino]-meth-yl}phenol.

The asymmetric unit of the title compound, C(16)H(17)NO(2), contains two mol-ecules in which the dihedral angles between the 3-eth-oxy-2-hy-droxy-benzaldehyde and toluidine moieties are 16.87 (8) and 19.93 (6)°. S(6) rings are present in both mol-ecules due to intra-molecular O-H⋯N hydrogen bonds. In the crystal, one of the mol-ecules is dimerized with an inversion-generated partner, due to two C-H⋯O inter-actions. This generates an R(2) (2)(8) loop.

5-Hy-droxy-2-{(E)-[(3-nitro-phen-yl)iminio]meth-yl}phenolate.

The title compound, C(13)H(10)N(2)O(4), crystallized as the zwitterionic tautomer. As a result, the phenolate C-O(-) bond [1.296 (2) Å] is shorter than a normal Csp(2)-O(H) bond, and the azomethine C=N bond [1.314 (2) Å] is longer than a normal C=N double bond. The mol-ecule is nearly planar, the mean plane of the nitro-substituted benzene ring forming dihedral angles of 9.83 (7) and 8.45 (9)° with the other benzene ring and with the nitro group, respectively. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond. In the crystal, strong O-H⋯O hydrogen bonds link the mol-ecules into double-stranded chains along the b-axis direction. Within the chains there are π-π interactions involving the benzene rings of adjacent molecules [centroid-centroid distance = 3.669 (1) Å]. The chains are linked via C-H⋯O hydrogen bonds, forming R(2) (1)(6), R(2) (1)(7) and R(2) (2)(10) ring motifs.

2-[(E)-N-(Adamantan-1-yl)carbox-imidoyl]-6-eth-oxy-phenol.

In the title compound, C(19)H(25)NO(2), the 3-eth-oxy-2-hy-droxy-benzaldehyde group is almost planar (r.m.s. deviation = 0.029 Å). An intra-molecular O-H⋯N hydrogen bond generates an S(6) ring. There are no inter-molecular hydrogen bonds.

High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes.

Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a-1c and 3-hydroxy-4-thiopyridones 1d-1f as well as their Ru(η6-p-cymene)Cl complexes 2a-2f, and report here the molecular structures of 1b and 1d as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones 1d-1f, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low µM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells.

A monoclinic polymorph of cysteamine hydro-chloride.

THE TITLE COMPOUND (SYSTEMATIC NAME: 2-mercaptoethan-aminium chloride), C(2)H(8)NS(+)·Cl(-), the hydro-chloride salt of cysteamine, in contrast to the previously reported triclinic polymorph [Kim et al. (2002 ▶). Polyhedron, 21, 225-228], crystallized in the monoclinic crystal system. In the crystal, the cysteaminium cations are linked to the chloride anions via one S-H⋯Cl and three N-H⋯Cl hydrogen bonds. Two-dimensional slab-like networks are formed, which are stacked in [100]. This arrangement is similar to that observed in the triclinic polymorph.

Bromidobis(N,N'-diphenyl-thio-urea-κS)copper(I) monohydrate.

In the title compound, [CuBr(C(13)H(12)N(2)S)(2)]·H(2)O, the Cu(I) atom adopts a slightly distorted trigonal-planar coordination arising from two S atoms of two diphenyl-thio-urea ligands and a bromide ion. There are two intra-molecular N-H⋯Br hydrogen bonds completing twisted six-membered rings with R(6) motifs. The dihedral angles between the aromatic rings in the ligands are 62.11 (13) and 85.73 (13)°. In the crystal, components are linked by N-H⋯O, O-H⋯S and O-H⋯π inter-actions. There also exist π-π inter-actions with a distance of 3.876 (2) Šbetween the centroids of benzene rings of two different ligands. Together, the inter-molecular inter-actions lead to a three-dimensional network.

5-Hydr-oxy-2-methyl-4H-pyran-4-one.

The title compound, C(6)H(6)O(3), is a member of the pyrone family. The mol-ecules are planar (r.m.s. deviation of the asymmetric unit is 0.0248 Å, whereas that of the dimer is 0.0360 Å) and they are dimerized due to inter-molecular O-H⋯O hydrogen bonds. The dimers are connected to each other through hydrogen bonds involving the CH(3) group and the hydr-oxy O atom. There are π-π inter-actions between the centroids of the pyrone rings at a distance of 3.8552 (13) Å. A C-H⋯π inter-action also exists between the carbonyl group and the centroid CgA of the pyrone ring, with O⋯CgA = 3.65 (1) Šand C⋯CgA = 4.363 (2) Å.

Enhanced photocatalytic H2 production under visible light on composite photocatalyst (CdS/NiSe nanorods) synthesized in aqueous solution.

Cocatalysts play a critical role in the activity and stability of photocatalytic systems. Currently, efficient cocatalysts mainly comprise of expensive noble metals. Herein we report a composite photocatalyst consisting of CdS nanorods (NRs) and noble-metal-free cocatalyst NiSe, which efficiently enhances the hydrogen production activity of CdS NRs under visible light. NiSe was synthesized through a facile aqueous solution method and CdS/NiSe NRs composites were prepared by in situ deposition of NiSe on CdS NRs. This provides increased contact between cocatalyst and photosensitizer leading to enhanced electron transfer at the interface of NiSe and CdS. The current photocatalytic system gave the highest hydrogen evolution rate of 340 µmol h-1 under optimal conditions. The enhanced stability of the system was observed for 30 h of irradiation resulting in 14 mmol of hydrogen evolution. The highest AQY of 12% was observed using the 420 nm monochromatic light. In addition, CdS/NiSe NRs showed significant higher H2 evolution rate than that of 1.0 wt% loaded CdS/Pt NRs proving NiSe as highly efficient cocatalyst. Photoluminescence spectra and the photocurrent response were used to confirm the efficient charge transfer at the interface of NiSe and CdS nanorods. The work presented here demonstrates the successful use of an inexpensive, non-noble-metal cocatalyst for enhanced photocatalytic hydrogen production.

Coordination Chemistry of Organoruthenium Compounds with Benzoylthiourea Ligands and their Biological Properties.

Benzoylthiourea derivatives feature several donor atoms capable of coordinating to metal centers. We report here a series of Ru(η6 -p-cymene) complexes employing benzoylthiourea derivatives as ligands. Such ligands often coordinate to metal centers through their S and O donor atoms. We isolated complexes where the ligands were mono- or bidentately coordinated to Ru involving the S donor atom and surprisingly in bidentate coordination mode a deprotonated thiourea nitrogen resulting in a 4-membered ring structure around the metal center. DFT calculations were used to explain the differences in coordination behavior. These were complemented by stability studies and biological investigations of the compounds as anticancer agents. Several of the synthesized derivatives exhibited significant cell growth inhibitory activity, with the complexes featuring bidentate ligands being more potent than their monodentate counterparts. This can be explained by the higher stability of the former under the conditions employed in cell culture assays.

Crystal structure of di-chlorido-bis-(N,N'-di-methyl-thio-urea-κS)mercury(II).

The mol-ecular structure of the title compound, [HgCl2(C3H8N2S)2], has point group symmetry 2, with the twofold rotation axis passing through the Hg(II) atom. The latter is coordinated by two Cl atoms and two N,N'-di-methyl-thio-urea (Dmtu) ligands through their S atoms, defining a distorted tetra-hedral coordination sphere with bond angles in the range 102.47 (4)-118.32 (4)°. Intra- and inter-molecular hydrogen bonds of the type N-H⋯Cl with S(6) and R 2 (2)(12) ring motifs are present. The inter-molecular contacts make up polymeric chains extending parallel to [101].

Growth and antioxidant response of Brassica rapa var. rapa L. (turnip) irrigated with different compositions of paper and board mill (PBM) effluent.

Current study presents the effect of irrigation with different compositions (0%, 20%, 40%, 60%, 80% and 100%) of PBM effluent on growth and antioxidant potential of Brassica rapa var. rapa L. plants. Seeds were exposed to different PBM effluent compositions, which resulted in significant decrease in their germination potential with elevated delay index. Significant changes in growth parameters (plant height, number of leaves and leaf area) were recorded for turnip plants at regular intervals (25, 50 and 75 d) as function of PBM effluent proportion. Response of biochemical and antioxidant constituents in different parts of turnip, against stress induced by PBM effluent, was assessed by estimating the contents of chlorophyll (a+b), carotenoids, protein, phenolics, flavonoids, ascorbic acid and malondialdehyde. Antioxidant activity was evaluated by measuring DPPH radical scavenging potential. The results of this study suggest that the impact of PBM effluent irrigation is dependent on concentration of effluent in irrigation mixture and is very clear on plant growth and antioxidant attributes. Maximum benefits were secured at 40% PBM effluent to irrigate turnip plants till maturity while higher concentrations were found useful for shorter period (25-50 d).

An economically viable method for the removal of selected divalent metal ions from aqueous solutions using activated rice husk.

Biosorption of divalent metal ions, i.e. Pb(II), Cd(II), Zn(II) and Cu(II) onto rice husk activated (RHA) is investigated over pH range (1-10) via batch adsorption technique. The chemical and thermal activation of rice husk with 0.1M HNO(3) and 1M K(2)CO(3) at 473 K enhanced the removal efficiency of RHA (35+/-2.1-99+/-0.5%, 33+/-1.2-97+/-0.6%, 32+/-1.3-96+/-0.8% and 28+/-1.8-95+/-0.9% before and after treatment, respectively). The surface area analysis of RHA by BET (Brunauer, Emmett and Teller) nitrogen adsorption method provided pore area and average pore diameter to be 542+/-2.3m(2)g(-1) and 1076+/-5.6 nm respectively. SEM and FTIR analyses of RHA were carried out to determine the surface morphology and functional groups involved in metal binding mechanism, respectively. The adsorption equilibrium was well described by Freundlich, Langmuir and Dubinin-Radushkevish (D-R) isotherm models by employing (4.8-48, 8.9-89, 15.3-153 and 15.7-157)x10(-5)M solution concentrations of sorbates, respectively, at equilibrium time of 20 min at pH 6 and onto 0.2g of sorbent. The kinetics of mass transfer and intra-particle diffusion for metal ions sorption onto RHA were studied with Lagergren and Morris-Weber kinetic models. The numerical values of thermodynamic parameters indicated the exothermic nature, spontaneity and feasibility of the sorption process. The desorption study of metal components from RHA surface was carried out with 0.1M HCl. The sorption mechanism developed illustrates the strong interactions of sorbates with the active sites of the sorbent coupled with efficient and environmentally clean exploitation of rice waste product.