Photochemistry of group 6 Fischer carbene complexes: beyond the photocarbonylation reaction

The seminal report by Hegedus in 1982, showing that alkoxychromium(0) carbenes reacted with imines under bright Colorado sunlight to yield β-lactams, marked the beginning of a key reaction in organometallic chemistry. Very little was known about the mechanism of this reaction. In fact, Hegedus proposed the reversible generation of a chromium-coordinated ketene, which would react with nucleophiles. This coordinated species would show all the advantages of ketenes without their shortcomings, namely, dimerization, formation of undesired adducts, and so forth. The quest for the detection of these species and the pursuit of the mechanism of the photocarbonylation (a reaction exclusive to Cr(0) and Mo(0) carbene complexes, not W(0) carbene complexes) remained unabated over the next 15 years. In fact, all attempts to experimentally determine the mechanism of this useful reaction have been fruitless. At the same time, the photocarbonylation of Cr(0) carbenes matured into a valuable synthetic reaction, allowing access to several families of organic compounds. Unfortunately, reactions other than photocarbonylation remained elusive. We used a combination of experimental and computational methodologies to study the photocarbonylation of Cr(0) carbene complexes and the subsequent reaction of the photogenerated ketenes with nucleophiles. In parallel, we discovered new photochemical processes and succeeded in making photoreactive the so-called "unreactive" W(0) carbene complexes. In this Account, we discuss the disentangling of the mechanisms of these transformations, thereby shedding some light onto the photochemistry of group 6 metal (Fischer) carbene complexes. The original designation of the electronic transitions of group 6 carbene complexes was reassigned, and the photocarbonylation step was analyzed again, resulting in the sequence S(0)-T(1)-S(0), which is far removed from conventional organic photochemistry. The T(1) species is a chromacyclopropanone; its unpaired electrons are primarily localized in the metal fragment and in the former carbene carbon atom. The T(1)-S(0) intersystem crossing occurs with the participation of the solvent through an unusual loose-bolt radiationless mechanism. The photogenerated S(0) species reacts with imines to form the final β-lactams in a mechanism that resembles the organic Staudinger reaction, but here the metal is present during the entire reaction coordinate. The selectivity of these reactions is defined by the nucleophilic attack on the O-bonded metallaketene instead of the subsequent conrotatory ring closure, a distinct departure from the organic reaction. Appropriate modification of the substituents of the carbene ligand or in the coordination sphere of the complex results in new photoprocesses; these include 1,2-metalladyotropic rearrangements as well as α-fragmentations in which W(0) carbene complexes become photoreactive. Moreover, the inclusion of additional metal centers usually results in new reactions, such as the formation of fulvenes by η(5)→ η(3) photoslippage, or in the complete inhibition of the photoreactivity. The photochemistry of group 6 metal-carbene complexes thus offers unexplored territory for pursuing new reactions and reaction mechanisms.     

gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway

Breast cancer research has developed rapidly in the past few decades, leading to longer survival times for patients and opening up the possibility of developing curative treatments for advanced breast cancer. Our increasing knowledge of the biological pathways associated with the progression and development of breast cancer, alongside the failure of conventional treatments, has prompted us to explore gene therapy as an alternative therapeutic strategy. We previously reported that gef gene from E. coli has shown considerable cytotoxic effects in breast cancer cells. However, its action mechanism has not been elucidated. Indirect immunofluorescence technique using flow cytometry and immunocytochemical analysis were used to detect breast cancer markers: estrogen (ER) and progesterone (PR) hormonal receptors, human epidermal growth factor receptor-2 proto-oncogene (c-erbB-2), ki-67 antigen and p53 protein. gef gene induces an increase in ER and PR expressions and a decrease in ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease-free interval and survival. It also increased p53 expression, suggesting that gef-induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer.     

The critical role of water in spider silk and its consequence for protein mechanics

Due to its remarkable mechanical and biological properties, there is considerable interest in understanding, and replicating, spider silk's stress-processing mechanisms and structure-function relationships. Here, we investigate the role of water in the nanoscale mechanics of the different regions in the spider silk fibre, and their relative contributions to stress processing. We propose that the inner core region, rich in spidroin II, retains water due to its inherent disorder, thereby providing a mechanism to dissipate energy as it breaks a sacrificial amide-water bond and gains order under strain, forming a stronger amide-amide bond. The spidroin I-rich outer core is more ordered under ambient conditions and is inherently stiffer and stronger, yet does not on its own provide high toughness. The markedly different interactions of the two proteins with water, and their distribution across the fibre, produce a stiffness differential and provide a balance between stiffness, strength and toughness under ambient conditions. Under wet conditions, this balance is destroyed as the stiff outer core material reverts to the behaviour of the inner core.     

Rational design of heating elements using CFD: Application to a bench-scale adiabatic reactor

This article explores the use of computational fluid dynamics (CFD) modelling for designing an oven which enables the adiabatic operation of a chemical reactor at bench-scale. For accomplishing this scope, the oven consists of electrical heating elements, air circulation system and a control loop that uses the temperature inside the reactor as set-point for the reactor wall temperature. Depending on the spatial configuration of the air flow and the heating elements, as well as the air flow rate, different temperature profiles within a given oven section are obtained, being appropriate those leading to uniform reactor wall temperatures and fast dynamic response. The use of CFD allows, by obtaining temperature maps within the oven, the selection of appropriate configurations. The optimal configuration adopted has been experimentally validated in a lab-scale adiabatic reactor working with both particulated and monolithic catalyst beds.     

Production of nanoparticles from natural hydroxylapatite by laser ablation

Laser ablation of solids in liquids technique has been used to obtain colloidal nanoparticles from biological hydroxylapatite using pulsed as well as a continuous wave (CW) laser. Transmission electron microscopy (TEM) measurements revealed the formation of spherical particles with size distribution ranging from few nanometers to hundred nanometers and irregular submicronic particles. High resolution TEM showed that particles obtained by the use of pulsed laser were crystalline, while those obtained by the use of CW laser were amorphous. The shape and size of particles are consistent with the explosive ejection as formation mechanism.     

The influence of chromate quenching and chloride contamination level on the performance of the painted hot-dipped galvanized steel (duplex system)

The influences of the chromate quenching step and the surface chloride contamination levels of galvanized steel on the performance of duplex systems were studied. Steel panels were galvanized in a commercial steel bath adopting three different postdipping procedures. A comparative study of the galvanized steel, both painted and nonpainted, was performed by electrochemical techniques. It was verified that the chloride contamination level of the galvanized steel surfaces is the main cause of duplex system failures. An explanation for the influence of the chromate quenching on the performance of duplex systems was presented.     

Oxygen migration on the graphene surface. 2. Thermochemistry of basal-plane diffusion (hopping)

Thermodynamic affinities, activation energies and diffusion coefficients for oxygen mobility on the graphene surface are calculated using density functional theory (DFT). We report and discuss the effects of geometry, charge distribution and heteroatom substitution on the migration of epoxy oxygen on the basal plane: both the driving force and the ease of surface hopping are very sensitive to their variations. A significant decrease in the hopping energy barrier is observed when graphene contains free edge sites and oxygen functionalities, as well as upon an increase in electron density; conversely, the barrier increases as a consequence of electron removal, and the propensity for graphene ‘unzipping’ also increases. There is a correlation between the hopping barrier and the C–O bond strength of the leaving epoxide group. Under the most favorable conditions investigated, oxygen mobility is quite high, of the same order as that of gas-phase O₂ in micropores (ca. 10⁻⁹ m²/s). This is consistent with the increasingly acknowledged role of basal-plane oxygen as a protagonist (e.g., reaction intermediate), instead of a spectator, in the wide variety of adsorption and reaction processes involving sp²-hybridized carbon materials.     

Timolol‐imprinted soft contact lenses: Influence of the template: Functional monomer ratio and the hydrogel thickness

Isothermal titration calorimetry (ITC) was used to identify the optimal timolol:functional monomer ratio for preparing soft contact lenses (SCLs) able to sustain drug release. ITC profiles revealed that each timolol molecule required six to eight acrylic acid (AAc) monomers to saturate the binding and that these ratios could be the most suitable for creating imprinted cavities. Various poly(hydroxyethyl methacrylate‐co‐AAc) hydrogels 0.2 and 0.9 mm thick were prepared with timolol:AAc molar ratios ranging from 1 : 6 to 1 : 32 and also in the absence of timolol. The hydrogels were reloaded with timolol by immersion in 0.04, 0.06, 0.08, and 0.10 mM drug solutions. Both imprinted and nonimprinted hydrogels showed a high affinity for the drug because of the presence of AAc. Nevertheless, the 1 : 6 and 1 : 8 imprinted hydrogels loaded less timolol but sustained the release better than the other hydrogels. These differences were explained in terms of the different arrangement of the functional monomers along the network. The imprinting effect was more noticeable in the case of the thinnest hydrogels, where the contribution of the diffusion path to the release rate was smaller. The results obtained prove the interest of ITC for the rational design of drug‐imprinted networks to be used as medicated SCLs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011