Structural changes by sulfoxidation of phenothiazine drugs

Summary The side-chain conformations of psychoactive phenothiazine drugs in crystals are different from those of biologically inactive ring sulfoxide metabolites. This study examines the potential energies, molecular conformations and electrostatic potentials in chlorpromazine, levomepromazine (methotrimeprazine), their sulfoxide metabolites and methoxypromazine. The purpose of the study was to examine the significance of the different crystal conformations of active and inactive phenothiazine derivatives, and to determine why phenothiazine drugs lose most of their biological activity by sulfoxidation. Quantum mechanics and molecular mechanics calculations demonstrated that conformations with the side chain folded over the ring structure had lowest potential energy in vacuo, both in the drugs and in the sulfoxide metabolites. In the sulfoxides, side chain conformations corresponding to the crystal structure of chlorpromazine sulfoxide were characterized by stronger negative electrostatic potentials around the ring system than in the parent drugs. This may weaken the electrostatic interaction of sulfoxide metabolites with negatively charged domains in dopamine receptors, and cause the sulfoxides to be virtually inactive in dopamine receptor binding and related pharmacological tests.     

Electronic, cyclic voltammetry, IR and EPR spectral studies of copper(II) complexes with 12-membered N4, N2O2 and N2S2 donor macrocyclic ligands

A new series of copper(II) complexes have been synthesized with macrocyclic ligands having three different donating atoms in the macrocyclic ring. It has been shown that the stereochemistry of complexes is dependent on the coordinated anions. These complexes are characterized by various physicochemical techniques, viz. elemental analysis, molar conductance, magnetic susceptibility measurements, IR, electronic, 1H NMR and EPR spectral studies. Cyclic voltammetric behavior of the complexes has also been discussed. The observed anisotropic g-values indicate that the chloro and acetato complexes are six-coordinate tetragonal. Whereas the sulfato and nitrato complexes are found to have five-coordinate square-pyramidal and four-coordinate square-planar geometry, respectively.     

Fermion masses

In this paper, we show that 2m _e m /(m _e ² +m ² = (g _V/g _A) _e ² . From this expression, the Weinberg mixing parameter is shown to be 0·2254 or 0·2746. Assuming that the electron and muon neutrino masses are degenerate, we find thatm _v = (g _V/g _A) _e ² . (m _e m )/M _WL, where M_WL is the mass of the standard W^± boson. The neutrino mass turns out to be 6·5 eV. The -neutrino mass is found to be about 81 MeV. The masses of c, t, s and b quarks are found to be respectively 1·7 GeV, 21·2 GeV, 0·57 GeV and 2·18 GeV by assumingm _d=m _u= 0·3 GeV. All these masses agree with other estimates except the b quark which has about half of its expected value.     

A convenient synthesis of linear pyranocoumarins. Xanthyletin and 3-Phenylxanthyletin

A convenient synthesis of linear pyranocoumarins, viz., 8,8-dimethyl-2H,8H-benzo[1,2-b; 5,4-b]dipyran-2-one (xanthyletin,1) and 8,8-dimethyl-3-phenyl-2H,8H-benzo[1,2-b; 5,4-b]dipyran-2-one (3-phenylxanthyletin,2) is described. The key steps are blocking the 8-position of appropriate 7-hydroxy-2H-1-benzopyran-2-one derivatives with iodine and 1,1-dimethyl-2-propynylation followed by cyclisation.

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Ein einfacher Syntheseweg zu linearen Pyranocumarinen. Xanthyletin und 3-Phenylxanthyletin

Zusammenfassung Es wird ein vorteilhafter Weg zur Synthese von linearen Pyranocumarinen am Beispiel von Xanthyletin und 3-Phenylxanthyletin gezeigt. Das Syntheseprinzip besteht in einer Blockierung der 8-Position des entsprechenden 7-Hydroxy-2H-1-benzopyran-2-ons mit Jod und einer 1,1-Dimethyl-2-propinylierung mit nachfolgender Cyclisierung.

     

A Two‐Dimensional Coordination Compound as a Zinc Ion Selective Luminescent Probe for Biological Applications

A 2D coordination compound {[Cu₂(HL)(N₃)]?ClO₄}_∞ ( 1 ; H₃L=2,6‐bis(hydroxyethyliminoethyl)‐4‐methyl phenol) was synthesized and characterized by single‐crystal X‐ray diffraction to be a polymer in the crystalline state. Each [Cu₂(HL)(N₃)]⁺ species is connected to its adjacent unit by a bridging alkoxide oxygen atom of the ligand to form a helical propagation along the crystallographic a axis. The adjacent helical frameworks are connected by a ligand alcoholic oxygen atom along the crystallographic b axis to produce pleated 2D sheets. In solution, 1 dissociates into [Cu₂(HL)₂(H₃L)]?2H₂O ( 2 ); the monomer displays high selectivity for Zn²⁺ and can be used in HEPES buffer (pH 7.4) as a zinc ion selective luminescent probe for biological application. The system shows a nearly 19‐fold Zn²⁺‐selective chelation‐enhanced fluorescence response in the working buffer. Application of 2 to cultured living cells (B16F10 mouse melanoma and A375 human melanoma) and rat hippocampal slices was also studied by fluorescence microscopy.     

Biligand metal chelates of 1,10-phenanthroline and several salicyclic acid derivatives in solution

Summary Mixed ligand complexes of copper(II), zinc(II), nickel(II) and cobalt(II) ions involving 1,10-phenanthroline (phen) as primary and 3,5-dinitrosalicylic acid (dnsa), 5-nitrosalicylic acid (nsa), 5-chlorosalicylic acid (csa) and 3,5-dibromosalicylic acid (dbsa) as secondary ligands in solution have been investigated potentiometrically [25°, µ = 0.1 M [NaClO₄], medium 50% v: v aqueous ethanol]. The stability order of mixed ligand complexes with respect to the metal ions obeys the natural order: cobalt(II) < nickel(II) < copper(II) > zinc(II). The stabilities of the heterometal chelates have been compared with the corresponding homometal chelates of the secondary ligands and have been interpreted in terms of metal-ligand effects and coulombic interactions between various ligand anion species present.     

Franck-Condon effects in collision-induced electronic energy transfer: I2(E; v = 1,2) + He, Ar

Collisions of I2 in the E electronic state with rare gas atoms result in electronic energy transfer to the D, beta, and D' ion-pair electronic states. Rate constants for each of these channels have been measured when I2 is initially prepared in the J = 55, nu = 1 and 2 levels in the E state. The rate constants and effective hard sphere collision cross sections confirm the trends observed when nu = 0 in the E state is initially prepared: He collisions favor population of the D state, while Ar collisions favor population of the beta state. Final state vibrational level distributions are determined by spectral simulation and are found to be qualitatively consistent with the trends in the Franck-Condon factors. The experimental distributions are also compared to the recent quantum scattering calculations of Tscherbul and Buchachenko.     

Total synthesis of (-)- and (+)-lentiginosine

Total synthesis of (-)-lentiginosine was achieved from D-mannitol using highly stereoselective reactions. Similarly, (+)-lentiginosine was synthesized from L-tartaric acid.     

2-(2-Selenocyanic acid ethyl ester)-1H-benz[de] isoquinoline-1,3-(2H)-dione, synthesis photophysics and interaction with bovine serum albumin: a spectroscopic approach

The compound 2-(2-selenocyanic acid ethyl ester)-1H-benz[de] isoquinoline-1,3-(2H)-dione (SEBID), a ubiquitous, bioactive naphthalimide derivative is expected to possess an anticancer, anti-tumor and other important therapeutic activities of significant potency with low systematic toxicity. In this paper, the synthesis of the compound, photophysics of the newly prepared naphthalimide derivative and its interaction with model transport protein Bovine serum albumin (BSA) have been reported using the absorption and steady state fluorescence spectroscopic techniques exploiting the intrinsic fluorescence emission properties of BSA as a probe. Interaction of this organoselenium compound in different dioxane-water mixtures with increase in the polarity of the medium has been studied spectroscopically. Interaction of SEBID with BSA leads to a dramatic decrease in the fluorescence intensity of BSA, which suggests the binding of SEBID with the tryptophan residue of BSA. Furthermore, different thermodynamic parameters for SEBID-BSA interaction have been calculated. Rationalization of the data has been attempted, particularly in relation to prospective applications in the biomedical research.