Reaction of 3-benzylidene-2,4-pentanedione and 3-methoxymethylene-2,4-pentanedione with aroylhydrazines

Aroylhydrazines 2 reacted with 3-benzylidene-2,4-pentanedione ( 1 ) to give 1-aroyl-3,5-dimethyl-1H-pyrazoles 5 and benzaldehyde aroylhydrazones 6 . From the reaction of 3-methoxymethylene-2,4-pentanedione ( 7 ) with aroylhydrazines 2 the unknown N-aroyl-4-acetyl-1H-pyrazoles 9 were exclusively isolated in good yields.     

Intrazeolite photooxidations of electron-poor alkenes

The inability of the intrazeolite environment to influence the regiochemistry of addition of singlet oxygen to electron-poor olefins is reported. This divergent behavior with respect to electron-rich alkenes is rationalized with a multicomplexation model that emphasizes the importance of intrazeolite substrate-cation binding.     

Time resolved infrared absorption studies of geminate recombination and vibrational relaxation in OClO photochemistry

Ultrafast time-resolved infrared absorption studies of aqueous chlorine dioxide (OClO) photochemistry are reported. Following photoexcitation at 401 nm, the evolution in optical density at frequencies between 1000 to 1100 cm(-1) is monitored to investigate vibrational energy deposition and relaxation along the asymmetric-stretch coordinate following the reformation of ground-state OClO via geminate recombination of the primary photofragments. The measured kinetics are compared to two proposed models for the vibrational-relaxation dynamics along the asymmetric-stretch coordinate. This comparison demonstrates that the perturbation model derived from molecular dynamics studies is capable of qualitatively reproducing the observed kinetics, where the collisional model employed in previous UV-pump, visible probe experiments demonstrates poor agreement with experiment. The ability of the perturbation model to reproduce the optical-density evolution observed in these studies demonstrates that for aqueous OClO, frequency dependence of the solvent-solute coupling is important in defining the level-dependent vibrational relaxation rates along the asymmetric-stretch coordinate. The absence of optical-density evolution corresponding to the population of higher vibrational levels (n>8) along the asymmetric-stretch coordinate suggests that following geminate recombination, energy is initially deposited into a local Cl-O stretch, with the relaxation of vibrational energy from this coordinate providing for delayed vibrational excitation of the asymmetric- and symmetric-stretch coordinates relative to geminate recombination, as previously observed.     

Applications of “Hot” and “Cold” Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging

The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using ⁶⁴CuATSM [copper (diacetyl‐bis(N4‐methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21^st century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in “cold” and “hot” Cu(II) and Ga(III) derivatives for PET applications and ¹¹¹In(III) derivatives for SPECT (single‐photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium‐based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications.     

Modeling,Simulation, and Implementation of Solar‐Driven Water‐Splitting Devices

An integrated cell for the solar‐driven splitting of water consists of multiple functional components and couples various photoelectrochemical (PEC) processes at different length and time scales. The overall solar‐to‐hydrogen (STH) conversion efficiency of such a system depends on the performance and materials properties of the individual components as well as on the component integration, overall device architecture, and system operating conditions. This Review focuses on the modeling‐ and simulation‐guided development and implementation of solar‐driven water‐splitting prototypes from a holistic viewpoint that explores the various interplays between the components. The underlying physics and interactions at the cell level is are reviewed and discussed, followed by an overview of the use of the cell model to provide target properties of materials and guide the design of a range of traditional and unique device architectures.     

Enantioselective,Stereodivergent Hydroazidation and Hydroamination of Allenes Catalyzed by Acyclic Diaminocarbene (ADC) Gold(I) Complexes

The gold‐catalyzed enantioselective hydroazidation and hydroamination reactions of allenes are presented herein. ADC gold(I) catalysts derived from BINAM were critical for achieving high levels of enantioselectivity in both transformations. The sense of enantioinduction is reversed for the two different nucleophiles, allowing access to both enantiomers of the corresponding allylic amines using the same catalyst enantiomer.     

Mechanisms of Cysteine-Lysine Covalent Linkage—The Role of Reactive Oxygen Species and Competition with Disulfide Bonds**

Recently, a new naturally occurring covalent linkage was characterised, involving a cysteine and a lysine, bridged through an oxygen atom. The latter was dubbed as the NOS bond, reflecting the individual atoms involved in this uncommon bond which finds little parallel in lab chemistry. It is found to form under oxidising conditions and is reversible upon addition of reducing agents. Further studies have identified the bond in crystal structures across a variety of systems and organisms, potentially playing an important role in regulation, cellular defense and replication. Not only that, double NOS bonds have been identified and even found to be competitive in relation to the formation of disulfide bonds. This raises several questions about how this exotic bond comes to be, what are the intermediates involved in its formation and how it competes with other pathways of sulfide oxidation. With this objective in mind, we revisited our first proposed mechanism for the reaction with model electronic structure calculations, adding information about the reactivity with alternative reactive oxygen species and other potential competing products of oxidation. We present a network with more than 30 reactions which provides one of the most encompassing pictures for cysteine oxidation pathways to date.     

Design,Synthesis, and Application of a Water-soluble Photocage for Aqueous Cyclopentadiene-based Diels-Alder Photoclick Chemistry in Hydrogels

Spatiotemporally functionalized hydrogels have exciting applications in tissue engineering, but their preparation often relies on radical-based strategies that can be deleterious in biological settings. Herein, the computationally guided design, synthesis, and application of a water-soluble cyclopentadienone-norbornadiene (CPD-NBD) adduct is disclosed as a diene photocage for radical-free Diels-Alder photopatterning. We show that this scalable CPD-NBD derivative is readily incorporated into hydrogel formulations, providing gels that can be patterned with dienophiles upon 365 nm uncaging of cyclopentadiene. Patterning is first visualized through conjugation of cyanine dyes, then biological utility is highlighted by patterning peptides to direct cellular adhesion. Finally, the ease of use and versatility of this CPD-NBD derivative is demonstrated by direct incorporation into a commercial 3D printing resin to enable the photopatterning of structurally complex, printed hydrogels.     

Release of rifampicin from chitosan, PLGA and chitosan-coated PLGA microparticles

Recently three groups of rifampicin (RIF)-loaded microparticles (MPs), consisting of chitosan (CHT), PLGA and PLGA/CHT mixtures, were assessed in terms of RIF-loading and retention during nebulisation. The CHT-coated PLGA MPs were found to exhibit high RIF-loading ability together with nebulisation ability, stability, and mucoadhesive properties. All MP types had comparable toxicity towards alveolar cells which was significantly lower than that of the free drug. Herein, we study the release of RIF from all MP-types, during incubation in buffer with pH values: 4.40 and 7.40. Results show that CHT particles exhibit a higher burst release compared to PLGA MPs; at pH 4.40, which is explained by the higher solubility of CHT in acidic media. At pH 7.40 burst release from CHT MP's is significantly lower when CHT is crosslinked with glutaraldehyde, which is consistent with their - previously observed - increased stability during nebulization. From PLGA MPs, RIF release was pH independent under the conditions applied, while the amount of PVA (stabilizer) considerably affected drug release. When PLGA MP's were coated with CHT, at pH 7.40 the retention of RIF increased further (compared to non-coated MPs), while at pH 4.40 the release was faster from the CHT-coated particles. Concluding, it is proven that when PLGA MPs are coated with CHT, in addition to increased particle mucoadhesive properties, the release kinetics of RIF are modified.     

PLGA, chitosan or chitosan-coated PLGA microparticles for alveolar delivery? A comparative study of particle stability during nebulization

Various types of rifampicin (RIF)-loaded microparticles were compared for their stability during nebulization. Poly(lactide-co-glycolide) (PLGA), chitosan (CHT) and PLGA/CHT microparticles (MPs) were prepared by emulsion or precipitation techniques. MPs ability to be nebulized (NE%) as well as stability during freeze-drying or/and nebulization (NEED%), were evaluated after RIF extraction from MPs and determination by light spectroscopy. MP mean diameters and ζ-potential values were measured by dynamic light scattering, morphology was assessed by SEM, cytotoxicity by MTT method and mucoadhesive properties by mucin association.

In all cases, freeze-drying prior to nebulization did not affect EE%, NE or NEED%. In CHT, MPs RIF encapsulation efficiency (EE%) decreased with increasing CHT concentration (viscosity) and CHT-MP NEED% was higher when the polymer was crosslinked by glutaraldehyde. PLGA MPs, exhibited both higher RIF EE% and also higher nebulization ability and NEED%, compared to CHT ones, but also higher cytotoxicity. However, when the two polymers were combined in the PLGA/CHT MPs, EE%, NE% and NEED% increased with increasing MP CHT-content. PLGA/CHT MPs with 0.50% or 0.75% CHT exhibited highest EE% for RIF and also best nebulization ability and stability, compared to all other MP formulations studied. Additionally they had good mucoadhesive properties and comparably low cytotoxicity.