Design, syntheses, theoretical calculations, MM-GBSA, potential anti-cancer and enzyme activities of novel Schiff base compounds.

In this study, new Schiff base compounds (SB-F-OH, SB-Cl-OH and SB-Br-OH) were derived from chalcone-derived amine compounds containing halogen groups and 4-hydroxybenzaldehyde. Also, their phthalonitrile compounds (SB-F-CN, SB-Cl-CN and SB-Br-CN) have been synthesized. The structures of these compounds were elucidated by NMR, FT-IR and Mass spectroscopic methods. The quantum chemical parameters were calculated at B3LYP/6-31++g(d,p), HF/6-31++g(d,p) and M062X/6-31++g(d,p) levels. As the biological application of the synthesized compounds, (i) their inhibition properties of the synthesized compounds on Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) metabolic enzymes were investigated, and their potential anticancer activities against neuroblastoma (NB; SH-SY5Y) and healthy fibroblast (NIH-3T3) cell lines were determined by in vitro assays. All compounds showed inhibition at nanomolar level with the Ki values in the range of 97.86 ± 30.51-516.82 ± 31.42 nM for AChE, 33.21 ± 4.45-78.50 ± 8.91 nM for BChE, respectively. It has been determined that all tested compounds have a remarkable cytotoxic effect against SH-SY5Y, and IC50 values were significantly lower than NIH-3T3 cells. The lowest IC50 value was observed in SB-Cl-OH (7.48 ± 0.86 µM) and SB-Cl-CN (7.31 ± 0.69 µM). The molecular docking of the molecules was also investigated using crystal structure of AChE enzyme protein (PDB ID: 4M0E), crystal structure of BChE protein (PDB ID: 6R6V) and SH-SY5Y cancer protein (PDB ID: 2F3F, 3PBL and 5WIV). The ADME properties of the compounds were investigated. MM/GBSA method is calculated binding free energy. Afterwards, ADME/T analysis was performed to examine the some properties of the molecules.Communicated by Ramaswamy H. Sarma.

Synthesis of peripheral and non-peripheral substituted metallophthalocyanines containing (E)-3-(5-bromo-2-hydroxphenyl)-1-o-tolyprop-2-en-1-one: Investigation of the photophysical and photochemical properties.

In this study, the novel peripherally (5-7) and non-peripherally (9-11) metallo (zinc, magnesium and lead) phthalocyanine derivatives were synthesized from their (E)-4-(4-bromo-2-(3-oxo-3-o-tolyprop-1-enyl)phenoxy) substituted phthalonitrile precursors (4 and 8). These novel phthalocyanine derivatives including chalcone groups were characterized by spectroscopic techniques such as FT-IR, UV-vis, 1H NMR, 13C NMR and MALDI-TOF mass spectra. In the next stage, the photophysical and photochemical properties of synthesized compounds were searched in DMSO which is not cause toxic effects at a certain concentration in biological applications. As a result of investigations, it was determined that phthalocyanine complexes did not demonstrate aggregation in DMSO solutions.

The use of new metallophthalocyanines carrying peripherally 4-methyl-N-(3-morpholinopropyl)benzenesulfonamide moieties for the sensitive fluorimetric determination of banned food dye Sudan II in red chili peppers.

The structural elucidation and syntheses methods of new peripherally tetra-substituted MPcs [CuII(6), CoII(7), MnCIIII(8), and NiII(9) phthalocyanines] carrying 4-methyl-N-(3-morpholinopropyl)benzenesulfonamide moieties were reported in the present study. The corroboration of the prepared compounds (3, 5, and 6 to 9) was made by LC-TOF/MS, UV-Vis, Fourier Infrared, 1H NMR, 13C NMR, and MALDI-TOF mass spectral data. Herein, we submit a new procedure that uses metallophthalocyanine complexes for the first time as spectrofluorimetric agents to detect and determine health-threatening food additive, Sudan II dye, with a new simpler, cheaper, and faster spectrofluorimetric method instead of time-consuming and expensive HPLC processes. Furthermore, the sensitivities of the proposed methods are good enough to determine the amount of dye at a concentration of 0.1 mg/L. The methods have LOD values between 0.035 and 0.050 mg/L. The linear ranges are found to be between 0 and 8.3 mg/L. The precision of the methods is determined to be between 1.1 and 2.4 as % RSD. Therefore, this study would make a good contribution to the food industry and phthalocyanine chemistry by detecting and determining the hazardous food colorant Sudan II with metal phthalocyanines.

The peripheral and non-peripheral 2H-benzotriazole substituted phthalocyanines: Synthesis, characterization, photophysical and photochemical studies of zinc derivatives.

In this study, the novel 3-(1H-benzo[d][1,2,3]triazol-1-yl)methoxy substituted novel phthalonitrile compounds (2 and 6) were synthesized. Their non-peripheral and peripheral zinc (II) (3 and 7), manganese (III) (4 and 8) and copper (II) (5 and 9) phthalocyanine complexes were synthesized for the first time. These novel compounds were characterized by elemental analysis and different spectroscopic techniques such as FT-IR, UV-Vis, 1H NMR, 13C NMR and MALDI-TOF mass. Also, photochemical and photophysical properties of non-peripheral and peripheral substituted zinc (II) phthalocyanines (3 and 7) were investigated for determination of photodynamic therapy applications of these phthalocyanines.

Simultaneous determination of theophylline and caffeine on novel [Tetra-(5-chloroquinolin-8-yloxy) phthalocyanato] manganese(III)-Carbon nanotubes composite electrode.

This work reports the synthesis of new symmetrically substituted manganese(III) phthalocyanine (2eOHMnPc) (2) containing tetra 5-chloroquinolin-8-yloxy group at the peripheral position for the first time. Manganese(III) phthalocyanine (2) was synthesized by cyclotetramerization of 4-(5-chloroquinolin-8-yloxy)phthalonitrile (1) in the presence of corresponding metal salt (manganese(II) chloride). This peripherally substituted phthalocyanine complex (2) was purified by column chromatography and characterized by several techniques such as IR, mass and UV-Visible spectral data. This novel synthesized phthalocyanine was mixed with multiwalled carbon nanotubes in order to prepare the novel catalytic surface on glassy carbon electrode for theophylline and caffeine detection in acidic medium. The novel composite electrode surfaces were characterized by scanning electron microscopy and electrochemical impedance spectroscopy. Individual and simultaneous determination of theophylline and caffeine were studied by differential pulse voltammetry. The detection limits were individually calculated for theophylline and caffeine as 6.6 × 10-9 M and 5.0 × 10-8 M, respectively. In simultaneous determination, LODs were calculated for theophylline and caffeine as 8.1 × 10-9 M and 3.0 × 10-7 M, respectively. The practical applicability of the proposed modified electrode was tested for the determination of theophylline and caffeine in green tea, cola and theophylline serum.

Novel water soluble morpholine substituted Zn(II) phthalocyanine: Synthesis, characterization, DNA/BSA binding, DNA photocleavage and topoisomerase I inhibition.

In this study, novel peripherally tetra 3-morpholinophenol substituted zinc(II) phthalocyanine (4) and its water soluble form quaternized zinc(II) phthalocyanine (ZnQ) were synthesized for the first time. These novel compounds were characterized by a combination of different spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR, UV-vis and mass. The DNA binding of ZnQ was investigated using UV-vis absorption titration, competitive ethidium bromide, thermal denaturation and viscosity experiments that the ZnQ bound to CT-DNA via intercalation mode. ZnQ indicated photocleavage activity on supercoiled pBR322 plasmid DNA via formation of singlet oxygen under irradiation at 700nm. Besides, the topoisomerase I inhibitory effect experiments showed that ZnQ inhibited topoisomerase I enzyme in a concentration-dependent manner. The bovine serum albumin (BSA) binding experiments indicated that ZnQ bound to proteins through a static quenching mechanism. All of these results claim that ZnQ has potential agent for photodynamic therapy owing to its nucleic acid interactions and photobiological or photochemical properties.

Metal Complexation Properties of Schiff Bases Containing 1,3,5-Triazine Derived from 2-Hydroxy-1-Naphthaldehyde in Solution. A Simple Spectrofluorimetric Method to Determine Mercury (II).

Four new Schiff base ligands carrying naphthalene groups were prepared from the reaction of 2,4-diamino-6-methyl-1,3,5-triazine and 2,4-diamino-6-undecyl-1,3,5-triazine with 2-hydroxy-1-naphthaldehyde. The influence of a series of metal ions including Cu2+, Co2+, Hg2+, Al3+, Cr3+, Fe3+, Pb2+, Ni2+, Cd2+, Zn2+, Mn2+, Ag+, Ba2+, Ca2+ and Mg2+ on the spectroscopic properties of the ligands was investigated by means of absorption and emission spectrometry. The results of spectrophotometric and spectrofluorimetric titrations disclosed the complexation stoichiometry and complex stability constant of the ligands with metal ions. A simple spectrofluorimetric method was developed using the Schiff base derived from 2,4-diamino-6-undecyl-1,3,5-triazine to determine Hg2+ ion. No cleanup or enrichment of the tap water sample was required. A modified standard addition method was used to eliminate matrix effect. The standard addition graph was linear between 0.2 and 2.6 mg/L in determination of Hg2+. Detection and quantification limits were 0.08 and 0.23 mg/L, respectively. The simple and cost-effective method can be applied to water samples.

A Simple Spectrofluorimetric Method Based on Quenching of a Nickel(II)-Phthalocyanine Complex to Determine Iron (III).

A new nickel(II)-phthalocyanine complex (NiPc) was synthesized and used as a fluorescent ligand in determination of iron in real samples. The NiPc compound, when excited at 350 nm, decreases of emission with increases of the iron(III) concentration at 425 nm were used analytical response in a modified standard addition method. The method was validated by analyzing two certified reference materials (CRM-SA-C Sandy Soil C and Mixed Polish Herbs (INCT-MPH-2). Food and drug samples were digested in a closed microwave system using nitric acid and hydrogen peroxide. Therefore, all iron in the samples converted to iron(III) ion. These solutions were used directly in determination of iron(III) ion. No cleanup or enrichment of the solutions was required. The calibration graph was linear until 14.00 µg mL(-1). Detection limit and quantification limit were 1.29 µg mL(-1) and 3.88 µg mL(-1), respectively. The method provided accurate results for the majority of the food samples tested, including spanich, dill, mint, purslane, rocket, red lentils, dry beans and two iron medicinal tablets. Also, the high recovery (95.6 %) was obtained for a fortified stream water sample. The simple and cost-effective method is suitable for monitoring total iron concentration in foods and drug samples.

The electrochemical and spectroelectrochemical properties of metal free and metallophthalocyanines containing triazole/piperazine units.

The synthesis and characterization of novel peripherally tetra [1,2,4]-triazole substituted metal-free phthalocyanine and its metal complexes (Zn(II), Ni(II), Pb(II), Cu(II) and Fe(II)) and the investigation of electrochemical and spectroelectrochemical properties of metal-free, Zn(II), Pb(II), Fe(II) phthalocyanines were performed for the first time in this study. Electrochemical characterizations of the complexes were performed with voltammetric and in situ spectroelectrochemical measurements. Voltammetric responses of the complexes supported the proposed structures, since complexes bearing redox inactive Pc ring metal centers just gave Pc based electron transfer reactions, while iron phthalocyanine went to metal based electron transfer reaction in addition to the Pc based ones. Electron withdrawing nature of [1,2,4]-triazole substituents shifted the redox processes toward the positive potentials. All complexes were electropolymerized during the oxidation reactions in dichloromethane (DCM) solvent. Types of the metal center of the complexes altered the electropolymerization reactions of the complexes. Spectra and colors of the electrogenerated redox species of the complexes were also determined with in situ spectroelectrochemical and in situ electrocolorimetric measurements.

Electrochemical and spectroelectrochemical properties of thiadiazole substituted metallo-phthalocyanines.

4-Thiadiazole substituted phthalonitrile and peripherally tetra-substituted phthalocyanine Cu(II), Fe(II) and Ti(IV)O complexes have been synthesized for the first time. Electrochemical properties of these complexes were determined with voltammetric and in situ spectroelectrochemical measurements. CuPc has redox inactive Cu(2+) center, therefore it gave three Pc based reduction and two Pc based oxidation processes. TiOPc and FePc complexes gave metal based redox processes in addition to Pc based redox reactions due to the redox activity of Ti(4+)O and Fe(2+) metal centers. Although FePc also gave three reduction and two oxidation reactions, peak potentials of these processes are different than those of CuPc due to the different assignments of the redox reactions. TiOPc went to five reduction and one oxidation reactions. Assignments of the redox processes were carried out with in situ spectroelectrochemical measurements. Spectra and color of the electrogenerated redox species of the complexes were also determined with in situ spectroelectrochemical and in situ electrocolorimetric measurements. Distinct color differences between the electrogenerated redox species were observed, which indicated their possible electrochromic usages.

Amphiphilic zinc phthalocyanine photosensitizers: synthesis, photophysicochemical properties and in vitro studies for photodynamic therapy.

Peripherally and non-peripherally tetra-substituted zinc(ii) phthalocyanines bearing 2-(2-{2-[3-(dimethylamino)phenoxy]ethoxy}ethoxy)ethoxy and 2-(2-{2-[3-(diethylamino)phenoxy]ethoxy}ethoxy)ethoxy groups (, , and ) were synthesized by cyclotetramerization of the corresponding phthalonitriles (, , and ). Their quaternized ionic derivatives (, , and ) were also synthesized by the reaction of them with methyl iodide. The novel compounds were characterized by using standard spectroscopic techniques such as FT-IR, (1)H NMR, (13)C NMR, UV-vis, mass and elemental analyses. The obtained quaternized phthalocyanines (, , and ) showed amphiphilic behaviour with excellent solubility in both organic and aqueous solutions, which makes them potential photosensitizers for use in photodynamic therapy (PDT) of cancer. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and photodegradation quantum yields) properties of these novel phthalocyanines were studied in DMSO for both non-ionic and ionic quaternized derivatives. However, these properties were examined in both DMSO and phosphate buffer solution (PBS) for quaternized ionic phthalocyanines. The effects of the positions of substituents (peripheral or non-peripheral) and the quaternization of the nitrogen atoms on the substituents about their photophysical and photochemical properties were also compared in this study. The bovine serum albumin (BSA) binding behaviours of the studied quaternized ionic zinc(ii) phthalocyanines were also described in PBS solutions. The quaternized phthalocyanines (, , and ) successfully displayed light-dependent photodamage in HeLa and HuH-7 cancer cells in photodynamic therapy treatment. The photosensitivity and the intensity of damage were found directly related to the concentration of the photosensitizers.

The influence of the various central metals on photophysical and photochemical properties of benzothiazole-substituted phthalocyanines.

The photophysical (fluorescence quantum yields and lifetimes, fluorescence quenching studies by 1,4-benzoquinone (BQ)) and photochemical (singlet oxygen quantum yields and photodegradation studies under light irradiation) properties of tetra-benzothiazole substituted metal-free (H2Pc, 1), lead (II) (PbPc, 2) and zinc(II) (ZnPc, 3) phthalocyanine compounds were investigated in tetrahydrofuran (THF) solution. All of these compounds did not show any aggregation and they produced good singlet oxygen (especially ZnPc). The influence of the various central metal ions (zinc, lead or without metal) on the photophysical and photochemical parameters was also investigated and compared.

4-[2-(Cyclo-hexa-1,4-dien-1-yl)eth-oxy]benzene-1,2-dicarbonitrile.

In the title compound, C(16)H(14)N(2)O, the dihedral angle between the aromatic rings is 70.23 (6)°. The linking chain has a zigzag conformation. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯N hydrogen bonds, forming a zigzag chain along the c axis.

17,18-Dibromo-8-methyl-4,12-ditosyl-3,4,5,6,7,8,9,10,11,12,13,14-dodeca-hydro-2H-benzo[b][1,4,7,11,15]dioxatriaza-cyclo-hepta-decine.

In the title compound, C(31)H(39)Br(2)N(3)O(6)S(2), a 17-membered aza-macrocyclic ligand containing two ether O and three aza N atoms, the three pendant aromatic rings form an 'E' shape. The dihedral angles between the central benzene ring and the side ones are 17.8 (3) and 7.4 (3)°, and the dihedral angle between the tosyl rings is 10.6 (3)°. The methyl group is disordered over two orientations, with occupancies of 0.52 (15) and 0.48 (15).

Selective recognition of cobalt (II) ion by a new cryptand compound with N2O2S2 donor atom possessing 2-hydroxy-1-naphthylidene Schiff base moiety.

A new cryptand compound carrying 2-hydroxy-1-naphthylidene Schiff base moiety (3) was designed and synthesized by reaction of the corresponding macrobicyclic amine compound (1) and 2-hydroxy-1-naphthaldehyde (2). The influence of metal cations such as Mg2+, Ca2+, Sr2+, Fe2+,Co2+, Mn2+, Zn2+, Cd2+, Hg2+, Al3+ and Pb2+ on the spectroscopic properties of the new fluoroionophore was investigated in acetonitrile-dichloromethane solution (9.5/0.5) by means of absorption and emission spectrometry. The blue shifts on the fluorescence spectrum were observed for all metal cations at 504 nm. At the same time the fluorescence spectrum of the ligand showed quenching in the intensity of the signal at 504 nm for all metal cations except for Zn2+. Interaction of Co2+ with the ligand caused quenching of naphtyl fluorescence higher than 84%. The method showed good selectivity and sensitivity for Co2+ with respect to other metal cations with linear range and detection limit of 1.5 x 10(-7) to 3.3 x 10(-6) M and 4.8 x 10(-8) M respectively.

Synthesis and metal ion binding properties of thiaaza crown macrocycles.

Two new macrocyclic ligands (3) and (4), containing nitrogen-sulfur donor atoms, were designed and synthesized in a multi-step reaction sequence. The macrocycles (3) and (4) were used in solvent extraction of metal picrates such as Ag(+), Hg(2+), Cd(2+), Zn(2+), Cu(2+), Ni(2+), Mn(2+), Co(2+), and Pb(2+) from aqueous phase to the organic phase. The metal picrate extractions were investigated at 25+/-0.1 degrees C by using UV-visible spectrometry. The extractability and selectivity of the mentioned metal picrates were evaluated according to the organic solvents. The values of the extraction constants (logK(ex)) and the complex compositions were determined for the extracted complexes.