pKa Values Research Articles

Thermodynamics of Proton-Coupled Electron Transfer at Tricopper μ-Oxo/Hydroxo/Aqua Complexes.

Multicopper oxidases (MCOs) utilize a tricopper active site to reduce dioxygen to water through 4H+ 4e- proton-coupled electron transfer (PCET). Understanding the thermodynamics of PCET at a tricopper cluster is essential for elucidating how MCOs harness the oxidative power of O2 while mitigating oxidative damage. In this study, we determined the O-H bond dissociation free energies (BDFEs) and pKa values of a series of tricopper hydroxo and tricopper aqua complexes as synthetic models of the tricopper site in MCOs. Tricopper intermediates on the path of alternating electron and proton transfer (ET-PT-ET-PT-ET) have modest BDFE(O-H) values in the range of 53.0-57.1 kcal/mol. In contrast, those not on the path of ET-PT-ET-PT-ET display much higher (78.1 kcal/mol) or lower (44.7 kcal/mol) BDFE(O-H) values. Additionally, the pKa of bridging OH and OH2 motifs increase by 8-16 pKa units per oxidation state. The same oxidation state changes have a lesser impact on the pKa of N-H motif in the secondary coordination sphere, with an increase of ca. 5 pKa units per oxidation state. The steeper pKa increase of the tricopper center promotes proton transfer from the secondary coordination sphere. Overall, our study shed light on the PCET pathway least prone to decomposition, elucidating why tricopper centers are an optimal choice for promoting efficient oxygen reduction reaction.

Energetics of the H-Bond Network in Exiguobacterium sibiricum Rhodopsin.

Exiguobacterium sibiricum rhodopsin (ESR) functions as a light-driven proton pump utilizing Lys96 for proton uptake and maintaining its activity over a wide pH range. Using a combination of methodologies including the linear Poisson-Boltzmann equation and a quantum mechanical/molecular mechanical approach with a polarizable continuum model, we explore the microscopic mechanisms underlying its pumping activity. Lys96, the primary proton uptake site, remains deprotonated owing to the loss of solvation in the ESR protein environment. Asp85, serving as a proton acceptor group for Lys96, does not form a low-barrier H-bond with His57. Instead, deprotonated Asp85 forms a salt-bridge with protonated His57, and the proton is predominantly located at the His57 moiety. Glu214, the only acidic residue at the end of the H-bond network exhibits a pKa value of ∼6, slightly elevated due to solvation loss. It seems likely that the H-bond network [Asp85···His57···H2O···Glu214] serves as a proton-conducting pathway toward the protein bulk surface.

A new fluorescent probe for detection of hydrazine and extremely acidic pH in different modes

Toxic hydrazine poses a huge threat to living organisms and our environment. Extremely acidic pH is also harmful to various ecosystems. Here, a coumarin-based dye called CMM has been synthesized for the ratiometric detection of hydrazine (F504 nm/F560 nm). CMM could detect gaseous hydrazine in the environment and endogenous hydrazine in live cells. Furthermore, the fluorescence at 563 nm of CMM was stable from pH 10.0 to 2.0, whereas increased greatly from pH 2.0 to 1.2. Thus, the probe could also detect extremely acidic pH with great fluorescence enhancement. The pKa value was determined to be as low as 1.41. We anticipate that the probe could provide a good candidate for detection of toxic hydrazine and extremely acidic pH.

The Impact of Water as an Additive on the Elution of Some Basic Organic Compounds in Supercritical Fluid Chromatography.

In this study, water was used as an additive in the methanol-modified carbon dioxide-based eluent for the elution of some basic organic compounds from a hybrid silica column via supercritical fluid chromatography (SFC). The experiments were applied to sulfonamides, propranolol, and other organic nitrogen compounds involving aromatic rings from different classes of amine, pyrimidine, and purine with different pKa values (the pKa values for the studied analytes range from 4.6 to 10.4). The results revealed different responses to the different percentages of water addition. Adding 1~2% of water to the modifier (methanol) led to a positive effect manifested by more symmetrical peak shapes and reduced retention times for most compounds. The key factor for this improvement in the properties of chromatographic peaks is due to the adsorption of water on the silanol groups of the stationary phase, consequently resembling the phenomena observed in hydrophilic interaction liquid chromatography (HILIC). Moreover, the availability of hydrogen bond acceptor and donor sites in the analyte structure is an important factor to be considered when adding water as an additive to the modifier for improving the chromatographic peaks. However, introducing water in an amount higher than 3% resulted in perturbed chromatographic signals. It was also found that water as an additive alone could not successfully elute propranolol from the hybrid silica column with an acceptable peak shape; thus, the addition of a strong base such as amine salts was also necessary. The proposed use of a particular amount of water in the mobile phase could have a positive effect compared to the same mobile phase without water, improving the chromatographic peak properties of the elution of some basic organic compounds from the hybrid silica column.

Towards elevated perfluorooctanoic acid (PFOA) enrichment in water: Sequential liquid-liquid extraction pretreatment for ion chromatography detection

The widespread detection of perfluorooctanoic acid (PFOA) in the environment has raised significant concerns. The standard PFOA analytical method relies on expensive solid-phase extraction (SPE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) instruments, making routine use prohibitive. We herein proposed a cost-effective yet novel enrichment method for determining PFOA at ng L−1 level. This method entailed a two-step sample preparation process: firstly, PFOA was extracted and enriched using a forward-extraction under acidic conditions, followed by a backward-extraction and enrichment step utilizing alkaline water. The enriched samples were subsequently subjected to a common ion chromatography (IC). Results reveal that maintaining a forward-extraction pH below its pKa value (2.8) is essential, as protonated PFOA proves effective in enhancing the enrichment factor (EF). The challenge lied in driving PFOA from forward-extractant to aqueous backward-extractant due to the decreased hydrophobicity of deprotonated PFOA (log Kow2 = 1.0). In addition, we found that evaporating forward-extractant with alkaline backward-extractant (containing 5% methanol) reduced potential analytical uncertainties associated with PFOA evaporation and sorption. Under optimal conditions, the method achieved a detection limit of 9.2 ng L−1 and an impressive EF value of 719. Comparison with SPE-LC-MS/MS confirmed the proposed method as a promising alternative for PFOA determination. Although initially targeted for PFOA, the novel methodology is likely applicable to preconcentration of other poly-fluoroalkyl substances.

Coprecipitation of Fe/Cr Hydroxides at Organic-Water Interfaces: Functional Group Richness and (De)protonation Control Amounts and Compositions of Coprecipitates.

Iron/chromium hydroxide coprecipitation controls the fate and transport of toxic chromium (Cr) in many natural and engineered systems. Organic coatings on soil and engineered surfaces are ubiquitous; however, mechanistic controls of these organic coatings over Fe/Cr hydroxide coprecipitation are poorly understood. Here, Fe/Cr hydroxide coprecipitation was conducted on model organic coatings of humic acid (HA), sodium alginate (SA), and bovine serum albumin (BSA). The organics bonded with SiO2 through ligand exchange with carboxyl (-COOH), and the adsorbed amounts and pKa values of -COOH controlled surface charges of coatings. The adsorbed organic films also had different complexation capacities with Fe/Cr ions and Fe/Cr hydroxide particles, resulting in significant differences in both the amount (on HA > SA(-COOH) ≫ BSA(-NH2)) and composition (Cr/Fe molar ratio: on BSA(-NH2) ≫ HA > SA(-COOH)) of heterogeneous precipitates. Negatively charged -COOH attracted more Fe ions and oligomers of hydrolyzed Fe/Cr species and subsequently promoted heterogeneous precipitation of Fe/Cr hydroxide nanoparticles. Organic coatings containing -NH2 were positively charged at acidic pH because of the high pKa value of the functional group, limiting cation adsorption and formation of coprecipitates. Meanwhile, the higher local pH near the -NH2 coatings promoted the formation of Cr(OH)3. This study advances fundamental understanding of heterogeneous Fe/Cr hydroxide coprecipitation on organics, which is essential for successful Cr remediation and removal in both natural and engineered settings, as well as the synthesis of Cr-doped iron (oxy)hydroxides for material applications.

Depletion of Free Chlorine and Generation of Trichloromethane in the Presence of pH Control Agents in Chlorinated Water at pH 6.5

Chlorine is commonly used by the fresh produce industry to sanitize water and minimize pathogen cross-contamination during handling. The pH of chlorinated water is often reduced to values of pH 6–7, most commonly with citric acid to stabilize the active antimicrobial, hypochlorous acid (a form of free chlorine). Previous studies have demonstrated that citric acid reacts with chlorine to form trichloromethane, a major chlorine by−product in water and a potential human carcinogen. However, it is unclear if other pH control agents could be used in the place of citric acid to minimize the formation of trichloromethane. The objective of the present study was to determine the reactivity of organic and inorganic pH control agents, with chlorine, to generate trichloromethane. Free chlorine (∼100 mg/L) was mixed with 10 mM of each of twelve organic acids and two inorganic pH control agents (i.e., sodium acid sulfate and phosphoric acid) to effect a pH level of 6.5. Free chlorine and trichloromethane levels were measured over 3 h at 3 and 22°C. Results demonstrated that ascorbic acid, dehydroascorbic acid, citric acid, and malic acid rapidly depleted free chlorine concentrations at both 22°C and 3°C, while tartaric acid and lactic acid decreased chlorine concentrations more slowly. Other pH control agents did not significantly reduce free chlorine either at 22 or 3°C. Citric acid led to the generation of significantly higher concentrations of trichloromethane than did other acids. Chloroacetone was also found in chlorinated water in the presence of citric acid and ascorbic acid. Taking buffering capacity and pKa values into account, phosphoric acid and some organic acids may be used to replace citric acid as pH control agents in chlorinated water for washing fresh produce, to stabilize free chlorine level and reduce the generation of trichloromethane.

Characterization and drug solubilization of arginine-based ionic liquids – Impact of counterions and stoichiometry

Ionic liquids (ILs) exhibit very diverse physicochemical properties, such as non-volatility, stability, and miscibility, which render them excellent candidate excipients for multi-purpose use. Six novel arginine (Arg)-based ILs were obtained using a one-step ultrasound method. Salt formation was confirmed by Fourier-transform infrared (FTIR), Raman, and nuclear magnetic resonance (NMR) spectroscopies. Moreover, the effects of anions and molar ratio on the molecular states and thermal properties of Arg-ILs were investigated. In addition, the solubilization of drugs with different pKa and LogP values was attempted using Arg-ILs consisting of asparagine, proline, octanoic acid, and malic acid, respectively, and a comparative study was performed. Furthermore, the interaction mode between the drugs and ILs was determined by FTIR and Raman spectroscopy. Presumably, partial interaction between the component of ILs and drugs such as ofloxacin and valsartan occurred, whereas flurbiprofen and isosorbide mononitrate were dispersed in the viscous IL. The development of strategies for the application of ILs as solubilizers or carriers of active pharmaceutical ingredients is an extremely promising and wide avenue of research

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.

Green DES based microextraction method for monitoring brilliant black BN (E151) in diverse food matrices

A green deep eutectic solvent (DES) based microextraction method was established for separation and spectrophotometric determination of E151 in food matrices. DES composed of tetra pentyl ammonium bromide and 1-octanol (1:5) was used. Important analytical microextraction parameters including pH, volume of DES and time of vortex mixing were optimized using Box-Behnken design of Response Surface Methodology. The other variables including composition ratio of DES and sample volume were optimized by one variable at a time optimization process. The method exhibited linear behaviour for E151 having concentration range between 132–12000 µg/L with 30 preconcentration factor. The relative standard deviation, detection limit and quantitation limit were determined to be 5 %, 40 and 132 µg/L, respectively. The scores of analytical greenness and applicability for the method were determined to be 0.69 and 62.5, respectively. pK values of E151 were determined. Extraction mechanisms of E151 were elucidated. The method was applied to foodstuffs and water samples to determine their E151 contents by analyte addition recovery tests with recovery values ranging between 94–103 %.

Developing a binary composite of covalent organic framework and gold microstructures: Highly efficient dual-mode catalyst for analysis of nitrophenol isomers and their oxidative products

As a key hazard, nitrophenol and its byproducts are a vital raw material in the industry and potentially released into aquatic environments, which affects the ecosystem and severely threatens living systems. It is crucial to detect nitro-hazards quantitatively and systematically. The unique structures of isomer separation and catalytic reduction are highly complex in a single system, not yet reported detection method. The present report constructed robust gold-microstructures (AuMSs) with bis-triazole-derived covalent organic framework (BTCOF) was developed to analyze the dual-mode application of electrochemical redox signals and catalytic degradation of nitrophenol isomers (NPIs) and their oxidative products. The synergistic interaction of tunable surfaces on binary materials enhanced catalytic efficiency, faster kinetic rates, and poor passivation effect. Based on the variance in pKa values, both NPIs and nitrosophenols (NSPIs) could be identified, peak separated, and sensed simultaneously. A catalyst combined with NaBH4, enabled NPIs reduction within 10 minutes. This proposed electrochemical method achieved a nanomolar LOD (1.82, 1.67, and 1.15 × 10−9 M for o-, m-, and p-NPs), excellent sensitivity to ultrawide linear range concentrations while being selective, and reproducible. Moreover, AuMSs-BTCOF/GCE detected NPIs in the industrial effluents and biofluids with recovery rates between 94.70 to 99.95 ± 0.18 % with RSD of 2.86 %. The electrochemical result was validated by conventional method with proven statistical analysis (error 4.02 %). In the catalytic reduction of NPIs, the catalyst is more than 89.24 % efficient, and durable stability. The designed system has proven to be an effective, sensitive, and accurate dual-detection tool for monitoring environmental targets and diagnosing diseases.

Direct infusion mass spectrometric analysis of ephedrine and pseudoephedrine

For thousands years Ephedrae herba has been used in traditional Chinese herbal medicine. Its main bioactive constituents are ephedrine and pseudoephedrine. Nowadays, these alkaloids have found application in various clinical treatments, as sports-enhancing drugs and for the illicit production of amphetamine-like drugs. Ephedrine and pseudoephedrine are diastereomers, and because of their high polarity and similar pKa values, their chromatographic separation may be a challenge. In this study a possible application of direct infusion mass spectrometry and direct infusion tandem mass spectrometry has been proposed for differentiation of ephedrine and pseudoephedrine as well as the relative determination of the contents of these compounds in a mixture. At low collision energy condition, the ratio of relative abundances of ions [M+H–H2O]+ and [M+H]+ permit distinction of the analyzed diastereomers, and enable evaluation of their relative content in a mixture with no need of chromatographic separation. The performed quantum chemical calculation have shown that protonated pseudoephedrine contains stronger hydrogen bond than protonated ephedrine, which can justify the observed higher relative abundance of ion [M+H–H2O]+ in the mass spectrum of pseudoephedrine, in comparison to that of ephedrine.

An audit of patient radiation doses during interventional cardiology procedures in Uttarakhand, India, and establishment of local diagnostic reference levels.

The objective of this study was to investigate patient radiation doses by a dose audit of three common interventional cardiology (IC) procedures: coronary angiography (CA), percutaneous transluminal coronary angioplasty (PTCA) and CA-PTCA procedures performed in IC centres in the Uttarakhand state of India, for the establishment of local diagnostic reference levels (DRLs) and the estimation of average effective dose (Eav) for these procedures. For each procedure, the values of kerma-area product (PKA), reference air kerma (Ka,r), fluoroscopy time (FT) and the number of cine images were recorded from 1233 CA, 458 PTCA and 736 CA-PTCA procedures performed over a 12-month period at 13 IC centres of the state. From the recorded dose data, 0.6%, 1.53% and 7.9% patients were identified to have exceeded the PKA trigger level of 500 Gy cm2 for possible skin injury for CA, PTCA and CA-PTCA procedures, respectively. The 3rd quartile of the distribution of the recorded PKA values for each type of procedure was calculated to estimate local DRL values. The estimated values of DRLs and Eav were 37, 153 and 224 Gy cm2, and 6.72, 23.97 and 34.79 mSv for CA, PTCA and CA-PTCA procedures, respectively. For about 77% of the surveyed centres, the recorded patient doses were in agreement with the international standards. The local DRLs proposed in this study may be used to achieve patient dose optimization during IC procedures and the obtained patient dose data may also be archived into national dose database for the establishment of national DRLs.

Comparison of Classical and Green RPLC Methods in the Determination of pKa Values of Some Piperazine Group Antihistamines.

In this study, protonation constant values and liquid chromatographic behaviors of hydrophobic cyclizine, chlorcyclizine, hydroxyzine, cinnarizine, cetirizine, meclizine, and buclizine in some water-organic solvent binary mixtures were examined for the first time using classical and green reverse phase liquid chromatography methods. In the isocratic study, the relationship of the retention time and mobile phase pH in water-organic solvent binary mixtures containing acetonitrile (45, 50, 55, 60, 65, v/v), methanol (60, 65, 70, 75, v/v) and ethanol (45, 50, 55, 56, 59, 60, 62, 65, v/v) were determined at 37 °C. In the study, XBridge C18 and Gemini NX C18 columns suitable for the chemical properties of basic compounds were used. The obtained liquid chromatographic data were analyzed using the linear solvation energy relationship methodology and the SOLVER program. The aqueous protonation constant values of the investigated compounds were calculated using the linear relationship between the protonation constant data calculated in studied binary mixtures and some macroscopic constant values of the solvents used. The greenness of methods developed using three different solvents was evaluated with the Analytical Greenness Metric Approach, the Green Analytical Procedures Index, and the Green Solvent Selection Tool approaches.

A potent bioreducible ionizable lipid nanoparticle enables siRNA delivery for retinal neovascularization inhibition

Small interfering RNA (siRNA) is emerging as a promising treatment for retinal neovascularization due to its specific inhibition of the expression of target genes. However, the clinical translation of siRNA drugs is hindered by the efficiency and safety of delivery vectors. Here, we describe the properties of a new bioreducible ionizable lipid nanoparticle (LNP) 2N12H, which is based on a rationally designed novel ionizable lipid called 2N12B. 2N12H exhibited degradation in response to the mimic cytoplasmic glutathione condition and ionization with a pKa value of 6.5, which remaining neutral at pH 7.4. At a nitrogen to phosphorus ratio of 5, 2N12H efficiently encapsulated and protected siRNA from degradation. Compared to the commercial vehicle Lipofectamine 2000, 2N12H demonstrated similar silencing efficiency and improved safety in the in vitro cell experiments. 2N12H/siVEGFA reduced the expression of VEGFA in retinal pigment epithelium cells and mouse retina, consequently suppressing cell migration and retinal neovascularization. In the mouse model, the therapeutic effect of 2N12H/siVEGFA was comparable to that of the clinical drug ranibizumab. Together, these results suggest the potential of this novel ionizable LNP to facilitate the development of nonviral ocular gene delivery systems.

PypKa server: online pKa predictions and biomolecular structure preparation with precomputed data from PDB and AlphaFold DB.

When preparing biomolecular structures for molecular dynamics simulations, pKa calculations are required to provide at least a representative protonation state at a given pH value. Neglecting this step and adopting the reference protonation states of the amino acid residues in water, often leads to wrong electrostatics and nonphysical simulations. Fortunately, several methods have been developed to prepare structures considering the protonation preference of residues in their specific environments (pKa values), and some are even available for online usage. In this work, we present the PypKa server, which allows users to run physics-based, as well as ML-accelerated methods suitable for larger systems, to obtain pKa values, isoelectric points, titration curves, and structures with representative pH-dependent protonation states compatible with commonly used force fields (AMBER, CHARMM, GROMOS). The user may upload a custom structure or submit an identifier code from PBD or UniProtKB. The results for over 200k structures taken from the Protein Data Bank and the AlphaFold DB have been precomputed, and their data can be retrieved without extra calculations. All this information can also be obtained from an application programming interface (API) facilitating its usage and integration into existing pipelines as well as other web services. The web server is available at pypka.org.

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.