Continuous flow synthesis of a pharmaceutical intermediate: a computational fluid dynamics approach.

Continuous flow chemistry has the potential to greatly improve efficiency in the synthesis of active pharmaceutical ingredients (APIs); however, the optimization of these processes can be complicated by a large number of variables affecting reaction success. In this work, a screening design of experiments was used to compare computational fluid dynamics (CFD) simulations with experimental results. CFD simulations and experimental results both identified the reactor residence time and reactor temperature as the most significant factors affecting product yield for this reaction within the studied design space. A point-to-point comparison of the results showed absolute differences in product yield as low as 2.4% yield at low residence times and up to 19.1% yield at high residence times with strong correlation between predicted and experimental percent yields. CFD was found to underestimate the product yields at low residence times and overestimate at higher residence times. The correlation in predicted product yield and the agreement in identifying significant factors in reaction performance reveals the utility of CFD as a valuable tool in the design of continuous flow tube reactors with significantly reduced experimentation.

Modulation of H-NS transcriptional silencing by magnesium.

The bacterial histone-like protein H-NS silences AT-rich DNA, binding DNA as 'stiffened' filaments or 'bridged' intrastrand loops. The switch between these modes has been suggested to depend on the concentration of divalent cations, in particular Mg2+, with elevated Mg2+ concentrations associated with a transition to bridging. Here we demonstrate that the observed binding mode is a function of the local concentration of H-NS and its cognate binding sites, as well as the affinity of the interactions between them. Mg2+ does not control a binary switch between these two modes but rather modulates the affinity of this interaction, inhibiting the DNA-binding and silencing activity of H-NS in a continuous linear fashion. The direct relationship between conditions that favor stiffening and transcriptional silencing activity suggests that although both modes can occur in the cell, stiffening is the predominant mode of binding at silenced genes.

Strong Dependence of Quantum-Dot Delayed Luminescence on Excitation Pulse Width.

Delayed luminescence involving charge-carrier trapping and detrapping has recently been identified as a widespread and possibly universal phenomenon in colloidal quantum dots. Its near-power-law decay suggests a relationship with blinking. Here, using colloidal CuInS2 and CdSe quantum dots as model systems, we show that short (nanosecond) excitation pulses yield less delayed luminescence intensity and faster delayed luminescence decay than observed with long (millisecond) square-wave excitation pulses. Increasing the excitation power also affects the delayed luminescence intensity, but the delayed luminescence decay kinetics appear much less sensitive to excitation power than to excitation pulse width. An idealized four-state kinetic model reproduces the major experimental trends and highlights the very slow approach to steady state during photoexcitation, stemming from extremely slow detrapping of the metastable charge-separated state responsible for delayed luminescence. The impacts of these findings on proposed relationships between delayed luminescence and blinking are discussed.

Luminescent Colloidal Semiconductor Nanocrystals Containing Copper: Synthesis, Photophysics, and Applications.

Copper-doped semiconductors are classic phosphor materials that have been used in a variety of applications for many decades. Colloidal copper-doped semiconductor nanocrystals have recently attracted a great deal of interest because they combine the solution processability and spectral tunability of colloidal nanocrystals with the unique photoluminescence properties of copper-doped semiconductor phosphors. Although ternary and quaternary semiconductors containing copper, such as CuInS2 and Cu2ZnSnS4, have been studied primarily in the context of their photovoltaic applications, when synthesized as colloidal nanocrystals, these materials have photoluminescence properties that are remarkably similar to those of copper-doped semiconductor nanocrystals. This review focuses on the luminescent properties of colloidal copper-doped, copper-based, and related copper-containing semiconductor nanocrystals. Fundamental investigations into the luminescence of copper-containing colloidal nanocrystals are reviewed in the context of the well-established luminescence mechanisms of bulk copper-doped semiconductors and copper(I) molecular coordination complexes. The use of colloidal copper-containing nanocrystals in applications that take advantage of their luminescent properties, such as bioimaging, solid-state lighting, and luminescent solar concentrators, is also discussed.

Photoluminescence Blinking and Reversible Electron Trapping in Copper-Doped CdSe Nanocrystals.

Single-particle photoluminescence blinking is observed in the copper-centered deep-trap luminescence of copper-doped CdSe (Cu(+):CdSe) nanocrystals. Blinking dynamics for Cu(+):CdSe and undoped CdSe nanocrystals are analyzed to identify the effect of Cu(+), which selectively traps photogenerated holes. Analysis of the blinking data reveals that the Cu(+):CdSe and CdSe nanocrystal "off"-state dynamics are statistically identical, but the Cu(+):CdSe nanocrystal "on" state is shorter lived. Additionally, a new and pronounced temperature-dependent delayed luminescence is observed in the Cu(+):CdSe nanocrystals that persists long beyond the radiative lifetime of the luminescent excited state. This delayed luminescence is analogous to the well-known donor-acceptor pair luminescence of bulk copper-doped phosphors and is interpreted as revealing metastable charge-separated excited states formed by reversible electron trapping at the nanocrystal surfaces. A mechanistic link between this delayed luminescence and the luminescence blinking is proposed. Collectively, these data suggest that electron (rather than hole) trapping/detrapping is responsible for photoluminescence intermittency in these nanocrystals.