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.     

Topography of the potential energy hypersurface and criteria for fast-ion conduction in perovskite-related A2B2O5 oxides

We discuss the importance of the topography of the potential energy hypersurface for the ionic conductivity of perovskite-related A(2)B(2)O(5) oxides. A correlation between the energetic preference of the cations for different coordination geometries and the ionic conductivity is proposed based on a first principles periodic density functional theory study of selected possible structures for Ba(2)In(2)O(5), Sr(2)Fe(2)O(5), Sr(2)Mn(2)O(5), and La(2)Ni(2)O(5). There are a large number of low-energy local minima on the potential energy hypersurfaces of the two first compounds due to an energetic preference for BO(4) tetrahedra. Tetrahedral environments are energetically unfavorable for Mn(III) in Sr(2)Mn(2)O(5) and for Ni(II) in La(2)Ni(2)O(5), and the number of low-energy configurations is relatively low in these two cases. Consistent with our findings, in contrast to Sr(2)Fe(2)O(5) and Ba(2)In(2)O(5), Sr(2)Mn(2)O(5) and La(2)Ni(2)O(5) do not exhibit transitions to disordered phases on heating, and there appear to be no reports of enhanced ionic conductivity for these compounds. Thus we suggest that the possibility of many different oxygen orderings associated with a variety of low-energy connectivity schemes within tetrahedral layers such as in the brownmillerite-based structures of Sr(2)Fe(2)O(5) and Ba(2)In(2)O(5) is a prerequisite for high ionic conductivity in perovskite-related A(2)B(2)O(5) oxides.     

Molecular structure of gaseous vanadyl(V) fluoride as studied by electron diffraction,and its modified valence force field

The molecular structure of gaseous OVF₃ has been determined by electron diffraction to be: r_g(V-O) = 1.570(5) Å, r_g(V-F) = 1.729(2) Å and ∠_α(OVF) = 107.5(4)°. A modified force field has been fitted to results from spectroscopic as well as diffractional studies. A similar attempt to determine the force field for OVCl₃ was not as successful as for OVF₃, probably because the Coriolis constants are less accurately determined for that molecule.     

Redox thermochemistry of SrFe1-xCoxO3-d

The enthalpy of oxidation of SrFe_1-xCo_xO_3-d with x=0.33 and 0.67 has been determined by adiabatic calorimetry; average values for x=0.33 and 0.67 are -67±11 and -49.5±9 kJ (mol O₂)^-1. These data and the previously reported value for SrFeO_3-d suggest that the enthalpy of oxidation for pure (perovskite-type) SrCoO_3-d is close to zero. Earlier reported composition - partial pressure data for SrFe_0.67Co_0.33O_3-d are reproduced when preferential oxidation of iron is assumed for low partial pressures of oxygen. This revised version was published online in August 2006 with corrections to the Cover Date.     

A coupled-cluster study of linear and rhombic boron nitride dimers: a revisit

The potential energy surfaces of both singlet and triplet B₂N₂ have been investigated computationally at the coupled-cluster level with a polarized triple zeta basis set augmented with diffuse functions. Calculated vibrational frequencies and intensities are also reported. The triplet species are consistently more stable than their singlet analogs and the stabilities of the linear B₂N₂ isomers increase with increasing number of B–N bonds. The most stable isomer is the linear triplet BNBN isomer with a rhombic form with a short diagonal BB distance close in energy. Our results are consistent with the results of the matrix IR studies of Andrews et al. nucleus-independent chemical shift (NICS) values were calculated for the singlet D_2h rhombic form and its C_2v dication, and these were compared to those of the D_2h cyclobutadiene and its D_2d dication, respectively. Electron density plots for the linear and rhombic B₂N₂ minima showed similar distributions for the singlet and triplet states. These plots confirmed weak BB bonding interactions in both rhombic forms but larger BN bond orders.     

The potential energy surface of singlet cyclobutadiene and substituted analogs: a coupled-cluster study

Coupled-cluster investigations (CCSD/cc-pVDZ and CCSD/cc-pVQZ//CCSD/cc-pVDZ) of singlet cyclobutadiene and fifteen-substituted analogs were conducted. A local minimum with a square frame does not exist on their potential surfaces. The well-known rectangular D_2h minimum, the square D_4h transition state, and two additional stationary points were found on cyclobutadiene’s potential surface. This included a transition state with a rhombic carbon ring and C_2h symmetry, separating two equivalent puckered C_2v local minima. The predicted barriers were 19.7 and 19.8 kcal/mol at the CCSD/cc-pVDZ and CCSD/cc-pVQZ//CCSD/cc-pVDZ levels, respectively. The relative strain energies of rectangular D_2h cyclobutadiene and all fifteen-substituted analogs were obtained from isodesmic reactions. Progressive substitution with methyl or BH₂ groups continuously lowers ring strain while increasing substitution with fluorines or trifluoromethyl groups steadily increases ring strain. C₄(BH₂)₄ is 16.6 and 13.3 kcal/mol less strained than cyclobutadiene while C₄F₄ is 17.7 and 21.5 kcal/mol more strained at the levels above. Cyclobutadiene is more strained than both cyclopropene and cyclobutene by 12.2 and 37.0 kcal/mol, respectively. Electron density contours indicate that fluorine substitution raised the electron density especially in the short C=C ring bonds above/below the ring plane (π-electrons) but not in the ring plane (σ-electrons). BH₂-substitutions lower the ring π-electron density with little effect in the ring plane. Methyl substituents have little effect on electron densities. All rings retain a strong bond alternation tendency (rectangular) whether substituted with electron-donating or -attracting groups. One-bond coupling constants and the percent p-character in ring C-to-C and C-to-substituent bonds are described.     

Acoustic measurements of the sound-speed profile in the bubbly wake formed by a small motor boat

In situ measurements of the bubble field within wakes generated by a small motorboat show that the bubble field, shortly after the initial turbulent generation period, consists mainly of bubbles with radii between 20 and 200 microm. The subsequent dispersion of the wake field can be described using a model that includes bubble buoyancy and dissolution only, and the air volume fraction within the wakes decay exponentially with an e-folding time of between 40 and 60 s. Simultaneous measurements of sound propagating through the bubbly wake exhibit spectral banding due to waveguide propagation. Inversions using the inverse-square theory developed by Buckingham [Philos. Trans. R. Soc. London, Ser. A 335, 513-555 (1991)] show that this acoustic inversion technique provide a viable means of estimating the low-frequency sound-speed profile in an upward refractive bubble layer when dispersion can be neglected.     

Structure of 1-Thia-closo-dodecaborane(11), 1-SB11H11, as determined by microwave spectroscopy complemented by quantum chemical calculations

The microwave spectrum of 1-thia-closo-dodecaborane(11), 1-SB(11)H(11), has been investigated in the 23-62 GHz spectral region. The molecule is found to have C(5v) symmetry. The spectra of several isotopomers have been assigned and a precise substitution structure of the non-hydrogen atoms has been determined. The structure is in quite good agreement with the one determined previously by electron diffraction. Density functional theory calculations at the B3LYP/cc-pVTZ level were found to predict a structure that is in good agreement with the substitution structure.     

NMR for equilateral triangular geometry under conditions of surface relaxivity—analytical and random walk solution

We consider analytical and numerical solution of NMR relaxation under the condition of surface relaxation in an equilateral triangular geometry. We present an analytical expression for the Green’s function in this geometry. We calculate the transverse magnetic relaxation without magnetic gradients present, single-phase, both analytically and numerically. There is a very good match between the analytical and numerical results. We also show that the magnetic signal from an equilateral triangular geometry is qualitatively different from the known solution: plate, cylinder, and sphere, in the case of a nonuniform initial magnetization. Nonuniform magnetization close to the sharp corners makes the magnetic signal very fast multiexponential. This type of initial configuration fits qualitatively with the experimental results by Song (Phys. Rev. Lett. 85, 3878 (2000)), Song et al. (Nature 406, 178 (2000)), Song (Mag. Reson. Imag. 19, 417 (2001)) and Lisitza and Song (Phys. Rev. B 65, 172406 (2002)). It should also be noted that the solution presented here can be used to describe absorption of a chemical substance in an equilateral triangular geometry (for a stationary fluid).