Solvent Water Molecules Research Articles

WaterAlignment: Identification of displaced water molecules in molecular docking using Jonker and Volgenant shortest path augmentation for linear assignment

The dynamics of individual water molecules has a strong effect on the energetics of biochemical interactions, such as peptide–protein binding. Existing software are able to predict the location of water molecules at the interface between a macromolecule and a ligand in a single state or at a particular time point. The program described in this article compares explicit solvent molecules from two different states within a given volume of space; for example between a free protein vs. the same protein with a ligand bound. This comparison creates a unique one-to-one matching between waters from the two states utilizing the Jonker and Volgenant algorithm for linear assignment. Matchings are deterministic and minimize the sum of the distance between matched pairs. Explicit solvent ligand docking can utilize this matching to understand how ligand binding affects the energy of interface waters. This algorithm can also be used to compare predicted water molecules to those seen in X-ray crystallography, or to compare two different methods of solvent prediction. Program summaryProgram title: WaterAlignmentProgram files doi:http://dx.doi.org/10.17632/pk6fnvwgg7.1Licensing provisions: GNU Lesser General Public LicenseProgramming language: PythonNature of problem: Comparison of the location of solvent water molecules present in the same volume under two conditions in order to ‘match’ waters between the two conditions; that is, to define matched waters that represent the same molecule. The algorithm was developed to compare waters present in the binding pocket of a protein with and without a bound ligand, in order to determine the effect of ligand binding on the energy of waters in the binding pocket.Solution method: The task is treated as a linear assignment problem solved by the Jonker and Volgenant algorithm. A bipartite graph is constructed with each part of the graph consisting of nodes representing one of the two set of waters. Edges facing from the first set of nodes to the second set are added with cost equal to the distance between the waters that the nodes represent. This data structure is then used to create propositional matches, with each new match able to replace prior matches when beneficial to the overall result.

Supramolecular assemblies of bi-component molecular solids formed between homopiperazine and organic acids

Three compounds constructed by homopiperazine with 1,5-naphthalenedisulfonic acid, 4,5-dichlorophthalic acid and 2,2′,5,5′-biphenyltetracarboxylic acid have been analyzed with respect to hydrogen bonds appeared in the crystal structures. Single crystal X-ray diffraction studies showed that partial protons were transferred to homopiperazine, which made it possible to form N–H⋯O hydrogen bonds in all three compounds. Moreover, O–H⋯O and C–H⋯O hydrogen bonds are founded in 2 and 3 respectively. All of the three compounds displayed 3D supramolecular network structures for the effect of various hydrogen bonds interactions. In addition solvent water molecules and ethanol molecules played an indispensable role in the construction of compounds 2 and 3. Some main supramolecular synthons observed in three compounds were shown to construct most of these hydrogen bonding networks. These new multi-component molecular solids of homopiperazine were characterized by powder X-ray diffraction, infrared spectroscopy, 1H nuclear magnetic resonance and thermogravimetric analysis.

Crystal structure of hexa-μ-chlorido-μ4-oxido-tetra-kis-{[1-(2-hy-droxy-eth-yl)-2-methyl-5-nitro-1H-imidazole-κN 3]copper(II)} containing short NO2⋯NO2 contacts.

The title tetra-nuclear copper complex, [Cu4Cl6O(C6H9N3O3)4] or [Cu4Cl6O-(MET)4] [MET is 1-(2-hy-droxy-eth-yl)-2-methyl-5-nitro-1H-imidazole or metronidazole], contains a tetra-hedral arrangement of copper(II) ions. Each copper atom is also linked to the other three copper atoms in the tetra-hedron via bridging chloride ions. A fifth coordination position on each metal atom is occupied by a nitro-gen atom of the monodentate MET ligand. The result is a distorted CuCl3NO trigonal-bipyramidal coordination polyhedron with the axial positions occupied by oxygen and nitro-gen atoms. The extended structure displays O-H⋯O hydrogen bonding, as well as unusual short O⋯N inter-actions [2.775 (4) Å] between the nitro groups of adjacent clusters that are oriented perpendicular to each other. The scattering contribution of disordered water and methanol solvent mol-ecules was removed using the SQUEEZE procedure [Spek (2015 ▸). Acta Cryst. C71, 9-16] in PLATON [Spek (2009 ▸). Acta Cryst. D65, 148-155].

Ultrafast Solvation Dynamics Reveal that Octa Acid Capsule's Interior Dryness Depends on the Guest.

Coumarins are well-known to exhibit environment-dependent excited-state behavior. We have exploited this feature to probe the accessibility of solvent water molecules to coumarins (guest) encapsulated within an organic capsule (host). Two sets of coumarins, one small that fits well within the capsule and the other larger that fits within an enlarged capsule, are used as guests. In our study, the two sets of coumarins serve different purposes: one is employed to explore electron transfer across the capsule and the other to release photoprotected acids into the aqueous environment. The capsule is made up of two molecules of octa acid (OA) and is soluble in an aqueous medium under slightly basic conditions. Molecular modeling studies revealed that while the OA capsule is fully closed with no access to water in the case of smaller coumarins, with the larger molecules, the capsule is not tight and the guest is in contact with water molecules, the number being dependent on the size of the coumarin. We have used the ultrafast time-dependent Stokes shift method to understand the solvent dynamics around the above guest molecules encapsulated within an OA capsule in an aqueous medium. Results depict that for the smaller sets of coumarins, water cannot access the guests within the OA cavity during their excited state lifetime. However, the case is completely different for the larger coumaryl esters. Distorted capsule structure exposes the guest to water, and a dynamics Stokes shift is observed. The average solvation time decreases with the increasing size of guests that clearly indicates accessibility of the encapsulated guests toward greater number of water molecules as the capsule structure distorts with increasing size of the guests. Results of the ultrafast solvation dynamics are consistent with that of molecular dynamics simulation.

Effect of a Competitive Solvent on Binding Enthalpy and Chain Intermixing in Hydrogen-Bonded Layer-by-Layer Films

This work is focused on the effect of a small-molecule/hydrogen-bonding competitor on the heat of complexation of hydrogen-bonding polymers in aqueous solutions, as well as on deposition of these molecules within layer-by-layer (LbL) films. Specifically, binding between poly(methacrylic acid) (PMAA) and poly(vinylpyrrolidone) (PVP) under acidic conditions in the presence of dimethyl sulfoxide (DMSO) has been explored. Isothermal titration calorimetry showed that with increasing concentration of DMSO in aqueous solution, the positive enthalpy of formation of PMAA/PVP complexes decreased and switched sign at ∼25 vol % DMSO. This change is interpreted as a transition from endothermal association between PMAA and PVP in water, driven by release of solvation water molecules, to exothermic association driven by the enthalpy of interpolymer hydrogen bonding. This switch is interpreted as destruction of polymer hydration shells by DMSO molecules. The content of DMSO also strongly impacted the growth of LbL films. With an increase in DMSO concentration from 0 to 60 vol %, polymer mass deposited within the bilayer increased, while larger DMSO concentrations suppressed film deposition. The effect of DMSO was also revealed in neutron reflectometry measurements, which showed enhanced interpenetration of deuterated PMAA chains within a hydrogenated LbL matrix at increasing concentration of DMSO. The dependence of film intermixing on DMSO content was strongly history dependent. While assembly of LbL films in aqueous solutions followed by exposure to a mixed solvent post-assembly did not significantly influence the internal film structure, the effect of DMSO on film intermixing was strongest when DMSO was present in the film deposition solutions.

Fully Polarizable QM/Fluctuating Charge Approach to Two-Photon Absorption of Aqueous Solutions.

We present the extension of the quantum/classical polarizable fluctuating charge model to the calculation of single residues of quadratic response functions, as required for the computational modeling of two-photon absorption cross sections. By virtue of a variational formulation of the quantum/classical polarizable coupling, we are able to exploit an atomic orbital-based quasienergy formalism to derive the additional coupling terms in the response equations. Our formalism can be extended to the calculation of arbitrary order response functions and their residues. The approach has been applied to the challenging problem of one- and two-photon spectra of rhodamine 6G (R6G) in aqueous solution. Solvent effects on one- and two-photon spectra of R6G in aqueous solution have been analyzed by considering three different approaches, from a continuum (QM/PCM) to two QM/MM models (nonpolarizable QM/TIP3P and polarizable QM/FQ). Both QM/TIP3P and QM/FQ simulated OPA and TPA spectra show that the inclusion of discrete water solvent molecules is essential to increase the agreement between theory and experiment. QM/FQ has been shown to give the best agreement with experiments.

Isotopic Fractionation of Potassium by Diffusion in Methanol.

We present the results of experiments involving the isotopic fractionation by diffusion of K+ cations in methanol at 298 K along with supporting molecular dynamic simulations. The experiments, using glass Rayleigh fractionators filled with a methanol solution of KCl, constrain the ratio of the individual diffusivities of 41K and 39K (D41K/D39K) in methanol, and so the isotopic fractionation of K+ due to diffusion in methanol, to 0.9995 ± 0.0001. This isotopic fractionation is 25% of the fractionation resulting from K+ diffusion in water. This is consistent with published molecular dynamics simulations indicating greater hydrodynamic coupling between K+ ions and solvating methanol molecules compared to K+ ions and solvating water molecules.

Crystal structure of tetra-kis-[μ-3-carboxy-1-(1,2,4-triazol-4-yl)adamantane-κ2 N 1:N 2]tetra-fluoridodi-μ2-oxido-dioxidodisilver(I)divanadium(V) tetra-hydrate.

The crystal structure of the title mol-ecular complex, [Ag2{VO2F2}2(C13H17N3O2)4]·4H2O, supported by the heterofunctional ligand tr-ad-COOH [1-(1,2,4-triazol-4-yl)-3-carb-oxy-adamantane] is reported. Four 1,2,4-triazole groups of the ligand link two AgI atoms, as well as AgI and VV centres, forming the heterobimetallic coordination cluster {AgI 2(VVO2F2)2(tr)4}. VV exists as a vanadium oxofluoride anion and possesses a distorted trigonal-bipyramidal coordination environment [VO2F2N]. A carb-oxy-lic acid functional group of the ligand stays in a neutral form and is involved in hydrogen bonding with solvent water mol-ecules and VO2F2 - ions of adjacent mol-ecules. The extended hydrogen-bonding network is responsible for the crystal packing in the structure.

Complexation of Lanthanides with N, N, N', N'-Tetramethylamide Derivatives of Bipyridinedicarboxylic Acid and Phenanthrolinedicarboxylic Acid: Thermodynamics and Coordination Modes.

The thermodynamics of Nd(III) and Eu(III) complexes with N, N, N', N'-tetramethyl-2,2'-bipyridine-6,6'-dicarboxamide (TMBiPDA) and N, N, N', N'-tetramethyl-1,10-phenanthroline-2,9-dicarboxamide (TMPhenDA) in CH3OH/10%(v)H2O solutions were studied. Stability constants and enthalpies of complexation were determined by absorption spectrophotometry, luminescence, and calorimetry. The stability constants of corresponding lanthanide complexes decrease in the order of TMPhenDA > TMBiPDA, while those of the corresponding ligand complexes with lanthanides decrease in the order of Nd(III) > Eu(III). The stepwise reactions for all 1:1 complexes as well as for the 1:2 Nd(III) complexes are driven by both enthalpy and entropy, while those for the 1:2 Eu(III) complexes are driven by entropy. The stronger affinity of TMPhenDA to Nd(III) and Eu(III) than that of TMBiPDA is predominantly arisen from its high preorganization. The spectra of the complexes in solutions are similar, implying that Nd(III) and Eu(III) coordinate with the two ligands in the same mode, which have been validated by 1H and 13C NMR titrations using La(III) as lanthanide tracer. The luminescence lifetimes of the Eu(III) complexes with TMBiPDA and TMPhenDA were evaluated by TRLFS. Structures of Nd(III)/TMPhenDA and Eu(III)/TMPhenDA complexes, identified by single-crystal X-ray diffractometry, show that ligand coordinates to metal in a tetradentate mode via two aromatic N-donors and two amide O-donors, and the central cation (Nd(III) or Eu(III)) is 10-coordinated by two whole TMPhenDA and two solvent (water or methanol) molecules. The M-O bond distances are almost identical, while the Nd-N bond distance is shorter than the Eu-O bond.

Synthesis, crystal structure, infrared spectrum, and thermal properties of [Ni(1,10-phenanthroline)3](fumarate)·9H2O complex with hydrogen bonded supramolecular layers involving fumarate anions

Abstract From the aqueous-ethanolic system Ni(OH)2—H2 fum—phen (H2fum = fumaric acid, phen = 1,10-phenanthroline), novel complex [Ni(phen)3](fum)·9H2O (1) was isolated and characterized by chemical analyses and FT-IR spectroscopy. Results of single crystal X-ray structure analysis have shown that the ionic crystal structure of 1 is built of [Ni(phen)3]2+ complex cations, fumarate dianions and nine crystallographically independent water molecules of crystallization. The Ni(II) atom exhibits hexa-coordination by three phen ligands with mean Ni-N bond length of 2.090 Å. Water molecules form hydrophilic supramolecular layers with fumarate dianions via extended network of O—H···O type hydrogen bonds with O···O distances from the range of 2.676(2)—2. 916(2) Å; hydrophobic complex cations are embedded between these layers. Thermal study of 1 has shown that endothermic dehydration in the temperature range of 95—195 °C takes at least two steps of the process. Graphical Abstract Crystal structure of [Ni(phen)3]fum·9H2O (phen = 1,10-phenanthroline; H2 fum = fumaric acid) which is built of supramolecular layers formed by hydrogen bonded water solvate molecules and fum dianions and between the supramolecular layers embedded [Ni(phen)3]2+ complex cations is described here.

Three-Dimensional Reference Interaction Site Model Self-Consistent Field Study on the Coordination Structure and Excitation Spectra of Cu(II)-Water Complexes in Aqueous Solution.

The molecular and solvation structures of the hydrated Cu2+ ions and their excitation spectra were investigated using the Kohn-Sham density functional theory (DFT) and the three-dimensional reference interaction site model (3D-RISM) self-consistent field method. Five stable geometrical structures were found to exist in aqueous solution: the distorted octahedral [Cu(H2O)6]2+ in C i and D2 h symmetries, the square pyramidal and trigonal bipyramidal [Cu(H2O)5]2+, and the square planar [Cu(H2O)4]2+. The distorted octahedral structure in the C i symmetry is preferred in [Cu(H2O)6]2+, and the square pyramidal and trigonal bipyramidal [Cu(H2O)5]2+ show almost the same stability. Among these geometries, the six-coordinate complex [Cu(H2O)6]2+ in the C i symmetry had the lowest Helmholtz energy. [Cu(H2O)6]2+ had a distorted octahedral structure, that is, two long axial bonds and four short equatorial bonds. The spatial and radial distribution function analyses for [Cu(H2O)5]2+ and [Cu(H2O)4]2+ showed that [Cu(H2O)5]2+ and [Cu(H2O)4]2+ had one and two solvent water molecules that constituted a distorted octahedron with ligand water distribution. The coordination numbers (CNs) derived from the distribution functions were 5.2-5.4 for [Cu(H2O)5]2+ and 5.3 for [Cu(H2O)4]2+. These results indicated that the Cu2+ ion in an aqueous solution had 5-6 coordination water molecules in the first hydration shell and some structures with different CNs may interchange in the solution. The excitation energies and electronic configurations of low-lying d-d excited states were calculated using the time-dependent DFT with the electric field generated by 3D-RISM. The orbital energies and electronic configurations were in a similar picture to those of the classical crystal field theory because of the highly symmetrical features of all structures. In [Cu(H2O)6]2+, the degeneracies of orbitals were resolved, whereas in [Cu(H2O)5]2+ and [Cu(H2O)4]2+, weak and strong quasi-degeneracies remained. As a result, only the four-coordinate complex generated third and fourth excited states, whereas in other complexes, there were no obvious characters of degeneracies. The resulting excitation energies were in good agreement with the absorption spectra.

Hydrating the Bispropionate Notch in Malaria Pigment: A New Structural Motif in the Iron(III)(deuteroporphyrin) Dimer.

Treating deuterohemin, chloro(deuteroporphyrinato)iron(III), with a non-coordinating base in DMSO/methanol allows for the isolation of [(deuteroporphyrinato)iron(III)]2 , deuterohematin anhydride (DHA), an analogue of malaria pigment, the natural product of heme detoxification by malaria. The structure of DHA obtained from this solvent system has been solved by X-ray powder diffraction analysis and displays many similarities, yet important structural differences, to malaria pigment. Most notably, a water molecule of solvation occupies a notch created by the propionate side chains and stabilizes a markedly bent propionate ligand coordinated with a long Fe-O bond, and a carboxylate cluster associated with water molecules is generated. Together, these features account for its increased solubility and more open structure, with an increased porphyrin-porphyrin separation. The IR spectroscopic signature associated with this structure also accounts for the strong IR band at 1587 cm-1 seen for many amorphous preparations of synthetic malaria pigment, and it is proposed that stabilizing these structures may be a new objective for antimalarial drugs. The important role of the vinyl substituents in this biochemistry is further demonstrated by the structure of deuterohemin obtained by single-crystal X-ray diffraction analysis.

Dynamics of Cl-(H2O) + CH3I Substitution Reaction: The Influences of Solvent and Nucleophile.

The study of microsolvation provides a deeper understanding of solvent effects on reaction dynamics. Here, the properties of the SN2 reaction of hydrated chloride with methyl iodide are investigated by direct dynamics simulations, and how the solute-solvent interactions and the basicity of nucleophiles can profoundly affect the atomic level dynamics is discussed in detail. The results show that the direct-rebound mechanism dominates the substitution reaction, and the roundabout mechanism, which prevails in the indirect unsolvated counterpart reaction, still accounts for a high proportion of the indirect mechanisms. The involvement of a solvent water molecule does not significantly reduce the cross section and rate constant compared to the unhydrated reaction at high collision energy. By varying solvated Cl- to F-, the dominant mechanisms are totally different and in contrast, the dynamics of water does not show much difference, and the departure of H2O tends to occur prior to the substitution reaction because of the facile breakage of the hydrogen bond at high collision energy.

Syntheses, crystal structures, antibacterial activities of Cu(II) and Ni(II) complexes based on terpyridine polycarboxylic acid ligand

Six metal complexes [Cu(Htpt)]n (1), {[Cu(H1.5tpt)Cl0.5(H2O)0.5]·1/5H2O}n (2), {[Cu(H2tpt)(H2O)]·1/2SO4·2H2O}n (3), [Cu(Htpt)]n (4), {[Ni2(Htpt)2(H2O)2]·CH3CN}n (5), [Ni(H2tpt)2]·3H2O (6) based on a multidentate 4-(2,4,6-tricarboxyphenyl)-2,2′,6,2″-terpyridine ligand (H3tpt) have been prepared by hydrothermal synthesis method and structurally characterized. 1, 2 and 3 show 1-D chain structures, the chains are further linked via π···π interactions or hydrogen bonds to generate 3-D supramolecular structures. 4 displays a 2-D binodal (3,3)-connected fes net with a Schläfli symbol of (4·82)(4·82), which has been reported. 5 also exhibits a 2-D (3,3)-connected hcb topology with Schläfli symbol of (63·63). 6 is a mononuclear structure. The microbiological properties of 1–6 were studied. 1–6 showed pretty good antibacterial activities towards B. subtilis compared to other bacterial strains. 5 exhibits the smallest MIC value of 1 μg/mL which may be related to the presence of easily-leaving solvent water molecules, thereby exposing more active sites easily.

Vibration Spectral Dynamics of Weakly Coordinating Water Molecules near an Anion: FPMD Simulations of an Aqueous Solution of Tetrafluoroborate.

The extent to which the ions affect the nearby water molecules will decide the structure-making or breaking nature of those ions in aqueous solutions. The effects of a weakly coordinating anion on the structure, dynamics, and vibrational properties of water molecules are not so significant as compared to an anion capable of making strong ion-water hydrogen bonds. The present work deals with the first-principles molecular dynamics study of an aqueous solution of such a weakly coordinating anion, tetrafluoroborate (BF4-), using dispersion-corrected DFT-based first-principles molecular dynamics (FPMD) simulations. Various structural, dynamical, and spectral properties, such as radial distribution functions (RDFs), rotational dynamics, vibrational density of states (VDOS), hydrogen bond as well as dangling OH autocorrelation functions, and residence dynamics, were calculated to investigate the effects of the anion on nearby water molecules. The process of spectral diffusion was assessed through a time series wavelet transformation of trajectories obtained from FPMD simulations. The first ion-water solvation shell extends up to 5.5 Å, containing around 20 water molecules. The lifetime of the ion-water hydrogen bond is found to be 1.19 ps, whereas the water-water hydrogen bond lifetime is found to be 1.13 ps. Inside the solvation shell, the persistence time of dangling OH chromophores and the average frequency of OH modes inside the solvation shell are found to be more compared to bulk. Three time scales are found for solvation shell OH modes from the frequency-frequency correlation function. A very short time scale is found for the intact ion-water interaction; the short time scale is for the ion-water hydrogen bond, and the long time scale is for escape dynamics of water molecules from the ion solvation shell. From the mean squared displacement, it is found that solvation water molecules diffuse slower than the bulk. However, solvation shell water molecules show faster relaxation from the analysis of rotational anisotropy. Within the longer time scale of spectral diffusion, this process (which is related to various dynamics of the molecules) is not yet complete, as compared to fast anisotropic decay. This fact is similar to the experimental finding of spectral diffusion and anisotropy time scales in the aqueous solution of borohydride anion. The calculated results are also compared with available experimental data wherever possible.

Molecular Dynamics Simulations of Molecules in Uniform Flow

Flow at the molecular level induces shear-induced unfolding of single proteins and can drive their assembly, the mechanisms of which are not completely understood. To be able to analyze the role of flow on molecules, we present uniform-flow molecular dynamics simulations at atomic level. The pull module of the GRoningen MAchine for Chemical Simulations package was extended to be able to force-group atoms within a defined layer of the simulation box. Application of this external enforcement to explicit water molecules, together with the coupling to a thermostat, led to a uniform terminal velocity of the solvent water molecules. We monitored the density of the whole system to establish the conditions under which the simulated flow is well-behaved. A maximal velocity of 1.3 m/s can be generated if a pull slice of 8 nm is used, and high velocities would require larger pull slices to still maintain a stable density. As expected, the target velocity increases linearly with the total external force applied. Finally, we suggest an appropriate setup to stretch a protein by uniform flow, in which protein extensions depend on the flow conditions. Our implementation provides an efficient computational tool to investigate the effect of the flow at the molecular level.

The comparative study of cocrystal/salt in simultaneously improving solubility and permeability of acetazolamide

With the purpose of improving solubility and permeability of acetazolamide (ACZ), two new solid forms including one salt with piperazine (PPZ), and one cocrystal with theophylline (THP), namely, ACZ-PPZ-H2O (1) and ACZ-THP (2), were synthesized and structurally characterized. The single-crystal X-ray diffraction analysis revealed that the three-dimensional structure of both 1 and 2 are maintained by abundant hydrogen bonding interaction. In molecular salt 1, PPZ2+ cations locate in and link to the cavities formed by ACZ− anions and solvent water molecules, while in cocrystal 2, the hydrogen bonding chains assembled by ACZ molecules weave the hydrogen bonding layer of THP molecules to a three-dimensional supramolecular structure. The powder dissolution and in vitro permeation experiments indicated that both solubility and permeability of ACZ were simultaneously improved after the formation of cocrystal and salt. Comparatively, the cocrystallization could remarkably enhance the permeability of ACZ, while the salt formation is more advantageous in increasing its solubility. The present study provides a new strategy of screening and prediction for simultaneously enhancing solubility and permeability of ACZ, which will be beneficial for the development of drugs with low solubility and poor permeability.

Solvent effect on Al(III) hydrolysis constants from density functional theory

ABSTRACTDensity functional theory was used to compute proton affinity constants (pKa values) for the four step-wise hydrolysis reactions of the aluminum cation (Al3+ through [Al(OH)4]−). The hydrolysis species were modelled as complexes. Solvation effects were evaluated combining two approaches; initially, microsolvation of the Al-species was achieved by varying the number of explicit solvation water molecules surrounding the Al-complexes and reaction partner H2O/H3O+ species. In the second approach, the long-range polar solvent effect (global solvation) was included by using the COSMO continuum solvation model in the DFT calculations. pKa values for the hydrolysis reactions were calculated using a thermodynamic cycle, and were calculated directly from the global solvation data. The computed energies, optimised coordination structures, bond lengths, charge from natural population analyses, ionic potential, and H-bonding for the Al-hydrolysis species varied depending on the solvation approach. Similarly, calculated pKa values varied for each solvation approach. Overall cumulative pKa values calculated directly from the global solvation showed good agreement with experimental data.

The solvation effect on the rattling behaviour of the hydrated excess proton in water.

The solvation effect on the kinetic rattling behaviour of the hydrated excess proton H+(aq) in water is theoretically modeled by using density functional theory (DFT) and the quantum chemical cluster model (CM). To test the solvation effects on the proton morphology and rattling kinetics, different solvation models for the proton are constructed based on the gas phase (GP) Zundel cation, which include the gas phase-polarizable continuum model (GP-PCM), the gas phase-supermolecule model (GP-SM), and the gas phase-supermolecule-polarizable continuum model (GP-SM-PCM). These solvation models consider either one or both of the short- and long-range solute-solvent interactions. Meanwhile, 1 to 6 explicit solvent water molecules (Nm' = 1-6) are added around the GP Zundel cation to test different explicit solvation environments. The calculation results show that the solvation environment has an important influence on the morphology and rattling kinetics of H+(aq). The proton rattling pathways are obtained only under the condition that both symmetrical explicit solvation environments and implicit bulk solvents are present. The zero-point contribution reduces the reaction energy barrier and enables the rattling to occur spontaneously at room temperature. The theoretical modeling results provide new insights into the microscopic kinetic behaviour of proton rattling in water at the molecular level, which are helpful in studying the proton transfer mechanism in aqueous systems.

The folding equilibria of enterobactin enantiomers and their interaction with actinides.

Enterobactin (Ent) is a typical siderophore with strong iron affinity. Its dynamics in its intact form and holo state remains to be studied to understand its role in the in vivo behavior of metal ions and to facilitate its potential application in drug design and environmental remediation. Here, we report molecular dynamics simulations of both Ent enantiomers and their complexes with key actinides (Am3+, Cm3+, Th4+, U4+, Np4+ and Pu4+) to study the folding equilibria of Ent enantiomers and their binding affinity with actinides. For comparison, the ferric cation was also considered. In their neutral state, both enantiomers may exist in their folded and extended states in the aqueous phase with the former more stable owing to the favorable cation-π, π-π, and H-bond interactions. A helicity preference was observed in the folded states of Ent enantiomers, which was solidified when binding with Fe3+ while disrupted when binding with actinides. Upon binding with metal ions, the dynamics of Ent enantiomers exhibited dependence on the metal ions, and appeared to be more flexible in An3+/4+-Ent complexes than in Fe3+-Ent complexes. The conformational analysis and the energy decomposition of M3+/4+-Ent complexes indicated that their distinct conformational variations and dynamic fluxionality are enthalpy driven behaviors and dependent on the nature of the loaded metal ions. The Fe3+-Ent complexes had a more compact conformation, while the relatively loosely bound An3+/4+-Ent complexes allowed solvent water molecules to access the first coordination shell of An3+/4+ and weaken the interaction between An3+/4+ and Ent. This work is expected to enrich our knowledge of the folding equilibria of Ent enantiomers and their An3+/4+-Ent complexes, and contribute to communities that concern the in vivo and in vitro behaviors of Ent enantiomers and actinides.