Photosensitized Electron Transfer Promoted Reductive Activation of Carbon-Selenium Bonds To Generate Carbon-Centered Radicals: Application for Unimolecular Group Transfer Radical Reactions

The investigation presented in this paper explores the mechanistic aspects and synthetic potentials of photosensitized electron transfer (PET) promoted reductive activation of organoselenium substrates. PET activation of substrates 1-5 is achieved through a photosystem comprised of light-absorbing 1,5-dimethoxynaphthalene (DMN) as electron donor and ascorbic acid as co-oxidant. The fluorescence quenching of (1)DMN by organoselenium compounds 1-5, correlation of fluorescence quenching rate constant with the reduction potentials of 1-5, and the dependence of photodissociation quantum yields of 1-5 on their concentration suggests the occurrence of electron-transfer (ET) processes between (1)DMN and 1-5. Steady state photolysis of organoselenium substrates (R(2)CHSePh) in the presence of (1)DMN and ascorbic acid leads to the cleavage of the -C-Se- bond to produce a carbon-centered radical and PhSe(-) species via the intermediacy of R(2)CH-SePh&uprhbr;(-)(*). The mechanistic interpretation for the reductive activation of -C-Se- bonds and the synthetic utility of observed cleavage pattern is extended for the unimolecular group transfer radical sequences.     

Interaction of Valdecoxib with β-cyclodextrin: Experimental and Molecular Modeling Studies

This study aimed to investigate the effect of β-cyclodextrin on aqueous solubility and dissolution rate of valdecoxib and also to get an insight of molecular interactions involved in formation of valdecoxib‐β-cyclodextrin inclusion complex. Phase solubility analysis indicated complex with possible stoichiometry of 1:1 and a stability constant of 234.01 M⁻¹. Thermodynamic studies in water indicated exothermic nature of inclusion complexation.␣Valdecoxib‐β-cyclodextrin complexes (1:1 M) were prepared by kneading method, solution method and␣freeze–drying method. The complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (P-XRD), Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance␣(¹H-NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of β-cyclodextrin with valdecoxib. ¹H-NMR analysis suggested that the unsubstituted phenyl ring of valdecoxib display favorable interaction with the hydrophobic cavity of β-cyclodextrin, which was confirmed by molecular dynamic simulations. An inclusion complex model has been established for explaining the observed enhancement of solubility of valdecoxib in water by β-cyclodextrin. Dissolution studies in water showed that the valdecoxib in freeze-dried complex dissolved much faster than the uncomplexed drug and physical mixture. This improvement in dissolution rate is attributed to the increased solubility and wettability due to encapsulation along with decreased crystallanity caused by complex formation, which is evident by DSC and P-XRD studies.     

The rearrangement of 2,3-epoxysulfonates and its application to natural products syntheses: formal synthesis of (-)-aphanorphine and total syntheses of (-)-alpha-herbertenol and (-)-herbertenediol

The Lewis acid treatment of 2,3-epoxysulfonates with 2,3-dialkyl substituents or 2-alkyl-3-aryl substituents produced the rearrangement products via C3-cleavage of the oxirane ring in high yields. On the other hand, 2-aryl-3-alkyl-2,3-epoxysulfonates produced the products via C2-cleavage of the oxirane ring. The sulfonyloxy groups of the alpha-sulfonyloxy ketones, having a chiral benzylic quaternary carbon center obtained by the rearrangement of 2-alkyl-3-aryl-2,3-epoxysulfonates, were reductively eliminated to give the ketones with a chiral benzylic quaternary carbon center. The method was applied to the formal synthesis of (-)-aphanorphine and total syntheses of (-)-alpha-herbertenol and (-)-herbertenediol.     

A concise methodology for the synthesis of (−)-Δ-tetrahydrocannabinol and (−)-Δ-tetrahydrocannabivarin metabolites and their regiospecifically deuterated analogs

The availability of tetrahydrocannabinols (Δ⁹-THC), tetrahydrocannabivarins (Δ⁹-THCV), and their metabolites in both their undeuterated and deuterated forms is critical for the analysis of biological and toxicological samples. We report here a concise methodology for the syntheses of (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in significantly improved overall yields using commercially available starting materials. Our approach allowed us to obtain the key intermediates (6aR,10aR)-9-nor-9-oxo-hexahydrocannabinols in four steps from (+)-(1R)-nopinone. This was followed by an optimized Shapiro reaction to give the (−)-11-nor-9-carboxy-metabolites, which were converted to their respective (−)-11-hydroxy analogs. The synthetic sequence involves a minimum number of steps, avoids undesirable oxidative conditions, and incorporates the costly deuterated resorcinols near the end of the synthetic sequence. This methodology enabled us to synthesize eight regiospecifically deuterated (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in a preparative scale and high optical purity without deuterium scrambling or loss.     

Efficient evaluation of highly oscillatory acoustic scattering surface integrals

We consider the approximation of some highly oscillatory weakly singular surface integrals, arising from boundary integral methods with smooth global basis functions for solving problems of high frequency acoustic scattering by three-dimensional convex obstacles, described globally in spherical coordinates. As the frequency of the incident wave increases, the performance of standard quadrature schemes deteriorates. Naive application of asymptotic schemes also fails due to the weak singularity. We propose here a new scheme based on a combination of an asymptotic approach and exact treatment of singularities in an appropriate coordinate system. For the case of a spherical scatterer we demonstrate via error analysis and numerical results that, provided the observation point is sufficiently far from the shadow boundary, a high level of accuracy can be achieved with a minimal computational cost.     

Asymptotics for the voltage potential in a periodic network with localized defects

We compare the potential u_h of a 2D regular lattice of conductors of size h, to the potential u_h,d of a defective lattice, where some conductive links have different conductivities. We show that to first order in h, each defect contributes to the difference u_h,d?u_h as a product of three terms: A polarization matrix, the gradient of the potential u of the limiting continuous medium obtained as h → 0, and the gradient of Green's function of the limiting medium. Establishing the asymptotics of u_h,d?u_h involves uniform W^1,∞ estimates on the potentials u_h. Copyright © 2007 John Wiley & Sons, Ltd.     

A Crank‐Nicolson Petrov‐Galerkin method with quadrature for semi‐linear parabolic problems

We propose and analyze an application of a fully discrete C² spline quadrature Petrov‐Galerkin method for spatial discretization of semi‐linear parabolic initial‐boundary value problems on rectangular domains. We prove second order in time and optimal order H¹ norm convergence in space for the extrapolated Crank‐Nicolson quadrature Petrov‐Galerkin scheme. We demonstrate numerically both L² and H¹ norm optimal order convergence of the scheme even if the nonlinear source term is not smooth. © 2005 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005.     

Protein Folding and β‐Sheet Proteins

The aim of this comprehensive review is to critically evaluate the progress in research in the area of protein folding. In the first section, we discuss the various models proposed to explain the protein folding paradox. In the succeeding section of the review, a detailed account of the developments in our understanding of the folding path ways of β‐sheet proteins is provided.