Stereocontrolled preparation of a nonpeptidal (-)-spirobicyclic NK-1 receptor antagonist

The synthesis of a spirobicyclic NK-1 receptor (Substance-P) antagonist 1 antipode is described. Retrosynthetic analysis reveals an allylic halide A bearing the cyclopropoxy-substituted aryl group and a 2-phenyl-3-piperidone B. The stereochemistry in the spirobicyclic system bearing three chiral centers is initially set via a highly diastereoselective zinc-mediated coupling of the allylic bromide 23 to the optically active ketopiperidine 3. The remaining benzylic asymmetric center is set by a diastereoselective hydroboration followed by cyclization to the spirobicyclic system.     

The rate of hydrolysis of chloroacetamide in aqueous acid

In 0-3N acid the hydrolysis of chloroacetamide follows a bimole-cular law with an activation energy and activation entropy both greater than the corresponding quantities for acetamide in accord with predictions based on the charge distribution. However, at even slightly lower acidity the free energy of activation is a continuous function of the hydrogen-ion concentration becoming more positive with decreasing acidity in the range studied.     

Some considerations on the determination of optical properties of adsorbed films

A discussion is presented of the criteria involved in the choice of parameters where it is desired to extend either basically ellipsometric or reflectometric measurements to three parameter measurements for refractive index determination of very thin adsorbed films. It is shown that even three parameters often fail to give unique values of film optical properties, and that the requirements for accuracy are frequently extreme for any reasonable error limits in the determination. It is therefore advantageous to extend the measurements to a further angle of incidence, unless the equivalent is provided by measurements at several wavelengths. Although varying the angle of incidence in ellipsometry is of very little value, it is some help in three parameter measurements provided a proper choice of angles is made. As an example the anodic oxidation of Pt and adsorption of benzene on Pt is discussed. Cases where no solution is found for isotropic film models are presented. As these films can well be expected to be uniaxially anisotropic, a search was extended into this case, although by no means exhaustive. Solutions were found for all the examples, but in the benzene case alone, the solutions are plausible.     

Rebek Imide Platforms as Model Systems for the Investigation of Weak Intermolecular Interactions

A Rebek imide receptor with an acetylene‐linked phenyl ring complexes 2,6‐di(isobutyramido)pyridine in (CDCl₂)₂ via triple H‐bonding and π–π‐stacking interactions, and the influence of para‐substituents on both rings was investigated by ¹H NMR binding titrations. When the phenyl ring was extended to biphenyl and the C(4)‐pyridine substituent varied, interaction energies increased in the order CH₃CH₂???phenyl<CH₃S???phenyl<phenyl???phenyl?N‐methylcarboxamide???phenyl, highlighting the energetic gain from π stacking on amide fragments. The predicted preference of amide–π stacking for an antiparallel alignment of the local dipoles could not be confirmed with the studied system. Different substituents were introduced in the para position of the phenyl ring and their interaction with bound 2,6‐di(isobutyramido)pyridine was investigated. Theoretical predictions that the mere introduction of a substituent has a stabilizing effect on π–π stacking, regardless of its electronic nature, were experimentally confirmed.     

Optimizing the formula of rare earth‐bearing materials: A computational chemistry investigation

We present a computational investigation into the nature of bonds formed by rare earth elements (REE) in materials. This study focuses on the incorporation of neodymium in minerals called apatites, which are derived from fluorapatite: Ca₁₀(PO₄)₆F₂. These minerals, which allow many substitutions on all three Ca, P, and F sites, are considered as potential host phases for radioactive elements separated from nuclear waste. Nd and trivalent actinides have very similar physical and chemical properties, and Nd is not radioactive and much more easily handled. It is therefore very often used as a surrogate for actinides with oxidation degree three in experimental studies. Several formulas can be considered to substitute Nd³⁺ to Ca²⁺ and maintain charge balance of the apatite. Existing experimental and theoretical studies, however, mostly concern the Ca₉Nd(PO₄)₅SiO₄F₂ formula, where the Nd incorporation is compensated by the replacement of one PO by a SiO group. Moreover, only the cation position has been studied, whereas the silicate position and its influence on stability are unknown. We present a more general investigation of possible charge compensations on the one hand, and of the various resulting configurations on the other. All possible configurations of the two formulas Ca₉Nd(PO₄)₅ SiO₄F₂ and Ca₈NdNa(PO₄)₆F₂ have been considered. Calculations have been performed within the framework of density functional theory (DFT). A computation scheme that permits good accuracy in these systems within reasonable computation times is determined. The results obtained for cohesion energies, geometries, and electronic densities are discussed. As for the formulation, it is shown that the Ca₈NdNa(PO₄)₆F₂ formula is less stable than the fluorapatite, while Ca₉Nd(PO₄)₅ SiO₄F₂ is more stable. For the structures, it is found that Nd substitutes preferably in the second cationic site. Moreover, the most stable structures exhibit the shortest Na–Nd or Nd–Si distances. Local charge balance therefore seems favorable. Then, it is shown that Nd forms covalent bonds both in apatite and in britholite, while Na forms ionic bonds. Finally, a first correlation between the material stability and the covalent character of the bonds formed is established. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Metabolite formation and toxicity measurements in evaluating bioremediation of a jet-fuel-contaminated aquifer

The metabolic capabilities of subsurface, jet-fuel-contaminated, aquifer microbial communities were characterized using an ecological approach to biotreatment assessment. A multifaceted experimental design was used that incorporated quantification of metabolite formation and toxicity screening along with the typical microbial activity measurements and pollutant degradation measurements used for assessing biorem ediation potential. Forselect experiments, dissolved oxygen levels and pH in microcosm systems were also monitored. Results suggest that a sizable, metabolically active microbial community exists in both contaminated and uncontaminated areas of the study site. Time course metabolism analyses indicated that the microbial communities were capable of degrading all three test compounds (amino acids, decane, and toluene) without any apparent adaptation period. Measurements of mineralization, cellular uptake, and metabolite formation indicated that metabolite formation was the predominant fate of the target pollutants in the microcosms. The results of toxicity screening time courses indicated that under oxygen-limiting conditions, the potential for the accumulation of toxic, acidic metabolites that could adversely affect the rates and extent of bioremediation existed. The experimental results indicate that the microbial communities at the site possess the metabolic potential for in situ biodegradation of the jet fuel. Care must be taken in the design of an in situ biodegradation treatment system (for this site and perhaps other petroleum-contaminated aquifers) to avoid the development of microaerophilic or oxygen-depleted zones; which could result in possible self-poisoning owing to acidic metabolite accumulation     

Probing the Interdigitated Phase of a DPPC Lipid Bilayer by Micropipette Aspiration

We used micropipette aspiration of giant unilamellar vesicles to directly measure the areal expansion of gel (L_β′) phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers induced by exposure to ethanol/water mixtures. Areal expansion began in 7 vol% ethanol and increased monotonically as the concentration of ethanol was increased to 15 vol% at which point areal expansion reached a plateau of 50%. This ethanol concentration range is in good agreement with that of the interdigitated phase (L_βI) of DPPC, therefore, we believe that this is the first direct measurement of the areal expansion accompanying interdigitation of gel-phase lipids. Our observations are consistent with the presence of coexisting L_βI and L_β′ phases in ethanol concentrations between 7% and 15 vol% and 100% L_βI phase in 15 vol% ethanol and higher. We observed a bimodal distribution of areal expansion (0% and 20%) induced by 7 vol% ethanol indicating that at the threshold concentration, interdigitation is induced in only a portion of DPPC vesicles. Areal expansion could not be easily reversed, consistent with kinetic trapping of the L_βI phase. DPPC vesicles exposed to butanol at the known threshold and plateau concentrations for the L_βI phase displayed areal expansion behavior consistent with our ethanol observations. However, the area expanded significantly faster for DPPC bilayers exposed to butanol vs. ethanol, which we attribute to enhanced partitioning of the longer-chained butanol into the lipid headgroups. Ethanol-induced areal expansion of DPPC bilayers was inhibited by inclusion of 10 mol% and 25 mol% cholesterol in the bilayer. However, areal expansion could be induced by application of tensions (∼8 mN/m) similar to the phenomena of interdigitation induced by high pressure. The presence of 20 vol% ethanol significantly decreased surface cohesion of DPPC bilayers containing 25 mol% cholesterol as evidenced by a decreased area compressibility modulus and lysis tension.