Identification of Novel Rab27a/Melanophilin Blockers by Pharmacophore-Based Virtual Screening

Melanocytes are unique cells that produce specific melanin-containing intracellular organelles called melanosomes. Melanosomes are transported from the perinuclear area of melanocytes toward the plasma membrane as they become more melanized in order to increase skin pigmentation. In this vesicular trafficking of melanosomes, Rab27a, melanophilin, and myosin Va play crucial roles in linking melanosomes to actin-based motors. To identify novel compounds to inhibit binding interface between Rab27a and melanophilin, a pharmacophore model was built based on a modeled 3D structure of the protein complex that describes the essential binding residues in the intermolecular interaction. A pharmacophore model was employed to screen a chemical library database. Finally, 25 virtual hits were selected for biological evaluations. The biological activities of 11 analogues were evaluated in a second assay. Two compounds were identified as having concentration-dependent inhibitory activity. By analyzing structure–activity relationships of derivatives of BMD-20, two hydroxyl functional groups were found to be critical for blocking the intermolecular binding between Rab27a and melanophilin.     

Selective C(sp3)−H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow

A mild and selective C(sp³)?H aerobic oxidation enabled by decatungstate photocatalysis has been developed. The reaction can be significantly improved in a microflow reactor enabling the safe use of oxygen and enhanced irradiation of the reaction mixture. Our method allows for the oxidation of both activated and unactivated C?H bonds (30 examples). The ability to selectively oxidize natural scaffolds, such as (?)‐ambroxide, pregnenolone acetate, (+)‐sclareolide, and artemisinin, exemplifies the utility of this new method.     

Ferrocene-based anion receptor bearing amide and triazolium donor groups

A novel ferrocene-based anion receptor bearing amide and triazolium donor groups and its anion complexation have been reported. We found that it shows marked electrochemical selectivity to F(-), followed by AcO(-) > Cl(-) > Br(-) > I(-), which is in accordance with (1)H NMR titration results.     

Dialkyl formyl-1 methylphosphonates α-fonctionnels—II : Preparation par voie thermique et transformation en heterocycles α-phosphoniques

The thermal condensation of functional phosphonates bearing strongly withdrawing groups (RO)₂P(O)CH₂Z1 with dimethylformamide dimethyl acetal gives corresponding β-functional, β-phosphonic enamines (RO)₂P(O)C(Z)=CHNMe₂2. Acid or basic hydrolysis of the enamines frequently gives the free aldehyde (RO)₂P(O)CH(Z)—CHO 3. We show that the enamines can be used with success for the synthesis of heterocycles like, pyrazoles 4, pyrimidines 5, benzodiazepine 6 or indole 7, all of them substituted with a phosphonate group.     

1,3‐Dipolar cycloaddition of nitrile oxides to methyl 3‐(p‐nitrobenzoyloxy)acrylate: Methyl 3‐(p‐nitrobenzoyloxy)acrylate as a methyl propiolate equivalent with reverse regioselectivity

3‐Aryl‐4‐methoxycarbonylisoxazoles were prepared from the reaction of a variety of substituted benzonitrile oxides with methyl 3‐(p‐nitrobenzoyloxy)acrylate in moderate to good yields.     

A partition coefficient calculation method with the SFED model

The Solvation Free Energy Density (SFED) model, a solvation model proposed by No et al. was modified to give better solvation free energies of the molecules having high polarizable groups. The SFED at a point around the molecule was represented by a linear combination of four basis functions, the contribution from the cavitation free energy of a solvent, and a constant. As an application of the SFED model, the linear expansion coefficients of the Hydration Free Energy Density (HFED) and the 1-Octanol Free Energy Density (1-OFED) were determined. Both calculated hydration free energy and 1-octanol solvation free energy of selected 95 organic molecules agreed well with experimental values. The standard errors were 0.47 and 0.39 kcal/mol, respectively. 1-Octanol/water partition coefficients (P) of the molecules were calculated from the difference of the HFE and 1-OFE of the molecules. At the same time, the logP density (LPD) of a molecule was represented by the same basis functional form with the SFED model. The logP of a molecule can be obtained by the integration of the LPD of the molecule. The coefficients of the basis functions were determined by using experimental logP as constraints through an optimization procedure. Both logPs calculated from the free energy difference and from the LPD agreed well with the experimental data. The absolute mean errors were obtained as 0.34 and 0.32, respectively.     

Amidation of Ethyl N-Benzoyl-1-adamantylacetimidate

Russian Journal of General Chemistry -     

Normal mode calculation and IR band assignments of A-type zeolite

Normal mode calculation of A-type zeolite was carried out with the potential energy functions obtained from the constraint method. Mass-weighted cartesian coordinates and the pseudo-lattice method were used. The assignments of IR absorption bands were made with the calculated normal modes, by using the calculated absorption intensities of the modes and the degrees of contribution of the internal coordinates to the modes. The force constants of internal coordinate motions within the framework were also calculated and are compared with the empirical values.     

Molecular design,synthesis, and properties of Y‐type nonlinear optical polyester containing tricyanovinylthiophene with enhanced thermal stability of second harmonic generation

1‐{3,4‐Di‐(2‐hydroxyethoxy)phenyl}‐2‐(2‐thiophenyl)ethene (5) was prepared and condensed with terephthaloyl chloride to yield polyester (6). Polymer 6 was reacted with tetracyanoethylene to give a new Y‐type polyester (7) containing 1‐(3,4‐dioxyethoxy)phenyl‐2‐{5‐(2,2,3‐tricyanovinyl)‐2‐thiophenyl)}ethenyl groups as NLO‐chromophores, which are components of the polymer backbones. Polyester 7 is soluble in common organic solvents such as N,N‐dimethylformamide and acetone. Polymer 7 showed a thermal stability up to 300 °C in thermogravimetric analysis with glass transition temperature (T_g) obtained from differential scanning calorimetry near 126 °C. The second harmonic generation (SHG) coefficient (d₃₃) of poled polymer film at the 1560 nm fundamental wavelength was around 6.57 × 10^?9 esu. The dipole alignment exhibited high thermal stability up to the T_g, and there was no SHG decay below 125 °C due to the partial main‐chain character of polymer structure, which is acceptable for NLO device applications. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1911–1919, 2009