Bond Proton Research Articles

The influence of base pair tautomerism on single point mutations in aqueous DNA.

The relationship between base pair hydrogen bond proton transfer and the rate of spontaneous single point mutations at ambient temperatures and pressures in aqueous DNA is investigated. By using an ensemble-based multiscale computational modelling method, statistically robust rates of proton transfer for the A:T and G:C base pairs within a solvated DNA dodecamer are calculated. Several different proton transfer pathways are observed within the same base pair. It is shown that, in G:C, the double proton transfer tautomer is preferred, while the single proton transfer process is favoured in A:T. The reported range of rate coefficients for double proton transfer is consistent with recent experimental data. Notwithstanding the approximately 1000 times more common presence of single proton transfer products from A:T, observationally there is bias towards G:C to A:T mutations in a wide range of living organisms. We infer that the double proton transfer reactions between G:C base pairs have a negligible contribution towards this bias for the following reasons: (i) the maximum half-life of the G*:C* tautomer is in the range of picoseconds, which is significantly smaller than the milliseconds it takes for DNA to unwind during replication, (ii) statistically, the majority of G*:C* tautomers revert back to their canonical forms through a barrierless process, and (iii) the thermodynamic instability of the tautomers with respect to the canonical base pairs. Through similar reasoning, we also deduce that proton transfer in the A:T base pair does not contribute to single point mutations in DNA.

Inter- vs. Intramolecular Hydrogen Bond Patterns and Proton Dynamics in Nitrophthalic Acid Associates.

Noncovalent interactions are among the main tools of molecular engineering. Rational molecular design requires knowledge about a result of interplay between given structural moieties within a given phase state. We herein report a study of intra- and intermolecular interactions of 3-nitrophthalic and 4-nitrophthalic acids in the gas, liquid, and solid phases. A combination of the Infrared, Raman, Nuclear Magnetic Resonance, and Incoherent Inelastic Neutron Scattering spectroscopies and the Car–Parrinello Molecular Dynamics and Density Functional Theory calculations was used. This integrated approach made it possible to assess the balance of repulsive and attractive intramolecular interactions between adjacent carboxyl groups as well as to study the dependence of this balance on steric confinement and the effect of this balance on intermolecular interactions of the carboxyl groups.

Pattern-free generation and quantummechanical scoring of ring-chain tautomers.

In contrast to the computational generation of conventional tautomers, the analogous operation that would produce ring-chain tautomers is rarely available in cheminformatics codes. This is partly due to the perceived unimportance of ring-chain tautomerism and partly because specialized algorithms are required to realize the non-local proton transfers that occur during ring-chain rearrangement. Nevertheless, for some types of organic compounds, including sugars, warfarin analogs, fluorescein dyes and some drug-like compounds, ring-chain tautomerism cannot be ignored. In this work, a novel ring-chain tautomer generation algorithm is presented. It differs from previously proposed solutions in that it does not rely on hard-coded patterns of proton migrations and bond rearrangements, and should therefore be more general and maintainable. We deploy this algorithm as part of a workflow which provides an automated solution for tautomer generation and scoring. The workflow identifies protonatable and deprotonatable sites in the molecule using a previously described approach based on rapid micro-pKa prediction. These data are used to distribute the active protons among the protonatable sites exhaustively, at which point alternate resonance structures are considered to obtain pairs of atoms with opposite formal charge. These pairs are connected with a single bond and a 3D undistorted geometry is generated. The scoring of the generated tautomers is performed with a subsequent density functional theory calculation employing an implicit solvent model. We demonstrate the performance of our workflow on several types of organic molecules known to exist in ring-chain tautomeric equilibria in solution. In particular, we show that some ring-chain tautomers not found using previously published algorithms are successfully located by ours.

Quantum chemical mass spectrometry: Ab initio study of b2 -ion formation mechanisms for the singly protonated Gln-His-Ser tripeptide.

Both amide bond protonation triggering peptide fragmentations and the controversial b2 -ion structures have been subjects of intense research. The involvement of histidine (H), with its imidazole side chain that induces specific dissociation patterns involving inter-side-chain (ISC) interactions, in b2 -ion formation was investigated, focusing on the QHS model tripeptide. To identify the effect of histidine on fragmentations issued from ISC interactions, QHS was selected for a comprehensive analysis of the pathways leading to the three possible b2 -ion structures, using quantum chemical calculations performed at the DFT/B3LYP/6-311+G* level of theory. Electrospray ionization ion trap mass spectrometry allowed the recording of MS2 and MS3 tandem mass spectra, whereas the Quantum Chemical Mass Spectrometry for Materials Science (QCMS2 ) method was used to predict fragmentation patterns. Whereas it is very difficult to differentiate among protonated oxazolone, diketopiperazine, or lactam b2 -ions using MS2 and MS3 mass spectra, the calculations indicated that the QH b2 -ion (detected at m/z 266) is probably a mixture of the lactam and oxazolone structures formed after amide nitrogen protonation, making the formation of diketopiperazine less likely as it requires an additional step for its formation. In contrast to glycine-histidine-containing b2 -ions, known to be issued from the backbone-imidazole cyclization, we found that interactions between the side chains were not obvious to perceive, neither from a thermodynamics nor from a fragmentation perspective, emphasizing the importance of the whole sequence on the dissociation behavior usually demonstrated from simple glycine-containing tripeptides.

Antioxidant vs. pro‐oxidant activities of quercetin in aqueous phase: A Density Functional Theory study

AbstractThe antioxidant potential of quercetin (Quer) has been investigated for its radical scavenging activity and Cu(II) ion chelating one. Two intrinsic reactivities including bond dissociation enthalpy (BDE) and proton affinity (PA) were systematically calculated in water at the M05‐2X/6‐311++G(d,p) level of theory. All possible hydrated Quer–Cu(II) complexes were also performed to consider its indirect antioxidant activity via the meal ion chelation capacity. Furthermore, reaction enthalpies as well as Gibbs free energies of reactions between Quer‐Cu(II) complexes with O2•‐ and ascorbate anion (Asc‐) in forming corresponding Quer‐Cu(I) ones have also been investigated to draw the larger picture on reduction potential of Cu(II)to Cu(I) ions which may involve in Fenton‐like reactions leading to HO• radical formation.

Effect of nitrogen substitution and π-conjugation on photophysical properties and excited state intramolecular proton transfer reactions of methyl salicylate derivatives: Theoretical investigation

Effects of nitrogen substitution and π-conjugation on the strength of intramolecular hydrogen bond (H-bond), photophysical properties, and excited-state intramolecular proton transfer (ESIPT) reactions of MS derivatives have been systematically investigated using DFT and TD-DFT methods at the B3LYP/TZVP level. The H-bond strength of all studied compounds becomes stronger in the S1 than in the S0. This result is confirmed by vibrational IR spectra and topological analysis. The H-bond strength of nitrogen substituted compounds is lower than those of compounds with the π-extended conjugation. For photophysical properties, the HOMO-LUMO energy gaps in normal and tautomer forms of nitrogen substituted compounds are insignificantly increased, whereas those of compounds with the π-extended conjugation are notably decreased. The slight widening of the energy gaps results in the slight blue-shifts of the absorption and emission peaks of nitrogen substituted compounds compared to those of MS, whereas the significant narrowing of the energy gaps makes the incredible red-shifts of both electronic spectra of compounds with the π-extended conjugation. Thus, remarkably large Stokes shifts of about 1000 cm−1 are observed for compounds with the π-extended conjugation (M3HN, M2HQC, and M3HQC). In addition, potential energy curves along the PT reaction indicate that the ESIPT of all studied compounds should occurred due to low PT barriers in the exothermic reaction. Dynamic simulations reveal that the ESIPT reactions of studied compounds are observed in an ultrafast time scale (38–130 fs). Most of them have remarkably high PT probabilities (0.84–1.00) except M3HP (0.56), which are in good agreement with the results of H-bond strength. Therefore, the photophysical properties of studied compounds can be significantly tuned by controlling the effect of π-conjugation.

N2O Reductase Activity of a [Cu4S] Cluster in the 4CuI Redox State Modulated by Hydrogen Bond Donors and Proton Relays in the Secondary Coordination Sphere

AbstractThe model complex [Cu4(μ4‐S)(dppa)4]2+ (1, dppa=μ2‐(Ph2P)2NH) has N2O reductase activity in methanol solvent, mediating 2 H+/2 e− reduction of N2O to N2+H2O in the presence of an exogenous electron donor (CoCp2). A stoichiometric product with two deprotonated dppa ligands was characterized, indicating a key role of second‐sphere N−H residues as proton donors during N2O reduction. The activity of 1 towards N2O was suppressed in solvents that are unable to provide hydrogen bonding to the second‐sphere N−H groups. Structural and computational data indicate that second‐sphere hydrogen bonding induces structural distortion of the [Cu4S] active site, accessing a strained geometry with enhanced reactivity due to localization of electron density along a dicopper edge site. The behavior of 1 mimics aspects of the CuZ catalytic site of nitrous oxide reductase: activity in the 4CuI:1S redox state, use of a second‐sphere proton donor, and reactivity dependence on both primary and secondary sphere effects.

N2 O Reductase Activity of a [Cu4 S] Cluster in the 4CuI Redox State Modulated by Hydrogen Bond Donors and Proton Relays in the Secondary Coordination Sphere.

The model complex [Cu4 (μ4 -S)(dppa)4 ]2+ (1, dppa=μ2 -(Ph2 P)2 NH) has N2 O reductase activity in methanol solvent, mediating 2 H+ /2 e- reduction of N2 O to N2 +H2 O in the presence of an exogenous electron donor (CoCp2 ). A stoichiometric product with two deprotonated dppa ligands was characterized, indicating a key role of second-sphere N-H residues as proton donors during N2 O reduction. The activity of 1 towards N2 O was suppressed in solvents that are unable to provide hydrogen bonding to the second-sphere N-H groups. Structural and computational data indicate that second-sphere hydrogen bonding induces structural distortion of the [Cu4 S] active site, accessing a strained geometry with enhanced reactivity due to localization of electron density along a dicopper edge site. The behavior of 1 mimics aspects of the CuZ catalytic site of nitrous oxide reductase: activity in the 4CuI :1S redox state, use of a second-sphere proton donor, and reactivity dependence on both primary and secondary sphere effects.

Dimethyl sulfoxide-aided copper(0)-catalyzed intramolecular decarbonylative rearrangement of N-aryl isatins leading to acridones

Described here is the first example of Cu(0)-catalyzed intramolecular decarbonylative rearrangements of readily available N-aryl isatins assisted by solvent dimethyl sulfoxide (DMSO) under air atmosphere and additive-free conditions leading to various biologically important acridones in good to excellent yields. This novel transformation is proposed to go through a sequential DMSO-aided Cu insertion into the amide CN bond, CO extrusion, Cu migration, reductive elimination and DMSO-aided proton migration processes, involving multiple types of bond cleavage and formation in a single chemical step.

Hydrogen bond configuration and protonation of ground and lowest excited triplet states of 4‑amino‑4'‑nitrobiphenyl based on nanosecond transient absorption spectroscopy.

Intramolecular charge transfer (ICT) is an important photochemical process. In contrast to those in singlet manifold, triplet ICT states were less studied. In this paper, the lowest excited triplet state (T1) of 4‑amino‑4'‑nitrobiphenyl (NH2-Bp-NO2) was recorded with nanosecond transient absorption spectroscopy in acidic acetonitrile and alcoholic solutions. By employing the Kamlet-Taft model to analyze the correlation between absorption maxima and alcohol solvent properties including polarity/polarizability, abilities of hydrogen bond donating and hydrogen bond accepting, hydrogen bond configuration in the ground state (S0) and T1 was resolved. The results suggest that the hydrogen bond between amino H and alcohol is dominant in S0, while in T1, hydrogen bonds between amino H and alcohol, between nitro O and alcohol have comparable contribution. By examination of the 1‑naphthol quench effect on T1, the hydrogen bond between nitro O and alcohol was confirmed present. Theoretical calculation results on the model of NH2-Bp-NO2-(MeOH)3 also indicate that hydrogen bonds between amino H and alcohol, between nitro O and alcohol are both much stronger in T1 than in S0. In acidic acetonitrile solution, in S0 of NH2-Bp-NO2 the amino group is protonated with pKa of 4.5, meanwhile in T1 the nitro group is much easier to be protonated than in S0. Its conjugated acid was measured to have a pKa of 3.1.

Ruthenium(II)-Catalyzed Distal Weak O-Coordinating C-H Alkylation of Arylacetamides with Alkenes: Combined Experimental and DFT Studies.

The C-H alkylation of arylacetamides with activated alkenes such as substituted acrylates and vinyl sulphone in the presence of a ruthenium catalyst and organic acid via the weak O-coordination under the redox free version is described. The present protocol was effective with different substituted arylacetamides including secondary and tertiary amides. The reaction mechanism including the ortho C-H bond activation, migratory insertion, and protonation by acetic acid was suggested and supported by the deuterium labeling experiments, competitive experiments, and DFT calculations including TS analysis.

Radical Scavenging Activity of Natural-Based Cassaine Diterpenoid Amides and Amines.

The radical scavenging capacities of four new cassaine diterpenoid amides including 3β-hydroxydinorerythrosuamide (1), 3β-acetoxydinorerythrosuamide (2), 3β-tigloyloxydinorerythrosuamide (3), and 6α-hydroxydinorcassamide (4) present in leaf extract and four new cassaine diterpenoid amines namely erythroformine A (5), erythroformine B (6), 6α-hydroxy-nor-cassamine (7), and nor-erythrosuamine (8) recently identified in the extract of the bark of Erythrophleum fordii were elucidated using density functional theory (DFT) method. Different thermochemical properties characterizing antioxidant potential including bond dissociation enthalpy (BDE), proton affinity (PA), and adiabatic ionization potential (IP) were calculated at the B3LYP/6-311G(d,p) level of theory. Scavenging reaction mechanisms of cassaine diterpenes toward HOO• radical including formal hydrogen transfer (FHT; either hydrogen atom transfer (HAT) or proton coupled electron transfer (PCET)), radical adduct formation (RAF), single electron transfer (SET), and proton transfer (PT) were studied in the gas phase, water, and benzene. The potential energy profiles and kinetic calculations for the FHT and RAF reactions were calculated at 298.15 K. The results showed that all the studied compounds present strong antioxidant activity via HAT mechanism with BDEs varying from 69.4 to 77.9 kcal/mol. While solvents have only a slight effect on HAT and RAF mechanisms, SET and PT reactions are likely to occur in polar media. Among the studied compounds, 3 is the most reactive one both for HAT (H-abstraction at C7, Δ H -11.3 kcal/mol) and for RAF (radical addition at C13 = C15 bond, Δ H -5.2 kcal/mol) reactions. The rate constants of these reactions are also comparable with several referenced antioxidants such as Trolox and ascorbic acid.

Substituent Effects on the Radical Scavenging Activity of Isoflavonoid.

Understanding the role of substituents is of great importance for the preparation of novel phenolic compounds with enhanced antioxidative properties. In this work, the antioxidative activity of isoflavonoid derivatives with different substituents placed at the C2 position was determined by density functional theory (DFT) calculations. The bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA) related to hydrogen atom transfer (HAT), single electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanisms were calculated. The strongest antioxidative group of isoflavonoid is not altered by the substituents. Excellent correlations were found between the BDE/IP/PA and Hammett sigma constants. Equations obtained from linear regression can be useful in the selection of suitable candidates for the synthesis of novel isoflavonoids derivatives with enhanced antioxidative properties. In the gas and benzene phases, the electron-donating substituents would enhance the antioxidative activity of isoflavonoids via weakening the BDE of 4′−OH. In water phase, they will reduce the antioxidative by strengthening the PA of 7−OH. Contrary results occur for the electron-withdrawing groups. In addition, the electronic effects of substituents on the BDE/IP/PA have also been analyzed.

Proton-Conductive Keggin-Type Clusters Decorated by the Complex Moieties of Cu(II) 2,2′-Bipyridine-4,4′-dicarboxylate/Diethyl Analogues

Three proton-conductive decorated Keggin-type clusters, {[Cu(debpdc)(H2O)3][Cu(debpdc)(H2O)Cl][PMo12O40]} ·2CH3OH ·1.5CH3CN ·3H2O (1), {[Cu(H2bpdc)(H2O)2Cl0.5]2[PW12O40]}·10H2O (2), and {[Cu(H2bpdc)(H2O)2.5]2[SiW12O40]}·10H2O (3) (where debpdc is diethyl 2,2'-bipyridine-4,4'-dicarboxylate and H2bpdc is 2,2'-bipyridine-4,4'-dicarboxylic acid), were synthesized through electrostatic and coordination interactions between Keggin-type anions and Cu(II) H2bpdc/debpdc complex moieties. Interestingly, in the three complexes, both the H2bpdc/debpdc and the Keggin anion are covalently linked to the Cu2+ ions as polydentate organic and inorganic ligands, respectively. Notably, complexes 2 and 3 are the first examples of the functionalization of a Keggin-type cluster with Cu(II)-H2bpdc complex moieties, thereby providing a pathway to design and synthesize multifunctional hybrid materials with cluster structures based on two building units. In them, the free COOH groups of the H2bpdc ligand can act as both hydrogen bond acceptors and proton carriers. 1 has debpdc ligands with ethoxycarbonyl groups, while 2 and 3 have the H2bpdc ligands with free COOH groups; thus, the three complexes help us to understand the influence of the different substituents on the proton conductivity. The measurement results reveal that 2 and 3 have a high conductivity value of over 10-3 S cm-1 at 100 °C under 98% relative humidity, which is 2 orders of magnitude higher than that of 1 under the same conditions.

Molecular dynamics involving proton exchange of a protic ionic liquid-water mixture studied by NMR spectroscopy.

Protic ionic liquids (PILs) are proposed as alternative anhydrous proton conducting electrolytes for intermediate temperature fuel cells. One of the key factors in their performance as electrolytes, as far as charge transport is concerned, is their proton conductivity. Noting the success of water-containing electrolytes and recognising faster proton mobility than structural relaxation (via mechanisms such as Grotthuss) as their advantage, such an advantage is envisaged for PILs and in some cases deduced. As extended hydrogen bond networks and proton exchange are at the heart of these mechanisms, here we report our results on a prototypical characterisation of proton exchange in a PIL (C2HimNTf2)-water mixture. NMR lineshape analysis and exchange spectroscopy (EXSY) are used to quantify the proton exchange rate. The obtained exchange rate is then used to explain the diffusion behaviour of the exchangeable proton as measured by pulse field gradient NMR methods; a marginal anomaly in the translational dynamics of the exchangeable proton in the form of a faster NH proton is observed. As far as we know this is the first report on systematic characterisation of proton exchange in PILs with the aim of understanding its effect on translational motion as a way of discerning exchange related mobility anomalies.

Effect of cyclization on bond dissociation enthalpies, acidities and proton affinities of carbamate molecules: A theoretical study

The effect of cyclization and inclusion of double bond in ring on structure, proton affinities, acidities and NH bond dissociation enthalpies (BDEs) of carbamate molecules NH2C(=X)YR (X, Y = O, S, Se; R = -C2H5, -CH=CH2) has been investigated in the present study. The S-conformer is more stable than A-conformer in acyclic carbamate molecule. The higher stability of S-conformer can be anticipated due to the decreased repulsive interactions of the lone pairs present on Y with the π cloud of CX bond as compared to the A-conformer. The cyclization increases the acidities as compared to the S-conformer due to unfavorable A conformation that the carbamate group is forced to adopt in cyclic carbamate molecule and stability of anion being more than that of acyclic analog. However, when compared with A-conformer of acyclic analogs acidities are slightly lower. The change in NH BDEs and proton affinities on cyclization is small but inclusion of double bond in the ring reduces NH BDEs to a large extent.

Synthesis, antioxidant, and anti-tyrosinase activity of some aromatic oximes: an experimental and theoretical study

In this study, five oximes were synthesized, characterized, and their antioxidant activity investigated experimentally and theoretically. Labeled OX1–OX5, our oximes were subjected to three antioxidant activity assays (1,1-diphenyl-2-picrylhydrazyl, cupric reducing antioxidant capacity test [CUPRAC], and ferric reducing antioxidant power test). The related results were very fulfilling presenting certain antioxidant properties for the majority of the studied compounds, especially with CUPRAC test where OX1 and OX2 presented a better result than the used standard antioxidants. Besides, the thermodynamic molecular descriptors (bond dissociation enthalpy, ionization potential, and proton affinity) of our molecules were calculated with the density functional theory to elucidate the experimental results. The resulting values were in a good agreement with the experimental results. The second part of this work consisted of an anti-tyrosinase activity evaluation of the five oximes where three of them displayed an inhibitory effect against this enzyme. To analyze this result, a molecular docking was conducted and the obtained values were in accordance with the experience. Absorption, distribution, metabolism, and excretion properties were also assessed via Molinspiration software and all our molecules satisfied the related conditions. Thus, the conducted theoretical and experimental studies were in excellent harmony, together supporting the antioxidant power of our compounds, which could permit their use in cosmetic, pharmaceutical, or food industry domains, after further clinical tests.

Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin⁻Spin Coupling Constants.

Density functional theory (DFT) has provided detailed information on the molecular structure and spin–spin coupling constants of heparin tetrasaccharide (GlcNS,6S-IdoA2S-GlcNS,6S-IdoA2S-OMe) representing the predominant heparin repeating-sequence. The fully optimised molecular structures of two tetrasaccharide conformations (differing from each other in the conformational form of the sulphated iduronic acid residue–one 1C4 and the other 2S0) were obtained using the B3LYP/6-311+G(d,p) level of theory and applying explicit water molecules to simulate the presence of a solvent. The theoretical data provided insight into variations of the bond lengths, bond angles and torsion angles, formations of intra- and intermolecular hydrogen bonds and ionic interactions. Optimised molecular structures indicated the formation of a complex hydrogen bond network, including interresidue and intraresidue bonds. The ionic interactions strongly influence the first hydration shell and, together with hydrogen bonds, play an important role in shaping the 3D tetrasaccharide structure. DFT-derived indirect three–bond proton–proton coupling constants (3JH-C-C-H) showed that the best agreement with experiment was obtained with a weighted average of 67:33 (1C4:2S0) of the IdoA2S forms. Detailed analysis of Fermi-contact contributions to 3JH-C-C-H showed that important contributions arise from the oxygen lone pairs of neighbouring oxygen atoms. The analysis also showed that the magnitude of diamagnetic spin–orbit contributions are sufficiently large to determine the magnitude of some proton–proton coupling constants. The data highlight the need to use appropriate quantum-chemical calculations for a detailed understanding of the solution properties of heparin oligosaccharides.

A path integral molecular dynamics study on intermolecular hydrogen bond of acetic acid-arsenic acid anion and acetic acid-phosphoric acid anion clusters.

We apply ab initio path integral molecular dynamics simulation employing ωB97XD as the quantum chemical calculation method to acetic acid-arsenic acid anion and acetic acid-phosphoric acid anion clusters to investigate the difference of the hydrogen bond structure and its fluctuation such as proton transfer. We found that the nuclear quantum effect enhanced the fluctuation of the hydrogen bond structure and proton transfer, which shows treatment of the nuclear quantum effect was essential to investigate these systems. The hydrogen bond in acetic acid-arsenic acid anion cluster showed characters related to low-barrier hydrogen bonds, while acetic acid-phosphoric acid anion cluster did not. We found non-negligible distinction between these two systems, which could not be found in conventional calculations. We suggest that the difference in amount of atomic charge of the atoms consisting the hydrogen bond is the origin of the difference between acetic acid-arsenic acid and acetic acid-phosphoric acid anion cluster. © 2018 Wiley Periodicals, Inc.

Probing Solvation-Induced Structural Changes in Conformationally Flexible Peptides: IR Spectroscopy of Gly3H+·(H2O).

IR predissociation spectroscopy of the Gly3H+(H2O) complex formed inside of a cryogenic ion trap reveals how the flexible model peptide structurally responds to solvation by a single water molecule. The resulting one-laser spectrum is quite congested, and the spectral analyses were assisted by both H2O/D2O substitution and IR-IR double resonance spectroscopy, revealing the presence of two contributing isomers and extensive anharmonic features. Comparisons to structures found via a systematic computational search identified the geometries of these two isomers. The major isomer, with all trans amide bonds and protonation on the terminal amine, represents ∼90% of the overall population. It noticeably differs from the unsolvated Gly3H+, which exists in two isomeric forms: one with a cis amide bond and the other with protonation on an amide C═O. These results indicate that interactions with just one water molecule can induce significant structural changes, i.e., cis- trans amide bond rotation and proton migration, even as the clustering occurs within an 80 K cryogenic ion trap. Calculations of the isomerization pathways further reveal that the binding energy of the water molecule provides sufficient internal energy to overcome the barriers for the observed structural changes, and the minor solvation isomer results from a small fraction of the ions being kinetically trapped along one of the pathways.