Synthesis of a Novel Type of 2,3'-BIMs via Platinum-Catalysed Reaction of Indolylallenes with Indoles.

Optimisation, scope and mechanism of the platinum-catalysed addition of indoles to indolylallenes is reported here to give 2,3'-BIMs with a novel core structure very relevant for pharmaceutical industry. The reaction is modulated by the electronic properties of the substituents on both indoles, with the 2,3'-BIMs favoured when electron donating groups are present. Although simple at first, a complex mechanism has been uncovered that explains the different behaviour of these systems with platinum when compared with other metals (e.g. gold). Detailed labelling studies have shown Pt-catalysed 6-endo-trig cyclisation of the indollylallene as the first step of the reaction and the involvement of two cyclic vinyl-platinum intermediates in equilibrium through a platinum carbene, as the key intermediates of the catalytic cycle towards the second nucleophilic attack and formation of the BIMs.

Heterobimetallic Catalysis: Platinum-Gold-Catalyzed Tandem Cyclization/C-X Coupling Reaction of (Hetero)Arylallenes with Nucleophiles.

Heterobimetallic catalysis offers new opportunities for reactivity and selectivity but still presents challenges, and only a few metal combinations have been explored so far. Reported here is a Pt-Au heterobimetallic catalyst system for the synthesis of a family of multi-heteroaromatic structures through tandem cyclization/C-X coupling reaction. Au-catalyzed 6-endo-cyclization takes place as the first fast step. Pt-Au clusters are proposed to be responsible for the increased reactivity in the second step, that is, the intermolecular nucleophilic addition which occurs through an outer-sphere mechanism by hybrid homogeneous-heterogeneous catalysis.

Gold catalyzed oxycyclizations of alkynols and alkyndiols.

Alkynols and alkyndiols represent excellent building blocks for oxycyclization reactions, leading to a large number of different cyclic structures in one single step. Recently, the use of gold salts and gold complexes has been introduced as an alternative to the traditional methods, providing mild reaction conditions and high group compatibility. This overview focuses on the most recent achievements on gold-catalyzed oxycyclizations, both from alkynols and alkyndiols, and their use in different cascade processes and total synthesis.

Platinum and Gold Catalysis: à la Carte Hydroamination of Terminal Activated Allenes with Azoles.

Nucleophilic additions to allenes catalyzed by transition metals represent a powerful tool to obtain selective access to diverse structures with numerous applications. Reported here is a straightforward methodology to achieve selective addition of azoles to the proximal or distal carbon of activated allenes depending on the catalyst used, unravelling a gold-platinum bimetallic catalysis approach for the 1,3-double addition of azoles to activated allenes to give 1,3-bisazole derivatives, an important scaffold in medicinal and organometallic chemistry.

Vulnerability to reentry in a regionally ischemic tissue: a simulation study.

Sudden cardiac death is mainly provoked by arrhythmogenic processes. During myocardial ischemia many malignant arrhythmias, such as reentry, take place and can degenerate into ventricular fibrillation. It is thus of great interest to unravel the intricate mechanisms underlying the initiation and maintenance of a reentry. In this computational study, we analyze the probability of reentry during different stages of the acute phase of ischemia. We also aimed at the understanding of the role of its main components: hypoxia, hyperkalemia, and acidosis analyzing the intricate ionic mechanisms responsible for reentry generation. We simulated the electrical activity of a ventricular tissue affected by regional ischemia based on a modified version of the Luo-Rudy model (LRd00). The ischemic conditions were varied to simulate different stages of this pathology. After premature stimulation, we evaluated the vulnerability to reentry. We obtained an unimodal behavior for the vulnerable window as ischemia progressed, peaking at the eighth minute after the onset of ischemia where the vulnerable window yielded 58 ms. Under more severe conditions the vulnerable window decreased and became zero for minute 8.75. The present work provides insight into the mechanisms of reentry generation during ischemia, highlighting the role of acidosis and hypoxia when hyperkalemia is present.