Standard Chemistry Research Articles

Construction of a Reduction-responsive DNA Microsphere using a Reduction-cleavable Spacer based on a Nitrobenzene Scaffold.

Here, we describe the design and synthesis of a new reduction-cleavable spacer (RCS) based on a nitrobenzene scaffold for constructing reduction-responsive oligonucleotides according to standard phosphoramidite chemistry. In addition, we demonstrate that the introduction of the RCS in the middle of an oligonucleotide (30 nt) enables the construction of a self-assembled microsphere capable of exhibiting a reduction-responsive disassembly.

Importance of Asparagine 202 in Manipulating Active Site Structure and Substrate Preference for Human CYP17A1.

The multifunctional cytochrome P450 17A1 (CYP17A1) plays a crucial role in human steroid hormone synthesis (UniProtKB─P05093). It first carries out standard monooxygenase chemistry, converting pregnenolone (PREG) and progesterone (PROG) into 17OH-PREG and 17OH-PROG, utilizing a "Compound I" to initiate hydrogen abstraction and radical recombination in the classic "oxygen rebound" mechanism. Additionally, these hydroxylated products also serve as substrates in a second oxidative cycle which cleaves the 17-20 carbon-carbon bond to form dehydroepiandrosterone and androstenedione, which are key precursors in the generation of powerful androgens and estrogens. Interestingly, in humans, with 17OH-PREG, this so-called lyase reaction is more efficient than with 17OH-PROG, based on Kcat/Km values. In the present work, the asparagine residue at 202 position was replaced by serine, an alteration which can affect substrate orientation and control substrate preference for the lyase reaction. First, we report studies of solvent isotope effects for the N202S CYP17A1 mutant in the presence of 17OH-PREG and 17OH-PROG, which suggest that the ferric peroxo species is the predominant catalytically active intermediate in the lyase step. This conclusion is further supported by employing a combination of cryoradiolysis and resonance Raman techniques to successfully trap and structurally characterize the key reaction intermediates, including the peroxo, the hydroperoxo, and the crucial peroxo-hemiketal intermediate. Collectively, these studies show that the mutation causes active site structural changes that alter the H-bonding interactions with the key Fe-O-O fragment and the degree of protonation of the reactive ferric peroxo intermediate, thereby impacting lyase efficiency.

Comparison of two glucose-monitoring systems for use in horses.

To determine the accuracy of 2 interstitial glucose-monitoring systems (GMSs) for use in horses compared with a point-of-care (POC) glucometer and standard laboratory enzymatic chemistry method (CHEM). 8 clinically normal adult horses. One of each GMS device (Dexcom G6 and Freestyle Libre 14-day) was placed on each horse, and blood glucose concentration was measured via POC and CHEM at 33 time points and compared with simultaneous GMS readings. An oral glucose absorption test (OGAT) was performed on day 2, and glucose concentrations were measured and compared. Glucose concentrations were significantly correlated with one another between all devices on days 1 to 5. Acceptable agreement was observed between Dexcom G6 and Freestyle Libre 14-day when compared with CHEM on days 1, 3, 4, and 5 with a combined mean bias of 10.45 mg/dL and 1.53 mg/dL, respectively. During dextrose-induced hyperglycemia on day 2, mean bias values for Dexcom G6 (10.49 mg/dL) and FreeStyle Libre 14-day (0.34 mg/dL) showed good agreement with CHEM. Serial blood glucose measurements are used to diagnose or monitor a variety of conditions in equine medicine; advances in near-continuous interstitial glucose monitoring allow for minimally invasive glucose assessment, thereby reducing stress and discomfort to patients. Data from this study support the use of the Dexcom G6 and Freestyle Libre 14-day interstitial glucose-monitoring systems to estimate blood glucose concentrations in horses.

MiCheck prostate blood test for aggressive prostate cancer designed for the clinical lab setting.

229 Background: Clinicians want a more accurate diagnostic test to identify patients for prostate biopsy. We have previously described the development of a Luminex based test for aggressive prostate cancer (MiCheck). To facilitate widespread deployment of MiCheck on standard clinical chemistry analysers such as Roche Cobas and Abbott ARCHITECT/Alinity systems, we have performed additional analytical validation and model development using the MiCheck-01 clinical samples. A novel algorithm, termed MiCheck Prostate, was developed to differentiate aggressive prostate cancer (Gleason 3+4 or above) from non-aggressive (GS3+3) or no cancer patients. Methods: Serum protein biomarkers were measured in 317 samples from the MiCheck-01 clinical trial using either Luminex Multiplex kits, Abbott ARCHITECT or Beckmann Coulter systems. Logistic regression models were used to select best analytes, then Monte Carlo cross-validation was applied to avoid overfitting. A final model was selected from the cross-validation models with best test specificity at 95% sensitivity. The MiCheck-01 samples were later all measured on a standard Abbott ARCHITECT system using commercial ARCHITECT IVD tests. The best cross-validated model was developed and the results compared to those obtained from the mixed analyte platforms using ROC curve analysis. Results: The MiCheck Prostate algorithm was developed to maximise discrimination between aggressive prostate cancer and no cancer or non-aggressive cancer. The MiCheck Prostate algorithm reports a percentage risk of aggressive prostate cancer on biopsy. MiCheck Prostate is a logistic regression algorithm that combines three serum protein markers and one clinical factor and was derived using data from the MiCheck-01 trial. The algorithm gave an AUC of 0.82, with a 48% specificity at a 95% sensitivity cutpoint, with a negative predictive value of 94% for GS3+4 and higher cancers. The samples were later re-measured using all ARCHITECT immunoassays. Good correlations of each analyte across different measurement platforms was observed (Pearson’s R > 0.9). The algorithm was revalidated using the new set of analyte values. AUC of 0.82 for the detection of aggressive CaP, and sensitivity of 95%, specificity of 47% were obtained for the best model, showing no statistical difference to the previous best model derived from the mixed platforms. NPV of 94% for GS3+4 or higher cancers was maintained. Conclusions: The MiCheck Prostate test shows high sensitivity, specificity and NPV for the detection of aggressive prostate cancer. It uses analytes widely available on standard clinical chemistry analysers such as Abbott Architect and Roche Cobas, hence is simple to deploy in the laboratory setting. Studies are ongoing to confirm the MiCheck Prostate algorithm performance using additional clinical sample cohorts.

Atmospheric Degradation of Cyclic Volatile Methyl Siloxanes: Radical Chemistry and Oxidation Products.

Cyclic volatile methyl siloxanes (cVMS) are anthropogenic chemicals that have come under scrutiny due to their widespread use and environmental persistence. Significant data on environmental concentrations and persistence of these chemicals exists, but their oxidation mechanism is poorly understood, preventing a comprehensive understanding of the environmental fate and impact of cVMS. We performed experiments in an environmental chamber to characterize the first-generation oxidation products of hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4), and decamethylcyclopentasiloxane (D5) under different peroxy radical fates (unimolecular reaction or bimolecular reaction with either NO or HO2) that approximate a range of atmospheric compositions. While the identity of the oxidation products from D3 changed as a function of the peroxy radical fate, the identity and yield of D4 and D5 oxidation products remained largely constant. We compare our results against the output from a kinetic model of cVMS oxidation chemistry. The reaction mechanism used in the model is developed using a combination of previously proposed cVMS oxidation reactions and standard atmospheric oxidation radical chemistry. We find that the model is unable to reproduce our measurements, particularly in the case of D4 and D5. The products that are poorly represented in the model help to identify possible branching points in the mechanism, which require further investigation. Additionally, we estimated the physical properties of the cVMS oxidation products using structure-activity relationships and found that they should not be significantly partitioned to organic or aqueous aerosol. The results suggest that cVMS first-generation oxidation products are also long-lived in the atmosphere and that environmental monitoring of these compounds is necessary to understand the environmental chemistry and loading of cVMS.

High Accuracy Transition Metal Effective Cores for the Many-Body Diffusion Monte Carlo Method.

Practical applications of the real-space diffusion Monte Carlo (DMC) method require the removal of core electrons, where currently localization approximations of semilocal potentials are generally used in the projector. Accurate calculations of complex solids and large molecules demand minimizing the impact of approximated atomic cores. Prior works have shown that the errors from such approximations can be sizable in both finite and periodic systems. In this work, we show that a class of differential pseudopotentials, known as pseudo-Hamiltonians, can be constructed for the 3d transition metal atoms, entirely removing the need for any localization scheme in the DMC projector. As a proof of principle, we demonstrate the approach for the case of Co. In order to minimize errors in the pseudo-Hamiltonian at the many-body level, we generalize the recently proposed correlation-consistent pseudopotential generation scheme to successively close semilocal representations of the differential potentials. Our generation scheme successfully produces potentials tailored specifically for real space projector quantum Monte Carlo methods with low error at the many-body level, i.e., with many-body scattering properties very close to relativistic all-electron results. In particular, we show that the agreement with respect to atomic and molecular quantities reach chemical accuracy in many cases─on par with the most accurate semilocal pseudopotentials available. Further, our pseudo-Hamiltonian generation scheme utilizes standard quantum chemistry codes designed only to work with semilocal pseudopotentials, enabling straightforward generation of pseudo-Hamiltonians for additional elements in future works.

Case Study of Hypertriglyceridemia from COVID-19 Pfizer-BioNTech Vaccination in a Patient with Familial Hypercholesteremia

Lead Author's Financial DisclosuresNothing to disclose.Study FundingNone.Background/SynopsisFamilial hypercholesterolemia (FH) is an autosomal codominant genetic disorder with very high levels of low-density lipoprotein cholesterol (LDL-C) due to defective hepatic uptake via LDL receptors. Little data are available about the impacts of a Coronavirus Disease 2019 (COVID-19) Pfizer-BioNTech vaccine on serum lipids in patients with FH.Objective/PurposeTo evaluate a FH patient presenting with severe hypertriglyceridemia after receiving his COVID-19 Pfizer-BioNTech vaccination.MethodsA history, physical examination, lipoprotein testing, and standard clinical chemistry laboratory testing were performed. Dextran sulfate cellulose LDL apheresis was performed with the Kaneka Medical America LLC Liposorber LA-15 system.ResultsA 60-year-old man has been treated for years with weekly or biweekly LDL apheresis treatments for FH, which was diagnosed >10 years ago using a Dutch Lipid Clinic Network score of 11. He has a history of hypertension, hypothyroidism, ischemic cardiomyopathy, heart failure with reduced ejection fraction, 5 myocardial infarctions (MI), status post coronary artery bypass graft, and 20 coronary artery stents. Medications include rosuvastatin 40 mg/d, ezetimibe 10 mg/d, fenofibrate 145 mg/d, icosapent ethyl 2 grams twice daily, alirocumab 150 mg biweekly, and levothyroxine 200 mcg/d. Prior to each apheresis treatment, he receives hydrocortisone 50 mg intravenously due to prior intolerance. He has maintained a Mediterranean diet and regularly exercises. Family history includes his father, paternal aunt, and paternal grandfather who all had MIs at or before the age of 50. Physical exam has been nonrevealing.He received his Pfizer-BioNTech vaccination doses on 3/10/21 and 3/31/2021. His lipid panel on 4/1/2021 revealed in mg/dL: triglyceride (TG) of 1308; total cholesterol (TC) of 285; direct LDL-C of 102; high-density lipoprotein cholesterol (HDL-C) of 35 (Table 1). LDL apheresis was attempted on 4/1/21, but failed, as the apparatus had very poor flow due to his very elevated triglycerides and cloudy blood (confirmed by Kaneka). He received apheresis 7 days later without complications with his pre-treatment lipid panel revealing in mg/dL: TG of 196; TC of 188; LDL-C of 106; HDL-C of 43. Prior to this, TG levels for the past 8 years averaged 277 mg/dL and 114 mg/dL pre- and post-apheresis, respectively.ConclusionsA potential increase in TG due to COVID-19 vaccination occurred in a patient with FH and serious atherosclerosis, which prevented a potentially life-saving treatment. This underscores the need to address any rare complications from novel COVID-19 treatments, minimize ASCVD risk, and determine if this is a common side effect of COVID-19 vaccination.

Clinical Implementation of NGAL Testing to Improve Diagnostic Assessment of AKI Episodes in a Canadian Center.

Background:The differential diagnosis of acute kidney injury (AKI) episodes is often challenging. Novel AKI biomarkers have shown their utility to improve prognostic prediction and diagnostic assessment in various research populations but their implementation in standard clinical practice is still rarely reported.Objective:To report the differential diagnostic ability and associated clinical utility of the neutrophil gelatinase-associated lipocalin (NGAL) testing in a real-life setting of a heterogeneous AKI population.Design:This is a retrospective cohort study combined with a clinical audit using questionnaires distributed to consultant nephrologists following NGAL results.Setting:The first 250 consecutive patients with a confirmed AKI where an NGAL test (plasma NGAL [pNGAL] or urine NGAL [uNGAL]) was ordered from a large academic center in Montreal, Canada from January 2021 to August 2021.Patients:Patients were classified into 3 groups based on the final AKI etiology category (functional, intrarenal, and postrenal) following definitive adjudication by 2 independent nephrologists.Methods:The ability of plasma NGAL (pNGAL), urine NGAL (uNGAL), and uNGAL-to-creatinine ratio (uNGAL/Cr) to discriminate intrarenal from functional AKI etiologies was compared to standard urine chemistry (FENa) and proteinuria. A logistic regression was used to evaluate the association between intrarenal AKI and increased biomarker levels. The overall clinical utility and appreciation of the NGAL test was evaluated using a questionnaire completed prospectively by the consultant nephrologist at the time of receiving the NGAL result. The NGAL results were prospectively available to clinicians with a median time of 2.9 (1.3-7.4) hours from the initial order.Results:A total of 214 uNGAL and 44 pNGAL were ordered from 100 functional, 139 intrarenal and 11 postrenal AKI episodes after final adjudication. The discriminative ability of FENa (AUC 0.68 [95% CI: 0.61-0.75]) was lower than uNGAL (AUC 0.80 [95% CI: 0.73-0.86]) and uNGAL/Cr (AUC 0.83 [95% CI: 0.77-0.88]) but better than pNGAL (AUC 0.66 [95% CI: 0.48-0.85]). According to consultant nephrologists, the NGAL testing has led to a change in clinical management in 42% of cases.Limitations:Data reported came from a single center and NGAL was reserved for more complex cases, which limits generalizability. No biopsy has been performed for most AKI cases as the final adjudication was based on a retrospective review of the hospitalization episode.Conclusions:Neutrophil gelatinase-associated lipocalin testing can be successfully integrated as part of the diagnostic workup for AKI in clinical practice. The integration of tubular damage biomarkers to functional biomarkers can further improve the differential diagnostic assessment. However, the impact of such biomarkers on AKI management and associated outcomes still needs further validation.

A simple and soft chemical deaggregation method producing single-digit detonation nanodiamonds.

Detonation nanodiamonds (DNDs) are a class of very small and spherical diamond nanocrystals. They are used in polymer reinforcement materials or as drug delivery systems in the field of nanomedicine. Synthesized by detonation, only the final deaggregation step down to the single-digit nanometer size (<10 nm) unfolds their full potential. Existing deaggregation methods mainly rely on mechanical forces, such as high-power sonication or bead milling. These techniques entail drawbacks such as contamination of the sample and the need for a specialized apparatus. In this paper, we report a purely chemical deaggregation method by simply combining oxidation in air followed by a boiling acid treatment, to produce highly stable single-digit DNDs in a suspension. The resulting DNDs are surface functionalized with carboxyl groups, the final boiling acid treatment removes primary metal contaminants such as magnesium, iron or copper and the nanoparticles remain dispersed over a wide pH range. Our method can be easily carried out in a standard chemistry laboratory with commonly available laboratory apparatus. This is a key step for many DND-based applications, ranging from materials science to biological or medical applications.

Non-Invasive Monitoring of Berry Ripening Using On-the-Go Hyperspectral Imaging in the Vineyard

Hyperspectral imaging offers enormous potential for measuring grape composition with a high degree of representativity, allowing all exposed grapes from the cluster to be examined non-destructively. On-the-go hyperspectral images were acquired using a push broom hyperspectral camera (400–100 nm) that was mounted in the front part of a motorized platform moving at 5 km/h in a commercial Tempranillo vineyard in La Rioja, Spain. Measurements were collected on three dates during grape ripening in 2018 on the east side of the canopy, which was defoliated in the basal fruiting zone. A total of 144 grape clusters were measured for Total soluble solids (TSS), Titratable acidity (TA), pH, Tartaric and Malic acid, Anthocyanins and Total polyphenols, using standard wet chemistry reference methods, throughout the entire experiment. Partial Least Squares (PLS) regression was used to build calibration, cross validation and prediction models for the grape composition parameters. The best performances returned determination coefficients values of external validation (R2p) of 0.82 for TSS, 0.81 for Titratable acidity, 0.61 for pH, 0.62 for Tartaric acid, 0.84 for Malic acid, 0.88 for Anthocyanins and 0.55 for Total polyphenols. The promising results exposed in this work disclosed a notable methodology on-the-go for the non-destructive, in-field assessment of grape quality composition parameters along the ripening period.

Constraints on Emission Source Locations of Methane Detected by Mars Science Laboratory

AbstractThe Sample Analysis at Mars (SAM) instrument on the Mars Science Laboratory (MSL) Curiosity rover has detected both methane spikes and variable background methane abundance in recent years in Gale Crater, Mars. While methane spikes have been attributed to a hypothetical local or regional source emission, the background measurements acquired during the nighttime were postulated to represent the global methane abundance on Mars. However, recent high‐accuracy observations by instruments on the Trace Gas Orbiter (TGO) in several locations around the planet have not detected methane at all, apparently contradicting the SAM measurements. This paper analyzes the constraints that TGO and MSL impose on the hypothetical location of the emission source of methane responsible for the levels detected by SAM. The numerical simulations presented here indicate that not only the spikes but also the background measurements performed by MSL must result from localized emissions, specifically in the northwest interior of Gale Crater. Other simulated emission source locations at a greater distance from MSL, even if still within Gale Crater, are difficult to reconcile with current observations by MSL and TGO. Confirming previous studies, these results therefore point either to an improbable scenario, in which the rover has landed close to one of only a few localized emission sources on Mars, or to a problematic scenario, in which an unknown loss mechanism must be invoked that is able to destroy methane orders of magnitude faster than predicted by standard gas chemistry or to a weighted action between both scenarios.

Binary-Encounter Model for Direct Ionization of Molecules by Positron-Impact

We introduce two models for the computation of direct ionization cross sections by positron impact over a wide range of collision energies. The models are based on the binary-encounter-Bethe model and take into account an extension of the Wannier theory. The cross sections computed with these models show good agreement with experimental data. The extensions improve the agreement between theory and experiment for collision energies between the first ionization threshold and the peak of the cross section. The models are based on a small set of parameters, which can be computed with standard quantum chemistry program packages.

Identification of VEGF Signaling Inhibition-Induced Glomerular Injury in Rats through Site-Specific Urinary Biomarkers.

Cancer therapies targeting the vascular endothelial growth factor (VEGF) signaling pathway can lead to renal damage by disrupting the glomerular ultrafiltration apparatus. The objective of the current study was to identify sensitive biomarkers for VEGF inhibition-induced glomerular changes in rats. Male Sprague-Dawley rats were administered an experimental VEGF receptor (VEGFR) inhibitor, ABT-123, for seven days to investigate the correlation of several biomarkers with microscopic and ultrastructural changes. Glomeruli obtained by laser capture microdissection were also subjected to gene expression analysis to investigate the underlying molecular events of VEGFR inhibition in glomerulus. ABT-123 induced characteristic glomerular ultrastructural changes in rats, including fusion of podocyte foot processes, the presence of subendothelial electron-dense deposits, and swelling and loss of fenestrations in glomerular endothelium. The subtle morphological changes cannot be detected with light microscopy or by changes in standard clinical chemistry and urinalysis. However, urinary albumin increased 44-fold as early as Day three. Urinary β2-microglobulin levels were also increased. Other urinary biomarkers that are typically associated with tubular injury were not significantly impacted. Such patterns in urinary biomarkers can provide valuable diagnostic insight to VEGF inhibition therapy-induced glomeruli injuries.

Synthesis and Purification of N3 -Methylcytidine (m3 C) Modified RNA Oligonucleotides.

This protocol describes a step-by-step chemical synthesis approach to prepare N3 -methylcytidine (m3 C) and its phosphoramidite. The method for synthesizing m3 C starts from commercially available cytidine, and proceeds via N3 -methylation in the presence of MeI, which generates the N3 -methylcytidine (m3 C) nucleoside, followed by the installation of several protecting groups at sites that include the 5'-hydroxyl group (4,4'-dimethoxytrityl protection), the 4-amino group (benzoyl protection), and the 2'-hydroxyl group (tert-butyldimethylsilyl, TBDMS, protection). Standard phosphoramidite chemistry is applied to prepare the final m3 C phosphoramidite for solid-phase synthesis of a series of RNA oligonucleotides. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of N3 -methylcytidine (m3 C) and its phosphoramidite Basic Protocol 2: Automated synthesis of m3 C modified RNA oligonucleotides.

The First Detection of CH2CN in a Protoplanetary Disk

Abstract We report the first detection of the molecule cyanomethyl, CH2CN, in a protoplanetary disk. Until now, CH2CN had only been observed at earlier evolutionary stages, in the molecular clouds TMC-1, Sgr2, and L483, in the prestellar core L1544, and toward the protostar L1527. We detect six transitions of ortho-CH2CN toward the disk around nearby T Tauri star TW Hya. An excitation analysis reveals that the disk-averaged column density, N , for ortho-CH2CN is (6.3 ± 0.5) × 1012 cm−2, which is rescaled to reflect a 3:1 ortho-para ratio, resulting in a total column density, N tot, of (8.4 ± 0.7) × 1012 cm−2. We calculate a disk-average rotational temperature, T rot = 40 ± 5 K, while a radially resolved analysis shows that T rot remains relatively constant across the radius of the disk. This high rotation temperature suggests that in a static disk and if vertical mixing can be neglected, CH2CN is largely formed through gas-phase reactions in the upper layers of the disk, rather than solid-state reactions on the surface of grains in the disk midplane. The integrated intensity radial profiles show a ring structure consistent with molecules such as CN and DCN. We note that this is also consistent with previous lower-resolution observations of centrally peaked CH3CN emission toward the TW Hya disks, since the observed emission gap disappears when convolving our observations with a larger beam size. We obtain a CH2CN/CH3CN ratio ranging between 4 and 10. This high CH2CN/CH3CN is reproduced in a representative chemical model of the TW Hya disk that employs standard static disk chemistry model assumptions, i.e., without any additional tuning.

Additive genetic variation in Pinus radiata bark chemistry and the chemical traits associated with variation in mammalian bark stripping.

Secondary metabolites are suggested as a major mechanism explaining genetic variation in herbivory levels in Pinus radiata. The potential to incorporate these chemical traits into breeding/deployment programmes partly depends on the presence of additive genetic variation for the relevant chemical traits. In this study, near-infrared spectroscopy was used to quantify the constitutive and induced levels of 54 compounds in the bark of trees from 74 P. radiata full-sib families. The trees sampled for chemistry were protected from browsing and induced levels were obtained by subjecting half of the trees to artificial bark stripping. The treatment effect on bark chemistry was assessed along with narrow-sense heritability, the significance of non-additive genetic effects and the additive genetic correlations of compounds with bark stripping by mammalian herbivores that was observed in unprotected replicates of the field trial. The results indicated: (i) significant additive genetic variation, with low-moderate narrow-sense heritability estimates for most compounds; (ii) while significant induced effects were detected for some chemicals, no significant genetic variation in inducibility was detected; and (iii) sugars, fatty acids and a diterpenoid positively genetically correlated while a sesquiterpenoid negatively genetically correlated with bark stripping by the mammalian herbivore, the Bennett's wallaby (Macropus rufogriseus). At the onset of browsing, a trade-off with height was detected for selecting higher amounts of this sesquiterpenoid. However, overall, results showed potential to incorporate chemical traits into breeding/deployment programmes. The quantitative genetic analyses of the near infrared predicted chemical traits produced associations with mammalian bark stripping that mostly conform with those obtained using standard wet chemistry.

Nazarov Cyclizations Catalyzed by BINOL Phosphoric Acid Derivatives: Quantum Chemistry Struggles To Predict the Enantioselectivity.

Quantum chemical calculations have successfully predicted the stereoselectivities of many BINOL phosphoric acid catalyzed reactions over the past 10-15 years. Herein we report a contrasting example: a reaction for which standard quantum chemistry techniques have proven unexpectedly ineffective at explaining the stereoselectivity. The Nazarov cyclizations of a divinyl ketone catalyzed by a BINOL phosphoric acid or H8-BINOL dithiophosphoric acid were studied with a conventional contemporary quantum chemical approach, consisting of transition state optimizations with B3LYP-D3(BJ) and single-point calculations with several functionals in implicit solvent. Unexpectedly, different functionals gave widely different predictions of the level of enantioselectivity and were unable even to agree on which enantiomer of the product would predominate. Molecular dynamics simulations with the OPLS-AA force field provided evidence that the transition state geometries optimized with DFT in the gas phase or in implicit solvent are not good representations of the true transition states of these reactions in solution. One possible reason for this, which may also explain the failure of quantum chemical techniques to reliably predict the enantioselectivity, is the fact that the transition states contain ion pairs which are not highly organized and do not contain any strongly directional noncovalent interactions between the substrate and the catalyst.

Influences of etching chemical parameters on AlGaN/GaN electrical degradation in power devices

The influence of chemical parameters on electrical degradation in an AlGaN/GaN heterostructure was investigated in order to improve performance in metal-oxide-semiconductor high-electron mobility transistor devices. We first examined the influence of plasma chemistry on electrical degradation by using different plasma chemistries for the SiN capping layer opening and comparing the results. The full standard chemistry was evaluated in order to determine the impact of each gas on the degradation. Rsheet and x-ray photoelectron microscopy characterizations and simulations were performed to better understand how light elements such as helium penetrate deeply into the heterostructure and degrade its electrical characteristics. The materials used as masks were also studied. A photoresist mask and a SiN mask were compared on an AlGaN/GaN heterostructure during plasma processing. Electrical degradation was always greater in the presence of a resist due to the decomposition of the resist under the plasma causing hydrogen to be released into the plasma. Simulation of hydrogen implantation in AlGaN was also performed to understand its impact on electrical performance.

S89 Is There More to Gas and Bloating, Abdominal Pain, and Diarrhea in Patients With Exocrine Pancreatic Insufficiency?

Introduction: Abdominal pain, diarrhea, and gas/bloating are among the most common gastrointestinal symptoms that bring patients to the clinic; comprising 21%, 25%, and 20% of presentations, respectively (1). Awareness of exocrine pancreatic insufficiency (EPI) has risen in recent years. Though some have underlying conditions such as cystic fibrosis, pancreatic surgeries, diabetes, chronic pancreatitis, and pancreatic cancer, most are idiopathic. In this study we reviewed 219 patients presenting with the aforementioned symptoms who were diagnosed with EPI without a predisposing condition. Previous reviews have discussed routine etiologies of gas/bloat syndrome with pain and perturbation of defecation (2,3). In this paper we describe the prevalence of comorbid disorders that contribute to this symptom complex. Methods: We identified 219 patients (147 female, 72 male) with idiopathic EPI in the outpatient clinic with any combination of gas/bloat, pain, and diarrhea. Ages ranged from 18-90 years (median 64). We obtained standard chemistries, CBC, thyroid profile, celiac panel, stool elastase, lactoferrin, and hydrogen breath testing for carbohydrate malabsorption and SIBO. If an elevated lactoferrin, suspicious celiac panel, or persistent diarrhea were observed, endoscopic examinations were performed. Patients were also evaluated for IBS using Rome IV criteria. Results: Of the 219 patients, we noted diagnoses that are associated with similar symptoms: 43 (19.6%) had SIBO, 43 (19.6 %) fructose intolerance, 28 (12.8%) lactose intolerance, 8 (3.7 %) with celiac, and 4 (1.8%) with sucrose intolerance. Notably, 14 (6.4 %) were diagnosed with microscopic colitis and 29 (13.2%) with IBS. Further analysis revealed that 24.7% had 2 conditions, 11% with 3, 6.8% with 4, and 2.3% with 5. Conclusion: EPI is a common and easily treated problem seen in clinic, but often is not a comprehensive diagnosis. A constellation of symptoms including gas/bloat, pain, and diarrhea are often indicative of a more complex and multifactorial phenomenon that requires meticulous evaluation.

ACE Inhibitory Peptides from Bellamya bengalensis Protein Hydrolysates: In Vitro and In Silico Molecular Assessment

Bellamya bengalensis muscle meat is known for ethnopharmacological benefits. The present study focuses on the identification of ACE inhibitory peptides from the proteolytic digests of muscle protein of Bellamya bengalensis and its underlying mechanism. After ultrafiltration of 120 min alcalase hydrolysates (BBPHA120) to isolate the small peptide fraction (&lt;3 kDa), in vitro ACE inhibitory activity was analyzed. The IC50 value of the 120 min hydrolysate ultrafiltered fraction was 86.74 ± 0.575 µg/mL, while the IC50 of lisinopril was 0.31 ± 0.07 µg/mL. This fraction was assessed in a MALDI-ToF mass spectrometer and five peptides were identified from the mass spectrum based on their intensity (&gt;1 × 104 A.U.). These peptides were sequenced via de novo sequencing. Based on the apparent hydrophobicity (%), the IIAPTPVPAAH peptide was selected for further analysis. The sequence was commercially synthesized by solid-phase standard Fmoc chemistry (purity 95–99.9%; by HPLC). The synthetic peptide (IC50 value 8.52 ± 0.779 µg/mL) was used to understand the thermodynamics of the inhibition by checking the binding affinity of the peptide to ACE by isothermal titration calorimetry compared with lisinopril, and the results were further substantiated by in silico site-specific molecular docking analysis. The results demonstrate that this peptide sequence (IIAPTPVPAAH) can be used as a nutraceutical with potent ACE inhibition.