Photoreaction of skin-sensitizing trimethyl psoralen with lipid membrane models

The concerted photoreaction between trimethyl psoralen (TMP) and isomeric model compounds of oleic acid methyl ester (OAME) and eadilic acid methyl ester (EAME) are explored using density functional theory. The S(1) surfaces all reveal large barriers (25-31 kcal/mol) to reach the decay channels, whereas the S(2) surfaces differ considerably between the furan and pyrone side adducts. For the pyrone side adducts, a small barrier to reach the intersection between the S(1) and S(2) states is found, followed by a small second barrier on the S(1) surface to the low-lying decay channel. For the furan-side adducts, no such intersection between S(1) and S(2) is seen, which thus prevents these products from being formed in high yields. The photoinduced cycloaddition is more favorable between OAME and the pyrone side double bond of TMP than for any of the other systems, which agrees with the experimental findings that this is formed in the highest yield. The computed UV absorption spectra of TMP and the TMP(pyrone)-OAME cycloadduct agree well with the experimental spectra.     

Feasibility of nonvolatile buffers in capillary electrophoresis-electrospray ionization-mass spectrometry of proteins

The combination of capillary electrophoresis (CE) and electrospray ionization-mass spectrometry (ESI-MS) via a triaxial interface was studied as a potential means for the characterization of intact proteins. To evaluate the possibility to use a nonvolatile electrolyte for CE, the effect of sodium phosphate and ammonium borate on the MS signal of the proteins insulin, myoglobin, and bovine serum albumin (BSA) was investigated by employing infusion experiments, and compared to the effect of ammonium formate and formic acid. The study shows that with formic acid (50 mM, pH 2.4) the most intense protein signals were obtained, while the use of sodium phosphate buffer (5 and 10 mM, pH 7.5) almost completely diminished the MS response. Ammonium formate and ammonium borate (up to 100 mM, pH 8.5) also caused protein ion suppression, but especially with the borate buffer significant MS intensity remained. MS analysis of myoglobin revealed the loss of the heme group when an acidic CE electrolyte was used. Using a background electrolyte containing 25 mM ammonium borate (pH 8.5), it is demonstrated that a CE separation of a protein test mixture can be monitored with ESI-MS without degrading the MS performance allowing molecular weight determinations of the separated compounds. In the presence of borate, detection limits were estimated to be 5-10 microM (ca. 100 fmol injected). The usefulness of the CE-MS system employing a borate buffer is indicated by the analysis of a stored sample of BSA revealing several degradation products. A sample of placental alkaline phosphatase (PLAP), a potential therapeutic agent, was also analyzed by CE-MS indicating the presence of a protein impurity. Probably due to insufficient ionization of the PLAP (a complex glycoprotein), no MS signals of the intact protein were observed.     

Diastereoselective Synthesis of Cyclopenta[c]furans by a Catalytic Multicomponent Reaction

A diastereoselective three‐component reaction between alkynyl enones, aldehydes and secondary amines is reported. With the aid of a benign indium catalyst, a range of highly substituted cyclopenta[c]furan derivatives can be obtained in a single‐step procedure. The formation of the stereodefined heterocyclic motifs takes place via in situ generation of enamines followed by two sequential cyclization steps.     

Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer

5-Aminolevulinic acid (5ALA) and ester derivates thereof are used as prodrugs in photodynamic therapy (PDT). The behavior of 5ALA and three esters of 5ALA in a DPPC lipid bilayer is investigated. In particular, the methyl ester displays a very different free energy profile, where the highest barrier is located in the region with highest lipid density, while the others have their peak in the middle of the membrane, and also displays a considerably lower permeability coefficient than neutral 5ALA and the ethyl ester. The zwitterion of 5ALA has the highest permeability constant, but a significant free energy minimum in the polar head-group region renders an accumulation in this region.     

Steric influence on the excited-state lifetimes of ruthenium complexes with bipyridyl-alkanylene-pyridyl ligands

The structural effect on the metal-to-ligand charge transfer (MLCT) excited-state lifetime has been investigated in bis-tridentate Ru(II)-polypyridyl complexes based on the terpyridine-like ligands [6-(2,2'-bipyridyl)](2-pyridyl)methane ( 1) and 2-[6-(2,2'-bipyridyl)]-2-(2-pyridyl)propane ( 2). A homoleptic ([Ru( 2) 2] (2+)) and a heteroleptic complex ([Ru(ttpy)( 2)] (2+)) based on the new ligand 2 have been prepared and their photophysical and structural properties studied experimentally and theoretically and compared to the results for the previously reported [Ru( 1) 2] (2+). The excited-state lifetime of the homoleptic Ru (II) complex with the isopropylene-bridged ligand 2 was found to be 50 times shorter than that of the corresponding homoleptic Ru (II) complex of ligand 1, containing a methylene bridge. A comparison of the ground-state geometries of the two homoleptic complexes shows that steric interactions involving the isopropylene bridges make the coordination to the central Ru (II) ion less octahedral in [Ru( 2) 2] (2+) than in [Ru( 1) 2] (2+). Calculations indicate that the structural differences in these complexes influence their ligand field splittings as well as the relative stabilities of the triplet metal-to-ligand charge transfer ( (3)MLCT) and metal-centered ( (3)MC) excited states. The large difference in measured excited-state lifetimes for the two homoleptic Ru (II) complexes is attributed to a strong influence of steric interactions on the ligand field strength, which in turn affects the activation barriers for thermal conversion from (3)MLCT states to short-lived (3)MC states.     

Hydration of lanthanoid(III) ions in aqueous solution and crystalline hydrates studied by EXAFS spectroscopy and crystallography: the myth of the "gadolinium break"

The structures of the hydrated lanthanoid(III) ions including lanthanum(III) have been characterized in aqueous solution and in the solid trifluoromethanesulfonate salts by extended X-ray absorption fine structure (EXAFS) spectroscopy. At ambient temperature the water oxygen atoms appear as a tricapped trigonal prism around the lanthanoid(III) ions in the solid nonaaqualanthanoid(III) trifluoromethanesulfonates. Water deficiency in the capping positions for the smallest ions starts at Ho and increases with increasing atomic number in the [Ln(H(2)O)(9-x)](CF(3)SO(3))(3) compounds with x=0.8 at Lu. The crystal structures of [Ho(H(2)O)(8.91)](CF(3)SO(3))(3) and [Lu(H(2)O)(8.2)](CF(3)SO(3))(3) were re-determined by X-ray crystallography at room temperature, and the latter also at 100 K after a phase-transition at about 190 K. The very similar Ln K- and L(3)-edge EXAFS spectra of each solid compound and its aqueous solution indicate indistinguishable structures of the hydrated lanthanoid(III) ions in aqueous solution and in the hydrated trifluoromethanesulfonate salt. The mean Ln--O bond lengths obtained from the EXAFS spectra for the largest ions, La-Nd, agree with estimates from the tabulated ionic radii for ninefold coordination but become shorter than expected starting at samarium. The deviation increases gradually with increasing atomic number, reaches the mean Ln-O bond length expected for eightfold coordination at Ho, and increases further for the smallest lanthanoid(III) ions, Er-Lu, which have an increasing water deficit. The low-temperature crystal structure of [Lu(H(2)O)(8.2)](CF(3)SO(3))(3) shows one strongly bound capping water molecule (Lu-O 2.395(4) A) and two more distant capping sites corresponding to Lu-O at 2.56(1) A, with occupancy factors of 0.58(1) and 0.59(1). There is no indication of a sudden change in hydration number, as proposed in the "gadolinium break" hypothesis.     

Effective thermostat induced by coarse graining of simple point charge water

We investigate how the transport properties of a united atom fluid with a dissipative particle dynamics thermostat depend on the functional form and magnitude of both the conservative and the stochastic interactions. We demonstrate how the thermostat strongly affects the hydrodynamics, especially diffusion, viscosity, and local escape times. As model system we use simple point charge (SPC) water, from which projected trajectories are used to determine the effective interactions in the united atom model. The simulation results support our argument that the thermostat should be viewed as an integral part of the coarse-grained dynamics rather than a tool for approaching thermal equilibrium. As our main result we show that the united atom model with the adjusted effective interactions approximately reproduces the diffusion constant and the viscosity of the underlying detailed SPC water model.     

Investigations of glycosylation reactions with 2-N-acetyl-2N,3O-oxazolidinone-protected glucosamine donors

NIS/AgOTf-promoted glycosylations with ethyl 2,3-N,O-carbonyl-2-deoxy-1-thio-beta-D-glucopyranoside donors can be performed with either alpha- or beta-selectivity by tuning the reaction conditions. Small amounts of AgOTf (0.1 equiv) and short reaction times give beta-selectivity, whereas 0.4 equiv of AgOTf and prolonged reaction times afford alpha-linked products. NMR-monitored glycosylation and anomerization experiments show initial formation of exclusively the beta-linkage, which anomerizes, through an intramolecular mechanism involving an endocyclic C-O bond cleavage, to the alpha-linkage.