Simultaneous LC−UV Analysis of Mirodenafil and Its Two Main Metabolites in Rat Plasma and Urine, and in Tissue Homogenates

A simple, rapid, and reproducible isocratic reversed-phase LC method has been established for simultaneous analysis of mirodenafil and its two main metabolites, SK3541 and SK3544, in rat plasma, urine, and tissue homogenates. Samples were deproteinized with acetonitrile containing sildenafil (internal standard). The compounds were separated on a C₁₈ column with 52:48 (v/v) 0.02 m ammonium acetate buffer (pH 6)—acetonitrile as mobile phase at a flow rate of 1.4 mL min^?1. UV detection was at 254 nm and detection limits of mirodenafil, SK3541, and SK3544 in plasma were 0.03, 0.05, and 0.1 μg mL^?1, respectively. The method is applicable to pharmacokinetic studies of mirodenafil and its metabolites in rats.     

Basicities of thiazole heterocyclic compounds and the reaction of 3-methyl-2-methylimino-Δ4-thiazolines with ethyl bromoacetate and 2-bromoacetophenone

The pK_a′s of several thiazole heterocyclic compounds have been determined and represent products with significantly high values. Because of their high basicities, sometimes these compounds were able to act as not only nucleophiles but also strong organic bases. 4-Substituted-3-methyl-2-methylimino-Δ⁴-thiazolines 5a-d reacted with ethyl bromoacetate in refluxing benzene, giving the corresponding N-alkylated salts 8a-d , while the products obtained from the reaction with 2-bromoacetophenone in the presence of base were pyrrolothiazines 10b-d.     

Thermal analysis on phase behavior of poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactic acid) interacting with aliphatic polyesters

Abstract  

Thermal behavior, miscibility, and crystalline morphology in blends of low-molecular-weight poly(l-lactic acid) (LM_w-PLLA) or high-molecular-weight PLLA (HM_w-PLLA) with various polyesters such as poly(butylene adipate) (PBA), poly(ethylene adipate) (PEA), poly(trimethylene adipate) (PTA), or poly(ethylene succinate) (PESu), respectively, were explored using differential scanning calorimeter (DSC), and polarized-light optical microscopy (POM). Phase behavior in blends of PLLA with other polyesters has been intriguing and not straight forward. Using a low- and high molecular weight PLLA, this study aimed at mainly using thermal analyses for probing the phase behavior, phase diagrams, and temperature dependence of blends systems composed of PLLA of two different molecular weights (low and high) with a series of aliphatic polyesters of different structures varying in the (CH₂/CO) ratio in main chains. The blends of LM_w-PLLA/PEA and LM_w-PLLA/PTA show miscibility in melt and amorphous glassy states. Meanwhile, the LM_w-PLLA/PESu blend is immiscible with an asymmetry-shaped upper critical solution temperature (UCST) at 220–240 °C depending on the blend composition. In contrast to miscibility in LM_w-PLLA/PTA and LM_w-PLLA/PEA blends, HM_w-PLLA with polyesters are mostly immiscible; and HM_w-PLLA/PTA blend is the only one showing an asymmetry-shaped UCST phase diagram with clarity points at 195–235 °C (depending on composition). Reversibility of UCST behavior, with no chemical transreactions, in these blends was proven by solvent recasting, gel permeation chromatography, and Fourier transform infrared spectroscopy (FT-IR). Crystalline morphology behavior of the LM_w-PLLA/PEA and LM_w-PLLA/PTA blends furnishes addition evidence for miscibility in the amorphous phase between LM_w-PLLA and PTA or PEA.     

2-dimensional analytic approach for anion differentiation with chromofluorogenic receptors

By linking the urea moiety at the 1,8 positions of the carbazole fragment, we synthesized host systems 1, 2, and 3 having both chromogenic and fluorogenic signaling subunits. The spectral changes in both the signaling subunits could be easily analyzed via a simple 2-dimensional (2D) analytic approach described here, which enables us to differentiate the given set of anions. Structural studies are also reported.     

Microsolvation of the dicyanamide anion: [N(CN)(2)(-)](H(2)O)n (n = 0-12)

Photoelectron spectroscopy is combined with ab initio calculations to study the microsolvation of the dicyanamide anion, N(CN)(2)(-). Photoelectron spectra of [N(CN)(2)(-)](H2O)n (n = 0-12) have been measured at room temperature and also at low temperature for n = 0-4. Vibrationally resolved photoelectron spectra are obtained for N(CN)(2)(-), allowing the electron affinity of the N(CN)2 radical to be determined accurately as 4.135 +/- 0.010 eV. The electron binding energies and the spectral width of the hydrated clusters are observed to increase with the number of water molecules. The first five waters are observed to provide significant stabilization to the solute, whereas the stabilization becomes weaker for n > 5. The spectral width, which carries information about the solvent reorganization upon electron detachment in [N(CN)(2)(-)](H2O)n, levels off for n > 6. Theoretical calculations reveal several close-lying isomers for n = 1 and 2 due to the fact that the N(CN)(2)(-) anion possesses three almost equivalent hydration sites. In all the hydrated clusters, the most stable structures consist of a water cluster solvating one end of the N(CN)(2)(-) anion.     

Magnesium ion selective two-photon fluorescent probe based on a benzo[h]chromene derivative for in vivo imaging

A novel, two-photon probe for the detection of free Mg2+ ions in living cells and live tissues has been developed. The probe can be excited by 880 nm laser photons, emits strong two-photon excited fluorescence in response to Mg2+ ions, can be easily loaded into the cell and tissue, shows high photostability, and can measure the Mg2+ ion concentration without interference by Ca2+ ions in living cells. The intracellular dissociation constant (Kdi) for Mg2+ determined by the two-photon process is 2.5 mM, which is suitable for dynamic Mg2+ concentration measurement. In addition, the probe is capable of imaging endogenous stores of free Mg2+ at a few hundred micrometers depth in live tissues using two-photon microscopy (TPM).     

Do homochiral aggregates have an entropic advantage?

The present work seeks to illuminate the underlying principles which control the aggregation of chiral building blocks into larger aggregates by examining the role that entropy plays in this process. Entropic effects are first examined within the confines of a simple model system, and the results are then compared to experimental data on clusters of amino acids. The model system predicts that the formation of a specific structure is more likely to occur from an enantiopure solution because forming a particular structure from a racemic solution is hindered by significant entropic barriers. These predictions are in good agreement with the experimental results. In our examination of clusters of all of the amino acids, clusters which are unusually abundant are found only when enantiopure solutions are sampled. Furthermore, the majority of all clusters exhibit no preference for chiral composition, suggesting that entropic effects negate any changes in enthalpy. Although the experimental data are not comprehensive, our results strongly suggest that specificity in homochiral clusters is entropically advantageous compared to specificity in racemic clusters.     

Application of divergent multi-component reactions in the synthesis of a library of peptidomimetics based on γ-amino-α,β-cyclopropyl acids

The multi-component condensation of organozirconocene, aldimine and zinc carbenoid was applied to the stereoselective synthesis of cyclopropane amino acid derivatives. These compounds served as scaffolds for the preparation of a 46-member library. The C- and N-termini of the cyclopropane amino acid derivatives were diversified by condensations with ten amines and ten acylating agents, respectively. To improve yields and accelerate library synthesis, most products were prepared under microwave irradiation and purified by polymer-bound scavengers and SPE methodology. All compounds were analyzed by LC-MS and a representative selection was fully characterized.     

Electronic structure and magnetic properties of small manganese oxide clusters

To investigate the electronic structure and magnetic properties of manganese oxide clusters, we carried out first-principles electronic structure calculations for small MnO clusters. Among various structural and magnetic configurations of the clusters, the bulklike [111]-antiferromagnetic ordering is found to be favored energetically, while the surface atoms of the clusters exhibit interesting electronic and magnetic characteristics which are different from their bulk ones. The distinct features of the surface atoms are mainly attributed to the reduction of Mn coordination numbers and the bond-length contractions in the clusters, which may serve as a key factor for the understanding of physical and chemical properties of magnetic oxide nanoparticles.     

Tandem time-of-flight mass spectrometer for photodissociation of biopolymer ions generated by matrix-assisted laser desorption ionization (MALDI-TOF-PD-TOF) using a linear-plus-quadratic potential reflectron

A tandem time-of-flight mass spectrometer for the study of photodissociation of biopolymer ions generated by matrix-assisted laser desorption ionization was designed and constructed. A reflectron with linear and quadratic (LPQ) potential components was used. Characteristics of the LPQ reflectron and its utility as the second stage analyzer of the tandem mass spectrometer were investigated. Performance of the instrument was tested by observing photodissociation of [M + H](+) from angiotensin II, a prototype polypeptide. Quality of the photodissociation tandem mass spectrum was almost comparable to that of the post-source decay spectrum. Monoisotopic selection of the parent ion was possible, which was achieved through the ion beam-laser beam synchronization. General theoretical considerations needed for a successful photodissociation of large biopolymer ions are also presented.