Proton Affinity Research Articles

Synthesis, characterization and evaluation of cellulose-graft-poly(4-vinylpirydine), using cellulose from a new pretreatment process, for heavy metal removal from wastewater

The synthesis, characterization and evaluation of cellulose-graft-poly(4-vinylpirydine) for heavy metal removal from wastewater, is reported. Cellulose was obtained from a corn cob biomass using a recently developed gas-phase acid pretreatment process (GPAPP). The obtained corn cob cellulose (CCC) was functionalized by partial esterification of the superficial -OH groups with α-bromoisobutyryl bromide (BIBB) under mild conditions (room temperature and dimethyl formamide, DMF as solvent). The functionalized cellulose was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM)/energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). The BIBB-functionalized CCC was used as initiator for surface-initiated (SI) atom transfer radical polymerization (ATRP) of 4-vinylpyridine (4VP). Grafting of the polymer (p4VP) onto cellulose was confirmed by FTIR, TGA and XPS. The same procedure was carried out with microcrystalline cellulose (MCC) as a reference. The performance of the cellulose copolymers for the removal of lead and iron from water was evaluated. Removal percentages of 83 % in 30 min for lead and 79 % in 180 min for iron were obtained with MCC-g-p4VP. In contrast, removal percentages of 50 % were obtained in 30 min for lead and 30 % for iron in 180 min, respectively, when CCC-g-p4VP was used.

Tuning Proton Affinity on Co-N-C Atomic Interface to Disentangle Activity-Selectivity Trade-off in Acidic Oxygen Reduction to H2O2.

In oxygen reduction reaction to H2O2 via two-electron pathway (2e- ORR), adsorption strength of oxygen-containing intermediates determines both catalytic activity and selectivity. However, it also causes activity-selectivity trade-off. Herein, we propose a novel strategy through modulating the interaction between protons and *OOH intermediates to break the activity-selectivity trade-off for highly active and selective 2e- ORR. Taking the typical cobalt-nitrogen-carbon single-atom catalyst as an example, boron heteroatoms doped into second coordination sphere of CoN4 (Co1-NBC) increase proton affinity on catalyst surface, facilitating proton attack on the former oxygen of *OOH and thereby promoting H2O2 formation. As a result, Co1-NBC simultaneously achieves prominent 2e- ORR activity and selectivity in acid with onset potential of 0.724 V vs. RHE and H2O2 selectivity of 94 %, surpassing most reported catalysts. Furthermore, Co1-NBC exhibits a remarkable H2O2 productivity of 202.7 mg cm-2 h-1 and a remarkable stability of 60 h at 200 mA cm-2 in flow cell. This work provides new insights into resolving activity-selectivity trade-off in electrocatalysis.

Tuning Proton Affinity on Co−N−C Atomic Interface to Disentangle Activity‐Selectivity Trade‐off in Acidic Oxygen Reduction to H2O2

AbstractIn oxygen reduction reaction to H2O2 via two‐electron pathway (2e− ORR), adsorption strength of oxygen‐containing intermediates determines both catalytic activity and selectivity. However, it also causes activity‐selectivity trade‐off. Herein, we propose a novel strategy through modulating the interaction between protons and *OOH intermediates to break the activity‐selectivity trade‐off for highly active and selective 2e− ORR. Taking the typical cobalt–nitrogen–carbon single‐atom catalyst as an example, boron heteroatoms doped into second coordination sphere of CoN4 (Co1‐NBC) increase proton affinity on catalyst surface, facilitating proton attack on the former oxygen of *OOH and thereby promoting H2O2 formation. As a result, Co1‐NBC simultaneously achieves prominent 2e− ORR activity and selectivity in acid with onset potential of 0.724 V vs. RHE and H2O2 selectivity of 94 %, surpassing most reported catalysts. Furthermore, Co1‐NBC exhibits a remarkable H2O2 productivity of 202.7 mg cm−2 h−1 and a remarkable stability of 60 h at 200 mA cm−2 in flow cell. This work provides new insights into resolving activity‐selectivity trade‐off in electrocatalysis.

Revealing the antioxidant properties of alkyl gallates: a novel approach through quantum chemical calculations and molecular docking.

This study investigates the antioxidant potential of alkyl gallates (C1-C10), focusing on the impact of alkyl chain length and solvent polarity on their antioxidant properties. Known for their biomedical relevance in mitigating oxidative stress, alkyl gallates' structure-activity relationships, particularly regarding chain length and environmental factors, still need to be explored. Key thermochemical parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton affinity (PA), and electron transfer enthalpy (ETE), reveal that shorter alkyl chains (C1-C4) exhibit superior antioxidant activity. In contrast, longer chains (C5-C10) show reduced effectiveness due to steric hindrance and lower solubility in polar solvents. Molecular docking studies also demonstrated favorable binding interactions with vital biological targets, further reinforcing their antioxidant potential. Quantum chemical calculations were performed using Gaussian 16 with the B3LYP/6-311G(dp) basis set for geometry optimizations. Solvent effects were modeled using the integral equation formalism-polarized continuum model (IEF-PCM). Molecular docking studies were conducted using AutoDockTools 4.2, targeting Tyrosine Kinase Hck, Heme Oxygenase, and Human Serum Albumin to evaluate fundamental binding interactions. These computational methods provided insights into alkyl gallates' chemical reactivity and antioxidant efficiency, allowing for the rational design of more potent antioxidant compounds.

Interfacial Proton Precompensation: Suppressing Deprotonation-Driven Lattice Collapse for Enhanced Efficiency and Stability in Perovskite Solar Cells.

The chemical property of the buried interface plays a crucial role in improving the performance and stability of perovskite solar cells (PSCs). The SnO2/perovskite interface prepared from SnO2 alkaline hydrogel with high proton affinity triggers directional migration and irreversible reactions of protons, exacerbating the disintegration of perovskite crystal. In this study, we proposed proton precompensation strategy to suppress the deprotonation effect of the buried interface and improve the durability of the devices. By modulating the chemical environment and surface energy state of the buried interface, the domain-limiting and spontaneous compensation of protons in formamidinium (FA+) under Coulomb force were achieved, thereby stabilizing the perovskite crystal structure. The stability of target perovskite films under UV illumination and heating at 85 °C was significantly enhanced. As a result, the devices can retain around 90% of their initial power conversion efficiency (PCE) after 1000 h of continuous irradiation at the maximum power point (MPP). Moreover, due to the reduction of defect content at the buried interface and the improvement of conductivity and carrier mobility by the precompensation treatment, the interfacial energy loss and non-radiative recombination were substantially diminished. The target PSC devices exhibited much higher PCE of 25.55% than the control devices (23.03%).

Interfacial Proton Precompensation: Suppressing Deprotonation‐Driven Lattice Collapse for Enhanced Efficiency and Stability in Perovskite Solar Cells

The chemical property of the buried interface plays a crucial role in improving the performance and stability of perovskite solar cells (PSCs). The SnO2/perovskite interface prepared from SnO2 alkaline hydrogel with high proton affinity triggers directional migration and irreversible reactions of protons, exacerbating the disintegration of perovskite crystal. In this study, we proposed proton precompensation strategy to suppress the deprotonation effect of the buried interface and improve the durability of the devices. By modulating the chemical environment and surface energy state of the buried interface, the domain‐limiting and spontaneous compensation of protons in formamidinium (FA+) under Coulomb force were achieved, thereby stabilizing the perovskite crystal structure. The stability of target perovskite films under UV illumination and heating at 85 °C was significantly enhanced. As a result, the devices can retain around 90% of their initial power conversion efficiency (PCE) after 1000 h of continuous irradiation at the maximum power point (MPP). Moreover, due to the reduction of defect content at the buried interface and the improvement of conductivity and carrier mobility by the precompensation treatment, the interfacial energy loss and non‐radiative recombination were substantially diminished. The target PSC devices exhibited much higher PCE of 25.55% than the control devices (23.03%).

Sidearm modified phosphine ligands for Rh complex-catalyzed hydroformylation: Mechanistic pathway and structure-activity relationship

Development of high-performance phosphine ligands is an effectual strategy to improve the homogeneous hydroformylation reaction. This study designed a series of amide/ester sidearms-modified phosphine ligands with different characteristics (e.g., proton affinity, steric hindrance) for homogeneous Rh-complex in hydroformylation of formaldehyde. The sidearms-modified ligands with the stronger proton affinity serve to transfer proton from the hydrido rhodium species to the activated formaldehyde via the sidearms to generate the critical hydroxymethyl rhodium species that favours the hydroformylation to glycolaldehyde, yielding significantly improved reaction rates (twice as much as PPh3). The bulky sidearm with larger steric hindrance can stretch the hydrogen bond between the product and the sidearm, suppressing the by-product production and improving the target selectivity. A potential reaction mechanism involving sidearm-induced deprotonation and inner-molecule proton transfer was proposed for the sidearm-modified phosphine ligands coordinated Rh complex based on the DFT calculation and experimental study. This study can trigger the innovative phosphine ligand design with special functional sidearms for hydroformylation.

Ligand-dependent redox-coupled spin crossover of a five coordinate cobalt salen complex

The electrochemical and spectroscopic behavior of a five-coordinate cobalt (III) salen (CoIIISalen+), where Salen is N,N′-bis(3,5-di-tert-butyl-2-hydroxybenzyliden)-1,7-diamino-4-methyl-4-azaheptane, is examined in the presence of a series of exogenous ligands. In non-coordinating solvents, and in the absence of suitable ligands, CoIIISalen+ prefers a high-spin configuration (S = 2/2) and has trigonal bipyramidal geometry. The binding of pyridyl- or imidazole-based ligands generate an octahedral complex that is low-spin (S = 0). X-ray crystallographic structures are reported for [CoIIISalen-ampy]Cl, [CoIIISalen-ampy](SbF6), and [CoIIISalen-cnpy](SbF6), all confirming the octahedral coordination environment. In the absence of exogenous ligands, CoSalen displays an electrochemically quasi-reversible redox wave in cyclic voltammograms for the CoII/III couple (E1/2 = −0.37 V vs Fc0/+). The addition of various ligands (L) to the electrolyte induces a pronounced increase in the anodic–cathodic peak splitting (Epa,hs – Epc,ls) due to a redox-coupled spin-crossover (RCSCO) mechanism. The reduction potential of CoIIISalen-L+ (Epc,ls) is highly dependent on the nature and charge of L. To better understand the relationship between ligand properties and the observed electrochemical shift, we performed spectroscopic binding studies of CoIISalen and CoIIISalen+ to establish a correlation of the observed redox potentials to well-established thermodynamic parameters, including Hammett parameters of para-substituted pyridines and gas phase basicity (GPB) of all ligands. The broad range of anodic/cathodic peak splitting generated by this series of ligands with CoIIISalen-L+ highlights the ability to tune the RCSCO properties and redox bistability of a complex through coordination changes with exogenous ligands.

What Is the Protonation State of Proteins in Crystals? Insights from Constant pH Molecular Dynamics Simulations.

X-ray crystallography is an important technique to determine the positions of atoms in a protein crystal. However, because the native environment in which proteins function, is not a crystal, but a solution, it is not a priori clear if the crystal structure represents the functional form of the protein. Because the protein structure and function often depend critically on the pH, the question arises whether proton affinities are affected by crystallization. X-ray diffraction usually does not reveal protons, which makes it difficult to experimentally measure pKa shifts in crystals. Here, we investigate whether this challenge can be addressed by performing in silico titration with constant pH molecular dynamics (MD) simulations. We compare the computed pKa values of proteins between solution and crystal environment and analyze these differences in the context of molecular interactions. For the proteins considered in this work, pKa shifts were mostly found for residues at the crystal interfaces, where the environment is more apolar in the crystal than in water. Although convergence was an obstacle, our simulations suggest that in principle it is possible to apply constant pH MD to protein crystals routinely and assess the effect of crystallization on protein function more systematically than with standard MD simulations. We also highlight technical challenges that need to be addressed to make MD simulations of crystals more reliable.

A Computational Analysis of the Proton Affinity and the Hydration of TEMPO and Its Piperidine Analogs.

The study investigated the impact of protonation and hydration on the geometry of nitroxide radicals using B3LYP and M06-2X methods. Results indicated that TEMPO exhibited the highest proton affinity in comparison to TEMPOL and TEMPONE. Two pathways contribute to hydrated protonated molecules. TEMPO shows lower first enthalpies of hydration (ΔH1-M), indicating stronger H-bonding interactions, while TEMPONE shows higher values, indicating weaker interactions with H2O. Solvent effects affect charge distribution by decreasing their atomic charge. Spin density (SD) is primarily concentrated in the NO segment, with minimal water molecule contamination. Protonation increases SD on N-atom, while hydration causes a more pronounced redistribution for water molecules. The stability of the dipolar structure (>N⋅+-O-) is evident in SD redistributions. The frontier molecular orbital (FMO) analysis of TEMPONE reveals a minimum EHOMO-LUMO gap (EH-L), enhancing the piperidine ring's reactivity. TEMPO is the most nucleophilic species, while TEMPONE exhibits strong electrophilicity. Transitioning from NO radicals to protonated forms increases the EH-L gap, indicating protonation stabilizes FMOs. Increased water molecules make the molecule less reactive, while increasing hydration decreases this energy gap, making the molecule more reactive. A smaller EH-L gap indicates the compound becomes softer and more prone to electron density and reactivity changes.

Gas phase proton affinities of proline-containing peptides. 1: ProGly, ProAla, ProVal, ProLeu, ProIle, and ProPro

The gas-phase proton affinities (PA) for a series of proline-containing dipeptides have been measured in an ESI triple quadrupole instrument using the extended kinetic method. Proton affinities for ProGly (1), ProAla (2), ProVal (3), ProLeu (4), ProIle (5), and ProPro (6) were determined to be 969.6 ± 7.8, 990.4 ± 7.7, 987.6 ± 7.9, 982.8 ± 8.0, 988.8 ± 10.1, and 996.5 ± 12.2 kJ/mol, respectively. Predictions for the proton affinities for 1–6 were also obtained through isodesmic calculations at the B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d) level of theory. The predicted proton affinities for 1 and 6 of 966.9 and 991.0 kJ/mol are in agreement with the experimental values. However, the predicted proton affinities for 2–5 of 973.5, 975.9, 975.7, and 975.9 are between 8 and 15 kJ/mol lower than the experimental values. Additional calculations with a larger basis set (B3LYP/6-311++G(2df,2p), inclusion of dispersion (B3LYP-D3/6-311++G(d,p)), switching to second order perturbation theory (MP2/6-31++G(d,p) and MP2/6-311++G(2df,2p), or switching density functional (M06-2x/6-311++G(d,p) and M06-2x/6-311++G(2df,2p) show only modest changes in derived thermochemistry lending support to the original calculations. We recommend using the experimental proton affinities for ProGly and ProPro and using the calculated values for ProAla, ProVal, ProLeu, and ProIle with the experimental proton affinities as upper limits.

Comprehensive targeted profiling of multiple steroid classes in rodent plasma using liquid chromatography-mass spectrometry

BackgroundReliable quantification of multiple steroid classes in biological fluids within a single method remains an analytical challenge despite many previously published methods. Crosstalk of positional isomers, overlap of stereoisomer fragmentation patterns, differing proton affinities, in-source fragmentation, varying stability of protonated ions in the gas phase across steroid classes, and non-existence of steroid-free matrix are the main challenges limiting the number of simultaneously profiled steroids. ResultsIn this study, we focused on the development of a derivatization-free, achiral, high-throughput, and cost-effective UHPLC-MS/MS approach that allows simultaneous profiling of a spectrum of 38 steroids covering progestogens, androgens, corticosteroids, and estrogens, while properly addressing the hurdles of steroid analysis. Within a 20-min method, 16 stereoisomers and 15 positional isomers were fully resolved within a single run while separated from 7 additional non-interfering steroids and matrix interferences in rodent plasma. Protein precipitation (PP) and supported liquid extraction (SLE) methods using only 40 μL of sample were developed to achieve the lowest possible limits of quantification. Nevertheless, 5α-dihydroprogesterone and 3α,5α-THDOC could be only qualitatively assessed when using PP. In contrast, DHEA-S could not be quantified or identified when using SLE. A novel surrogate matrix-background subtraction approach, using rat plasma after the animal's adrenalectomy, has been implemented into the optimized PP-UHPLC-MS/MS workflow, successfully validated according to the unified ICH/EMA M10 guidelines, and compared to the traditional quantification strategies. Moreover, the validity of the newly adopted approach has been verified by the targeted profiling of multiple biologically active endogenous steroids in more than 500 samples of mouse plasma in total. SignificanceUnderestimation of hurdles associated with steroid analysis often compromises the accurate steroid quantification. Our comprehensive, fully validated UHPLC-MS/MS method targeting a wide spectrum of endogenous steroids, mitigating steroid crosstalk and using a minimal sample volume together with a novel surrogate matrix-background subtraction approach significantly advances steroid analysis for research and clinical applications covering multiple biological scopes.

H+/X− Co‐Transport Driven by Azobenzene Containing Aromatic Amides

AbstractNatural ion‐transporters in cellular membranes play a critical role in maintaining cell homeostasis. Synthetic ion‐transporters are attractive model systems for understanding and addressing dysfunction of natural transporters. Herein, a simple amide derived from azobenzene and m‐aminobenzoic acid achieves photoregulated ion transport across lipid membranes. The amide forms pores or channels that selectively co‐transport H+/X− across the lipid membrane. Photoisomerization from the trans to cis form results in a 2‐fold increase in ion‐transport rates due to the higher proton affinity of the cis isomer.

An SLC12A9-dependent ion transport mechanism maintains lysosomal osmolarity.

Ammonia is a ubiquitous, toxic by-product of cell metabolism. Its high membrane permeability and proton affinity cause ammonia to accumulate inside acidic lysosomes in its poorly membrane-permeant form: ammonium (NH4+). Ammonium buildup compromises lysosomal function, suggesting the existence of mechanisms that protect cells from ammonium toxicity. Here, we identified SLC12A9 as a lysosomal-resident protein that preserves organelle homeostasis by controlling ammonium and chloride levels. SLC12A9 knockout (KO) cells showed grossly enlarged lysosomes and elevated ammonium content. These phenotypes were reversed upon removal of the metabolic source of ammonium or dissipation of the lysosomal pH gradient. Lysosomal chloride increased in SLC12A9 KO cells, and chloride binding by SLC12A9 was required for ammonium transport. Our data indicate that SLC12A9 function is central for the handling of lysosomal ammonium and chloride, an unappreciated, fundamental mechanism of lysosomal physiology that may have special relevance in tissues with elevated ammonia, such as tumors.

Impact of Protonation Sites on Collision-Induced Dissociation-MS/MS Using CIDMD Quantum Chemistry Modeling.

Protonation is the most frequent adduct found in positive electrospray ionization collision-induced mass spectra (CID-MS/MS). In a parallel report Lee, J. J. Chem. Inf. Model. 2024, 10.1021/acs.jcim.4c00760, we developed a quantum chemistry framework to predict mass spectra by collision-induced dissociation molecular dynamics (CIDMD). As different protonation sites affect fragmentation pathways of a given molecule, the accuracy of predicting tandem mass spectra by CIDMD ultimately depends on the choice of its protomers. To investigate the impact of molecular protonation sites on MS/MS spectra, we compared CIDMD-predicted spectra to all available experimental MS/MS spectra by similarity matching. We probed 10 molecules with a total of 43 protomers, the largest study to date, including organic acids (sorbic acid, citramalic acid, itaconic acid, mesaconic acid, citraconic acid, and taurine) as well as aromatic amines including uracil, aniline, bufotenine, and psilocin. We demonstrated how different protomers can converge different fragmentation pathways to the same fragment ions but also may explain the presence of different fragment ions in experimental MS/MS spectra. For the first time, we used in silico MS/MS predictions to test the impact of solvents on proton affinities, comparing the gas phase and a mixture of acetonitrile/water (1:1). We also extended applications of in silico MS/MS predictions to investigate the impact of protonation sites on the energy barriers of isomerization between protomers via proton transfer. Despite our initial hypothesis that the thermodynamically most stable protomer should give the best match to the experiment, we found only weak inverse relationships between the calculated proton affinities and corresponding entropy similarities of experimental and CIDMD-predicted MS/MS spectra. CIDMD-predicted mechanistic details of fragmentation reaction pathways revealed a clear preference for specific protomer forms for several molecules. Overall, however, proton affinity was not a good predictor corresponding to the predicted CIDMD spectra. For example, for uracil, only one protomer predicted all experimental MS/MS fragment ions, but this protomer had neither the highest proton affinity nor the best MS/MS match score. Instead of proton affinity, the transfer of protons during the electrospray process from the initial protonation site (i.e., mobile proton model) better explains the differences between the thermodynamic rationale and experimental data. Protomers that undergo fragmentation with lower energy barriers have greater contributions to experimental MS/MS spectra than their thermodynamic Boltzmann populations would suggest. Hence, in silico predictions still need to calculate MS/MS spectra for multiple protomers, as the extent of distributions cannot be readily predicted.

Roundabout Mechanism of Ion-Molecule Nucleophilic Substitution Reactions.

Roundabout (RA) is an important indirect mechanism for gas-phase X- + CH3Y → XCH3 + Y- SN2 reactions at a high collision energy. It refers to the rotation of the CH3-group by half or multiple circles upon the collision of incoming nucleophiles before substitution takes place. The RA mechanism was first discovered in the Cl- + CH3I SN2 reaction to explain the energy transfer observed in crossed molecular beam imaging experiments in 2008. Since then, the RA mechanism and its variants have been observed not only in multiple C-centered SN2 reactions, but also in N-centered SN2 reactions, proton transfer reactions, and elimination reactions. This work reviewed recent studies on the RA mechanism and summarized the characteristics of RA mechanisms in terms of variant types, product energy partitioning, and product velocity scattering angle distribution. RA mechanisms usually happen at small impact parameters and tend to couple with other mechanisms at relatively low collision energy, and the available energy of roundabout trajectories is primarily partitioned to internal energy. Factors that affect the importance of the RA mechanism were analyzed, including the type of leaving group and nucleophile, collision energy, and microsolvation. A massive leaving group and relatively high collision energy are prerequisite for the occurrence of the roundabout mechanism. Interestingly, when reacting with CH3I, the importance of RA mechanisms follows an order of Cl- > HO- > F-, and such a nucleophile dependence was attributed to the difference in proton affinity and size of the nucleophile.

Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1

Human voltage-gated proton (hHv1) channels are crucial for regulating essential biological processes such as immune cell respiratory burst, sperm capacitation, and cancer cell migration. Despite the significant concentration difference between protons and other ions in physiological conditions, hHv1 demonstrates remarkable proton selectivity. Our calculations of single-proton, cation, and anion permeation free energy profiles quantitatively demonstrate that the proton selectivity of the wild-type channel originates from its strong proton affinity via the titration of the key residues D112 and D174, although the channel imposes similar kinetic blocking effects for protons compared to other ions. A two-proton knock-on model is proposed to mathematically explain the electrophysiological measurements of the pH-dependent proton conductance in the conductive state. Moreover, it is shown that the anion selectivity of the D112N mutant channel is tied to impaired proton transport and substantial anion leakage.

Exclusive catalytic hydrogenation of nitrobenzene toward p-aminophenol over atomically precise Au36(SR)24 clusters.

Despite the advances in devising green methodologies for selective hydrogenation of nitrobenzene toward p-aminophenol, it is still difficult to realize p-aminophenol as the exclusive product in heterogeneous metal catalysis, as the excessive hydrogenation of nitrobenzene usually results in the aniline byproduct. Herein we report that a metal cluster containing 36 gold atoms capped by 24 thiolate ligands provides a unique pathway for nitrobenzene hydrogenation to achieve a p-aminophenol selectivity of ∼100%. The gold cluster can efficiently suppress the over-hydrogenation of amino groups via hydroxyl rearrangement with the aid of water and sequentially the proton transfer promoted by acid toward p-aminophenol. More notably, remarkable catalytic performances can be extended to clusters with similar structures such as Au28(SR)20 and Au44(SR)28, where only an atomic layer change of 2.1 Å thickness in the Au36(SR)24 cluster can tailor the proton affinity for the amino group of the key intermediate phenylhydroxylamine, thereby altering the activity while the p-aminophenol selectivity remained.

The structure of water-ammonia mixtures from classical and abinitio molecular dynamics.

The structure of aqueous ammonia solutions is investigated through classical molecular dynamics (MD) and abinitio molecular dynamics (AIMD) simulations. We have preliminarily compared three well-known classical force fields for liquid water (SPC, SPC/E, and TIP4P) in order to identify the most accurate one in reproducing AIMD results obtained at the Generalized Gradient Approximation (GGA) and meta-GGA levels of theory. Liquid ammonia has been simulated by implementing an optimized force field recently developed by Chettiyankandy et al. [Fluid Phase Equilib. 511, 112507 (2020)]. Analysis of the radial distribution functions for different ammonia concentrations reveals that the three water force fields provide comparable estimates of the mixture structure, with the SPC/E performing slightly better. Although a fairly good agreement between MD and AIMD is observed for conditions close to the equimolarity, at lower ammonia concentrations, important discrepancies arise, with classical force fields underestimating the number and strength of H-bonds between water molecules and between water and ammonia moieties. Here, we prove that these drawbacks are rooted in a poor sampling of the configurational space spanned by the hydrogen atoms lying in the H-bonds of H2O⋯H2O and, more critically, H2O⋯NH3 neighbors due to the lack of polarization and charge transfer terms. This way, non-polarizable classical force fields underestimate the proton affinity of the nitrogen atom of ammonia in aqueous solutions, which plays a key role under realistic dilute ammonia conditions. Our results witness the need for developing more suited polarizable models that are able to take into account these effects properly.

Rational Design of Cyclopentadiene-Based Super- and Hyperacids Based on Aromaticity.

The design and synthesis of neutral organic superacids have been of interest recently due to their vast applications in chemistry and material sciences, for example, olefinic polymerization, isolation of highly reactive short-lived cations, etc. Cyclopentadiene behaves as a mild organic acid, producing a stable conjugate base by gaining aromaticity and conjugation after deprotonation. To stabilize conjugate bases of organic acids to show superacidities and hyperacidities, we considered aromatic phenyl substituents with cyclopentadiene (mono-, di-, and triphenyl-substituted cyclopentadiene and their cyano derivatives). The MP2, DFT (B3LYP, M06-2X), and CBS-QB3 methods were used to calculate the gas-phase proton affinities of the parent cyclopentadiene, and the DFT methods were chosen for the substituted cyclopentadiene as they yield an experimental proton affinity of cyclopentadiene of 253.66 kcal/mol (Expt. 253.6 ± 1.3 kcal/mol). The stable trisubstituted cyclopentadiene derivative shows gas-phase enthalpies of deprotonation (ΔHacid) of 245 and 239 kcal/mol with DFT B3LYP and M06-2X methods, respectively, with values in the range of hyperacidity. Some of the tautomers of cyclopentadiene derivatives show hyperacidity, with proton affinity values of 205-240 kcal/mol. Triphenyl-substituted cyclopentadiene behaves as a moderate acid but transforms into a superacid after replacing the phenyl group with nitrobenzene, which is a stronger acid than H2SO4 (ΔHacid = 298 kcal/mol). The nucleus-independent chemical shift (NICS) shows the extent of conjugation in the derivatives of cyclopentadienyl anions after deprotonation, which affects the stabilities of conjugate bases, i.e., the acidities of the protonated species. The calculated harmonic oscillator model of aromaticity and NICS indices reveal that the stability of conjugate bases as well as their acidities increase with increasing aromaticity of cyclopentadiene rings after deprotonation in all molecules.