Reactions of HNO with Metal Porphyrins: Underscoring the Biological Relevance of HNO

Azanone (1 HNO, nitroxyl) shows interesting yet poorly understood chemical and biological effects. HNO has some overlapping properties with nitric oxide (NO), sharing its biological reactivity toward heme proteins, thiols, and oxygen. Despite this similarity, HNO and NO show significantly different pharmacological effects. The high reactivity of HNO means that studies must rely on the use of donor molecules such as trioxodinitrate (Angeli’s salt). It has been suggested that azanone could be an intermediate in several reactions and that it may be an enzymatically produced signaling molecule. The inherent difficulty in detecting its presence unequivocally prevents evidence from yielding definite answers. On the other hand, metalloporphyrins are widely used as chemical models of heme proteins, providing us with invaluable tools for the study of the coordination chemistry of small molecules, like NO, CO, and O2. Studies with transition metal porphyrins have shown diverse mechanistic, kinetic, structural, and reactive aspects related to the formation of nitrosyl complexes. Porphyrins are also widely used in technical applications, especially when coupled to a surface, where they can be used as electrochemical gas sensors. Given their versatility, they have not escaped their role as key players in chemical studies involving HNO. This Account presents the research performed during the last 10 years in our group concerning azanone reactions with iron, manganese, and cobalt porphyrins. We begin by describing their HNO trapping capabilities, which result in formation of the corresponding nitrosyl complexes. Kinetic and mechanistic studies of these reactions show two alternative operating mechanisms: reaction of the metal center with HNO or with the donor. Moreover, we have also shown that azanone can be stabilized by coordination to iron porphyrins using electron-attracting substituents attached to the porphyrin ring, which balance the negatively charged NO¯. Second, we describe an electrochemical HNO sensing device based on the covalent attachment of a cobalt porphyrin to gold. A surface effect affects the redox potentials and allows discrimination between HNO and NO. The reaction with the former is fast, efficient, and selective, lacking spurious signals due to the presence of reactive nitrogen and oxygen species. The sensor is both biologically compatible and highly sensitive (nanomolar). This time-resolved detection allows kinetic analysis of reactions producing HNO. The sensor thus offers excellent opportunities to be used in experiments looking for HNO. As examples, we present studies concerning (a) HNO donation capabilities of new HNO donors as assessed by the sensor, (b) HNO detection as an intermediate in O atom abstraction to nitrite by phosphines, and (c) NO to HNO interconversion mediated by alcohols and thiols. Finally, we briefly discuss the key experiments required to demonstrate endogenous HNO formation to be done in the near future, involving the in vivo use of the HNO sensing device.Fil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Bikiel, Damian Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Pellegrino, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Suarez, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Water-Soluble Nitroxyl Porphyrin Complexes FeIITPPSHNO and FeIITPPSNO- Obtained from Isolated FeIITPPSNO·

The first biomimetic water soluble FeII-porphyrin nitroxyl complexes were obtained and characterized by UV-Vis in protonated and deprotonated forms by reduction of previously isolated and characterized FeIITPPSNO?. The pKa involved in the FeII-HNO ⇄ FeII-NO− + H+ equilibrium was estimated to be around 9.7. The FeIITPPSHNO complex spontaneously reoxidizes to the nitrosyl form following a first order kinetic decay with a measured kinetic constant of k = 0.017 s-1. Experiments show that the HNO adduct undergoes unimolecular homolytic cleavage of the H-NO bond. DFT calculations suggest a phlorin radical intermediate for this reaction. The deprotonated NO− complex resulted more stable, with a half-life of about 10 minutes.Fil: Mazzeo, Agostina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Pellegrino, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Relazione annuale al Parlamento sullo stato delle tossicodipendenze in Italia nel 1999

not availableLa Relazione 1999, seguendo l\u27impostazione dello scorso anno, ? articolata in tre parti, con il fine di contenerne la dimensione complessiva. La prima parte ? centrata sulle politiche di contrasto del fenomeno che il Parlamento ed il Governo hanno messo in atto nel corso dell\u27anno. Per farsi un\u27idea immediata dell\u27entit? del fenomeno sono stati inseriti i risultati delle indagini condotte dalle Amministrazioni sui soggetti che fanno uso di sostanze illegali. Al fine di rendere pi? completa la visione della prevalenza del fenomeno si ? aggiunta la descrizione della distribuzione nelle diverse Regioni Italiane rapportata alla popolazione a rischio tra 15 e 54 anni di et?, in accordo con le indicazioni dell\u27Osservatorio europeo per le droghe e le tossicodipendenze. Nella seconda parte sono descritti gli interventi messi in atto in campo nazionale ed internazionale dalle Amministrazioni centrali dello Stato e dalle Regioni e Province Autonome. Sono state, inoltre, riportate le modalit? di utilizzo del Fondo nazionale di intervento per la lotta alla droga al fine di avere una panoramica complessiva degli interventi. La terza parte prende in considerazione ed approfondisce argomenti di particolare interesse, legati alla situazione del nostro Paese nei confronti del problema della diffusione dell\u27uso e abuso di sostanze illegali, facendo riferimenti e confronti con altri Paesi dell\u27Unione europea. Negli allegati, infine, trovano spazio documenti di pratica utilit?, come le tavole statistiche, la bibliografia di riferimento aggiornata e ragionata e gli indirizzi dei siti Web, nazionali ed internazionali, di maggiore interesse ed utilit? nel settore delle droghe illegali e delle tossicodipendenze

RELAZIONE ANNUALE AL PARLAMENTO SULLO STATO DELLE TOSSICODIPENDENZE IN ITALIA ANNO 2000

not availableLa Relazione sullo stato delle tossicodipendenze nel 2000 si articola in tre parti: La prima parte ? centrata sulle politiche di contrasto del fenomeno che l\u27Unione europea, il Parlamento ed il Governo italiano hanno messo in atto nel corso dell\u27anno. Sono riportati, inoltre, gli interventi svolti, nei rispettivi ambiti istituzionali, dai Ministeri dell\u27interno, della sanit?, della giustizia, della difesa, della pubblica istruzione e del lavoro. Particolarmente ampio e dettagliato ? il capitolo che riguarda gli interventi delle Regioni e delle province autonome, redatto autonomamente dal coordinamento interregionale per le tossicodipendenze. Nel quinto capitolo ? evidenziato, per l\u27ultimo quinquennio, lo stato di utilizzazione delle risorse finanziarie erogate dal Fondo nazionale d\u27intervento per la lotta alla droga per la realizzazione di progetti di prevenzione, recupero e reinserimento sociale e lavorativo dei tossicodipendenti. Nella seconda parte della Relazione sono riportati in aggiunta ai dati riportati dai Ministeri interessanti ed inediti dati statistici sul consumo di sostanze stupefacenti e psicotrope per aree territoriali regionali, nonch? le tendenze temporali degli indicatori del fenomeno esaminati ad un livello di dettaglio territoriale provinciale. Nella terza parte sono approfonditi argomenti di particolare interesse, legati al problema della diffusione dell\u27uso e abuso di sostanze illegali in Italia. Negli allegati, infine, trovano spazio documenti di pratica utilit?, come le tavole statistiche, la bibliografia di riferimento aggiornata e ragionata e gli indirizzi dei siti Web, nazionali ed internazionali, di maggiore interesse nel settore delle droghe illegali e delle tossicodipendenze

Association Between Periodontal Disease and Left Ventricle Mass in Essential Hypertension

Chronic periodontitis has been associated with an increased risk for cardiovascular disease. Left ventricular mass is an established independent predictor of cardiovascular disease. In the present cross-sectional study, we tested the association between periodontitis and left ventricular mass in subjects with essential hypertension. One hundred four untreated subjects with essential hypertension underwent clinical examinations, including echocardiographic study, laboratory tests, and assessment of periodontal status according to the community periodontal index of treatment needs (CPITN). With increasing severity of periodontitis, there was a progressive increase in left ventricle mass. Mean values (g/height2.7) were 39.0 (±2.7) in CPITN 0 (periodontal health), 40.2 (±6.4) in CPITN 1 (gingival bleeding), 42.7 (±6.8) in CPITN 2 (calculus), 51.4 (±11.7) in CPITN 3 (pockets 4 to 5 mm), and 76.7 (±11.3) in CPITN 4 (pockets ≥6 mm) (overall F 51.2;P<0.0001). Body surface area (P=0.04), systolic (P<0.0001) and diastolic (P<0.01) blood pressure, and left ventricular mass (P<0.0001) were determinants of a composite of CPITN 3 and 4. In a multivariate logistic analysis, left ventricular mass was the sole determinant (P<0.0001) of CPITN stages 3 and 4. Our findings suggest a direct association between severity of periodontitis and left ventricular mass in subjects with essential hypertension. Periodontal evaluation might contribute to refine cardiovascular risk assessment in hypertensive subjects

Sensitive determination of lysinoalanine for distinguishing natural from imitation Mozzarella cheese

Abstract A new method of reverse-phase HPLC was used to determine the crosslinked amino acid lysinoalanine in natural Mozzarella cheese, dairy-based substitutes, and related ingredients. Commercial samples manufactured under known conditions or collected at the market were analyzed. The acid-hydrolyzed sample derivatized by 9-fluorenyl-methylchloro-formate was submitted to solid-phase extraction on an amino cartridge to extract selectively the lysinoalanine derivatives that were chromatographed under fluorescence detection. Lysinoalanine was not found ( X ¯ = 1.7 ; n=30) were present in natural Mozzarella cheese. Because of the ingredient characteristics and the more severe thermal processing conditions, the different types of processed cheese and imitation Mozzarella cheese exhibited much higher lysinoalanine contents, ranging from 15 to 421ppm ( X ¯ = 54 ; n=29). Hence, a highly significant distinction between natural Mozzarella cheese and imitations, even those that did not contain added milk protein, could be achieved by the lysinoalanine index. Conversely, the furosine index distinguished the imitation products only when the quantity of reducing sugars allowed the early Maillard reaction to be extensive

Structural characterization of the water-soluble porphyrin complexes [FeII(TPPS) (NO•)]4─ and [μ-O-([FeIII(TPPS)])2]8─

Iron water-soluble porphyrins have been long used as biomimetic compounds for modelling the active sites found in heme-enzymes. In this regard, the anionic porphyrin [FeIII(TPPS)]3─ and its coordination complexes have been repeatedly chosen as suitable water-soluble platforms for bioinorganic chemistry studies. In this work we report for the first time the crystal structure of the water-soluble nitrosyl complex [FeII(TPPS) (NO•)]4─ along with that of oxodimeric ferric species [μ-O-([FeIII(TPPS)])2]8─.Fil: Mazzeo, Agostina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Gaviglio, Carina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área Investigaciones y Aplicaciones no Nucleares; ArgentinaFil: Pellegrino, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Structural characterization of the water-soluble porphyrin complexes [FeII(TPPS) (NO•)]4─ and [μ-O-([FeIII(TPPS)])2]8─

Iron water-soluble porphyrins have been long used as biomimetic compounds for modelling the active sites found in heme-enzymes. In this regard, the anionic porphyrin [FeIII(TPPS)]3─ and its coordination complexes have been repeatedly chosen as suitable water-soluble platforms for bioinorganic chemistry studies. In this work we report for the first time the crystal structure of the water-soluble nitrosyl complex [FeII(TPPS) (NO•)]4─ along with that of oxodimeric ferric species [μ-O-([FeIII(TPPS)])2]8─.Fil: Mazzeo, Agostina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Gaviglio, Carina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área Investigaciones y Aplicaciones no Nucleares; ArgentinaFil: Pellegrino, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

A novel methodology to spatially evaluate DGP classes by means of vertical illuminances. Preliminary results

A novel methodology to overcome the main limit of the Daylight Glare Probability DGP (i.e. the heavy computational time for an annual analysis of the DGP profile in one point) is presented. This uses a proxy based on the vertical illuminance (Ev) at the eye level. To do so, the most suitable value of Ev, to substitute DGP, is found by means of a comparison to the corresponding DGP value through a fault-detection diagnosis technique. The methodology was applied to a representative enclosed office with one South-facing window (Window-to-Wall Ratio of 50%) located in Turin. The glazing was assumed to have different transmission properties (specular and scattering) with different visible transmittances (in the range 3%-66%). The error in the estimation of the DGP classes calculated through the eye vertical illuminance was evaluated, for an analysis period of a whole year. The main advantages of the methodology proposed lie (i) in a significant reduction of the computational time required for its application and (ii) in the possibility of evaluating glare conditions not only for one or few points, but for a grid of points across a considered space. Its main limitation lies on its inability to quantify the exact DGP value, returning instead, at every time-step, the DGP class of performance