Charged Form Research Articles

The method of capillary electrophoresis for quantitative determination of hydrophobized hyaluronic acid in its micellar forms

Micelles based on hydrophobized hyaluronic acid (HA) are frequently used in targeted drug delivery systems. Capillary zone electrophoresis (CZE) was utilized for the quantitative determination of hydrophobized and native HA. A universal methodology was developed, suitable for the quantitative analysis of amphiphilic derivatives of hyaluronan (oleyl hyaluronan and hyaluronan conjugate with naphthalimide fluorophore) and native HA with varying molecular weights (15, 150, and 800 kDa). Furthermore, methodologies were proposed for the simultaneous quantification of a drug substance and oleyl hyaluronan in micellar forms based on the latter. The CE technique was applied for analyzing oleyl-hyaluronan-based micellar forms of two poorly soluble drug substances with oppositely charged ionic forms (loperamide and rifabutin). The examples contained in the study demonstrate a range of analytical sensitivity (LOD) for hyaluronan from 11 to 40 μg/mL and for the drug substance from 0.4 to 0.6 μg/mL. The study also showcases the accurate quantitative determination of rifabutin and loperamide in oleyl-hyaluronan-based micellar forms without the need for sample preparation. Thus, the proposed methodologies can be used to quantify native HA or its amphiphilic derivatives and simultaneously determine drug substances of various nature.

Влияние цетиламина на спектры поглощения и протолитические свойства люмогаллиона и магнезона ХС

The interaction of monoazo compounds lumogallion (LG) and magnezon HS (MHS) with cetylamine (CA) in a wide pH range has been studied using a spectrophotometric method.It has been shown that the formation of ionic associates of CA under the interaction of its cation with sulfo group of azo compounds in the pH range 1–4 does not change the electronic absorption spectra of the azodyes. The interaction of CA at dissociated OH groups conjugated with the π-system of the azo compounds leads to a bathochromic shift in the maximum of the absorption spectrum of the corresponding ionic form of the reagents by 15 and 30 nm for the doubly and triply charged forms of LG, respectively, and by 50 nm for the doubly charged form of MHS. The shift in the maximum of the absorption spectrum is accompanied by the shift in the apparent pK value of the reagents by 2–4 pH units, caused by the binding of the dissociated form of the reagents. The reason for these changes in the absorption spectra and protolytic properties of both reagents is the formation of hydrophobically hydrated ionic associates of azo compounds with the cetylamine cation.

Photophysical Response of Propranolol in Biomimetic Micellar Media of Alkyltrimethylammonium Bromide Surfactants: Effect of pH and Alkyl Chain Length.

The photophysical behavior of a β-blocker drug propranolol (PPL) in micellar environments, formed by alkyltrimethylammonium bromide surfactants viz.; Cetyltrimethylammonium bromide (CTAB), Tetradecyltrimethylammonium bromide (TTAB), and Dodecyltrimethylammonium bromide (DTAB), has been investigated through fluorescence and UV-visible spectroscopic techniques at pH levels of 3.5, 7.4, and 10.4. The impact of pH on the critical micelle concentration (cmc) and micropolarity of micelles were assessed using pyrene as a photophysical probe. The cmc values were found to be lower at pH 10.4 compared to pH 7.4 and pH 3.5. Fluorescence emission intensities of PPL at 323nm, 338nm, and 352nm were significantly influenced by pH, hydrophobic alkyl chain length of surfactants, and their concentrations. Quenching experiments with Cetylpyridinium chloride (CpCl) indicated the localization of charged and uncharged forms of PPL within micelles, with quenching constant (Ksv) values dependent on alkyl chain length and pH. At pH < pKa, PPL is positioned near the Stern layer, whereas at pH 10.4, its naphthalene moiety resides near the hydrophobic micellar core. UV spectroscopy showed that the charged form of PPL interacted with micelles only above cmc, while the neutral form interacted even below the cmc. Density Functional Theory (DFT) reveals the HOMO of the surfactants to be localized on the hydrocarbon chains, and the LUMO localized around the quaternary ammonium unit. Upon complexation with PPL, both HOMO and LUMO shifted to the drug, thereby decreasing energy levels. The findings are explained based on weak noncovalent interactions, further supported and analyzed through Reduced Density Gradient (RDG) and Noncovalent Interaction (NCI) methods, confirming synergistic non-covalent interactions in surfactant-PPL complexes.

Reduced sialylation of airway mucin impairs mucus transport by altering the biophysical properties of mucin

Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific α-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases.

Two-electron sulfonyl(trifluoromethanesulfonyl)imide-anthraquinone redox electrolytes for high-energy density supercapacitors

Organic redox electrolyte-enhanced electrochemical double layer capacitors (ORECs) are potentially better solution for combining both high power and energy density. The critical factor of ORECs is to develop high-performance organic redox electrolytes. Anthraquinone (AQ) derivatives are the promising organic redox electrolyte candidates because of their low redox potential and fast two-electron redox kinetics. Low solubility and poor longevity in aprotic solvents of charged AQ species are main issues for effective enhancement. Here we report two-electron redox ionic compounds by functionalizing AQ with a robustly electron-withdrawing sulfonyl(trifluoromethanesulfonyl)imide (AQSTFSI) anion and pairing counter monovalent cations for high-performance ORECs. The highly electron-conjugate substitute markedly stabilizes the radical and 2e−-charged forms of AQ by decentralizing the electron density of the CO heads, preventing the adverse reaction of electrophilic/nucleophilic attack, revealing by theoretical simulation. Also, the STFSI− substituent enables AQSTFSI-compounds significantly improved solubility, thermostability, and redox reversibility. Consequently, the AQSTFSI-K applied in OREC shows all-roundly superior performance containing 3.2 V cell voltage, specific energy of 58 Wh kg−1 with 1.8 times of corresponding electrochemical double layer capacitors (EDLCs), specific power over 8 kW kg−1, cycling stability over 12,000 cycles, low self-discharge, and wide working-temperature range. This molecular strategy grounded on electron density modulation of redox electrolyte structures provides valuable insights into the design for high-performance ORECs in practical applications.

Carboxyl-group compounds activate voltage-gated potassium channels via a distinct mechanism.

Voltage-gated ion channels are responsible for the electrical excitability of neurons and cardiomyocytes. Thus, they are obvious targets for pharmaceuticals aimed to modulate excitability. Compounds activating voltage-gated potassium (KV) channels are expected to reduce excitability. To search for new KV-channel activators, we performed a high-throughput screen of 10,000 compounds on a specially designed Shaker KV channel. Here, we report on a large family of channel-activating compounds with a carboxyl (COOH) group as the common motif. The most potent COOH activators are lipophilic (4 < LogP <7) and are suggested to bind at the interface between the lipid bilayer and the channel's positively charged voltage sensor. The negatively charged form of the COOH-group compounds is suggested to open the channel by electrostatically pulling the voltage sensor to an activated state. Several of the COOH-group compounds also activate the therapeutically important KV7.2/7.3 channel and can thus potentially be developed into antiseizure drugs. The COOH-group compounds identified in this study are suggested to act via the same site and mechanism of action as previously studied COOH-group compounds, such as polyunsaturated fatty acids and resin acids, but distinct from sites for several other types of potassium channel-activating compounds.

Reduced Sialylation of Airway Mucin Impairs Mucus Transport by Altering the Biophysical Properties of Mucin.

Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific α-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases.

Enhanced boron removal without pre-pH adjustment via redox-mediated electrodialysis assisted by ion-exchange resins

Boron presents challenges in desalination owing to its small size and lack of charge. While various methods, such as reverse osmosis, capacitive deionization, and electrodeionization, have been utilized to control boron, they often suffer from high levels of energy consumption and complex processes requiring pH adjustment to generate the charged form of boron. Herein, we introduce a novel approach, i.e., redox-mediated electrodialysis (redox-ED) assisted by ion-exchange resins, aimed at energy-efficient boron control without requiring pH adjustment. Our system displays a remarkable boron removal efficiency of 99% with a low energy consumption of 0.009 kWh/g (0.09 kWh/m3). These results are likely due to the dissociation of water on the surface of the ion-exchange resins, which led to a local pH gradient and reduced systemic resistance through additional ion flux. Furthermore, via techno-economic analysis, the total cost of the redox-ED for boron removal revealed a 50% reduction with the scale-up strategy of electrode stacking, compared to those of traditional EDI systems. Overall, this study demonstrates the new potential of a sustainable boron removal technology without pH adjustment through the redox-ED system assisted by ion-exchange resins, providing an attractive option applicable to the boron removal industry.

Molecular Model of Norfloxacin Translocation Through the &lt;i&gt;Yersinia pseudotuberculosis&lt;/i&gt; OmpF Porin Channel

The interaction of Yersinia pseudotuberculosis OmpF (YpOmpF) porin with the fluoroquinolone antibiotic norfloxacin (Nf) and its derivatives (mono- and dihydrochloride) was studied using methods based on the use of bilayer lipid membranes (BLM), molecular modeling, and antibacterial activity testing. Asymmetric behavior of charged Nf (NfH+1) and (Nf2H+2) molecules was found to move through the YpOmpF channel depending on the membrane voltage and the side of antibiotic addition. Electrophysiological data were confirmed by computer modeling. For charged forms of the antibiotic, the presence of two peripheral high-affinity binding sites (NBS1 and NBS2), as well as an asymmetric current blocking site near the channel constriction zone (NBS3), was detected. The NBS1 site located near the channel mouth has almost the same affinity for both charged forms of Nf, while the localization of the more energetically favorable NBS2 site for the two salt forms of the antibiotic differs significantly. Nf has only one binding site near the channel constriction zone, which is a cluster of sites with lower overall affinity compared to the peripheral binding sites mentioned above. Slight differences were found in the antibacterial activity of the three forms of Nf, which is likely due to their different charge states and, accordingly, different permeability and/or ability to bind within the YpOmpF channel.

The rotamer of the second-sphere histidine in AA9 lytic polysaccharide monooxygenase is pH dependent

Lytic polysaccharide monooxygenases (LPMOs) catalyze a reaction that is crucial for the biological decomposition of various biopolymers and for the industrial conversion of plant biomass. Despite the importance of LPMOs, the exact molecular-level nature of the reaction mechanism is still debated today. Here, we investigated the pH-dependent conformation of a second-sphere histidine (His) that we call the stacking histidine, which is conserved in fungal AA9 LPMOs and is speculated to assist catalysis in several of the LPMO reaction pathways.Using constant-pH and accelerated molecular dynamics simulations, we monitored the dynamics of the stacking His in different protonation states for both the resting Cu(II) and active Cu(I) forms of two fungal LPMOs. Consistent with experimental crystallographic and neutron diffraction data, our calculations suggest that the side chain of the protonated and positively charged form is rotated out of the active site toward the solvent. Importantly, only one of the possible neutral states of histidine (HIE state) is observed in the stacking orientation at neutral pH or when bound to cellulose. Our data predict that, in solution, the stacking His may act as a stabilizer (via hydrogen bonding) of the Cu(II)-superoxo complex after the LPMO-Cu(I) has reacted with O2 in solution, which, in fine, leads to H2O2 formation. Also, our data indicate that the HIE-stacking His is a poor acid/base catalyst when bound to the substrate and, in agreement with the literature, may play an important stabilizing role (via hydrogen bonding) during the peroxygenase catalysis.Our study reveals the pH titration midpoint values of the pH-dependent orientation of the stacking His should be considered when modeling and interpreting LPMO reactions, whether it be for classical LPMO kinetics or in industry-oriented enzymatic cocktails, and for understanding LPMO behavior in slightly acidic natural processes such as fungal wood decay.

THE INFLUENCE OF THEOSOPHY ON MODERN PAINTING

An interesting subject that delves into the junction of spirituality, philosophy, and creative expression is the effect of Theosophy on contemporary painting. In the late 19th century, Helena Petrovna Blavatsky established the spiritual movement known as Theosophy. Theosophy is a belief system that seeks to discover the truth about the oneness of all faiths and delve further into the secrets of life, positing the existence of concealed realities beyond the material world. During the late 19th and early 20th centuries, Theosophy wielded a transformative influence on the field of contemporary art. Its principles were not just influential, but potent enough to reshape the work of even the most prominent painters. Russian artist Wassily Kandinsky is a testament to this; his journey was not just instrumental, but transformative in the ascent of abstract expressionism.Theosophical teachings resonated deeply with Kandinsky, echoing not just his profound spirituality, but his personal quest to uncover art's hidden significance. Theosophy posited the existence of concealed realities beyond the material world, placing not just a premium, but a profound importance on the spiritual facets of life. For Kandinsky, art was not just a portal, but a profound conduit for these higher realms, a conduit for the cosmic spirit to manifest. This profoundly impacted Kandinsky as he veered away from realistic imagery and delved into the realm of abstract painting. He aimed to articulate spiritual experiences and emotions through the medium of color and shape. For instance, in his painting 'Composition VII, 'Kandinsky used vibrant colors and dynamic shapes to convey a sense of spiritual energy and movement. Driven by the belief that art could convey profound, transcendent truths, his work progressively shed its symbolic nature. Famous for his geometric abstract paintings, Piet Mondrian was another artist impacted by Theosophy. Theosophy's principles of spiritual progress and cosmic oneness resonated with Mondrian's search for inner peace and a sense of cosmic order, which were crucial to his creative process. For instance, in his painting 'Composition with Red, Yellow, and Blue, 'Mondrian used primary colors and straight lines to represent the harmony and balance he believed existed in the universe, a concept aligned with philosophical ideas. Beyond specific artists, the influence of Theosophy on contemporary art might be seen in more systemic currents like Abstract Expressionism and Symbolism. Some artists, like the symbolists, drew inspiration from the theosophical tradition's emphasis on introspection and mystical themes. Theosophy had not just a significant but a lasting impact on contemporary painting. It inspired painters to seek not just new ways but innovative ways of expressing themselves that went beyond traditional depictions. Modern painting's enduring legacy is not just profoundly rooted but intricately intertwined with theosophical ideas of spirituality, oneness, and inner change, which fostered not just the emergence but the flourishing of abstract and emotionally charged art forms, such as Wassily Kandinsky's abstract expressionism and Piet Mondrian's geometric abstraction, which aimed not just to convey, but to evoke spiritual and emotional experiences through non-representational forms.

Development of a non-destructive depth-selective quantification method for sub-percent carbon contents in steel using negative muon lifetime analysis

The amount of C in steel, which is critical in determining its properties, is strongly influenced by steel production technology. We propose a novel method of quantifying the bulk C content in steel non-destructively using muons. This revolutionary method may be used not only in the quality control of steel in production, but also in analyzing precious steel archaeological artifacts. A negatively charged muon forms an atomic system owing to its negative charge, and is finally absorbed into the nucleus or decays to an electron. The lifetimes of muons differ significantly, depending on whether they are trapped by Fe or C atoms, and identifying the elemental content at the muon stoppage position is possible via muon lifetime measurements. The relationship between the muon capture probabilities of C/Fe and the elemental content of C exhibits a good linearity, and the C content in the steel may be quantitatively determined via muon lifetime measurements. Furthermore, by controlling the incident energies of the muons, they may be stopped in each layer of a stacked sample consisting of three types of steel plates with thicknesses of 0.5 mm, and we successfully determined the C contents in the range 0.20–1.03 wt% depth-selectively, without sample destruction.

Dinitrogen Activation Mediated by the (P2PPh)Fe Complex: Electronic Structure, Dimerization Mechanism, and Magnetic Coupling.

Herein, we report the estimation of the extent of dinitrogen activation by different charged and structural forms of (P2PPh)Fe biomimetic catalysts, which, in the presence of light, exhibit significant yield in the N2-to-NH3 conversion. Complete active space self-consistent field (CASSCF) calculations have been used to determine the electronic structure of different reduced forms of the mononuclear complexes: the neutral (P2PPh)Fe(N2)2 adduct and the anionic [(P2PPh)Fe(N2)]- and [(P2PPh)Fe(N2)]2- complexes. These calculations also revealed that the extent of reduction of a dinitrogen molecule reaches up to one electron (N21-) due to the back-bonding from the Fe center, in agreement with the changes observed in the vibration frequency of the N-N bond in these complexes. In addition, the energy profile of the dimerization of the mononuclear (P2PPh)Fe(N2)2 complex to the dinuclear mono-N2-bridged [(P2PPh)Fe]2(μ-N2) complex has been determined by means of density functional theory (DFT) calculations. A three-step mechanism has been proposed for the dimerization, favored by both kinetics and thermodynamics criteria. Finally, the magnetic coupling constant in the diiron (μ-N2) complex is estimated from CASSCF/NEVPT2 calculations. Such a dinuclear complex presents a strong antiferromagnetic coupling resulting from the interaction between two S = 1 d6 Fe2+ ions, bridged by a highly activated dinitrogen molecule (N22-) with two electrons on the π* orbitals.

Conductance and assembly of quasi-1D coordination chain molecular junctions with triazole derivatives.

Incorporating transition metal atoms into metal-molecule-metal junctions presents opportunities for exploring the electronic properties of coordination complexes, organometallics and metal-organic materials on the single molecule level. Recent single molecule conductance studies have shown that in situ incorporation of electrode metal atoms into coordination chains formed in the junction can occur with deprotonated, negatively charged organic ligands, such as the imidazolate (Im-) anion. However, the mechanism and chemical principles, such as the role of the charge state of the ligand, for the construction of such coordination chains are still debated. Here, we probe the role of the ligand charge state and electronic structure in single-molecule conductance and formation of metal-molecule coordination chains. We perform break junction measurements with triazole isomers, which can bridge junctions both in their neutral and charged forms, and find that prior deprotonation of the ligands is not required for coordination complex assembly, but can affect the molecular conductance and junction formation probability. Our results indicate that coordination chains can form with neutral ligands, as long as the electron density in the frontier MOs is concentrated at the binding sites and along the direction of pulling, promoting ligand binding and incorporation of gold atoms into the junction during elongation. Our findings may provide insight into design principles for in situ assembled molecular wires with transition metal atoms and open the door to electronic and spintronic studies of such materials.

Characterization of solar cell passivating contacts using time-of-flight elastic recoil detection analysis

The unambiguous detection of hydrogen in solar cell contact structures is critical to understanding passivation and degradation phenomena. Deuterium is often used to depict the distribution of hydrogen more clearly. However, experimental noise and artifacts can hinder the clear identification of species. This work provides a report of time-of-flight elastic recoil detection (ToF-ERD) analysis to identify H/D contents in a thin poly-Si/SiOx passivating contact. The structure contained a 1.3 nm interfacial SiOx and an n+ doped poly-Si layer with a partly deuterated SiNx coating. The samples were annealed to release H/D, and ToF-ERD was used to detect H/D in monatomic, singly charged forms, without the detection artifacts associated with conventional secondary ion mass spectroscopy. Chlorine ions were used to recoil surface species, which were analyzed to clearly and unambiguously resolve H and D. Depth profiles for the recoiled Si, N, O, D, and H atoms were calculated from the energy and velocity information registered after scattering events, which enabled the analysis of the structure of the multilayer stack. Even though the surface roughness and experimental limitations cause visible broadening of the profiles, which can hinder clear detection at the interfacial oxide, the ability to resolve hydrogen-related species makes ToF-ERD a significant and promising tool for studying the role of hydrogen in the performance and degradation of solar cell passivating contacts.

Ability of Antibodies Immobilized on Gold Nanoparticles to Bind Small Antigen Fluorescein

The analytical applications of antibodies are often associated with their immobilization on different carriers, which is accompanied by a loss of antigen-binding activity for a sufficient proportion of the bound antibodies. In contrast to data on plain carriers, minimal data are available on the properties of antibodies on the surfaces of nanoparticles. Protein antigens have been predominantly investigated, for which space restrictions do not allow them to occupy all active sites of immobilized antibodies. This study considered a low-molecular-weight compound, fluorescein, as an antigen. Spherical gold nanoparticles with five different sizes, two differently charged forms of fluorescein, and three different levels of surface coverage by immobilized antibodies were tested. For gold nanoparticles with diameters from 14 to 35.5 nm with monolayers of immobilized antibodies, the percentage of molecules capable of binding carboxyfluorescein varied from 6% to 17%. The binding of aminofluorescein was more efficient; for gold nanoparticles with an average diameter of 21 nm, the percentage of active binding sites for the immobilized antibodies reached 27% compared with 13% for the carboxyfluorescein case. A fourfold reduction in the coverage of the nanoparticles’ surface compared with that of the monolayer did not lead to reliable changes in the percentage of active binding sites. The obtained data demonstrate that an antigen’s binding to immobilized antibodies is limited even for small antigens and depends on the size of the nanoparticles and the electrostatic repulsion near their surface.

Structural modeling of hERG channel-drug interactions using Rosetta.

The human ether-a-go-go-related gene (hERG) not only encodes a potassium-selective voltage-gated ion channel essential for normal electrical activity in the heart but is also a major drug anti-target. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome, which predisposes individuals to potentially deadly arrhythmias. However, not all hERG-blocking drugs are proarrhythmic, and their differential affinities to discrete channel conformational states have been suggested to contribute to arrhythmogenicity. We used Rosetta electron density refinement and homology modeling to build structural models of open-state hERG channel wild-type and mutant variants (Y652A, F656A, and Y652A/F656A) and a closed-state wild-type channel based on cryo-electron microscopy structures of hERG and EAG1 channels. These models were used as protein targets for molecular docking of charged and neutral forms of amiodarone, nifekalant, dofetilide, d/l-sotalol, flecainide, and moxifloxacin. We selected these drugs based on their different arrhythmogenic potentials and abilities to facilitate hERG current. Our docking studies and clustering provided atomistic structural insights into state-dependent drug-channel interactions that play a key role in differentiating safe and harmful hERG blockers and can explain hERG channel facilitation through drug interactions with its open-state hydrophobic pockets.

Intrinsic Solubility of Ionizable Compounds from pKa Shift.

Aqueous solubility of pharmaceutical substances plays an important role in small molecule drug discovery and development, with ionizable groups often employed to enhance solubility. Drug candidate compounds often contain ionizable groups to increase their solubility. Recognizing that the electrostatically charged form of the compound is much more soluble than the uncharged form, this work proposes a model to explore the relationship between the pKa shift of the ionizable group and dissolution equilibria. The model considers three forms of a compound: dissolved-charged, dissolved-uncharged, and aggregated-uncharged. It analyzes two linked equilibria: the protonation of the ionizable group and the dissolution-aggregation of the uncharged form, with the observed pKa shift depending on the total concentration of the compound. The active concentration of the aggregates determines this shift. The model was explored through the determination of the pKa shift and intrinsic solubility of specific compounds, such as ICPD47, a high-affinity inhibitor of the Hsp90 chaperone protein and anticancer target, as well as benzoic acid and benzydamine. The model holds the potential for a more nuanced understanding of intrinsic solubility and may lead to advancements in drug discovery and development.

Electromagnetic time-like form factors

We present the calculation of charged pion and kaon electromagnetic form factors in the time-like regime using Schwinger-Dyson equations and the Poincare covariant Bethe-Salpeter equations within an SU(2) isospin symmetric limit. To accurately represent the behavior of a time-like photon, we have incorporated non-valence contributions into the system of equations, enabling the decays ρ → ππ and φ → KK. The inclusion of these decay mechanisms is essential for capturing the expected behavior of the electromagnetic pion and kaon form factors. Our results for the form factors reasonably reproduce the experimental data for a time-like photon.

Study of damped oscillating structures from charged and neutral K-meson electromagnetic form factors data

The damped oscillating structures were recently revealed in the proton “effective” form factor data. For the time being they can neither be confirmed nor disproved by investigations of the individual proton form factors data because the data have not yet achieved the required level of precision. On the other hand, conjectures that the oscillating structures are direct manifestations of the quark-gluon structure of the proton indicate that they should not be specific only to the proton and neutron. This opens a possibility to find these structures also in the data of other hadrons by the same procedure as for the proton. In this paper the oscillatory structures are investigated in the electromagnetic form factor data of the charged and neutral K-mesons. If the charged and neutral K-meson data are described by the three parametric formula by means of which the oscillating structures have been revealed for the proton (although with a large value of chi ^2/ndf) then oscillating structures appear. On the other hand, if the physically well founded Unitary and Analytic model of the K-meson electromagnetic structure is used for the description of the charged K-meson data, no damped oscillating structures are visible. However, in the case of the neutral K-meson data one cannot make a definite conclusion, and more precise data are needed. These results indicate that also the damped oscillating structures obtained from the “effective” proton form factor data are likely an artefact of the three parametric formula, which cannot describe the data with sufficient precision.