<Emphasis Type="Italic">L</Emphasis>-Carnitine Supplementation: A New Paradigm for its Role in Exercise

Summary. Early research investigating the effects of L-carnitine supplementation has examined its role in substrate metabolism and in acute exercise performance. These studies have yielded equivocal findings, partially due to difficulties in increasing muscle carnitine concentrations. However, recent studies have proposed that L-carnitine may play a different role in exercise physiology, and preliminary results have been encouraging. Current investigations have theorized that L-carnitine supplementation facilitates exercise recovery. Proposed mechanism is as follows: 1) increased serum carnitine concentration enhances capillary endothelial function; 2) increased blood flow and reduced hypoxia mitigate the cascade of ensuing, destructive chemical events following exercise; 3) thus allowing reduced structural damage of skeletal muscle mediated by more intact receptors in muscle needed for improved protein signaling. This paradigm explains decreased markers of purine catabolism, free radical formation, and muscle tissue disruption after resistance exercise and the increased repair of muscle proteins following long-term L-carnitine supplementation.     

Synthesis of some dibenzodiazepinone derivatives as potent and m2-selective antimuscarinic compounds

Two series of 5-[[4-[4-(dialkylamino)butyl]-l-cyclohexyl]acetyl], and 5-[(dialkylamino)acyl]-10,11-dihydro-5H- dibenzo[b,e][1,4]diazepin-11-ones were synthesized as potential m2-selective ligands 1,2. Their affinity and selectivity for the muscarinic cholinergic receptor m-AChR subtypes were determined. Replacing a nitrogen with CH in the piperidine ring of 5-[[4-[4-(dialkylamino)butyl]-l-piperidinyl]acetyl]-10,11-dihydro-5H-dibenzo-[b,e][1,4]diazepin-11-ones 3 significantly altered the affinity and selectivity to the muscarinic receptor subtypes.     

The fast multipole boundary element method for molecular electrostatics: An optimal approach for large systems

We propose a fast implementation of the boundary element method for solving the Poisson equation, which approximately determines the electrostatic field around solvated molecules of arbitrary shape. The method presented uses computational resources of order O(N) only, where N is the number of elements representing the dielectric boundary at the molecular surface. The method is based on the Fast Multipole Algorithm by Rokhlin and Greengard, which is used to calculate the Coulombic interaction between surface elements in linear time. We calculate the solvation energies of a sphere, a small polar molecule, and a moderately sized protein. The values obtained by the boundary element method agree well with results from finite difference calculations and show a higher degree of consistency due to the absence of grid dependencies. The boundary element method can be taken to a much higher accuracy than is possible with finite difference methods and can therefore be used to verify their validity. © 1995 by John Wiley & Sons, Inc.     

Anodic hydroxylation of 1-carbomethoxy-1,2,3,4-tetrahydrocarbazoles

1-Carbomethoxy-1,2,3,4-tetrahydrocarbazole (1) and its 7-methoxy derivative (2) were oxidized at carbon felt anodes in acetonitrile containing 0.2 M LiClO₄ and 2-17 M water at potentials on the rising portion of the primary oxidation peak to yield products formed by formal substitution of the C-1 H atom with hydroxide. The resulting 1-hydroxy-l-carbomethoxy-1,2,3,4-tetrahydrocarbazole and its 7-methoxy derivative were isolated in 44 and 22% yields, respectively, when sodium bicarbonate was used to control acidity of the medium. Structures were elucidated by NMR, IR, elemental analysis, and mass spectrometry. Voltammetry at carbon-paste and glassy carbon electrodes showed that the oxidations proceed by an ECE or DISPI pathway. The rate-determining step is the reaction of water with a cation radical electrochemically generated from 1 or 2, involving either proton abstraction or nucleophilic addition.     

Role for bound water and CH-pi aromatic interactions in photosynthetic electron transfer

Photosystem I (PSI) is one of two photosynthetic reaction centers present in plants, algae, and cyanobacteria and catalyzes the reduction of ferredoxin and the oxidation of cytochrome c or plastocyanin. The PSI primary chlorophyll donor, which is oxidized in the primary electron-transfer events, is a heterodimer of chl a and a' called P700. It has been suggested that protein relaxation accompanies light-induced electron transfer in this reaction center (Dashdorj, N.; Xu, W.; Martinsson, P.; Chitnis, P. R.; Savikhin, S. Biophys. J. 2004, 86, 3121. Kim, S.; Sacksteder, C. A.; Bixby, K. A.; Barry, B. A. Biochemistry 2001, 40, 15384). To investigate the details of electron transfer and relaxation events in PSI, we have employed several experimental approaches. First, we report a pH-dependent viscosity effect on P700+ reduction; this result suggests a role for proton transfer in the PSI electron-transfer reactions. Second, we find that changes in hydration alter the rate of P700+ reduction and the interactions of P700 with the protein environment. This result suggests a role for bound water in electron transfer to P700+. Third, we present evidence that deuteration of the tyrosine aromatic side chain perturbs the vibrational spectrum, associated with P700+ reduction. We attribute this result to a linkage between CH-pi interactions and electron transfer to P700+.     

Total synthesis of (+)-amphidinolide A. Structure elucidation and completion of the synthesis

The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of NMR chemical shift analysis and total synthesis. The 20-membered ring of amphidinolide A was formed by a ruthenium-catalyzed alkene-alkyne coupling to forge the C15-C16 bond. Using the reported structure 1 as a starting point, a number of diastereomers of amphidinolide A were prepared. Deviations of the chemical shift of key protons in each isomer relative to the natural material were used as a guide to determine the locations of the errors in the relative stereochemistry. The spectroscopic data for the synthetic and natural material are in excellent agreement.     

Dynamic,computer-assisted interpretation of infrared spectra of condensed-phase mixtures

A knowledge-based system, MIXIR, designed to assist researchers in interpreting the infrared spectra of condensed-phase mixtures is described. This system overcomes many of the inherent limitations of static-rule-based systems. An iterative problem-solving approach is permitted, making use of information gained during the interpretation process. The dynamic rule selection and significance evaluation alos allow the user to provide information on the sample matrix, or to select a subset of the compounds for rule derivation. The MIXIR system was evaluated with a knowledge base compiled using IRBASE, a complementary program, and a test set of 20 mixtures.     

Synthesis of methyl-1,6-dioxaspiro[4,5]decanes using organoselenium mediated cyclization reactions

Three naturally occurring methyl-1,6-dioxaspiro[4.5]decanes have been prepared in good yield using organoselenium mediated reactions during the crucial cyclization process.     

The application of diethylaminosulfur trifluoride in the synthesis of fluorinated sterols and bile acids

Methyl 3,3-(ethylenedioxy)-6β-fluoro-5β-cholan-24-oate has been prepared starting from hyodeoxycholic acid and 3,3-(ethylenedioxy)-7( and β)-fluorocholestan-22-al starting from stigmasterol, using diethylaminosulfur trifluoride as the fluorinating agent. These molecules will be used to synthesize analogs of the aminosterol antibiotic squalamine.