Molecular Dynamic Simulations of Aqueous Micellar Organometallic Catalysis: Methane Functionalization as a Case Study.

Molecular Dynamics (MD) simulations constitute a powerful tool that provides a 3D perspective of the dynamical behavior of chemical systems. Herein the first MD study of the dynamics of a catalytic organometallic system, in micellar media, is presented. The challenging methane catalytic functionalization into ethyl propionate through a silver-catalyzed process has been targeted as the case study. The intimate nature of the micelles formed with the surfactants sodium dodecylsulfate (SDS) and potassium perfluorooctane sulfonate (PFOS) has been ascertained, as well as the relative distribution of the main actors in this transformation, namely methane, the diazo reagent and the silver catalyst, the latter in two different forms: the initial compound and a silver-carbene intermediate. Catalyst deactivation occurs with halide containing surfactants dodecyltrimethylammonium chloride (DTAC) and Triton X-100. Computed simulations allow explaining the experimental results, indicating that micelles behave differently regarding the degree of accumulation and the local distribution of the reactants and their effect in the molecular collisions leading to net reaction.

Intramolecular Interception of the Remote Position of Vinylcarbene Silver Complex Intermediates by C(sp3 )-H Bond Insertion.

The trapping of the elusive vinylogous position of a vinyl carbene with an aliphatic C(sp3 )-H bond has been achieved for the first time during a silver-catalyzed carbene/alkyne metathesis (CAM) process. A Tpx -containing silver complex first promotes the generation of a donor-acceptor silver carbene which triggers CAM, generating a subsequent donor-donor vinyl silver carbene species, which then undergoes a selective vinylogous C(sp3 )-H bond insertion, leading to the synthesis of a new family of benzoazepines. Density functional theory (DFT) calculations unveil the reaction mechanism, which allows proposing that the C-H bond insertion reaction takes place in a stepwise manner, with the hydrogen shift being the rate determining step.

Direct Benzene Hydroxylation with Dioxygen Induced by Copper Complexes: Uncovering the Active Species by DFT Calculations.

The direct oxidation of benzene into phenol using molecular oxygen at very mild temperatures can be promoted in the presence of the copper complex TpBr3Cu(NCMe) in the homogeneous phase in the presence of ascorbic acid as the source of protons and electrons. The stoichiometric nature, relative to copper, of this transformation prompted a thorough DFT study in order to understand the reaction pathway. As a result, the dinuclear species TpBr3CuII(µ-O•)(µ-OH)CuIITpBr3 is proposed as the relevant structure which is responsible for activating the arene C-H bond leading to phenol formation.

Micellar Catalysis as a Tool for C-H Bond Functionalization toward C-C Bond Formation.

Micelles generated upon dissolving surfactants in water can be employed as nanovessels for catalytic transformations, in the so-called micellar catalysis methodology. This review is focused on the use of micellar catalysis in the context of the catalytic functionalization of carbon-hydrogen bonds. The micelles accumulate catalyst and reactants in their inner volume in such a high local concentration that kinetics are favored. The consequence is that, in most cases, processes that in conventional organic solvents require high temperatures and long reaction times are achieved in milder conditions when micellar catalysis is employed.

Synthesis and structural characterization of homochiral coordination polymers with imidazole-based monocarboxylate ligands.

Chiral Na[(S)-LR] (R = Me, 1a; iPr, 1b; CH2iPr, 1c, and (S)-secBu, 1d) and Na[(R)-LR] (R = Me, 1a') compounds were synthesised following standard procedures. New compounds 1d and 1a' were analytically and spectroscopically characterised. 1a and 1c were structurally identified by single-crystal X-ray diffraction methods as homochiral 2D coordination polymers, {Na(H2O)[(S)-LMe]}n and {Na[(S)-LCH2iPr]}n, respectively. Both (S)-2alkyl,2-(1H-imidazol-1-yl)acetate anions displayed unprecedented coordination modes in these coordination polymers: µ3κ2OκO' for 1a and µ4κ2Oκ2O' for 1c. Enantiomeric species 1a', {Na(H2O)[(R)-LMe]}n, showed the same X-ray powder diffractogram (XRPD) as 1a, in agreement with a similar crystal structure. DFT calculations on the [LR]- anions confirmed their coordination capabilities as ditopic linkers. In fact, the reaction of Na[LR] with several metal salts yielded the following coordination polymers: {Ag[(S)-LMe]}n, 2a, {Ag[(R)-LMe]}n, 2a', {Cu[(S)-LR]2}n (R = Me, 3a; iPr, 3b), {Cu[(R)-LMe]}n, 3a', {Zn[(S)-LR]2}n (R = Me, 4a; iPr, 4b; (S)-secBu, 4d) and {Zn[(R)-LMe]2}n, 4a'. For the known compounds 3a and 4a, this procedure is a new synthetic route that avoided high temperature reaction conditions. New complexes 2, 3a', b, and 4a', b, d were characterised by elemental analysis, infrared and XRPD methods and complex 2a by single-crystal X-ray diffraction. This complex is also a two-dimensional coordination polymer in which the [(S)-LMe]- anion acts as a µ4κN,κ2O,κ2O' bridging ligand. Compounds 1-4a' are the first examples of homochiral coordination polymers with imidazole-monocarboxylate ligands based on non-natural amino acids. Preliminary studies on the metal-catalysed preparation of chiral α-aminophosphonates were carried out but, unfortunately, no enantioselectivity was observed.

Fentanyl as pre-emptive treatment of pain associated with turning mechanically ventilated patients: a randomized controlled feasibility study.

PURPOSE: To compare pain incidence and changes in pain scores with fentanyl versus placebo as pre-emptive treatment during turning and 30 min post-turning in mechanically ventilated critically ill patients. METHODS: We performed a randomized, double-blind, parallel-group, placebo-controlled clinical trial in the intensive care unit of a university hospital. Seventy-five mechanically ventilated patients were randomized to an intervention group (fentanyl) or a control group (placebo). Patients in the intervention group received 1 µg/kg (medical patients) or 1.5 µg/kg (surgical patients) of fentanyl 10 min before turning. Pain indicators were assessed using the behavioral pain scale. Safety was assessed by determining the frequency and severity of pre-defined adverse events. Pain was evaluated at rest (T0), at turn start and end (T1 and T2) and at 5, 15 and 30 min post-turning (T3, T4 and T5). RESULTS: The two groups had similar baseline characteristics. The area under the curve for BPS values was significantly smaller in the fentanyl group than in the control group [median and interquartile range (IQR): 132 (108-150) vs. 147 (125-180); p = 0.016, respectively]. Nineteen non-serious adverse events were recorded in 14 patients, with no significant between-group differences (23 % fentanyl group vs. 14 % control group; p = 0.381). CONCLUSIONS: These results suggest an intravenous bolus of fentanyl of 1 µg/kg for medical patients or 1.5 µg/kg for surgical patients reduces the incidence of turning-associated pain in critically ill patients on mechanical ventilation. ClinicalTrials.gov: NCT 01950000.

Stem cells in current paediatric dentistry practice.

New protocols for regenerative endodontic treatment along with the parallel development of tissue engineering technologies are changing traditional knowledge and treatment possibilities for young patients with pulp-affected permanent immature teeth. The regeneration and completion of apical root development in pathological situations such as these is a clinical challenge that traditional treatments have not so far been able to resolve with complete success. In clinical terms, the decision of whether to perform apexogenesis or apexification on an immature tooth is determined by whether the pulp tissue is vital or non-vital. Recent evidence and reports in the literature have questioned the old dogmas. In this respect, the ever growing scientific literature in this field makes it essential to compile a critical reflection and summary of everything that has been written to date, in order to understand the biological basis of current clinical advances and ensuing lines of future therapy. In this paper, we wish to give scientific coverage and background to more recent clinical and molecular advances described in the field of apical regeneration using stem cell therapy and their potentially key role in the future clinical success of new pulp regenerative protocols.