Low Ee Research Articles

(Invited) Introducing Selectivity into Electrochemical Reactions: From Solution to Surfaces

Induction of asymmetry into electrosynthetic reactions has taken off in recent years for the electrochemical community. As of late most transformations have focused on either simple electrochemical oxidations or reductions, such as the reduction of various ketones to chiral alcohol feedstock molecules, or transition metal cross coupling reactions. At the same time, there has been little effort to introduce asymmetry into cyclization reactions that capitalize on highly reactive radical ion intermediates to accomplish umpolung-type transformations or to fully take advantage of electrode surfaces for manipulating the selectivity of synthetically more complex transformations like transition metal cross coupling reactions. In the case more complex electrochemical transformations, many of the reactions studied have led to either high ee and low yield or low ee and high yield. With this in mind, we are looking new approaches for introducing selectivity into electrochemical transformations by taking advantage of high yielding cathodic cyclization reactions and the Heck reaction. The influence of chiral electrolytes, chiral catalysts and mediators, and modified electrode surfaces on these transformations is being explored with a particular emphasis on both the induction of asymmetry into the reactions and the use of remote functionality in the molecules as a control element. This presentation to be given will detail our progress in these areas.

CHEMICAL COMPOSITION AND THE COEFFICIENT OF PREFERENCE BY RABBITS OF TROPICAL FORAGES

The suitability and chemical composition of seven forages (M. oleifera, F. thonningii, L. leucocephala, E. cyclocarpum, G. sepium, A. saman and A. indica) as feed resources for feeding domestic rabbits during the dry season was studied. The acceptability was determined by cafeteria method using five adult rabbits weighing 700-750g. The acceptability of the forages was best in M. oleifera followed by F. thoninngii. G. sepium, L. leucocephala and E. cyclocarpum had similar acceptability while A. indica and A. Saman had low acceptability. The order of acceptability was: M. oleifera, F. thonningii, L. leucocephala, E. cyclocarpum, G. sepium, A. indica, and A. saman. The chemical analysis of the five most acceptable forages showed that F. thoninngii had the least CP of 10.3% compared to the others forages that had CP ranging from 24 -30%. M. oleifera also had the least CF of 9.0% compared to the other forages CF which range 14 -19% F. thonningii and L. leucocephala also had low EE of 6.0 and 8.0 % respectively. The ADF and NDF fractions of the five most acceptable forages were in the same range. In conclusion all the five most acceptable forages namely: M. oleifera, F. thonningii, L .leucocephala, E. cyclocarpum, G. sepium are possible feed resources suitable for feeding rabbits especially during the dry season.

Chiral Diselenophosphoric Acids for Ion Pair Catalysis: A Novel Approach to Enhance Both Proton Donating and Proton Accepting Properties.

The activation of poorly reactive substrates via strong chiral acids is a central topic in asymmetric ion pair catalysis these days. Despite highly successful scaffolds such as N-triflylphosphoramides, these catalysts either lack C2-symmetry or provide multiple H-bond acceptor sites, leading to lower ee values for certain reactions. We present BINOL-based diselenophosphoric acids (DSA) as an extremely promising alternative. Using an intertwined approach of synthesis and NMR studies, we developed a synthetic approach to DSA with up to 98 % NMR yield. The obtained acids provide both very high proton donor and proton acceptor properties, a bifunctionality, which is key to catalytic applications. Indeed, first reactivity test proved the much higher acidity of DSA and its ability to initiate Mukaiyama-Mannich reaction and protodesilylation of silyl ethers. Together with their C2-symmetry, the single donor and single acceptor situation, the decreased tendency of self-association, and the straightforward synthesis with potential 3,3'-substitution, the DSA provide all features ideal for the further development of ion pair catalysis.

Transmit antenna selection in M-MIMO system using metaheuristic aided model

Massive MIMO (M-MIMO) devices are the key tool to meet the performance stards established for 5G-wireless communication. However, more Radio Frequency (RF) chains needed in base station (BS) with a huge count of transmitting antennas, involve expensive hardware and computing complexities. In order to decrease the RF chains needed in BS, this work intended to use the optimal transmit antenna selection (TAS) strategy. This strategy is gaining a lot of interest since the optimization algorithm aids in the ability to enhance the system performance considerably the efficiency and secrecy rate. This work proposes a novel Coati Adopted Pelican Optimization (CA-PO) for choosing the optimal TA by considering efficiency as well as secrecy rate. In addition, the CA-PO algorithm makes the decision on which antenna to be elected. At last, the supremacy of CA-PO-based TAS is proven from the analysis regarding secrecy rate and EE analysis. Accordingly, the proposed CA-PO method for MF for set up 2 has attained a higher EE of 0.976; whereas, the DMOA, COA, MRFO, POA and BEA techniques have got a relatively lower EE of 0.968.

Microencapsulation of Acalypha indica Linn. Extracts Using Chitosan-Polycaprolactone Blends

Polymer encapsulation is commonly adopted in drug delivery systems to form encapsulation that can assist in delivering active compounds to the targeted area. Acalypha indica (AI) crude extract was obtained from AI plants through ultrasound-assisted extraction. It is naturally unstable in the external environment and, thus, needs to be encapsulated to protect against volatility. Herein, this study emphasized the development of the encapsulations of AI extracts using a chitosan-polycaprolactone (PCL) blend by emulsion-solvent evaporation and freeze-dried methods. Four parameters for Al encapsulation were studied by fixing one parameter at a time. The percentage of encapsulation efficiency (EE%) was recorded as a response for each parameter. The study proceeded with central composite design (CCD) as the response surface methodology (RSM) optimization tool to study the interactions between the factors. Central points were taken from the preliminary data obtained in one-parameter experiments. The validation was carried out with two data of the highest and lowest EE% suggested by CCD. The highest EE% recorded was 98.70%, and the lowest EE% was 87.80%. The results showed a difference between predicted and experimental values at a percentage lower than 7.5%. Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM), particle size analyzer, and zeta potential were used to analyze the properties of selected microencapsulated samples. Overall, the encapsulation of AI extracts was successful and has the potential to be used in drug delivery.

Prevalence of burnout among urologist and its risk factors in Indonesia

ObjectiveTo evaluate burnout syndrome among Indonesian urologists by describing its prevalence and risk factors.Materials and methodsThis is a cross-sectional study conducted from February to April 2020. A validated Indonesian version of the Maslach Burnout Inventory that consists of 22 questions addressing emotional exhaustion, depersonalization, and personal achievement was utilized. The questionnaire was constructed using Google Forms (Google, Inc.) and was distributed via e-mail and WhatsApp Messenger (Facebook, Inc.). Burnout was defined as either high score on emotional exhaustion, or high score on depersonalization, or low score on personal achievement. Several variables were analyzed as risk factors to burnout using multivariate analysis. All statistical analyses were carried out using Statistical Software for Social Science (SPSS) version 23.ResultsFrom 486 eligible members of IUA, 184 (37%) respondents completed the questionnaire. Burnout syndrome was detected in 43 respondents (23.4%). From the results, most of the respondents have low EE (54.9%), low DP (77.7%), and moderate PA (45.7%). Bivariate analysis showed that age of less than 44 years old and being single were associated with increased risk of burnout with OR 2.2 (1.0–5.1, 95% CI, p-value 0.04) while being married decreases risk of burnout with OR 0.2 (0.1–0.8, 95% CI, p-value < 0.01). Lower work load in COVID-19–19 era was related to protective results with OR 0.4 (0.2–0.9, 95% CI, p-value 0.03). Multivariate analysis showed that being married decreases risk of burnout with OR 0.3 (0.1–0.9, 95% CI, p-value 0.04). Multivariate analysis showed that being married was the only significantly protective factor from burnout.ConclusionBurnout syndrome among majority of urologists in Indonesia has a moderate degree of burnout, with being married the only significant factor influencing burnout in this study.

Enhanced viability and stability of the Lactobacillus reuteri DSM 17938 probiotic strain following microencapsulation in pea and rice protein-inulin conjugates

Probiotics, which offer various health benefits can face challenges in terms of stability during food processing, storage, and gastrointestinal digestion. Therefore, this study aimed to improve the stability and survival of probiotics during various processing conditions and storage. To address this issue, the study was designed to microencapsulate Lactobacillus reuteri DSM 17938 within plant proteins (specifically rice protein (RP) and pea protein (PeP)) and their Maillard reaction conjugated with inulin by spray-drying. The encapsulation efficiency (EE%), stability during storage and temperature, and the viability after simulated gastrointestinal digestion of the microcapsules were examined. The results demonstrate that individual proteins exhibited lower EE%; however, the Maillard conjugates showed increased EE%, with RC (rice protein conjugates) displaying a higher EE% (96.99%) than PC (pea protein conjugates) (92.87%) (p &amp;lt; 0.05). Fourier Transform Infrared Spectroscopy verified the interaction between different functional groups of the proteins and Maillard conjugated and indicated the successful encapsulation of Lactobacillus reuteri DSM 17938 cells. The results also suggested that RC-encapsulated probiotic cells exhibited maximum survival upon gastrointestinal transit, with a decline of only 1.24 and 1.52 log CFU/g after gastric and complete simulated gastrointestinal digestion, respectively. The viability of probiotics encapsulated with RC and PeC showed improvement compared to those encapsulated with RP and PeP, particularly during refrigerated and room temperature storage, thermal challenge, and simulated gastrointestinal transit. Overall, these findings suggest that plant proteins and prebiotic inulin conjugates could serve as promising new encapsulation matrices for the encapsulation of probiotics in food applications.

Nanoencapsulation of Maqui (Aristotelia chilensis) Extract in Chitosan-Tripolyphosphate and Chenopodin-Based Systems.

Maqui berries contain a high percentage of anthocyanins with high antioxidant and anti-inflammatory capacity but that are unstable in the colonic site. Nanocarriers based on polysaccharides and/or proteins can protect against the degradation of anthocyanins. The aim of this study was the nanoencapsulation of maqui extract (ME) in chitosan-tripolyphosphate (CTPP-ME), chenopodin (CH-ME), and chenopodin-alginate (CHA-ME). A standardised ME was prepared and then encapsulated in the nanosystems. The physicochemical properties, encapsulation parameters, and the interactions of ME with the nanovehicles were characterised. The cyanidin-3-glucoside released and ORAC activity in phosphate buffer at pH 7.4 were evaluated. The content of ME was 8-9 mg of cyanidin-3-glucoside/g of extract. CTPP with ME at 3% obtained the highest encapsulation efficiency (EE = 91%), and no significant differences were observed in size (274-362 nm), PDI (0.5-0.7), and zeta potential (+34-+41 mV) when the concentration of ME changed from 1% to 5%. CH-ME was shown to be smaller (152 nm) than CTPP-ME, and CH-ME and CHA-ME showed lower EE (79% and 54%, respectively) than CTPP-ME. FT-IR revealed a stronger interaction of ME with CTPP-ME than with CH-ME. Both systems showed a significantly lower release than free ME, and the T50 value of CTPP-ME 3% (328 min) was higher than CH-ME (197 min). Both protected the ORAC activity of ME.

Insight into the liposomal encapsulation of mono and bis-naphthalimides.

Mitonafide-loaded liposomes are a promising strategy to overcome the neurotoxicity observed in clinical trials for this drug. This study investigates the influence of loaded mitonafide or a dimer analogue on different liposomal formulations and their therapeutic efficacy in vitro. Physicochemical properties of the liposomes were manipulated using different loading methods (namely bilayer or core loading) and varying the rigidity of the bilayer using distinct phospholipid compositions. Our results demonstrated that the mitonafide dimer analogue had a comparable encapsulation efficiency (EE%) into the liposomes when loaded into rigid or flexible bilayers in contrast to the low mitonafide monomer EE%. A pH gradient core loading method resulted in a more efficient mechanism to load the monomer into the liposomes. DOSY NMR and spectrofluorometric studies revealed key differences in the structure of the vesicles and the arrangement of the monomer or the dimer in the bilayer or the core of the liposomes. The in vitro assessment of the formulations using MDA-MB-231 and RT-112 cells revealed that a flexible lipid bilayer allows a faster drug release, which correlated well with the spectroscopy studies. This study investigated for the first time that the characteristics of the lipid bilayer and the loading method influence the encapsulation efficacy, colloidal properties, photoactivity and stability of mono and bis-naphthalimides loaded in a liposomal carrier, essential factors that will impact the performance of the formulation in a biological scenario.

Preparation and characterization of acetylated starch/papain composites.

This research aimed to prepare and characterize acetylated starch/papain composites by encapsulating papain within acetylated cassava starch with a low degree of substitution (DS = 0.037) through a stepwise antisolvent precipitation method. The effects of starch concentrations, starch solution volumes, and surfactant types and concentrations were examined. An increase in starch concentration generally enhanced EE, but an excessive concentration led to a decrease in performance due to the aggregation of starch. Furthermore, LC decreased as the starch concentration increased, while the volume of the starch solution primarily influenced LC. Surfactants were employed to disperse the particles and prevent their aggregation during encapsulation, with higher concentrations, particularly of Tween 80, improving both EE and LC but reducing the activity of papain. Optimal results were achieved with a starch concentration of 30 mg mL-1, solution volume of 7 mL, and 3% v/v Tween 80, resulting in an EE of 96.23% and LC of 12.40%. However, the residual papain activity under these conditions dropped to approximately 56%. In contrast, Tween 20 at 1% v/v preserved higher papain activity (87%), although it yielded a lower EE of 69.87% and LC of 9.32%. SEM images revealed that the resulting composite particles had rough, indistinct clusters with surfaces featuring clustered starch nanoparticles. Confirmatory analyses via fluorescence spectra and FTIR confirmed successful entrapment of papain within acetylated starch with a lower degree of substitution.

Occult right ventricular dysfunction and right ventricular-vascular uncoupling in left ventricular assist device recipients

BackgroundCurrent assessments remain insensitive for detecting right heart failure post left ventricular assist device (LVAD). Sensitive pressure-volume loop assessments of right ventricle (RV) contractility may improve our appreciation of post-LVAD RV dysfunction. MethodsThirteen LVAD patients and 20 reference (non-LVAD) subjects underwent comparison of echocardiographic, right heart cath hemodynamic, and pressure-volume loop-derived assessments of RV contractility using end-systolic elastance (Ees), RV afterload by effective arterial elastance (Ea), and RV-pulmonary arterial (RV-PA) coupling (ratio of Ees/Ea). ResultsLVAD patients had lower RV Ees (0.20±0.08 vs. 0.30±0.15 mmHg/ml, p=0.01) and lower RV Ees/Ea (0.37±0.14 vs 1.20±0.54, p<0.001) versus reference subjects. Low RV Ees correlated with reduced RV septal strain, an indicator of septal contractility, in both the entire cohort (r=0.68, p=0.004) as well as the LVAD cohort itself (r=0.78, p=0.02). LVAD recipients with low RV Ees/Ea (below the median value) demonstrated more clinical heart failure (71% vs 17%, p=0.048), driven by an inability to augment RV Ees (0.22±0.11 vs 0.19±0.02 mmHg/ml, p=0.95) to accommodate higher RV Ea (0.82±0.38 vs 0.39±0.08 mmHg/ml, p=0.002). Pulmonary artery pulsatility index (PAPi) best identified low baseline RV Ees/Ea (≤0.35) in LVAD patients (AUC=0.80); during ramp study, change in PAPi also correlated with change in RV Ees/Ea (r=0.58, p=0.04). ConclusionsLVAD patients demonstrate occult intrinsic RV dysfunction. In the setting of excess RV afterload, LVAD patients lack the RV contractile reserve to maintain ventriculo-vascular coupling. Depression in RV contractility may be related to LVAD LV unloading which reduces septal contractility.

High prevalence of burnout syndrome in Czech general practitioners: A cross-sectional survey

ObjectiveA wide range in prevalence rates of burnout among general practitioners (GPs) has been reported in various regions, with an increasing trend. This nationwide cross-sectional study aimed to estimate the prevalence and associated determinants of burnout in Czech GPs. Methods1000 randomly selected physicians from the Czech Society of General Practitioners (through a pseudorandom number generator) were emailed an online survey based on the Maslach Burnout Inventory – Human Services Survey. Data collection was performed between January and February 2023. Results331 questionnaires were obtained (227 females and 104 males, mean age – 49.9 years, the mean number of registered patients – 1951). 21.8 % of GPs scored a high level of burnout in all three of its dimensions and 23.9 % in no dimension at all. The most prevalent dimension was reduced personal accomplishment (PA, 56.2 %) followed by emotional exhaustion (EE, 50.2 %) and depersonalization (DP, 40.5 %). Reaching burnout in all three dimensions was significantly more frequent in males and in GPs registering a number of patients above the median. Increasing age and years of practice were protective factors for DP but risk factors for reduced PA. Employed GPs had lower EE scores than GP practice owners. The respondents' basic characteristics reflected their presence among Czech GPs, which testifies against selection bias. ConclusionsThe high rate of burnout (∼22 %) should be addressed by promoting personal resources along with the perception of the importance of GPs in society. A sufficiently dense network of GPs should allow them to register a lower number of patients.

Reduced left ventricular elastance as a novel marker of cardiac dysfunction in patients with severe liver disease

Abstract Introduction Left ventricular (LV) elastance reflects the contractility of the myocardium and is an index of cardiac performance. Liver cirrhosis is characterized by reduced systemic vascular resistance, leading to reduced afterload on the LV. This, combined with increased blood volume, results in increased preload, increased stroke volume and remodeling of the LV. The latter may result to alterations in end-systolic LV elastance (Ees) a parameter that has not been extensively studied in cirrhotics. Purpose To investigate the relationship between Ees and the severity of liver cirrhosis. Methods We conducted a cross-sectional study in which transthoracic echocardiography was performed in 75 patients with liver cirrhosis (mean age 58.9±8.5 years, 74.7% males). A verified noninvasive single-beat formula was used to calculate Ees. Specifically, Ees was calculated employing systolic and diastolic blood pressures, echo-derived stroke volume (SV), ejection fraction (LVEF) and the estimated normalized ventricular elastance at arterial end-diastole (ENd). The ENd was estimated from a group-averaged value adjusted for individual contractile/loading effects. The Model for End-Stage Liver Disease-Sodium (MELDNa) score, a widely used tool for assessing liver disease severity was also calculated. We compared Ees between patients with MELDNa scores above and below 15, which is the cutoff commonly used to indicate severe liver disease. Results Mean Ees in the cohort of the 75 patients was 2.34±0.81mmHg/ml. Ees was correlated with end-systolic LV volume (rho=-0.448, p&amp;lt;0.001), SV (rho=-0.568, p&amp;lt;0.001) and systolic blood pressure (rho=0.283, p=0.014), but not with LVEF. Mean MELDNa score was 15.5±7.3 and 32 (42.7%) of patients had MELDNa score ≥ 15. Mean Ees in patients with MELDNa score above 15 was significantly lower than in patients with MELDNa score below 15 (2.08±0.61mmHg/ml vs 2.54±0.89mmHg/ml, p=0.015). The association remained significant in a multivariate model after adjusting for age, sex, and body surface area (B=-0.426, p=0.015). Conclusion Our study demonstrates that patients with severe liver disease have lower Ees, indicating impaired LV function. Ees could be a useful marker for identifying patients with liver cirrhosis who are at increased risk of cardiovascular complications. Further research is needed to better understand the mechanisms underlying this association and to propose therapeutic interventions aimed at improving LV function in this special population.

Green chiral separation of racemic mixture via crystallization induced deracemization process synergistically intensified by ultrasound and temperature cycling

Deracemization is a promising chiral resolution technique that combines racemization reaction with stereoselective crystallization for complete chiral symmetry breaking and has attracted much attention. However, the integration process of reaction-crystallization is rather complex and often requires long operation time with high initial solid enantiomer excess which greatly limits its wide application. Herein, we proposed a novel strategy that combines the use of both ultrasound and temperature cycles to accelerate the process of deracemization and thereby chiral separation. A chiral compound, N-acetyl-dl-leucine, was selected as a model drug for experimental validation. We found that either ultrasound or temperature cycle process was capable of accelerating the deracemization efficiency, nonetheless, the combination of the two methods leads to the antagonistic action, decreasing process efficiency and product chiral purity. Through the time-elapsed characterizations on enantiomeric purity of N-acetyl-l-leucine over the course of deracemization, we revealed that the ultrasound negatively impacted the process efficiency of chiral separation via promotion of primary heterogeneous nucleation during the cooling stage. Finally, we strategically designed a synergistic process intensification of crystallization-induced deracemization between temperature cycling and the periodic ultrasound that switches on only during the heating stage to achieve highly efficient separation of pure N-acetyl-l-leucine with theoretical 100% yield at extremely low initial solid ee%.

How Medium Affects the Activity and Stereopreference of Thermoanaerobacter ethanolicus Secondary Alcohol Dehydrogenase Catalyzed Reduction of Ketones

Abstract: The activity and selectivity of W110G Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase were altered by cosubstrate and cosolvent at varying temperatures. A sharp drop in the enantiomeric excess (ee) was observed at 60 oC in the first 3 h, suggesting increased selectivity mistakes in the reduction of 4-phenyl-2-butanone to the expected (S)-4-phenyl-2-butanol using 5% v/v of 2-propanol as a cosubstrate. The ee increased exponentially with cosubstrate concentration, reaching ≥94% with 30-70% v/v 2-propanol. However, a decrease in enzyme activity was noticed at ≥30% v/v 2-propanol by a sharp drop in conversion. The lowest ee (&lt;3%) was registered using 5% v/v 2- propanol at 30-40 oC, which prolonged enzyme life that allowed reversible redox reaction with selectivity mistakes to give the R-alcohol compared to ≥18% ee at 50-60 oC, where faster reaction rates promoted selectivity mistake, but enzyme life was shortened by protein denaturation at the elevated temperatures. Water-miscible and immiscible organic cosolvents (25% v/v) increased enzyme selectivity. For methanol, ethanol, ethylene glycol and tert-butanol, the activity/conversion decreased with an increase in pKa and log P while the stereoselectivity/ee increased.

Small Intestinal Digestive Functions and Feed Efficiency Differ in Different Pig Breeds

Small intestinal growth and health affect its digestion and absorption ability, while little information exists about the small intestinal morphology and function differences among the different pig breeds. Therefore, 90 healthy 35 days of age Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) pigs (30 pigs per breed) with similar body weight (BW) of the same breed were reared to 185 days of age to evaluate the potential relationship between feed efficiency and small intestinal morphology and function at 80, 125, and 185 days of age. The results show that the TB and XB pigs had lower initial and final BW, ADG, and ADFI and plasma CHO and LDL-C levels, whereas they had higher plasma LIP levels and jejunal trypsin, invertase, lactase, and maltase activities and higher DM, ADF, Tyr, Arg, and His digestibility at 80 days of age compared with the DR pigs. At 125 days of age, TB and XB pigs had lower apparent total tract digestibility and plasma CHO, HDL-C, LDL-C, and NH3 levels; XB pigs had lower DM and NDF digestibility, and TB pigs had higher jejunal lactase and maltase activities. At 185 days of age, TB and XB pigs had lower DM, EE, ADF, and GE digestibility, while having higher plasma ALT and UN levels; TB pigs had higher plasma AST level and jejunal chymase activity. Furthermore, the plasma free amino acid contents, small intestinal VH, and nutrient transporter expression levels differed at different ages. Therefore, the different pig breeds exhibited significantly different growth performance and small intestinal growth, mainly resulting from the differences in digestive enzymes and nutrient transporters in the small intestine.

Asymmetric synthesis of aryl-substituted pyrrolidines by using CFAM ligand-AgOAc chiral system via 1,3-dipolar cycloaddition reaction.

We have prepared a ligand library based on a ferrocenyl aziridinyl methanol core unit (simply called FAM) having a phenyl group, a cyclohexyl group, and a naphthyl group to be used in 1,3-dipolar cycloaddition (1,3-DC) reactions for the synthesis of chiral pyrrolidines. These chiral ligands were used with AgOAc in 1,3-DC reactions taking place between the aryl-substituted azomethine ylides and N-methylmaleimide as the dipolarophile. In each case, the expected aryl-substituted pyrrolidines were obtained in good to excellent yields with acceptable enantioselectivities favoring only the endo product. The chiral catalyst system CFAM4-AgOAc was also used in 1,3-DC reaction with different dipolarophiles such as dimethyl maleate, tert-butyl acrylate, methyl acrylate, trans-chalcone, and vinyl sulfone. In each case, the cycloadducts were obtained in acceptable yields albeit with low ee. Fortunately, it was possible to increase the ee up to >99% upon crystallization.

Synthesis of P-stereogenic 1-phosphanorbornane-derived phosphine-phosphite ligands and application in asymmetric catalysis.

A convenient synthesis of enantiopure mixed donor phosphine-phosphite ligands has been developed incorporating P-stereogenic phosphanorbornane and axially chiral bisnaphthols into one ligand structure. The ligands were applied in Pd-catalyzed asymmetric allylic substitution of diphenylallyl acetate, Rh-catalyzed asymmetric hydroformylation of styrene and Rh-catalyzed asymmetric hydrogenation of an acetylated dehydroamino ester. Excellent branched selectivity was observed in the hydroformylation although low ee was found. Moderate ee's of up to 60% in allylic substitution and 50% in hydrogenation were obtained using bisnaphthol-derived ligands.

Abstract 11886: Unique Insights of Pressure-Volume Loop Analysis During LVAD Ramp Study

Introduction: Late right ventricular (RV) failure in left ventricular assist device (LVAD) patients leads to poor outcomes and mortality. Traditional hemodynamic assessment of RV function may lack sensitivity. Invasive pressure-volume loop assessment of RV function may prove more enlightening than currently available measures. Methods: Pressure-volume loop-derived RV end-systolic elastance (Ees) and effective arterial elastance (Ea)—indices of load-independent RV contractility and summated pulmonary arterial (PA) afterload respectively—were determined for control (n=14), PH (n=38), and LVAD (n=12) patients referred for right heart catheterization. LVAD patients were further dichotomized by referral reason: routine assessment vs. clinical heart failure (HF) (n=6 each). Results: At baseline, LVAD patients had lower RV Ees versus both PH (0.21 vs 0.41 mmHg/mL, p&lt;0.001) and control (0.21 vs. 0.36 mmHg/mL, p=0.05) patients. Adjusting for age and afterload, RV-PA coupling, indexed by the ratio of Ees/Ea, was significant lower in LVAD vs matched non-LVAD patients (0.37 vs 0.65, p=0.01). Among LVAD patients, RV-PA coupling was significantly worse in those with clinical HF (0.26 vs 0.49, p=0.002), corresponding with depressed cardiac index (1.6 vs 2.3 L/min/m 2 , p=0.04) and a trend towards higher biventricular filling pressures. RV-PA coupling also responded differently with respect to speed change: while Ees/Ea improved with speed increase in well-compensated LVAD patients, it declined in those with HF (p=0.02 for interaction term, see Figure), driven by declining Ees. Conclusion: Intrinsic RV contractility is worse in LVAD patients versus control and non-LVAD PH; this drives significantly worse RV-PA coupling in LVAD patients. In LVAD patients with HF, RV-PA coupling is significantly reduced and not necessarily improved by increases in speed.

Fluoride Additive as a Simple Tool to Qualitatively Improve Performance of Nickel-Catalyzed Asymmetric Michael Addition of Malonates to Nitroolefins.

Nowadays, design of the new chiral ligands for organometallic catalysts is often based on the step-by-step increase in their complexity to improve efficiency. Herein we describe that simple in situ addition of the fluoride source to the asymmetric organometallic catalyst can improve not only activity but also enantioselectivity. Bromide-nickel diimine complexes were found to catalyze asymmetric Michael addition in low yields and ee, but activation with fluoride leads to a significant improvement in catalyst performance. The developed approach was applied to prepare several enantioenriched GABA analogues.