Computer-Assisted 3D Structure Elucidation of Natural Products using Residual Dipolar Couplings.

An enhanced computer-assisted procedure for the determination of the relative configuration of natural products, which starts from the molecular formula and uses a combination of conventional 1D and 2D NMR spectra, and residual dipolar couplings (RDCs), is reported. Having already the data acquired (1D/2D NMR and RDCs), the procedure begins with the determination of the molecular constitution using standard computer-assisted structure elucidation (CASE) and is followed by fully automated determination of relative configuration through RDC analysis. In the case of moderately flexible molecules the simplest data-explaining conformational model is selected by the use of the Akaike information criterion.

Self-Sensitized Photooxygenation of 2H-Pyrans: Characterization of Unexpected Products Assisted by Computed Structural Elucidation and Residual Dipolar Couplings.

The UVA (350 nm) irradiation of an α-pyran in the presence of oxygen led to the unexpected formation of a tetraoxygenated compound whose structure could not be unambiguously determined on the basis of conventional (1)H-(13)C correlated experiments. 1,1-ADEQUATE (adequate double quantum transfer experiment) and 1,n-ADEQUATE combined with computer-assisted structure elucidation software led to two structural possibilities involving the formation of either an epoxide or an oxetane. Residual dipolar couplings allowed not only the identification of the compound as a spiroepoxide but also the determination of its relative configuration. To account for its formation, we propose a bisepoxide intermediate that, as opposed to most α,ß-epoxyketones under irradiation, undergoes O-Cß cleavage probably due to the presence of an extra oxygen substituent in the ß position. 1,2-Acyl migration would then proceed stereoselectively to the final product obtained as a single diastereomer.

Disodium cromoglycate: exploiting its properties as a NMR weak-aligning medium for small organic molecules.

Chromonic phases are a family of lyotropic liquid crystals (LC) formed by ionic aromatic mesogens such as disodium cromoglycate (cromolyn), sunset yellow and others. It is well known that chromonic phases are oriented in the presence of external magnetic fields, leading to the observation of anisotropic NMR observables such as quadrupolar splittings or residual dipolar couplings. Despite the fact that the cromolyn nematic LC phase (N) presents important advantages like great homogeneity, small line broadening, and easy sample preparation, it has been scarcely used as a water-compatible NMR orienting medium, in part due to a too strong induced degree of alignment on the guest molecules. However, the use of cromolyn-brine mixtures led to the optimum degree of alignment allowing to record (1)H-(13)C dipolar couplings with good accuracy.

New strategy for RDC-assisted diastereotopic proton assignment using a combination of J-scaled BIRD HSQC and J-scaled BIRD HMQC/HSQC.

A new strategy to assign diastereotopic protons was developed on the basis of residual dipolar couplings (RDCs) collected in compressed poly(methyl methacrylate) (PMMA) gels. A combination of 2D J-scaled BIRD HSQC and J-scaled BIRD HMQC/HSQC NMR experiments was used to collect the RDC data. In the proposed strategy, the first experiment is used to measure (1)D(CH) for methine groups, the sum of (1)D(CHa) + (1)D(CHb) for methylene groups and the average (1)D(CH3) value for methyl groups. In turn, the small molecule alignment tensor is calculated using these D values without the a priori assignment of CH(2) diastereotopic protons. The D values of each individual CH bond (CHa and CHb) of each methylene group in the molecule are then predicted using the calculated alignment tensor and these values compared with the results from the HMQC/HSQC experiment, leading to their unambiguous assignment. This strategy is demonstrated with the alkaloid strychnine that contains five methylene groups with diastereotopic protons, and our results fully agree with the previously reported assignment using combinations of permutated assignments.

[Facing the HIV/AIDS epidemic in Mexico: the response of the health sector]. / Haciendo frente a la epidemia de VIH/SIDA en México: una respuesta organizada?

OBJECTIVE: To analyze the challenges and accomplishments of the Mexican health system as it faced the HIV/AIDS epidemic over the 20 years since discovery of the virus. METHODS: A review of the relevant literature was done. The topics revised were: HIV/AIDS epidemiology, the early response of the health system and civil society, prevention and risk behaviors, care and treatment, and financing and resources allocation. DISCUSSION: In Mexico a rapid initial public response surely contributed to containing any early spread of the epidemic to select populations; whether that spread will continue to be contained is an open question. Sexual risk practices remain high not only among traditional risk populations but also among youth. Even though the epidemic remains concentrated in Mexico, principally among MSM and IDU, only 13% of public HIV prevention funds are directed to key populations at especially high risk of becoming infected or infecting others. In recent years antiretroviral coverage has increased rapidly with funding increasing from 30 to 367 million pesos from 2001 to 2003 and coverage now approaching 100%. Of all health spending on HIV/AIDS in the public sector, 82.4% is spent by the social security institutes and 17.6% by the Ministry of Health. The former provides medical care to about half of PLHA while the latter, in addition to caring for the other half, supports the large majority of prevention expenses. One of the challenges faced by the health system which has largely achieved universal antiretroviral coverage is how to provide quality care with appropriate monitoring, promotion of adherence and recognition and treatment of resistance and adverse effects--without dramatically increasing costs.

Haciendo frente a la epidemia de VIH/SIDA en México: ¿Una respuesta organizada? / Facing the HIV/AIDS epidemic in Mexico: The response of the health sector

Objetivo. Analizar los retos y logros de los sistemas de salud mexicano en la lucha contra el VIH/SIDA a 20 años del descubrimiento del virus. Material y métodos. Se realizó una revisión de la bibliografía pertinente para el caso de México. Los tópicos principales revisados son el perfil epidemiológico del VIH/SIDA; las primeras respuestas del sistema y de la sociedad civil hacia la epidemia; la prevención y los comportamientos de riesgo; atención y tratamiento con énfasis en cobertura y normas terapéuticas; y financiamiento y asignación de recursos. Discusión. En México se produjo una rápida respuesta inicial ante la epidemia que contribuyó a mantenerla limitada a ciertos grupos de la población, no obstante, sin garantizar la protección futura de la población general y de los grupos más afectados. Las prácticas sexuales de riesgo se mantienen elevadas tanto en los grupos considerados tradicionalmente con más prácticas de riesgo como entre los jóvenes. A pesar de que la epidemia en México se considera como concentrada, principalmente en hombres que tienes sexo con hombres (HSH) y usuarios de drogas inyectables (UDI), los esfuerzos de prevención no tienen la suficiente focalización: sólo 13% del gasto en prevención se encuentra dirigido a la población de mayor vulnerabilidad para contraer el VIH. Por otra parte, en los últimos años ha habido un incremento importante en materia de provisión de antirretrovirales: el gasto en los mismos pasó de 30 millones en el año 2001 a 367 millones de pesos para el año 2003 alcanzando una cobertura cercana a 100%. Del total del gasto público en VIH/SIDA, 82.4% lo ejerció la seguridad social y el restante 17.6% lo ejerció la Secretaría de Salud; los fondos de la seguridad social se destinan a la atención y tratamiento de alrededor de 50% de las personas viviendo con VIH/SIDA, mientras que de los de la Secretaría de Salud se financia la otra mitad y la mayor parte de los gastos en prevención. Uno de los retos a que se enfrenta el sistema de salud, que ha logrado una cobertura cercana a 100% de atención con antirretrovirales es el cómo proveer de una atención de calidad, con un monitoreo adecuado, promoción de la adhesión y reconocimiento del problema de resistencia y efectos secundarios, sin un incremento explosivo en los costos.

Objective. To analyze the challenges and accomplishments of the Mexican health system as it faced the HIV/AIDS epidemic over the 20 years since discovery of the virus. Methods. A review of the relevant literature was done. The topics revised were: HIV/AIDS epidemiology, the early response of the health system and civil society, prevention and risk behaviors, care and treatment, and financing and resources allocation. Discussion. In Mexico a rapid initial public response surely contributed to containing any early spread of the epidemic to select populations; whether that spread will continue to be contained is an open question. Sexual risk practices remain high not only among traditional risk populations but also among youth. Even though the epidemic remains concentrated in Mexico, principally among MSM and IDU, only 13% of public HIV prevention funds are directed to key populations at especially high risk of becoming infected or infecting others. In recent years antirretroviral coverage has increased rapidly with funding increasing from 30 to 367 million pesos from 2001 to 2003 and coverage now approaching 100%. Of all health spending on HIV/AIDS in the public sector, 82.4% is spent by the social security institutes and 17.6% by the Ministry of Health. The former provides medical care to about half of PLHA while the latter, in addition to caring for the other half, supports the large majority of prevention expenses. One of the challenges faced by the health system which has largely achieved universal antiretroviral coverage is how to provide quality care with appropriate monitoring, promotion of adherence and recognition and treatment of resistance and adverse effects - without dramatically increasing costs.