Efficient Synthesis of Submicrometer-Sized Active Pharmaceuticals by Laser Fragmentation in a Liquid-Jet Passage Reactor with Minimum Degradation

One challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well-known method that leads to an increase in solubility due to an elevated total surface area. However, state-of-the-art comminution techniques like cryo-milling suffer from degradation and contamination of the drugs, particularly when sub-micrometer diameters are aspired that require long processing times. In this work, picosecond-pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid-jet passage reactor is used as a wear-free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid-jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), high-performance liquid chromatography (HPLC), and X-ray diffraction (XRD). Moreover, the underlying predominantly photo-mechanically induced laser fragmentation mechanisms of organic microparticles (MP) are discussed.     

A Combined Spectroscopic and Theoretical Study on a Ruthenium Complex Featuring a π-Extended dppz Ligand for Light-Driven Accumulation of Multiple Reducing Equivalents

The design of photoactive systems capable of storing and relaying multiple electrons is highly demanded in the field of artificial photosynthesis, where transformations of interest rely on multielectronic redox processes. The photophysical properties of the ruthenium photosensitizer [(bpy)₂Ru( oxim-dppqp )]²⁺ ( Ru ), storing two electrons coupled to two protons on the π-extended oxim-dppqp ligand under light-driven conditions, are investigated by means of excitation wavelength-dependent resonance Raman and transient absorption spectroscopies, in combination with time-dependent density functional theory; the results are discussed in comparison to the parent [(bpy)₂Ru(dppz)]²⁺ and [(bpy)₂Ru( oxo-dppqp )]²⁺ complexes. In addition, this study provides in-depth insights on the impact of protonation or of accumulation of multiple reducing equivalents on the reactive excited states.     

The Varied Frustrated Lewis Pair Reactivity of the Germylene Phosphaketene (CH{(CMe)(2,6-iPr2C6H3N)}2)GePCO

The germylene species (CH{(CMe)(2,6-iPr₂C₆H₃N)}₂)GePCO 1 is shown to react with the Lewis acids (E(C₆F₅)₃ E=B, Al). Nonetheless, 1 participates in FLP chemistry with electron deficient alkynes or olefins, acting as an intramolecular FLP. In contrast, in the presence of B(C₆F₅)₃ and an electron rich alkyne, 1 behaves as Ge-based nucleophile to effect intermolecular FLP addition to the alkyne. This reactivity demonstrates that the reaction pathway is controlled by the nature of the electrophile and nucleophile generated in solution, as revealed by extensive DFT calculations.     

The Non-Ancillary Nature of Trimethylsilylamide Substituents in Boranes and Borinium Cations

The known boranes (R(Me₃Si)N)₂BF (R=Me₃Si 1 , tBu 2 , C₆F₅ 3 , o-tol 4 , Mes 5 , Dipp 6 ) and borinium salts (R(Me₃Si)N)₂B][B(C₆F₅)₄] (R=Me₃Si 7 , tBu 8 ) are prepared and fully characterized. Compound 7 is shown to react with phosphines to generate [R₃PSiMe₃]⁺ and [R₃PH]⁺ (R=Me, tBu). Efforts to generate related borinium cations via fluoride abstraction from (R(Me₃Si)N)₂BF (R=C₆F₅ 3 , o-tol 4 , Mes 5 ) gave complex mixtures suggesting multiple reaction pathways. However for R=Dipp 6 , the species [(μ-F)(SiMe₂N(Dipp))₂BMe][B(C₆F₅)₄] was isolated as the major product, indicating methyl abstraction from silicon and F/Me exchange on boron. These observations together with state-of-the-art DFT mechanistic studies reveal that the trimethylsilyl-substituents do not behave as ancillary subsitutents but rather act as sources of proton, SiMe₃ and methyl groups.     

Pyrimidoquinazolinophenanthroline Opens Next Chapter in Design of Bridging Ligands for Artificial Photosynthesis**

The synthesis and detailed characterization of a new Ru polypyridine complex containing a heteroditopic bridging ligand with previously unexplored metal-metal distances is presented. Due to the twisted geometry of the novel ligand, the resultant division of the ligand in two distinct subunits leads to steady state as well as excited state properties of the corresponding mononuclear Ru(II) polypyridine complex resembling those of prototype [Ru(bpy)₃]²⁺ (bpy=2,2'-bipyridine). The localization of the initially optically excited and the nature of the long-lived excited states on the Ru-facing ligand spheres is evaluated by resonance Raman and fs-TA spectroscopy, respectively, and supported by DFT and TDDFT calculations. Coordination of a second metal (Zn or Rh) to the available bis-pyrimidyl-like coordination sphere strongly influences the frontier orbitals, apparent by, for example, luminescence quenching. Thus, the new bridging ligand motif offers electronic properties, which can be adjusted by the nature of the second metal center. Using the heterodinuclear Ru−Rh complex, visible light-driven reduction of NAD⁺ to NADH was achieved, highlighting the potential of this system for photocatalytic applications.     

Numbering homoclinic points of diffeomorphisms in the plane

In this paper we introduce a numerical conjugacy invariant for planar maps with homoclinic points. This invariant can be estimated based on partial information about the location of compact pieces of the stable and unstable manifolds of the system. The invariant is also related to topological entropy, and we indicate a method by which good bounds on the entropy of a system can be obtained.     

Multiphase Thermohaline Convection in the Earth’s Crust: I. A New Finite Element – Finite Volume Solution Technique Combined With a New Equation of State for NaCl–H2O

We present a new finite element – finite volume (FEFV) method combined with a realistic equation of state for NaCl–H₂O to model fluid convection driven by temperature and salinity gradients. This method can deal with the nonlinear variations in fluid properties, separation of a saline fluid into a high-density, high-salinity brine phase and low-density, low-salinity vapor phase well above the critical point of pure H₂O, and geometrically complex geological structures. Similar to the well-known implicit pressure explicit saturation formulation, this approach decouples the governing equations. We formulate a fluid pressure equation that is solved using an implicit finite element method. We derive the fluid velocities from the updated pressure field and employ them in a higher-order, mass conserving finite volume formulation to solve hyperbolic parts of the conservation laws. The parabolic parts are solved by finite element methods. This FEFV method provides for geometric flexibility and numerical efficiency. The equation of state for NaCl–H₂O is valid from 0 to 750°C, 0 to 4000 bar, and 0–100 wt.% NaCl. This allows the simulation of thermohaline convection in high-temperature and high-pressure environments, such as continental or oceanic hydrothermal systems where phase separation is common.     

Convective heat transfer characteristics of microencapsulated phase change material suspensions in minichannels

A comparative experimental study was conducted in order to investigate the convective heat transfer characteristics of water-based suspensions of microencapsulated phase change material (MEPCM) flowing through rectangular copper minichannels. The hydraulic diameter of the channels was 2.71 mm. MEPCM particles with an average size of 4.97 μm were used to form suspensions with mass concentrations ranging from 0 to 20%. The comparative experiments were performed for varying mass flow rates in the laminar region and varying thermal conditions. The cooling performance of the MEPCM suspensions strongly depended on the mass flow rate and the MEPCM mass concentration. The 5% suspension always showed a better cooling performance than water resulting in lower wall temperatures and enhanced heat transfer coefficients within the whole range of mass flow rates. The suspensions with higher mass concentrations, however, were more effective only at low mass flow rates. At higher mass flow rates they showed a less effective cooling performance than water.     

Diphospha-Ureas from the Phosphaketene Ph3GePCO

The phosphaketene Ph₃GePCO is shown to react with the phosphide KP(tBu)₂ to generate the anion [Ph₃GePC(O)P(tBu)₂]⁻ 1 . This species reacts with CH₃I or ClGePh₃ to give the dissymmetric diphospha-ureas (tBu)₂PC(O)P(GePh₃)(CH₃) 2 and (Ph₃Ge)₂PC(O)P(tBu)₂ 3 respectively. Sequential treatment of 2 with a base and CH₃I affords a route to (tBu)₂PC(O)P(CH₃)₂ 5 . These species are products of the first modular diphospha-urea synthesis. The subsequent thermal and photochemical reactivity of these species was also probed and described.     

Determination of boron and hydrogen in materials for multicrystalline solar cell production with prompt gamma activation analysis

Journal of Radioanalytical and Nuclear Chemistry - For the optimization of the manufacturing process of multicrystalline silicon (mc-Si) for solar cells in order to reduce energy consumption and...