Semi-rigid analogues of the calcium antagonist verapamil: A molecular modelling study

Summary In this work the rigid-analogue approach has been used to obtain information on the active conformation(s) of the calcium antagonist verapamil. A series of semi-rigid analogues of verapamil were synthesized and their biological activities evaluated on guinea-pig heart and aorta. These molecules were analysed by means of molecular modelling techniques.On the basis of the pharmacological profile and conformational analysis of these compounds, two different models for negative inotropic and negative chronotropic activity are proposed. The two actions seem to be due to conformations of the molecules which differ in the orientation of their phenylethylamino groups.     

Sulla risolubilita' degli operatori differenziali invarianti sul gruppo di Heisenberg

In questa nota si considera il problema della risolubilità per operatori del secondo ordine, invarianti a sinistra e omogenei, sul gruppo di HeisenbergH _n. Si presenta un approccio al problema basato sul prolungamento analitico dei coefficienti degli operatori, a partire dai risultati noti per il sub-Laplaciano. I dettagli sono contenuti in due articoli degli autori, in collaborazione con F. De Mari [DPR] e D. Müller [MPR]. Conferenza tenuta da F. Ricci il 25 ottobre 1995     

Femtosecond dynamics of Co thin films on Si support

The ultrafast electron and spin dynamics of Co films was investigated using a femto-second pump-probe technique. The samples were magnetically characterized by means of magnetooptical Kerr effect and non-optical magnetometers, i.e. superconductive quantum interference device and alternating gradient field magnetometer. Time evolution of both, Kerr rotation and ellipticity, was measured at different points of the static hysteresis cycle. This allowed separating magnetic and non-magnetic contributions to the signal. The sample magnetization was found to drop within 200 fs, following the pulse cross-correlation trace, while the magnetization recovery time was found to last few picoseconds.     

X-ray single-crystal structure and magnetic properties of Fe[CH(3)PO(3))] x H(2)O: a layered weak ferromagnet

The crystal and molecular structure of the layered weak-ferromagnet Fe[CH(3)PO(3)] x H(2)O has been solved by X-ray single-crystal diffraction techniques. Crystal data for Fe[CH(3)PO(3)] x H(2)O are the following: orthorhombic space group Pna2(1); a =17.538(2), b = 4.814(1), c = 5.719(1) A. The structure is lamellar, and it consists of alternating organic and inorganic layers along the a direction of the unit cell. The inorganic layers are made of Fe(II) ions octahedrally coordinated by five phosphonate oxygen atoms and one from oxygen of the water molecule. Each phosphonate group coordinates four metal ions, through chelation and bridging, making in this way a cross-linked Fe-O network. The resultant layers are then separated by bilayers of the methyl groups, with van der Waals contacts between them. The compound is air stable, and it dehydrates under inert atmosphere at temperatures above 120 degrees C. The oxidation state of the metal ion is +2, and the electronic configuration is d(6)( )()high spin (S = 2), as determined from dc magnetic susceptibility measurements from 150 K to ambient temperature. Below 100 K, the magnetic moment of Fe[CH(3)PO(3)] x H(2)O rises rapidly to a maximum at T(max) approximately equal to 24 K, and then it decreases again. The onset of peak at T = 25 K is associated with the 3D antiferromagnetic long-range ordering, T(N). The observed critical temperature, T(N), is like all the other previously reported Fe(II) phosphonates, and it appears to be nearly independent of the interlayer spacing in this family of hybrid organic-inorganic layered compounds. Below T(N), the compound behaves as a "weak ferromagnet", and represents the third kind of magnetic materials with a spontaneous magnetization below a finite critical temperature, ferromagnets and ferrimagnets being the other two types.     

Halogenation of the N-Terminus Tyrosine 10 Promotes Supramolecular Stabilization of the Amyloid-β Sequence 7–12

Here, we demonstrate that introduction of halogen atoms at the tyrosine 10 phenol ring of the DSGYEV sequence derived from the flexible amyloid-β N-terminus, promotes its self-assembly in the solid state. In particular, we report the crystal structures of two halogen-modified sequences, which we found to be stabilized in the solid state by halogen-mediated interactions. The structural study is corroborated by Non-Covalent Interaction (NCI) analysis. Our results prove that selective halogenation of an amino acid enhances the supramolecular organization of otherwise unstructured biologically-relevant sequences. This method may develop as a general strategy for stabilizing highly polymorphic peptide regions.     

Comparative LC Enantioseparation of Novel PPAR Agonists on Cellulose- and Amylose-Based Chiral Stationary Phases

The LC enantiomeric separation of several dual PPARα/γ agonists on the commercially available Chiralcel OD and Chiralpak AD columns has been evaluated in normal phase mode using a mobile phase consisting in a mixture of n-hexane, 2-propanol and trifluoroacetic acid at constant volume ratio. Most compounds were separated as underivatized acids without requiring time consuming analysis. Some complementary selectivity was evidenced on the two investigated chiral stationary phases related to the different accessibility of the active sites of the helical cavities. Additional information on the chiral recognition mechanism were deduced from the chromatographic behaviour of some selected methyl esters.     

The redox behavior of 9-nickelafluorenyl sandwich complexes

A collection of nickelocene and cobaltocene analogs with one or two nickelafluorenyl rings has been recently synthesized starting from 9-nickelafluorenyllithium complex. The redox ability of the whole series of derivates has been investigated by electrochemical techniques, and the nature of the frontier orbitals responsible for the electron transfer activity of this class of compounds has been supported by extended Hückel calculations. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Antihepatotoxic and antioxidant activities of methanol extract and isolated compounds from Ficus chlamydocarpa

Free radicals, in particular radical oxygen species (ROS), play an important role in the aetiology and pathogenesis of various diseases. Current research in many countries focuses on the use of local medicinal plants as a promising source of liver protective agents. This paper describes the hepatoprotective effects of the methanol extract and four isolated compounds from Ficus chlamydocarpa on CCl4-induced liver damage, as well as the possible antioxidant mechanisms involved in this protection. The DPPH test, along with the beta-Carotene-Linoleic Acid Model System and Ferric-Reducing Antioxidant Power assays, as well as the inhibition of microsomal lipid peroxidation were used to measure radical-scavenging and antioxidant activities. Pretreatment of rats with the methanol extract of F. chlamydocarpa before CCl4 administration, significantly prevented serum increase of hepatic enzyme markers, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), in a dose-dependent manner. The hepatoprotection was also associated with a significant enhancement in hepatic reduced glutathione (GSH) and a marked decrease of liver malondialdehyde (MDA). Among the four compounds 1-4, isolated from the methanol extract, alpha-amyrin acetate (1) and luteolin (4) showed a significant hepatoprotective activity, as indicated by their ability to prevent liver cell death and lactate dehydrogenase (LDH) leakage during CCl4 intoxication.