pKa Values Research Articles

Tuning Mechanical Characteristics and Permeability of Alginate Hydrogel by Polyvinyl Alcohol and Deep Eutectic Solvent Addition.

Alginate-based hydrogels are widely utilized for various applications, including enzyme immobilization and the development of drug delivery systems, owing to their advantageous characteristics, such as low toxicity, high availability and cost-effectiveness. However, the broad applicability of alginate hydrogels is hindered by their limited mechanical and chemical stability, as well as their poor permeability to hydrophobic molecules. In this study, we addressed the mechanical properties and chemical resistance of alginate hydrogels in a high-pKa environment by the copolymerization of alginate with polyvinyl alcohol (PVA). The addition of PVA resulted in a threefold improvement in the shear modulus of the copolymeric hydrogel, as well as enhanced chemical resistance to (S)-α-methylbenzylamine, a model molecule with a high pKa value. Furthermore, we addressed the permeability challenge by introducing a betaine-propylene glycol deep eutectic solvent (DES) into the PVA-alginate copolymer. This led to an increased permeability for ethyl 3-oxobutanoate, a model molecule used for bioreduction to chiral alcohols. Moreover, the addition of the DES resulted in a notable improvement of the shear modulus of the resulting hydrogel. This dual effect highlights the role of the DES in achieving the desired improvement of the hydrogel as an immobilization carrier.

Dissociation Constant of Di‐ and Tri‐Basic Solvents Based on Piperazine and Its Derivatives for Post‐Combustion CO2 Capture

AbstractAmine solvents remain popular in the industries for post combustion carbon dioxide (CO2) capture. Dissociation constant of basic amine solvents plays significant role to influence the CO2 absorption. It is thus important to study the dissociation of new amine solvents for assessing their viability for CO2 capture. In the present work, potentiometric titration method is employed to determine the dissociation constants of dibasic (e. g., Piperazine (PZ), 1‐methyl piperazine (1‐MPZ) and tribasic amines (1‐(2‐aminoethyl‐piperazine) (AEPZ) which could be promising for formulating blended solvent system towards enhancing the rate of CO2 absorption. The estimated dissociation constants for the PZ and 1‐MPZ while match well with reported results, the dissociation constants for AEPZ has been determined newly here within the temperature range 298—318 K. In addition, the structural geometric parameters and Natural Bond Order (NBO) calculations of the amine solvents are performed based on Density Functional Theory (DFT). The NBO calculations predict charge distribution on the nitrogen and other elements, and envisage its effect on the pKa values of the amines. Further, potential energy surface (PES) scanning calculations are performed for AEPZ to explain it's ring inversion which is responsible for obtaining a single pKa value in experimental studies.

Enhancing SN38 prodrug delivery using a self-immolative linker and endogenous albumin transport

Enhancing the delivery and release efficiency of hydroxyl agents, constrained by high pKa values and issues of release rate or unstable linkage, is a critical challenge. To address this, a self-immolative linker, composed of a modifiable p-hydroxybenzyl ether and a fast cyclization adapter (N-(ortho-hydroxyphenyl)-N-methylcarbamate) was strategically designed, for the synthesis of prodrugs. The innovative linker not only provides a side chain modification but also facilitates the rapid release of the active payloads, thereby enabling precise drug delivery. Particularly, five prodrug model compounds (J1, J2, J3, J5 and J6) were synthesized to evaluate the release rates by using β-glucuronic acid as trigger and five hydroxyl compounds as model payloads. Significantly, all prodrug model compounds could efficiently release the hydroxyl payloads under the action of β-glucuronidase, validating the robustness of the linker. And then, to assess the drug delivery and release efficiency using endogenous albumin as a transport vehicle, J1148, a SN38 prodrug modified with maleimide side chain was synthesized. Results demonstrated that J1148 covalently bound to plasma albumin through in situ Michael addition, effectively targeting the tumor microenvironment. Activated by β-glucuronidase, J1148 underwent a classical 1, 6-elimination, followed by rapid cyclization of the adapter, thereby releasing SN38. Impressively, J1148 showed excellent therapeutic efficacy against human colonic cancer xenograft model, leading to a significant reduction or even disappearance of tumors (3/6 of mice cured). These findings underscore the potential of the designed linker in the delivery system of hydroxyl agents, positioning it at the forefront of advancements in drug delivery technology.

Tuning Acid-Base Chemistry at an Electrified Gold/Water Interface.

Acid-base reactions are ubiquitous in solution chemistry, as well as in electrochemistry. However, macroscopic concepts derived in solutions, such as pKa and pH, differ significantly at electrified metal-aqueous interfaces due to specific solvation and applied voltage. Here, we measure the pKa values of an amino acid, glycine, at a gold/water interface under a varying applied voltage by means of spectroscopic titration. With the help of simulations, we propose a general model to understand potential-dependent shifts in pKa values in terms of local hydrophobicity and electric fields. These parameters can be tuned by adjusting the metal surface and applied voltage, respectively, offering promising, but still unexplored, paths to regulate reactivity. Our results change the focus with respect to common interpretations based on, for example, apparent local pH effects and open interesting perspectives for electrochemical reaction steering.

Peroxydisulfate-Driven Reductive Dechlorination as Affected by Soil Constituents: Free Radical Formation and Conversion.

We report a previously unrecognized but efficient reductive degradation pathway in peroxydisulfate (PDS)-driven soil remediation. With supplements of naturally occurring low-molecular-weight organic acids (LMWOAs) in anaerobic biochar-activated PDS systems, degradation rates of 12 γ-hexachlorocyclohexanes (HCH)-spiked soils boosted from 40% without LMWOAs to a maximum of 99% with 1 mM malic acid. Structural analysis revealed that an increase in α-hydroxyl groups and a diminution in pKa1 values of LMWOAs facilitated the formation of reductive carboxyl anion radicals (COO•-) via electrophilic attack by SO4•-/•OH. Furthermore, degradation kinetics were strongly correlated with soil organic matter (SOM) contents than iron minerals. Combining a newly developed in situ fluorescence detector of reductive radicals with quenching experiments, we showed that for soils with high, medium, and low SOM contents, dominant reactive species switched from singlet oxygen/semiquinone radicals to SO4•-/•OH and then to COO•- (contribution increased from 30.8 to 66.7%), yielding superior HCH degradation. Validation experiments using SOM model compounds highlighted critical roles of redox-active moieties, such as phenolic - OH and quinones, in radical formation and conversion. Our study provides insights into environmental behaviors related to radical activation of persulfate in a broader soil horizon and inspiration for more advanced reduction technologies.

TBA magnetically functionalized materials combined with biomass-derived fluorescent probe for Listeria monocytogenes detection in a sandwich-like strategy

Ultrasensitive and simultaneous quantitative detection of Listeria monocytogenes (L. monocytogenes) that can survive in vacuum packaging and frozen food is critical to public health. Herein, teamed boronate affinity (TBA) magnetically functionalized materials combined with biomass fluorescent probe for L. monocytogenes detection in a sandwich-like strategy was established. Firstly, we prepared new TBA magnetically functionalized materials by reducing the pKa value of phenylboronic acid through the TBA strategy in the form of self-assembled intermolecular B-N coordination bonding. To our knowledge, this is the first study where TBA magnetically functionalized materials were utilized for the identification and capture of bacteria, with a high capture efficiency of over 90.8% in spiked lettuce samples for L. monocytogenes (within 35 min), showing superior capture ability. Then, Anti-L. monocytogenes monoclonal antibody was labeled in biomass-derived fluorescent probe with the help of biotin-streptavidin system to achieve specific and sensitive detection of L. monocytogenes. The sandwich-like strategy shows high sensitivity of designed fluorescence sensing platform for L. monocytogenes with a wide linear range (2.2 × 101–2.2 × 106 CFU/mL), a low limit of detection (2.2 × 101 CFU/mL), and a satisfactory recovery rate (85.19%–106.69%) spiked lettuce sample. Notably, the method was low-cost, general and had strong application prospects in the field of food safety.

Ionizable Lipids from Click Reactions for Lipid Nanoparticle Assembling and mRNA Delivery.

Ionizable lipid-containing lipid nanoparticles (LNPs) are regarded as promising nonviral vectors for gene therapy delivery systems. Rationale design of the ionizable lipid structure based on initial screening of ionizable lipid molecule libraries combined with systematic comparison and analysis on the physical chemical parameters related to delivery efficiency greatly accelerated the discovery of novel LNP candidates for delivering various nucleic acid therapeutics like mRNAs (mRNAs). Based on the copper-catalyzed azide-alkyne click reaction, which is highly efficient and biocompatible, we were able to obtain the lipid molecule library containing a common triazole moiety between different lipid tails and various substituents as hydrophilic head groups. Herein, we systematically investigated the change of pKa values of different ionizable lipid molecules with different substituents as head groups in the click-based lipid library, mapping the pKa value change to different steps in the process of the LNP assembly and mRNA delivery. Systematic analyses on the data including the pKa value of the ionized lipids and the encapsulation and delivery efficiency of mRNA in LNPs with these ionized lipids provided the possibility of rational design on the head and tail structure for the triazole containing ionized lipids to realize highly efficient delivery of different mRNAs.

Substitution of both histidines in the active site of yeast alcohol dehydrogenase 1 exposes underlying pH dependencies

Histidine residues 44 and 48 in yeast alcohol dehydrogenase (ADH) bind to the coenzymes NAD(H) and contribute to catalysis. The individual H44R and H48Q substitutions alter the kinetics and pH dependencies, and now the roles of other ionizable groups in the enzyme were studied in the doubly substituted H44R/H48Q ADH. The substitutions make the enzyme more resistant to inactivation by diethyl pyrocarbonate, modestly improve affinity for coenzymes, and substantially decrease catalytic efficiencies for ethanol oxidation and acetaldehyde reduction. The pH dependencies for several kinetic parameters are shifted from pK values for wild-type ADH of 7.3–8.1 to values for H44R/H48Q ADH of 8.0–9.6, and are assigned to the water or alcohol bound to the catalytic zinc. It appears that the rate of binding of NAD+ is electrostatically favored with zinc-hydroxide whereas binding of NADH is faster with neutral zinc-water. The pH dependencies of catalytic efficiencies (V/EtKm) for ethanol oxidation and acetaldehyde reduction are similarly controlled by deprotonation and protonation, respectively. The substitutions make an enzyme that resembles the homologous horse liver H51Q ADH, which has Arg-47 and Gln-51 and exhibits similar pK values. In the wild-type ADHs, it appears that His-48 (or His-51) in the proton relay systems linked to the catalytic zinc ligands modulate catalytic efficiencies.

Determination and Validation of pKa value of Atropine Sulfate using Spectrophotometry

The ionization state (pKa) of a compound influences its absorption, distribution, metabolism and excretion. Therefore, proper knowledge of the pKa is crucial in understanding the behavior of a compound behavior inside the body. In this research paper, we validate the pKa of muscarinic acetylcholine receptor antagonist atropine sulfate using Uv-Vis spectroscopy, to validate the use of this method and to re-evaluate the of atropine sulfate. The pKa value from absorption measurements is first estimated using 3rd degree polynomial and then precisely calculated according to the Albert-Sergeant method. We established that the pKa value of Atropine sulfate is 9.94±0.050 which is comparable to the values present in the literature.

Iota carrageenan linked barium ion nanoparticle synthesis for the selective targeted imaging and inhibition of cancer cells

Abstract The development of stable carrageenan nanoparticles connected to the sulfate functional group of carrageenan and barium ion for the use of selectively targeting cancer cell and imaging contrast to help with diagnosis (tracing/imaging) is the concern of the present research. This study provides an overview of ion substitution chemistry, highlighting the role of ions and how they affect the applicability of carrageenan. The characteristic of barium sulfate, which is widely used as radiopaque to provide contrast for diagnostic radiographic examinations in the gastrointestinal mucosa, is provided by its linkage with the barium ion despite K+’s natural binding with carrageenan. The additional role of the Ba ion linked carrageenan was found highly selective for cancer cell through the in vitro cell line assay; however, the nonattachability to the normal cell makes useful to trace and treat the cancer cell. The tracing is possible because of the barium sulfate functional group and its nanosize molecule, which shows precision medicine, fluorescence, and X-ray/CT imaging character, to be utilized as the diagnostic purpose, especially to tumor cell. The apoptosis from the Ba2+ ion by the inhibition of outflux of K+ to disturb the osmosis of cell and selectivity of the molecules because of high pKa (Logarithms of acid dissociation constant) value, which makes the drug more active anionic (nonpolar) form in the cancer cell and ionic form (polar) in the normal cell, which avoids the interaction with normal cell and facilitate the interaction with cancer cell. In conclusion, the cancer cell selectivity with fluorescence and radiopaque properties of Ba ion linked carrageenan makes the molecule useful for tracing, imaging, and treating cancer cell with high selectivity.

Protolytic properties of methyl yellow both in water-ethanol medium and in hardened gelatin gel with the presence of sodium dodecylsulphate and tetrabutylammonium chloride

This paper presents the results of studying the acid-base properties of the indicator dye methyl yellow in water–ethanol solutions with a volume fraction of alcohol of 10 % and 50 %. The influence of the addition of NaCl salts and tetrabutylammonium chloride, as well as the anionic surfactant sodium dodecylsulfate (SDS) on the acidity constant of the indicator, was evaluated. Under the chosen conditions, ethanol additives have a more significant effect on the pKa value. For the first time, using the dynamic light scattering method, the particle sizes, polydispersity index, and ζ-potential of colloidal particles in pure aqueous and mixed water–ethanol solutions of methyl yellow (φalcohol from 0.2 % to 50 %) in the presence of NaCl and SDS were estimated. In solutions with φalcohol = 50 % colloidal particles were not found. It has been shown that the hardened gelatin gel of photographic film can be used as a convenient sorbent for methyl yellow. In the process of dye extraction into a gelatin film from water-alcohol solutions containing SDS and NaCl, the acid-base properties of the methyl yellow remained almost unchanged. The difference between the pKa values obtained for the indicator both in solution and in the film did not exceed the measurement error.

Variations in proton transfer pathways and energetics on pristine and defect-rich quartz surfaces in water: Insights into the bimodal acidities of quartz

HypothesisUnderstanding the mechanisms of proton transfer on quartz surfaces in water is critical for a range of processes in geochemical, environmental, and materials sciences. The wide range of surface acidities (>9 pKa units) found on the ubiquitous mineral quartz is caused by the structural variations of surface silanol groups. Molecular scale simulations provide essential tools for elucidating the origin of site-specific surface acidities. SimulationsWe used density-functional tight-binding-based molecular dynamics combined with rare-event metadynamics simulations to probe the mechanisms of deprotonation reactions from ten representative surface silanol groups found on both pristine and defect-rich quartz (101) surfaces with Si vacancies. FindingsThe results show that deprotonation is a highly dynamic process where both the surface hydroxyls and bridging oxygen atoms serve as the proton acceptors, in addition to water. Deprotonation of embedded silanols through intrasurface proton transfer exhibited lower pKa values with less H-bond participation and higher energy barriers, suggesting a new mechanism to explain the bimodal acidity observed on quartz surface. Defect sites, recently shown to comprise a significant portion of the quartz (101) surface, diversify the coordination and local H-bonding environments of the surface silanols, changing both the deprotonation pathways and energetics, leading to a wider range of pKa values (2.4 to 11.5) than that observed on pristine quartz surface (10.4 and 12.1).

The pKa Values of Water in Water: A Long-Standing, Tiresome, yet Soon Forgotten Issue?

The pKa values of water and the hydrogen ion (proton) in water are 14 and 0, respectively. Yet, many textbooks of general, organic, and, to a lesser extent, inorganic chemistry provide the incorrect values 15.74 and -1.74, respectively. This column briefly introduces the long-standing issue of these two different pairs of values, the consequences it bears when teaching general chemistry, and expresses the hope that it may be solved soon.

Determination of dissociation constants of cephalosporin antibiotics by cellmetry method

Acid dissociation constants of three cephalosporin antibiotics (cefapirin, ceftiofur, and cefotaxime) were calculated by a newly developed methodology. Plane-wave DFT calculations were performed to determine the pKa values, and by choosing the appropriate cell sizes, accurate values could be calculated. Some characteristic points were found which helped us to find correlations among the structural and physic-chemical parameters, and correlation factors were defined as well. This present study can be a base for further approaches to determining acid dissociation constants of cephalosporin molecules.Graphical

Aggregation of graphene oxide upon the stripping of oxidized debris: An experimental and molecular dynamics simulation study

The most recent structural study of graphene oxide (GO) indicates that the oxidized debris (ODs) adhered to as-prepared GO will strip in certain aquatic settings. The impact of ODs stripping on the characteristics of GO has been widely reported, but its effects on GO aggregation have received less attention. Here, the influence of OD stripping on the GO aggregation property was identified, and the aggregation of as-prepared GO and GO upon OD stripping was compared. Upon ODs stripping, the pKa values of GO shifted from 3.91, 6.25, and 9.84 to 4.54, 6.65, and 10.21, respectively. Further analysis indicated the removal of ODs reduced the net negative charge and improved the hydrophobicity of GO, hence promoting the aggregation of GO. The acceleration of GO-Ca2+-OD aggregate formation was facilitated by the collective effects of ODs stripping, functional group deprotonation, double layer compression, OD bridging, and charge neutralization. The metal ions and stripped ODs attach to GO edges and link GO, which perform like bridges and contribute to further aggregation. In general, the existence of ODs adds complexity to the constructions and characteristics of GO, and it is important to take this into account while evaluating the aggregation characteristic of GO-based materials.

PH-sensitive cationic nanoparticles for endosomal cell-free DNA scavenging against acute inflammation

Cell-free DNA (cfDNA) released from dead cells could be a player in some autoimmune disorders by activating Toll-like receptor 9 (TLR9) and inducing proinflammatory cytokines. Cationic nanoparticles (cNPs) address cfDNA clearance, yet challenges persist, including toxicity, low specificity and ineffectiveness against endocytosed cfDNA. This study introduced pH-sensitive cNPs, reducing off-target effects and binding cfDNA at inflammatory sites. This unique approach inhibits the TLR9 pathway, offering a novel strategy for inflammation modulation. Synthesized cNPs, with distinct cationic moieties, exhibit varied pKa values, enhancing cfDNA binding. Comprehensive studies elucidate the mechanism, demonstrating minimal extracellular binding, enhanced endosomal DNA binding, and optimal tumor necrosis factor-α suppression. In a traumatic brain injury mice model, pH-sensitive cNPs effectively suppress inflammatory cytokines, highlighting their potential in acute inflammation regulation.

β-Dicarbonyls Facilitate Engineered Microbial Bromoform Biosynthesis.

Ruminant livestock produce around 24% of global anthropogenic methane emissions. Methanogenesis in the animal rumen is significantly inhibited by bromoform, which is abundant in seaweeds of the genus Asparagopsis. This has prompted the development of livestock feed additives based on Asparagopsis to mitigate methane emissions, although this approach alone is unlikely to satisfy global demand. Here we engineer a non-native biosynthesis pathway to produce bromoform in vivo with yeast as an alternative biological source that may enable sustainable, scalable production of bromoform by fermentation. β-dicarbonyl compounds with low pKa values were identified as essential substrates for bromoform production and enabled bromoform synthesis in engineered Saccharomyces cerevisiae expressing a vanadate-dependent haloperoxidase gene. In addition to providing a potential route to the sustainable biological production of bromoform at scale, this work advances the development of novel microbial biosynthetic pathways for halogenation.

Thermodynamic property estimations for aqueous primary, secondary, and tertiary alkylamines, benzylamines, and their corresponding aminiums across temperature and pressure are validated by measurements from experiments

On Earth and beyond, organic chemistry often occurs in the presence of water within environments that deviate drastically from ambient conditions (25 °C and 1 bar). Accurately predicting aqueous organic reaction pathways is crucial toward understanding planetary scale processes such as the cycling of elements crucial for life (e.g., carbon and nitrogen). Advanced thermodynamic modeling can be utilized to determine the favorability of various organic reactions based on geologically relevant ranges of temperature and pressure, as well as compositional variables (e.g., pH). However, data that would otherwise allow for a diversity of organic compounds and environmental conditions to be modeled are sparse and rarely tested with experiments, particularly with regard to organic-nitrogen compounds. In this work, we develop a framework to estimate thermodynamic properties at ambient conditions that can then be extrapolated across ranges of temperature and pressure for aqueous primary, secondary, and tertiary amines and aminiums (protonated amines), specifically those structures containing linear alkyl chains and benzyl functional groups. We also performed hydrothermal experiments (250 °C, ∼40 bar) involving reactions of methylamines to test our resulting thermodynamic models, and we compare our models for other alkylamines and benzylamines to previous empirical measurements from the literature. Specifically, we use existing thermodynamic data along with our estimates at ambient conditions in combination with a variety of existing extrapolation methods related to the revised Helgeson-Kirkham-Flowers (HKF) equations of state to generate temperature- and pressure-dependent predictions of acid dissociation constants (i.e., pKa values) that strongly agree with previous empirical measurements. We use similar methods to predict product distributions for reactions involving primary, secondary, and tertiary amines/aminiums, as well as ammonia/ammonium and corresponding alcohols whose collective distributions depend on reversible substitution reactions. Our predictions are in good agreement with our experimental results involving the methylamine reaction system as well as previous experiments involving the benzylamine reaction system, for which we also produced thermodynamic estimates involving benzyl alcohol. The agreement between independent theoretical predictions and experimental measurements suggests that our estimated properties can be applied to modeling amine chemistry in other experimental and natural aqueous systems that range in temperature and pressure, providing new tools for planetary exploration.

Fabrication of pH-Responsive PDPAEMA Thin Film Using a One-Step Environmentally Friendly Plasma Enhanced Chemical Vapor Deposition

In recent years, there has been growing interest in pH-responsive polymers. Polymers with ionizable tertiary amine groups, which have the potential to be used in many critical application areas due to their pKa values, have an important place in pH-responsive polymers. In this study, poly(2-Diisopropyl aminoethyl methacrylate) (PDPAEMA) thin films were coated on various substrates such as glass, fabric, and silicon wafer using a one-step environmentally friendly plasma enhanced chemical vapor deposition (PECVD) method. The effects of typical PECVD plasma processing parameters such as substrate temperature, plasma power, and reactor pressure on the deposition rate were studied. The highest deposition rate was obtained at a substrate temperature of 40 °C, a reactor pressure of 300 mtorr, and a plasma power of 60 W. The apparent activation energy was found to be 17.56 kJ/mol. Based on the results of this study, uniform film thickness and surface roughness were observed in a large area. The PDPAEMA thin film was exposed to successive acid/base cycles. The results showed that the pH sensitivity of the thin film produced by the PECVD method is permanent and reversible.

A novel dual-color fluorescent sensor with two pKas for on-site detection of pH in food

Tracking pH fluctuations in food samples is important for ensuring food freshness. Fluorescent probes have been widely applied as promising tools for the on-site detection of pH changes; however, most of them can be applied only at either lower or higher pH ranges because their response structures commonly have a single acid dissociation constant (pKa). To address this problem, we designed a fluorescent sensor, called HMB, containing a methylpiperazine group with two pKa values, which exhibited a unique dual-color response to pH changes over a wide pH range. Furthermore, the HMB-based test strips are easily prepared and used as portable labels for the visual monitoring of food spoilage that results in microbial and anaerobic glycolytic pathways in real food (such as cheese and shrimp). To the best of our knowledge, this is the first fluorescent pH sensor with two pKa values, and we expect that this work will inspire more sensor designs for food quality control.