Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical, and Theoretical Study

Alkylation patterns and excited-state properties of pterins were examined both experimentally and theoretically. 2D NMR spectroscopy was used to characterize the pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the pterin. At a temperature of 70°C, the pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namely N,N-dimethylformamide and N,N-dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O-isomer forms in higher yield than the more stable N-isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular ?walk? rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of the O-isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated pterins as 1 O 2 sensitizers. Insight on thermal and photostability of the alkylated pterins is also provided.Fil: Walalawela, Niluksha. City University of New York; Estados UnidosFil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. City University of New York; Estados UnidosFil: Urrutia, María Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Belh, Sarah J.. City University of New York; Estados UnidosFil: Greer, Edyta M.. City University of New York; Estados UnidosFil: Thomas, Andrés Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Greer, Alexander. City University of New York; Estados Unido

Kinetic control in the regioselective alkylation of pterin sensitizers: a synthetic, photochemical, and theoretical study

Alkylation patterns and excited-state properties of pterins were examined both experimentally and theoretically. 2D NMR spectroscopy was used to characterize the pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the pterin. At a temperature of 70°C, the pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namely N,N-dimethylformamide and N,N-dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O-isomer forms in higher yield than the more stable N-isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular "walk" rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of the O-isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated pterins as 1 O2 sensitizers. Insight on thermal and photostability of the alkylated pterins is also provided.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Ebola Preparedness and Risk in Latin America

Until today, February 22, 2016, no confirmed Ebola cases have been diagnosed in Americas (except USA, four cases with one death). Confusion, lack of knowledge, and fear have led to quickly misclassify cases as suspected, when in fact most of them are false alarms. Nevertheless, European governments summoned to mobilize resources to attend the Ebola outbreak in West Africa. And also Latin American governments should contribute to halt this humanitarian crisis and to be prepared for the potential arrival of this deadly virus in the Caribbean, Central, and South American mainland. In this chapter, we described the experience of preparedness as well as risk assessment done in Latin America regarding the threat of Ebola for the region

Additive QTLs on three chromosomes control flowering time in woodland strawberry (Fragaria vesca L.)

Flowering time is an important trait that affects survival, reproduction and yield in both wild and cultivated plants. Therefore, many studies have focused on the identification of flowering time quantitative trait locus (QTLs) in different crops, and molecular control of this trait has been extensively investigated in model species. Here we report the mapping of QTLs for flowering time and vegetative traits in a large woodland strawberry mapping population that was phenotyped both under field conditions and in a greenhouse after flower induction in the field. The greenhouse experiment revealed additive QTLs in three linkage groups (LG), two on both LG4 and LG7, and one on LG6 that explain about half of the flowering time variance in the population. Three of the QTLs were newly identified in this study, and one co-localized with the previously characterized FvTFL1 gene. An additional strong QTL corresponding to previously mapped PFRU was detected in both field and greenhouse experiments indicating that gene(s) in this locus can control the timing of flowering in different environments in addition to the duration of flowering and axillary bud differentiation to runners and branch crowns. Several putative flowering time genes were identified in these QTL regions that await functional validation. Our results indicate that a few major QTLs may control flowering time and axillary bud differentiation in strawberries. We suggest that the identification of causal genes in the diploid strawberry may enable fine tuning of flowering time and vegetative growth in the closely related octoploid cultivated strawberry.Peer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Historical biogeography identifies a possible role of Miocene wetlands in the diversification of the Amazonian rocket frogs (Aromobatidae: Allobates

Aim: We investigate the spatiotemporal context of the diversification of Allobates, a widespread genus of Amazonian frogs with high species diversity particularly in western Amazonia. We tested if that diversity originated in situ or through repeated dispersals from other Amazonian areas and if this diversification took place during or after the Pebas system, a vast lacustrine system occupying most western Amazonia between 23 and 10 million years ago (Mya). Location: Amazonia. Taxon: Allobates (Anura: Aromobatidae). Methods: We gathered a spatially and taxonomically extensive sampling of mitochondrial DNA sequences from 932 Allobates specimens to delimit Operational Taxonomic Units (OTUs). Complete mitogenomes of these OTUs were assembled to reconstruct a time-calibrated phylogeny used to infer the historical and spatial origin of the Amazonian Allobates lineages. Results: Phylogenetic analyses and ancestral area reconstruction suggested that most of the western Amazonian lineages resulted from in situ diversification and that these events occurred between the inferred origin of the genus (25 Mya) and 10 Mya, with a possible peak between 14 and 10 Mya. Dispersal among areas mostly occurred from western Amazonia towards the Brazilian and the Guiana Shields. Closely related Allobates OTUs display an allopatric pattern of distribution, matching interfluves delimited by modern Amazonian rivers. Main Conclusions: In western Amazonia, diversification of Allobates appears to have been simultaneous with the last stages of the Pebas system (14–10 Mya). Subsequently (within the last 10 Mya), modern Amazonian river courses shaped the distribution pattern of Allobates species and possibly promoted allopatric speciation.This study benefited from an “Investissement d’Avenir” grant managed by the Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01; TULIP, ref. ANR-10-LABX-0041; ANAEE-France: ANR-11-INBS-0001). AF and FPW acknowledge the French/Brazilian GUYAMAZON program action (IRD, CNRS, CTG, CIRAD and Brazilian Fundação de Amparo à Pesquisa do Estado do Amazonas-FAPEAM 062.00962/2018) and co-coordinated by A. Fouquet and F. P. Werneck. MTR thanks Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grant numbers: 2003/10335-8, 2011/50146-6 and NSF-FAPESP Dimensions of Biodiversity Program [grant numbers: BIOTA 2013/50297-0, NSF-DEB 1343578]) and NASA. SRR acknowledges a grant from SENESCYT (Arca de Noé Initiative). FPW thanks CNPq (Productivity Fellowship), FAPEAM, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Visiting Professor Fellowship) and the L’Oréal-UNESCO For Women In Science Program. AFJ is supported by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior-Brasil (CAPES Finance Code: 88882.462010/2019-01). JM is supported by the Ministry of Culture of the Czech Republic (DKRVO 2019-20023/6.VI.b, National Museum Prague, 00023272). PJRK was supported by research grants from the Fonds voor Wetenschappelijk Onderzoek (FWO12A7614N and FWO12A7617N). AJC was supported by Research Program INV-2017-51-1432 from the School of Sciences, Universidad de los Andes. RE was supported by research grants from the Deutsche Forschungsgemeinschaft (DFG ER 589/1-1 & ER 589/2-1)

Historical biogeography identifies a possible role of Miocene wetlands in the diversification of the Amazonian rocket frogs (Aromobatidae: Allobates)

Aim: We investigate the spatiotemporal context of the diversification of Allobates, a widespread genus of Amazonian frogs with high species diversity particularly in western Amazonia. We tested if that diversity originated in situ or through repeated dispersals from other Amazonian areas and if this diversification took place during or after the Pebas system, a vast lacustrine system occupying most western Amazonia between 23 and 10 million years ago (Mya). Location: Amazonia. Taxon: Allobates (Anura: Aromobatidae). Methods: We gathered a spatially and taxonomically extensive sampling of mitochondrial DNA sequences from 932 Allobates specimens to delimit Operational Taxonomic Units (OTUs). Complete mitogenomes of these OTUs were assembled to reconstruct a time-calibrated phylogeny used to infer the historical and spatial origin of the Amazonian Allobates lineages. Results: Phylogenetic analyses and ancestral area reconstruction suggested that most of the western Amazonian lineages resulted from in situ diversification and that these events occurred between the inferred origin of the genus (25 Mya) and 10 Mya, with a possible peak between 14 and 10 Mya. Dispersal among areas mostly occurred from western Amazonia towards the Brazilian and the Guiana Shields. Closely related Allobates OTUs display an allopatric pattern of distribution, matching interfluves delimited by modern Amazonian rivers. Main Conclusions: In western Amazonia, diversification of Allobates appears to have been simultaneous with the last stages of the Pebas system (14–10 Mya). Subsequently (within the last 10 Mya), modern Amazonian river courses shaped the distribution pattern of Allobates species and possibly promoted allopatric speciation.This study benefited from an “Investissement d’Avenir” grant managed by the Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01; TULIP, ref. ANR-10-LABX-0041; ANAEE-France: ANR-11-INBS-0001). AF and FPW acknowledge the French/Brazilian GUYAMAZON program action (IRD, CNRS, CTG, CIRAD and Brazilian Fundação de Amparo à Pesquisa do Estado do Amazonas-FAPEAM 062.00962/2018) and co-coordinated by A. Fouquet and F. P. Werneck. MTR thanks Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grant numbers: 2003/10335-8, 2011/50146-6 and NSF-FAPESP Dimensions of Biodiversity Program [grant numbers: BIOTA 2013/50297-0, NSF-DEB 1343578]) and NASA. SRR acknowledges a grant from SENESCYT (Arca de Noé Initiative). FPW thanks CNPq (Productivity Fellowship), FAPEAM, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Visiting Professor Fellowship) and the L’Oréal-UNESCO For Women In Science Program. AFJ is supported by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior-Brasil (CAPES Finance Code: 88882.462010/2019-01). JM is supported by the Ministry of Culture of the Czech Republic (DKRVO 2019-20023/6.VI.b, National Museum Prague, 00023272). PJRK was supported by research grants from the Fonds voor Wetenschappelijk Onderzoek (FWO12A7614N and FWO12A7617N). AJC was supported by Research Program INV-2017-51-1432 from the School of Sciences, Universidad de los Andes. RE was supported by research grants from the Deutsche Forschungsgemeinschaft (DFG ER 589/1-1 & ER 589/2-1)