3‐(3‐Oxo‐1,3‐dihydroisobenzofuran‐1‐ylidene)pentane‐2,4‐dione

In the title compound, C₁₃H₁₀O₄, prepared by the condensation reaction between phthalic anhydride and pentane‐2,4‐dione, one of the acetyl groups in the pentane‐2,4‐dione fragment is almost coplanar with the isobenzofuran ring system, while the other group is twisted out of this plane by almost 80°. The corresponding C—C and C—O distances in the two acetyl units are consistent with dipolar delocalization into the coplanar unit only. There is no supramolecular aggregation of the molecules, but a number of rather short intermolecular contacts of C—H...O, O...O and O...C types occur.     

Amedeo Avogadro The Man, the Hypothesis, and the Number

Amedeo Avogadro was a multifaceted and prolific scientist active in many areas of physics and chemistry, but most of his results did not make a scientific impact. His hypothesis, equal volumes = equal number of molecules remained in obscurity until Cannizaro rekindled it by making it a stepping-stone in the development of the atomic theory.     

Environmental UV‐A and UV‐B Threshold Doses for Apoptosis and Necrosis in Humans Fibroblasts¶

Apoptosis involves a highly organized and programmed series of events aimed at maintaining genomic stability by eliminating defective host cells. The purpose of this study was to determine the threshold doses and environmental UV‐A and UV‐B exposure times necessary to produce apoptosis and necrosis in the normal cells of a human fibroblast cell line. Enviromental UV‐A and UV‐B doses were measured over a 6 year period with a four‐channel UV radiometer. The fibroblasts were irradiated once using an Oriel UV Solar Simulator with six doses of environmentally‐based UV. Doses corresponded to 0,11,19,23 and 45 min of average environmental UV‐A and UV‐B radiation at solar noon in Puerto Rico. The Annexin‐V binding method was used to differentiate between normal fibroblasts and apoptotic or necrotic fibroblasts. The threshold dose from apoptosis to necrosis was found between 24–28 kJ/m², which corresponded to 19 and 23 min of environmental UV‐A and UV‐B exposure. This study provides the first data that specify the environmental threshold doses of UV‐A and UV‐B at which human fibroblasts undergo apoptosis and necrosis. These results may provide valuable dose‐response thresholds for apoptosis and necrosis for future mechanistic studies and baseline data for skin cancer prevention programs.     

Plutonium Activity Ratios in Plankton: New Evidence of Hold-Up Time in Irish Sea Sediments

The determination of activity ratios for radioisotopes of different half-lives can be used to estimate transit times from a point source to locations further away. For conservative elements, this time is approximately equivalent to the net hydrological transport. However, for non-conservative elements such as plutonium, the additional influence of biogeochemical processes decreases the net transport time. In this study, ²⁴¹Pu and ^239,240Pu concentrations in Irish Sea plankton samples, collected in May 1994, were determined and the ²⁴¹Pu/^239,240Pu ratios calculated. Plutonium-239,240 was measured using a standard method by ion exchange chromatography and alpha counting, and ²⁴¹Pu was determined by liquid scintillation counting using the disk-supported technique. The latter showed some methodological problems, which are briefly discussed. The ²⁴¹Pu/^239,240Pu ratios gave an estimate of the "transit time" from Sellafield to the different sampling points. In fact, this time represents the age of plutonium in plankton, i.e., the time lag between release from Sellafield and detection at the different sampling stations. The mean plutonium age was 17±2 years (n = 10) and 18.6±0.8 years (n = 13) in phytoplankton and zooplankton, respectively. The spatial distribution was reasonably homogeneous over the Irish Sea. The assimilation-elimination processes of plutonium in plankton are rather rapid. Therefore, it may be assumed that, in this time scale, the plutonium concentrations were in equilibrium with surrounding waters. Thus, it is concluded that plutonium was rather old because resuspension-sedimentation processes had occurred that delayed its transport within the Irish Sea. Therefore, the age of plutonium in plankton represented the hold-up time of plutonium in the sediments from the Irish Sea.     

Origin of enantioselection in chiral alcohol oxidation catalyzed by Pd[(-)-sparteine]Cl2

A kinetic investigation into the origin of enantioselectivity for the Pd[(-)-sparteine]Cl(2)-catalyzed aerobic oxidative kinetic resolution (OKR) is reported. A mechanism to account for a newly discovered chloride dissociation from Pd[(-)-sparteine]Cl(2) prior to alcohol binding is proposed. The mechanism includes (1) chloride dissociation from Pd[(-)-sparteine]Cl(2) to form cationic Pd(-)-sparteine]Cl, (2) alcohol binding, (3) deprotonation of Pd-bound alcohol to form a Pd-alkoxide, and (4) beta-hydride elimination of Pd-alkoxide to form ketone product and a Pd-hydride. Utilizing the addition of (-)-sparteine HCl to control the [Cl(-)] and [H(+)] and the resulting derived rate law, the key microscopic kinetic and thermodynamic constants were extracted for each enantiomer of sec-phenethyl alcohol. These constants allow for the successful simulation of the oxidation rate in the presence of exogenous (-)-sparteine HCl. A rate law for oxidation of the racemic alcohol was derived that allows for the successful prediction of the experimentally measured k(rel) values when using the extracted constants. Besides a factor of 10 difference between the relative rates of beta-hydride elimination for the enantiomers, the main enhancement in enantiodetermination results from a concentration effect of (-)-sparteine HCl and the relative rates of reprotonation of the diastereomeric Pd-alkoxides.     

Weak intramolecular proton-hydride and proton-fluoride interactions: experimental (NMR, X-ray) and DFT studies of the bis(NBH(3)) and bis(NBF(3)) adducts of 1,3-dimethyl-1,3-diazolidine

Bis(NBH(3)), bis(NBF(3)), and NBF(3)/NBH(3) adducts 1-3 were prepared from 1,3-dimethyl-1,3-diazolidine and characterized by the (1)H, (13)C, (11)B, (19)F, 2D (1)H(-13)C HETCOR and NOESY NMR spectra. The structures and conformations of the adducts were established by the variable-temperature (1)H NMR spectra, the X-ray diffraction method (adduct 2A), and density functional calculations at different theoretical levels. The experimental and theoretical data have revealed that bis adducts 1-3 prefer trans orientations of the borane groups (1A, 2A, 3A) in solution, the solid state, and the gas phase. The studies have shown that the energetic preference of trans adducts with respect to cis compounds, decreasing as 2A (2.9 kcal/mol) > 3A (2.7 kcal/mol) > 1A (1.4 kcal/mol), is dictated by spatially repulsive interactions between the CH(3), BH(3), and BF(3) groups. The results of DFT calculations agree well with an experimental trans/cis isomeric ratio of 9:1 determined in solutions of adduct 1. The calculated geometry and energy, as well as the topological analysis of electronic densities, show that trans adducts 1-3 should exist in gas phase as twist conformations T-2 stabilized by the intramolecular C-H(delta+)...(-delta)H-B or C-H(delta+)...(-delta)F-B interactions. These interactions are characterized as closed-shell. The energy of one proton-hydride and proton-fluoride intramolecular contact, estimated as 1.9 (1A-T-2) and 0.7 (2A-T-2) kcal/mol, respectively, classifies the "elongated" intramolecular interactions CH(delta+)...(-delta)HB and CH(delta+)...(-delta)FB as weak ones. It has been established that, on going from gas phase to a condensed phase (solution and solid), the twist-conformations T-2 transform to conformations T-1, probably by intermolecular dipole-dipole interactions. The data presented in this work show that despite a weakness of the "elongated" proton-hydride and proton-fluoride interactions, they can play a significant role in the stabilization of conformational molecular states, especially when cooperativity is in action.     

Experimental (NMR) and Computational (MD) Studies on the Inclusion Complexes of 1-Bromoadamantane with alpha-, beta-, and gamma-Cyclodextrin

The inclusion complexes between the most commonly used cyclodextrins (alpha-, beta-, and gamma-CD) and 1-bromoadamantane were prepared and studied experimentally by NMR methods and by molecular dynamics simulations (AMBER force field) with solvation. The NMR results suggest host/guest ratios of 2:1, 1:1, and 1:1 for the complexes with alpha-, beta-, and gamma-cyclodextrin, respectively, as well as defined geometries for the complexes. Averaged geometrical data from the molecular dynamics simulations agree with the complexation geometries deduced experimentally.     

Analogs of propranolol. Synthesis of 3-alkylamino-1-(3-benzo[b]thienyloxy)-2-propanols

The synthesis by two alternative routes of 1-(3-benzo[b]thienyloxy)-3-isopropylamino-2-propanol hydrochloride ( 1a HCl), a thiophenic isoster of Propranolol, and related compounds, is reported. The protecting and enolizing properties of the 2-methoxycarbonyl group on benzo[b]thiophene-3-one, along with its facile removal, are utilized in the first route. In the second one, conversion of 3-bromobenzo[b]thiophene in 1-(3-benzo[b]thienyloxy)-2,3-o-isopropylidenepropane is the key step. On the other hand, hydrolysis of 1-(3-benzo[b]furanyloxy)-2,3-o-isopropylidenepropane to the corresponding diol, in order to obtain a furanic isoster of Propranolol (17a ), was unsuccessful.     

Selective crystallization of calcium salts by poly(acrylate)-grafted chitosan

The biopolymer chitosan was chemically modified by grafting polyacrylamide or polyacrylic acid in a homogeneous aqueous phase using potassium persulfate (KPS) as redox initiator system in the presence of N,N-methylene-bis-acrylamide as a crosslinking agent. The influence of the grafted chitosan on calcium salts crystallization in vitro was studied using the sitting-drop method. By using polyacrylamide grafted chitosan as substrate, rosette-like CaSO4 crystals were observed. This was originated by the presence of sulfate coming from the initiator KPS. By comparing crystallization on pure chitosan and on grafted chitosan, a dramatic influence of the grafted polymer on the crystalline habit of both salts was observed. Substrates prepared by combining sulfate with chitosan or sulfate with polyacrylamide did not produce similar CaSO4 morphologies. Moreover, small spheres or donut-shaped CaCO3 crystals on polyacrylic acid grafted chitosan were generated. The particular morphology of CaCO3 crystals depends also on other synthetic parameters such as the molecular weight of the chitosan sample and the KPS concentration.     

Dual role of (-)-sparteine in the palladium-catalyzed aerobic oxidative kinetic resolution of secondary alcohols

The mechanistic details of the palladium-catalyzed aerobic oxidative kinetic resolution of secondary alcohols have been elucidated. (-)-Sparteine was found to have a dual role as a chiral ligand and an exogenous base. Saturation kinetics were observed for the dependence on (-)-sparteine concentration. A first-order dependence on [alcohol] and [catalyst] as well as inhibition by addition of (-)-sparteine HCl were observed. These results are consistent with rate-limiting deprotonation under low (-)-sparteine concentrations and rate-limiting beta-hydride elimination using saturating (-)-sparteine concentrations. This conclusion is further supported by a kinetic isotope effect of 1.31 +/- 0.04 under saturation. The enantioselectivity events are also controlled by addition of (-)-sparteine in which high concentrations afford a more selective kinetic resolution.