Synthesis of substituted 5-aminomethyl tetrahydro-isoquinolines and dihydro-isoindoles

The synthesis of ten substituted aminomethylene tetrahydro-isoquinolines is described, proceeding in eight steps from 5-hydroxyisoquinoline via reductive amination of N-Boc tetrahydro-isoquinoline 5-carboxaldehyde. Likewise, reductive amination was used to prepare four substituted dihydro-isoindoles from the corresponding aldehyde. The dihydro-isoindole ring system was conveniently accessed via a 2+2+2 cycloaddition reaction.     

Mechanistic study of alcohol oxidation by the Pd(OAc)(2)/O(2)/DMSO catalyst system and implications for the development of improved aerobic oxidation catalysts

The Pd(OAc)2/O2/DMSO catalyst system displays impressive versatility in the aerobic oxidation of organic substrates, ranging from alcohols to olefins. This report details mechanistic insights into these reactions. Dimethyl sulfoxide (DMSO) plays no redox role in the chemistry, and kinetic experiments identify the turnover-limiting step as DMSO-promoted oxidation of palladium(0) by molecular oxygen. The "chemical oxidase" pathway characterized for this catalyst system holds great promise for the design of new aerobic oxidation reactions.     

Mechanistic characterization of aerobic alcohol oxidation catalyzed by Pd(OAc)(2)/pyridine including identification of the catalyst resting state and the origin of nonlinear [catalyst] dependence

The Pd(OAc)(2)/pyridine catalyst system is one of the most convenient and versatile catalyst systems for selective aerobic oxidation of organic substrates. This report describes the catalytic mechanism of Pd(OAc)(2)/pyridine-mediated oxidation of benzyl alcohol, which has been studied by gas-uptake kinetic methods and (1)H NMR spectroscopy. The data reveal that turnover-limiting substrate oxidation by palladium(II) proceeds by a four-step pathway involving (1) formation of an adduct between the alcohol substrate and the square-planar palladium(II) complex, (2) proton-coupled ligand substitution to generate a palladium-alkoxide species, (3) reversible dissociation of pyridine from palladium(II) to create a three-coordinate intermediate, and (4) irreversible beta-hydride elimination to produce benzaldehyde. The catalyst resting state, characterized by (1)H NMR spectroscopy, consists of an equilibrium mixture of (py)(2)Pd(OAc)(2), 1, and the alcohol adduct of this complex, 1xRCH(2)OH. These in situ spectroscopic data provide direct support for the mechanism proposed from kinetic studies. The catalyst displays higher turnover frequency at lower catalyst loading, as revealed by a nonlinear dependence of the rate on [catalyst]. This phenomenon arises from a competition between forward and reverse reaction steps that exhibit unimolecular and bimolecular dependences on [catalyst]. Finally, overoxidation of benzyl alcohol to benzoic acid, even at low levels, contributes to catalyst deactivation by formation of a less active palladium benzoate complex.     

Facilitated phosphatidylserine flip-flop across vesicle and cell membranes using urea-derived synthetic translocases

Tris(2-aminoethyl)amine derivatives with appended urea and sulfonamide groups are shown to facilitate the translocation of fluorescent phospholipid probes and endogenous phosphatidylserine across vesicle and erythrocyte cell membranes. The synthetic translocases appear to operate by binding to the phospholipid head groups and forming lipophilic supramolecular complexes which diffuse through the non-polar interior of the bilayer membrane.     

Radical cyclisation reactions with indoles

Several radical cyclisation reactions involving indoles are described. Most notably, we have shown that radical additions to C3 of an indole are frequently facile. A dichotomy in the course of radical cyclisation reactions to C2 of the indole has also been exposed wherein 6-endo-trig cyclisations are propagated by the loss of a hydrogen atom from C2 while 5-exo-trig cyclisations are propagated by hydrogen atom abstraction at C3 from tributyltin hydride. Cyclisations involving the addition of indolyl radical intermediates to arenes have also been demonstrated.     

Multiple sprayer system for high-throughput electrospray ionization mass spectrometry

A multiple sprayer electrospray ion source for high-throughput analysis is described. The ion source is comprised of multiple electrospray capillaries, each with an ion lens located near the tip. The electric potentials applied to the ion lenses are used to control the sprayers. The use of ion lenses eliminates the need for mechanical blocking devices to selectively enable or disable the sprayers, and results in a less expensive and more reliable set-up. Sprayers can be enabled or disabled within approximately 50-250 ms when the lens potentials are controlled manually. For simultaneous operation of multiple electrospray capillaries, it is advantageous to orient the capillaries so that the spray from each passes directly in front of the entrance aperture of the mass spectrometer.     

Selective, controllable, and reversible aggregation of polystyrene latex microspheres via DNA hybridization

The directed three-dimensional self-assembly of microstructures and nanostructures through the selective hybridization of DNA is the focus of great interest toward the fabrication of new materials. Single-stranded DNA is covalently attached to polystyrene latex microspheres. Single-stranded DNA can function as a sequence-selective Velcro by only bonding to another strand of DNA that has a complementary sequence. The attachment of the DNA increases the charge stabilization of the microspheres and allows controllable aggregation of microspheres by hybridization of complementary DNA sequences. In a mixture of microspheres derivatized with different sequences of DNA, microspheres with complementary DNA form aggregates, while microspheres with noncomplementary sequences remain suspended. The process is reversible by heating, with a characteristic "aggregate dissociation temperature" that is predictably dependent on salt concentration, and the evolution of aggregate dissociation with temperature is observed with optical microscopy.     

Real-time picosecond measurements of electronic energy transfer from DODCI to malachite green and DQOCI

Singlet-singlet resonance energy transfers from DODCI (donor) to malachite green and to DQOCI in ethanolic solutions have been investigated with a real-time picosecond streak-camera (time-resolution 3–5 ps) operating at a repetition rate of 140 MHz, in synchronism with the pulse train from a mode-locked cw dye laser used as excitation source. Acceptor concentrations from 10^?5 M to 7.5 × 10^?3 M were studied and average R_o values of 45.6 Å for malachite green and 61.8 Å for DQOCI are obtained from the directly measured fluorescence decay curves. Departure from Förster kinetics is seen at the lower acceptor concentrations employed.