Impact of non-ideality on reconstructing spatial and temporal variations in aerosol acidity with multiphase buffer theory

Aerosol acidity is a key parameter in atmospheric aqueous chemistry and strongly influences the interactions of air pollutants and the ecosystem. The recently proposed multiphase buffer theory provides a framework to reconstruct long-term trends and spatial variations in aerosol pH based on the effective acid dissociation constant of ammonia (Ka,NH3∗). However, non-ideality in aerosol droplets is a major challenge limiting its broad applications. Here, we introduced a non-ideality correction factor (cni) and investigated its governing factors. We found that besides relative humidity (RH) and temperature, cni is mainly determined by the molar fraction of NO3- in aqueous-phase anions, due to different NH4+ activity coefficients between (NH4)2SO4- and NH4NO3-dominated aerosols. A parameterization method is thus proposed to estimate cni at a given RH, temperature and NO3- fraction, and it is validated against long-term observations and global simulations. In the ammonia-buffered regime, with cni correction, the buffer theory can reproduce well the Ka,NH3∗ predicted by comprehensive thermodynamic models, with a root-mean-square deviation ∼ 0.1 and a correlation coefficient ∼ 1. Note that, while cni is needed to predict Ka,NH3∗ levels, it is usually not the dominant contributor to its variations, as ∼ 90 % of the temporal or spatial variations in Ka,NH3∗ are due to variations in aerosol water and temperature.

Concentration effect of Sodium Chloride Salt on Benzoic Acid Solubility and Dissociation into Water at 298 K Temperature

In article, we have been reported the study of a concentration effect of sodium chloride (NaCl) salt on benzoic acid solubility and its dissociation in water at 298 K temperature. At this temperature the benzoic acid solubility into water and their dissociation value for six samples in range of 0.00, 0.05, 0.10, 0.30, 0.40 and 0.50 M. Each of these different ionic strength or concentration of sodium chloride is analyzed by titrimetrically against of 0.05 M sodium hydroxide (NaOH) basic solution. The pH of each solution is measured well by using of calibrated pH-meter. Observation reveals that the value of pH of benzoic acid into water at applying temperature is may inversely related with concentration of NaCl. Graphically, the value of ionic strength (I) of that benzoic acid is plotted versus with dissociation constant (Kc) of acid into water at specific 298 K temperature. The value of benzoic acid dissociation constant for given each six concentration of NaCl is found to be -4.169, -4.045, -3.993, -3.885, -3.848 and -3.788, respectively.

Physical compatibility of Normosol-R with critical care medications used in patients with COVID-19 during simulated Y-site administration

Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Guidelines from the National Institutes of Health support the use of balanced crystalloid solutions such as Normosol-R (Hospira, Lake Forest, IL) for patients with coronavirus disease 2019 (COVID-19). However, their clinical utility is hindered by a lack of Y-site compatibility data that is essential for use in patients with limited intravenous access. The objective of this study was to determine the physical compatibility of selected intensive care unit medications with Normosol-R. Methods The study involved laboratory simulation of Y-site compatibility. Medications tested included amiodarone, caspofungin, dexmedetomidine, dobutamine, dopamine, epinephrine, levofloxacin, norepinephrine, pantoprazole, phenylephrine, piperacillin/tazobactam, vancomycin, and vasopressin. Tests performed were visual assessment with Tyndall light, turbidity measurement, and pH assessment. Tests were performed immediately after mixing (with the exception of turbidity testing) and after 1 hour and 4 hours. Results Incompatibility was defined as observation of haze, gas, particulate, or color change or admixture turbidity above 0.3 or above 0.5 nephelometric turbidity unit (NTU), depending on whether the baseline turbidity was less than or greater than 0.5 NTU, respectively. Analysis of solubility and compatibility based on change from baseline to admixture pH in relation to reported acid dissociation constant (pKa) was performed. There was no evidence of visual incompatibility for any of the admixtures when mixed with Normosol-R. Turbidity exceeded the defined threshold with pantoprazole, phenylephrine, and highly concentrated norepinephrine. Pantoprazole was the only test medication with a significant pH change when compared to its pKa. Conclusion Normosol-R is compatible for Y-site administration with all tested medications except for pantoprazole, phenylephrine, and highly concentrated norepinephrine, allowing for potential increased use in patients with COVID-19.

Prediction of n-octanol/water partition coefficients and acidity constants (pKa) in the SAMPL7 blind challenge with the IEFPCM-MST model

Within the scope of SAMPL7 challenge for predicting physical properties, the Integral Equation Formalism of the Miertus-Scrocco-Tomasi (IEFPCM/MST) continuum solvation model has been used for the blind prediction of n-octanol/water partition coefficients and acidity constants of a set of 22 and 20 sulfonamide-containing compounds, respectively. The log P and pKa were computed using the B3LPYP/6-31G(d) parametrized version of the IEFPCM/MST model. The performance of our method for partition coefficients yielded a root-mean square error of 1.03 (log P units), placing this method among the most accurate theoretical approaches in the comparison with both globally (rank 8th) and physical (rank 2nd) methods. On the other hand, the deviation between predicted and experimental pKa values was 1.32 log units, obtaining the second best-ranked submission. Though this highlights the reliability of the IEFPCM/MST model for predicting the partitioning and the acid dissociation constant of drug-like compounds compound, the results are discussed to identify potential weaknesses and improve the performance of the method.

Impact of non-ideality on reconstructing spatial and temporal variations of aerosol acidity with multiphase buffer theory

Aerosol acidity is a key parameter in atmospheric aqueous chemistry and strongly influence the interactions of air pollutants and ecosystem. The recently proposed multiphase buffer theory provides a framework to reconstruct long-term trends and spatial variations of aerosol pH based on the effective acid dissociation constant of ammonia (Ka,NH3*). However, non-ideality in aerosol droplets is a major challenge limiting its broad applications. Here, we introduced a non-ideality correction factor (cni) and investigated its governing factors. We found that besides relative humidity (RH) and temperature, cni is mainly determined by the molar fraction of NO3− in aqueous-phase anions, due to different NH4+ activity coefficients between (NH4)2SO4− and NH4NO3-dominated aerosols. A parameterization method is thus proposed to estimate cni at given RH, temperature and NO3− fraction, and is validated against long-term observations and global simulations. In the ammonia-buffered regime, with cni correction the buffer theory can well reproduce the Ka,NH3* predicted by comprehensive thermodynamic models, with root-mean-square deviation ~0.1 and correlation coefficient ~1. Note that, while cni is needed to predict Ka,NH3* levels, it is usually not the dominant contributor to its variations, as ~90 % of the temporal or spatial variations in Ka,NH3* is due to variations in aerosol water and temperature.

The impact of non-ideality on reconstructing spatial and temporal variations of aerosol acidity with multiphase buffer theory

<p>Aerosol acidity is a key parameter in atmospheric aqueous chemistry and strongly influence the interactions of air pollutants and ecosystem. The recently proposed multiphase buffer theory provides a framework to reconstruct long-term trends and spatial variations of aerosol pH based on the effective acid dissociation constant of ammonia (K<sub>a,NH3</sub><sup>*</sup>). However, non-ideality in aerosol droplets is a major challenge limiting its broad applications. Here, we introduced a non-ideality correction factor (c<sub>ni</sub>) and investigated its governing factors. We found that besides relative humidity (RH) and temperature, c<sub>ni</sub> is mainly determined by the molar fraction of NO<sub>3</sub><sup>-</sup> in aqueous-phase anions, due to different NH<sub>4</sub><sup>+</sup> activity coefficients between (NH<sub>4</sub>)<sub>2</sub>SO<sub>4</sub>- and NH<sub>4</sub>NO<sub>3</sub>-dominated aerosols. A parameterization method is thus proposed to estimate c<sub>ni</sub> at given RH, temperature and NO<sub>3</sub><sup>-</sup> fraction, and is validated against long-term observations and global simulations. In the ammonia-buffered regime, with c<sub>ni</sub> correction the buffer theory can well reproduce the K<sub>a,NH3</sub><sup>*</sup> predicted by comprehensive thermodynamic models, with root-mean-square deviation ~0.1 and correlation coefficient ~1. Note that, while c<sub>ni</sub> is needed to predict K<sub>a,NH3</sub><sup>*</sup> levels, it is usually not the dominant contributor to its variations, as ~90% of the temporal or spatial variations in K<sub>a,NH3</sub><sup>*</sup> is due to variations in aerosol water and temperature.</p>

Synthesis, Molecular Docking, BSA, and in-vitro reactivation study of imidazopyridine oxime against paraoxon inhibited acetylcholinesterase

Aim: To synthesize and evaluate the fused heterocyclic imidazopyridine oxime as a reactivator against paraoxon inhibited acetylcholinesterase. Background: Organophosphorus compounds (OPs) include parathion, malathion, chlorpyrifos, monocrotophos, and diazinon which are commonly used in agriculture for enhancing agricultural productivity via killing crop-damaging pests. However, people may get exposed to OPs pesticides unintentionally/intentionally via ingestion, inhalation or dermal. The current treatment regimen includes reactivator such as mono or bis-pyridinium oximes along with anticholinergic and an anticonvulsant drugs are recommended for the treatment of OP poisoning. Unfortunately, the drawback of the existing reactivator is that owing to the permanent charge present on the pyridinium makes them inefficient to cross the blood-brain barrier (BBB) and reactivate OP-inhibited central nervous system (CNS) acetylcholinesterase. Therefore, there is a need of reactivator that could cross the BBB and reactivate the OP inhibited acetylcholinesterase. Objective: The objectives of the study were synthesis, molecular docking, BSA binding and in-vitro estimation of oximes of various substituted imidazo [1,2-a]pyridine against paraoxon inhibited acetylcholinesterase. Method: The reactivators were synthesized in three steps and characterized using various spectroscopic techniques. Molecular docking study was performed on 2WHP and 3ZLV PDB using Autodock tool. The acid dissociation constant (pKa) of oximes was calculated experimentally and drug-likeness properties of the oximes were calculated In silico using mole inspiration and Swiss ADME software. The binding of oximes with bovine serum albumin (BSA) was also investigated by UV-Vis spectrophotometer. The reactivation potential of the oximes was determined by in vitro enzymatic assay. Result: in-silico study inferred that synthesized molecules fulfilled the parameters that required for a successful CNS drug candidate. Further, in-vitro enzymatic assay indicated reasonable reactivation potential of the oximes against paraoxon-inhibited AChE. The binding of oximes with bovine serum albumin (BSA) revealed static quenching of intrinsic fluorescence of BSA by oxime. The binding constant value and number of binding sites were found 0.24 mol-1 and 1 respectively. Conclusion: The results of study concluded that this scaffold could be used for further designing of more efficient uncharged reactivators.