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Resume Objectifs Exposer les resultats de notre centre dans l’angioplastie des nonagenaires pour en evaluer l’utilite mais aussi les risques, les MACE et la mortalite a court et a long terme. Methodes Etude retrospective de 98 patients realisee au centre hospitalier d’Antibes de novembre 2013 a septembre 2018. Resultats La mediane d’âge etait de 91,8 [90,8–93,4]. Au total, 52,6 % etait de sexe masculin. Parmi les malades, 9,7 % avaient un terrain polyvasculaire. De plus, 50,6 % des patients avaient une insuffisance renale moderee. La voie radiale etait la voie la plus utilisee avec un desilet 6 French dans 88,4 % des cas. Parmi les patients, 21,6 % presentaient des lesions tritronculaires, alors que 46,4 % etaient monotronculaires, l’IVA etait l’artere coupable dans 67 % des cas. En moyenne on a utilise un stent par lesion chez nos patients. Notre taux de succes etait de 90 %. Apres angioplastie 96 % des malades etaient sous double anti-agregation plaquettaire, dont 74,4 % sous clopidogrel. La presence de troubles du rythme avant angioplastie, la voie d’abord femorale, la dissection coronaire et le choc cardiogenique en post-angioplastie etaient des facteurs predictifs de mortalite a court et a long termes. Le diabete, l’antecedent d’infarctus du myocarde, la fraction d’ejection du ventricule gauche alteree, les lesions calcifiees coronaires, la survenue de troubles du rythme ou d’insuffisance cardiaque en post-procedure etaient des facteurs predictifs de survenue de MACE. Conclusions Cette etude demontre que l’angioplastie chez une population selectionnee de nonagenaires est parfaitement realisable avec un bon rapport benefices/risques et precise les differents facteurs predictifs de MACE, mortalite a court et a long termes.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Background Following acute myocardial infarction (AMI), most patients receive potent antithrombotic medications, which may promote nuisance bleedings (ecchymoses, minor nose or dental bleeds etc.). Little information is available on the factors related to nuisance bleedings, nor on their prognostic significance in post-AMI patients. Aims and methods A health status questionnaire was sent to all patients participating in the nationwide French FAST-MI cohorts (2010 and 2015) one year after the acute episode, with a specific question on the presence of nuisance bleedings. Overall, 3968 patients answered the question on the presence nuisance bleedings. In the 2010 cohorts, we also analysed whether the presence of nuisance bleedings at one year was an independent correlate of 5-year mortality. Results 54% of the patients reported the presence of nuisance bleedings (59% in 2010 and 51% in 2015). In univariate analyses, nuisance bleedings were more frequently found in younger patients, women, patients with STEMI, current smokers, patients treated with PCI, those receiving newer P2Y12 inhibitors or ACE-inhibitors but less frequent in patients with diabetes, hypertension, or those receiving ARBs or direct oral anticoagulants. Using logistic regression analysis, however, the only independent correlates of nuisance bleedings were: female gender (OR 1.45, 1.25–1.68), age ≤60 years (OR 1.22, 1.06–1.41), VKAs (OR 1.72, 1.28–2.31), clopidogrel (OR 1.62, 1.29–2.03), prasugrel (OR 3.16, 2.43–4.09), ticagrelor (OR 2.61, 2.04–3.35) at discharge, diabetes (OR 0.74, 0.63–0.88) and year 2015 vs 2010 (OR 0.62, 0.53–0.73). In the 2010 cohort, the presence of nuisance bleeding at one year was not a predictor of mortality at 5 years (90% survival in both patients with or without nuisance bleedings; adjusted HR 0.96, 95% CI 0.69–1.33) (Figure). Figure 1. 5-yr survival by nuisance bleed Conclusion Nuisance bleedings one year after AMI are extremely frequent. They are more common in women, younger patients, in patients receiving P2Y12 inhibitors, especially newer P2Y12-i, and in those receiving VKAs; in contrast, diabetic patients report less nuisance bleedings. The presence of nuisance bleeding at one year does not appear to impact 5-year mortality. Acknowledgement/Funding Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Pfizer, Sanofi, Servier

To expose our center results in the angioplasty in nonagenarians and to evaluate its effectiveness but also the MACEs and the mortality in the short and long term.A retrospective study of 98 patients admitted to the Antibes hospital center from November 2013 to September 2018.The median age was 91.8 [90.8-93.4]. 52.6% was male. 9.7% of the patients had a polyvascular site. 50.6% of patients had moderate renal failure. The radial approach was used in 88.4% of cases. 21.6% of patients had tri-truncal lesions, while 46.4% were monotruncular, LAD artery was the culprit artery in 67% of cases. One stent per lesion was used in the majority of cases. Our successful rate was 90%. After angioplasty, 96% of the patients underwent double antiaggregation platelet therapy, 74.4% under clopidogrel. The presence of arrhythmias before angioplasty, the femoral approach, the coronary dissection and cardiogenic shock after angioplasty were predictors of short- and long-term mortality. Diabetes, history of myocardial infarction, impaired left ventricular ejection fraction, calcified coronary lesions, occurrence of arrhythmias or signs of heart failure on post-procedure were predictors of MACE occurrence.This study demonstrates that angioplasty in selected population of nonagenarians is perfectly feasible with a good risk/benefit ratio and specifies the different predictors of MACE, both short- and long-term mortality.

Background Almost 4 years ago, a severe weather with exceptional gravity floods has hit the French Riviera with significant damage estimated to half a billion euros and 20 deaths. The prevalence of cardiovascular events has been studied in the triangle Antibes, Cannes, Grasse, and the analysis showed an excess prevalence of Non-ST elevation myocardial infarction (NSTEMI +78%, P Methods 2015 torrential rains lasted a week and reached a spike of 180 mm over 2 h. In 2019, we assisted 3 weekends of floods with a spike of 113 mm over 3 h. We applied a comparison analysis based on 2 identical timelines. We looked for all the ACS and NSTEMI admitted before and during the weekend floods in the 3 centers Antibes, Cannes, Grasse. Floods periods (P1) were respectively: 11/22/19 to 11/24/19–11/29/19 to 12/01/19–12/19/19 to 12/21/19 control weekends (P2) were 11/01/19 to 11/03/19–11/08/19 to 11/10/19–11/15/19 to 12/17/19. ACS codes were: R07*(exceptR07.0) +I20* to +I24* + I428 + I516 + I518 + I519, and NSTEMI: I20 + I24. The comparison was based on the Fisher exact test ( Fig. 1 ). Results During P1, on 1492 patients tested 10 experienced a NSTEMI (0.7%) and 63 an ACS (4.2%). During P2, on 1308 patients tested 11 experienced a NSTEMI (0.8%) and 64 an ACS (4.9%) (respectively P = 0.8 & P = 0.7, Table 1 ) Conclusion We found no excess of prevalence of NSTEMI nor ACS. We could assume a positive impact of the public preventive measures to diminish the burden of environmental stress especially on the cardiovascular patients. Climatic changing is happening now, we should be aware and prepare for all repercussions on the healthcare system.

Conocer los parámetros de historia de vida de las especies de condrictios es uno de los principales requisitos para evaluar el estado de sus poblaciones y vulnerabilidad a la explotación pesquera. En este estudio se estimó el crecimiento en longitud, la talla de madurez (LM50%), la longevidad (Emax) y la tasa de mortalidad natural (M) del pez gallo, Callorhinchus callorynchus, en el Golfo San Matías, Argentina. En los muestreos de las capturas comerciales se obtuvo un rango de tallas de 22 a 58 cm para machos y de 25 a 76 cm para las hembras, mientras que en las campañas de investigación fue de 13 a 59 cm para los machos y de 14 a 69 cm para las hembras. La proporción de sexos estuvo sesgada hacia los machos. El modelo de crecimiento de Gompertz L0 fijo fue el más adecuado según el criterio biológico de selección. Los parámetros fueron: i) hembras: L∞= 70,75 cm y K= 0,17 año-1; ii) machos: L∞= 56,11 cm y K= 0,257 año-1. Para machos se obtuvo un LM50%= 43,39 cm, una Emax= 13,7 años y una Mmedia= 0,35 año-1 y para hembras se obtuvo un LM50%= 47,48 cm, una Emax= 21,4 años y una Mmedia= 0,23 año-1. Los resultados de este estudio indican que existe dimorfismo sexual en la especie, siendo las hembras las que alcanzan mayor talla, maduran más tarde, crecen más lento y son más longevas que los machos.

The catch per unit of effort (CPUE) data of cockfish, Callorhinchus callorynchus, during 1986-2011 was evaluated for the bottom trawl fishery of the San Matías gulf (Patagonia, Argentina). The objective of this work was to detect what are the factors related to fishery dynamic that affect catch rate of cockfish and to assess standardized CPUE by General linear models (GLMs) and General linear mixed models (GLMMs) as a relative abundance index. The annual trend of the catch rate indicated an increase during the evaluated period. The nominal CPUE and the indices standardized by the Delta-GLM and Delta-GLMM showed the same annual trend, with increases of 57%, 61.1% and 60.7%, respectively. The LogNormal models have the best-fit model and explained 23.5% of the total variability. The factors year, month, depth and hake CPUE explained the highest variability. The analysis of the models indicated that the catch rate of cockfish is subject to the lack of an homogeneous distribution of the fishing effort during different years, months and vessels. This was related to the fleet dynamic searching the targets species. The increasing trend of CPUE and landings would be indicating an increase in effort directionality to the cockfish in the last decade. Resumo Dados de captura por unidade de esforço (CPUE) do peixe-galo Callorhinchus callorynchus foram avaliados para a pesca de arrasto de fundo no Golfo de San Matías (Patagonia, Argentina), durante o período 1986-2011. Os objetivos do trabalho foram identificar quais os fatores relacionados à dinâmica pesqueira que afetam a taxa de captura do peixe-galo e verificar a viabilidade em utilizar dados de CPUEs padronizadas pelos Modelos Lineares Gerais (GLM) e Modelos Lineares Gerais Mistos (GLMMs) como índices de abundância relativa. A tendência anual da taxa de captura indicou um aumento durante o período avaliado. A CPUE nominal e os índices padronizados pelo Delta-GLM e Delta-GLMM apresentaram a mesma tendência anual, com aumentos de 57%, 61.1% e 60.7%, respectivamente. Os modelos LogNormal foram os de melhor ajuste e explicaram 23,5% da variabilidade total dos dados. Ano, mês, profundidade e "hake" CPUE foram os fatores mais explicativos. A análise dos modelos indicou que a taxa de captura do peixe-galo está ligada à falta de distribuição homogênea do esforço de pesca durante os diferentes anos, meses e navios. Este fato esteve relacionado à dinâmica das frotas na busca das espécies alvo. A tendência crescente no aumento das CPUE e descargas em terra estaria indicando a mudança do esforço de pesca direcionado ao peixe-galo na última década.

Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic errors were identified. The genetic length of a map created from the MI errors was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls. No significant differences were detected in the distribution of recombination events along the chromosome arm and a reduction was seen for most of the chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to MI non-disjunction were achiasmate, which may account for most or all of the reduction in recombination noted. The mean age of mothers of cases involving MI errors which showed no transitions from heterodisomy to isodisomy was significantly lower (32.7) than cases showing one or more observable transitions (36.3) (P < 0.003, t -test). However, even among chiasmate pairs the highest mean maternal age was seen for multiple exchange tetrads. Chromosome-specific differences in maternal age effects may be related to the normal distribution of exchanges (and their individual susceptibilities) for each chromosome. However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by maternal age in a different way and varying in importance for each chromosome.

Percutaneous coronary interventions of saphenous vein grafts are associated with an increased risk of periprocedural complications; among these, the rupture of the vein graft is probably the less common and the most dangerous; it is even more exceptional when it occurs on a stented portion of the graft. We report the case of a 75-year-old man who presented during a balloon angioplasty of intent restenosis of a saphenous vein graft a spectacular graft rupture at the level of the previously stented site and who was ultimately successfully treated with a covered stent.

The question as to what extent aromaticity in a reactant or product is expressed in the transition state of a reaction has only recently received serious attention. Inasmuch as aromaticity is related to resonance, one might expect that, in a reaction that leads to aromatic products, its development at the transition state should lag behind bond changes as is invariably the case for the development of resonance in reactions that lead to delocalized products. However, recent experimental and computational studies on proton transfers from carbon acids suggest the opposite behavior, i.e., the development of aromaticity at the transition state is more advanced than the proton transfer. The evidence for this claim is based on the determination of intrinsic barriers that show a decrease with increasing aromaticity. According to the Principle of Nonperfect Synchronization (PNS), this decrease in the intrinsic barrier implies a disproportionately large amount of aromatic stabilization of the transition state. Additional evidence for the high degree of transition state aromaticity comes from the calculation of aromaticity indices such as HOMA, NICS, and the Bird Index. Possible reasons why the degree to which aromaticity and resonance are expressed at the transition state is different are discussed.

An ab initio study of six carbon-to-carbon identity proton transfers is reported. They refer to the benzenium ion/benzene (C6H7(+)/C6H6), the 2,4-cyclopentadiene/cyclopentadienyl anion (C5H6/C5H5(-)), and the cyclobutenyl cation/cyclobutadiene (C4H5(+)/C4H4) systems and their respective noncyclic reference systems, that is, [structure: see text], [structure: see text] and [structure: see text]. For the aromatic C6H7(+)/C6H6 and C5H6/C5H5(-) systems, geometric parameters and aromaticity indices indicate that the transition states are highly aromatic. The proton-transfer barriers in these systems are quite low, which is consistent with a disproportionately high degree of transition-state aromaticity. For the antiaromatic C4H5(+)/C4H4 system, the geometric parameters and aromaticity indices indicate a rather small degree of antiaromaticity of the transition state. However, the proton-transfer barrier is higher than expected for a transition state with a low antiaromaticity. This implies that another factor contributes to the barrier; it is suggested that this factor is angle and torsional strain in the transition state. The question whether charge delocalization at the transition state might correlate with the development of aromaticity was also examined. No such correlation was found, that is, charge delocalization lags behind proton transfer as is commonly observed in nonaromatic systems involving pi-acceptor groups.

A kinetic study of the reactions of thiolate ions with three Fischer-type [aryloxy(phenyl)carbene]pentacarbonyl chromium(0) complexes in 50% MeCN-50% water (v/v) is reported. Brønsted plots of the second-order rate constants are biphasic with an initial steep rise for weakly basic thiolate ions (beta(nuc) approximately equal to 1.0) followed by a slightly descending leg with a negative slope (beta(nuc) approximately equal to -0.2) for strongly basic thiolate ions. This indicates a change from rate-limiting leaving group departure at low pK(RSH)(a) to rate-limiting nucleophilic attachment at high pK(RSH)(a). The negative beta(nuc) values result from a combination of minimal progress of C-S bond formation at the transition state and the requirement for partial desolvation of the nucleophile before it enters the transition state. Possible factors that may affect the degree of bond formation in reactions of Fischer carbene complexes as well as reactions of other unsaturated electrophiles with thiolate ions are discussed.

A kinetic study of the reversible deprotonation of methylnitroacetate (4H) by primary aliphatic amines, secondary alicyclic amines, hydroxide ion, and water in water at 25 degrees C and in 50% DMSO/50% water (v/v) at 20 degrees C is reported. Intrinsic rate constants, k0, determined by extrapolation or interpolation of Brønsted plots have been determined. In comparison to proton transfers involving other nitroalkanes, the intrinsic rate constants for 4H are exceptionally high; for example, log k0 for the reaction of 4H with secondary alicyclic amines in water (1.22) is 1.81 log units higher than log k0 for nitromethane (-0.59), while in 50% DMSO/50% water, log k0 for 4H (2.44) is 1.71 log units higher than that for nitromethane (0.73). A general discussion of the factors affecting intrinsic rate constants of proton transfer from nitroalkanes is presented; it provides the context for an understanding as to why k0 is so high for the proton transfers from 4H. The correlation between intrinsic rate constants for the addition of nucleophiles to alkenes of the type R'R' 'C=CXY and the intrinsic rate constants of proton transfers from carbon acids of the type H2CXY is also discussed as a general proposition as well as with specific reference to the Ph(SMe)C=C(NO2)CO2Me/H2C(NO2)CO2Me pair.

A spectroscopic and kinetic study of the reaction of methyl beta-methylthio-alpha-nitrocinnamate (4-SMe) with morpholine, piperidine, and hydroxide ion in 50% DMSO/50% water (v/v) at 20 degrees C is reported. The reactions of 4-SMe with piperidine in a pH range from 10.12 to 11.66 and those with morpholine at pH 12.0 are characterized by two kinetic processes when monitored at lambdamax (364 nm) of the substrate, but by only one process when monitored at lambdamax (388) nm of the product. The rate constants obtained at 388 nm were the same as those determined for the slower of the two processes at 364 nm. These rate constants refer to product formation, whereas the faster process observed at 364 nm is associated with the loss of reactant to form an intermediate. In contrast, for the reaction of 4-SMe with morpholine at pH 8.62 the rates of product formation and disappearance of the substrate were the same, i.e., there is no accumulation of an intermediate. Likewise, the reaction of 4-SMe with OH- did not yield a detectable intermediate. The factors that allow the accumulation of intermediates in certain SNV reactions but not in others are discussed in detail, and structure-reactivity comparisons are made with reactions of piperidine and morpholine with other highly activated vinylic substrates.

The aim of this study was to compare the morbidity and short-term efficacy of retro-pubic (TVT) and inside-out trans-obturator (TVT-O) sub-urethral sling in the treatment of stress urinary incontinence. This was a prospective multi-centre randomised trial; 231 women with primary stress urinary incontinence were randomised to TVT (114) or TVT-O (117). The International Consultation on Incontinence-Short Form (ICIQ-SF), Women Irritative Prostate Symptoms Score (W-IPSS) and Patient Global Impression of Severity (PGI-S) questionnaires were used to evaluate the impact of incontinence and voiding dysfunction on QoL and to measure the patient's perception of incontinence severity. The primary and secondary outcome measures were rates of success and complications. The SPSS software was used for data analysis. The TVT-O procedure was associated with significantly shorter operation time and with a more extensive use of general anaesthesia when compared with TVT. There were 5 (4%) bladder perforations in the TVT group compared with none in the TVT-O group. Rates of early post-operative urinary retention and voiding difficulty were similar for both groups and no difference was found in the average hospital stay. Six patients (5%) in the TVT-O group complained of thigh pain in the post-operative course. The median follow-up time was 6 months. Two hundred eighteen patients were available for the analysis of outcomes. Subjective and objective cure rates were 92% and 92% in the TVT group and 87% and 89% in the TVT-O group. The ICIQ-SF questionnaire symptoms score showed a highly statistical decrease in both groups, the W-IPSS on the contrary was unchanged. Our data show that both procedures were equally effective in the short-term for the treatment of stress urinary incontinence with a highly significant improvement in incontinence-related QoL.

A kinetic study of the reversible deprotonation of benzofuran-3(2H)-one (3H-O) and benzothiophene-3(2H)-one (3H-S) by amines and hydroxide ion in water at 25 degrees C is reported. The respective conjugate bases, 3--O and 3--S, represent benzofuran and benzothiophene derivatives, respectively, and thus are aromatic. The main question addressed in this paper is whether this aromaticity has the effect of enhancing or lowering intrinsic barriers to proton transfer. These intrinsic barriers were either determined from Brønsted plots for the reactions with amines or calculated on the basis of the Marcus equation for the reaction with OH-; they were found to be lower for the more highly aromatic benzothiophene derivative, indicating that aromaticity lowers the intrinsic barrier. It is shown that the reduction in the intrinsic barrier is not an artifact of other factors such as inductive, steric, resonance, polarizability, and pi-donor effects, although these factors affect the intrinsic barriers in a major way. Our results imply that aromatic stabilization of the transition state is ahead of proton transfer; this contrasts with simple resonance effects, which typically lag behind proton transfer at the transition state, thereby increasing intrinsic barriers.

We evaluated the efficacy of the Pelvicol porcine collagen implant for preventing recurrent anterior vaginal wall prolapse in women undergoing primary surgery for pelvic organ prolapse.This was a prospective, randomized, multicenter trial in 206 women with stage II or greater anterior vaginal wall prolapse (point Ba -1 or greater) according to the pelvic organ prolapse quantification system. The patients were randomly assigned to undergo anterior vaginal repair or the same procedure with Pelvicol implant reinforcement. SPSS software was used for data analysis.A total of 201 women were available for surgical outcome analysis, including 98 and 103 in the implant and no implant groups, respectively. All completed the 1-year followup visit. Most women were satisfied with the postoperative condition with a significant decrease in the visual analog scale score in each group (p0.001). Anatomical anterior recurrence (point Ba greater than -1) was observed in 7 women (7%) in the implant group and in 20 (19%) in the other groups (OR 3.13, 95% CI 1.26-7.78, p = 0.019). Additionally, there were 11 women (3 and 8, respectively, or 5%) with posterior recurrence and 6 (3 per group or 3%) with unsatisfactory results at the upper vaginal segment. One patient who received a porcine implant had vaginal extrusion of the mesh 1 month after surgery.Our data show that the Pelvicol implant can be easily and readily used to augment and reinforce anterior colporrhaphy. The prolapse recurrence rate was considerably lower in the implant group compared with outcomes in patients treated with simple anterior repair.

A kinetic study of the aminolysis of substituted (methylthio)benzylidene Meldrum's acids, 2-SMe-Z with the aliphatic primary amines, n-butylamine, glycinamide, methoxyethylamine, and aminoacetonitrile, in aqueous DMSO at 20 °C is reported. With all amines the reaction is strictly second-order, that is, first-order in 2-SMe-Z and first-order in the amine. A three steps mechanism has been proposed. The first step is a rate-limiting attachment of the amine to form the tetrahedral intermediate (T), and the subsequent steps are a fast acid–base equilibrium followed by a fast R‴CH2NH or H2O catalyzed expulsion of the leaving group. The Bronsted plot for k1 for the reaction of 2-SMe-H with four primary amines showed a good correlation between log k1 and pK with βnuc = 0.32 ± 0.02, a slightly lower value than that for the reactions of secondary amines (βnuc = 0.41 ± 0.01). The Hammett plot for n-butylamine yields ρ(k1) = 0.40 ± 0.05 which is smaller than that for the reaction of piperidine with the same substrates (ρ(k1) = 0.72 ± 0.07) and also for the reactions of HOCH2CH2S− (ρ(k1) = 1.18), CF3CH2O− (ρ(k1) = 1.14) and OH− (ρ(k1) = 1.11) addition to 2-H-H (ρ(k1) = 1.11). All these observations are consistent with the suggested mechanism. Copyright © 2006 John Wiley & Sons, Ltd.

Rates of the reversible deprotonation of benzo[b]-2,3-dihydrofuran-2-one (6H-O) and benzo[b]-2,3-dihydrothiophene-2-one (6H-S) by OH-, primary aliphatic amines, secondary alicyclic amines, and carboxylate ions have been determined in water at 25 degrees C. As noted earlier by Kresge and Meng, 6H-S (pKa = 8.82) is considerably more acidic than 6H-O (pKa = 11.68), which mainly reflects the greater aromatic stabilization of the conjugate base of 6H-S (thiophene derivative) compared to that of 6H-O (furan derivative). The main focus of this paper is to assess how the difference in the aromaticity of the two enolate ions affects the intrinsic barrier to the proton transfer. These intrinsic barriers were determined from Brønsted plots for the reactions with the amines and carboxylate ions or calculated on the basis of the Marcus equation for the reactions with OH-. They are consistently somewhat higher for the reactions of 6H-S than for the reactions of 6H-O, implying that the aromaticity in the anion enhances the intrinsic barrier. This contrasts with a previous report on the deprotonation of some cyclic rhenium Fischer-type carbene complexes where the reaction that leads to the most aromatic conjugate base (thiophene derivative) has a lower intrinsic barrier than the reaction that leads to the less aromatic furan analogue. We are offering a detailed analysis of other potential factors that may affect the intrinsic barriers and which could explain these contradictory results.

A kinetic study of the reaction of hydroxide ion with (CO) 5 Mo C(XCH 2 CH 2 OH)(C 6 H 5 ) (X = O for Mo–OR , and X = S for Mo–SR ), and (CO) 5 W C(OCH 2 CH 2 OH)(C 6 H 4 –Z) ( W–OR(Z) ) is reported. The results are consistent with a pathway in basic solution that involves rapid deprotonation of the OH group followed by rate-limiting cyclization. The parameter k 1 K OH for the reaction of W–OR(Z) was determined as a function of the phenyl substituents. They were found to correlate well with the Hammett equation. The dependence of the reactivity on the metal atoms in the complexes M–OR (M = Cr, Mo and W) shows that the reactivity decreases slightly down the group of the Periodic Table, while for M–SR the reactivity increases slightly down the group. A plausible explanation of these results is offered based on electronegativity values of the metal atoms. The much higher ρ ( k 1 K OH ) value for W–OR(Z) over W–SR(Z) arises mainly due to the stabilization of the reactant carbene complex by the stronger π-donor effect of oxygen over sulfur.

The synthesis and characterization of [Cp(NO)(PPh3)Re(2,5-dimethyl-3-thienyl)carbene]+ (3H+(S)), a novel Fischer carbene complex, is described. 3H+(S) undergoes reversible deprotonation with a pKa of 2.64 in 50% MeCN−50% water (v/v). Rate constants for the deprotonation of 3H+(S) by carboxylate ions and by primary aliphatic and secondary alicyclic amines were determined. A major focus of this paper is a comparison of the kinetic and thermodynamic acidities of 3H+(S) with those of [Cp(NO)(PPh3)Re(2-thienyl)carbene]+, 1H+(S). The pKa of 1H+(S) (2.51) is virtually the same as that of 3H+(S). This appears to be the result of a fortuitous cancellation of acidity-reducing and acidity-enhancing factors, a conclusion supported by a computational study of gas phase acidities. An analysis of Bronsted plots indicates that the intrinsic rate constants for proton transfer are about 2 orders of magnitude lower for 3H+(S) than for 1H+(S). This reduction is the result of steric effects and of electronic effects connected...

A kinetic study of the reversible deprotonation of [Cp*(CO) 2 Fe C(OMe)Me] + ( 16H + ) by primary aliphatic amines, secondary alicyclic amines and carboxylate ions in 50% MeCN–50% water (v/v) at 25 °C is reported. A p K a value of 8.25 for 16H + was determined kinetically. Intrinsic rate constants, k 0 for each buffer family were obtained by suitable extrapolation or interpolation of the corresponding Bronsted plots; they are log k 0 RNH 2 = 2.64 , log k 0 R 2 NH = 2.99 and log k 0 RCOO = 3.42 , respectively. A major focus of this paper is a discussion of how structural variations of Fischer carbenes affect their acidities and intrinsic rate constants for proton transfer and how the results obtained for 16H + add new insights into the interplay of these structural factors. These factors include the charge type of the carbene complex, the metal/ligand combination, the π-donor group attached to the carbene carbon, the push–pull resonance effect in conjunction with the metal moiety, the π-acceptor groups attached to the carbene carbon, and the potential for aromaticity/antiaromaticity of the conjugate base.

Rate constants for the attachment of CH(CN)2- to Fischer carbene complexes of the type (CO)5MC(XR)C6H4Z with M = Cr, W and XR = OMe, OEt, SMe in 50% MeCN−50% water (v/v) at 25 °C are reported. The ...

There is much debate whether the fatty acid substrate of lipoxygenase binds "carboxylate-end first" or "methyl-end first" in the active site of soybean lipoxygenase-1 (sLO-1). To address this issue, we investigated the sLO-1 mutants Trp500Leu, Trp500Phe, Lys260Leu, and Arg707Leu with steady-state and stopped-flow kinetics. Our data indicate that the substrates (linoleic acid (LA), arachidonic acid (AA)), and the products (13-(S)-hydroperoxy-9,11-(Z,E)-octadecadienoic acid (HPOD) and 15-(S)-hydroperoxyeicosatetraeonic acid (15-(S)-HPETE)) interact with the aromatic residue Trp500 (possibly pi-pi interaction) and with the positively charged amino acid residue Arg707 (charge-charge interaction). Residue Lys260 of soybean lipoxygenase-1 had little effect on either the activation or steady-state kinetics, indicating that both the substrates and products bind "carboxylate-end first" with sLO-1 and not "methyl-end first" as has been proposed for human 15-lipoxygenase.

The deprotonation of pentacarbonyl[(3-diethylamino-2,4-dimethyl)cyclobut-2-ene-1-ylidene]chromium (1d) and pentacarbonyl[(3-diethylamino-4-methyl-2-phenyl)cyclobut-2-ene-1-ylidene]chromium (1e) leads to antiaromatic conjugate anions by virtue of their being cyclobutadiene derivatives. Rate constants for the deprotonation of 1d and 1e by P2-Et and pKa values were determined in acetonitrile. Gas-phase B3LYP calculations of 1d, 1e, and their respective conjugate anions, using a generalized basis set, were also performed. Furthermore, for purposes of comparison with carbene complexes of similar structures, but having conjugate anions that are not antiaromatic, corresponding calculations were performed on pentacarbonyl[3-diethylamino-2,5-dimethyl)cyclopent-2-ene-1-ylidene]chromium (5), [dimethylamino(methyl)carbene]pentacarbonylchromium (3a), and [dimethylamino(iso-propyl)carbene]pentacarbonylchromium (3b) and their respective conjugate anions, and solution-phase pKa and kinetic measurements were carried out for 3a and 3b. Major points of interest include the effect of antiaromaticity on the kinetic and thermodynamic acidities of 1d and 1e, the large effect of the phenyl group on the gas-phase acidity of 1e, the strong attenuation of the acidities and the effect of the phenyl group in acetonitrile, and the position of the C=C double bonds in the cyclobutadiene ring of the conjugate anion of 1e.

A kinetic study of the aminolysis of (CO)5CrC(OEt)C6H5 (7-Cr) and (CO)5CrC(OEt)C6H5(Cr(CO)3) (8-Cr) by five primary aliphatic amines and of the hydrolysis of 8-Cr in 50% MeCN−50% water (v/v) at 25 °C is reported. The introduction of the Cr(CO)3 group has only a minor effect on the electrophilic reactivity of the carbene carbon; that is, the nucleophilic attack by OH- and the amines on 7-Cr and 8-Cr occurs at similar rates. However, the Cr(CO)3 group exerts a strong influence on the mechanisms of both types of reactions, which results in changes of what steps are rate limiting. In the hydrolysis reaction these changes lead to a more complex rate versus pH profile for 8-Cr compared to the previously reported one for 7-Cr. In the aminolysis the effect is to change the mechanism of general base catalysis from rate-limiting leaving group departure for the reactions of 7-Cr to rate-limiting proton transfer for the reactions of 8-Cr. We provide a detailed analysis of the reasons for these changes.

We derive the first six coefficients of the heat kernel expansion for the electromagnetic field in a cavity by relating it to the expansion for the Laplace operator acting on forms. As an application we verify that the electromagnetic Casimir energy is finite., 12 pages

We report an ab initio study of the identity carbon-to-carbon proton-transfer NCCH(2)Y + NCCH=Y(-) right arrow over left arrow NCCH=Y(-) + NCCH(2)Y in the gas phase, where Y = H, CH=CH(2), CH=O, CH=S, CN, NO, and NO(2). The main focus is on a comparison with the previously reported systems CH(3)Y + CH(2)=Y(-) right arrow over left arrow CH(2)=Y(-) + CH(3)Y, i.e., on the effect of the cyano group on acidities, proton-transfer barriers, and transition state structures. The conclusions of this study are as follows: (1) The transition state for the NCCH(2)Y/NCCH=Y(-) systems is more imbalanced than that for the CH(3)Y/CH(2)=Y(-) systems. (2) The cyano group leads to an increase in the acidities but to a decrease in the proton transfer barriers. This barrier reduction results from the fact that the stabilizing effect of the cyano group on the transition state is greater than that on the anion. (3) Within a reaction series, the barriers are largely dominated by the pi-acceptor strength of Y, i.e., the strongest pi-acceptors lead to the highest barriers. This is similar to proton transfers in solution but quite different from the CH(3)Y/CH(2)=Y(-) systems in the gas phase; in these latter systems pi-acceptor effects play a minor role while the barrier lowering field effect of Y is dominant.

Herein, we report on the role of the allosteric site in the activation mechanism of soybean lipoxygenase-1 utilizing stopped-flow inhibition kinetic studies. The K(D) for the activation was determined to be 25.9 +/- 2.3 microM and the rate constant for the oxidation of the iron cofactor, k(2), to be 182 +/- 4 s(-1). Two inhibitors were employed in this study, (Z)-9-octadecenyl sulfate (OS) and (Z)-9-palmitoleyl sulfate (PS), of which OS is an allosteric inhibitor of the turnover process, while PS is a linear mixed inhibitor with a K(i) of 13.7 +/- 1.3 microM for the catalytic site and a K(i)' of 140 +/- 9 microM for the allosteric site. It was found that OS does not inhibit the activation of soybean lipoxygenase-1, while PS acts as a competitive inhibitor versus the product, 13-hydroperoxy-9,11-(Z,E)-octadecadienoic acid, with a K(i) of 17.5 +/- 3.8 microM. These results suggest that OS binds to an allosteric site that is separate from the catalytic iron site. We further observed that the allosteric site binding selectivity is sensitive to inhibitor length as seen by its preference for OS over that of PS, which is two carbons longer than PS.

A kinetic study of the reactions of (CO)5CrC(SMe)C6H4Z (Z = 4-CF3, 4-Cl, 4-F, 4-Me, 4-MeO, and 4-Me2N) with n-butylamine, 2-chloroethylamine, piperidine, and 1-(2-hydroxyethyl)piperazine in 50% MeCN−50% water (v/v) at 25 °C is reported. In all cases the nucleophilic attachment of the amine to the carbene complex is rate limiting, which contrasts with the previously reported aminolysis of the methoxy analogues ((CO)5CrC(OMe)C6H4Z), where leaving group departure is rate limiting in most cases. The substituent effect on the nucleophilic attachment step is much weaker (average ρ = 0.55) than for the methoxy analogue (ρ = 2.03). It is shown that the small ρ value for (CO)5CrC(SMe)C6H4Z is “normal” and reflects the near cancellation of the substituent effects on the partial positive and partial negative charges at the transition state. These findings provide evidence that the high ρ value for (CO)5CrC(OMe)C6H4Z is “abnormal” and the result of the strong π-donor effect of the methoxy group on the reactant carben...

The kinetics of the reactions of (CO)5CrC(SMe)Ph (4-Cr) with five primary aliphatic and four secondary alicyclic amines have been investigated in 50% MeCN−50% water (v/v) at 25 °C. With n-butylamine, 2-methoxyethylamine, 2-chloroethylamine, glycinamide, piperidine, piperazine, and 1-(2-hydroxyethyl)piperazine, the reaction is strictly second order, i.e., first order in 4-Cr and first order in the amine. With morpholine, base catalysis by the amine and by OH- was observed while with aminoacetonitrile, OH- catalysis but no amine catalysis was detected. These results are interpreted in terms of a three-step reaction mechanism (Scheme 1): the first step is nucleophilic attachment of the amine to the carbene complex, to form a zwitterionic intermediate, ; the second step is a fast equilibrium deprotonation of to generate the anionic intermediate ; the third step is MeS- expulsion by two concurrent pathways, one being spontaneous (solvent catalyzed) expulsion of MeS-, the other being RR‘NH2+ catalyzed loss of ...

Acidity constants of six substituted 1-benzyl-1-methoxy-2-nitroethylenes (2-Z with Z = m-NO(2), m-CF(3), m-Cl, H, p-Me, p-MeO) and their respective nitronic acids were determined in 50% DMSO-50% water (v/v) at 20 degrees C. Kinetic data were obtained on the reversible deprotonation of all six 2-Z by OH(-) and piperidine and on the reversible deprotonation of 2-NO(2)() by piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine in the same solvent. These data allowed a determination of the Brønsted coefficients alpha (dependence on acidity of 2-Z) and beta (dependence on amine basicity). The fact that alphabeta indicates the presence of a transition state imbalance which, however, is much smaller than that for the deprotonation of arylnitromethanes. The reasons for this reduction in the imbalance and their relevance to a recent study of the deprotonation of Fischer carbene complexes are discussed.

A kinetic study of the reversible deprotonation of phenyl-substituted (benzylmethoxycarbene)pentacarbonylchromium(0) complexes by OH(-) and by a series of primary aliphatic and a series of secondary alicyclic amines in 50% MeCN-50% water (v/v) at 25 degrees C is reported. Brønsted alpha(CH) values (dependence on carbene complex acidity) and beta(B) values (dependence on amine basicity) were determined. According to current notions about proton transfers involving carbon acids activated by pi-acceptors, alpha(CH) was expected to substantially exceed beta(B), the result of transition-state imbalances that are characteristic of such reactions. However we find that alpha(CH) and beta(B) have essentially the same values, which are close to 0.5. It is shown that these findings do not indicate the absence of an imbalance but rather suggest that the manifestation of the imbalance is masked by the pi-donor effect (3H-Z--3H-Z(+/-)) of the methoxy group.

Percutaneous coronary interventions of saphenous vein grafts are associated with an increased risk of periprocedural complications; among these, the rupture of the vein graft is probably the less common and the most dangerous; it is even more exceptional when it occurs on a stented portion of the graft. We report the case of a 75-year-old man who presented during a balloon angioplasty of intent restenosis of a saphenous vein graft a spectacular graft rupture at the level of the previously stented site and who was ultimately successfully treated with a covered stent.

The pKa values of a cationic selenyl- (5H+) and a benzothienylcarbene complex (6H+) and rate constants for the reversible deprotonation of these complexes by water, carboxylate ions, primary aliphatic amines, secondary alicyclic amines (5H+ only), and OH- (5H+ only) were determined in 50% MeCN−50% water (v/v) at 25 °C. In comparison with neutral Fischer-type carbene complexes such as 1H, the cationic complexes 5H+ and 6H+ are much more acidic, and the intrinsic barriers to proton transfer are substantially higher. This paper discusses a variety of factors that contribute to these differences, with the most important ones being that 5H+ and 6H+ are cationic, which makes the C5H5(NO)(PPh3)Re moiety a stronger π-acceptor than the (CO)5M moieties, coupled with the fact that the deprotonated forms of 5H+ and 6H+ are aromatic molecules.

A kinetic study of the reversible cyclization of (((2-hydroxyethyl)thio)arylcarbene)pentacarbonyltungsten(0) complexes, 2-SR(Z), in 50% MeCN−50% water (v/v) at 25 °C is reported. The results are co...

The kinetics of the title reactions were determined in 50% DMSO-50% water (v/v) at 20 degrees C; n-BuS-, HOCH2CH2S-, and MeO2CCH2S- were used as thiolate ions. The reactions with the thiolate ions gave rise to two separate kinetic processes. The first refers to rapid, reversible attachment of RS- to the substrate leading to a tetrahedral intermediate (k1RS), k(-1)RS, the second to the conversion of the intermediate to products (k2RS). In most cases all of the rate constants (k1RS, k(-1)RS and k2RS could be determined. In combination with results from previous studies, a detailed discussion regarding the effects of activating substituents and leaving groups on rate and equilibrium constants as well as on intrinsic rate constants is presented. The reaction with OH- only allowed a determination of k1OH for nucleophilic attack on the substrate; in this case the tetrahedral intermediate remains at steady-state levels under all conditions.

A kinetic study of the hydrolysis of (CO)5MC(SMe)Ph (M = Cr and W) in 50% MeCN−50% water (v/v) at 25 °C over a pH range from 1.7 to 14.2 is reported. The reaction occurs in two stages: the first is formation of (CO)5MC(O-)Ph or (CO)5MC(OH)Ph while the second stage leads to the formation of PhCHO and (CO)5MOH-. This paper is concerned with the first stage. The rate−pH profiles are complex and consistent with a mechanism (Scheme 1) that involves water/OH- addition to the substrate to form a tetrahedral intermediate ( ), followed by product formation via five potential pathways whose relative importance depends on the pH. A more limited study of the reactions of (CO)5MC(SCH2CH2CH3)Ph (M = Cr and W) and (CO)5MC(SMe)C6H4-3-Cl (M = Cr and W) with OH- is also reported. The main focus of the discussion is aimed at understanding the reactivity differences between (CO)5MC(SMe)Ph and the corresponding methoxy analogues studied earlier. This understanding is in large measure based on an analysis of how the intrinsic...

A kinetic study of the reactions of (CO)5Cr C(OMe)C6H4X (X=4-Cl, 4-F, H, 4-Me, 4-OMe and 4-NMe2) and the respective tungsten carbene complexes with primary aliphatic amines (mainly n-butylamine) in 50% MeCN–50% water (v/v) at 25°C is reported. The rate law is complex and shows OH− and amine catalysis at low amine and OH− concentrations but not at high concentrations. The results are consistent with a three-step mechanism: the first step is nucleophilic addition of the amine to the carbene complex to form a zwitterionic steady state intermediate, TA±, which, in the second step, is followed by a rapid deprotonation of TA± to form the anionic steady state intermediate TA−, while the third step involves water and RNH3+ catalyzed methoxide ion expulsion, respectively, to form the substitution product, (CO)5M C(NHR)C6H4X (M=Cr or W). It is shown that the third step is rate limiting at low OH− and amine concentrations while the first step is rate limiting at high OH− and/or amine concentrations. The reasons why TA± and TA− cannot be observed directly are discussed and a detailed analysis of the substituent effects on various kinetic parameters is presented.

Rate and equilibrium constants for the nucleophilic addition of MeO- in methanol and in 90% MeCN−10% MeOH, of HC⋮CCH2O- and CF3CH2O- in 50% MeCN−50% water, and of OH- in 50% MeCN−50% water (rate constants only) to Fischer carbene complexes of the type (CO)5MC(OMe)C6H4-4-Z (M = Cr and W) are reported. The reactions lead to the formation of tetrahedral adducts of the type (CO)5M−C(OMe)(OR)C6H4-4-Z. The kinetics of general acid catalyzed loss of MeO- from the MeO- adducts by phenol, 4-bromophenol, and 3,5-dichlorophenol, to regenerate the carbene complex, were also investigated. Hammett ρ and ρn values as well as approximate βnuc ( ) values were determined. They suggest that the transition state for alkoxide ion addition to the carbene complexes is imbalanced in the sense that charge delocalization into the CO ligands lags somewhat behind C−O bond formation. This finding is consistent with the fact that the intrinsic rate constants for these reactions are substantially lower than those for alkoxide ion addi...

Rate and equilibrium constants for the conversion of (CO)5CrC(OCH2CH2OH)Ph (8-CrOOH), (CO)5WC(OCH2CH2OH)Ph (8-WOOH), (CO)5CrC(SCH2CH2OH)Ph (8-CrSOH), and (CO)5WC(SCH2CH2OH)Ph (8-WSOH) into the corresponding cyclic adducts (9-CrOO- for M = Cr, X = O; 9-WOO- for M = W, X = O; 9-CrSO- for M = Cr, X = S; 9-WSO- for M = W, X = S) are reported. Under basic conditions the reaction occurs via the respective oxyanions, (CO)5CrC(OCH2CH2O-)Ph (8-CrOO-), etc.; under acidic conditions the reaction may either be concerted with water acting as a general base catalyst or stepwise via a zwitterionic intermediate. The absence of buffer catalysis suggests but does not prove the operation of the stepwise mechanism. The equilibrium constants for cyclization of 8-CrSO- and 8-WSO- are about 1 order of magnitude higher than for 8-CrOO- and 8-WOO-, respectively. For the rate constants the situation is reversed, with 8-CrOO- and 8-WOO- being substantially more reactive than 8-CrSO- and 8-WSO-, respectively. These results reflect t...