Characterization of the non-stoichiometric and isomorphic hydration and solvation in FK041 clathrate

FK041 crystallizes as a non-stoichiometric hydrate or as solvated hydrates which were characterized as isomorphic clathrates by powder X-ray diffractometry. Moisture and organic solvent vapor sorption studies, differential scanning calorimetry and thermogravimetric analysis revealed that FK041 monohydrate forms a physically stable host crystal, which has lattice channels for guest water and/or organic solvent molecules. The hydration state varies non-stoichiometrically between dihydrate and tetrahydrate depending on the relative humidity and the mol content of the co-existing organic solvent, that is 2-propanol, ethanol, or acetone. These organic solvents are thought to replace a part of originally present water with a mol ratio of 1:3. 2-Propanol exhibited the most stable solvation, indicating that the size and shape of 2-propanol are the most preferable to the lattice channels.     

Enantioselective Synthesis of a Tricyclic,sp3-Rich Diazatetradecanedione: an Amino Acid-Based Natural Product-Like Scaffold

6-, 7-, and 8-membered rings are assembled from a linear precursor by successive cyclisation reactions to construct a tricyclic diazatricyclo[6.5.1.0^{4, 9}]-tetradecanedione scaffold. Advanced building blocks based on d -aspartic acid and l -pyroglutamic acid were combined by a sp³−sp² Negishi coupling. A carbamate-guided syn-diastereoselective epoxidation followed by an intramolecular epoxide opening allowed the construction of the piperidine ring. An efficient one-pot hydroxyl-group protection twofold deprotection reaction prepared the ground for the cyclisation to the bicycle. A final deprotection of the orthogonal protecting groups and lactamisation led to the novel, sp³-rich tricycle. The final compound is a substrate mimic of peptidyl-prolyl cis-trans isomerases featuring a locked trans-amide bond. Cheminformatic analysis of 179 virtual derivatives indicates favourable physicochemical properties and drug-like characteristics. As proof of concept we, show a low micromolar activity in a fluorescence polarisation assay towards the FK506-binding protein 12.     

Exponential decay of connectivities in the two-dimensional ising model

We prove some results concerning the decay of connectivities in the low-temperature phase of the two-dimensional Ising model. These provide the bounds necessary to establish, nonperturbatively, large-deviation properties for block magnetizations in these systems. We also obtain estimates on the rate at which the finite-volume, plus-boundary-condition expectation of the spin at the origin converges to the spontaneous magnetization.On leave from São Paulo University, Brazil.     

Study of the effect of Wuzhi tablet (Schisandra sphenanthera extract) on tacrolimus tissue distribution in rat by liquid chromatography tandem mass spectrometry method

A liquid chromatography/tandem mass spectrometry (LC‐MS/MS) method was developed and validated for determining tacrolimus (FK506) in rat tissues to study the effect of Schisandra sphenanthera extract on FK506 tissue distribution. After a liquid–liquid extraction with ethyl acetate, FK506 and ascomycin (IS) were subjected to LC‐MS/MS analysis using positive electrospray ionization under multiple reactions monitoring mode. Chromatographic separation of FK506 and ascomycin was achieved on a Hypersil BDS C₁₈ column with a mobile phase consisting of methanol‐water (containing 2 mM ammonium acetate, 95 : 5, v/v). The intra‐ and inter‐batch precision of the method were less than 8.8 and 9.8%, respectively. The intra‐ and inter‐batch accuracies ranged from 97.5 to 104.0%. The lowest limit of quantification for FK506 was 0.5 ng/mL. The method was applied to a FK506 tissue distribution study with or without a dose of Wuzhi (WZ) tablet. Most of the FK506 tissue concentrations were slightly increased after a concomitant WZ tablet dose, but the whole blood concentration of FK506 was dramatically increased 3‐fold after a concomitant WZ tablet dose. These results indicated that the LC‐MS/MS method was rapid and sensitive enough to quantify FK506 in different rat tissues, and strict drug monitoring is recommended when co‐administering WZ tablet in clinical use. Copyright © 2009 John Wiley & Sons, Ltd.     

Label-free quantification of Tacrolimus in biological samples by atomic force microscopy

In the present paper we describe an atomic force microscopy (AFM)-based method for the quantitative analysis of FK506 (Tacrolimus) in whole blood (WB) samples. Current reference methods used to quantify this immunosuppressive drug are based on mass spectrometry. In addition, an immunoenzymatic assay (ELISA) has been developed and is widely used in clinic, even though it shows a small but consistent overestimation of the actual drug concentration when compared with the mass spectrometry method. The AFM biosensor presented herein utilises the endogen drug receptor, FKBP12, to quantify Tacrolimus levels. The biosensor was first assayed to detect the free drug in solution, and subsequently used for the detection of Tacrolimus in blood samples. The sensor was suitable to generate a dose–response curve in the full range of clinical drug monitoring. A comparison with the clinically tested ELISA assay is also reported.     

Identification of stiffness, dissipation and input parameters of randomly excited non-linear systems: Capability of restricted potential models (RPM)

A dynamic identification technique in the time domain for time invariant systems under random external forces is presented. This technique is based on the use of the class of restricted potential models (RPM), which are characterized by a non-linear stiffness and a special form of damping, that is a product of the input power spectral density (PSD) matrix and the velocity gradient of a non-linear function of the total mechanical energy. By applying stochastic differential calculus and by specific analytical manipulations, some algebraic equations, depending on the response statistics and on the mechanic parameters that characterize RPM, are obtained. These equations can be used for the dynamic identification of the above mechanic parameters once the response statistics of the system to be identified are evaluated. The proposed technique allows one to identify single-degree-of-freedom or multi-degrees-of-freedom systems in the case of unmeasurable input. Further, the probabilistic characteristics of the external forces can be completely estimated in terms of PSD matrix.     

Nonlinear Waves in Two-Dimensional （2D） Square Lattice Frenkel-Kontorova （FK） System

A 2D square lattice is studied. By using the continuum approximation, we set up the differential equations of motion for an arbitrary particle in the square lattice which subjects to an external periodic substrate potential. The exact solitary waves of the system are found for special cases. We conclude that the adhesive force f and the angle between propagation directions of upper and lower layers can affect these waves.     

Frenkel-Kontorova Model with Alternant Coupling Potential

We have studied a modified Frenkel-Kontorova (FK) model with alternant coupling potential. From it, we obtain a coupling conservative map, it shows that the gold-mean number is not the last broken winding number, and the broken critical value is varied with the variance of strength of spire. The phase diagram becomes asymmetric in a period. The Devil's staircase and generalized dimension are different from those of the standard FK model.PACS numbers: 64.60.Fr, 05.70.Fh, 05.70.Jk     

s-Prime elements in multiplicative lattices

Let be aC-lattice which is strong join principally generated. In this paper, we consider prime elements of for which every semiprimary element is primary. We show, for example, that a compact nonmaximal primep with this property is principal. We also show that if every primepm has this property, then is either a one dimensional domain or a primary lattice. It follows that if every primep satisfies the property, and if there are only a finite number of minimal primes in , then is the finite direct product of one-dimensional domains and primary lattices.     

Efficient and stereoselective synthesis of thiosulfinates from disulfide using cumene hydroperoxide in the presence of titanium-based catalyst systems

Abstract

An efficient and stereoselective procedure of oxidizing disulfide to thiosulfinate 2a using CHP as the oxidant and economically available Ti(O-i-Pr)₄/L-DET/H₂O as catalysts were developed. The reaction went smoothly under mild conditions with synthetic useful yield and the workup for obtaining the final product is quite convenient.