Validation and clinical application of an LC‐ESI‐MS/MS method for simultaneous determination of tolmetin and MED5, the metabolites of amtolmetin guacil in human plasma

A highly sensitive, rapid assay method has been developed and validated for the simultaneous estimation of tolmetin (TMT) and MED5 in human plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. A simple solid‐phase extraction process was used to extract TMT and MED5 along with mycophenolic acid (internal standard, IS) from human plasma. Chromatographic separation was achieved with 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 0.50 mL/min on an X‐Terra RP₁₈ column with a total run time of 2.5 min. The MS/MS ion transitions monitored were 258.1 → 119.0 for TMT, 315.1 → 119.0 for MED5 and 321.2 → 207.0 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 20 ng/mL and the linearity was observed from 20 to 2000 ng/mL, for both the anlaytes. The intra‐day and inter‐day precisions were in the range 3.27–4.50 and 5.32–8.18%, respectively for TMT and 4.27–5.68 and 5.32–8.85%, respectively for MED5. This novel method has been applied to a clinical pharmacokinetic study. Copyright © 2010 John Wiley & Sons, Ltd.     

Palladium‐Catalyzed Carbonylations of Aryl Bromides using Paraformaldehyde: Synthesis of Aldehydes and Esters

Carbonylation reactions represent useful tools for organic synthesis. However, the necessity to use gaseous carbon monoxide is a disadvantage for most organic chemists. To solve this problem, novel protocols have been developed for conducting palladium‐catalyzed reductive carbonylations of aryl bromides and alkoxycarbonylations using paraformaldehyde as an external CO source (CO gas free). Hence, aromatic aldehydes and esters were synthesized in moderate to good yields.     

Hybrid systems through natural product leads: an approach towards new molecular entities

Hybrid systems are constructs of different molecular entities, natural or unnatural, to generate functional molecules in which the characteristics of various components are modulated, amplified or give rise to entirely new properties. These hybrids can be designed from carefully selected components either through domain integration of key structural/functional features or via straightforward covalent linkages. Some of the recently reported hybrid systems based on steroid, carbohydrate, C60-fullerene platforms, amongst others, mainly crafted with the object of enhancement of the therapeutical spectrum, will be discussed.     

Mechanistic studies on the pyrolysis and combustion of polystyrene/ammonium perchlorate propellants in the presence of transition metal oxides

The effect of transition metal oxides (Fe₂O₃, MnO₂, Ni₂O₃ and Co₂O₃) on polystyrene/ammonium perchlorate propellant systems has been examined. The mechanism of action of the oxides in increasing the burning rate was examined by studying the effect of the oxides on the thermal decomposition and combustion of the oxidizer and the propellant. It has been concluded that one of the mechanisms by which the oxides act is by promoting the charge-transfer process, which is indicated by the enhancement of the electron-transfer process in ammonium perchlorate and by the correlation between the redox potential of the metal ions and the corresponding burning rates of the propellant.     

On the fluxional behaviour of a polycyclic (4.4.2) propella-2,4-diene

Existence of bicyclo (4.2.0) octa-2,4-diene ? 1,3,5-cyclooctatriene type of valence isomerisation in a polycyclic propellane framework has been demonstrated through cycloaddition and thermolysis reactions.     

Protein recognition using synthetic surface-targeted agents

The design of synthetic agents to disrupt protein-protein interactions has received relatively little attention in recent years. In this review we describe strategies for targeting different types of protein surfaces using mimetics of protein secondary or tertiary structure. In this way strong and selective binding to a protein surface has be achieved and disruption of clinically important protein-protein interactions has been demonstrated in models of human disease.     

Tetrakis-heteroleptic complexation at porphyrins: a convenient route to diversely functionalized aggregates

[structure: see text] Using a novel tetraphenanthrolinated porphyrin building block and heteroleptic bisphenanthroline complexation, copper-instructed multicomponent assemblies exhibiting distinct electrochemical and photoactive behavior were accessed.     

Directed denaturation: room temperature and stoichiometric unfolding of cytochrome C by a metalloporphyrin dimer

Using circular dichroism, UV-vis, and trypsin proteolysis, we have shown how a metalloporphyrin dimer induces the unfolding of a protein, cytochrome c, under physiologically relevant conditions and accelerates its rate of proteolytic degradation.