Free Base Form Research Articles

A Doubly meso-α Linked N-Confused Porphyrin Tape Silver(III) Complex Comprising an Antiaromatic Pyrrolo[2,3-f]indole Segment.

The free base form of doubly meso-α linked N-confused porphyrin (NCP) tape 3 was successfully synthesized via Ir(I) mediated intramolecular coupling. The following silver complexation afforded the Ag(III) complex of doubly meso-α linked NCP tape 4. While 3 exhibited 38π aromatic characters, 4 exhibited not only 18π aromatic NCP-type characteristics but also a decent antiaromatic contribution of 12π pyrrolo[2,3-f]indole segment, as probed by NMR spectra, absorption spectra, and DFT calculations.

Immobilization of Levocetirizine on Mesoporous Silica for Antiallergenic Gel Formulation

Levocetirizine dihydrochloride is an effective antiallergenic drug applied mostly orally; however, developing a topical formulation for localized treatment could be beneficial. To achieve this, a modified formulation technique is necessary to enhance bioavailability efficiency and minimize possible side effects. Therefore, levocetirizine particles were prepared by immobilization on mesoporous silica material. Both the dihydrochloride form and its free base of levocetirizine were fixed on a silica-type Syloid support. Immobilization of the active ingredient levocetirizine in a free base form on a Syloid support by mixing in a dichloromethane solution provides better surface coverage (65.5%) than immobilization in the dihydrochloride form in water or methanol (24.5% for both). The successful binding of levocetirizine was confirmed by X-ray photoelectron spectroscopy and infrared measurements. The active ingredient in the form of hydrochloride is more likely to be in the pores, while the free base is bound to the surface in larger quantities. The time-dependent levocetirizine release showed that the liberation of the active ingredient from the Syloid is slower than the dissolution of the starting active ingredient itself, so it may be suitable for exerting a more reliable and prolonged local effect. A gel containing a Syloid-fixed levocetirizine free base was tested in vivo in a croton oil-induced ear edema mouse model. When compared to a reference gel, the half-dose formulation containing levocetirizine free base demonstrated a similar efficacy to Fenistil gel, indicating that the new formulation may offer superior effectiveness at lower doses.

Design, Synthesis, and Characterization of Novel Thiazolidine-2,4-Dione-Acridine Hybrids as Antitumor Agents.

This study focuses on the synthesis and structural characterization of new compounds that integrate thiazolidine-2,4-dione, acridine moiety, and an acetamide linker, aiming to leverage the synergistic effects of these pharmacophores for enhanced therapeutic potential. The newly designed molecules were efficiently synthesized through a multi-step process and subsequently transformed into their hydrochloride salts. Comprehensive spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and elemental analysis, were employed to determine the molecular structures of the synthesized compounds. Biological evaluations were conducted to assess the therapeutic potential of the new compounds. The influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. An in-depth analysis of the structure-activity relationship (SAR) revealed intriguing insights into their cytotoxic profiles. Compounds with electron-withdrawing groups generally exhibited lower IC50 values, indicating higher potency. The presence of the methoxy group at the linking phenyl ring modulated both the potency and selectivity of the compounds. The variation in the acridine core at the nitrogen atom of the thiazolidine-2,4-dione core significantly affects the activity against cancer cell lines, with the acridin-9-yl substituent enhancing the compounds' antiproliferative activity. Furthermore, compounds in their hydrochloride salt forms demonstrated better activity against cancer cell lines compared to their free base forms. Compounds 12c·2HCl (IC50 = 5.4 ± 2.4 μM), 13d (IC50 = 4.9 ± 2.9 μM), and 12f·2HCl (IC50 = 4.98 ± 2.9 μM) demonstrated excellent activity against the HCT116 cancer cell line, and compound 7d·2HCl (IC50 = 4.55 ± 0.35 μM) demonstrated excellent activity against the HeLa cancer cell line. Notably, only a few tested compounds, including 7e·2HCl (IC50 = 11.00 ± 2.2 μM), 7f (IC50 = 11.54 ± 2.06 μM), and 7f·2HCl (IC50 = 9.82 ± 1.92 μM), showed activity against pancreatic PATU cells. This type of cancer has a very high mortality due to asymptomatic early stages, the occurrence of metastases, and frequent resistance to chemotherapy. Four derivatives, namely, 7e·2HCl, 12d·2HCl, 13c·HCl, and 13d, were tested for their interaction properties with BSA using fluorescence spectroscopic studies. The values for the quenching constant (Ksv) ranged from 9.59 × 104 to 10.74 × 104 M-1, indicating a good affinity to the BSA protein.

Encapsulation of Gemcitabine on Porphyrin Aluminum Metal-Organic Framework by Mechano-Chemistry, Delayed Drug Release and Cytotoxicity to Pancreatic Cancer PANC-1 Cells.

Gemcitabine is a widely used antimetabolite drug of pyrimidine structure, which can exist as a free-base molecular form (Gem). The encapsulated forms of medicinal drugs are of interest for delayed and local drug release. We utilized, for the first time, a novel approach of mechano-chemistry by liquid-assisted grinding (LAG) to encapsulate Gem on a "matrix" of porphyrin aluminum metal-organic framework Al-MOF-TCPPH2 (compound 2). The chemical bonding of Gem to compound 2 was studied by ATR-FTIR spectroscopy and powder XRD. The interaction involves the C=O group of Gem molecules, which indicates the formation of the encapsulation complex in the obtained composite. Further, the delayed release of Gem from the composite was studied to phosphate buffered saline (PBS) at 37 °C using an automated drug dissolution apparatus equipped with an autosampler. The concentration of the released drug was determined by HPLC-UV analysis. The composite shows delayed release of Gem due to the bonded form and constant concentration thereafter, while pure Gem shows quick dissolution in less than 45 min. Delayed release of Gem drug from the composite follows the kinetic pseudo-first-order rate law. Further, for the first time, the mechanism of delayed release of Gem was assessed by the variable stirring speed of drug release media, and kinetic rate constant k was found to decrease when stirring speed is decreased (diffusion control). Finally, the prolonged time scale of toxicity of Gem to pancreatic cancer PANC-1 cells was studied by continuous measurements of proliferation (growth) for 6 days, using the xCELLigence real-time cell analyzer (RTCA), for the composite vs. pure drug, and their differences indicate delayed drug release. Aluminum metal-organic frameworks are new and promising materials for the encapsulation of gemcitabine and related small-molecule antimetabolites for controlled delayed drug release and potential use in drug-eluting implants.

Dose-response study on the transfer of pyrrolizidine alkaloids from a tansy ragwort extract (Jacobaea vulgaris Gaertn.) to bovine milk

Ragworts like tansy ragwort (J. vulgaris Gaertn., syn. Senecio jacobaea L.) contain hepatotoxic and cancerogenic pyrrolizidine alkaloids (PA) and their corresponding pyrrolizidine alkaloid N-oxides (PANO). Due to increasing spread of ragworts (Jacobaea spp.) PA/PANO may pose a health risk to animals and humans consuming contaminated feed and food. Therefore, the aim of the present study was to investigate the transfer of individual PA/PANO originating from a well-defined PA/PANO extract into the milk of dairy cows. For this objective, 16 German Holstein cows were assigned to four treatment groups (n = 4) in a 28-day dose-response study. Administration into the reticulorumen was performed daily by gavage after the morning milking. Three groups received different amounts of the J. vulgaris extract resulting in a PA/PANO exposure of 0.47, 0.95, or 1.91 mg PA/PANO/kg body weight/day, respectively. Furthermore, a control group received molasses to account for the sugar content of the used PA/PANO extract. While the composition of the PA/PANO extract was more diverse, the PA/PANO pattern in milk was dominated by the PA in their free base form. It was shown that mainly PA considered stable in the rumen environment were transferred into the milk. The main compounds in milk were jacoline (74.3 ± 2.4% of the PA/PANO sum), jaconine (11.2 ± 1.3%), and jacobine (7.2 ± 0.6%) with concentrations up to 29.7, 4.65 µg/l, or in the highest exposed group, 3.44 µg/l. There was no dose-dependent effect on the total PA/PANO transfer rate into the milk. The average transfer rate was 0.064 ± 0.005% of the administered content.

The Excited-State N-H Tautomerization Rate in Free-Base Corroles.

Corrole is a tetrapyrrolic dye with a structure that resembles porphyrin, apart from a single missing carbon. The absence of this carbon results in the re-arrangement of the double bonds within the macrocycle, and the presence of three pyrrolic protons in the central cavity in its free-base form. These protons lead to the existence of two distinct tautomeric structures that exist in a dynamic equilibrium. Although the ground-state energies of the tautomers are similar, the excited states show a significant difference in energy which unbalances the equilibrium between the tautomers and results in rapid excited-state tautomerization, favouring one tautomeric species over the other. Although the excited-state tautomerization process has been known for a long time, very few studies have been performed on it, leaving many key aspects of the process poorly understood. Herein we show how ultrafast photoluminescence can be used to experimentally determine the rates of excited-state tautomerization and activation energies of three free-base corrole derivatives thus allowing us to completely describe the excited-state dynamics of the unusual excited state of free-base corrole and opening the door to the development of new materials that can exploit its unique characteristics.

Biochemical characterization of a unique cytokinin and nucleotide phosphoribohydrolase Lonely Guy protein from Dictyostelium discoideum

Lonely guy (LOG) proteins are phosphoribohydrolases (PRHs) that are key cytokinin (CK)-activating enzymes in plant and non-plant CK-producing organisms. During CK biosynthesis, LOGs catalyze the conversion of precursor CK-nucleotides (CK-NTs) to biologically active free base forms. LOG/PRH activity has been detected in bacteria, archaea, algae, and fungi. However, in these organisms, the LOG/PRH activity for CK-NTs and non-CK-NTs (e.g., adenine-NTs) has not been assessed simultaneously, which leaves limited knowledge about the substrate specificity of LOGs. Thus, we performed bioinformatic analyses and a biochemical characterization of a LOG ortholog from Dictyostelium discoideum, a soil-dwelling amoeba, which produces CKs during unicellular growth and multicellular development. We show that DdLog exhibits LOG/PRH activity on two CK-NTs, N6-isopentenyladenosine-5′-monophosphate (iPMP) and N6-benzyladenosine-5′-monophosphate (BAMP), and on adenosine 5′-monophosphate (AMP) but not on 3′, 5′-cyclic adenosine-monophosphate (cAMP). Additionally, there were higher turnover rates for CK-NTs over AMP. Together, these findings confirm that DdLog acts as a CK-activating enzyme; however, in contrast to plant LOGs, it maintains a wider specificity for other substrates (e.g., AMP) reflecting it has maintained its original, non-CK related role even after diversifying into a CK-activating enzyme.

Targeting pentamidine towards CD44-overexpressing cells using hyaluronated lipid-polymer hybrid nanoparticles.

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150nm, a negative zeta potential of -35mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner.

Rationalizing Counterion Selection for the Development of Lipophilic Salts: A Case Study with Venetoclax.

The use of lipid-based formulations (LBFs) can be hindered by low dose loading due to solubility limitations of candidate drugs in lipid vehicles. Formation of lipophilic salts through pairing these drugs with a lipophilic counterion has been demonstrated as a potential means to enhance dose loading in LBFs. This study investigated the screening of appropriate counterions to form lipophilic salts of the BCS class IV drug venetoclax. The physical properties, lipid solubility, and in vitro performance of the salts were analyzed. This study illustrated the versatility of alkyl sulfates and sulfonates as suitable counterions in lipophilic salt synthesis with up to ∼9-fold higher solubility in medium- and long-chain LBFs when compared to that of the free base form of venetoclax. All salts formulated as LBFs displayed superior in vitro performance when compared to the free base form of the drug due to the higher initial drug loadings in LBFs and increased affinity for colloidal species. Further, in vitro studies confirmed that venetoclax lipophilic salt forms using alkyl chain counterions demonstrated comparable in vitro performance to venetoclax docusate, thus reducing the potential for laxative effects related to docusate administration. High levels of the initial dose loading of venetoclax lipophilic salts were retained in a molecularly dispersed state during dispersion and digestion of the formulation, while also demonstrating increased levels of saturation in biorelevant media. The findings of this study suggest that alkyl chain sulfates and sulfonates can act as a suitable alternative counterion to docusate, facilitating the selection of counterions that can unlock the potential to formulate venetoclax as an LBF.

Reliable I/V characteristics and long lifetime of porphyrin-based single-molecule junctions

In this work diamino-porphyrin derivatives, in their free base or cobalt complex forms, have been used to construct SMJs.

Abstract B115: Preclinical characterization of LY3962673, an orally bioavailable, highly potent, and selective KRAS G12D inhibitor

Abstract KRAS G12D mutations are activating oncogenic events that occur in approximately 35%, 13%, and 4% of pancreatic, colorectal, and non-small cell lung cancers, respectively and less commonly in other cancers. Here, we describe LY3962673, a highly potent inhibitor of KRAS G12D that is selective against wild-type (WT) KRAS and orally bioavailable. Compound potency and selectivity were measured using surface plasmon resonance (SPR) and cell-based assays monitoring the inhibition of pERK (Thr202/Tyr204) and cell growth. In SPR assays, LY3962673 had Kd values of 0.058 and 4.7 nM for GDP-bound KRAS G12D and WT KRAS, respectively (81-fold selective). In KRAS G12D-mutant HPAC, LY3962673 inhibited ERK1/2 phosphorylation with an IC50 of 4.2 nM contrasting 231 nM IC50 in WT KRAS MKN45 cells (55-fold selective). Similarly, LY3962673 inhibited cell growth in KRAS G12D and WT KRAS cell lines with IC50 values of 7.7 nM and 1800 nM, respectively (233-fold selective). LY3962673 shows a clean safety profile in a 133 off-target panel screen. LY3962673 demonstrates favorable in vitro ADME properties. LY3962673 shows oral bioavailability across preclinical species when dosed either as freebase or salt form. Tumor growth inhibition and PK/PD studies were performed in mice. In vivo, LY3962673 administered orally demonstrated tumor regressions in KRAS G12D-driven tumor models, without body weight loss. This wide therapeutic index is predicted to allow for maximizing dose intensity and efficacy in patients. These data demonstrate that LY3962673 potently inhibits KRAS G12D while sparing WT KRAS and other off-targets with its selectivity. We hypothesize that LY3962673’s low nanomolar potency, desirable selectivity profile, and oral bioavailability will provide efficacy and tolerability in patients with KRAS G12D-driven cancers. An IND submission is planned in the first half of 2024. Citation Format: Chandrasekar Iyer, Binghui Li, Trent R Stewart, Tao Wang, Andrew Capen, Rachel Cavitt, Bryan D Anderson, Wayne Bocchinfuso, Gaiying Zhao, Michael J Rodriguez, Santiago Carballares, Andrew Cooke, Robert Bondi, Lee Burns, Lakshmi Kelamangalath, Ross Wallace, Gabrielle Kolakowski, James R Henry, Chong Si. Preclinical characterization of LY3962673, an orally bioavailable, highly potent, and selective KRAS G12D inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B115.

Analytical Methods Based on the Mass Balance Approach for Purity Evaluation of Tetracycline Hydrochloride.

Analytical methods based on the mass balance approach were developed for the purity evaluation of tetracycline hydrochloride, a representative salt compound used in pure veterinary drug analysis. The purity assignment method was used to quantify individual classes of impurities via independent analytical techniques. The mass fraction of the free base or salt form contained in a high-purity organic compound with a hydrochloride salt can be determined. The chloride content by ion chromatography-conductivity detector (IC-CD) and general classes of impurities, including structurally related impurities by liquid chromatography-ultraviolet (LC-UV) detector, water by Karl Fischer (KF) coulometric titration, residual solvents by headspace sampler gas chromatography/mass spectrometry (HS-GC/MS), and non-volatiles by thermogravimetric analyzer (TGA), were considered to calculate the purity of the mass fraction. The chloride content of the salt compound can be considered the main impurity in the mass fraction of the free base in the salt compound. A purity assay using quantitative nuclear magnetic resonance (q-NMR) as a direct determination method was performed to confirm the results of the mass balance method. The assigned purities of the tetracycline free form and its salt form in mass fraction were (898.80 ± 1.60) mg/g and (972.65 ± 1.58) mg/g, respectively, which are traceable to the international system of units (SI). Thus, the procedure for evaluating the purity of the free base and salt forms in the salt compound is newly demonstrated in this study.

28π Non‐Fused Hexaphyrin: Synthesis, Protonation Triggered Möbius Aromaticity and Structural Properties

AbstractSynthesis of core‐modified 28π non‐fused hexaphyrin is reported. The optical and 1H NMR spectral analysis reveals the non‐aromatic nature of the macrocycle in its freebase form at 298 K. However, the non‐aromatic nature of the macrocycle remains unaltered upon lowering the temperature. The structural elucidations for the freebase macrocycle also justify the non‐aromaticity of the freebase 8, where the thiophene units of the 1,2 diphenyl 1,2 dithienyl ethene moiety is deviated maximum from the overall macrocyclic framework. Protonation on the imino pyrrolic nitrogens results in single–crystal X‐ray structures of 8 which show essential distortion in macrocyclic framework needed for the effective π‐electron delocalization, attaining Möbius aromaticity. The Nucleus Independent Chemical Shift (NICS) values for the freebase and protonated macrocycles are −2.0 ppm and −5.6 ppm. The Anisotropy Induced Current density shows the clockwise delocalization of current density vectors. Overall, the spectral, structural and theoretical analysis suggests nonaromatic in freebase and Möbius aromatic nature of the protonated hexaphyrin.

Single-Molecule Conductance of Intramolecular Hydrogen Bonding in Histamine on Gold.

We perform single-molecule conductance measurements and DFT calculations on histamine, a biogenic amine that contains a flexible aliphatic linker and several nitrogen moieties with a potential for hydrogen bonding. Our study determines that junctions containing the free-base form of histamine can bridge through a molecular structure containing an intramolecular hydrogen bond. Conductance of this structure is higher than that through the saturated aliphatic linker. Flicker noise analysis of junction conductance confirms that transport occurs through the hydrogen bond and establishes a benchmark for noise measurements in hydrogen-bonded junctions. Overall, our work provides insights into the formation and conduction of intramolecular hydrogen bonding in single-molecule conductance measurements and into the conformations of the neurotransmitter histamine on noble metal surfaces.

Nicotine–magnesium aluminum silicate complexes processed by blending: Characterization for usage as drug carriers in mucoadhesive buccal discs

Complexation of nicotine (NCT) and magnesium aluminum silicate (MAS) has been formed in the dispersions that required multiple preparation steps. In this study, physical blending was used to produce NCT–MAS complexes. NCT, a free-base liquid state form, was adsorbed onto the MAS granules, where the diffusion and intercalation of NCT molecules into the MAS silicate layers occurred. These processes required a minimum of the 7-d-resting period to reach NCT complete distribution. FTIR, XRD, and 29Si NMR suggest that NCT could interact with MAS via hydrogen bonding, water bridging, and ionic electrostatic force. The 12 % NCT–MAS complexes enabled a sustained release of NCT, after a 2-min burst, in pH 6 phosphate buffer through a particle diffusion-controlled mechanism. Buccal discs formulated with NCT–MAS complexes and sodium alginate (SA) as drug carriers and matrix former could control NCT released through drug diffusion and swelling-controlled mechanisms. NCT release and membrane permeation increased with increasing NCT–MAS complexes or decreasing SA concentration. All NCT–MAS-containing buccal discs exhibited mucoadhesive properties related to the swelling characteristics of SA and MAS. Conclusively, NCT–MAS complexes can be produced through an uncomplicated single-step blending process, and the complexes obtained presented a potential to serve as drug carriers in buccal matrix formulations.

1,4-Phenylene incorporated decaphyrin tetrarhodium(I) complex: Synthesis, structures, and chiroptical properties

1,4-Phenylene-incorporated decaphyrin(1.0.1.0.0.1.0.1.0.0) 1 has been previously synthesized and optically resolved in the free-base form; however, it undergoes racemization at elevated temperature. In this study, we fixed the figure-of-eight conformation by means of rhodium(I) coordination. The resulting tetranuclear Rh(I) complex 1-Rh[Formula: see text], which is scarcely reported to date, exhibited considerable conformational stability. Accordingly, it could be readily resolved by high-performance liquid chromatography (HPLC) on a chiral stationary phase, and no racemization was observed even at 110[Formula: see text]C. Importantly, the tetranuclear porphyrinoid complex bearing a unique edge-to-edge alignment of the two 1,4-phenylene spacers revealed a relatively large molar circular dichroism (CD) with an absorption dissymmetry factor ([Formula: see text] of 0.018. While a two-fold larger [Formula: see text] of up to 0.036 was seen for the structural congener 1, wherein the 1,4-phenylene spacers adopt a face-to-face orientation. Thus, it serves to be an attractive basis to explore the structural effect on the chiroptical properties of the expanded porphyrinoid.

Ring-opening of 5,15-dioxaporphyrin into 1,9-diaryldipyrrin by a reaction with Grignard reagents

A ring-opening of nickel 10,20-dimesityl-5,15-dioxaporphyrin (NiDOP) proceeded in a reaction with aryl Grignard reagents to afford 1,9-diaryldipyrrins instead of demetallation reaction to form a free base form. A reagent scope for the ring-opening reaction revealed that reactions with less-sterically hindered aryl Grignard reagents, such as phenyl and para-substituted phenylmagnesium bromides, provided the dipyrrin products. In contrast, no reaction occurred, and unreacted NiDOP was recovered when alkyl, ethynyl, and 2-thienylmagnesium bromides and sterically hindered mesitylmagnesium bromide were used for the reactions. Herein, the unique ring-opening reactivity of NiDOP and characterization of the 1,9-diaryldipyrrin products are reported.

Developing In Situ Chemometric Models with Raman Spectroscopy for Monitoring an API Disproportionation with a Complex Polymorphic Landscape.

An in situ Raman method was developed to characterize the disproportionation of two salts involving a complex polymorphic landscape comprising up to two metastable and one stable freebase forms. Few precedents exist for Raman calibration procedures for solid form quantitation involving more than two polymorphs, while no literature examples were found for cases with multiple metastable forms. Therefore, a new Raman calibration procedure was proposed by directly using disproportionation experiments to generate multiple calibration samples encompassing a range of polymorph ratios through in-line Raman measurements complemented by off-line reference X-ray diffraction measurements. The developed Raman methods were capable of accurately quantitating each solid form in situ when solid concentration variation was incorporated into the calibration dataset. The kinetic understanding of the thermodynamically driven polymorphic conversions gained from this Raman method guided the selection of the salt best suited for the delivery of the active ingredient in the drug product. This work provided a spectroscopic and mathematical approach for simultaneously quantitating multiple polymorphs from a complex mixture of solids with the objective of real-time monitoring.

Mechanochemistry Facilitates a Single-Crystal X-ray Structure Determination of Free Base Naloxone Anhydrate.

A method to obtain single crystals of the opioid antagonist naloxone in the free base form is facilitated using mechanochemistry. The application of mechanochemistry reduces the number of steps and makes single crystals readily available from solution compared to using an approach based exclusively on solution or the reported method based on sublimation. The X-ray structure confirms the structure determined using powder diffraction and provides details of hydrogen bonding.

(Digital Presentation) Electrocatalytic CO2 Reduction to Formic Acid: Kinetics and Equilibrium Modeling for the Downstream Separation of Formic Acid with Anion Exchange Resins

Electrocatalytic carbon dioxide reduction reaction (CO2RR) technology can simultaneously minimize the CO2 concentration in the atmosphere and generate useful chemicals and fuels. Liquid formic acid (FA) produced from CO2RR is a chemical feedstock for industrial purposes as well as a potential hydrogen storage medium. The downstream separation of liquid FA from the CO2RR effluent increases the total costs in addition to the electrolysis and can also affect the environment adversely. Therefore, efficient, low-cost, and environmentally benign technologies for FA separation from the CO2RR are important for life cycle analysis and techno-economic analysis for this technology. Ion exchange has been proven as an advanced process for FA separation from aqueous solution. This method has attractive due to its high selectivity, low cost, ease of operation and recovery, availability to integrate with other systems, and environmentally benign nature.In this work, three anion exchange resins: Ambersep 900 hydroxide, Amberlite IRA-96 free base, and Amberlite IRA-910 chloride forms have been tested to separate FA from the aqueous solution under varying resin loading (10-60 mg/mL) and initial FA concentration (0.05-0.50 M). The effect of potassium bicarbonate, a commonly used catholyte in electrochemical CO2RR on equilibrium FA adsorption capacity has been investigated with resin loading of 10 and 60 mg/mL under similar initial FA concentrations.Kinetics and equilibrium studies data for the FA adsorption on three resins are interpreted using several kinetics and isotherm models. The kinetics data fits better with pseudo first order at high initial FA concentration and pseudo second order at low initial FA concentration. The results show that the Ambersep 900 hydroxide form with adsorption capacity of 430.8 mg of FA per g of resin is more efficient than the Amberlite IRA-96 free base form (369.9 mg/g) and Amberlite IRA-910 chloride form (291.2 mg/g) in the absence of potassium bicarbonate in the range of parameters studied. However, Amberlite IRA-96 (153.4 mg/g) and Amberlite IRA-910 (143.4 mg/g) can separate FA more efficiently from the potassium bicarbonate aqueous solution than the Ambersep 900 (94.1 mg/g). The experimental data for all resins can be well explained with the Freundlich isotherm model. In the presence of potassium bicarbonate, competitive adsorption of bicarbonate and formic acid reduces the FA adsorption capacity of resins. Experimental and modeling results will be discussed.