Acid-base Balance Research Articles

#3853 THE EFFECT OF PERITONEAL CAVITY FLUSHING ON ACID BASE BALANCE OF PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Flushing peritoneal cavity with dialysis fluid with short time dwells it is a necessity in some cases for peritoneal dialysis patients. Such cases are overhydration with pulmonary congestion or peritonitis before the initiation of antibiotic treatment as an effort to reduce pain. The aim of this study was to investigate the effect of frequent exchanges with peritoneal dialysis (PD) fluid with bicarbonate as a buffer on acid base balance of peritoneal dialysis patients. Method This is a single center cohort study of 18 stable PD patients (m=10.f=8). Their median age was 57 (47, 71) years, their median PD duration was 33 (16, 89) months and they all fulfill the criteria for achieving adequacy targets [median Kt/V 2.17 (1.99, 3.3)] with good nutrition markers [ median albumin levels 3.9 (3.6, 4) gr/dl]. A sample of arterial blood gas (ABG) was taken from the patients before the procedure and after full drainage of the peritoneal cavity . The procedure included 4 times flushing of 1000 ml of dialysis fluid remaining for15 minutes In the peritoneal cavity each time . At the end of the procedure a new blood sample for ABG was taken. We used PD solution with bicarbonate as a buffer (34 mmol/Lt). We estimated the alterations of pH, of bicarbonate (HCO3-), of pCO2, of Base Excess(ΒΕ), of ionized calcium (iCa++) and lactate (Lac) Results Using the non parametric related samples Wilcoxon signed method we found a statistically significant increase in arterial HCO3- concentration between the values before and after the procedure [HCO3-before:25.4 (22, 28), HCO3after:26.5 (24, 29) mEq/lt-P = .023]. Likewise there was a statistically significant increase in BE with median values before the procedure 1 (-1.2,2.9) and after the flushing 2 (-0.6,3,8), P = .018. Even though there was a statistically significant increase in the bases expression of the acid base balance of the patients there wasn't any statistically significant alterations in pH levels- i.e. Alkalemia (pHbefore=7.41,pHafter=7.42 – P = .35) or pCO2 levels i.e. Compensatory Respiratory Acidosis (pCO2προ=40, pCO2μετα=40 – P = .179) nor to the levels of ionized calcium Conclusion Flushing of peritoneal cavity using peritoneal dialysis solution with bicarbonate as a buffer is safe and in this study was not correlated with the development of metabolic alkalosis

#4178 HYPERCHLOREMIC METABOLIC ACIDOSIS AFTER PLASMAPHERESIS IN A PATIENT WITH RENAL TRANSPLANT REJECTION: A CASE REPORT

Abstract Background and Aims Plasmapheresis is an effective therapeutic intervention for several renal disorders, including renal transplant rejection. However, repeated plasmapheresis can cause various side effects and complications. Method We present a 61-year-old male with a medical history of type 2 diabetes, hypertension, successfully treated multiple myeloma and a post-mortem kidney transplantation 7 months ago. The patient was hospitalized because of rapid deterioration of his renal function (eGFR CKD-EPI 15 ml/min/1.73m2). Renal biopsy of the transplanted kidney confirmed the diagnosis of antibody-mediated transplant rejection. Treatment with methylprednisolone, plasmapheresis with a 40 g/L albumin solution as a replacement fluid and intravenous immunoglobulins was initiated. After 4 plasmapheresis treatments, the patient developed gastrointestinal complaints and muscle weakness. Despite the patient's use of 3 grams of oral sodium bicarbonate supplements a day, laboratory tests revealed a hyperchloremic metabolic acidosis: bicarbonate 11.7 mmol/L, chloride 111 mmol/L, sodium 138 mmol/L. Metabolic acidosis due to citrate accumulation was ruled out with a normal total-to-ionized calcium ratio. After treatment with intravenous bicarbonate supplementation, the symptoms disappeared. Analysis of the albumin plasmapheresis solution showed a chloride concentration of 132 mmol/L. Results This is the first case that describes metabolic acidosis after albumin plasmapheresis in a patient with impaired renal function. The observed hyperchloremic metabolic acidosis is most likely the result of the administration of large volumes (3.5 litres per session) of a 4% albumin solution with high chloride concentrations. We hypothesize that patients with renal impairment are more prone to develop metabolic acidosis after plasmapheresis with albumin-saline replacement fluids due to their reduced renal capacity to excrete excess acid and chloride. Conclusion Special attention should be paid to the acid-base balance during plasmapheresis in patients with impaired renal function. Future research should investigate the incidence of hyperchloremic metabolic acidosis during albumin plasmapheresis in different eGFR categories.

On energetics of proton and electron transfer of selected phenol derivatives: Theoretical investigation of radical and oxonium cations

AbstractIn this paper, the systematic theoretical study of phenol and 36 compounds representing various ortho, meta and para‐substituted (R‐PhOH) phenols is presented. The hydroxyl group acidity is a characteristic feature of phenol which can be modified using substitution of phenyl ring. The proton‐coupled electron transfer was investigated for parent neutral phenols, R‐PhOH, their cation radicals, R‐PhOH+•, and oxonium cations, R‐PhOH2+. Density functional theory calculations were combined with solvent continuum model for water and dimethyl sulfoxide environment. For aqueous solution, the Pourbaix diagrams (electrochemical potential vs. pH) were constructed from the theoretically predicted acidity constants and electrochemical standard potentials. From the thermodynamic point of view, the obtained theoretical results allow the estimation of the thermodynamically preferred process and alternative reaction pathways of phenolic derivatives in very acidic media.

Predictive Potential of Acido-Basic Properties, Solubility and Food on Bioequivalence Study Outcome: Analysis of 128 Studies.

Risk assessment related to bioequivalence study outcome is critical for effective planning from the early stage of drug product development. The objective of this research was to evaluate the associations between solubility and acido-basic parameters of an active pharmaceutical ingredient (API), study conditions and bioequivalence outcome. We retrospectively analyzed 128 bioequivalence studies of immediate-release products with 26 different APIs. Bioequivalence study conditions and acido-basic/solubility characteristics of APIs were collected and their predictive potential on the study outcome was assessed using a set of univariate statistical analyses. There was no difference in bioequivalence rate between fasting and fed conditions. The highest proportion of non-bioequivalent studies was for weak acids (10/19 cases, 53%) and neutral APIs (23/95 cases, 24%). Lower non-bioequivalence occurrence was observed for weak bases (1/15 cases, 7%) and amphoteric APIs (0/16 cases, 0%). The median dose numbers at pH1.2 and pH3 were higher and the most basic acid dissociation constant (pKa) was lower in the non-bioequivalent group of studies. Additionally, APIs with low calculated effective permeability (cPeff) or low calculated lipophilicity (clogP) had lower non-bioequivalence occurrence. Results of the subgroup analysis of studies under fasting conditions were similar as for the whole dataset. Our results indicate that acido-basic properties of API should be considered in bioequivalence risk assessment and reveal which physico-chemical parameters are most relevant for the development of bioequivalence risk assessment tools for immediate-release products.

Understanding the Transition from High-Selective to High-Efficient Chiral Separations by Changing the Organic Modifier with Zwitterionic-Teicoplanin Chiral Stationary Phase.

The retention behavior of small molecules and N-protected amino acids on a zwitterionic teicoplanin chiral stationary phase (CSP), prepared on superficially porous particles (SPPs) of 2.0 μm particle diameter, has shown that efficiency and enantioselectivity, and so enantioresolution, dramatically change depending on the employed organic modifier. In particular, it was found that while methanol permits the boost of enantioselectivity and resolution of the amino acids, at the cost of efficiency, acetonitrile allows for the ability to reach extraordinary efficiency even at high flow rates (with reduced plate height <2 and up to 300,000 plates/m at the optimum flow rate). To understand these features, an approach based on the investigation of mass transfer through the CSP, the estimation of the binding constants of amino acids on the CSP, and the assessment of compositional properties of the interfacial region between bulk mobile phase and solid surface has been adopted.

Renal Oxygen Demand and Nephron Function: Is Glucose a Friend or Foe?

The kidneys and heart work together to balance the body's circulation, and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidneys physiology are primarily designed to maintain a stable metabolic rate and have a limited capacity to cope with any steep increase in renal metabolism. In the kidneys, glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances, including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of the renal glucose transport in disease states provides a better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance, glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

Halochromic properties of new nitrophenol-based azochromophores

A number of new azo dyes were synthesized using azo-coupling of nitrohydroxyphenols (2-nitroresorcinol and nitrophloroglicinol) with ortho-aminophenol and its nitro- and sulfonic-substituted derivatives. The dye molecules contain multiple hydroxy groups which can be easily deprotonated, and their ionization affects the conjugated π-electron system of the dye molecule leading to the significant spectral changes. Spectrophotometric titration of the obtained dyes with an acid and an alkali revealed their halochromic behaviour, i.e. an ability to alter color upon pH change. All the dyes absorb light with wavelength shorter 500 nm in acidic media, and with wavelength longer 500 nm in alkaline media. Variation of substituents in the dye molecules allows to tune the pH range of the color change. The obtained dye series covers the pH range from 0 to 10. DFT calculations of the dye molecules revealed their structures and preferential isomeric forms. TD-DFT calculations of the excited states allowed to clarify the acid-base equilibrium based on the spectrophotometric titration, and to determine the nature of the observed absorption bands. The dyes were adsorbed on polyamide fabrics, and the dyed fabrics reversibly changed their color upon treating with acids and alkalis. These fabrics with applied dyes showed good resistance to aggressive environments and mechanical influences. Results of tests of the dyed fabrics showed that the obtained materials can be used as flexible textile pH sensors.

Clinical Overview and Treatment of Hypokalemia in Pediatric Patients: A Narrative Literature Review

Hypokalemia is a condition in which the blood potassium levels are below the normal range, which is typically between 3.5 and 5.0 mEq/L. Potassium is an essential electrolyte that plays a critical role in many physiological processes in the body, including nerve and muscle function, heart rhythm, and acid-base balance. This literature review aimed to describe the clinical and current management aspects of hypokalemia in pediatric patients. The pathophysiology of hypokalemia involves a disturbance in the balance of potassium in the body, which can occur due to several mechanisms, including reduced intake of potassium-rich foods, increased loss of potassium, and redistribution of potassium. In children, clinical symptoms of hypokalemia may include weakness and fatigue, abdominal discomfort, cardiac symptoms, respiratory symptoms, neurological symptoms, polyuria, and renal symptoms. There are several diseases and conditions that can cause hypokalemia in children, including renal tubular acidosis, prolonged diarrhea, cystic fibrosis, hyperaldosteronism, malnutrition, medication, type 1 Bartter syndrome, type 2 Bartter syndrome, and Liddle syndrome. Some options for hypokalemia treatment are potassium supplements, a potassium-rich diet, intravenous potassium, and treating underlying conditions. In conclusion, hypokalemia is an overview of the underlying disease and requires immediate management. Understanding the pathophysiology of hypokalemia will increase the accuracy of diagnosis and accelerate hypokalemia intervention in children, as well as prevent complications due to hypokalemia.

Distinct Alterations in Oxygenation, Ion Composition and Acid-Base Balance in Cerebral Collaterals During Large-Vessel Occlusion Stroke

PurposeDisturbances of blood gas and ion homeostasis including regional hypoxia and massive sodium (Na+)/potassium (K+) shifts are a hallmark of experimental cerebral ischemia but have not been sufficiently investigated for their relevance in stroke patients.MethodsWe report a prospective observational study on 366 stroke patients who underwent endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) of the anterior circulation (18 December 2018–31 August 2020). Intraprocedural blood gas samples (1 ml) from within cerebral collateral arteries (ischemic) and matched systemic control samples were obtained according to a prespecified protocol in 51 patients.ResultsWe observed a significant reduction in cerebral oxygen partial pressure (−4.29%, paO2ischemic = 185.3 mm Hg vs. paO2systemic = 193.6 mm Hg; p = 0.035) and K+ concentrations (−5.49%, K+ischemic = 3.44 mmol/L vs. K+systemic = 3.64 mmol/L; p = 0.0083). The cerebral Na+:K+ ratio was significantly increased and negatively correlated with baseline tissue integrity (r = −0.32, p = 0.031). Correspondingly, cerebral Na+ concentrations were most strongly correlated with infarct progression after recanalization (r = 0.42, p = 0.0033). We found more alkaline cerebral pH values (+0.14%, pHischemic = 7.38 vs. pHsystemic = 7.37; p = 0.0019), with a time-dependent shift towards more acidotic conditions (r = −0.36, p = 0.055).ConclusionThese findings suggest that stroke-induced changes in oxygen supply, ion composition and acid-base balance occur and dynamically progress within penumbral areas during human cerebral ischemia and are related to acute tissue damage.

Defining Physiological Ketosis Following Very-Low-Calorie Diets

IntroductionVery low-calorie diets (VLCDs) are used preoperatively in bariatric-metabolic surgery; however, this can lead to physiological ketosis. Euglycemic ketoacidosis is an increasingly recognized complication in diabetic patients on sodium-glucose-cotransporter-2 inhibitors (SGLT2i) undergoing surgery and requires assessment of ketones for diagnosis and monitoring. VLCD induced ketosis may confound monitoring in this group. We aimed to evaluate the influence of VLCD, compared to standard fasting, on perioperative ketone levels and acid-base balance. Materials and methodsTwenty-seven patients were prospectively recruited to the intervention group and 26 to the control group from two tertiary referral centres in Melbourne, Australia. Intervention group patients were severely obese (body mass index) (BMI) (≥35), undergoing bariatric-metabolic surgery, and prescribed 2 wk of VLCD preoperatively. Control group patients underwent general surgical procedures and prescribed standard procedural fasting only. Patients were excluded if diabetic or prescribed SGLT2i. Ketone and acid-base measurements were taken at regular intervals. Univariate and multivariate regression was utilised with significance defined as P < 0.005. ClinicalTrials.gov ID: NCT05442918. ResultsPatients on VLCD, compared to standard fasting, had an increased median preoperative (0.60 versus 0.21 mmol/L), immediate postoperative (0.99 versus 0.34 mmol/L) and day 1 postoperative (0.69 versus 0.21 mmol/L) ketone level (P < 0.001). Preoperative acid-base balance was normal in both groups, however VLCD patients were found to have a metabolic acidosis immediately postoperatively (pH 7.29 versus pH 7.35) (P = 0.019). Acid-base balance had normalized in VLCD patients on postoperative day 1. ConclusionsPreoperative VLCD resulted in increased pre- and postoperative ketone levels with immediate postoperative values consistent with metabolic ketoacidosis. This should be considered particularly when monitoring diabetic patients prescribed SGLT2i.

BIO12: Toward a Wearable Extracorporeal CO2 Removal System with Integrated Exhaust Gas CO2 Sensing

Purpose: Extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R) have been used frequently in the last ten years to treat patients with severe respiratory failure. These therapeutic strategies mitigate the complications associated with invasive mechanical ventilation. Further, concurrent ambulatory and physical therapy is demonstrated to improve patient outcomes, reduce hospital cost, and enhance patient quality-of-life. However, the complexity of these extracorporeal systems and rapid changes in patient metabolism and acid-base balance complicate logistics for ambulation. Here we present a wearable ECCO2R system with exhaust gas CO2 (EGCO2) sensing capabilities. Methods: The wearable ECCO2R system (Fig 1) integrates a blower module, a membrane oxygenator optimized for CO2 removal (MLung), and an exhaust module. Two redundant blowers push air through a flow sensor, to maintain fixed flow rates, then through the MLung. A CO2 sensor (STC31) in the exhaust module senses MLung EGCO2. It is preceded by a water trap, sampling pump, Nafion tubing, and heater which remove moisture and protect the STC31. Pressure sensors record the gas-side pressure drop of the MLung. First, control of sweep flow and CO2 sensing were tested individually. The blower module was attached to the MLung and commanded to maintain a set of target flows. The exhaust module was directly fed compressed CO2 and N2 to ensure it could measure a range of CO2 concentrations. Finally, as a system in-vitro test (Fig 2), the device was electronically integrated and connected to a conditioning lung fed by compressed CO2 and N2. The CO2 concentration in the sweep gas of the conditioning lung was varied to simulate metabolic changes. Results: The assembled device measures 23x20x8 cm and weighs 1.4 kg (with primed MLung and tubing; without batteries). The device quickly (<2s) attained target sweep up to 4 L/min (Fig 3A), and has a maximum sweep flow of 7 L/min with the MLung. It measured EGCO2 for all values tested (Fig 3B; up to 50 mmHg; <1 mmHg error). During the system test with water, the ECCO2R system was able to qualitatively detect changes in EGCO2 caused by the simulated metabolic changes. Conclusion: We present progress toward the first wearable ECCO2R system. Its integrated CO2 sensing makes it a suitable platform for future use as the first ECCO2R with closed-loop feedback control to automatically respond to the respiratory needs of the patient.Figure 1. (A) Blower module showing internals. (B): Sensor module; most components are enclosed. (C) Rendering of system on a patient, with arteriovenous access to the subclavian a. and v.Figure 2. System-level test setup. Blue arrows denote gas flows, and red arrows denote water flows (water is used as an analog for blood). In this test, compressed CO2 was fed into the conditioning lung. The CO2 was dissolved into the circulating water, and then removed by the MLung. Finally, it went to the exhaust module.Figure 3. (A) The device quickly attains desired sweep flows. It has a 7 L/min maximum flow rate when used with the MLung. (B) With a 2-point calibration, the device accurately (<1mmHg) measures CO2 in a gas stream, in reference to an arterial-blood-gas machine.

Application of blood purification technology in severe fever with thrombocytopenia syndrome

ABSTRACT Objective: The purpose of this paper is to summarize the blood purification technology applied in patients with severe fever with thrombocytopenia syndrome (SFTS) in the clinical treatment effect. Methods: The medical records of 96 patients with severe SFTS admitted to Weihai Municipal Hospital affiliated to Shandong University from May 2014 to November 2019 were retrospectively analyzed, and they were divided into survival group and death group. The differences in basic data test indexes and treatment method selection during intensive care unit (ICU) admission between the two groups were significantly analyzed, and the indexes with statistically significant differences were included in the multivariate logistic regression analysis related to prognosis. Results: There were no statistically significant differences in age, sex composition, white blood cell count, platelet count, creatine kinase (CK), activated partial thromboplastin time (APTT), serum creatinine and hemofiltration renal replacement therapy between the survival group and the death group. There were statistically significant differences between the two groups in viral load bilirubin and the treatment methods of plasma exchange (PE) or hemoperfusion (HP). Plasma exchange group (78 cases), hemofiltration group (12 cases), hemoperfusion group (6 cases), plasma exchange and hemoperfusion and other blood purification treatment of the prognosis were statistically different. Conclusions: Compared with the three blood purification methods, plasmapheresis has a significant effect on virus removal, improvement of coagulation function and survival rate in patients with severe SFTS. Hemofiltration plays a role in removing inflammatory mediators, replacing renal function, maintaining electrolytes and acid-base balance, but not in removing viruses.

Investigation on water resistance of basic magnesium sulfate cement containing weak organic acids

Magnesium oxysulfate cement has low strength and poor water resistance, so an additive is essential for the preparation of basic magnesium sulfate cement (BMSC). In this paper, the effects and the mechanisms of three organic weak acids on the water resistance in relation to flexural strength of BMSC are investigated. The results show that malic acid fails to ameliorate the water resistance in relation to flexural strength, but citric acid and tartaric acid are successful. The ionisation constant and molecular formulas of different weak organic acids can affect the performance, such as fluidity, strength and water resistance. Therefore, the effect of citric acid is better than tartaric acid, and the optimal dosage of citric acid is 1.0%.

Prediction of alkaline earth metal ion adsorption on goethite for various background electrolytes with the CD-MUSIC model

As water scarcity drives the use of more saline water sources, contaminant fate and transport models must capture the impact of high concentrations of alkaline earth metal ions (AEMs) and background electrolytes in these more complex waters. By utilizing macroscopic adsorption data from various electrolyte systems, a Charge Distribution – Multisite Complexation (CD-MUSIC) model, capable of incorporating electrolyte adsorption, was able to accurately simulate the adsorption behavior of alkaline earth metal ions onto goethite. The modeling effort was guided by previous spectroscopic and surface complexation modeling of alkaline earth metal adsorption and built on previous CD-MUSIC modeling that accounted for changes in crystal face contributions to the surface site density as a function of specific surface area. The model was constrained to consider only two dominant surface complex species for each metal ion adsorption reaction. These two species were selected from 44 possible species through objective curve fitting of single-solute macroscopic adsorption data. While most of the alkaline earth metal surface complexes formed outer-sphere complexes at the goethite surface, an inner-sphere species was utilized for Mg2+. With the surface complex species and equilibrium constants obtained from this study, the calibrated model successfully predicted alkaline earth metal ion adsorption over a wide range of solution and surface conditions; the model predictions encompassed a wide range of pH (5–11), solute/solid ratio (1.37 × 10−5– 8.33 × 10−4 mol-solute/g-solid), ionic strengths (0.01 M – 0.7 M), and background electrolytes (Na+, Cs+, Rb+, Cl−, and NO3−) using the same crystal face contribution methodology for site density, capacitance values, and surface acidity constants adopted for proton and cadmium adsorption in previous work (Han and Katz, 2019). Model simulations for a range of background water chemistries demonstrated the potential for Mg2+ to reduce Cd2+ adsorption to goethite in model seawater and oil- and gas-produced waters.

The AE4 transporter mediates kidney acid-base sensing

The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl−/HCO3− exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl−/HCO3− exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.

Proton solvation: competition between acetone and dimethyl sulfoxide

This paper presents results of quantum-chemical study of proton exchange equilibrium between acetone (AC) and dimethyl sulfoxide (DMSO). Basing on the previous study of acid-base equilibria in AC with small additives of DMSO, the most probable composition of the lyonium ion is taken as H(DMSO)2+. The equilibrium geometries and energies of solvents molecules and all possible combinations of proton complexes with one or two solvent molecules were calculated in DFT level of theory using B3LYP functional and 6-31G++(d,p) basis set. The energies of solvated proton complexes were then calculated using PCM method. The energy change corresponding to the equilibrium H(AС)2+ + 2 DMSO ⇄ H(DMSO)2+ + 2 AС is –63.1 kJ mol–1 in the gas phase, which is in qualitative agreement with the standard Gibbs energy data, obtained experimentally in the gas phase by Kebarle’s group, –77.6 kJ mol–1, and with ΔGo298 = –49.3 kJ mol–1 for AC solution with small additions of DMSO, determined by the Guss and Kolthoff method.

Anti‐inflammatory Potential of 1,4‐Naphthoquinone Acyl Thiourea Hybrids on Lipopolysaccharide‐Activated Mammalian Macrophages, and Their Acid Dissociation Constants

AbstractIn this study, seven new and known 1,4‐naphthoquinone acyl thiourea hybrids were synthesized and their molecular structures were confirmed by various analytical methods. These derivatives were tested for their anti‐inflammatory potential on the murine macrophages. Pro‐inflammatory cytokine production levels and cell viabilities were compared between the groups and with LPS positive control groups to determine the most potent anti‐inflammatory drug candidate. Our results suggest that these derivatives had anti‐inflammatory activity without exerting major cytotoxicity. Their future evaluation in inflammatory and autoimmune disease settings will be crucial for their possible utilization in the clinical setting. The acid dissociation constants of synthesized hybrids 1–7 were determined potentiometrically at 25.0±0.1 °C, at an ionic strength of 0.1 M NaCl in 20 % (v/v) DMSO – water hydro‐organic solvent mixture in an acidic medium. Three acid dissociation constants were calculated for each hybrid with the HYPERQUAD computer program using the data obtained as a result of potentiometric titrations under the specified conditions.

Effect of Acidic Strength of Surface Ligands on the Carrier Relaxation Dynamics of Hybrid Perovskite Nanocrystals.

Perovskite nanocrystals (PeNCs) are known for their use in numerous optoelectronic applications. Surface ligands are critical for passivating surface defects to enhance the charge transport and photoluminescence quantum yields of the PeNCs. Herein, we investigated the dual functional abilities of bulky cyclic organic ammonium cations as surface-passivating agents and charge scavengers to overcome the lability and insulating nature of conventional long-chain type oleyl amine and oleic acid ligands. Here, red-emitting hybrid PeNCs of the composition CsxFA(1-x)PbBryI(3-y) are chosen as the standard (Std) sample, where cyclohexylammonium (CHA), phenylethylammonium (PEA) and (trifuluoromethyl)benzylamonium (TFB) cations were chosen as the bifunctional surface-passivating ligands. Photoluminescence decay dynamics showed that the chosen cyclic ligands could successfully eliminate the shallow defect-mediated decay process. Further, femtosecond transient absorption spectral (TAS) studies uncovered the rapidly decaying non-radiative pathways; i.e., charge extraction (trapping) by the surface ligands. The charge extraction rates of the bulky cyclic organic ammonium cations were shown to depend on their acid dissociation constant (pKa) values and actinic excitation energies. Excitation wavelength-dependent TAS studies indicate that the exciton trapping rate is slower than the carrier trapping rate of these surface ligands.

Substituted furan sulfonamides as carbonic anhydrase inhibitors: Synthesis, biological and in silico studies

Carbonic Anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide involved in several of biological processes, such as respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show wide diversity in tissue distribution and in their subcellular localization. Fifteen novel furyl sulfonamides were designed, synthesized and evaluated against four human isoforms: hCA I, hCA II, hCA IV and hCA IX. Compounds appeared to be very active mostly against hCAI (8) and hCA IV (11) isoforms being more potent than reference drug acetazolamide (AAZ). It should be mentioned that four compounds were more active than AAZ against hCA IX isoform, with compound 13d to be selective against hCA I (SI 70), hCA II (SI 13.5) and hCA IV (SI 20). Furthermore, docking was performed for some of these compounds on all isoforms I order to understand the possible interactions with the active site. The most active compounds showed good bioavailability and drug likeness scores.

Structure, Stability, and Acidity of the Uranyl Arsenate Dimer in Aqueous Solution.

The migration of uranium (U) in the surficial environment has received considerable attention. Due to their high natural abundance and low solubility, autunite-group minerals play a key role in controlling the mobility of U. However, the formation mechanism for these minerals has yet to be understood. In this work, we took the uranyl arsenate dimer ([UO2(HAsO4)(H2AsO4)(H2O)]22-) as a model molecule and carried out a series of first-principles molecular dynamics (FPMD) simulations to explore the early stage of the formation of trögerite (UO2HAsO4·4H2O), a representative autunite-group mineral. By using the potential-of-mean-force (PMF) method and vertical energy gap method, the dissociation free energies and the acidity constants (pKa's) of the dimer were calculated. Our results show that the U in the dimer holds a 4-coordinate structure, which is consistent with the coordination environment observed in trögerite mineralogy, in contrast to the 5-coordinate U in the monomer. Furthermore, the dimerization is thermodynamically favorable in solution. The FPMD results also suggest that tetramerization and even polyreactions would occur at pH > 2, as observed experimentally. Additionally, it is found that trögerite and the dimer have very similar local structural parameters. These findings imply that the dimer could serve as an important link between the U-As complexes in solution and the autunite-type sheet of trögerite. Given the nearly identical physicochemical properties of arsenate and phosphate, our findings suggest that uranyl phosphate minerals with the autunite-type sheet may form in a similar manner. This study therefore fills a critical gap in atomic-scale knowledge of the formation of autunite-group minerals and provides a theoretical basis for regulating uranium mobilization in P/As-bearing tailing water.