Design and Synthesis of New Porphyrin Analogues as Potent Photosensitizers for Photodynamic Therapy: Spectroscopic Approach.

New porphyrin analogues have been designed and synthesized using pyrrole, various aldehydes and propionic acid. The formation of desired compounds was analyzed by utilizing the spectral analysis such as IR, NMR and Mass spectroscopy. The studies on absorption and fluorescence emission of synthesized porphyrins were used to evaluate photophysical characteristics such as molar excitation coefficient and Stokes shift. The estimated values of fluorescence lifetime and fluorescence quantum yield of synthesized porphyrins were found to be variable due to the presence of change in the electron donating and withdrawing characters. The efficiency of generation of singlet oxygen by each synthesized porphyrin as photosensitizer was measured in terms of singlet oxygen quantum yield through photooxidation of 9,10-dimethylantharacene. The obtained singlet oxygen quantum yield values were found to be higher in case of porphyrins those have more electron withdrawing characters rather than donating characters as compared to reference 5,10,15,20-tetraphenylporphyrin (H2TPP). The singlet oxygen quantum yield values of synthesized porphyrins varied from 0.52 to 0.66. Pleasingly, some of synthesized porphyrins are found to be photostable and competent to discover as PDT agents as compared to reference H2TPP.

Synthesis and biological evaluation of 1,2,4-triazolidine-3-thiones as potent acetylcholinesterase inhibitors: in vitro and in silico analysis through kinetics, chemoinformatics and computational approaches.

We have designed and synthesized a novel acidic ionic liquid and explored its catalytic efficiency for the synthesis of 1,2,4-triazolidine-3-thione derivatives. A simple reaction between aldehydes and thiosemicarbazide for short time in 60:40 v/v water/ethanol at room temperature offers target 1,2,4-triazolidine-3-thione derivatives. The formation of target compounds is confirmed by NMR, IR and ESI-MS analysis. Pleasingly, synthesized compounds show noteworthy acetylcholinesterase (AChE) inhibitory activity with much lower IC50 values 0.0269 ± 0.0021-1.1725 ± 0.0112 µM than standard Neostigmine methylsulphate. In addition, synthesized 1,2,4-triazolidine-3-thiones exhibits significant free radical scavenging activity as compared to standard vitamin C. The studies on validation of Lipinski's rule through chemoinformatics properties and molecular docking analysis are in support of in vitro analysis. Therefore, overall present study illustrates synthesis of some new 1,2,4-triazolidines-3-thiones which can serve as a template for drug designing such as AChE inhibitors. Herein, we proposed ionic liquid-catalyzed ease of synthetic approach for medicinally important 1,2,4-triazolidine-3-thiones and their bio-evaluations.

NHC-copper-thiophene-2-carboxylate complex for the hydroboration of terminal alkynes.

An air-stable N-heterocyclic carbene-copper thiophene-2-carboxylate (CuTC) complex has been prepared for the stereoselective hydroboration of terminal alkynes using pinacolborane (HBpin) or 1,8-naphthalenediaminatoborane (HBdan). The newly synthesized complex can be directly activated by hydroboranes without a cocatalyst such as a base, and exhibits high reactivity for the hydroboration of alkynes under mild conditions. A gram-scale hydroboration of terminal phenylacetylene demonstrated the applicability of the copper complex for the preparation of alkenyl boronates.

Facile Synthesis, Crystal Structure, DFT Calculation and Biological Activities of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazol-5 (4H)-one (5).

BACKGROUND: In the past few decades, design, synthesis, and characterization of novel heterocyclic compounds with auspicious biological profile received the considerable attention of the scientific community. Among them, the small and simple organic molecular backbone like triazole moiety have a broad spectrum of applications in the medicinal as well as diagnostic areas. OBJECTIVE: The objective of present study was synthesis, characterization, and exploration of biological profile of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazole-5(4H)-one (5). The tautomeric interconversion of the molecule was observed by the single crystal XRD and DFT analysis. METHODS: N-(2-fluorophenyl)-2-[2-(3-methoxyphenyl)acetyl]hydrazine carboxamide (4) was synthesized by the condensation of 2-(3-methoxyphenyl)acetohydrazide (3) with 1-fluoro-2- isocyanatobenzene. The dehydrocyclization of compound (4) yielded target compound (5) by refluxing in 2 N aqueous sodium hydroxide solutions. The target molecule was characterized by FTIR, 1H NMR, 13C NMR, single crystal X-ray diffraction analysis and DFT calculation. The enzymatic assay measurements were carried out by using a microplate reader (OPTI Max, Tunable Microplate Reader; Wavelength range: 340-850 nm; for 96-well plates) while DFT calculation was performed by Gaussian 09 package. RESULTS: The XRD result and DFT calculations showed that molecule 5 predominantly exists in thione conformation and crystallized in the triclinic system of P-1 space group. Furthermore, for the practical applicability of synthesized compound 5, the in vitro acetylcholinesterase as well as α-glucosidase inhibition activities were performed and found moderate enzyme inhibition potential comparable with that of reference inhibitors. CONCLUSION: This study might be helpful for future design and development of potent enzyme inhibitor to control Alzheimer's as well as diabetic disease. The DFT and single crystal XRD analysis data might be helpful for understanding the mechanism of drug binding and its mode of action.

The determination of polycyclic aromatic hydrocarbons in human urine by high-resolution gas chromatography-mass spectrometry.

Polycyclic aromatic hydrocarbons (PAHs), organic compounds formed by at least two condensed aromatic rings, are ubiquitous environmental pollutants that are produced by incomplete combustion of organic materials. PAHs have been classified as carcinogenIC to humans by the International Agency for Research on Cancer, because they can bind to DNA, causing mutations. Therefore, the levels of PAHs in human urine can be used as an indicator for potential carcinogenesis and cell mutation. An analytical method was developed for the accurate measurement of PAHs in urine using high-resolution gas chromatography-mass spectrometry. Urine samples were extracted by an Oasis HLB extraction cartridge after enzymatic hydrolysis with a ß-glucuronidase/arylsulfatase cocktail. The 18 PAHs were separated using an Agilent DB-5 MS capillary column (30 m × 0.25 mm, 0.25 µm) and monitored by time-of-flight mass spectrometry. Under the optimized method, the linearity of calibration curves was >0.994. The limits of detection at a signal-to-noise ratio of 3 were 10-100 ng/L. The coefficients of variation were in the range of 0.4-9.0%. The present method was highly accurate for simultaneous determination of 18 PAHs in human urine and could be applied to monitoring and biomedical investigations to check exposure of PAHs.

Simultaneous determination of bisphenol A and estrogens in hair samples by liquid chromatography-electrospray tandem mass spectrometry.

Bisphenol A (BPA), an endocrine disrupter, is widely used to make chemicals for polycarbonate, plastics, beverage containers, epoxy resins, and cash register receipts. BPA is one of the known xenoestrogens, which have weak estrogenic activity and cause obesity, diabetes, breast cancer, and reproductive disorders. Even though the concentration level of metabolomes in hair is usually lower than that in urine and blood, there are several reasons why we chose to use hair samples. First, the sampling procedure of hairs is simple. Second, it is also easy to preserve the sample for long term and track the drug-exposure record of a given sample. Third, deformation and contamination of samples rarely occur. In this study, an improved analytical method to determine the levels of BPA and estrogens in hair samples was developed by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI/MS/MS). Hair samples were extracted by an Oasis HLB extraction cartridge after incubation with 1N HCl and derivatized with dansyl chloride to increase sensitivity. BPA and estrogens (estrone, 17ß-estradiol, and estriol) were separated using Shiseido CAPCELL PAK C18 column (2.0×100mm, 3µm) and a mobile phase consisting of 10mM ammonium acetate in water and acetonitrile with a gradient program at a flow rate of 0.3mL/min and were monitored with electrospray tandem mass spectrometry (ESI-MS/MS). The linearity of this method was over 0.995. The limits of detection (LOD) at a signal-to-noise (S/N) ratio of 3 were 0.25-6.0ng/g. The alteration of estrogens levels induced by BPA may play important role to understanding probable endocrine disruptive exposure, and the described methods could be used to evaluate and monitor exposure of endocrine disruptor.

Simultaneous determination of volatile organic compounds with a wide range of polarities in urine by headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry.

RATIONALE: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that have a high vapor pressure at room temperature. Some VOCs have been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC), because they can bind to DNA and cause cell mutations. Therefore, monitoring of VOCs in human urine is very important to evaluate the correlation between exposure to VOCs and human disease. METHODS: We have developed an improved analytical method for the simultaneous determination of VOCs with a wide range of polarities in human urine samples by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography/mass spectrometry (GC/MS). In the improved method, a bi-polar carboxen-polydimethylsiloxane (CAR/PDMS) fiber was used for the optimized extraction of 15 VOCs with a wide range of polarities, including benzene, toluene, ethylbenzene, xylenes (BTEX), alkylbenzenes, cresols, and naphthalene, in human urine samples. Extracted VOCs from the human urine were effectively separated by GC using a mid-polarity column (DB-35, 35% phenylmethylpolysiloxane) and monitored by MS using extracted ion monitoring (EIM) mode. RESULTS: Under the optimized method, the linearity of the calibration curves was greater than 0.993. The limits of detection (LODs) at a signal-to-noise (S/N) ratio of 3 were 0.3-0.6 ng/mL. The coefficients of variation were in the range of 0.1-9.7% for within-day variation and 0.2-14.2% for day-to-day variation. CONCLUSIONS: The method was shown to be rapid and simple for the simultaneous determination of VOCs with a wide range of polarities in human urine and it could be applied to monitoring and to biomedical investigations to check exposure to VOCs. Copyright © 2017 John Wiley & Sons, Ltd.

2-[(1H-Pyrrol-2-yl)meth-yl]-1H-pyrrole.

In the title compound, C9H10N2, the two pyrrole ring planes are twisted by a dihedral angle of 69.07 (16)° and the C-C-C methane angle is 115.1 (2)°. In the crystal, mol-ecules are connected into layers in the bc plane by N-H⋯π inter-actions.

[5-Hydroxy-3-phenyl-1-(pyridin-2-yl)pyrazol-5-olato]diphenylboron.

In the title compound, C(26)H(20)BN(3)O, the B atom has tetra-hedral geometry and is linked to two phenyl rings, the O atom of the hy-droxy-pyrazole ring and the N atom of the pyridinyl ring. A six-membered BOCNCN ring forms by coordination of the B atom and the pyridinyl N atom. The BOCNCN ring has an envelope conformation [dihedral angle = 36.7 (1)° between the planar ring atoms and the flap] with the B atom out of the plane. In the 1-(2-pyridin-yl)-3-phenyl-5-hy-droxy-pyrazole group, the pyridinyl ring, the phenyl ring and the pyrazole ring are almost coplanar: the pyrazole ring makes a dihedral angle of 9.56 (8)° with the pyridinyl ring and 17.68 (7)° with the phenyl ring. The crystal structure is stabilized by π-π stacking inter-actions involving the pyridinyl and pyrazole rings of centrosymmetrically related mol-ecules, with ring centroid separations of 3.54 (5) Å.

Methyl 9-diethyl-amino-2,2-bis-(4-meth-oxy-phen-yl)-2H-benzo[h]chromene-5-carboxyl-ate.

In the title compound, C(31)H(29)NO(5), the methyl carboxyl-ate and dimethyl-amino groups on the naphtho-pyran group are almost coplanar with the naphtho-pyran ring system [r.m.s. deviations = 0.08 (2) and 0.161 (2) Å, respectively]. The dihedral angle between the methyl carboxyl-ate and dimethyl-amino groups is 4.9 (1)°. The pyran ring has an envelope conformation with the quaternary C atom out of plane by 0.4739 (13) Å. The meth-oxy-phenyl substituent forms a dihedral angle of 16.6 (1)° with the plane of the benzene ring, while the other meth-oxy-phenyl group is almost coplanar, making a dihedral angle of 1.4 (1)°.

(S)-[5-Methyl-3-(3-methyl-thio-phen-2-yl)-4,5-dihydro-isoxazol-5-yl]methanol.

In the title compound, C(10)H(13)NO(2)S, the thio-phene and isoxazoline rings are almost coplanar, the dihedral angle between their least-squares planes being 2.08 (1)°. The O-H atoms of the methyl hy-droxy group and the N atom of the isoxazole ring are orientated in the same direction to allow for the formation of inter-molecular O-H⋯N hydrogen bonds that lead to a supra-molecular chain along the a axis.

N,N-Diethyl-4-[9-meth-oxy-6-(4-methoxy-phen-yl)-5-methyl-2-phenyl-2H-benzo[h]chromen-2-yl]aniline.

In the title compound, C(38)H(37)NO(3), the pyran ring has an envelope conformation with the quaternary C(q) atom as the flap atom. The dihedral angle formed between the meth-oxy-phenyl group and the naphthalene ring system is 67.32 (6)°. The ethyl-amino groups lie to the same side of the plane through the phenyl ring and form dihedral angles of 84.6 (3) and 75.8 (2)° with it.

Bis(2-amino-1,3-thia-zole-κN)diazido-zinc.

In the title complex, [Zn(N(3))(2)(C(3)H(4)N(2)S)(2)], the Zn(II) atom is tetra-hedrally coordinated by two terminal azide ligands and by the ring N atoms of two different 2-amino-thia-zole ligands. Intra-molecular N-H⋯N hydrogen bonds between the amino groups of both 2-amino-thia-zole ligands and the N atom of one of the azide ligands ensure that the heterocyclic rings are oriented in the same direction. Inter-molecular N-H⋯N hydrogen bonds link the mol-ecules into zigzag sheets in the ac plane.

Methyl 6-dimethyl-amino-4-hy-droxy-2-naphtho-ate.

In the title compound, C(14)H(15)NO(3), the ester group is oriented so that the carbonyl group points in the opposite direction to the hy-droxy group. The mol-ecule as a whole is almost planar (the r.m.s. deviation of the non-H atoms is 0.0268 Å). In the crystal, mol-ecules are linked by inter-molecular O-H⋯O hydrogen bonds into infinite chains that propagate parallel to the c axis.

Bis(2-amino-benzothia-zole-κN)bis-(thio-cyanato-κN)zinc(II).

The Zn(II) ion in the title complex, [Zn(NCS)(2)(C(7)H(6)N(2)S)(2)], is tetra-hedrally coordinated within an N(4) donor set defined by two N atoms of two terminal isothio-cyanate ligands and by two heterocyclic N atoms of two different 2-amino-benzothia-zole ligands. This arrangement is stabilized by intra-molecular N-H⋯N hydrogen bonds. In the crystal structure, mol-ecules are linked through N-H⋯S hydrogen bonds to form a two-dimensional array.

Tetra-kis(2-amino-thia-zole-κN)dichloridocadmium(II).

In the title complex, [CdCl(2)(C(3)H(4)N(2)S)(4)],the Cd(II) atom has an trans-Cl(2)N(4) octa-hedral coordination geometry defined by four N atoms derived from the four 2-amino-thia-zole ligands and two Cl atoms. The amino groups participate in intra- and inter-molecular N-H⋯N and N-H⋯Cl hydrogen bonding that stabilizes both the mol-ecular and crystal structures.

(7-Dimethylamino-1-hydroxy-3-naphthyl)(morpholino)methanone.

In the title compound, C(17)H(20)N(2)O(3), the morpholine ring is in a slightly distorted chair form. The crystal structure is stabilized by an inter-molecular O-H⋯O hydrogen bond between the H atom of the hydroxyl group and the O atom of a neighbouring carbonyl group. A weak inter-molecular C-H⋯π inter-action is also present.

Tetraaqua-1kappaO,2kappa3O-(mu-2,4-dinitrophenolato-1kappa2O1,O2:2kappaO1)(2,4-dinitrophenolato-1kappa2O1,O2)dilithium(I): a dinuclear lithium(I) complex.

The title complex, [Li2(C(6)H(3)N(2)O(5))2(H2O)4], contains two kinds of Li atoms, viz. five-coordinated and four-coordinated. The five-coordinated Li ion has a tetragonal-pyramidal geometry, with a water molecule in the apical position and four O atoms from two 2,4-dinitrophenolate (2,4-DNP) ligands in the basal plane. The four-coordinated Li ion has a tetrahedral geometry, with three water molecules and one phenolate O atom of a 2,4-DNP ligand. The Li ions are bridged by a phenolate O atom, giving the complex a dinuclear structure. The crystal packing is stabilized by O-H...O hydrogen-bonding interactions involving the water molecules and nitro O atoms.

A one-dimensional coordination polymer with metal-metal interactions: catena-poly[[triaquabarium(II)]-mu-aqua-kappa2O:O-di-mu-thiosalicylato-kappa4O:O].

In the title compound, [Ba(C(7)H(5)O(2)S)(2)(H(2)O)(4)](n), the Ba(II) atom lies on a mirror plane and is nine-coordinated by four bridging carboxylate O atoms of the thiosalicylate ligands, two bridging water molecules and three terminal water molecules. There is an intramolecular S-H.O hydrogen bond between the S and O atoms in the thiosalicylate ligand. A one-dimensional coordination polymer is formed via weak metal-metal interactions along polymeric zigzag chains.

Diaquabis(1,3-propanediamine-kappa(2)N,N')nickel(II) bis(sulfanilate).

The title compound, [Ni(C(3)H(10)N(2))(2)(H(2)O)(2)](C(6)H(6)NO(3)S)(2), contains alternating layers of sulfanilate anions and diaquabis(1,3-propanediamine)nickel(II) cations. The Ni atom lies on an inversion centre and is hexacoordinated by the 1,3-propanediamine ligands, which function as N,N'-bidentate ligands, and the water molecules, which are in a trans arrangement. The sulfanilate anions are arranged in layers, with the sulfonate and amine groups directed towards opposite sides of the layer. The structure is stabilized by a network of hydrogen bonding between the O and N atoms of the sulfanilate anions, the water molecules, and the N atoms of the 1,3-propanediamine ligands.