Stabilizing σ-hole Dimethyl Interactions.

Methyl groups bound to electronegative atoms, such as N or O, are recognized to participate in tetrel bonding as Lewis acids. On the other hand, the capability of methyl groups bound to electropositive atoms, such as B or Al, to act as Lewis bases has been recently reported. Herein, we analyze the combination of these two behaviors to establish attractive methyl···methyl interactions. We have explored the Cambridge Structural Database to find experimental examples of these dimethyl-bound systems, finding a significant degree of directionality in the relative disposition of the two methyl groups. Moreover, we have carried out a comprehensive computational analysis at the DFT level of the dimethyl interactions, including the natural bond orbital, energy decomposition analysis, and topological analysis of the electron density (QTAIM and NCI). The dimethyl interaction is characterized as weak yet attractive and based on electrostatics, with a non-negligible contribution from orbital charge transfer and polarization.

Mechanism Insights into the Iridium(III)- and B(C6F5)3-Catalyzed Reduction of CO2 to the Formaldehyde Level with Tertiary Silanes.

The catalytic system [Ir(CF3CO2)(κ2-NSiMe)2] [1; NSiMe = (4-methylpyridin-2-yloxy)dimethylsilyl]/B(C6F5)3 promotes the selective reduction of CO2 with tertiary silanes to the corresponding bis(silyl)acetal. Stoichiometric and catalytic studies evidenced that species [Ir(CF3COO-B(C6F5)3)(κ2-NSiMe)2] (3), [Ir(κ2-NSiMe)2][HB(C6F5)3] (4), and [Ir(HCOO-B(C6F5)3)(κ2-NSiMe)2] (5) are intermediates of the catalytic process. The structure of 3 has been determined by X-ray diffraction methods. Theoretical calculations show that the rate-limiting step for the 1/B(C6F5)3-catalyzed hydrosilylation of CO2 to bis(silyl)acetal is a boron-promoted Si-H bond cleavage via an iridium silylacetal borane adduct.

Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor.

Human riboflavin kinase (HsRFK) catalyzes vitamin B2 (riboflavin) phosphorylation to flavin mononucleotide (FMN), obligatory step in flavin cofactor synthesis. HsRFK expression is related to protection from oxidative stress, amyloid-ß toxicity, and some malignant cancers progression. Its downregulation alters expression profiles of clock-controlled metabolic-genes and destroys flavins protection on stroke treatments, while its activity reduction links to protein-energy malnutrition and thyroid hormones decrease. We explored specific features of the mechanisms underlying the regulation of HsRFK activity, showing that both reaction products regulate it through competitive inhibition. Fast-kinetic studies show that despite HsRFK binds faster and preferably the reaction substrates, the complex holding both products is kinetically most stable. An intricate ligand binding landscape with all combinations of substrates/products competing with the catalytic complex and exhibiting moderate cooperativity is also presented. These data might contribute to better understanding the molecular bases of pathologies coursing with aberrant HsRFK availability, and envisage that interaction with its client-apoproteins might favor FMN release. Finally, HsRFK parameters differ from those of the so far evaluated bacterial counterparts, reinforcing the idea of species-specific mechanisms in RFK catalysis. These observations support HsRFK as potential therapeutic target because of its key functions, while also envisage bacterial RFK modules as potential antimicrobial targets.

Towards the competent conformation for catalysis in the ferredoxin-NADP+ reductase from the Brucella ovis pathogen.

Brucella ovis encodes a bacterial subclass 1 ferredoxin-NADP(H) reductase (BoFPR) that, by similarity with other FPRs, is expected either to deliver electrons from NADPH to the redox-based metabolism and/or to oxidize NADPH to regulate the soxRS regulon that protects bacteria against oxidative damage. Such potential roles for the pathogen survival under infection conditions make of interest to understand and to act on the BoFPR mechanism. Here, we investigate the NADP+/H interaction and NADPH oxidation by hydride transfer (HT) to BoFPR. Crystal structures of BoFPR in free and in complex with NADP+ hardly differ. The latter shows binding of the NADP+ adenosine moiety, while its redox-reactive nicotinamide protrudes towards the solvent. Nonetheless, pre-steady-state kinetics show formation of a charge-transfer complex (CTC-1) prior to the hydride transfer, as well as conversion of CTC-1 into a second charge-transfer complex (CTC-2) concomitantly with the HT event. Thus, during catalysis nicotinamide and flavin reacting rings stack. Kinetic data also identify the HT itself as the rate limiting step in the reduction of BoFPR by NADPH, as well as product release limiting the overall reaction. Using all-atom molecular dynamics simulations with a thermal effect approach we are able to visualise a potential transient catalytically competent interaction of the reacting rings. Simulations indicate that the architecture of the FAD folded conformation in BoFPR might be key in catalysis, pointing to its adenine as an element to orient the reactive atoms in conformations competent for HT.

Proteasome versus Thioredoxin Reductase Competition as Possible Biological Targets in Antitumor Mixed Thiolate-Dithiocarbamate Gold(III) Complexes.

New mixed gold(III) derivatives with dithiocarbamate and thiolate ligands have been synthesized and characterized. They display high anticancer activity against colon cancer cell lines without affecting to differentiated enterocytes, high stability in phosphate-buffered saline solution, and resistance to gold reduction in the presence of reducing agents in the majority of the derivatives. Some of them show interaction with thioredoxin reductase as derived from in vitro analysis and computational studies. However, a competition between this enzyme and proteasome is detected in cells, which is corroborated by the determination of proteasomal chymotrypsin-like activity inhibition. In addition, some of these dithiocarbamate gold(III) derivatives reduce cell viability and proliferation by intrinsic apoptotic pathway, with changes in mitochondrial membrane potential, cytochrome c release and caspase-3 activation. Consequently, our results show new complexes with proteasome as possible target in colorectal cancer.

Desarrollo de un servicio en línea para la gestión tecnológica en salud / Development of a service on line advice and information technology management for health

Desarrollar un servicio de asesoría en línea para la gestión tecnológica en salud, que contribuya a realizar procesos de evaluación y adquisición de equipos médicos según el mercado y las necesidades de las instituciones de salud. Materiales y métodos. Se desarrolló una solución tecnológica vía Internet soportada en una base de datos con información sistematizada y actualizada de especificaciones técnicas de 25 equipos médicos, precios referenciales, lista de proveedores, representantes y/o fabricantes y normas técnicas, así como un servicio de asesoría técnica ôvirtualõ. La validación del servicio se realizó mediante la participación de especialistas en el tema de gestión de tecnologías en salud, de diferentes disciplinas y que laboraban en entidades de salud, públicas y privadas. Ellos utilizaron el servicio durante un período para comprobar su factibilidad de uso. A dichos expertos se les aplico una encuesta antes y después de darles a conocer el software desarrollado en el presente proyecto. Resultados. Se encontró que es usual el uso de Internet para buscar información sobre equipos médicos. Asimismo, se observó un incremento sobre la opinión de que el aplicativo será de ayuda en las adquisiciones de equipos biomédicos (de 40 a 78%), mejorará el sistema de información (de 40 a 89%) y la comunicación entre médicos, enfermeras, planificadores, ingenieros y demás profesionales que participan en dicho proceso (de 20 a 78%). Conclusiones. Existe la necesidad de tener disponible una herramienta tecnológica con tales características que contribuya a la gestión tecnológica en el Perú...

To validate an advisory service and online information technology management for health and helps to make assessment and acquisition processes an informed medical equipment according to the market and the needs of thehealth institutions. Materials and methods. Internet via a technological solution supported on a data base containing systematic and updated information on technical specifications of 25 compared medical equipment, the same reference prices, list of suppliers, agents and / or producers and technical standards are developed. The õvirtualõ technical assistance was made with the support of a team of specialists in Health Technology Management, the decision makers in the planning, evaluation and procurement of biomedical equipment. The validation of the service was conducted by involving specialists in the field of Health Technology Management, from different disciplines and institutions who worked in health, public and private. They used the service for a period of time to verify its feasibility of use as well as its usefulness for their planning, evaluation and procurement of biomedical equipment. To these experts we applied a survey before and afterthem about the software developed in this project. Results. We found that it is common to use the internet to search forinformation on medical equipment. Also, an increase on the view that the application will help in procurement of biomedical equipment (40% to 78%) was observed, it will improve the information system (40% to 89%) and communication among physicians, nurses, planners, engineers and other professionals involved in this process (20% to 78%). Conclusions. There is a need for a technological tool available with such features contribute to technology management in Peru...

New insights into the chemistry of di- and trimetallic iron dithiolene derivatives. Structural, Mössbauer, magnetic, electrochemical and theoretical studies.

Reaction of Fe3(CO)12 with 1,2-dithiolene HSC6H2Cl2SH affords a mixture of complexes [Fe2(CO)6(µ-SC6H2Cl2S)] 1, [Fe2(SC6H2Cl2S)4] 2 and [Fe3(CO)7(µ3-SC6H2Cl2S)2] 3. In the course of the reaction the trimetallic cluster 3 is first formed and then converted into the known dinuclear compound 1 to afford finally the neutral diiron tetrakis(dithiolato) derivative 2. Compounds 2 and 3 have been studied by Mössbauer spectroscopy, X-ray crystallography and theoretical calculations. In compound 2 the metal atoms are in an intermediate-spin Fe(III) state (S(Fe) = 3/2) and each metal is bonded to a bridging dithiolene ligand and a non-bridging thienyl radical (S = 1/2). Magnetic measurements show a strong antiferromagnetic coupling in complex 2. Cyclic voltammetry experiments show that the mixed valence trinuclear cluster 3 undergoes a fully reversible one electron reduction. Additionally, compound 3 behaves as an electrocatalyst in the reduction process of protons to hydrogen.

Theoretical study on the reaction mechanism of VO2+ with propyne in gas phase.

Possible molecular mechanisms of the gas-phase ion/molecule reaction of VO2+ in its lowest singlet and triplet states (1A1/3A' ') with propyne have been investigated theoretically by density functional theory (DFT) methods. The geometries, energetic values, and bonding features of all stationary and intersystem crossing points involved in the five different reaction pathways (paths 1-5), in both high-spin (triplet) and low-spin (singlet) surfaces, are reported and analyzed. The oxidation reaction starts by a hydrogen transfer from propyne molecule to the vanadyl complex, followed by oxygen migration to the hydrocarbon moiety. A hydride transfer process to the vanadium atom opens four different reaction courses, paths 1-4, while path 5 arises from a hydrogen transfer process to the hydroxyl group. Five crossing points between high- and low-spin states are found: one of them takes place before the first branching point, while the others occur along path 1. Four different exit channels are found: elimination of hydrogen molecule to yield propynaldehyde and VO+ (1Sigma/3Sigma); formation of propynaldehyde and the moiety V-(OH2)+; and two elimination processes of water molecule to yield cationic products, Prod-fc+ and Prod-dc+ where the vanadium atom adopts a four- and di-coordinate structure, respectively.

Toward an understanding of the catalytic role of hydrogen-bond donor solvents in the hetero-Diels-Alder reaction between acetone and butadiene derivative.

A detailed theoretical investigation of the catalytic role of hydrogen-bond- (HB-) donor molecules (water, methanol, chloroform, dichloromethane, and chloromethane) in the hetero-Diels-Alder reaction between acetone and N,N-dimethyl-1-amino-3-methoxy-1,3-butadiene is presented. This work extends a previous study (Domingo, L. R.; Andres, J. J. Org. Chem. 2003, 68, 8662) in which the importance of weak HB-donor solvents to catalyze more effectively than solvents with a higher dielectric constant but no HB-donor capability was analyzed. Now, based on density functional theory (DFT) at B3LYP/6-31+G(d) level calculations, different techniques for analyzing the nature of HB interaction, namely, natural bond orbital (NBO) theory, topological analysis of the electron density (atoms in molecules, AIM, theory), and the electron localization function (ELF) and decomposition of the interaction energy between monomers (energy decomposition analysis, EDA), have been applied to understand why only some HB-donor solvents are able to catalyze the reaction. The catalytic effect of the solvent arises from the improved HB-acceptor capability of the oxygen atom at the transition structure (TS) due to the strong polarization of the carbonyl group. The HB acceptor presents three lone pairs (NBO analysis), and the ELF shows an increment of the electronic charge of the lone pairs of 0.50e with respect to the reactant. All solvent molecules form stronger HB interactions at the TS, but only those presenting larger charge-transfer interactions (water, methanol, chloroform) benefit more from the polarization of the carbonyl group than other solvents (dichloromethane, chloromethane) with less "covalent" character.

Factores asociados a la infección del virus de inmunodeficiencia humana: estudio caso control / Factors associated with acquired immunodefiency syndrome: care control study

Se realizó un estudio caso-control apareado para identificar los factores de riesgo asociados a la infección del HIV. Se entrevistió a 69 pacientes que resultaron positivos al test de ELISA y al Wester blot (casos) y a 133 pacientes que resultaron negativos a las mismas pruebas (controles). Dichos pacientes, acudieron al Hospital General Cayetano Heredia y al Hospital del Seguro Social E. Rebagliatti entre setiembre de 1990 y Octubre de 1991. De los 69 casos, 5 fueron mujeres. Cada caso fué apareado con 2 controles excepto las mujeres que tuvieron un solo control. Con el análisis apareado se identificó a los siguientes factores asociados para adquirir la infección del HIV: consumir alcohol o drogas antes de tener relaciones sexuales (OR igual 7.33); tener pareja homosexuales (OR igual 3.50); tener gran número de relaciones sexuales (OR igual 3.45); tener relaciones sexuales en grupo (OR igual 4.50); tener relaciones sexuales con extranjeros en el Perú (OR igual 5.60); practicar la relación orogenital receptiva o ambos (OR igual 2.88); practicar la relación anal receptiva o ambos (OR igual 2.76); no usar preservativo al practicar la relación anal (OR igual 10.4); practicar la relación oroanal (OR igual 3.57); el presentar el antecedente de Sífilis (OR igual 2.54) y presentar el antecedente de proctitis (OR igual 5.33). No hay razón para que estos factores no sean intervenidos a nivel educativo, sobretodo en grupos de alto riesgo predominantemente homosexual y/o bisexual