The dual inhibition against the activity and expression of tyrosine phosphatase PRL-3 from a rhodanine derivative.

Increasing evidences demonstrated that PRL-3 was associated with metastatic potential in a variety of cancers including CRC, gastric cancer, ovarian cancer and so on. PRL-3 knock down inhibited the development of metastasis by reducing the size of primary tumors and inhibiting the invasion and growth of cancer cells. Therefore, PRL-3 is a promising diagnostic marker and therapeutic target in tumors. So far, only several PRL-3 inhibitors have been reported. In this study, six rhodanine derivatives were synthesized and characterized. The compounds were evaluated against tyrosine phosphatase PRL-3. Among these compounds, 5-(5-chloro-2-(trifluoromethyl)benzylidene)-2-thioxothiazolidin-4-one (4) could effectively inhibit PRL-3 with IC50 value of 15.22 µM. Fluorescent assays suggested compound 4 tightly bound to tyrosine phosphatase PRL-3 with the molar ratio of 1:1, and the binding constant of 1.74 × 106 M-1. Compound 4 entered into SW-480 cells, selectively inhibited the expression of PRL-3 and increased the phosphorylation of PRL-3 substrates, and decreased the survival rate of SW-480 cells with IC50 of 6.64 µM and induced apoptosis. The results revealed that compound 4 is a dual functional inhibitor against the activity and expression of PRL-3 and a promising anti-cancer candidate targeting PRL-3.

4-Bromo-2-[(phenyl-imino)-meth-yl]phenol.

The title compound, C13H10BrNO, is essentially planar (r.m.s. deviation = 0.026 Å) and the dihedral angle between the planes of the two aryl rings is 1.5 (3)°. An intra-molecular O-H⋯N hydrogen bond generates an S(6) ring.

4-[(5-Chloro-2-hy-droxy-benzyl-idene)amino]-3-ethyl-1H-1,2,4-triazole-5(4H)-thione.

The title compound, C11H11ClN4OS, crystallizes with two mol-ecules, A and B, in the asymmetric unit in which the dihedral angles between the triazole and benzene rings are 54.6 (3) and 56.0 (3)°. Both mol-ecules feature an intra-molecular O-H⋯N hydrogen bond, which generates an S(6) ring. In the crystal, A-B dimers are linked by pairs of weak C-H⋯S hydrogen bonds along with π-π stacking inter-actions between the triazole rings [centroid-centroid separations = 3.631 (3) and 3.981 (4)Å]. N-H⋯S hydrogen bonds link the dimers into [100] chains, which feature R 2 (2)(8) loops.

2-[(E)-(4-Bromo-phenyl)imino-methyl]-4-chloro-phenol.

In the title compound, C13H9BrClNO, the dihedral angle between the substituted benzene rings is 44.25 (11)°. There are strong intra-molecular O-H⋯N hydrogen bonds, which generate S(6) rings, and also inter-molecular Cl⋯Cl [3.431 (3) Å] and Br⋯ Br [3.846 (1) Å] contacts. The crystal packing a C-H⋯O and C-H⋯π inter-actions.

Crystal structure of diethyl [(4-nitro-phenyl-amino)(2-hy-droxy-phen-yl)meth-yl]phospho-nate methanol monosolvate.

In the title compound, C17H21N2O6P·CH3OH, the planes of the 4-nitro-aniline and 2-hy-droxy-phenyl groups form a dihedral angle of 84.04 (8)°. The P atom exhibits tetra-hedral geometry involving two O-ethyl groups, a Cα atom and a double-bonded O atom. In the crystal, O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds link the α-amino-phospho-nic acid and methanol mol-ecules into chains that propagate parallel to the a axis.

4-[(5-Bromo-2-hy-droxy-benzyl-idene)amino]-3-ethyl-1H-1,2,4-triazole-5(4H)-thione.

The title compound, C11H11BrN4OS, crystallized as a racemic twin with two symmetry-independent mol-ecules in the asymmetric unit. The dihedral angles between the benzene and triazole rings of the two independent mol-ecules are 56.41 (18) and 54.48 (18)°. An intra-molecular O-H⋯N hydrogen bond occurs in each mol-ecule. In the crystal, pairs of symmetry-independent mol-ecules are linked by pairs of almost linear N-H⋯S hydrogen bonds, forming cyclic dimers characterized by an R 2 (2)(8) motif. There are weak π-π inter-actions between the benzene rings of symmetry-independent mol-ecules, with a centroid-centroid distance of 3.874 (3) Å.

Analogy to a Chinese knot in an ion-pair copper(II)-neodymium(III) complex based on a hexadentate Schiff base condensation product of 5-bromosalicylaldehyde and glycylglycine.

Self-assembly of CuCl2, NdCl3, 5-bromosalicylaldehyde and glycylglycine yields the ion-pair copper(II)-neodymium(III) complex, poly[[decaaquabis[µ3-2-({2-[(5-bromo-2-oxidobenzylidene)amino]acetyl}azanidyl)acetato]bis[µ2-2-({2-[(5-bromo-2-oxidobenzylidene)amino]acetyl}azanidyl)acetato]tetracopper(II)dineodymium(III)] bis{[2-({2-[(5-bromo-2-oxidobenzylidene)amino]acetyl}azanidyl)acetato]cuprate(II)} tetradecahydrate], {[Cu4Nd2(C11H8BrN2O4)4(H2O)10][Cu(C11H8BrN2O4)]2·14H2O}n. The anion is planar and mononuclear, showing an approximately square-planar coordination of the metal atom, while the cation is a hexanuclear centrosymmetric transition metal-lanthanide (Cu-Nd) heterometallic complex, with the independent copper cations in square-planar and square-pyramidal coordinations. The asymmetric unit comprises one half of this cation, one anion and seven solvent water molecules. The positions of the six metal centres in the cation reproduce a Chinese knot arrangement. The dipeptidic Schiff base releases three H atoms and can act as a tetradentate, a pentadentate or a hexadentate ligand. Longer interactions between the pentadentate ligands and the Jahn-Teller Cu(II) cation link the hexanuclear aggregates into cationic chains in the [010] direction in which 14- and 22-membered subloops occur. Extensive hydrogen bonding in three dimensions involves both the coordinated and the solvent water molecules.

Exploration of biguanido-oxovanadium complexes as potent and selective inhibitors of protein tyrosine phosphatases.

The inhibitory effects of three biguanido-oxovanadium complexes ([VO(L(1-3))(2)]·nH(2)O: HL(1) = metformin, HL(2) = phenformin, HL(3) = moroxydine) against four protein tyrosine phosphatases (PTPs) and an alkaline phosphatase (ALP) were investigated. The complexes display strong inhibition against PTP1B and TCPTP (IC(50), 80-160 nM), a bit weaker inhibition against HePTP (IC(50), 190-410 nM) and SHP-1(IC(50), 0.8-3.3 µM) and much weaker inhibition against ALP (IC(50), 17-35 µM). Complex 3 is about twofold less potent against PTP1B, TCPTP and HePTP than complexes 1 and 2, while complex 2 inhibits SHP-1 more strongly (about three to fourfold) than the other two complexes. These results suggest that the structures of the ligands slightly influence the potency and selectivity against PTPs. The complexes inhibit PTP1B and ALP with a typical competitive type.

2,2',2'',2'''-(1,4-Phenyl-enedinitrilo)-tetra-acetic acid dihydrate.

In the title compound, C(14)H(16)N(2)O(8)·2H(2)O, the complete organic molecule is generated by crystallographic inversion symmetry. The dihedral angles between the aniline ring and the acetic acid groups are almost identical, viz. 82.61 (7) and 80.33 (7)°. In the crystal, O-H⋯O hydrogen bonds link the organic mol-ecules and water mol-ecules, forming zigzag chains the c axis. An intra-molecular O-H⋯O hydrogen bond is also observed.

4-[(5-Bromo-2-hy-droxy-benzyl-idene)amino]-3-propyl-1H-1,2,4-triazole-5(4H)-thione.

The asymmetric unit of the title compound, C(12)H(13)BrN(4)OS, contains two independent mol-ecules in which the dihedral angles between the triazole and benzene rings are 2.9 (3) and 7.5 (3)°. The thione group is of the form R(2)C=S. An intra-molecular O-H⋯N hydrogen bond occurs in each mol-ecule. The crystal structure features weak N-H⋯S inter-actions and π-π stacking of the benzene rings [centroid-centroid distance = 3.667 (3) Å].

Seven Ln(III) coordination polymers with two kinds of geometric coordination but the same 3D topological property: luminescence sensing and magnetic property.

Two series of seven lanthanide metal coordination polymers (Ln-CPs) formulated as {[Ln(dttpa)1.5(H2O)2]·H2O}n [Ln = La3+ (1), Ce3+ (2), Nd3+ (3), Sm3+ (4) and Eu3+ (5)] and {[Ln (dttpa)1.5(H2O)]·xH2O}n [Ln = Tb3+ (6) and Er3+ (7), x = 0.75] have been successfully constructed using Ln3+ ions and 2,5-di(1H-1,2,4-triazol-1-yl)terephthalic acid (H2dttpa) via a hydrothermal method. Their 3D structures are fully characterised by Fourier transform infrared (FT-IR) spectroscopy, X-ray single-crystal analyses, powder diffraction analyses (PXRD), elemental analyses (EAs) and thermogravimetric analyses (TGAs). All Ln-CPs display the same topological property with the point symbol of {42·84}{44·62}2{49·66}2, and crystallize in the triclinic space group P1̄. Interestingly, Eu-CP (5) effectively sensitizes the visible emission of Tb3+ and shows high selectivity and stable response with the lowest detection limit of 9.88 nM. Furthermore, Tb-CP (6) acts as a good luminescence sensor to detect nitrobenzene (NB) with a detection limit of 12.5 nM. In addition, the magnetic susceptibility measurement for Er-CP (7) further shows that compounds constructed by dttpa2- are a kind of promising functional material.

Structure, magnetic properties and spin density of two alternative Mn(II) coordination polymers based on 1,4-bis(2'-carboxyphenoxy)benzene.

Two novel manganese coordination polymers [Mn2(µ2-bcpb)(µ4-bcpb)(2,2'-bipy)2]n (1) and [Mn2(µ3-bcpb)2(2,2'-bipy)2(H2O)]n (2) (H2bcpb = 1,4-bis(2'-carboxylato phenoxy)-benzene; 2,2'-bipy = 2,2'-bipyridine), have been synthesized successfully from the same reactants. This unusual selectivity was corroborated by X-ray powder diffraction. Single crystal X-ray diffraction analysis of complex 1 reveals that neighboring Mn(II) ions are linked via two bcpb2- anions to form a dinuclear Mn(II) subunit [Mn2(µ1,1-COO)2]2+ with a Mn⋯Mn distance of 3.3758 (6) Å. And π⋯π interactions between aromatic rings of the bcpb2- and 2,2'-bipy ligands stabilize the two-dimensional extended coordination network with the unprecedented Schläfli symbols {4·62}2{42·62·82}. In the [Mn2(µ1,3-COO)2]2+ subunit of 2, two linking bcpb2- ligands subtend an interaction distance of 4.4048(6) Å. Intermolecular O-H⋯O hydrogen bonds involving oxygen atoms of carboxylic acid and coordinated water molecules connect adjacent 1D chain molecules into a 2D network. Experimental temperature-dependent magnetic susceptibility measurements and spin density analyses by DFT disclose that compounds 1 and 2 display different magnetic properties.

Potent inhibition of protein tyrosine phosphatases by copper complexes with multi-benzimidazole derivatives.

A series of copper complexes with multi-benzimidazole derivatives, including mono- and di-nuclear, were synthesized and characterized by Fourier transform IR spectroscopy, UV-Vis spectroscopy, elemental analysis, electrospray ionization mass spectrometry. The speciation of Cu/NTB in aqueous solution was investigated by potentiometric pH titrations. Their inhibitory effects against human protein tyrosine phosphatase 1B (PTP1B), T-cell protein tyrosine phosphatase (TCPTP), megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2), srchomology phosphatase 1 (SHP-1) and srchomology phosphatase 2 (SHP-2) were evaluated in vitro. The five copper complexes exhibit potent inhibition against PTP1B, TCPTP and PTP-MEG2 with almost same inhibitory effects with IC(50) at submicro molar level and about tenfold weaker inhibition versus SHP-1, but almost no inhibition against SHP-2. Kinetic analysis indicates that they are reversible competitive inhibitors of PTP1B. Fluorescence study on the interaction between PTP1B and complex 2 or 4 suggests that the complexes bind to PTP1B with the formation of a 1:1 complex. The binding constant are about 1.14 × 10(6) and 1.87 × 10(6) M(-1) at 310 K for 2 and 4, respectively.

2-(4-Methyl-phen-yl)-1H-imidazo[4,5-f][1,10]phenanthroline.

In the title compound, C(20)H(14)N(4), all the non-H atoms are roughly coplanar with an r.m.s. deviation of 0.0776 Å. In the crystal, mol-ecules are linked by N-H⋯N hydrogen bonds, forming chains along the ([Formula: see text]). The chains are connected by inter-molecular C-H⋯N hydrogen bonds and π-π stacking inter-actions between inversion-related phenanthroline, imidazole and phenyl rings with centroid-centroid distances in the range 3.777 (1)-3.905 (1) Å.

Design and synthesis of three new copper coordination polymers: efficient degradation of an organic dye at alkaline pH.

Three new coordination polymers (CPs) based on Cu(II), namely {[Cu6(H2L)4(4,4'-bpy)6(H2O)2]·16H2O}n(1), {[Cu(H3L)(1,4-bib)]·3H2O}n(2), and {[Cu2(H2L)2(1,4-bib)2][Cu(1,4-bib)(H2O)2]}n·4nH2O(3) (H5L = 6-(3',4'-dicarboxyphenoxy)-2,3,5-benzene tricarboxylic acid, 4,4'-bpy = 4,4'-bipyridine and 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene) were synthesized under hydrothermal conditions and characterized. 1 adopts a three-dimensional structure and can be described with the point symbol {4·52}2{42·54·64·83·92}{5·104·12} whereas 2 shows a layered structure. 3 can be perceived as a complex salt of two coordination polymers: the cationic component [Cu(1,4-bib)(H2O)2]n2+ (3a) represents a chain polymer and the second anionic moiety [Cu2(H2L)2(1,4-bib)2]n2- (3b) corresponds to a 2D sub-structure. In the presence of H2O2, all complexes 1-3 act as efficient photocatalysts for the degradation of the dye methylene blue (MB). The effects of properties such as initial MB concentration, catalyst dosage, pH value, and H2O2 concentration on MB degradation were also investigated and analyzed in detail. Compounds 1-3 exhibit excellent structural stability during the catalytic process and can be reused at least three times. The hydroxyl radical (OH˙) and holes (h+) were confirmed as the main active species in the degradation process.

Analysis of the Oxygen Passivation Effects on MAPbI3 and MAPbBr3 in Fresh and Aged Solar Cells by the Transient Photovoltage Technique.

Previous studies have revealed that for some perovskite compositions, power conversion efficiencies (PCEs) improved after storing the devices in different ambient conditions. With the aim of better understanding such improvements, we focus our attention on the carrier/ionic dynamic kinetics of fresh and aged PSCs with different perovskite compositions (MAPbI3 and MAPbBr3 ) and using spiro-OMeTAD as HTM. For that, we use transient photovoltage (TPV), a technique used to analyse the different recombination kinetics at equilibrium and at different illumination times. We observe that the aging treatment causes significant changes on the kinetics behaviour for bromide-based devices, resulting in a positive influence on the cell performance (from 3.5 % to 6.1 % PCE, in reverse scan). However, the kinetics for those iodide-based perovskite solar cells remains unchangeable (from 16.3 % to 15.0 % PCE, in reverse scan).

Syntheses, crystal structures, and biological evaluations of new dinuclear platinum(ii) complexes with 1,2,4-triazole derivatives as bridging ligands.

A series of new dinuclear platinum(ii) complexes with the general formula [Pt2(µ-HL)4] (1-4), where H2L is 4-[(5-chloro-2-hydroxy-benzylidene)-amino]-3-R-1,2,4-triazole-5-thione: R = H (1), methyl (2), ethyl (3) and propyl (4), were synthesized and characterized. The X-ray crystal structures of 2, 3 and 4 reveal that the two platinum atoms form a paddlewheel core with four chelating triazole ligands as bridges, revealing a radically different structure than those of the traditional anticancer platinum(ii) complexes. These complexes show higher in vitro antiproliferative activity against human liver hepatocellular carcinoma (HepG2) and human breast adenocarcinoma (MCF7) than human lung cancer (A549) and human normal hepatocyte (HL-7702) cell lines. In particular, 3 exhibits antiproliferative activity (IC50 = 5.5 µM) against HepG2 cells comparable to that of cisplatin. Different from the traditional anticancer platinum(ii) complexes with high DNA affinity, 3 binds very weakly to DNA. Upon comparison, it exhibits potent inhibiting activity against protein tyrosine phosphatases 1B (PTP1B, IC50 = 16 µM) through possible binding to its active sites and its binding constant is 5.28 × 104 M-1. The results suggest that the antiproliferative mechanism of 3 against HepG2 cells may be different from that of cisplatin.

Inhibition protein tyrosine phosphatases by an oxovanadium glutamate complex, Na2[VO(Glu)2(CH3OH)](Glu = glutamate).

The insulin-sensitizing effect of vanadium complexes has been linked to their ability to inhibit protein tyrosine phosphatases (PTPs). Considering that vanadium complexes may exchange in vivo with amino acids, forming in situ vanadium-amino acid complexes, we have synthesized and characterized an oxovanadium glutamate complex, Na(2)[V(IV)O(Glu)(2)(CH(3)OH)]H(2)O (1·H(2)O). The complex showed potent inhibition against four human PTPs (PTP1B, TCPTP, HePTP, and SHP-1) with IC(50) in the 0.21-0.37 µM ranges. Fluorescence titration studies suggest that the complex binds to PTP1B with the formation of a 2:1 complex. Enzyme kinetics analysis using Lineweaver-Burk plots indicates a typical competitive inhibition mode.

Benzoic acid-2,2'-biimidazole (2/1).

In the title compound, C(6)H(6)N(4)·2C(7)H(6)O(2), the asymmetric unit contains a half-mol-ecule of biimidazole and one benzoic acid mol-ecule. The unit cell contains two biimidazole mol-ecules and four benzoic acid mol-ecules, giving the reported 2:1 ratio of benzoic acid to biimidazole. The biimidazole mol-ecule is located on an inversion center (passing through the central C-C bond). Strong N-H⋯O and O-H⋯N hydrogen bonds link the benzoic acid mol-ecules with the neutral biimidazole mol-ecules, which lie in planar sheets. In the crystal packing, the parallel sheets are related by a twofold rotation axis and an inversion centre, respectively, forming an inter-woven three-dimensional network via weak C=O⋯π inter-molecular inter-actions between neighboring mol-ecules.

Tris[2-(1H-imidazol-2-yl)imidazol-1-ido]cobalt(III).

In the title compound, [Co(C(6)H(5)N(4))(3)], the Co(III) atom adopts a distorted octa-hedral CoN(6) coordination geometry, arising from three N,N'-bidentate deprotonated 2,2'-biimidazole ligands. The dihedral angles between the five-membered rings of the ligands are 4.1 (2), 9.4 (2) and 10.5 (2)°. In the crystal, mol-ecules are linked by N-H⋯N hydrogen bonds, generating a layered network lying in (11).