An efficient synthesis of 7-hydroxy-2,6-dimethylchromeno[3,4-d]oxazol-4-one—a protected fragment of novenamine

The high-yielding six-step synthesis of 7-hydroxy-2,6-dimethylchromeno[3,4-d]oxazol-4-one 17 from commercially available 2,4-dihydroxy-3-methylacetophenone is described. Coumarin 17 constitutes a useful synthon for coumarin antibiotic synthesis. A new methodology for oxazole formation applicable to 3-aminocoumarins has been developed, and a mechanistic rationalization is proposed.     

A New Procedure for Highly Regio‐ and Stereoselective Iodoacetoxylation of Protected Glycals and α‐1,2‐Cyclopropanated Sugars

Protected glycals and α‐1,2‐cyclopropanated sugars were converted in high yields and selectivities in less than 2 h at low temperatures to 2‐deoxy‐2‐iodoglycosyl acetates or novel 2‐deoxy‐2‐iodomethylglycosyl acetates using the simple, inexpensive reagent mixture of ammonium iodide, hydrogen peroxide, and acetic anhydride/acetic acid in acetonitrile. The protected glycals gave rise to 2‐deoxy‐2‐bromoglycosyl acetates when ammonium bromide was used instead of the iodide, although longer reaction times were required and selectivities were inferior. Other simple olefins such as styrene and indene were also converted to their corresponding 1,2‐trans‐iodoacetates.     

Fast spin state initialization in a singly charged InAs-GaAs quantum dot by optical cooling

Quantum computation requires a continuous supply of rapidly initialized qubits for quantum error correction. Here, we demonstrate fast spin state initialization with near unity efficiency in a singly charged quantum dot by optically cooling an electron spin. The electron spin is successfully cooled from 5 to 0.06 K at a magnetic field of 0.88 T applied in Voigt geometry. The spin cooling rate is of order 10(9) s-1, which is set by the spontaneous decay rate of the excited state.     

Stimulated and spontaneous optical generation of electron spin coherence in charged GaAs quantum dots

We report on the coherent optical excitation of electron spin polarization in the ground state of charged GaAs quantum dots via an intermediate charged exciton (trion) state. Coherent optical fields are used for the creation and detection of the Raman spin coherence between the spin ground states of the charged quantum dot. The measured spin decoherence time, which is likely limited by the nature of the spin ensemble, approaches 10 ns at zero field. We also show that the Raman spin coherence in the quantum beats is caused not only by the usual stimulated Raman interaction but also by simultaneous spontaneous radiative decay of either excited trion state to a coherent combination of the two spin states.     

Directed evolution of cyclic peptides for inhibition of autophagy

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Unfortunately, chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of the autophagosome maturation machinery—with mid-nanomolar affinities and disrupted protein–protein interactions (PPIs) between LC3 and its binding partners in vitro. The most promising LC3-binding SUPR peptide accessed the cytosol at low micromolar concentrations as measured by chloroalkane penetration assay (CAPA) and inhibited starvation-mediated GFP-LC3 puncta formation in a concentration-dependent manner. LC3-binding SUPR peptides re-sensitized platinum-resistant ovarian cancer cells to cisplatin treatment and triggered accumulation of the adapter protein p62 suggesting decreased autophagic flux through successful disruption of LC3 PPIs in cell culture. In mouse models of metastatic ovarian cancer, treatment with LC3-binding SUPR peptides and carboplatin resulted in almost complete inhibition of tumor growth after four weeks of treatment. These results indicate that SUPR peptide mRNA display can be used to develop cell-penetrating macrocyclic peptides that target and disrupt the autophagic machinery in vitro and in vivo.

SUPR peptide mRNA display was used to evolve a cell-permeable, macrocyclic peptide for autophagy inhibition.     

Optically detected resonance spectroscopy of interface fluctuation quantum dots

We have performed optically detected resonance (ODR) spectroscopy on modulation-doped GaAs/AlGaAs quantum wells of different widths in which lateral fluctuations of the well width were purposely introduced by growth interruption at the interfaces. These monolayer fluctuations form quantum dots for which confinement and Coulomb correlation energies are comparable. By monitoring resonant changes of the dot ensemble photoluminescence induced by far-infrared (FIR) radiation in a magnetic field, we have observed cyclotron resonance (CR) of free electrons in the widest wells, as well as internal transitions of mobile and localized charged excitons. The latter, which are forbidden by magnetic translational invariance, have previously not been observed. For the narrower wells the effects of non-parabolicity and carrier localization on the CR and CR-like transitions have to be included for a proper interpretation of the measurements.     

Photoluminescence spectroscopy of the molecular biexciton in vertically stacked InAs-GaAs quantum dot pairs

We present photoluminescence studies of the molecular neutral biexciton-exciton spectra of individual vertically stacked InAs/GaAs quantum dot pairs. We tune either the hole or the electron levels of the two dots into tunneling resonances. The spectra are described well within a few-level, few-particle molecular model. Their properties can be modified broadly by an electric field and by structural design, which makes them highly attractive for controlling nonlinear optical properties.     

Analytical gradients of a state average MCSCF state and a state average diagnostic

An efficient method for calculating the Lagrange multipliers and the analytical gradients of one state included in a state average MCSCF wave function is presented. It is demonstrated that the state average energy of an ‘equal-weight’ scheme is invariant to rotations within the state average subspace and that the corresponding rotations should be eliminated from the Lagrangian equations. Finally, a diagnostic is presented, which gauges the energy difference between a state defined by a state average calculation and the corresponding fully variational multi-configurational SCF state.