Ortho Effect in the Bergman Cyclization: Electronic and Steric Effects in Hydrogen Abstraction by 1-Substituted Naphthalene 5,8-Diradicals

We present a detailed theoretical study of geometries, electronic structure, and energies of transition states and intermediates completing the full Bergman cycloaromatization pathway of ortho-substituted enediynes with a focus on polar and steric contributions to the kinetics and thermodynamics of hydrogen abstraction. This study provides a rare unambiguous example of remote substitution that affects reactivity of a neutral reactive intermediate through an σ framework.

Steric and mass-induced sea level variations in the Mediterranean Sea revisited

The total sea level variation (SLV) is the combination of steric and mass␣induced SLV, whose exact shares are key to understanding the oceanic response to climate system changes. Total SLV can be observed by radar altimetry satellites such as TOPEX/POSEIDON and Jason 1/2. The steric SLV can be computed through temperature and salinity profiles from in situ measurements or from ocean general circulation models (OGCM), which can assimilate the said observations. The mass-induced SLV can be estimated from its time-variable gravity (TVG) signals. We revisit this problem in the Mediterranean Sea estimating the observed, steric, and mass-induced SLV, for the latter we analyze the latest TVG data set from the GRACE (Gravity Recovery and Climate Experiment) satellite mission launched in 2002, which is 3.5 times longer than in previous studies, with the application of a two-stage anisotropic filter to reduce the noise in high-degree and -order spherical harmonic coefficients. We confirm that the intra-annual total SLV are only produced by water mass changes, a fact explained in the literature as a result of the wind field around the Gibraltar Strait. The steric SLV estimated from the residual of “altimetry minus GRACE” agrees in phase with that estimated from OGCMs and in situ measurements, although showing a higher amplitude. The net water fluxes through both the straits of Gibraltar and Sicily have also been estimated accordingly.

On the steric and mass-induced contributions to the annual sea level variations in the Mediterranean Sea

The sea level variation (SLVtotal) is the sum of two major contributions: steric and mass-induced. The steric SLVsteric is that resulting from the thermal and salinity changes in a given water column. It only involves volume change, hence has no gravitational effect. The mass-induced SLVmass, on the other hand, arises from adding or subtracting water mass to or from the water column and has direct gravitational signature. We examine the closure of the seasonal SLV budget and estimate the relative importance of the two contributions in the Mediterranean Sea as a function of time. We use ocean altimetry data (from TOPEX/Poseidon, Jason 1, ERS, and ENVISAT missions) to estimate SLVtotal, temperature, and salinity data (from the Estimating the Circulation and Climate of the Ocean ocean model) to estimate SLVsteric, and time variable gravity data (from Gravity Recovery and Climate Experiment (GRACE) Project, April 2002 to July 2004) to estimate SLVmass. We find that the annual cycle of SLVtotal in the Mediterranean is mainly driven by SLVsteric but moderately offset by SLVmass. The agreement between the seasonal SLVmass estimations from SLVtotal – SLVsteric and from GRACE is quite remarkable; the annual cycle reaches the maximum value in mid-February, almost half a cycle later than SLVtotal or SLVsteric, which peak by mid-October and mid-September, respectively. Thus, when sea level is rising (falling), the Mediterranean Sea is actually losing (gaining) mass. Furthermore, as SLVmass is balanced by vertical (precipitation minus evaporation, P–E) and horizontal (exchange of water with the Atlantic, Black Sea, and river runoff) mass fluxes, we compared it with the P–E determined from meteorological data to estimate the annual cycle of the horizontal flux.

Reply to comment by L. Fenoglio-Marc et al. on “On the steric and mass-induced contributions to the annual sea level variations in the Mediterranean Sea”

Reply to comment by L. Fenoglio-Marc et al. on “On the steric and mass-induced contributions to the annual sea level variations in the Mediterranean Sea”.

Steric sea-level variations inferred from combined Topex/Poseidon altimetry and GRACE gravimetry

In this study, we propose to estimate the steric sea-level variations over a < 2-year period (April 2002 through December 2003) by combining global mean sea level (GMSL) based on Topex/ Poseidon (T/P) altimetry with time-variable geoid averaged over the oceans, as observed by the GRACE (Gravity Recovery and Climate Experiment) satellite. In effect, altimetry-derived GMSL changes results from two contributions: Steric (thermal plus salinity) effects due to sea water density change and ocean mass change due to water exchange with atmosphere and continents. On the other hand, GRACE data over the oceans provide the ocean mass change component only. The paper first discusses the corrections to apply to the GRACE data. Then the steric contribution to the GMSL is estimated using GRACE and T/P data. Comparison with available thermal expansion based on in situ hydrographic data is performed.

Skeleton outline of a plan for developing the Delta-Mendota irrigation water supply and salt-water repulsion in the Sacramento-San Joaquin Delta Region, Central Valley Project, California /

Mode of access: Internet.

On the motions of the earth and heavenly bodies, as explainable by electro-magnetic attraction and repulsion, and on the conception, growth, and decay of man, and cause and treatment of his diseases, as referable to galvanic action.

Mode of access: Internet.

The role of the 8-18 helix of CGRP 8-37 in mediating high affinity binding to CGRP receptors; coulombic and steric interactions

1. The role of individual residues in the 8-18 helix of CGRP 8-37 in promoting high-affinity binding to CGRP 1 receptors expressed on rat L6 and human SK-N-MC cells has been examined. The relative potencies of various derivatives were estimated from their ability to inhibit the human αCGRP-mediated increase in cyclic AMP production and the binding of [ 125I]-human αCGRP. 3. Arg 11 and Arg 18 were replaced by serines to give [Ser 11.18]CGRP 8-37. These bound with pKi values <6 to SK-N-MC cells and had apparent pA 2 values of 5.81 ± 0.04 and 5.31 ± 0.11 on SK-N-MC and L6 cells. CGRP 8-37 had a pKi of 8.22 on SK-N-MC cells and pK b values on the above cell lines of 8.95±0.04 and 8.76±0.04. 3. The arginines were replaced with glutamic acid residues. [Glu 11]CGRP 8-37 had a pK b of 7.14±0.14 on SK-N-MC cells (pKi=7.05±0.05) and 6.99±0.08 on L6 cells. [Glu 18]CGRP 8-37 had a pK b of 7.10±0.0.08 on SK-N-MC cells (pKi=6.91±0.23) and 7.12±0.09 on L6 cells. 4. Leu 12, Leu 15 and Leu 16 were replaced by benzoyl-phenylalanine (bpa) residues. On SK-N-MC cells, the apparent pA 2 values of [bpa 12]-, [bpa 15]- and [bpa 16]CGRP 8-37 were respectively 7.43±0.23, 8.34±0.11 and 5.66±0.16 (pKi values of 7.14±0.17, 7.66±0.21 and <6): on L6 cells they were 7.96±0.36, 8.28±0.21 and 6.09±0.04 (all n=3). 5. It is concluded that the Arg 11 and Arg 18 are involved in specific electrostatic interactions with other residues, either on the CGRP 1 receptors or elsewhere on CGRP 8-37. Leu 16 is in a conformationally restricted site when CGRP 8-37 binds to CGRP 1 receptors, unlike Leu 12 and Leu 15.

Novel imprinted polymers as artificial enzymes

Derivatives of L-histidine were investigated as suitable models for the Asp-His couple found in the catalytic triad of serine proteases. A combination of molecular dynamics and IH NMR spectroscopy suggested that the most populous conformations of N-acetyl-L-histidine and the N-acetyl-L-histidine anion were predominated by those in which the carboxylate group was gauche to the imidazole ring overcoming steric and electrostatic repulsion, suggesting there is an interaction between the carboxylate group and the imidazole ring. Kinetic studies, using imidazole, N-acetyl-L-histidine and the N-acetyl-L-histidine anion showed that in a DMSO/H20 9: 1 v/v solution, the N-acetyl-L-histidine anion catalysed the hydrolysis of p-nitrophenyl acetate at a greater rate than using either imidazole or N-acetyl-L-histidine as catalyst. This indicates that the carboxylate group affects the nucleophilicity of the unprotonated imidazole ring. 31P MAS NMR spectroscopy was investigated as a new technique for the study of the template molecule environment within the polymer networks. It was found that it was possible to distinguish between template associated with the polymer and that which was precipitated onto the surface, though it was not possible to distinguish between polymer within imprinted cavities and that which was not. Attempts to study the effect of the carboxylate group/imidazole ring interaction in the imprinted cavity of a molecularly imprinted polymer network were hindered by the method used to follow the reaction. It was found though that in a pH 8.0 buffered solution the presence of imprinted cavities increased the rate of reaction for those polymers derived from L-histidine. Some preliminary investigations into the design and synthesis of an MIP which would catalyse the oxy-Cope rearrangement were carried out but the results were inconclusive.

Steric stabilization and dissolution characteristics of aqueous suspensions of pharmaceutical interest

The adsorption of two qroups of nonionic surface active agents and a series of hiqh molecular weiqht hydrophilic polymer fractions onto a polystyrene latex and a drug substance diloxanide furoate B.P. has been investigated. The presence of pores within the drug surface has been demonstrated and this is shown to increase the adsorption of low molecular weight polymer species. Differences in the maximum amount of polymer adsorbed at both solid-solution interfaces have been ascribed to the different hydrophobicities of the surface as determined by contact angle measurements. Adsorbed layer thicknesses of polymer on polystyrene latex have been determined by three techniques: microelectrophoresis, intensity fluctuation spectroscopy and by viscometric means. These results, in combination with adsorption data, were used to interpret the configuration of the adsorbed polymer molecules at the interface. The type of druq suspension produced on adsorbing the different polymers in the absence of electrostatic stabilization was correlated with theoretical prediuctions of suspension characteristics deduced from potential energy diagrams, The agreement was good for the adsorption of short chain length surfactants, but for the polyvinylalcohols, discrepancies were found between experiment and theory. This was attributed to the inappropriate use of a mean segment density approximation within the adsorbed layer to calculate attractive potentials between particles. A maximum in the redispersibility values for suspensions coated with adsorbed nonylphenylethoxylates was attributed to "partial static stabilization" of the particles in conjunction with the attractive forces operating in the sediment between bare surface patches on neighbouring particles. No significant change in the dissolution of the drug was observed when nonylphenylethoxylates were adsorbed due to desorption upon contact with the dissolution medium. Pluronic F68 and all the polyvinylalcohol fractions caused a reduction in the dissolution rate which is explained by the decreased diffusion of drug' through the adsorbed polymer layer.