Donor-substituted triaryl-1,3,5-triazinanes-2,4,6-triones: octupolar NLO-phores with a remarkable transparency-nonlinearity trade-off

International audienceWe report in this letter the measurement of the hyperpolarizabilities of a series of donor-substituted triaryl-1,3,5-triazinanes-2,4,6-triones by hyper Rayleigh scattering (HRS). A remarkable transparency-nonlinearity trade-off is evidenced for these octupolar NLO-phores which might be accessed in a straightforward synthetic way and in a few steps from commercial isocyanates

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Stoichiometric and Catalytic Synthesis of Alkynylphosphines

International audienceAlkynylphosphines or their borane complexes are available either through C-P bond forming reactions or through modification of the phosphorus or the alkynyl function of various alkynyl phosphorus derivatives. The latter strategy, and in particular the one involving phosphoryl reduction by alanes or silanes, is the method of choice for preparing primary and secondary alkynylphosphines, while the former strategy is usually employed for the synthesis of tertiary alkynylphosphines or their borane complexes. The classical C-P bond forming methods rely on the reaction between halophosphines or their borane complexes with terminal acetylenes in the presence of a stoichiometric amount of organometallic bases, which precludes the access to alkynylphosphines bearing sensitive functional groups. In less than a decade, efficient catalytic procedures, mostly involving copper complexes and either an electrophilic or a nucleophilic phosphorus reagent, have emerged. By proceeding under mild conditions, these new methods have allowed a significant broadening of the substituent scope and structure complexity

Triaryl-1,3,5-triazinane-2,4,6-triones functionalized with electron-rich Fe(II) and Ru(II) acetylide complexes: new organometallic octupoles with large hyperpolarizabilities.

International audienceThe synthesis and study of a series of trinuclear organometallic triaryl-1,3,5-triazinane-2,4,6-triones functionalized by d(6)-transition metal acetylides complexes at their periphery are reported. Remarkably large hyperpolarizabilities, far superior to those of related purely organic derivatives, are measured by hyper-Rayleigh scattering (HRS) for these new octupolar chromophores

Silyl alkynylphosphine-boranes: key precursors of triazolylphosphines via tandem desilylation-Click chemistry

International audienceA versatile synthesis of 1,2,3-triazolyl-4-phosphines from the borane complexes of phosphino-alkynes is reported. The efficiency of the procedure relies on the use of readily available silyl-protected alkynylphosphine-boranes, which were subjected to desilylation with TBAF followed by copper-catalyzed azide–alkyne-cycloaddition in one pot. Subsequent treatment with DABCO afforded the targeted triazolylphosphines in high yields. The reported method was applied to the synthesis of the first example of an enantioenriched P-stereogenic triazolylphosphine (98.8% ee).A versatile synthesis of 1,2,3-triazolyl-4-phosphines from the borane complexes of phosphino-alkynes is reported. The efficiency of the procedure relies on the use of readily available silyl-protected alkynylphosphine-boranes, which were subjected to desilylation with TBAF followed by copper-catalyzed azide–alkyne-cycloaddition in one pot. Subsequent treatment with DABCO afforded the targeted triazolylphosphines in high yields. The reported method was applied to the synthesis of the first example of an enantioenriched P-stereogenic triazolylphosphine (98.8% ee)

Impact du traitement par ablation de la fibrillation atriale paroxistiques isolée sur le remodelage ventriculaire gauche [Early and late cardiac ventricular reverse remodeling after catheter ablation for lone paroxysmal atrial fibrillation.]

International audienceAIM: We sought to explore ventricular function in patients with lone paroxysmal atrial fibrillation (AF) and determine the mid- and long-term impact of pulmonary vein isolation on cardiac remodeling. BACKGROUND: The relationship between tachyarrhythmia and ventricular dysfunction is still a matter of debate. Tachycardia-induced cardiomyopathy is defined as reversible myocardial dysfunction following treatment for tachyarrhythmia. METHOD: We prospectively studied 31 patients (56.4 ± 10 years) presenting with paroxysmal-AF who were treated successfully by catheter ablation and 15 age-matched controls. Left and right ventricular functions were assessed by echocardiography at baseline and at 3-month and 1-year follow-up. RESULTS: In AF-patients, LV-function was slightly lower at baseline than controls (LV-ejection fraction was 60% versus 64%; P = 0.06). More impressive, systolic peak velocity on Doppler tissue imaging was 9 cm/s in AF patients (versus 12 cm/s; P = 0.0004). LV global longitudinal strain was also significantly different between the two groups (patients: -16% versus controls: -19%; P = 0.005). At 1-year follow-up, most functional parameters significantly improved in the AF-patients and no longer differed from the controls. Right ventricular (RV) function was also depressed in AF patients at baseline. At 1-year follow-up, tissue Doppler showed improvement in RV-S' (+27%, P = 0.007) and RV peak systolic strain (+36%, P<0.0001) and became comparable to controls. CONCLUSION: We demonstrate that some degree of arrhythmic cardiomyopathy exists in patients presenting with lone paroxysmal-AF. Catheter ablation improved RV and LV functions. Longitudinal function is the most sensitive component of ventricular systole to monitor when looking for this cardiac reverse remodeling

Frequency and predictors of renal artery stenosis in patients with coronary artery disease.

International audienceBACKGROUND: Renal artery stenosis (RAS) remains underdiagnosed because of nonspecific clinical manifestations, including in patients with coronary artery disease (CAD). AIMS: To estimate the prevalence and identify predictors of RAS in patients with CAD undergoing coronary angiography. SETTING: University-based medical centre. METHODS: We enrolled 650 consecutive patients (mean age=67+/-10 years, 80% men) with confirmed CAD. All patients underwent selective renal arteriography in the same procedure. We estimated the prevalence of RAS, defined as a >50% lesion. Multiple variable analysis of factors associated with presence of RAS was carried out using a logistic regression model. Variables that emerged as predictors by single-variable analysis were included in the model, along with variables that were tentatively associated with RAS, based on a literature review. RESULTS: RAS was detected in 94 patients (14.5%, 95% CI: 11.8-17.2%), including 20 (3.1%) with bilateral lesions. By single-variable analysis and presence and number of coronary artery stenoses (P<.001), hypertension (P=.001), and creatinine clearance <90 ml/min (P<.001) were associated with an increased risk of RAS. By multiple variable analysis, male sex (P<.05), presence and number of coronary artery lesions (P<.01), hypertension (P=.001), and renal insufficiency (P<.001) predicted the presence of RAS. CONCLUSIONS: The main clinical predictors of RAS in patients with CAD were hypertension, renal insufficiency, and multivessel CAD. These observations might help defining a high-risk subgroup of patients in need of meticulous investigations of both CAD and RAS

Triaryl-1,3,5-triazinane-2,4,6-triones (Isocyanurates) Peripherally Functionalized by Donor Groups: Synthesis and Study of Their Linear and Nonlinear Optical Properties

International audienceThe linear optical (LO) and nonlinear optical (NLO) properties of a series of isocyanurates functionalized by donor arms at the periphery are reported herein. These octupolar derivatives were obtained in a straightforward way from commercial isocyanate derivatives and were fully characterized. Although several of these compounds are known, those that exhibited the largest NLO activities are all new compounds. In terms of second-order activity, several of these derivatives exhibit remarkable activity/transparency tradeoffs. In terms of third-order activity, the longer derivatives with the stronger donor groups (X=NH2, NMe2, or NPh2) were shown to possess significant two-photon absorption cross sections. These strongly luminescent derivatives exhibit two-photon absorption cross sections up to 410 GM. DFT computations were also conducted to unravel their electronic structures and to rationalize their NLO properties. To our knowledge, the present study is the first concerned with the nonlinear optical properties of these original cyclotrimers

Turning unreactive copper acetylides into remarkably powerful and mild alkyne transfert reagents by oxidative umpolung

International audienceThis is not breaking news: copper acetylides, readily available polymeric rock-stable solids, have been known for more than a century to be unreactive species and piteous nucleophiles. This lack of reactivity actually makes them ideal alkyne transfer reagents that can be easily activated under mild oxidizing conditions. When treated with molecular oxygen in the presence of simple chelating nitrogen ligands such as TMEDA, phenanthroline or imidazole derivatives, they are smoothly oxidized to highly electrophilic species that formally behave like acetylenic carbocations and can therefore be used for the mild and practical alkynylation of a wide range of nitrogen, phosphorus and carbon nucleophiles