Mapping the potential energy surfaces for ring-closing metathesis reactions of prototypical dienes by electronic structure calculations

The potential energy surfaces for ring-closing metathesis reactions of a series of simple alpha,omega-dienes which lead to 5-10 membered ring products, have been explored using density functional theory methods. We have investigated both the conformational aspects of the hydrocarbon chain during the course of the reactions, as well as the stationary structures on the corresponding potential energy surfaces. Extensive conformational searches reveal that the reaction proceeds via the conformation that would be expected for the cycloalkene product, though most unexpectedly, cyclohexene forms via complexes in boat-like conformations. The M06-L density functional has been used to map out the potential energy surfaces, and has identified metallocyclobutane fragmentation as being generally the highest barrier along the pathway. The structural variations along the pathway have been discussed for the reactant hydrocarbons of differing chain length to identify points at which cyclisation events may begin to affect reaction rates. Our study provides an excellent starting point from which to begin to learn about the way RCM reaction outcomes are controlled by diene structur

A surprising steric effect on a tandem cycloaddition/ring-opening reaction : rapid syntheses of difluorinated analogues of (hydroxymethyl)conduritols

Difluorinated analogues of (hydroxymethyl)conduritols can be synthesised from selected furans and a difluorinated dienophile in two reaction steps

The management of diabetic ketoacidosis in children

The object of this review is to provide the definitions, frequency, risk factors, pathophysiology, diagnostic considerations, and management recommendations for diabetic ketoacidosis (DKA) in children and adolescents, and to convey current knowledge of the causes of permanent disability or mortality from complications of DKA or its management, particularly the most common complication, cerebral edema (CE). DKA frequency at the time of diagnosis of pediatric diabetes is 10%–70%, varying with the availability of healthcare and the incidence of type 1 diabetes (T1D) in the community. Recurrent DKA rates are also dependent on medical services and socioeconomic circumstances. Management should be in centers with experience and where vital signs, neurologic status, and biochemistry can be monitored with sufficient frequency to prevent complications or, in the case of CE, to intervene rapidly with mannitol or hypertonic saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours; an initial bolus of 10–20 mL/kg 0.9% saline is followed by 0.45% saline calculated to supply maintenance and replace 5%–10% dehydration. Potassium (K) must be replaced early and sufficiently. Bicarbonate administration is contraindicated. The prevention of DKA at onset of diabetes requires an informed community and high index of suspicion; prevention of recurrent DKA, which is almost always due to insulin omission, necessitates a committed team effort

The calculated defect structure of ZnO

Les énergies des défauts fondamentaux dans ZnO sont calculées et comparées avec les résultats expérimentaux obtenus par Kroger. L'énergie correspondante à la bande de conduction est calculée en considérant des défauts neutres ou chargés. Les effets de dopage avec des impuretés cationiques : Li+, Na+, Al3+, Ga3+, In3+ et H+ sont analysés. Enfin les énergies associées aux centres F+ et F sont calculées théoriquement.We report the energies of the fundamental defects in ZnO and compare these with values that can be deduced from Kroger's analysis of the experimental data. We consider neutral, singly-charged and doubly-charged defects and from our analysis estimate the edge of the conduction band. We also consider the effect of dopants such as Li+, Na+, Al3+, Ga3+, In3+ and H+. Finally we consider the energetics involved in the formation of the F+ and F centres

Conformational analysis of peptides and proteins

Some major problems in the calculation of structures and properties of peptide molecules have been reviewed. Recent results from empirical calculations and extended basis set ab initio calculations have been summarized. The importance of fully flexible geometry and vibrational free energy has been discussed as has the effect of explicit Inclusion of the solvent molecules upon the conformation of peptides. Finally, the problem of "folding" a protein, i.e. predicting Its tertiary structure from Its primary sequence, has also been reviewed along with the description of a new technique which avoids the structural oversimplifications employed by other workers, at least as far as the backbone Is concerned. Although this procedure requires further Improvement, preliminary results are reported for pancreatic trypsin Inhibitor, myoglobin and serine proteases

The interplay of structure and reactivity in a most unusual furan diels-alder reaction

Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2-propenoate reacts rapidly and in high yield with furan and a range of substituted furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N-diethylcarbamoyloxy)-2-propenoate fails to react at all under the same conditions. These reactions have been explored using density functional theory (DFT) calculations. They reveal a highly polar transition state, which is stabilized by the Lewis acid catalyst SnCl4 and by polar solvents. In the presence of both catalyst and solvent, a two-step reaction is predicted, corresponding to the stepwise formation of the two new carbon−carbon bonds via transition states which have similar energies in all cases. Our experimental observations of the lack of reaction of the non-fluorinated dienophile, the stereochemical outcomes, and the rate acceleration accompanying furan methylation are all well predicted by our calculations. The calculated free energy barriers generally correlate well with measured reaction rates, supporting a reaction mechanism in which zwitterionic character is developed strongly. An in situ ring opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3-difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H-benzo[1,3]dioxole-3a-carboxylate by a Curtin−Hammett mechanism, has also been examined. Substantial steric opposition to Lewis acid binding prevents carbonate formation from 2-substituted furans

N to C aryl migration in lithiated carbamates: α-arylation of benzylic alcohols

We report a new mode of reactivity displayed by lithiated O-benzyl carbamates carrying an N-aryl substituent: upon lithiation, the N-aryl group is transferred cleanly from N to C. An arylation of the carbamate results, providing a route to alpha,alpha-arylated secondary or tertiary alcohols. We also report density functional theory calculations supporting the proposal that arylation proceeds through a dearomatizing attack on the aromatic ring, a significantly lower energy pathway than the 1,2-acyl transfer observed with related N-alkyl carbamates