Discovery and preliminary SAR of 5-arylidene-2,2-dimethyl-1,3-dioxane- 4,6-diones as platelet aggregation inhibitors

We herein document the discovery of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones as a novel family of platelet aggregation inhibitors. The preliminary optimization study enabled us to establish the most salient features of the structure-activity relationships in this series as well as to identify novel derivatives that are upto 60 times more potent than the hit structure 1 and slightly superior to the reference drug Milrinone.     

Structure and magnetic properties of a non-heme diiron complex singly bridged by a hydroxo group

The synthesis of the first singly bridged non-heme diiron complex with a mu-hydroxo bridging ligand, [{(salten)Fe}2(OH)][B(C6H5)4].(CH3CN)x.(H2O)y (1) [H2salten = 4-azaheptane-1,7-bis(salicylideneiminate)], is reported. The complex has been characterized with X-ray crystallography, FTIR, magnetic susceptibility measurements, and M?ssbauer spectroscopy. The data have been compared with the results of DFT calculations on both 1 and a model with an unsupported mu-oxo bridge (2) to verify the formulation of the complex as a mu-hydroxo-bridged species. The X-ray structure [Fe-O(H) = 1.997(1) A and Fe-O(H)-Fe = 159 degrees ] is consistent with the DFT-optimized geometry of 1 [Fe-O(H) = 2.02 A and Fe-O(H)-Fe = 151 degrees ]; the Fe-O(H) distance in 1 is about 0.2 A longer than the Fe-O separations in the optimized geometry of 2 (1.84 A) and in the crystallographic structures of diiron(III) compounds with unsupported mu-oxo bridges (1.77-1.81 A). The formulation of 1 as a hydroxo-bridged compound is also supported by the presence of an O-H stretch band in the FTIR spectrum of the complex. The magnetic susceptibility measurements of 1 reveal antiferromagnetic exchange (J = 42 cm(-1) and H(ex) = JS(1).S(2)). Nearly the same J value is obtained by analyzing the temperature dependence of the M?ssbauer spectra (J = 43 cm(-1); other parameters: delta = 0.49 mm s(-1), DeltaE(Q) = -0.97 mm s(-1), and eta = 0.45 at 4.2 K). The experimental J values and M?ssbauer parameters agree very well with those obtained from DFT calculations for the mu-hydroxo-bridged compound (J = 46 cm(-1), delta = 0.48 mm s(-1), DeltaE(Q) = -1.09 mm s(-1), and eta = 0.35). The exchange coupling constant in 1 is distinctly different from the value J approximately 200 cm(-1) calculated for the optimized mu-oxo-bridged species, 2. The increased exchange-coupling in 2 arises primarily from a decrease in the Fe-O bond length.     

Asymmetric synthesis of highly functionalized tetrahydrothiophenes by organocatalytic domino reactions

A simple approach for the formation of optically active highly functionalized tetrahydrothiophenes, which might find important use in biochemistry, pharmaceutical science, and nanoscience is presented. Development of new organocatalytic Michael-aldol domino reactions is outlined, and with the appropriate choice of additives it is possible to control the regioselectivity of these domino reactions, yielding diastereomerically pure (tetrahydrothiophen-2-yl)phenyl methanones or tetrahydrothiophene carbaldehydes in good yields and with excellent enantioselectivities up to 96% ee. The stereochemical outcome of these reactions is investigated, and the mechanism of these organocatalytic domino processes is presented.     

Constitutional self-selection of [2 x 2] homonuclear grids from a dynamic mixture of copper(I) and silver(I) metal complexes

This paper describes the controlled self-selection and quantitative parallel amplification of the homonuclear grid architectures derived from the same ligand 1 of different conformational geometries and Cu+ and Ag+ metal ions of different coordination behavior and ionic size.     

Die Trennung des Magnesiums von den Alkalien durch alkoholisches Ammoniumkarbonat

Ohne Zusammenfassung     

Detection of human and rodent 5-HT3B receptor subunits by anti-peptide polyclonal antibodies

Background  

The 5-HT₃ receptor is a member of a neurotransmitter-gated ion channel family which includes nicotinic acetylcholine, GABA_A, and glycine receptors. While antibodies specific for the 5-HT_3A receptor subunit are plentiful, and have revealed a wealth of structural and functional information, few antisera exist for the detection of 5-HT_3B receptor subunits. Here we describe the generation and characterisation of a rabbit polyclonal antiserum that specifically recognises 5-HT_3B receptor subunits     

Hysteretic Spin Crossover above Room Temperature and Magnetic Coupling in Trinuclear Transition‐Metal Complexes with Anionic 1,2,4‐Triazole Ligands

The reaction of 4‐(1,2,4‐triazol‐4‐yl)ethanesulfonate ( L ) with Zn²⁺, Cu²⁺, Ni²⁺, Co²⁺, and Fe²⁺ gave a series of analogous neutral trinuclear complexes with the formula [M₃(μ‐ L )₆(H₂O)₆] ( 1 – 5 ). These compounds were characterized by single‐crystal X‐ray diffraction, thermogravimetry, and elemental analysis. The magnetic properties of compounds 2 – 5 were studied. Complexes 2 – 4 show weak antiferromagnetic superexchange, with J values of ?0.33 ( 2 ), ?9.56 ( 3 ), and ?4.50 cm^?1 ( 4 ) (exchange Hamiltonian H=?2 J (S₁S₂+S₂S₃)). Compound 5 shows two additional crystallographic phases ( 5 b and 5 c ) that can be obtained by dehydration and/or thermal treatment. These three phases exhibit distinct magnetic behavior. The Fe²⁺ centers in 5 are in high‐spin (HS) configuration at room temperature, with the central one exhibiting a non‐cooperative gradual spin transition below 250 K with T_1/2=150 K. In 5 b , the central Fe²⁺ stays in its low‐spin (LS) state at room temperature, and cooperative spin transition occurs at higher temperatures and with the appearance of memory effect (T_1/2↑=357 K and T_1/2↓=343 K). In the case of 5 c , all iron centers remain in their HS configuration down to very low temperatures, with weak antiferromagnetic coupling (J=?1.16 cm^?1). Compound 5 b exhibits spin transition with memory effect at the highest temperature reported, which matches the remarkable features of coordination polymers.