The design of H-atom transfer catalysts requires the control of redox potential and proton affinity to direct the mechanism, rate, and selectivity of proton-coupled electron transfer (PCET). In the present study, we demonstrate that a series of reduced and protonated vanadium-substituted Keggin-type polyoxotungstates ([XVW11O39(OH)]n-, X=Si, n=5; X=P, n=4; X=S, n=3), exhibit invariant bond dissociation free energies of surface O─H bonds (BDFE(O─H)s). Despite uniform driving forces for H-atom uptake, kinetic analysis with a variety of H-atom donors (5,10-dihydrophenazine, hydrazobenzene, and hydroquinones) reveals differences in rates of substrate oxidation, which are ascribed to disparate PCET mechanisms. Together, these findings show that substitution at the central heteroatom tunes the electron- and proton-transfer driving forces (ΔGPT and ΔGET) thereby dictating the operative PCET mechanism.

Carbonic anhydrase (CA) is a zinc-containing metalloenzyme essential for key physiological functions such as pH balance, CO2 transport, and bicarbonate formation. While CA inhibitors have been extensively studied for therapeutic purposes, activators of CA remain underexplored despite their promising roles in medicine and industry. In this study, we employed a comprehensive quantum mechanical framework to elucidate the activation mechanism of β-CA. Six small-molecule activators – 1-(2-aminoethyl) piperazine, dopamine, glutamine, histamine, pyridyl methylamine, and asparagine – were systematically evaluated using DFT calculations (B3LYP/6-311++G**) in both gas and aqueous phases, incorporating solvation effects through explicit water molecules and the Polarisable Continuum Model (PCM). Transition state optimizations and IRC analyses confirmed feasible proton transfer pathways and allowed comparison of activation energy barriers. Reactivity indices, including HOMO–LUMO energy gaps, provided further insight into proton affinity and electronic features of each activator. Among the candidates, 2-aminoethylpiperazine emerged as the most efficient activator, displaying the lowest energy barrier and protonation enthalpy. These findings offer a validated theoretical basis for the rational design of potent CA activators, supporting future applications in therapeutics and carbon capture technologies. This study highlights the utility of DFT-based modelling in uncovering molecular-level mechanisms of enzyme activation.

Gas phase acidity of H2S clusters: A computational study

N-Heterocyclic carbenes (NHCs) containing an amide group in the ring are a rare class of cyclic carbenes, but increasingly more examples are being reported. Most of them were designed to participate as electrophiles; however, they exhibit electrophilic as well as nucleophilic characteristics. A comprehensive analysis of the electronic characteristics of the cyclic amido carbenes (amNHCs) has been carried out in this work by using density functional theory (DFT) methods to explore ambiphilicity. The stability parameters (ΔGS-T, carbene stabilization energy, dimerization energy), the basicity parameter (proton affinity), the nucleophilicity parameters (N, ΔGAuCl, and TEP), and the electrophilicity parameters (hydride ion affinity, fluoride ion affinity, ω values, and ΔGB) were estimated to perform comparative analysis. The tendency to exhibit greater nucleophilicity vs electrophilicity can be established using the ΔGB value estimation. Fine-tuning of the structural features of amNHCs helps in realizing the parameters responsible in identifying ambiphilic amNHCs in relation to those of purely nucleophilic amNHCs.

Herein, we report theoretical investigations of the imidazo[1,2-a]pyridine derivative IPD (systematic name 2-(1-(4-bromophenyl)-5-methyl-1H-1,2,3-triazol-4-yl)imidazo[1,2-a]pyridine), and compare the computational outcome with experimental data available from X-ray crystallography studies and spectroscopic analysis. Density functional theory (DFT) was employed as a computational chemistry approach to optimize the geometry and investigate the electronic properties, molecular descriptors, and frontier molecular orbital features of the investigated compound. The DFT-optimized molecular geometry showed good agreement with the experimental structure determined by single-crystal X-ray diffraction (RMSD = 0.2074Å). The electrostatic potential map of the IPD molecule revealed potential sites for electrophilic attack at the nitrogen in the imidazole ring and at the nitrogen atoms within the 1,2,3-triazole moiety. Additional calculations, however, indicated a higher proton affinity (246.44kcal/mol) at the aforementioned nitrogen atom in the imidazo[1,2-a]pyridine ring system, suggesting it is the most likely site of protonation. Molecular docking simulations were conducted to investigate the inclusion of the title compound into β-cyclodextrin and to explore the interactions of the IPD molecule with the epidermal growth factor receptor tyrosine kinase (EGFR-TK) as part of an in silico anticancer study. The electronic structures of the docked complexes were further explored using the DFT method, revealing that the intermolecular interactions between the IPD ligand and the receptors also involved a coupling of frontier molecular orbitals.

This study explores the representativeness of fulvic acid (FA) and humic acid (HA) in characterizing the seasonal and annual reactivity of riverine dissolved organic matter (DOM). Consequently, proton titrations were performed on samples from the Sorocabinha and Itapanhau Rivers (Brazil), focusing on purified FA and HA fractions, concentrated humic substances (HS), and untreated river water. The results demonstrated consistent proton-binding properties of purified FA/HA from both rivers across dry and rainy seasons and years (2014 and 2022), suggesting a potential averaging effect from purification that may obscure natural DOM variations. Significant differences in proton reactivity were observed between FA/HA and their parent HS in 2022, highlighting the necessity for separate characterization, an aspect sometimes overlooked in the literature. Notably, the proton affinity spectrum for untreated Sorocabinha River water exhibited three peaks, in contrast to the two peaks for its purified FA/HA, consistent with the presence of a hydrophilic acid fraction (HPI) also evidenced in other major rivers. Accordingly, we argue that relying solely on FA and HA reactivity parameters for modeling DOM in, for example, risk assessment, is inaccurate in the presence of HPI. We advocate for future research to improve DOM modeling by addressing the limitations of the FA/HA-based approach and formulating realistic alternatives when necessary.

Carbon and hydrocarbons are fundamental building blocks of life. Here, we present a comprehensive computational study on the stability and reactivity of CHx±n (X = 0, 1, 2, 3, 4) species across charge states n ranging from -4 to +4 and multiplicities from singlet to quintet. We benchmark suitable methods and select CCSD(T)/aug-cc-pVQZ for computing the bond dissociation energies (BDEs), proton affinities (PAs), hydride affinities (HAs), electron affinities (EAs), and ionization potentials (IPs). We discuss observed trends in charge-dependent stability and reactivity, with implications for a fundamental understanding of carbon-hydrogen species. We believe that these data will be useful for further investigations of highly reactive hydrocarbons in unusual electronic states.

Two novel, structurally different perfluoroalkyl ionic liquids with bicyclic guanidinium cation have been synthesized and applied as a surfactant component for selected active pharmaceutical ingredients (APIs). The addition of perfluoroalkyl ionic liquid to hydrophobic APIs significantly improves their solubility. One of the key and characteristic properties of guanidine derivatives is their strong ability to chemisorb protons (proton affinity). This property enables them to form stable ionic-type aggregates (adducts) with selected hydrophobic APIs containing carboxylic groups. Therefore, these new compounds are, in fact, API-IL ionic adducts formed as hydrogen bond donor-acceptor systems. The obtained adducts are characterized by significantly better solubility than the initial APIs. The presence of perfluoroalkyl chains with unique surface-active properties enables to obtain a solubility of new adducts to reach level sufficient for typical ophthalmic preparations. (e.g., eye drops or lens care). The ionic API-IL adducts obtained in the described studies can be considered as examples of a new class of active derivatives with pharmaceutical potential.

Icy interstellar dust grains are a source of complex organic molecule (COM) production, although the formation mechanisms of these molecules are debated. Laboratory experiments show that atomic carbon deposited onto interstellar ice analogs can readily react with solid-phase ammonia to form the CHNH2 radical, a possible precursor to COMs, including aminoketene ( NH2CHCO We used astrochemical kinetics models to explore the role of the reaction of atomic C with ammonia as well as the subsequent reaction with CO in the formation of aminoketene and other COMs, including ethanolamine ( NH2CH2CH2OH ) and glycine ( NH2CH2COOH We applied the three-phase chemical model MAGICKAL to hot molecular core conditions from the cold-collapse through to the hot-core stage. The chemical network was extended to include NH2CHCO and a range of associated gas-phase, grain-surface, and bulk-ice products and reactions. We also implemented a model approximating conditions in a shocked cloud, including sputtering of the ice mantles. Aminoketene is formed on grains at low temperatures (∼10 K) with a peak solid-phase abundance of ∼2times10^-10 n_ H . Its formation is driven by nondiffusive reactions, in particular the Eley-Rideal reaction of C with surface NH_3, followed by immediate reaction with CO. Surface hydrogenation of aminoketene produces ethanolamine with a significant abundance of ∼8times10^-8 n_ H . In the gas-phase, although ethanolamine reaches a modest abundance peak immediately following its desorption from grains under hot-core conditions, it is destroyed more rapidly due to its high proton affinity. Molecular survival is much higher in the shocked regions, where these species seem most likely to be detected. Glycine abundances are modestly enhanced by the new chemistry. Aminoketene is produced efficiently on simulated interstellar grain surfaces, acting subsequently as an important precursor to more complex organics, including ethanolamine and glycine. Ion-molecule gas-phase destruction of amine-bearing COMs is less efficient in (weakly) shocked lower-density regions, in contrast to hot cores, enhancing their abundances and lifetimes.

The structures of nucleophilic reactants affect theircoordinationbehavior among solvent molecules and kinetics of reactions with surfaceintermediates within the confines of fluid-filled pores of zeolitesand other microporous materials. Consequently, rates and regioselectivitiesof diverse chemistries may depend sensitively on nucleophile identityin manners not observed for classic fluid phase reactions. Here, weexamine the impact of varying the primary alcohol (ROH) chain lengthon the kinetics of 1,2-epoxybutane (C4H8O) ring-openingwithin Brønsted (Al-BEA) and Lewis acid (Zr-BEA) zeolites. Turnoverrates increase by factors of ∼6 (Al-BEA) and 4-fold (Zr-BEA)between methanol and 1-hexanol, yet the reaction mechanisms remaincomparable. Despite modest rate differences, apparent activation enthalpiescalculated from rates and activities of solvated reactants decreaselinearly by 12 (Al-BEA) to 33 kJ mol–1 (Zr-BEA)with increased proton affinity, which suggests bond formation energiesfor the nucleophile strongly influence rate increases. The molecularinterpretation of these trends demonstrates, however, that the solvationof ring-opening transition states by zeolite pore structures and solventmolecules also governs rates. The impact of local solvating interactionsappears most directly as changes in regioselectivities, which tendto enhance terminal alcohol formation with increasing ROH chain length.Regioselectivities largely do not vary with differences in fluid compositionfor a given ROH. The addition of H2O increases the numberof hydrogen bonds among reactive species, and trends in regioselectivitiesimply that the decreased hydrogen bonding ability of longer chainROH, and not the nucleophile strength or steric bulk, determines theregioselectivities of the resulting products. This work provides directexperimental evidence that nucleophilicity and hydrogen bonding influencereaction barriers and regioselectivities in zeolite-catalyzed epoxidering-opening, offering pathways to better control reaction kinetics.

Solar-driven photocatalytic oxygen reduction reaction using covalent organic frameworks (COFs) offers a promising approach for sustainable hydrogen peroxide (H2O2) production. Despite their advantages, the reported COFs-based photocatalysts suffer insufficient photocatalytic H2O2 efficiency due to the mismatched electron-proton dynamics. Herein, we report three one-dimensional (1D) COF photocatalysts for efficient H2O2 production via the hydrogen radical (H•) mediated concerted electron-proton transfer (CEPT) process. The DOTh-COF which features dibenzo[b,d]thiophene sulfone (DOTh) moieties in the 1D skeleton edges achieves a high H2O2 production rate of 10.87mmol g-1 h-1 and an apparent quantum efficiency of 13.5% at 420nm in a biphasic water/benzyl alcohol system. The fs-TAS and in-situ EPR analyses demonstrate the DOTh moieties facilitate the charge separation, proton affinity, and exciton dissociation, enabling enhanced H• production. Mechanistic studies reveal that the H• reacts with O2 with high rate through both one-step and two-step 2e- pathways, thereby achieving efficient photosynthesis of H2O2. This work provides an effective design strategy for COFs-based photocatalysts and highlights the significance of H• mediated CEPT process in artificial photosynthesis.

Ammonia (NH3), a critical precursor in the atmospheric formation of fine particulate matter (particularly PM2.5), poses significant environmental challenges by contributing to eutrophication and acidification as its concentration increases. Consequently, the real-time and accurate monitoring of atmospheric NH3 is of great environmental and regulatory importance. In this study, an innovative technique for the rapid switching of reagent ions between (C4H8O)2H+ and (H2O)nH+ in dopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS) within 2 s by simply controlling the on-off of water dopant is proposed. This facilitates NH3 detection under two distinct modes: high selectivity and high sensitivity. In the high-selectivity mode, 2-butanone is employed as the dopant, generating (C4H8O)2H+ as the predominant reagent ion. Under these conditions, the method achieves a limit of detection (LOD) of 5 ppb, enabling selective quantification of NH3 in complex matrices. To achieve high-sensitivity detection, we introduce a synergistic 2-butanone/water dopant system. This dual strategy enables the efficient conversion of (C4H8O)2H+ to (H2O)nH+ at ambient temperature. The resulting reagent ion, possessing a lower proton affinity, emerged as the predominant species. As a result, the NH3 LOD is significantly lowered to 0.47 ppb, an improvement in sensitivity by approximately an order of magnitude. It exhibits superior stability, robust resistance to humidity interference, and enhanced peak-to-peak resolution, with a remarkably low relative standard deviation (RSD) of just 1.24%. The DAPP-IMS method thus offers robust, highly selective, and sensitive long-term online monitoring of NH3 concentrations in diverse environments, including vehicle emissions and humid outdoor atmospheres. The rapid reagent ion switching mechanism not only suppresses interference from complex matrices but also significantly enhances detection stability and sensitivity.

ABSTRACTA theoretical investigation at MP2 = full/aug‐cc‐pVTZ level has been carried out on the hydrogen and halogen bonded complexes of the HOCl molecule with various Lewis bases (N‐, S‐, and O‐bases), aiming to identify a suitable descriptor for evaluating the bond strength in a generalized manner. A total of 24 halogen and hydrogen bonded complexes formed between the HOCl molecule and different electron donors have been investigated. The binding strength of these complexes was analyzed in relation to several descriptors, including proton affinity (PA), negative electrostatic potential (Vs,min), electron density ρ(rc) at the bond critical point (BCP), charge transfer (CT), and hyperconjugation energy. Among these, the electron density emerged as the most reliable descriptor, showing a strong correlation with the binding strength across all the studied complexes, followed by hyperconjugation energy. In contrast, other parameters exhibited good correlations only when evaluated for specific bases but failed to maintain consistency across all types of complexes. These correlations not only contribute to a better understanding of the nature of hydrogen and halogen bonds with the HOCl molecule but also offer an effective approach for predicting their relative strengths, particularly in scenarios where both types of interactions coexist and compete with each other.

Native electrospray ionization-mass spectrometry (ESI-MS) is inherently susceptible to nonvolatile salts in solution, due to ion formation resulting from the so-called "charged-residue mechanism" (CRM). The presence of nonvolatile salts leads to peak broadening and shifting to higher mass due to salt condensation onto the analyte, and in the worst-case scenario, can totally suppress the observation of the analyte ions of interest. However, salts are known to play roles in protein conformation and dynamics. Previously, we showed how native ESI-MS implemented with theta emitters, glass emitters with a septum that divides the capillary into two channels, with inner diameters of ∼1.4 μm, allows for the identification of proteins and protein complexes in solutions containing biological buffers and nonvolatile salts at physiologically relevant concentrations. However, the signal-to-noise (S/N) ratios of the bio-ions of interest were significantly lower compared with the bio-ions' signals in the absence of biological buffers. Here, implementing theta emitters for sample introduction, we show how the delivery of anions with relatively low proton affinities during the ESI droplet formation can significantly reduce ionization suppression through mitigation of chemical noise. Importantly, this strategy increases S/N ratios, method reproducibility, and robustness compared to our previous work. These advantages are important for the mass analysis of protein complexes extracted from biological tissues, where the amount of starting material is limited.

The cage‐amine molecules nona(ethylene)hexamine and dodeka(ethylene)octamine, have been prepared by coupling 1,4,7‐triazacyclononane (tacn) or 1,4,7,10‐tetraazacyclododecane (cyclen) to the corresponding α‐chloroacetamide derivatives of these macrocycles. The formed tri‐ or tetra‐amide cryptands were then reduced to the corresponding hexamine and octamine with borane. In all cases, the amide and amine cryptands were isolated as protonated ammonium salts, with the proton oriented to the inside of the cage molecules (i.e., endohedral). Deprotonation studies on the hexamine and octamine showed the encapsulated protons are highly inert, with no evidence of deprotonation or deuterium exchange. Detailed theoretical studies predict very high proton affinity and basicity of 1118.7 and 1086.7 kJ mol−1, respectively, for dodeka(ethylene)octamine, and 1108.3 and 1083.7 kJ mol−1, respectively, for nona(ethylene)hexamine, placing them among the strongest amine bases ever prepared and firmly within the realm of “superbases”.

Background/Objectives: Recent evidence challenges the classical chemiosmotic theory, suggesting that proton movement along membrane surfaces—not bulk-phase gradients—drives bioenergetic processes. Proton accumulation on membranes like the myelin sheath and endoplasmic reticulum (ER) may represent a universal mechanism for cellular energy storage. This study investigates whether phospholipids from these membranes, combined with anionic bee venom proteins, enhance proton absorption, potentially elucidating a novel bioenergetic pathway. Methods: Five phospholipids (phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, phosphatidylcholine) from rat liver were isolated to model myelin/ER membranes. Anionic proteins (pI 5.65–5.80) were purified from bee venom via cation exchange chromatography. Liposomes (with/without proteins) were prepared, and proton absorption was quantified by pH changes in suspensions versus pure water. Statistical significance was assessed via ANOVA and t-tests. Results: All phospholipid liposomes examined in this study absorbed protons under the tested conditions, with phosphatidylethanolamine showing the highest capacity (pH increase: 7.00 → 7.18). Liposomes enriched with anionic proteins exhibited significantly greater proton absorption (e.g., phosphatidylserine + proteins: pH 8.15 vs. 7.15 alone; p < 2.43 × 10−6). Sphingomyelin-protein liposomes absorbed the most protons, suggesting that protein–phospholipid interactions modulate surface proton affinity. Conclusions: Anionic bee venom proteins amplify proton absorption by phospholipid membranes, supporting the hypothesis that lipid–protein complexes act as “proton capacitors”. This mechanism may underpin extramitochondrial energy storage in myelin and ER. Pharmacologically, targeting these interactions could mitigate bioenergetic deficits in aging or disease. Further research should define the structural basis of proton capture by membrane-anchored proteins.

Predicting the physicochemical properties of ionizable solutes, including solubility and lipophilicity, is of broad significance. Such predictions rely on the accurate determination of solvation free energies for ions. However, the limited availability of high-quality reference data poses a challenge in developing accurate, inexpensive computational prediction methods. In this study, we address both issues of data quality and availability. We present three databases and models related to ionic phenomena: (1) 8,241 pKa data points across 8 solvents, (2) 5,536 gas-phase acidities from DLPNO-CCSD(T) QM calculations, and (3) 6,090 solvation free energies of anions across 8 solvents obtained from a thermodynamic cycle. We also report 6,088 solvation free energies of neutral conjugate solutes computed using the COSMO-RS method. The pKa data were obtained from the iBonD database, cleaned, and combined with a separate compilation of trustworthy reference pKa data. Gas-phase acidities were computed for most of the acids present in the pKa corpus. Leveraging these data, we compiled values for solvation free energies of anions. We then trained several graph neural network models, which can be used as an alternative to QM approaches to quickly estimate these properties. The pKa and gas-phase acidity models accept reaction SMILES strings of the acid dissociation as inputs, whereas the solvation energy model accepts the SMILES string of the anion. Our microscopic pKa model achieves good accuracy, with an overall test mean average error of 0.58 units on unseen solutes and 0.59 on the SAMPL7 challenge (the lowest error so far among multisolvent models). Our gas-phase acidity model had mean absolute errors slightly above 2 kcal mol-1 when evaluated against experimental data. The anionic solvation free energy model had mean absolute errors of less than 3 kcal mol-1 in several test evaluations, comparable to (though less reliable than) several widely used QM-based solvation models. The models and data are free and publicly available at doi.org/10.5281/zenodo.13987781.

Optimization of q Value for Sensitive Detection of Uridine and Thymidine Nucleosides by MS3.

Based on DFT calculations (ωB97XD/def-TZVP) throughout this report we have examined the affinity of container-like molecules to accommodate halogenide anions. Those container-like molecules consist of two planar systems (triazine, cyanuric acid, boroxine and benzene) linked by three diethylamine groups. Selected host for halogenide anions accommodation were mainly chosen based on their different π-acidity or π-basicity properties. Besides investigation of encapsulation affinity of selected hosts, additional study of their proton affinity and aromaticity properties, measured through NICS aromaticity indices and magnetically induced current densities, was also carried out. Those additional studies were performed before and after encapsulation of guest halogenides, with the aim of finding the connection between those properties and encapsulation energy.

Mass spectrometry (MS) has frequently been applied for the identification of molecules and structure determination due to its sensitivity and versatility. It is frequently coupled with soft ionization processes, such as electrospray ionization; however, the presence of microsolvated phases generated during these processes─intermediates between the condensed and gas phase─can alter the chemistry of analytes and therefore their detection and identification. To understand these processes, we use computational methods (semiempirical methods and density functional theory) to probe the ionization propensity of four small aliphatic amino acids─alanine, glycine, valine, and proline─in the gas phase and aqueous microsolvated clusters. We show that the tautomeric form of each amino acid is altered by the presence of water, with glycine requiring as little as three water molecules to stabilize the zwitterionic form and the other amino acids requiring four to five water molecules. We also show that the inclusion of ionic cosolutes can stabilize the zwitterion with even fewer (one or two) water molecules present. Ionization propensity as measured by gas phase basicity (GB) is also altered in the microsolvated state─distinct gas phase values in each of the four amino acids show remarkably similar GB values in the cluster form, revealing the sensitivity of the analyte to the solvation environment. The structural characteristics of these amino acid-water clusters are also determined, including symmetry, the total number of hydrogen bonds, and hydrogen bonding networks.