Intramolecular energy transfer and its influence on the overall quantum yields of Eu and Tb chelates with dimethyl(phenylsulfonyl)amidophosphate ligands.

Lanthanide chelates with dimethyl(phenylsulfonyl)amidophosphate (labeled as HSP) and Lewis base ligands (bpy = 2,2;-bipyridine and phen = 1,10-phenanthroline) of formula Na[Ln(SP)] (1Ln), [Ln(SP)bpy] (2Ln); [Ln(SP)phen] (3Ln) (Ln = Eu, Gd, Tb and Lu) were obtained and characterized by the X-ray, photoluminescence spectroscopy at 293 and 77 K as well as by intrinsic (Q) and overall (Q) luminescence quantum yields. These phosphors manifest a very strong emission after excitation in the UV range of the molecular singlet states (S) and two of them have very high Q values (Eu and Tb chelates of the type 2Ln and 3Ln). The dynamics of the excited states are discussed based on the intramolecular energy transfer theory, considering the dipole-dipole, the dipole-multipole and the exchange mechanisms.

Crystal structure of the sodium salt of mesotrione: a triketone herbicide.

The crystal structure of the sodium salt of mesotrione, namely, -poly[[sodium-μ-2-[(4-methane-sulfonyl-2-nitro-phen-yl)carbon-yl]-3-oxo-cyclo-hex-1-en-1-olato] ethanol monosolvate], {[Na(CHNOS)]CHOH}, is described. The X-ray structural analysis results reveal that the coordination sphere is established by two chelating O atoms, the O atom of the coordinated ethanol mol-ecule, and an O atom from the methyl-sulfonyl group of a neighboring mol-ecule. Simultaneously, an O atom of the cyclo-hexane fragment serves as a bridge to a neighboring sodium ion, forming a flat Na-O-Na-O quadrangle, thereby forming a mono-periodic polymer.

Enzymatic nucleosome acetylation selectively affects activity of histone methyltransferases in vitro.

Posttranslational modification of histones plays a critical role in regulation of gene expression. These modifications include methylation and acetylation that work in combination to establish transcriptionally active or repressive chromatin states. Histone methyltransferases (HMTs) often have variable levels of activity in vitro depending on the form of substrate used.

New Luminescent Lanthanide Tetrakis-Complexes NEt [LnL ] Based on Dimethyl-N-Benzoylamidophosphate.

New lanthanide dimethyl-N-benzoylamidophosphate (HL) based tetrakis-complexes NEt [LnL ] (Ln =La, Nd, Sm, Eu, Gd, Tb, Dy) are reported. The complexes are characterized by means of NMR, IR, absorption, and luminescent spectroscopy as well as by elemental, X-Ray, and thermal gravimetric analyses. The phenyl groups of the four ligands of the complex anion are directed towards one side, while the methoxy groups are directed in the opposite side, which makes the complexes under consideration structurally similar to calixarenes.

Spectroscopic aspects for the Yb coordination compound with a large energy gap between the ligand and Yb excited states.

We present the experimental and theoretical results that made it possible to propose the energy transfer mechanism for a Yb complex with a large energy gap between the ligand and Yb excited states using a theoretical model and experimental data. Absorption and emission spectroscopy in the 300-4 K range is used for the study of the Yb compound with N-phosphorylated sulfonamide (Na[YbL]), which, despite the large energy gap, is characterized by high emission sensitization efficiency (η = 40%) and relatively long Yb emission lifetime (27 μs). The crystal structure of Na[YbL], radiative lifetime (930 μs), refractive index (1.

Discovery of the SMYD3 Inhibitor BAY-6035 Using Thermal Shift Assay (TSA)-Based High-Throughput Screening.

SMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase that was initially described as an H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has been reported to methylate and regulate several nonhistone proteins relevant to cancer, including mitogen-activated protein kinase kinase kinase 2 (MAP3K2), vascular endothelial growth factor receptor 1 (VEGFR1), and the human epidermal growth factor receptor 2 (HER2). In addition, overexpression of SMYD3 has been linked to poor prognosis in certain cancers, suggesting SMYD3 as a potential oncogene and attractive cancer drug target.

Efficient Sensitized Luminescence of Binuclear Ln(III) Complexes Based on a Chelating Bis-Carbacylamidophosphate.

Binuclear rare earth complexes LnLphen (Ln = Nd, Sm, Eu, Tb, Dy, Yb and Y) with bis-CAPh type ligand - tetramethyl N,N'-(2,2,3,3,4,4-hexafluoro-1,5-dioxopentane-1,5-diyl)bis(phosphoramidate) (HL) and 1,10-phenanthroline (phen) were synthesized and characterized by elemental analysis, IR, NMR, absorption and luminescence spectroscopy. Luminescence measurements were performed for all the complexes in solid state and for the Eu, Tb and Y complexes - in solution in DMSO as well. The effective energy transfer from organic ligands to Ln ions strongly sensitizes the Ln ions emission and under excitation by UV light, the complexes exhibited bright characteristic emission of lanthanide metal centers.

A First-in-Class, Highly Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 6.

Protein arginine methyltransferase 6 (PRMT6) catalyzes monomethylation and asymmetric dimethylation of arginine residues in various proteins, plays important roles in biological processes, and is associated with multiple cancers. To date, a highly selective PRMT6 inhibitor has not been reported. Here we report the discovery and characterization of a first-in-class, highly selective allosteric inhibitor of PRMT6, (SGC6870).

Structures and Spectral and Magnetic Properties of a Series of Carbacylamidophosphate Pentanuclear Lanthanide(III) Hydroxo Complexes.

A series of pentanuclear lanthanide complexes LnL(μ-L)(μ-OH)(μ-OH) (Ln = Nd, Dy, Ho, Er, Yb; L = dimethyl -benzoylamidophosphate ion, [CHC(O)-N-P(O)(OCH)]) was obtained by the reaction of sodium dimethyl -benzoylamidophosphate with the corresponding lanthanide nitrates. The pentanuclear cores formed as a result of self-arrangement and their composition did not depend on the lanthanide ion. The complexes and sodium dimethyl -benzoylamidophosphate have been characterized by single-crystal X-ray diffraction.

Selective, Small-Molecule Co-Factor Binding Site Inhibition of a Su(var)3-9, Enhancer of Zeste, Trithorax Domain Containing Lysine Methyltransferase.

The first chemical probe to primarily occupy the co-factor binding site of a Su(var)3-9, enhancer of a zeste, trithorax (SET) domain containing protein lysine methyltransferase (PKMT) is reported. Protein methyltransferases require -adenosylmethionine (SAM) as a co-factor (methyl donor) for enzymatic activity. However, SAM itself represents a poor medicinal chemistry starting point for a selective, cell-active inhibitor given its extreme physicochemical properties and its role in multiple cellular processes.

Crystal structure of -(di-phenyl-phosphor-yl)-2-meth-oxy-benzamide.

In the title compound, CHNOP, the C=O and P=O groups of the carbacyl-amido-phosphate (CAPh) fragments are located in a synclinal position relative to each other and are pre-organized for bidentate chelate coordination of metal ions. The N-H group is involved in the formation of an intra-molecular hydrogen bond. In the crystal, mol-ecules do not form strong inter-molecular inter-actions but the mol-ecules are linked weak C-H⋯π inter-actions, forming chains along [001].

Pharmacophores Modeling in Terms of Prediction of Theoretical Physicochemical Properties and Verification by EXPERIMENTAL correlations of Carbacylamidophosphates (CAPh) and Sulfanylamidophosphates (SAPh) Tested as New Carbonic Anhydrase Inhibitors.

Background: The function of Carbonic anhydrase is to facilitate the physiological process i.e. interconversion of CO2 to HCO3 - by hydration.

Calixarene-based phosphinic acids as inhibitors of protein tyrosine phosphatases.

In the present work, the derivatives of calix[4]arene, thiacalix[4]arene, and sulfonylcalix[4]arene bearing four methylene(phenyl)phosphinic acid groups on the upper rim of the macrocycle were synthesized and studied as inhibitors of human protein tyrosine phosphatases. The inhibitory capacities of the three compounds towards PTP1B were higher than those for protein tyrosine phosphatases TC-PTP, MEG1, MEG2, and SHP2. The most potent sulfonylcalix[4]arene phosphinic acid displayed K value of 32 nM.

C Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro.

New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C fullerene.According to molecular simulation results, C fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C fullerene and DNA G nucleotide, as well as by interactions of HL CCl group by ion-π bonds with C molecule and by electrostatic bonds with DNA G nucleotide.With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC value detected at 10 μM concentration at 72 h of cells treatment was shown.

Tris(-{bis-[meth-yl(phen-yl)amino]-phosphor-yl}benzene-sulfonamidato-κ,')(1,10-phenanthroline-κ,')lanthanum(III).

The asymmetric unit of [La(CHNOPS)(CHN)] is created by one La ion, three deprotonated -{bis-[meth-yl(phen-yl)amino]-phosphor-yl}benzene-sulfonamidate () ligands and one 1,10-phenanthroline (Phen) mol-ecule. Each La ion is eight-coordinated (6O+2N) by three phosphoryl O atoms, three sulfonyl O atoms of three ligands and two N atoms of the chelating Phen ligand, leading to the formation of six- and five-membered metallacycles, respectively. The lanthanum coordination polyhedron has a bicapped trigonal-prismatic geometry.

Contribution of Energy Transfer from the Singlet State to the Sensitization of Eu and Tb Luminescence by Sulfonylamidophosphates.

A series of stable lanthanide complexes Na[Ln(L) ] (Ln=La , Eu , Gd , Tb , with L=dimethyl(4-methylphenylsulfonyl)amidophosphate and dimethyl-2-naphthylsulfonylamidophosphate) were synthesized. The compounds were characterized by single-crystal X-ray diffraction, IR, absorption, and emission spectroscopy at 293 and 77 K. In contrast to the usual and well-known dominant role of the ligand triplet state in intramolecular energy transfer processes in Ln complexes, in this particular new class of Ln compounds with sulphonylamidophosphate ligands, strong experimental and detailed theoretical evidence suggest a dominant role is played by the ligand first excited singlet state.

Influence of iatrogenic hypercorticoidism induced by long-term application of dexamethasone on power of muscular contraction of white rats.

Unlabelled: Research objective consisted in detection of nature of the changes of the myothermiс and the ergometric parameters of the contraction of the forward tibial muscle of rats in the course of performing of the tiring work at the saturation of an organism by therapeutic doses of dexamethasone.

Method: The experiments were performed on sexually mature rats-females (200-220 g), divided into control (n = 10) and experimental (n = 60) groups. The animals of experimental group received dexamethasone (D, KRKA, Slovenia) in a dose of 0,25 mg/kg (intraperitoneal, 1 time in 2 days) during from 10 to 60 days.

[AMPLITUDE-FREQUENCY'S DEPENDENCE OF M-RESPONSE OF THE SKELETAL MUSCLE OF RATS WITH EXPERIMENTAL HYPERCORTICOIDIZM].

In experiments over the mature white female rats the influence of the hypercorticoidizm (simulated by daily parenteral injection of hydrocortisone in a dose of 3 mg/kg/days for 30 days) on some parameters of the M-response of the forward tibial muscle with a different frequency of stimulation of the low-tibial nerve is studied. It is established that the hypercorticoidizm is followed by lengthening of the chronaxia of the forward tibial muscle at its indirect irritation (by 69 per cent), deterioration of stability of M-response's generation, lengthening of the latent period (by 30 per cent) and to reduction of amplitude (by 29 per cent) of single M-responses against increase in frequency of polyphase potentials (to 35 per cent). At animals with hypercorticoidizm in the range of low frequencies of nerve's stimulation (10-30 imp/s) periodic generation of higher-amplitude M-responses, than at control, against their low initial amplitude was observed, which can testify in a favor of an initial partial blocking of synapses.

INHIBITORY POTENTIAL OF POLYHYDROXYLATED FULLERENES AGAINST PROTEIN TYROSINE PHOSPHATASE 1B.

Inhibition of PTP1B by polyhydroxylated fullerenes was studied in silico and in vitro. The enzyme kinetics in the presence of polyhydroxy small gap fullerenes showed that reciprocal value of maximum velocity non-linearly increases with increasing the inhibitor concentration. Analysis of the dose-dependent curve of PTP1B inhibition suggests an apparent positive cooperativity with involvement of at least two binding sites for the hydroxylated fullerene cages.

Phosphonate monoesters on a thiacalix[4]arene framework as potential inhibitors of protein tyrosine phosphatase 1B.

Monoester derivatives of thiacalix[4]arene tetrakis(methylphosphonic) acid were found to be capable of inhibiting protein tyrosine phosphatase 1B. In addition, these compounds can strongly bind to human serum albumin.

Crystal structure of {μ-6,6'-dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methanylyl-idene)]diphenolato}(meth-anol)(nitrato)nickel(II)sodium.

In the molecular structure of the title compound, [NaNi(C18H18N2O4)(NO3)(CH3OH)], the Ni(2+) ion has a slightly distorted square-planar coordination environment defined by two N and two O atoms which belong to a Schiff base ligand, viz. 6,6'-dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methanylyl-idene)]diphenolate. Seven O atoms form the coordination environment of the Na(+) ion: four from the Schiff base ligand, two from a bidentate chelating nitrate anion and one O atom from a coordinating methanol mol-ecule.

[Thyroxine caused modulation of dexamethasone effects on the skeletal muscle of white rats].

Experiments in situ on mature white female rats performed with the use of electrophysiological methods allowed to investigate the modulatory influence of thyroxin at the dose which does not cause the signs of hyperthyroidism (10 mkg/ kg), upon the manifestation of the dexamethasone effects on the functional state of the anterior tibial muscle. It has been established that the chronic isolated application of dexamethasone was accompanied by reduction of the amplitude ofmuscle contraction (by 29.7-59.

{Dimeth-yl [(phenyl-sulfon-yl)amido-]phosphato-κ(2) O,O'}bis-(tri-phenylphosphane-κP)copper(I).

In the title complex, [Cu(C8H11NO5PS)(C18H15P)2], the Cu(I) ion is coordinated by two tri-phenyl-phosphane mol-ecules and two O atoms of the chelating dimeth-yl(phenyl-sulfon-yl)amido-phosphate anion, generating a squashed CuO2P2 tetrahedron. In the six-membered chelate ring, the Cu, P and O atoms are almost coplanar (r.m.

Fullerene derivatives as a new class of inhibitors of protein tyrosine phosphatases.

In this study, we identified water-soluble C60 and C70 fullerene derivatives as a novel class of protein tyrosine phosphatase inhibitors. The evaluated compounds were found to inhibit CD45, PTP1B, TC-PTP, SHP2, and PTPβ with IC50 values in the low micromolar to high nanomolar range. These results demonstrate a new strategy for designing effective nanoscale protein tyrosine phosphatase inhibitors.

Calix[4]arene methylenebisphosphonic acids as inhibitors of protein tyrosine phosphatase 1B.

Сalix[4]arenes bearing methylenebisphosphonic or hydroxymethylenebisphosphonic acid fragments at the wide rim of the macrocycle were studied as inhibitors of PTP1B. Some of the inhibitors showed IC50 values in the micromolar range and good selectivity in comparison with other protein tyrosine phosphatases such as TC-PTP, PTPβ, LAR, and CD45. Kinetic studies indicated that the calix[4]arene derivatives influence PTP1B activity as slow-binding inhibitors.