Experimental and Theoretical Exploration of the Kinetics and Thermodynamics of the Nucleophile-Induced Fragmentation of Ylidenenorbornadiene Carboxylates.

Ylidenenorbornadienes (YNDs), prepared by [4 + 2] cycloadditions between fulvenes and acetylene carboxylates, react with thiol nucleophiles to yield mixtures of four to eight diastereomers depending on the symmetry of the YND substrate. The mixtures of diastereomers fragment via a retro-[4 + 2] cycloaddition with a large variation in rate, with half-lives ranging from 16 to 11,000 min at 80 °C. The diastereomer-enriched samples of propane thiol adducts [YND-propanethiol (PTs)] were isolated and identified by nuclear Overhauser effect spectroscopy (NOESY) correlations. Simulated kinetics were used to extrapolate the rate constants of individual diastereomers from the observed rate data, and it correlated well with rate constants measured directly and from isolated diastereomer-enriched samples. The individual diastereomers of a model system fragment at differing rates with half-lives ranging from 5 to 44 min in CDCl3. Density functional theory calculations were performed to investigate the mechanism of fragmentation and support an asynchronous retro-[4 + 2] cycloaddition transition state. The computations generally correlated well with the observed free energies of activation for four diastereomers of the model system as a whole, within 2.6 kcal/mol. However, the observed order of the fragmentation rates across the set of diastereomers deviated from the computational results. YNDs display wide variability in the rate of fragmentation, dependent on the stereoelectronics of the ylidene substituents. A Hammett study showed that the electron-rich aromatic rings attached to the ylidene bridge increase the fragmentation rate, while electron-deficient systems slow fragmentation rates.

Ylidenenorbornadiene Carboxylates: Experimental Kinetic Analysis of a Nucleophile-Induced Fragmentation Reaction.

Ylidenenorbornadienes (YNDs), prepared by [4 + 2] cycloadditions between fulvenes and acetylene carboxylates, react with beta-mercaptoethanol to yield a mixture of four diastereomers. These four diastereomers fragment via a retro-[4 + 2] cycloaddition at differing rates. A simulated kinetics approach extrapolated the rate constants of the diastereomers from the observed rate data. YNDs display wide variability in rate of fragmentation, dependent on the stereoelectronics of the ylidene substituents. A substrate containing one carboxylic ester proved exceptionally stable to fragmentation.

High prevalence of pulmonary hypertension in children with sickle cell disease.

Pulmonary hypertension (PHT) affects approximately 30% of adults with sickle cell disease. Adults with PHT have a significantly higher mortality rate. We report the results of a prospective study of the prevalence of PHT among children with sickle cell disease. In our cohort, 31% of children>or=10 years of age have evidence of PHT by Doppler echocardiography. Factors associated with the presence of PHT are male sex and elevated reticulocyte count. We recommend screening all children for PHT starting at the age of 10 years.

Weekend very high-dose intravenous deferoxamine in children with transfusional iron overload.

Iron overload can be a major complication in children requiring chronic red cell transfusions. Compliance with subcutaneous deferoxamine is often poor. We report the use of very high-dose deferoxamine in 14 children. Patients received intravenous deferoxamine at 15 mg/kg/h over 48 hours every 2 or 4 weeks. The mean duration of treatment was 18 months. Therapy was well tolerated and our regimen was successful in removing excess iron. Intermittent very high-dose intravenous deferoxamine is practical, safe, and effective in managing iron overload in children. Treatment can be given as an outpatient without a central venous catheter.