Importance of the Electron Correlation and Dispersion Corrections in Calculations Involving Enamines, Hemiaminals, and Aminals. Comparison of B3LYP, M06-2X, MP2, and CCSD Results with Experimental Data.

While B3LYP, M06-2X, and MP2 calculations predict the ΔG° values for exchange equilibria between enamines and ketones with similar acceptable accuracy, the M06-2X/6-311+G(d,p) and MP2/6-311+G(d,p) methods are required for enamine formation reactions (for example, for enamine 5a, arising from 3-methylbutanal and pyrrolidine). Stronger disagreement was observed when calculated energies of hemiaminals (N,O-acetals) and aminals (N,N-acetals) were compared with experimental equilibrium constants, which are reported here for the first time. Although it is known that the B3LYP method does not provide a good description of the London dispersion forces, while M06-2X and MP2 may overestimate them, it is shown here how large the gaps are and that at least single-point calculations at the CCSD(T)/6-31+G(d) level should be used for these reaction intermediates; CCSD(T)/6-31+G(d) and CCSD(T)/6-311+G(d,p) calculations afford ΔG° values in some cases quite close to MP2/6-311+G(d,p) while in others closer to M06-2X/6-311+G(d,p). The effect of solvents is similarly predicted by the SMD, CPCM, and IEFPCM approaches (with energy differences below 1 kcal/mol).

Total Synthesis of Amphidinolide K, a Macrolide That Stabilizes F-Actin.

The total synthesis of (-)-amphidinolide K (1) based on asymmetric addition of allylsilane C1-C8 to enal C9-C22 is reported. The 1,9,18-tris-O-TBDPS ether was converted into the desired 9,18-dihydroxy acid. Its macrolactonization was accomplished by the Shiina method. Compound 1 together with some of its stereoisomers and analogues were subjected to evaluation of the possible disruption of the α,ß-tubulin-microtubule and/or G-actin-F-actin equilibria. Compound 1 behaves as a stabilizer of actin filaments (F-actin) in vitro.

[Healthy heart: Results of a community education program on cardiovascular health]. / «Salut al cor/salud en el corazón¼: resultados del programa de educación sanitaria en salud cardiovascular de Mútua Terrassa.

OBJECTIVE: To improve the knowledge of the population about heart-healthy habits through a training program supplemented by a web site and community activities. DESIGN: A controlled clinical trial with intervention done through participation in the Cardiovascular Health Training Classroom (CHTC) LOCATION: A town of 80,000 inhabitants. PATIENTS: both sexes, aged 55 to 70 years, with at least one cardiovascular risk factor (CVRF). INTERVENTION: The intervention group (IG) consisted of patients who participated in the CHTC. Intervention was carried out through a 20-hour presential group course in which a support web site was offered and complementary activities were organized. Classes were taught by three Primary Care nurses. MAIN MEASUREMENTS: The primary endpoint was knowledge of CVRF. The secondary variables were age, sex, CVRF, lifestyle, visits to health centers, pharmaceutical use adherence, and satisfaction with the program. RESULTS: Data from patients in the first 10 courses (n=150) were evaluated. A statistically significant improvement was observed in overall knowledge of CVRF in the IG (87.3% to 100%) compared with control group (GC) (84.5% to 92.7%), p<.001, as well as an improvement in physical activity is (IG: 71.2% to 83.1% versus CG: 72.6% to 78.2%), p=.05. The total number of Primary Care visits (medical and nursing) decreased in the IG more than in the CG. The satisfaction rate of the course was very high. CONCLUSIONS: This experience is effective in improving cardiovascular health knowledge and promoting some healthy habits.

A multifunctional toolkit for target-directed cancer therapy.

Here we present 2shRNA, a shRNA-based nanobinder, which can simultaneously attack two therapeutic targets involved in drug resistance pathways and can additionally bind accessory molecules such as cell targeting peptides or fluorophores. We create 2shRNAs designed to specifically kill HER2+ breast cancer cells in the absence of a transfecting agent.

Efficient siRNA-peptide conjugation for specific targeted delivery into tumor cells.

Despite the broad applicability of the Huisgen cycloaddition reaction, the click functionalization of RNAs with peptides still remains a challenge. Here we describe a straightforward method for the click functionalization of siRNAs with peptides of different sizes and complexities. Among them, a promising peptide carrier for the selective siRNA delivery into HER2+ breast cancer cell lines has been reported.

Transfer of 1-alkenyl groups between secondary amines. relative stability and reactivity of enamines from popular organocatalysts.

Enamines from 3-methylbutanal and several Pro- and Phe-derived secondary amines were prepared in DMSO-d6, CD3CN, and CDCl3. For the first time, the relative thermodynamic stabilities of these and other enamines were compared, and rapid exchanges of 1-alkenyl groups were demonstrated. Competition experiments showed that the most favored enamines (without significant steric inhibition of resonance) react more rapidly with electrophiles.

Relative tendency of carbonyl compounds to form enamines.

Equilibria between carbonyl compounds and their enamines (from O-TBDPS-derived prolinol) have been examined by NMR spectroscopy in DMSO-d(6). By comparing the exchange reactions between pairs (enamine A + carbonyl B → carbonyl A + enamine B), a quite general scale of the tendency of carbonyl groups to form enamines has been established. Aldehydes quickly give enamines that are relatively more stable than those of ketones, but there are exceptions to this expected rule; for example, 1,3-dihydroxyacetone acetals or 3,5-dioxacyclohexanones (2-phenyl-1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one) show a greater tendency to afford enamines than many α-substituted aldehydes.