Protonation Sites Research Articles

Stability and Structure of Potentially Atmospherically Relevant Glycine Ammonium Bisulfate Clusters.

New particle formation (NPF) is the process by which trace atmospheric acids and bases cluster and grow into particles that ultimately impact climate. Sulfuric acid concentration drives NPF, but nitrogen-containing bases promote the formation of more stable clusters via salt bridge formation. Recent computational efforts have suggested that amino acids can enhance NPF, predicting that they can stabilize new particles via multiple protonation sites, but there has yet to be experimental validation of these predictions. We used mass spectrometry and infrared spectroscopy to study the structure and stability of cationic clusters composed of glycine, sulfuric acid, and ammonia. When collisionally activated, clusters were significantly more likely to eliminate ammonia or sulfuric acid than glycine, while quantum chemical calculations predicted lower binding free energies for ammonia but similar binding free energies for glycine and sulfuric acid. These calculations predicted several low-energy structures, so we compared experimental and computed vibrational spectra to attempt to validate the computationally predicted minimum energy structure. Unambiguous identification of the experimental structure by comparison to these calculations was made difficult by the complexity of the experimental spectra and the fact that the identity of the computed lowest-energy structure depended strongly on temperature. If their vapors are present, amino acids are likely to be enriched in new particles by displacing more weakly bound ammonia, similar to the behavior of other atmospheric amines. The carboxylic acid groups were found to preferentially interact with other carboxylic acids, suggesting incipient organic/inorganic phase separation even at these small sizes.

Strong Bases and beyond: The Prominent Contribution of Neutral Push-Pull Organic Molecules towards Superbases in the Gas Phase.

In this review, the principles of gas-phase proton basicity measurements and theoretical calculations are recalled as a reminder of how the basicity PA/GB scale, based on Brønsted-Lowry theory, was constructed in the gas-phase (PA-proton affinity and/or GB-gas-phase basicity in the enthalpy and Gibbs energy scale, respectively). The origins of exceptionally strong gas-phase basicity of some organic nitrogen bases containing N-sp3 (amines), N-sp2 (imines, amidines, guanidines, polyguanides, phosphazenes), and N-sp (nitriles) are rationalized. In particular, the role of push-pull nitrogen bases in the development of the gas-phase basicity in the superbasicity region is emphasized. Some reasons for the difficulties in measurements for poly-functional nitrogen bases are highlighted. Various structural phenomena being in relation with gas-phase acid-base equilibria that should be considered in quantum-chemical calculations of PA/GB parameters are discussed. The preparation methods for strong organic push-pull bases containing a N-sp2 site of protonation are briefly reviewed. Finally, recent trends in research on neutral organic superbases, leaning toward catalytic and other remarkable applications, are underlined.

Proton Domino Reactions at an Imidazole Relay Control the Oxidation of a TyrZ-His190 Artificial Mimic of Photosystem II.

A close mimic of P680 and the TyrosineZ-Histidine190 pair in photosystem II (PS II) has been synthesized using a ruthenium chromophore and imidazole-phenol ligands. The intramolecular oxidation of the ligands by the photoproduced Ru(III) species is characterized by a small driving force, very similar to PS II where the complexity of kinetics was attributed to the reversibility of electron transfer steps. Laser flash photolysis revealed biphasic kinetics for ligand oxidation. The fast phase (τ<50 ns) corresponds to partial oxidation of the imidazole-phenol ligand, proton transfer within the hydrogen bond, and formation of a neutral phenoxyl radical. The slow phase (5-9 μs) corresponds to full oxidation of the ligand which is kinetically controlled by deprotonation of the distant 1-nitrogen of the imidazolium. These results show that imidazole with its two protonatable sites plays a special role as a proton relay in a 'proton domino' reaction.

Catalytic, Spectroscopic, and Theoretical Studies of Fe4S4-Based Coordination Polymers as Heterogenous Coupled Proton-Electron Transfer Mediators for Electrocatalysis.

Iron-sulfur clusters play essential roles in biological systems, and thus synthetic [Fe4S4] clusters have been an area of active research. Recent studies have demonstrated that soluble [Fe4S4] clusters can serve as net H atom transfer mediators, improving the activity and selectivity of a homogeneous Mn CO2 reduction catalyst. Here, we demonstrate that incorporating these [Fe4S4] clusters into a coordination polymer enables heterogeneous H atom transfer from an electrode surface to a Mn complex dissolved in solution. A previously reported solution-processable Fe4S4-based coordination polymer was successfully deposited on the surfaces of different electrodes. The coated electrodes serve as H atom transfer mediators to a soluble Mn CO2 reduction catalyst displaying good product selectivity for formic acid. Furthermore, these electrodes are recyclable with a minimal decrease in activity after multiple catalytic cycles. The heterogenization of the mediator also enables the characterization of solution-phase and electrode surface species separately. Surface enhanced infrared absorption spectroscopy (SEIRAS) reveals spectroscopic signatures for an in situ generated active Mn-H species, providing a more complete mechanistic picture for this system. The active species, reaction mechanism, and the protonation sites on the [Fe4S4] clusters were further confirmed by density functional theory calculations. The observed H atom transfer reactivity of these coordination polymer-coated electrodes motivates additional applications of this composite material in reductive H atom transfer electrocatalysis.

Imparting Stable and Ultrahigh Proton Conductivity to a Layered Rare Earth Hydroxide via Ion Exchange.

Proton conductors are essential functional materials with a wide variety of potential applications in energy storage and conversion. In order to address the issues of low proton conductivity and poor stability in conventional proton conductors, a simple and valid ion-exchange method was proposed in this study for the introduction of stable and ultrahigh proton conductivity in layered rare earth hydroxides (LRHs). Test analyses by solid-state nuclear magnetic resonance, Fourier transform infrared spectroscopy, and powder X-ray diffraction revealed that the exchange of H2PO4- not only does not disrupt the layered structure of LRHs, but also creates more active proton sites and channels necessary for proton transport, thereby creating a high-performance proton conductor (LRH-H2PO4-). By utilizing this ion-exchange method, the proton conductivity of LRHs can be significantly enhanced from a low level to an ultrahigh level (>10-2 S·cm-1), while maintaining excellent long-term stability. Moreover, through methodically manipulating the guest ions and molecules housed within the interlayers of LRHs, a comprehensive explanation has been presented regarding the proficient mechanism of proton conduction in LRH-H2PO4-. As a result, this investigation presents a feasible and available approach for advancing proton conductor.

Characterization of the fragmentation mechanisms in electrospray ionization tandem mass spectrometry of chloroquinoline derivatives with larvicidal activity against Aedes aegypti.

4,7-Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high-resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI-MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC50 values against Aedes aegypti larvae. Five DCQ derivatives were synthesized by using previously described protocols. ESI-MS/MS analyses were carried out with a quadrupole/time-of-flight and ion-trap instrument. The proposed gas-phase protonation sites and fragmentation were supported by density functional theory calculations. The larvicidal tests were performed with the Ae. aegypti Rockefeller strain, and the LC50 values were determined by employing five test concentrations. Larval mortality was determined after treatment for 48 h. DCQ bromides or aldehydes (C-3 or C-8 positions), as well as the trimethylsilyl derivative (C-3 position), were prepared. Detailed ESI-MS/MS data revealed heteroatom elimination through an exception to the even-electron rule, to originate open-shell species. Computational studies were used to define the protonation sites and fragmentation pathways. High activity of DCQ and its derivatives against Ae. aegypti larvae was demonstrated. Our results provided a well-founded characterization of the fragmentation reactions of DCQ and its derivatives, which can be useful for complementary studies of the development of a larvicidal product against Ae. aegypti.

Advancing water treatment: Harnessing cyclodextrin metal-organic frameworks with dual protonation sites for enhanced sulfate adsorption efficiency

TTH-CD-MOF was synthesized for sulfate ion adsorption from aqueous solutions, employing cross-linking modification of γ-CD-MOF with N-hydroxyethyl-morpholine as the modifier and triisocyanate as the cross-linking agent. The adsorbent underwent characterization through Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, N2 adsorption-desorption, and other analytical methods. Additionally, the impact of factors such as pH, adsorbent dosage, initial concentration, and ionic strength on adsorption performance was investigated. Adsorption experiments demonstrated the robust efficiency of TTH-CD-MOF for SO42- up to 95.3%, conforming to Langmuir isothermal and pseudo-second-order kinetic models, and higher temperatures favored SO42- adsorption. The maximum adsorption capacity was 189.51 mg·g−1 (25 °C). The adsorption mechanism comprised electrostatic interaction, adsorption within the cavities and pores of γ-CD-MOF. TTH-CD-MOF demonstrates effective sulfate removal from aqueous solutions, establishing its potential as an efficient anion adsorbent.

Observation of Solvent-Dependence in the Mechanism of Neutral-Catalyzed Isomerization of para-Aminobenzoic Acid Protomers.

Proton-transfer reactions are commonplace during electrospray ionization (ESI) mass spectrometry experiments and are often responsible for imparting charge to analyte molecules. Multiple protonation-site isomers (protomers) can arise for polyfunctional molecules and these isomers can interconvert via solvent-mediated proton transfer reactions during various stages of the ESI process. Studying the populations and interconversion of protonation isomers provides key insight into the ESI process, ion-molecule interactions, and ion dissociation mechanisms. An archetype molecule to study protomer interconversion fundamentals in this context is para-aminobenzoic acid (pABA), where both the amino and carboxylic acid protomers are typically formed under ESI and the mechanisms for interconversion are still under refinement. Using ion-trap mass spectrometry reaction kinetics (2.5 mTorr, 300 K), this study examines gas-phase interconversion catalysis of pABA protomers by seven neutral species, which are commen solvents and additives used for ESI: water, formic acid, methanol, ethanol, propanol, ammonia, and acetonitrile. Three distinct reaction cases are reported: (i) formic acid, methanol, ethanol, propanol, and ammonia each catalyze the interconversion between the amino and carboxylic acid protomers via a n = 1 solvent-molecule vehicle mechanism; (ii) for water, however, a n = 6 adduct complex is detected and this suggests that the observed protomer interconversion occurs through a Grotthuss mechanism, in accord with literature reports; (iii) acetonitrile inhibits proton transfer by the formation of particularly stable n = 1 and 2 adduct complexes. The second-order rate constants for the protomer interconversion are observed to increase in the following order: H2O < HCO2H < MeOH < EtOH < PrOH < NH3. Potential energy schemes are reported for all neutral-catalyzed proton transfer reactions using the DSD-PBEP86-D3(BJ)/aug-cc-pVDZ level of theory. A central transition state, which connects the protonation site adducts, is shown to be the key rate-limiting step. The energy of this transition state is sensitive to the proton affinity of the neutral solvent, and this is supported by the correlation between the reaction rate and the solvent proton affinity.

CREST-A program for the exploration of low-energy molecular chemical space.

Conformer-rotamer sampling tool (CREST) is an open-source program for the efficient and automated exploration of molecular chemical space. Originally developed in Pracht et al. [Phys. Chem. Chem. Phys. 22, 7169 (2020)] as an automated driver for calculations at the extended tight-binding level (xTB), it offers a variety of molecular- and metadynamics simulations, geometry optimization, and molecular structure analysis capabilities. Implemented algorithms include automated procedures for conformational sampling, explicit solvation studies, the calculation of absolute molecular entropy, and the identification of molecular protonation and deprotonation sites. Calculations are set up to run concurrently, providing efficient single-node parallelization. CREST is designed to require minimal user input and comes with an implementation of the GFNn-xTB Hamiltonians and the GFN-FF force-field. Furthermore, interfaces to any quantum chemistry and force-field software can easily be created. In this article, we present recent developments in the CREST code and show a selection of applications for the most important features of the program. An important novelty is the refactored calculation backend, which provides significant speed-up for sampling of small or medium-sized drug molecules and allows for more sophisticated setups, for example, quantum mechanics/molecular mechanics and minimum energy crossing point calculations.

Elucidating the Structure of the Eu‐EDTA Complex in Solution at various Protonation States

Ethylenediaminetetraacetic acid (EDTA), which has two amine and four carboxylate protonation sites, forms stable complexes with lanthanide ions. This work analyzes the coordination structure, in atomic resolution, of the Eu3+ ion complexed with EDTA in all its protonation states in aqueous solution. Eu‐EDTA complexes were modeled using classical molecular dynamics (MD) simulations using force field parameters optimized with ab initio molecular dynamics (AIMD) simulations. Structures from the MD simulations were used to predict extended X‐ray absorption fine structure (EXAFS) spectra and compared with EXAFS measurements of the Eu3+ aqua ion and Eu‐EDTA complexes at pH 3 and 11. This work details how Eu‐EDTA complex coordination structures change with increasing protonation of the EDTA ligand in the complex, from the tightly bound unprotonated complex to the unbinding of the fully protonated EDTA ligand from the Eu3+ ion as both become solvated by water. Agreement between predicted and measured EXAFS spectra supports the findings from simulation.

Electrochemical synthesis of donor-acceptor triazine based polymers with halochromic and electrochromic properties

Two triazine monomers substituted with aromatic α,β unsaturated ketones (chalcones) as connecting arms, holding triphenylamine or carbazole ending groups, were by the first time synthesized using commercial and inexpensive starting materials in just two steps. Triphenylamine and carbazole groups were strategically introduced in order to allow electrochemical polymerization and redox activity of the obtained films. The chalcone, together with the triphenylamine or carbazole outer groups, give rise to the formation of a donor-acceptor systems, allowing the generation of photoinduced intramolecular charge transfer (ICT) electronic transitions and providing basic sites for protonation. Because of the star-like chemical structure of the used triazine, electrochemical polymerization of these monomers conducted to the formation of hyperbranched structures. The polymeric materials exhibited not only electrochromic properties but also showed a halochromic behavior. Spectroelectrochemical studies of the films showed different colorations in the three redox states (neutral, semioxidized and fully oxidized). The color changes are fast and easily detected by the naked eye. Electrochemical parameters such as optical contrast, coloration efficiency, optical memory, and long-term stability for both films were obtained and compared. A quasi-solid window-type electrochromic device was assembled using the electrogenerated polymer with the best electrochromic performance and stability. Moreover, the triphenylamine based polymer showed reversible color changes upon acid-base vapor exposure cycles, demonstrating that this polymer can be used not only in electrochromic devices but also in acid vapor sensors.

A general, most basic rule for ion dissociation: Protonated molecules.

Contrary to the common but potentially misleading belief that when a protonated molecule is excited, it is its most stable protomer that will mandatorily dissociate, we demonstrate herein that, when rationalizing or predicting the chemistry of such ions, we should always search for the most labile protomer. This "most labile protomer" rule, based on the mobile proton model, states therefore that when a protonated molecule is heated, during ionization or by collisions for instance, the loosely bonded proton (H+ ) can acquire enough energy to detach itself from the most basic site of the molecule and then freely "walk through" the molecular framework to eventually find, if available, another protonation site, forming other less stable but more labile protomers, that is, protomers that may display lower dissociation thresholds. To demonstrate the validity of the "most labile protomer" rule as well as the misleading nature of the "most stable protomer" rule, we have selected several illustrative molecules and have collected their ESI(+)-MS/MS. To compare energies of precursors and products, we have also performed PM7 calculations and elaborated potential energy surface diagrams for their possible protomers and dissociation thresholds. We have also applied the "most labile protomer" rule to reinterpret-exclusively via classical charge-induced dissociation cleavages-several dissociation processes proposed for protonated molecules. In an accompanying letter, we have also applied a similar "most labile electromer" rule to ionized molecules.

Mechanism-Guided Kinetic Analysis of Electrocatalytic Proton Reduction Mediated by a Cobalt Catalyst Bearing a Pendant Basic Site.

Cobalt polypyridyl complexes stand out as efficient catalysts for electrochemical proton reduction, but investigations into their operating mechanisms, with broad-reaching implications in catalyst design, have been limited. Herein, we investigate the catalytic activity of a cobalt(II) polypyridyl complex bearing a pendant pyridyl base with a series of organic acids spanning 20 pKa units in acetonitrile. Structural analysis, as well as electrochemical studies, reveals that the Co(III) hydride intermediate is formed through reduction of the Co(II) catalyst followed by direct metal protonation in the initial EC step despite the presence of the pendant base, which is commonly thought of as a more kinetically accessible protonation site. Protonation of the pendant base occurs after the Co(III) hydride intermediate is further reduced in the overall ECEC pathway. Additionally, when the acid used is sufficiently strong, the Co(II) catalyst can be protonated, and the Co(III) hydride can react directly with acid to release H2. With thorough mechanistic understanding, the appropriate electroanalytical methods were identified to extract rate constants for the elementary steps over a range of conditions. Thermodynamic square schemes relating catalytic intermediates proposed in the three electrocatalytic HER mechanisms were constructed. These findings reveal a full description of the HER electrocatalysis mediated by this molecular system and provide insights into strategies to improve synthetic fuel-forming catalysts operative through metal hydride intermediates.

Proton Affinity and Conformational Integrity of a 24-Atom Triazine Macrocycle across Physiologically Relevant pH.

For 24-atom triazine macrocycles, protonation of the heterocycle leads to a rigid, folded structure presenting a network of hydrogen bonds. These molecules derive from dynamic covalent chemistry wherein triazine monomers bearing a protected hydrazine group and acetal tethered by the amino acid dimerize quantitatively in an acidic solution. Here, lysine is used, and the product is a tetracation. The primary amines of the lysine side chains do not interfere with quantitative yields of the desired bis(hydrazone) at concentrations of 5-125 mg/mL. Mathematical modeling of data derived from titration experiments of the macrocycle reveals that the pKa values of the protonated triazines are 5.6 and 6.7. Changes in chemical shifts of resonances in the 1H NMR spectra corroborate these values and further support assignment of the protonation sites. The pKa values of the lysine side chains are consistent with expectation. Upon deprotonation, the macrocycle enjoys greater conformational freedom as evident from the broadening of resonances in the 1H and 13C NMR spectra indicative of dynamic motion on the NMR time scale and the appearance of additional conformations at room temperature. While well-tempered metadynamics suggests only a modest difference in accessible conformational footprints of the protonated and deprotonated macrocycles, the shift in conformation(s) supports the stabilizing role that the protons adopt in the hydrogen-bonded network.

Switching of Protonation Sites in Hydrated Nicotine via a Grotthuss Mechanism.

The switching of the protonation sites in hydrated nicotine, probed by experimental infrared (IR) spectroscopy and theoretical ab initio calculations, is facilitated via a Grotthuss instead of a bimolecular proton transfer (vehicle) mechanism at the experimental temperature (T = 130 K) as unambiguously confirmed by experiments with deuterated water. In contrast, the bimolecular vehicle mechanism is preferred at higher temperatures (T = 300 K) as determined by theory. The Grotthuss mechanism for the concerted proton transfer results in the production of nicotine's bioactive and addictive pyrrolidine-protonated (Pyrro-H+) protomer with just 5 water molecules. Theoretical analysis suggests that the concerted proton transfer occurs via hydrogen-bonded bridges consisting of a 3 water molecule "core" that connects the pyridine protonated (Pyri-H+) with the pyrrolidine-protonated (Pyrro-H+) protomers. Additional water molecules attached as acceptors to the hydrogen-bonded "core" bridge result in lowering the reaction barrier of the concerted proton transfer down to less than 6 kcal/mol, which is consistent with the experimental observations.

Preferences of interaction sites for proton-induced photophysical signalling with a derivatized rhodamine probe

Chemosensors for selective and sensitive detection of analytes were developed following various structural, functional and operational design methodologies. The interaction between probe and analyte has been vital in chemosensor-based detection technologies. A pertinent question in such a system is to be convincingly addressed, that if the probes incorporating spatially-positioned multiple interaction sites offer preferences towards analyte binding for a favourable and optimal interaction. The derivatized Rhodamine based probe 1 exhibiting proton-induced dual mode signalling here contained several protonation sites. The absorption and fluorescence signal enhancement on protonation of the probe attributed to its proton-mediated spiro-ring opening. Out of several plausible conformations of protonated probe [1.H+], their DFT calculations revealed the proton binding preferentially to the N-donor atom on spiro-ring of 1 instead at other probable sites of protonation such as other hetero- donor atoms on the xanthene core or the carbonyl O- atom on the spiro-ring as the energetically favourable conformation. It was verified with the protonated probe complex's X-ray diffracted single crystal structure.

Vibrational and electronic spectra of protonated vanillin: exploring protonation sites and isomerisation.

Photofragmentation spectra of protonated vanillin produced under electrospray ionisation (ESI) conditions have been recorded in the 3000-3700 cm-1 (vibrational) and 225-460 nm (electronic) ranges, using room temperature IRMPD (infrared multiphoton dissociation) and cryogenic UVPD (ultraviolet photodissociation) spectroscopies, respectively. The cold (∼50 K) electronic UVPD spectrum exhibits very well resolved vibrational structure for the S1 ← S0 and S3 ← S0 transitions, suggesting long excited state dynamics, similar to its simplest analogue, protonated benzaldehyde. The experimental data were combined with theoretical calculations to determine the protonation site and configurational isomer observed in the experiments.

Identification of Amide Oxygen as First Protonation Site in Gaseous Short Peptides: Theoretical Evidence from a First-Principles Study

Identification of Amide Oxygen as First Protonation Site in Gaseous Short Peptides: Theoretical Evidence from a First-Principles Study

Advances and challenges in designing active site environments in zeolites for Brønsted acid catalysis.

Zeolites contain proton active sites in diverse void environments that stabilize the reactive intermediates and transition states formed in converting hydrocarbons and oxygenates to chemicals and energy carriers. The catalytic diversity that exists among active sites in voids of varying sizes and shapes, even within a given zeolite topology, has motivated research efforts to position and quantify active sites within distinct voids (synthesis-structure) and to link active site environment to catalytic behavior (structure-reactivity). This Feature Article describes advances and challenges in controlling the position of framework Al centers and associated protons within distinct voids during zeolite synthesis or post-synthetic modification, in identifying and quantifying distinct active site environments using characterization techniques, and in determining the influence of active site environments on catalysis. During zeolite synthesis, organic structure directing agents (SDAs) influence Al substitution at distinct lattice positions via intermolecular interactions (e.g., electrostatics, hydrogen bonding) that depend on the size, structure, and charge distribution of organic SDAs and their mobility when confined within zeolitic voids. Complementary post-synthetic strategies to alter intrapore active site distributions include the selective removal of protons by differently-sized titrants or unreactive organic residues and the selective exchange of framework heteroatoms of different reactivities, but remain limited to certain zeolite frameworks. The ability to identify and quantify active sites within distinct intrapore environments depends on the resolution with which a given characterization technique can distinguish Al T-site positions or proton environments in a given zeolite framework. For proton sites in external unconfined environments, various (post-)synthetic strategies exist to control their amounts, with quantitative methods to distinguish them from internal sites that largely depend on using stoichiometric or catalytic probes that only interact with external sites. Protons in different environments influence reactivity by preferentially stabilizing larger transition states over smaller precursor states and influence selectivity by preferentially stabilizing or destabilizing competing transition states of varying sizes that share a common precursor state. We highlight opportunities to address challenges encountered in the design of active site environments in zeolites by closely integrating precise (post-)synthetic methods, validated characterization techniques, well-defined kinetic probes, and properly calibrated theoretical models. Further advances in understanding the molecular details that underlie synthesis-structure-reactivity relationships for active site environments in zeolite catalysis can accelerate the predictive design of tailored zeolites for desired catalytic transformations.

Searching low-energy conformers of neutral and protonated di-, tri-, and tetra-glycine using first-principles accuracy assisted by the use of neural network potentials.

In the last ten years, combinations of state-of-the-art gas-phase spectroscopies and quantum chemistry calculations have suggested several intuitive trends in the structure of small polypeptides that may not hold true. For example, the preference for the cis form of the peptide bond and multiple protonated sites was proposed by comparing experimental spectra with low-energy minima obtained from limited structural sampling using various density functional theory methods. For understanding the structures of polypeptides, extensive sampling of their configurational space with high-accuracy computational methods is required. In this work, we demonstrated the use of deep-learning neural network potential (DL-NNP) to assist in exploring the structure and energy landscape of di-, tri-, and tetra-glycine with the accuracy of high-level quantum chemistry methods, and low-energy conformers of small polypeptides can be efficiently located. We hope that the structures of these polypeptides we found and our preliminary analysis will stimulate further experimental investigations.