Elucidation of the Pyridine Ring-Opening Mechanism of 2,2'-Bipyridine or 1,10-Phenanthroline Ligands at Re(I) Carbonyl Complexes.

The cleavage of the C-N bonds of aromatic heterocycles, such as pyridines or quinolines, is a crucial step in the hydrodenitrogenation (HDN) industrial processes of fuels in order to minimize the emission of nitrogen oxides into the atmosphere. Due to the harsh conditions under which these reactions take place (high temperature and H2 pressure), the mechanism by which they occur is only partially understood, and any study at the molecular level that reveals new mechanistic possibilities in this area is of great interest. Herein, we unravel the pyridine ring-opening mechanism of 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) ligands coordinated to the cis-{Re(CO)2(N-RIm)(PMe3)} (N-RIm= N-alkylimidazole) fragment under mild conditions. Computational calculations show that deprotonation of the pyridine ring, once dearomatized, is crucial to induce ring contraction, triggering extrusion of the nitrogen atom from the ring and cleavage of the C-N bond. It is noteworthy that different products (regioisomers) are obtained depending on whether the ligand used is bipy or phen due to the additional rigidity and stability conferred by the central ring of the phen ligand, an issue also addressed and clarified computationally. Strong support for the proposed mechanism is provided by the characterization and isolation, including three single-crystal X-ray diffraction structures, of several of the proposed reaction intermediates.

Computational Design of Rhenium(I) Carbonyl Complexes for Anticancer Photodynamic Therapy.

New Re(I) carbonyl complexes are proposed as candidates for photodynamic therapy after investigating the effects of the pyridocarbazole-type ligand conjugation, addition of substituents to this ligand, and replacement of one CO by phosphines in [Re(pyridocarbazole)(CO)3(pyridine)] complexes by means of the density functional theory (DFT) and time-dependent DFT. We have found, first, that increasing the conjugation in the bidentate ligand reduces the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gap of the complex, so its absorption wavelength red-shifts. When the enlargement of this ligand is carried out by merging the electron-withdrawing 1H-pyrrole-2,5-dione heterocycle, it enhances even more the stabilization of the LUMO due to its electron-acceptor character. Second, the analysis of the shape and composition of the orbitals involved in the band of interest indicates which substituents of the bidentate ligand and which positions are optimal for reducing the HOMO-LUMO energy gap. The introduction of electron-withdrawing substituents into the pyridine ring of the pyridocarbazole ligand mainly stabilizes the LUMO, whereas the HOMO energy increases primarily when electron-donating substituents are introduced into its indole moiety. Each type of substituents results in a bathochromic shift of the lowest-lying absorption band, which is even larger if they are combined in the same complex. Finally, the removal of the π-backbonding interaction between Re and the CO trans to the monodentate pyridine when it is replaced by phosphines PMe3, 1,4-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA), and 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane (CAP) causes another extra bathochromic shift due to the destabilization of the HOMO, which is low with DAPTA, moderate with PMe3, but especially large with CAP. Through the combination of the PMe3 or CAP ligands with adequate electron-withdrawing and/or electron-donating substituents at the pyridocarbazole ligand, we have found several complexes with significant absorption at the therapeutic window. In addition, according to our results on the singlet-triplet energy gap, all of them should be able to produce cytotoxic singlet oxygen.

Influence of the Nucleophilic Ligand on the Reactivity of Carbonyl Rhenium(I) Complexes towards Methyl Propiolate: A Computational Chemistry Perspective.

A comparative theoretical study on the reactivity of the complexes [ReY(CO)3(bipy)] (Y = NH2, NHMe, NHpTol, OH, OMe, OPh, PH2, PHMe, PMe2, PHPh, PPh2, PMePh, SH, SMe, SPh; bipy = 2,2'-bipyridine) towards methyl propiolate was carried out to analyze the influence of both the heteroatom (N, O, P, S) and the alkyl and/or aryl substituents of the Y ligand on the nature of the product obtained. The methyl substituent tends to accelerate the reactions. However, an aromatic ring bonded to N and O makes the reaction more difficult, whereas its linkage to P and S favour it. On the whole, ligands with O and S heteroatoms seem to disfavour these processes more than ligands with N and P heteroatoms, respectively. Phosphido and thiolato ligands tend to yield a coupling product with the bipy ligand, which is not the general case for hydroxo, alcoxo or amido ligands. When the Y ligand has an O/N and an H atom the most likely product is the one containing a coupling with the carbonyl ligand, which is not always obtained when Y contains P/S. Only for OMe and OPh, the product resulting from formal insertion into the Re-Y bond is the preferred.

Regiochemistry Control by Bipyridine Substituents in the Deprotonation of ReI and MoII N-Alkylimidazole Complexes.

Compounds containing N-alkylimidazoles (N-RIm) and 4,4'-disubstituted 2,2'-bipyridines (4,4'-R'2 bipy) coordinated to cationic {Mo(η3 -C4 H7 )(CO)2 } and {Re(CO)3 } fragments undergo deprotonation of the C2-H group of the N-RIm ligands in their reactions with KN(SiMe3 )2 . The resulting internal nucleophile adds either to one pyridyl ring, which becomes dearomatized and can undergo ring opening in the subsequent reaction with excess MeOTf, or to the metal center, yielding imidazol-2-yl complexes, which in turn add HOTf or MeOTf, affording N-heterocyclic carbene complexes. Which pathway is followed is dictated by the metal and the nature of the imidazole (R) and bipyridine (R') substituents. For ReI compounds, addition to pyridine is found with R'=tBu and OMe, whereas for R=Me and R'=NMe2 , imidazolyl formation is preferred. Coordination of 4,7-Cl2 -1,10-phenanthroline to MoII favors C-C coupling, in contrast to the analogous parent bipy or phenanthroline complexes, for which formation of the imidazol-2-yl complexes had been found. DFT calculations showed the theoretically expected products in each case, and following their predictions new types of products were obtained experimentally.

Phosphinous Acid-Assisted Hydration of Nitriles: Understanding the Controversial Reactivity of Osmium and Ruthenium Catalysts.

The synthesis and catalytic behavior of the osmium(II) complexes [OsCl2 (η6 -p-cymene)(PR2 OH)] [R=Me (2 a), Ph (2 b), OMe (2 c), OPh (2 d)] in nitrile hydration reactions is presented. Among them, the best catalytic results were obtained with the phosphinous acid derivative [OsCl2 (η6 -p-cymene)(PMe2 OH)] (2 a), which selectively provided the desired primary amides in excellent yields and short times at 80 °C, employing directly water as solvent, and without the assistance of any basic additive (TOF values up to 200 h-1 ). The process was successful with aromatic, heteroaromatic, aliphatic, and α,ß-unsaturated organonitriles, and showed a high functional group tolerance. Indeed, complex 2 a represents the most active and versatile osmium-based catalyst for the hydration of nitriles reported so far in the literature. In addition, it exhibits a catalytic performance similar to that of its ruthenium analogue [RuCl2 (η6 -p-cymene)(PMe2 OH)] (4). However, when compared to 4, the osmium complex 2 a turned out to be faster in the hydration of less-reactive aliphatic nitriles, whereas the opposite trend was generally observed with aromatic substrates. DFT calculations suggest that these differences in reactivity are mainly related to the ring strain associated with the key intermediate in the catalytic cycle, that is, a five-membered metallacyclic species generated by intramolecular addition of the hydroxyl group of the phosphinous acid ligand to the metal-coordinated nitrile.

Insights on the Reactivity of Terminal Phosphanido Metal Complexes toward Activated Alkynes from Theoretical Computations.

Herein we present a theoretical study on the reaction of [Re(PPh2) (CO)3(phen)] (phen = 1,10-phenanthroline) and [Re(PPh2) (CO)3(bipy)] (bipy = 2,2'-bipyridine) toward methyl propiolate. In agreement with experimental results for the phen ligand, the coupling of the substituted acetylenic carbon with the nonsubstituted ortho carbon of the phen ligand is the preferred route from both kinetic and thermodynamic viewpoints with a Gibbs energy barrier of 18.8 kcal/mol and an exoergicity of 11.1 kcal/mol. There are other two routes, the insertion of the acetylenic fragment into the P-Re bond and the coupling between the substituted acetylenic carbon and a carbonyl ligand in cis disposition, which are kinetically less favorable than the preferred route (by 2.8 and 1.9 kcal/mol, respectively). Compared with phen, the bipy ligand shows less electrophilic character and also less π electron delocalization due to the absence of the fused ring between the two pyridine rings. As a consequence, the route involving the coupling with a carbonyl ligand starts to be kinetically competitive, whereas the product of the attack to bipy is still the most stable and would be the one mainly obtained after spending enough time to reach thermal equilibrium.

Nucleophilic Additions to Coordinated 1,10-Phenanthroline: Intramolecular, Intermolecular, Reversible, and Irreversible.

KN(SiMe3 )2 reacts with [Re(CO)3 (phen)(PMe3 )]OTf via reversible addition to the phen ligand and irreversible deprotonation of the PMe3 ligand followed by intramolecular attack to phen by the deprotonated phosphane, whereas MeLi irreversibly adds to phen. The addition of MeLi has been shown to be intermolecular, unlike previously known nucleophilic additions to pyridines.

Activation of Aromatic C-C Bonds of 2,2'-Bipyridine Ligands.

4,4'-Disubstituted-2,2'-bipyridine ligands coordinated to MoII and ReI cationic fragments become dearomatized by an intramolecular nucleophilic attack from a deprotonated N-alkylimidazole ligand in cis disposition. The subsequent protonation of these neutral complexes takes place on a pyridine carbon atom rather than at nitrogen, weakening an aromatic C-C bond and affording a dihydropyridyl moiety. Computational calculations allowed for the rationalization of the formation of the experimentally obtained products over other plausible alternatives.

The role of CuCl on the mechanism of dibenzo-p-dioxin formation from poly-chlorophenol precursors: A computational study.

A computational study is performed for the elucidation of the role played by CuCl in the condensation of two polychlorophenol molecules to yield PCDDs. The mechanism found consists of six sequential steps, which allow the final recuperation of the CuCl molecule, and applies for phenol molecules with an ortho chlorine. In the temperature range of 453-473 K (previously reported as adequate to diminish PCDDs formation in the post-combustion area), CuCl is able to softly retain chlorophenol molecules, mainly those less chlorinated. After a first HCl release, Cu(I) remains bonded to phenol oxygen atom, thus avoiding the formation of phenoxy radicals and the subsequent radical processes. A temperature raise up to 1200 K destabilizes the initial CuCl-chlorophenol complexes and causes that the rate limiting step change from the formation of the first oxygen bridge to HCl elimination. It has been checked that tetra and penta-chlorophenols undergo essentially the same reaction process of 2-chlorophenol. In view of our results and trying to arrive at a practical way to diminish the rate of formation of PCDDs, we propose that an extra addition of powdered CuCl to the post-combustion zone, cooled down to temperatures lower than 473 K, could act as an inhibitor in the formation of these pollutants.

Unraveling the intramolecular cyclization mechanism of oxidized tryptophan in aqueous solution as a function of pH.

The aqueous intramolecular cyclization of 3a-hydroperoxitryptophan, Trp-OOH, (an intermediate in the photodynamic treatment of cancer) is studied at the PCM-MP2/aug-cc-pVDZ//PCM-B3LYP/aug-cc-pVDZ computational level with and without explicit water molecules. The three-cycle product may evolve to the metabolite N-formyl kynurenine in living beings or can be a building block in the formation of indole alkaloids in organic synthesis. When the pH is close to the isoelectric point of tryptophan, we have found two cyclization mechanisms, one passing along zwitterion intermediates, I-route (beginning with a proton transfer from the ammonium to the N-indole atom) and the other involving neutral isomers, C-route (starting with the attack of N-amino to C2-indole). At this pH, the discrete-continuum model with six explicit water molecules predicts a Gibbs energy barrier of 14.6 kcal mol(-1) for the I-route and of 11.6 kcal mol(-1) for the C-route. It is possible to experimentally tune the operating mechanism since in acidic environments only the I-route is available (Gibbs energy barrier of 8.4 kcal mol(-1)) whereas in basic media only the C-route can operate (Gibbs energy barrier of 6.7 kcal mol(-1)). These data explain the trend of Trp-OOH to easily decompose under basification.

Theoretical study on the electronic excitations of a porphyrin-polypyridyl ruthenium(II) photosensitizer.

In this work, we investigated the UV-vis spectra of the [Ru(bipy)(2)(MPyTPP)Cl](+) (MPyTPP = 5-pyridyl-15,20,25-triphenylporphyrin) complex and its related species [Ru(bipy)(2)(py)Cl](+) and MPyTPP, by using time-dependent density functional theory and a set of functionals (B3LYP, M05, MPWB1K, and PBE0) in chloroform with the basis set 6-31++G(d,p) for nonmetal atoms and the pseudopotential LANL2DZ for Ru. Practically no geometrical changes are observed in the Ru environment when py ligand is replaced by MPyTPP. This replacement favors the electronic redistribution from bipy ligands to Ru, and from the metal to MPyTPP ligand, as indicated by NBO analysis. We found that M05 functional predicts very well the UV-vis spectra, as it shows a low deviation with respect to the experimental data, with a maximum error of 0.19 eV (11 nm). M05 theoretical electronic spectrum of [Ru(bipy)(2)(MPyTPP)Cl](+) complex indicates that the presence of the Ru complex does not alter Q porphyrin bands, while charge transfer bands from Ru to bipy and porphyrin ligands mixes up in the region close to the porphyrin Soret band. Theoretical analysis allows the decomposition of this broad experimental band into specific ones identifying the Soret band and new metal to ligand charge transfers toward porphyrin at 425 and 478 nm, which were not possible in none of the moieties MPyTPP and [Ru(bipy)(2)(Py)Cl](+) complex. In the UV region, the most intense intraligand band of bipy ligands becomes slightly blue-shifted both in the experimental and in the theoretical spectrum of [Ru(bipy)(2)(MPyTPP)Cl](+) complex compared to that in [Ru(bipy)(2)(py)Cl](+) complex. Some of the bands of [Ru(bipy)(2)(MPyTPP)Cl](+) showed in this theoretical study may have practical applications. That is the case for the band at 478 nm, with potential use in PDT, and those more energetic at 348 and 329 nm, which could help in the cleavage mechanism of DNA performed by this ruthenium complex.

Subporphyrinoid systems: a theoretical study of the effects of the diheteroatom substitution in pyrrole subunits and of the nature of the bridging meso linkages.

A theoretical study of the geometry, the electronic structure, the electronic absorption spectra, and (1)H and (13)C NMR spectra of the [14]subporphine(1.1.1)-hydroxyboron(III) complex, free-base subporphyrin, and its dioxygen and dithio pyrrole substituted derivatives using CH, N, and P as bridging meso linkages was performed at the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) theory level. The geometrical structure of these systems is mainly determined by the internal area delimited by the meso atoms and the alpha-carbon atoms of the pyrrolic rings, and by the number and nature of the atoms located on this area. All the hydroxyboron subporphyrins and dioxo and dithio subporphyrins with CH meso connectors display a conical shaped geometry. The presence of strong repulsions between the atoms on the central zone of the remaining systems provokes a correlative tilting of one of the three rings with loss of the conical shape with important consequences on spectroscopic properties. A particularly interesting case is the dioxosubporphyrin with P connectors in which the large area of the central zone determined by these connectors allows for an almost planar geometry that endows it with special features. The molecules presenting a tilted ring display weak absorption bands. Generally, the intensity of the bands moderately increases when the geometry is cone shaped. The dioxo heterosubporphyrins with CH (conical shape) and P (almost planar) connectors present strong absorption bands. (1)H and (13)C chemical shifts clearly reflect the effect of geometry distortion provoked by the repulsion among the atoms of the central area of the system indicating a deep perturbation of the pi system of the molecules.

On the mechanism of cyclization of 5-hexenylchromate intermediates in the reactions of Fischer carbene complexes with a lithium enolate and allylmagnesium bromide.

The mechanisms for the evolution of pentacarbonyl-5-hexenylchromate complexes, unsubstituted and methyl substituted at C2, formed from a pentacarbonyl(alkoxy)carbene complex of chromium, the corresponding ketone lithium enolate, and allylmagnesium bromide, were theoretically investigated by using DFT (Density Functional Theory) at the B3PW91/6-31G* level (LANL2DZ for Cr and Br) taking into account the effect of THF solvent through the PCM model (Polarizable Continuum Model). Methyl substitution at C2 provokes a shortening of about 5 degrees in the C1-C2-C3 angle that favors the formation of the pentacyclic product. Also, the presence of this methyl substituent at C2 sterically disfavors the formation of the hexacyclic product. Thus, our results yield the hexacyclic system as the most favored product for the evolution of the unsubstituted alkylpentacarbonylchromate complex, and the pentacyclic product in the case of the substituted system, in good agreement with the experimental findings. The stereochemistry of the products experimentally observed is determined at the transition state for the migration of the Cr(CO)(5) fragment from C1 to C6 and the conformational rearrangement of the C1-C6 skeleton. Amine molecules, present in the reaction medium, can play a catalytic role by assisting the 1,2-H migration in the last step for the formation of hexacyclic products.

Theoretical insight into pyrrole inversion and planarity in 5,10,15,20-tetraphenylsapphyrin and 5,10,15,20-tetraphenyl-26,28-diheterosapphyrins with two O, S, or Se atoms.

Density functional calculations at the B3LYP/6-31+G(d) (LACVP(D) for Se) theory level have been carried out on 5,10,15,20-tetraphenylsapphyrin ( TPS), 5,10,15,20-tetraphenyl-26,28-dioxasapphyrin ( TP2OS), 5,10,15,20-tetraphenyl-26,28-dithiasapphyrin ( TP2SS), and 5,10,15,20-tetraphenyl-26,28-diselenasapphyrin ( TP2SeS). In agreement with experimental findings, our theoretical results show that TPS and TP2OS present an inverted conformation, whereas TP2SS and TP2SeS are more stable in the normal one. It was found that the relative stability of the normal and inverted conformers of the just mentioned sapphyrins correlates positevily with their degree of planarity and aromaticity, which depends on the size of the heteroatom, the steric repulsions produced by phenyl rings at the meso C atoms, and the network and nature of the bond critical points (BCPs) inside the macrocycle. These BCPs have been characterized by means of the AIM analysis and, some selected ones, by the changes in the total energy of significant fragments when distorted to avoid them.

[Appropriate use of benzodiazepines zolpidem and zopiclone in diseases attended in primary care]. / Adecuación del uso de las benzodiacepinas zolpidem y zopiclona en problemas atendidos en atención primaria.

OBJECTIVES: To estimate the proportion of benzodiazepine prescriptions that comply with the guidelines for appropriate prescription. To identify the variables associated with appropriate prescription. DESIGN: Observational, cross-sectional study. SETTING: Monóvar Health Centre in Area IV, Madrid, Spain. SUBJECTS: Random sample of 270 active benzodiazepine prescriptions in adult patients from the prescriptions record of the OMI-AP V. 5.0 computer system. MEASUREMENTS: The chosen dimensions for appropriate prescription were: a) correct diagnostic indication; b) absence of benzodiazepines with long half-life in the elderly; c) existence of support or monitoring visits; d) overall appropriateness or coexistence of correct diagnostic indications and monitoring visits. Independent variables were recorded in relation to patient, person prescribing and prescription. RESULTS: Diagnostic indication, 75.6%; absence of benzodiazepines with long half-life in the elderly, 79.8%; existence of support visits, 63.3%; overall appropriateness, 53%. Main diagnoses: pure anxiety, 29%; anxiety related to other illness, 18.6%; insomnia, 14.8%; cardiovascular illness, 14.8%; alcohol and drug abuse, 4.5%; osteo-muscular illness, 4.4%; schizophrenia, 4.4%. Most prescribed substances: lorazepam, 27.8%; bromazepam, 23.7%. Average life of prescriptions: 18.58 months. Origins: health centre, 68.5%; out-patient psychiatry, 10%; hospital, 10%. The variable that is most closely associated with overall appropriateness, fitted with the rest of the variables, is out-patient psychiatry prescription (OR, 6.67; 95% CI, 1.92-23.18). CONCLUSIONS: The mean duration of the prescriptions infringes all standards. The overall appropriateness or correct coexistence of adequate diagnostic indication with follow-up visits is associated with out-patient Psychiatry prescription.

Adecuación del uso de las benzodiacepinas zolpidem y zopiclona en problemas atendidos en atención primaria

Objetivo. Estimar la proporción de prescripciones de las benzodiacepinas zolpidem y zopiclona que cumplen criterios normativos de adecuada prescripción. Identificar las variables asociadas con una adecuada prescripción. Diseño. Observacional, transversal. Ámbito. Centro de Salud de Monóvar del Área IV de Madrid. Sujetos: Muestra aleatoria de 270 prescripciones activas de benzodiacepinas en adultos del registro de prescripciones del sistema informático OMI-AP versión 5.0. Mediciones. Dimensiones: a) correcta indicación diagnóstica; b) ausencia de benzodiacepinas de vida media larga en ancianos; c) existencia de visitas de apoyo o seguimiento, y d) adecuación global o coexistencia de indicaciones correctas y visitas de seguimiento. Variables independentes recogidas en relación con el paciente, el prescriptor y la prescripción. Resultados. Correcta indicación diagnóstica en el 75,6 por ciento, ausencia de benzodiacepinas de vida media larga en ancianos del 79,8 por ciento, existencia de visitas de apoyo en el 63,3 por ciento y adecuación global en el 53 por ciento. Principales diagnósticos: ansiedad pura en el 29 por ciento, ansiedad relacionada con otros procesos en el 18,6 por ciento, insomnio en el 14,8 por ciento, enfermedades circulatorias en el 14,8 por ciento, abuso de alcohol y drogas en el 4,5 por ciento, enfermedad osteomuscular en el 4,4 por ciento y esquizofrenia en el 4,4 por ciento. Sustancias más prescritas: lorazepamen el 27,8 por ciento y bromazepam en el 23,7 por ciento. Duración media de las prescripciones: 18,58 meses. Origen: el 68,5 por ciento en el centro de salud y el 10 por ciento en el hospital. La variable que más se asocia con la adecuación global tras ajustar por las restantes variables es la prescripción originada en salud mental (odds ratio [OR] = 6,67; intervalo de confianza [IC] del 95 por ciento, 1,92-23,18). Conclusiones. La duración media de las prescripciones contraviene todos los estándares. La adecuación global o coexistencia de indicación diagnóstica correcta con presencia de visitas de seguimiento se asocia con la prescripción en el ámbito de la salud mental.(AU)

A theoretical proposal for the synthesis of carbapenems from 4-(2-propynyl)azetidinones promoted by [W(CO)5] as an alternative to the Ag+-assisted process.

The synthesis of carbapenems from 4-(2-propynyl)azetidinones assisted by both Ag+ and [W(CO)5] was theoretically investigated by using the B3LYP/6-31+G(d)-LANL2DZ level, taking into account the effect of solvent by the PB-SCRF model implemented in Jaguar. According to our results, the silver-assisted cyclization is a concerted process for which the low yield experimentally observed could mainly stem from the alkaline hydrolysis of the beta-lactam ring. This process is very efficiently catalyzed by Ag+, making it competitive with the formation of the carbapenem. The cycloisomerization of 4-(2-propynyl)azetidinone promoted by [W(CO)5] is proposed as an alternative synthetic strategy to obtain the carbapenem. The endo cycloisomerization is by far the most favorable one. When the process is assisted by [(thf)W(CO)5], although the main product is the carbapenem, the formation of a carbene complex represents a certain competition. The presence of a Me3N molecule from the very start of the reaction causes an important catalytic effect considerably reducing the energy barriers corresponding to the H atom transfers and rendering a very efficient process. Moreover, this catalytic action determines the evolution of the system through only one mechanistic route which produces the carbapenem, hindering the formation of the carbene. Therefore, the cycloisomerization of 4-(2-propynyl)azetidinone promoted by [(Me3N)W(CO)5] constitutes an interesting alternative to the silver-assisted cyclization.

Adecuación del uso de las benzodiacepinas zolpidem y zopiclona en problemas atendidos en atención primaria / Appropriate use of benzodiazepines zolpidem and zopidone in diseases attended in primary care

Objetivo. Estimar la proporción de prescripciones de las benzodiacepina zolpidem y zopiclona que cumplen criterios normativos de adecuada prescripción. Identificar las variables asociadas con una adecuada prescripción. Diseño. Observacional, transversal. Ámbito. Centro de Salud de Monóvar del Área IV de Madrid. Sujetos. Muestra aleatoria de 270 prescripciones activas de benzodiacepinas en adultos del registro de prescripciones del sistema informático OMI-AP versión 5.0. Mediciones. Dimensiones: a) correcta indicación diagnóstica; b) ausencia de benzodiacepinas de vida media larga en ancianos; c) existencia de visitas de apoyo o seguimiento, y d) adecuación global o coexistencia de indicaciones correctas y visitas de seguimiento. Variables independientes recogidas en relación con el paciente, el prescriptor y la prescripción. Resultados. Correcta indicación diagnóstica en el 75,6%, ausencia de benzodiacepinas de vida media larga en ancianos del 79,8%, existencia de visitas de apoyo en el 63,3% y adecuación global en el 53%. Principales diagnósticos: ansiedad pura en el 29%, ansiedad relacionada con otros procesos en el 18,6%, insomnio en el 14,8%, enfermedades circulatorias en el 14,8%, abuso de alcohol y drogas en el 4,5%, enfermedad osteomuscular en el 4,4% y esquizofrenia en el 4,4%. Sustancias más prescritas: lorazepam en el 27,8% y bromazepam en el 23,7%. Duración media de las prescripciones: 18,58 meses. Origen: el 68,5% en el centro de salud, el 10% en el cantro de salud mental y el 10% en el hospital. La variable que más se asocia con la adecuación global tras ajustar por las restantes variables es la prescripción originada en salud mental (odds ratio [OR] = 6,67; intervalo de confianza [IC] del 95%, 1,92-23,18). Conclusiones. La duración media de las prescripciones contraviene todos los estándares. La adecuación global o coexistencia de indicación diagnóstica correcta con presencia de visitas de seguimiento se asocia con la prescripción en el ámbito de la salud mental

Objetives. To estimate the proportion of benzodiazepine prescriptions that comply with the guidelines for appropriate prescription. To identify the variables associated with appropriate prescription. Design. Observational, cross-sectional study. Setting. Monóvar Health Centre in Area IV, Madrid, Spain. Subjets. Random sample of 270 active benzodiazepine prescriptions in adult patients from the prescriptions record of the OMI-AP V. 5.0 computer system. Measurements. The chosen dimensions for appropriate prescription were: a) correct diagnostic indication; b) absence of benzodiazepines with long half-life in the elderly; c) existence of support or monitoring visits; d) oerall appropriateness or coexistence of correct diagnostic indications and monitoring visits. Independent variables were recorded in relation to patient, person prescribing and prescription. Results. Diagnostic indication, 75.6%; absence of benzodiazepines with long half-life in the elderly, 79.8%; existence of support visits, 63.3%; overall appropriateness, 53%. Main diagnoses: pure anxiety, 29%; anxiety related to other illness, 18.6%; insomnia, 14.8%; cardiovascular illness, 14.8%; alcohol and drug abuse, 4.5%; osteo-muscular illness, 4.4%; schizophrenia, 4.4%. Most prescribed substances: lorazepam, 27.8%; bromazepam, 23.7%. Average life of prescriptions: 18.58 months. Origins: health centre, 68.5%; out-patient psychiatry, 10%; hospital, 10%. The variable that is most closely associated with overall appropriateness, fitted with the rest of the variables, is out-patient psychiatry prescription (OR, 6.67; 95% CI, 1.92­23.18). Conclusions. The mean duration of the prescriptions infringes all standards. The overall appropriateness or correct coexistence of adequate diagnostic indication with follow-up visits is associated with out-patient Psychiatry prescription

Computational predictions and experimental affinity distributions for a homovanillic acid molecularly imprinted polymer.

Density Functional Theory calculations have been used to select, among a set of chemicals traditionally used in the formulation of non-covalent molecularly imprinted polymers (MIPs), the best functional monomer and porogenic solvent for the construction of a recognition element for the dopamine metabolite homovanillic acid (HVA). Theoretical predictions were confirmed through batch binding assays and voltammetric detection. The computational method predicts that trifluoromethacrylic acid and toluene are the monomer and solvent rendering the highest stabilization energy for the pre-polymerization adducts. HVA-MIP prepared using this formulation gives rise to a binding isotherm that is accurately modelled by the Freundlich isotherm. The binding properties of this polymer were estimated using affinity distribution analysis. An apparent number of sites of 13 micromol g(-1) with an average affinity constant of 2 x 10(4) M(-1) was obtained in the concentration window studied.

Mechanism of cycloaddition reactions between ketene and N-silyl-, N-germyl-, and N-stannylimines: a theoretical investigation.

A theoretical study of the cycloaddition reactions of ketene and N-silyl-, N-germyl-, and N-stannylimines were performed at the B3LYP/6-311+G(d,p) theory level using the LANL2DZ effective core potential for Ge and Sn and taking into account the effect of diethyl ether solvent by means of the polarizable continuum model method. According to the obtained results the reaction between ketene and N-germylimine is a two-step process due to the effect of solvent, whereas the cycloaddition of ketene and N-silylimine follows a three-step mechanism because in this case the evolution of the electronic energy along the reaction coordinate predominates over the effect of solvent. For N-stannylimine the two- and three-step mechanisms are competitive. In all the cases the rate-determining barrier corresponds to the evolution of the azadiene intermediate. The cycloaddition of ketene and N-germylimine is kinetically the most favorable reaction of the three studied by us and can take place as a domino process. In the three cases the isomerization of the imine through the inversion at the nitrogen atom is easier than the formation of the azadiene intermediate so that the three processes would afford the trans-beta-lactam.