Mesoionic N-Heterocyclic Olefins as Initiators for the Lewis Pair Polymerization of Epoxides.

Mesoionic N-heterocyclic olefins (mNHOs) have recently emerged as a novel class of highly nucleophilic and super-basic σ-donor compounds. Making use of these properties in synthetic polymer chemistry, it is shown that a combination of a specific mNHO and a Mg-based Lewis acid (magnesium bis(hexamethyldisilazide), Mg(HMDS)2) delivers poly(propylene oxide) in quantitative yields from the polymerization of the corresponding epoxide (0.1 mol% mNHO loading). The initiation mechanism involves monomer activation by the Lewis acid and direct ring-opening of the monomer by nucleophilic attack of the mNHO, forming a zwitterionic propagating species. Modulation of the mNHO properties is thereby a direct tool to impact initiation efficiency, revealing a sterically unencumbered triazole-derivative as particularly useful. The joint application of mNHOs together with borane-type Lewis acids is also outlined, resulting in high conversions and fast polymerization kinetics. Importantly, while molar mass distributions remain relatively broad, indicating faster propagation than initiation, the overall molar masses are significantly lower than found in the case of regular NHOs, underlining the increased nucleophilicity and ensuing improved initiation efficiency of mNHOs.

Two-dimensional speckle tracking echocardiography in fetuses with critical aortic stenosis before and after fetal aortic valvuloplasty.

BACKGROUND: Critical aortic stenosis (AS) in fetuses may progress to hypoplastic left heart syndrome (HLHS) with need for postnatal single ventricular (SV) palliation. Fetal aortic valvuloplasty (FAV) is performed to achieve postnatal biventricular (BV) circulation. However, the impact of FAV on fetal myocardial function is difficult to measure. Prediction of postnatal circulatory status and, therefore, counseling is challenging. METHODS: Retrospective study of fetuses with critical AS who underwent FAV. Global Longitudinal Peak Systolic Strain (GLPSS) of the left ventricle (LV) and right ventricle (RV) were retrospectively analyzed before and after intervention. Fisher's Exact Test and Mann-Whitney-U Test were used for univariant statistical analysis. RESULTS: 23 fetuses with critical AS were included. After intervention fetuses demonstrated more negative LV-GLPSS mean values post- vs. pre-intervention (- 5.36% vs. - 1.57%; p < 0.05). RV-GLPSS was decreased in all fetuses, there was no peri-interventional change. 20 fetuses were born alive. Postnatally, 10 had BV and 10 SV circulation. Improved post-interventional LV-GLPSS strain values correlated with BV outcome (p < 0.05). Pre-interventional continuous LV-GLPSS values correlated with postnatal SV vs. BV outcome (p < 0.05). CONCLUSION: In some fetuses, LV myocardial function assessed by speckle tracking echocardiography (STE) improves after FAV. Improved post-interventional LV-GLPSS correlates with biventricular postnatal outcome. Furthermore, pre-interventional LV- and RV-GLPSS correlate with postnatal outcome. Further studies are needed to asses, if pre-interventional STE parameters might predict which fetuses will benefit from FAV with postnatal BV circulation.

Brain injury and neurodevelopmental outcomes in children undergoing surgery for congenital heart disease.

Objectives: Brain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. Methods: Term newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included. Those with underlying genetic conditions were excluded. Brain injury was characterized using an magnetic resonance imaging scoring system. Neurodevelopmental outcomes were assigned using the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Independent risk factors for poor neurodevelopmental outcomes were determined by multivariable Cox regression. Results: A total of 122 patients were included. New or progressive postoperative brain injury was noted in 69 patients (57%). A total of 101 patients (83%) had at least 1 neurodevelopmental assessment (median age 36 months) with an early assessment (5-24 months) performed in 95 children. Multivariable Cox regression analysis of early neurodevelopmental outcomes identified new stroke on postoperative magnetic resonance imaging to be an independent predictor of poor neurodevelopmental outcome. Postoperative peak lactate was an independent predictor of poor outcome assessed by the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Conclusions: Our study reveals that evidence of new stroke on magnetic resonance imaging after infant congenital heart surgery is a predictor of poor neurodevelopmental outcomes in early childhood. Postoperative lactic acidosis is associated with poor neurodevelopmental outcome and may be a surrogate biomarker for ischemic brain injury.

Self-Assembled Monolayers of N-Heterocyclic Olefins on Au(111).

Self-assembled monolayers (SAMs) of N-heterocyclic olefins (NHOs) have been prepared on Au(111) and their thermal stability, adsorption geometry, and molecular order were characterized by X-ray photoelectron spectroscopy, polarized X-ray absorption spectroscopy, scanning tunneling microscopy (STM), and density functional theory (DFT) calculations. The strong σ-bond character of NHO anchoring to Au induced high geometrical flexibility that enabled a flat-lying adsorption geometry via coordination to a gold adatom. The flat-lying adsorption geometry was utilized to further increase the surface interaction of the NHO monolayer by backbone functionalization with methyl groups that induced high thermal stability and a large impact on work-function values, which outperformed that of N-heterocyclic carbenes. STM measurements, supported by DFT modeling, identified that the NHOs were self-assembled in dimers, trimers, and tetramers constructed of two, three, and four complexes of NHO-Au-adatom. This self-assembly pattern was correlated to strong NHO-Au interactions and steric hindrance between adsorbates, demonstrating the crucial influence of the carbon-metal σ-bond on monolayer properties.

Pushing the Upper Limit of Nucleophilicity Scales by Mesoionic N-Heterocyclic Olefins.

A series of mesoionic, 1,2,3-triazole-derived N-heterocyclic olefins (mNHOs), which have an extraordinarily electron-rich exocyclic CC-double bond, was synthesized and spectroscopically characterized, in selected cases by X-ray crystallography. The kinetics of their reactions with arylidene malonates, ArCH=C(CO2 Et)2 , which gave zwitterionic adducts, were investigated photometrically in THF at 20 °C. The resulting second-order rate constants k2 (20 °C) correlate linearly with the reported electrophilicity parameters E of the arylidene malonates (reference electrophiles), thus providing the nucleophile-specific N and sN parameters of the mNHOs according to the correlation lg k2 (20 °C)=sN (N+E). With 21

Room-Temperature-Stable Diazoalkenes by Diazo Transfer from Azides: Pyridine-Derived Diazoalkenes.

Recently, stable diazoalkenes have received significant attention as a new substance class in organic chemistry. While their previous synthetic access was exclusively limited to the activation of nitrous oxide, we here establish a much more general synthetic approach utilizing a Regitz-type diazo transfer with azides. Importantly, this approach is also applicable to weakly polarized olefins such as 2-pyridine olefins. The new pyridine diazoalkenes are not accessible by the activation of nitrous oxide, allowing for a considerable extension of the scope of this only recently accessed functional group. The new diazoalkene class has properties distinct from the previously reported classes, such as photochemically triggered loss of dinitrogen affording cumulenes and not C-H insertion products. Pyridine-derived diazoalkenes represent the so far least polarized stable diazoalkene class reported.

The Evolution and Developing Importance of Fetal Magnetic Resonance Imaging in the Diagnosis of Congenital Cardiac Anomalies: A Systematic Review.

Magnetic Resonance Imaging (MRI) is a reliable method, with a complementary role to Ultrasound (US) Echocardiography, that can be used to fully comprehend and precisely diagnose congenital cardiac malformations. Besides the anatomical study of the fetal cardiovascular system, it allows us to study the function of the fetal heart, remaining, at the same time, a safe adjunct to the classic fetal echocardiography. MRI also allows for the investigation of cardiac and placental diseases by providing information about hematocrit, oxygen saturation, and blood flow in fetal vessels. It is crucial for fetal medicine specialists and pediatric cardiologists to closely follow the advances of fetal cardiac MRI in order to provide the best possible care. In this review, we summarize the advance in techniques and their practical utility to date.

Cerebral Sinus Venous Thrombosis in Infants after Surgery for Congenital Heart Disease.

OBJECTIVE: To determine the prevalence of and risk factors for cerebral sinus venous thrombosis (CSVT) in neonates undergoing congenital heart disease (CHD) repair. STUDY DESIGN: Neonates who had CHD repair with cardiopulmonary bypass and postoperative brain magnetic resonance imaging (MRI) between 2013 and 2019 at a single tertiary care center were identified from institutional databases. Demographic, clinical, and surgical data were abstracted from these databases and from the medical record; 278 neonates with CHD had cardiopulmonary bypass, 184 of whom had a postoperative brain MRI. RESULTS: Eight patients (4.3%) had a CSVT. Transposition of the great arteries with an intact ventricular septum (P < .01) and interrupted aortic arch (P = .02) were associated with an increased risk for CSVT. Other risk factors for CSVT included cross-clamp time (98 [IQR, 77.5-120] minutes vs 67 [IQR, 44-102] minutes; P = .03), units of platelets (3.63 [IQR, 3-4] vs 2.17 [IQR, 1-4]; P < .01) and packed red blood cells (0.81 [IQR, 0.25-1] vs 1.21 [IQR, 1-1]; P = .03) transfused intraoperatively, and time between surgery and MRI (10 [IQR, 7-12.5] days vs 20 [IQR, 12-35] days; P < .01). Five patients (62.5%) were treated with anticoagulation. All patients had complete or partial resolution of their CSVT, regardless of treatment. CONCLUSIONS: Brain MRI after cardiopulmonary bypass in neonates revealed a low prevalence of CSVT (4.3%). Further studies are needed to establish best practices for surveillance, prevention, and treatment of CSVT in this population.

Predictors of Neurological Outcome Following Infant Cardiac Surgery Without Deep Hypothermic Circulatory Arrest.

The aim of this study is to describe the clinical characteristics, perioperative course and neuroimaging abnormalities of infants with congenital heart disease (CHD) undergoing heart surgery without deep hypothermic circulatory arrest (DHCA) and identify variables associated with neurological outcome. Infants with CHD undergoing open-heart surgery without DHCA between 2009 and 2017 were identified from a cardiac surgery database. Full-term infants < 10 weeks of age at the time of surgery who had both a pre- and postoperative brain magnetic resonance imaging exam (MRI) were included. Clinical characteristics and perioperative variables were collected from the electronic medical record. Brain Injury Scores (BIS) were assigned to pre- and postoperative brain MRIs. Variables were examined for association with neurological outcome at 12 months of age or greater. Forty-two infants were enrolled in the study, of whom 69% (n = 29) had a neurological assessment ≥ to 12 months of age. Adverse neurological outcome was associated with longer intensive care unit (ICU) stay (P = 0.003), lengthier mechanical ventilation (P = 0.031), modified Blalock-Taussig (MBT) shunt procedure (P = 0.005) and postoperative seizures (P = 0.005). Total BIS scores did not predict outcome but postoperative infarction and/or intraparenchymal hemorrhage (IPH) was associated with worse outcome by multivariable analysis (P = 0.018). Infants with CHD undergoing open-heart surgery without DHCA are at increased risk of worse neurological outcome when their ICU stay is prolonged, mechanical ventilation is extended, MBT shunt is performed or when postoperative seizures are present. Cerebral infarctions and IPH on postoperative MRI are also associated with worse outcome.

Characterization of a Triplet Vinylidene.

Singlet vinylidenes (R2C═C:) are proposed as intermediates in a series of organic reactions, and very few have been studied by matrix isolation or gas-phase spectroscopy. Triplet vinylidenes, however, featuring two unpaired electrons at a monosubstituted carbon atom are thus far only predicted as electronically excited-state species and represent an unexplored class of carbon-centered diradicals. We report the photochemical generation and low-temperature EPR/ENDOR characterization of the first ground-state high-spin (triplet) vinylidene. The zero-field splitting parameters (D = 0.377 cm-1 and |E|/D = 0.028) were determined, and the 13C hyperfine coupling tensor was obtained by 13C-ENDOR measurements. Most strikingly, the isotropic 13C hyperfine coupling constant (50 MHz) is far smaller than the characteristic values of triplet carbenes, demonstrating a unique electronic structure which is supported by quantum chemical calculations.

N2/CO Exchange at a Vinylidene Carbon Center: Stable Alkylidene Ketenes and Alkylidene Thioketenes from 1,2,3-Triazole Derived Diazoalkenes.

We present a new class of room-temperature stable diazoalkenes featuring a 1,2,3-triazole backbone. Dinitrogen of the diazoalkene moiety can be thermally displaced by an isocyanide and carbon monoxide. The latter alkylidene ketenes are typically considered as highly reactive compounds, traditionally only accessible by flash vacuum pyrolysis. We present a new and mild synthetic approach to the first structurally characterized alkylidene ketenes by a substitution reaction. Density functional theory calculations suggest the substitution with isocyanides to take place via a stepwise addition/elimination mechanism. In the case of carbon monoxide, the reaction proceeds through an unusual concerted exchange at a vinylidene carbon center. The vinylidene ketenes react with carbon disulfide via a four-membered thiete intermediate to give vinylidene thioketenes under release of COS. We present spectroscopic as well as structural data for the complete isoelectronic series (R2C═C═X; X = N2, CO, CNR, CS) including 1J(13C-13C) data. As N2, CO, and isocyanides belong to the archetypical ligands in transition-metal chemistry, this process can be interpreted in analogy to coordination chemistry as a ligand exchange reaction at a vinylidene carbon center.

Determinants of neurological outcome in neonates with congenital heart disease following heart surgery.

BACKGROUND: The objective was to determine the association between perioperative risk factors and brain imaging abnormalities on neurologic outcome in neonates with hypoplastic left heart syndrome (HLHS) or d-Transposition of the great arteries (d-TGA) who underwent cardiac surgery including cardiopulmonary bypass. METHODS: A retrospective analysis of neonates with HLHS or d-TGA undergoing cardiac surgery including cardiopulmonary bypass between 2009 and 2017 was performed. Perioperative risk factors and Andropoulos' Brain Injury Scores from pre- and postoperative brain magnetic resonant images (MRI) were correlated to outcome assessments on patients between 5 and 23 months of age. Neurologic outcome was measured using the Pediatric Stroke Outcome Measure (PSOM) and Pediatric Version of the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Fifty-three neonates met our enrollment criteria (24 HLHS, 29 d-TGA). Mechanical ventilation > 12 days and DHCA > 40 min were associated with worse outcome. MRI measures of brain injuries were not associated with worse outcome by PSOM or GOS-E. CONCLUSION: For HLHS and d-TGA patients, duration of mechanical ventilation and DHCA are associated with adverse neurologic outcome. Neonatal brain MRI commonly demonstrates acquired brain injuries, but the clinical impact of these abnormalities are not often seen before 2 years of age. IMPACT: Acquired brain injury is common in high-risk neonates with CHD but poor neurological outcome was not predicted by severity of injury or lesion subtype. Longer stay in ICU is associated with postoperative brain injuries on MRI. Total duration of ventilation > 12 days is predictive of adverse neurological outcome scores. DHCA > 40 min is associated with adverse neurological outcome scores. Neurological outcome before 2 years of age is more affected by the clinical course than by cardiac diagnosis.