Structural implications of SARS-CoV-2 Surface Glycoprotein N501Y mutation within receptor-binding domain [499-505]–computational analysis of the most frequent Asn501 polar uncharged amino acid mutations

The aim of this study was to evaluate the impact of the most frequent Asn501 polar uncharged amino acid mutations upon important structural properties of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Surface Glycoprotein RBD–hACE2 (human angiotensin-converting enzyme 2) heterodimer. Mutations N501Y, N501T and N501S were considered and their impact upon complex solubility, secondary motifs formation and intermolecular hydrogen bonding interface was analyzed. Results and findings are reported based on 50 ns run in Gromacs molecular dynamics simulation software. Special attention is paid on the biomechanical shifts in the receptor-binding domain (RBD) [499-505]: ProThrAsn(Tyr)GlyValGlyTyr, having substituted Asparagine to Tyrosine at position 501. The main findings indicate that the N501S mutation increases SARS-CoV-2 S-protein RBD–hACE2 solubility over N501T, N501 (wild type): (Formula presented.), (Formula presented.). The N501Y mutation shifts (Formula presented.) -helix S-protein RBD [366-370]: SerValLeuTyrAsn into π-helix for t > 38.5 ns. An S-protein RBD [503-505]: ValGlyTyr shift from (Formula presented.) -helix into a turn is observed due to the N501Y mutation in t > 33 ns. An empirical proof for the presence of a Y501-binding pocket, based on RBD [499-505]: PTYGVGY (Formula presented.) 's RMSF peak formation is presented. There is enhanced electrostatic interaction between Tyr505 (RBD) phenolic -OH group and Glu37 (hACE2) side chain oxygen atoms due to the N501Y mutation. The N501Y mutation shifts the (Formula presented.) hydrogen bond into permanent polar contact;(Formula presented.);(Formula presented.). © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Amorphous Solid Dispersion of Niclosamide with Water-Soluble β-Cyclodextrins for Dissolution and Bioavailability Enhancement

Cyclodextrins (CDs) are cyclic oligosaccharides widely employed for the solubility enhancement of poorly water-soluble drugs. Niclosamide is a BCS class II drug for tapeworm infections and is currently under repurposing for various other indications, including COVID-19. Due to its low aqueous solubility, a high daily dose (2 g) is required for clinical efficacy. Herein, we investigate the potential of beta-cyclodextrin (β-CD) and its sulfobutylether and hydroxypropyl derivatives for the dissolution enhancement of niclosamide. The solid dispersions were prepared by kneading the drug and cyclodextrins together by adding solvent, water: methanol (1 : 1 v/v). Among various CDs studied, 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) in the 1: 2 molar ratio (SB-IC-N4 batch) shows the most significant improvement in water solubility of niclosamide (6.3 vs. 182 μg/ml), resulting in 2-fold improved in-vitro dissolution. The comparative oral pharmacokinetics in Wistar rats at 50 mg/kg produced 1.69-fold higher plasma exposure of niclosamide. The spectral characterization provided molecular insights into interactions of niclosamide with HP-β-CD. These results suggest that the dispersion of niclosamide with HP-β-CD aid in faster dissolution and better drug bioavailability. © 2023 Wiley-VCH GmbH.

Antimicrobial Activity: Different Mechanistic Elucidation of Antibacterial, Antiviral, Antifungal & Antialgae Agents

In recent days, the increasing number of microbes and their increasing resistance power against conventional drugs have led to enormous worldwide mortalities, hence they pose a great threat to human health. The modern era is already going through the threat of COVID-19, also caused by one of those microbes called the virus. In order to get a clear understanding, all the microbes have been classified in certain types. Nowadays, to develop new alternative antimicrobial medicines, scientists must acquire clarity about the responsible functional groups of different conventional drugs with proper mechanistic elucidation on different types of microbes. This information not only clarifies the functionalities and properties responsible for exhibiting antimicrobial effects, but also facilitates the idea of new drug development through proper functional group incorporation or modification. These modifications increase the efficacy of antimicrobial drugs as well as their activity and water solubility. In this review, my focus will majorly be on the four main types of microbes and their possible mechanistic elucidation of commonly used antibiotics and alternative antimicrobial medicines discovered till now. I thank the Science and Engineering Research Board (SERB), Council of Scientific and Industrial Research (CSIR), and Government of India for my fellowship and research grants during my Ph.D in Indian Institute of Science Education and Research, Kolkata and Postdoctoral journey in the University of Burdwan. I acknowledge Prof. Bimalendu Ray (Chemistry department, The University of Burdwan), Prof. Priyadarsi De, (Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata), Prof. Punyasloke Bhadury (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata), Dr. Anwesha Ghosh (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata) for many helpful discussions and laboratory use.Copyright © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research.

Thioester Electrophiles as a New Class of SHAPE Probes

RNA is a multifunctional molecule capable of regulating gene expression, in large part because it can form a variety of RNA secondary and tertiary structures. The emergence of RNA viruses like SARS-CoV-2 emphasizes the need to accelerate our understanding of how viral RNA structure dictates its function. One approach to map RNA secondary structure, called Selective 2'-OH Acylation Analyzed by Primer Extension (SHAPE), utilizes select electrophiles that unbiasedly modifies the 2'-hydroxyl of riboses in unpaired nucleotides, forming adducts that are detected through a variety of sequencing methods. While SHAPE is widely utilized, most existing SHAPE reagents suffer from several drawbacks: 1) poor water solubility;2) limited commercial availability;and 3) they function optimally when freshly synthesized, requiring synthetic organic expertise. To overcome these obstacles, our goal is to develop a userfriendly SHAPE reagent kit that provides highly reactive, soluble SHAPE reagents capable of probing RNA structure in vitro as well as in vivo. We present our investigations on developing thioester electrophiles as a new class of SHAPE reagents. Our reagent is prepared by mixing two stable components to generate the reactive thioester electrophile in situ. We report our preliminary results in model systems and the scope to expand the library of our reagents.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Improving properties of baricitinib due to interaction with Pluronic micelles

Baricitinib is a new generation medicinal compound that has been recommended for the treatment of rheumatoid arthritis in 2017 as well as alopecia areata and COVID-19 in 2022. The use of baricitinib is complicated by its poor aqueous solubility and unwanted side effects. Therefore, the aim of this work is an improvement of the baricitinib solubility using Pluronic micelles. The effect of the micelles on the solubility and membrane permeability of baricitinib is revealed using the isothermal saturation method and the Franz diffusion cell, respectively. It was observed that degree of baricitinib solubilization depends on the Pluronics structure and pH. The regularities of the interaction of the drug with the micelles were established by means of light scattering and 1D and DOSY 1H NMR. It was demonstrated that the ionization state of baricitinib, depending on pH, affects the drug ability to be included in the micelles. The most effective solubilizer of baricitinib among the Pluronics under study was proposed. The data obtained may be useful for the development of water-soluble formulations of baricitinib.

Liquid Chromatographic Approach for Analysis of Favipiravir–A Repurpose Drug for COVID-19

Favipiravir is a potential repurpose moiety to treat COVID-19 by depletion of virus load in infectious patients. To analyze and separate Favipiravir with remarkable efficiency, X-Bridge C8 column (150 x 4.6 mm, 5 µ) and a solvent phase of 0.1% TEA and acetonitrile (40:60 v/v) with 1-mL/min flow rate were used. The eluted favipiravir and possible degradants were detected at 225 nm. Further, the process was validated by using ICH (Q2R1) guidelines to ensure the method's suitability in the pharmaceutical sector. The RT of Favipiravir was observed at 3.7 min with good linearity of 2 to 30 µg/mL. %RSD of both system and method precision was assessed in the series of 0.32 to 0.98. The mean percentage recovery of Favipiravir was in the range of 99.0–100.4%. The limit of detection (LoD) and limit of quantification (LoQ) were assessed to be 0.024 and 0.084 μg/mL for favipiravir. The outcomes confirmed that the projected approach was economical, insightful, simple and precise with better sensitivity. Investigation of Favipiravir in the incidence of a variety of stressed or forced degradation environments ensures stability indicating quality of the developed approach. © 2023, Dr. Yashwant Research Labs Pvt. Ltd.. All rights reserved.

Efficacy Evaluation of Silty-Sandy Soil and Chrysopogon zizanioides to Attenuate Doxycycline from Wastewater in a Constructed Wetland System

In recent years, the emergence of COVID-19 has created disastrous health effects worldwide. Doxycycline, a member of the tetracycline group, has been prescribed as a treatment companion for attending this catastrophe. Due to extensive use and high solubility, a significant amount of un-metabolized doxycycline has been found to reach water bodies within a short time, and consumption of this water may lead to the development of fatal resistance in organisms and create health problems. Therefore, it has become necessary to develop suitable technologies from a geoenvironmental point of view to remove these unwanted antibiotics from wastewater. In this context, locally obtainable silty-sandy soil was explored as a low-cost material in a constructed wetland with Chrysopogon zizanioides (vetiver sp.) for phytoremediation to mitigate doxycycline spiked wastewater. The obtained soil hydraulic conductivity was 1.63×10-7 m/s. Batch adsorption tests conducted on silty-sandy soil, vetiver leaf, and vetiver root provided maximum removal efficiencies of 90%, 72%, and 80% percent, respectively, at optimal sorbent doses of 10 g/L, 17 g/L, and 16 g/L, and contaminant concentrations of 25 mg/L, 20 mg/L, and 23 mg/L, with a 30-min time of contact. The Freundlich isotherm was the best fit, indicative of sufficient sorption capacity of all the adsorbents for doxycycline. The best match in the kinetic research was pseudo-second-order kinetics. A one dimensional vertical column test with the used soil on doxycycline revealed a 90% breakthrough in 24 h for a soil depth of 30 mm. Studies on a laboratory-scale wetland and numerically modeled yielded removal of around 92% by the selected soil and about 98% combined with Chrysopogon zizanioides for 25 mg/L of initial doxycycline concentration, which is considered quite satisfactory. Simulated results matched the laboratory tests very well. The study is expected to provide insight into remedies for similar practical problems. © 2023 American Society of Civil Engineers.

Recent Progress of Lipid Nanoparticles-Based Lipophilic Drug Delivery: Focus on Surface Modifications.

Numerous drugs have emerged to treat various diseases, such as COVID-19, cancer, and protect human health. Approximately 40% of them are lipophilic and are used for treating diseases through various delivery routes, including skin absorption, oral administration, and injection. However, as lipophilic drugs have a low solubility in the human body, drug delivery systems (DDSs) are being actively developed to increase drug bioavailability. Liposomes, micro-sponges, and polymer-based nanoparticles have been proposed as DDS carriers for lipophilic drugs. However, their instability, cytotoxicity, and lack of targeting ability limit their commercialization. Lipid nanoparticles (LNPs) have fewer side effects, excellent biocompatibility, and high physical stability. LNPs are considered efficient vehicles of lipophilic drugs owing to their lipid-based internal structure. In addition, recent LNP studies suggest that the bioavailability of LNP can be increased through surface modifications, such as PEGylation, chitosan, and surfactant protein coating. Thus, their combinations have an abundant utilization potential in the fields of DDSs for carrying lipophilic drugs. In this review, the functions and efficiencies of various types of LNPs and surface modifications developed to optimize lipophilic drug delivery are discussed.

Tenofovir antiviral drug solubility enhancement with ß-cyclodextrin inclusion complex and in silico study of potential inhibitor against SARS-CoV-2 main protease (Mpro).

Tenofovir (TFR) is an antiviral drug commonly used to fight against viral diseases infection due to its good potency and high genetic barrier to drug resistance. In physiological conditions, TFR is less water soluble, more unstable, and less permeable, limiting its effective therapeutic applications. In addition to their use in treating the Coronavirus disease 2019 (COVID-19), cyclodextrins (CDs) are also being used as a molecule to develop therapies for other diseases due to its enhance solubility and stability. This study is designed to synthesize and characterization of ß-CD:TFR inclusion complex and its interaction against SARS-CoV-2 (MPro) protein (PDB ID;7cam). Several techniques were used to characterize the prepared ß-CD:TFR inclusion complex, including UV-Visible, FT-IR, XRD, SEM, TGA, and DSC, which provided appropriate evidence to confirm the formation. A 1:1 stoichiometry was determined for ß-CD:TFR inclusion complex in aqueous medium from UV-Visible absorption spectra by using the Benesi-Hildebrand method. Phase solubility studies proposed that ß-CD enhanced the excellent solubility of TFR and the stability constant was obtained at 863 ± 32 M-1. Moreover, the molecular docking confirmed the experimental results demonstrated the most desirable mode of TFR encapsulated into the ß-CD nanocavity via hydrophobic interactions and possible hydrogen bonds. Moreover, TFR was validated in the ß-CD:TFR inclusion complex as potential inhibitors against SARS-CoV-2 main protease (Mpro) receptors by using in silico methods. The enhanced solubility, stability, and antiviral activity against SARS-CoV-2 (MPro) suggest that ß-CD:TFR inclusion complexes can be further used as feasible water-insoluble antiviral drug carriers in viral disease infection.

DEVELOPMENT AND EVALUATION OF FAVIPIRAVIR AGGLOMERATES FOR DIRECT COMPRESSION BY CRYSTALLO-CO-AGGLOMERATION TECHNIQUE

During the severe worldwide pandemic caused due to SARS COV-2 Corona virus, Favipiravir has been used for the treatment. It is a water insoluble anti-viral drug with poor dissolution and poor flow properties, resulting in poor oral absorption and less bioavailability. For a long time, the phrase "direct compression" was used to describe the compression of a single crystalline component into a compact without the addition of any other materials. Using excipients and solvents, the crystallo-co-agglomeration process aggregates drug crystals in the form of small spherical particles to create an intermediate product with better micromeritic and mechanical characteristics, solubility, and dissolution. Crystallo-co-agglomeration is a unique approach in which the pharmaceuticals or excipients are crystallized and agglomerated concurrently from a good solvent and/or bridging liquid by adding a non-solvent. The present study aims to formulate crystallo-co-agglomerates of Favipiravir to improve its physicochemical and mechanical properties. Results obtained during the evaluation showed that CCA technique could be successfully employed as an alternative to conventional wet agglomeration.

Nanosponges: Advancement in Nanotherapeutics

The emergence of nanotechnology paves the way for improving disease therapy strategies. An investigation into the progression of the release of the medication targeting the specified predetermined location is a significant factor to consider. Due to the ability to advance existing products and to develop new products in a variety of applications, the nanotechnology industry is considered an evolving technology. Cyclodextrin-based porous nanoparticles or unique nano-sponges (NSs) which have recently been used in the pharmaceutical, biomedical, and cosmetic industries are the main elements of this growth. This superior technology can circumvent the defects of current techniques by its ability to attack and visualize tumour sites. A biodegradable and biocompatible feature along with a built-in high surface area resulting in enormous amounts of drug loading and biomimetic design, and the ability to control nanoparticles size are just a handful of good attractive attributes that find this technique as an overwhelming advantage in the field of nanomedicine. This review article is organized such that we first explored the unique features of these nanosponges and the diverse methods for synthesizing, followed by the drug loading and release principle and application based on drug delivery, targeting, boosting solubility of BCS Class II and IV drugs, others in biomedicine and more. Finally, the recent progress on the use of biomimetic nanosponge as a pandemic tool due to the SARS-CoV-2 virus briefly comes into line. Copyright © RJPT All right reserved.

Effect of Pregelatinized Starch on the Properties of Poly (Vinyl Alcohol) Film for the Water-Soluble Laundry Bag

The goal of this study was to develop pregelatinized starch (P-St) and polyvinyl alcohol (PVOH) films as water-soluble laundry plastic bags to avoid having contact with COVID-19 infected clothes by extrusion method. The effects of pregelatinized starch (P-St) content on the properties of polyvinyl alcohol (PVOH) films were examined. PVOH and P-St blend were compounded by twin-screw extruder with various P-St content of 0, 10, 20, 30, and 40% by weight with fixed glycerol content of 20 phr. The blend films were produced by blown film extrusion. The chemical structure, thermal properties, water-solubility, mechanical properties, and the cross-sections morphological properties of PVOH/G/P-St were characterized. As a result, the formation of intermolecular interactions between PVOH, glycerol and P-St was confirmed by FTIR. Moreover, the addition of P-St on PVOH could reduce the thermal stability due to the content of P-St with amylose, a substance of amorphous structure, affecting the chains flexibility of PVOH/G/P-St. From the differential scanning calorimeter result, the glass transition temperature was increased with the increment of P-St content because the chains entanglement between PVOH and P-St had affected the reduction in crystallinity and led to the decrement of the melting temperature. Furthermore, the water solubility would strongly be dependent on the percentage of the gelatinized starch (%GS). The solubility decreased as the percentage of the GS increased. In addition, PVOH with 20% of P-St film possessed the highest value in tensile strength and modulus, and the particles of P-St have a good distribution in PVOH/G indicating to stronger interaction of P-St and PVOH/G. © 2022, Chiang Mai University. All rights reserved.

Computational demonstration of cheminformatics and machine learning in coronavirus drug discovery

Computational tools in drug discovery involve the use of algorithms in predicting properties of potential drugs as ligands as well as biological targets in structural forms. This dates back to more than 30 years ago and have been perfected with time and advancement of technology. They are reliable to varying extents depending on the nature of the study, complexity among other factors. Computational tools help medicinal chemists, computational chemists, and structural biologists to design and optimize potential drugs as early as possible and reduce or completely avoid attrition in the drug discovery pipeline. The search for drugs to cure or manage COVID-19 is made relatively easier and more efficient by the use of computational tools to help understand the ADMET properties of possible drugs under development. This chapter demonstrates how computational tools in cheminformatics and machine learning can be used in the fight against COVID-19 from a medicinal chemistry perspective using selected parameters. © 2022 Elsevier Inc. All rights reserved.

Theoretical and experimental study on Chloroquine drug solubility in supercritical carbon dioxide via the thermodynamic, multi-layer perceptron neural network (MLPNN), and molecular modeling

The design and development of supercritical carbon dioxide (sc-CO2) based processes for production of pharmaceutical micro/nanoparticles is one of the interesting research topics of pharmaceutical industries owing to its attractive advantages. The solubility of drugs in sc-CO2 at different temperatures and pressures is an essential parameter which should be determined for this purpose. Chloroquine as a traditional antirheumatic and antimalarial agent is approved as an effective drug for the treatment of Covid-19. Pishnamazi et al. (Pishnamazi et al., 2021) measured the solubility of this drug in sc-CO2 at the pressure range of 120-400 bar and temperature range of 308-338 K, and correlated the obtained data using some empirical models. In this work, a comprehensive computational approach was developed to more accurately study the supercritical solubility of Chloroquine. The thermodynamic models include two equations-of-state based models (Peng-Robinson and Soave-Redlich-Kowang) and two activity coefficient-based models (modified Wilson's and UNIQUAC)), as well as, a multi-layer perceptron neural network (MLPNN)) were used for this purpose. Also, molecular modeling was performed to study the electronic structure of Chloroquine and identify the potential centers of intermolecular interactions during the dissolution process. According to the obtained results, all of the theoretical models can predict Chloroquine solubility in sc-CO2 with acceptable accuracy. Among these models, the MLPNN model possesses the highest precision with the lowest average absolute relative deviation (AARD%) of 1.76% and the highest Radj value of 0.999.

BOOZE, BETAS, AND A FATTY SOLUTION TO SPARE PANDEMIC WOES

SESSION TITLE: Cases of Overdose, OTC, and Illegal Drug Critical Cases Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The COVID-19 pandemic raised economic strife, social isolation, fear from contagion, and anxiety to a level where 45% of surveyed U.S. adults report a detriment to their mental health. With U.S. suicide rates up from 10 to 14 cases per 100,000 over the past 20 years, the health and safety of a vulnerable mental health population becomes more of a concern. We report a case of an individual with depression who was resuscitated after severe toxicity from alcohol and beta-blocker ingestions. CASE PRESENTATION: A 58-year-old woman with prior suicide attempts was found in an obtunded state after finishing a 20-pack of beer and swallowing a propranolol 20 mg pill bottle. On admission, she presented with bradycardia, hypotension, and alteration to a Glasgow Coma Scale of 9 with emesis residue on her face. Her blood gas revealed an anion-gap metabolic acidosis with a pH of 7.26, lactate of 2.53, normal potassium and calcium, and glucose of 134 mg/dL. Toxicity labs were notable for an alcohol of 199 mg/dL. Her EKG demonstrated a junctional bradycardia with a p-wave complex after the QRS consistent with retrograde depolarization of the atrium (Image 1). She was intubated to protect her airway. She subsequently developed cardiac arrest secondary to pulseless electrical activity. She underwent CPR for 33 minutes with boluses of intravenous epinephrine, glucagon, insulin, calcium gluconate, and sodium bicarbonate prior to return of spontaneous circulation. Due to failure of transcutaneous pacing, a transvenous pacer was placed. In concert with Poison Control, she was started on an a euglycemic insulin drip and an intralipid infusion. Her hemodynamics improved, and she was weaned off pacing and ICU interventions within 24 hours. She was discharged a week after admission with no residual morbidities. DISCUSSION: Overdose from nonselective beta-blockers can result in bradycardia, hypotension, seizures, QRS widening, QTc prolongation with ventricular tachy-arrhythmias, hyperkalemia, and hypoglycemia. Understanding the pharmacodynamics of beta-blocker toxicity enables targeted interventions to improve: chronotropy with epinephrine, glucagon, and pacing;inotropy with insulin, calcium, glucagon, and phosphodiesterase inhibitors;QRS widening with sodium bicarbonate;and QTc prolongation with magnesium or lidocaine. The high lipid solubility of propanol allows for intravenous lipid infusions to aid in drug elimination for patients in refractory cardiogenic shock. CONCLUSIONS: Despite a lack of labs for monitoring beta blocker toxicity, our case demonstrates successful resuscitation in a severe overdose. Perhaps an absence of hyperkalemia, hypoglycemia, QRS and QTc changes, and tachy-arrhythmias in this incident portended to a decreased morbidity and mortality. Ultimately, we reaffirmed the role of intralipid infusions as a critical treatment adjunct for recovery from cardiogenic shock secondary to beta blockade. Reference #1: Sher L. The impact of the COVID-19 pandemic on suicide rates. QJM. 2020;113(10):707-712. Reference #2: Kerns W 2nd. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-viii. Reference #3: Anderson AC. Management of beta-adrenergic blocker poisoning. Clin Pediatr Emerg Med. 2008;9(1):4–16. DISCLOSURES: No relevant relationships by Jackie Hayes No relevant relationships by Andrew Salomon

Cationic Perylene Antivirals with Aqueous Solubility for Studies In Vivo.

Perylene-based compounds are attracting significant attention due to their high broad-spectrum antiviral activity against enveloped viruses. Despite unambiguous results of in vitro studies and high selectivity index, the poor water solubility of these compounds prevented in vivo evaluation of their antiviral properties. In this work, we synthesized a series of compounds with a perylene pharmacophore bearing positively charged substituents to improve the aqueous solubility of this unique type of antivirals. Three types of charged groups were introduced: (1) quaternary morpholinium salts (3a-b); (2) a 2'-O-l-valinyl-uridine hydrochloride residue (8), and (3) a 3-methylbenzothiazolium cation (10). The synthesized compounds were evaluated based both on antiviral properties in vitro (CHIKV, SARS-CoV-2, and IAV) and on solubility in aqueous media. Compound 10 has the greatest aqueous solubility, making it preferable for pre-evaluation by intragastrical administration in a mouse model of lethal influenza pneumonia. The results indicate that the introduction of a positively charged group is a viable strategy for the design of drug candidates with a perylene scaffold for in vivo studies.

Estimating thermodynamic equilibrium solubility and solute-solvent interactions of niclosamide in eight mono-solvents at different temperatures.

Niclosamide is an FDA-approved oral anthelmintic drug currently being repurposed for COVID-19 infection. Its interesting applicability in multiple therapeutic indications has sparked interest in this drug/ scaffold. Despite its therapeutic use for several years, its detailed solubility information from Chemistry Manufacturing & Controls perspective is unavailable. Thus, the present study is intended to determine the mole fraction solubility of niclosamide in commonly used solvents and cosolvents at a temperature range of 298.15-323.15 K. The polymorphic changes from crystalline to monohydrate forms post-equilibration in various solvents were observed. The maximum mole fraction solubility of niclosamide at 323.15 K is 1.103 × 10-3 in PEG400, followed by PEG200 (5.272 × 10-4), 1-butanol (3.047 × 10-4), 2-propanol (2.42 × 10-4), ethanol (1.66 × 10-4), DMSO (1.52 × 10-4), methanol (7.78 × 10-5) and water (3.27 × 10-7). The molecular electrostatic potential showed a linear correlation with the solubility. PEG400 has higher electrostatic potential, and H-bond acceptor count, which forms a hydrogen bond with phenolic -OH of niclosamide and thus enhances its solubility. This data is valuable for the drug discovery and development teams working on the medicinal chemistry and process chemistry of this scaffold.

Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with ß-Cyclodextrin: A Spectroscopic Assessment.

Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7-O-glucoside inclusion complex with ß-cyclodextrin (HEPT7G/ßCD; SunActive® HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with naringinase enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis. The objective of this study was to investigate the stability, solubility, and spectroscopic features of the HEPT7G/ßCD inclusion complex using Fourier-transform infrared (FTIR), Raman, ultraviolet-visible absorption (UV-vis), 1H- and 13C- nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC-MS), scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) spectroscopic techniques including zeta potential, Job's plot, and phase solubility measurements. The effects of complexation on the profiles of supramolecular interactions in analytic features, especially the chemical shifts of ß-CD protons in the presence of the HEPT7G moiety, were evaluated. The stoichiometric ratio, stability, and solubility constants (binding affinity) describe the extent of complexation of a soluble complex in 1:1 stoichiometry that exhibits a greater affinity and fits better into the ß-CD inner cavity. The NMR spectroscopy results identified two different configurations of the HEPT7G moiety and revealed that the HEPT7G/ßCD inclusion complex has both -2S and -2R stereoisomers of hesperetin-7-O-glucoside possibly in the -2S/-2R epimeric ratio of 1/1.43 (i.e., -2S: 41.1% and -2R: 58.9%). The study indicated that encapsulation of the HEPT7G moiety in ß-CD is complete inclusion, wherein both ends of HEPT7G are included in the ß-CD inner hydrophobic cavity. The results showed that the water solubility and thermal stability of HEPT7G were apparently increased in the inclusion complex with ß-CD. This could potentially lead to increased bioavailability of HEPT7G and enhanced health benefits of this flavonoid.

A green closed-loop process for selective recycling of lithium from spent lithium-ion batteries

As the economy started to recover from the COVID pandemic, the price of Li2CO3 skyrocketed to its highest. This situation has aggravated concerns about the supply chain for lithium-ion batteries (LIBs). Recycling spent LIBs is a potential solution to alleviate the bottleneck of the supply chain and prevent environmental pollution, and has attracted lots of attention. However, lithium recycling is generally disregarded because of the complex recycling process and its low recycling efficiency. Here, in this work we developed a sustainable lithium recovery process, which can selectively leach and recover lithium with formic acid before recycling valuable metals. With the reported method, lithium can be 99.8% recovered from layered oxide cathode materials with 99.994% purity. In addition, this lithium recovery process is affordable, compared to the typical hydrometallurgical process, by saving 11.15% per kilogram of spent LIBs. Therefore, this research provided a new solution to eliminating the effects of lithium ions on valuable metal separation and the co-precipitation reaction and precluding the influence of other metal ions on lithium recovery. This simplified lithium recovery process provides new opportunities for sustainable recycling of LIBs and economical restoration of the lithium supply chain.