DFT study of geometrical and vibrational features of a 3′,5′-deoxydisugar-monophosphate (dDSMP) DNA model in the presence of counterions and solvent

The B3LYP/6–31++G* theoretical level was used to study the influence of various hexahydrated monovalent (Li⁺, Na⁺, K⁺) and divalent (Mg²⁺) metal counterions in interaction with the charged PO₂^? group, on the geometrical and vibrational characteristics of the DNA fragments of 3′,5′-dDSMP, represented by four conformers (g⁺g⁺, g⁺t, g^?g^? and g^?t). All complexes were optimized through two solvation models [the explicit model (6H₂O) and the hybrid model (6H₂O/Continuum)]. The results obtained established that, in the hybrid model, counterions (Li⁺, Na⁺, K⁺, Mg²⁺) always remain in the bisector plane of the O1–P–O2 angle. When these counterions are explicitly hydrated, the smallest counterions (Li⁺, Na⁺) deviate from the bisector plane, while the largest counterions (K⁺ and Mg²⁺) always remain in the same plane. On the other hand, the present calculations reveal that the g⁺g⁺ conformer is the most stable in the presence of monovalent counterions, while conformers g⁺t and g^?t are the most stable in the presence of the divalent counterion Mg²⁺. Finally, the hybrid solvation model seems to be in better agreement with the available crystallographic and spectroscopic (Raman) experiments than the explicit model. Indeed, the six conformational torsions of the C4′-C3′-O3′-PO^?₂-O5′-C5′-C4′ segment of all complexes of the g^?g^? conformer in 6H₂O/Continuum remain similar to the available experimental data of A- and B-DNA forms. The calculated wavenumbers of the g⁺g⁺ conformer in the presence of the monovalent counterion and of g^?t conformer in presence of the divalent counterion in the hybrid model are in good agreement with the Raman experimental data of A- and B-DNA forms. In addition, the maximum deviation between the calculated wavenumbers in the 6H₂O/Continuum for the g⁺g⁺ conformer and experimental value measured in an aqueous solution of the DMP-Na⁺ complex, is <1.07% for the PO₂^? (asymmetric and symmetric) stretching modes and <2.03% for the O5′-C5′ and O3′-C3′ stretching modes.

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Graphical abstract dDSMP-(OO)^? Mg²⁺/6W/Continuum

     

An insight into hydration structure of sodium glycinate from <Emphasis Type="Italic">ab initio</Emphasis> quantum chemical study

The hydration structure of sodium glycinate (Na⁺GL^?) is probed by the Monte-Carlo multiple minimum (MCMM) method combined with quantum mechanical (QM) calculations at the MP2/6-311++G(d,p) level. In the gas phase, the energy of [Na⁺GL^?]_β is more than 30 kJ mol^?1 higher than [Na⁺GL^?]_α. With higher degrees of hydration, our results indicate that the most stable conformers of [Na⁺GL^?]?(H₂O)₈ were derived from [Na⁺GL^?]_β instead of [Na⁺GL^?]_α. The stable conformers determined by the conductor-like polarizable continuum model (CPCM) also show that [Na⁺GL^?]_β is more stable than [Na⁺GL^?]_α in the liquid phase. By analyzing the hydration process, water…water hydrogen bonding interaction will be more preferable than ion…water interaction as the number of water molecules increases. According to the electronic density at the bond critical point on the Na-X bonds (X?=?O1, O2, N) in the low-energy conformers, Na⁺GL^? will be dissociated as Na⁺ and GL^? in the bulk water, which is not predicted by the CPCM model. The structure features and the charge redistribution of Na⁺GL^? will provide a physical explanation for the weakening Na-O1 interaction.

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Graphical Abstract Hydration structure of sodium glycinate from ab initio quantum chemical study

     

Structure of aggregates of water and Li+, Na+, or K+ counterions with nucleic acid in solution

The position and orientation of water molecules hydrating fragments of DNA in the B and Z conformations are analyzed with the help of computer simulations. Monte Carlo studies are carried out at room temperature, high relative humidity (500 water molecules per pitch) and in the presence of counterions such as Li⁺, Na⁺, and K⁺. Differences in hydration patterns and in the counterionic structures were found by compairing B-DNA with Z-DNA double helices and B-DNA helices with different base-pair distributions. The present extension of our similations to Z-DNA and to Li⁺ and K⁺ counterions permits some general conclusions concerning nucleic acids in solution.     

Theoretical insights into the properties of amino acid ionic liquids in aqueous solution

This report presents a systematic investigation of the interactions of water molecule(s) with a series of amino acid cations (Gly⁺, Ala⁺, Val⁺, and Leu⁺), halogen anions (Cl^?, Br^?, BF₄ ^?, and PF₆ ^?), and clusters (GlyCl) _n (n?=?1–5). The results reveal that H-bonds between amino acid ionic liquids (AAILs) and water molecules are crucial to the properties of aqueous solution of AAILs. The properties of AAIL in water solution depend on the alkyl chain of the amino acid cation, the size of the halogen anion, and the number of water molecules, which provides a certain theoretical basis for the design and application of new AAILs. A series of calculations for some different models showed that quadruple-GlyCl hydrate represents a basic unit for the Gly–water binary system, and can be employed as the simplest model for studying an AAIL–water cluster. On the basis of this model, the effects of water on the hygroscopicity, speed of solubility, viscosity, density, solution enthalpy, and polarity of the AAIL were also predicted. Most importantly, unlike traditional ILs, the novel GlyCl-type AAIL favors interaction of its cationic part, rather than its anionic part, with surrounding water molecules, thus amino acid cationic ILs expand the types of IL available, increasing the choice of ILs for different purposes. We hope that the application of this AAIL in many fields will lead to optimization of this class of compound and be of benefit to the environment.

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Graphical Abstract Quadruple-GlyCl hydrate represents the basic unit for a GlyCl-water binary system, which can be employed as the simplest model for studying an amino acid ionic liquid (AAIL)-water cluster. The effects of available water on some properties of AAIL are predicted. GlyCl-type AAIL is a novel IL, which prefers its cationic part over its anionic part for interaction with surrounding water molecules. The properties of AAIL in water solution can be adjusted by varying the ion used and the solvent.

     

A structural DFT study of MM,GG, MG,and GM alginic acid disaccharides and reactivity of the MG metallic complexes

The density functional theory method using the B3LYP/6-31G(d,p) level of theory was used to perform isoenergetic maps in order to determine the lower energy conformers of four disaccharides constituting alginic acids, which are based on β-D-mannuronic (M) and α-L-guluronic acid (G), called MM, GG, MG, and GM. The preferred structures are combined to monovalent (Li⁺, Na⁺, and K⁺) cations and further fully optimized, and an isoenergetic map corresponding to the complex (MG^2?, 2Na⁺) was performed. Then, the reactivity of MG complexes with mono- and bivalent cations was studied using the global nucleophilic index. The position selectivity was also predicted using the local nucleophilic indices. It was demonstrated that experimental trends of relative reactivity and regioselectivity of the complexes are correctly predicted using these empirical indices of reactivity.

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Graphical abstract MM, GG, MG, and GM alginic acid disaccharides and reactivity of the MG metallic complexes

     

Buoyant density and solvation of magnesium DNA

The buoyant density of T-4 DNA was determined by equilibrium sedimentation in a density gradient, of mixed solutions of cesium and magnesium chlorides and bromides. The preferential hydration was calculated from these data, allowing appropriately for the exchange equilibrium of DNA with Cs⁺ and Mg⁺⁺ ions. The charge and intrinsic solvation of the counterions were found to have no appreciable effect on the hydration of the DNA, the extent of solvation depending only on the thermodynamic, activity of the water. Various reasonable hypotheses are discussed to account for these results.     

Predicting substituent effects on activation energy changes by static catalytic fields

Catalytic fields illustrate topology of the optimal charge distribution of a molecular environment reducing the activation energy for any process involving barrier crossing, like chemical reaction, bond rotation etc. Until now, this technique has been successfully applied to predict catalytic effects resulting from intermolecular interactions with individual water molecules constituting the first hydration shell, aminoacid mutations in enzymes or Si→Al substitutions in zeolites. In this contribution, hydrogen to fluorine (H→F) substitution effects for two model reactions have been examined indicating qualitative applicability of the catalytic field concept in the case of systems involving intramolecular interactions.

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Graphical abstract Hydrogen to fluorine (H→F) substitution effects on activation energy in [kcal/mol]

     

First report of a planar and a quasi-planar Al<Subscript>13</Subscript><Superscript>+</Superscript> cluster having localized antiaromatic deltas within an aromatic sea: NICS,ELF, AIM,and AdNDP bonding analysis

A perfectly planar Al₁₃⁺ cluster (CI) and a quasi-planar Al₁₃⁺ cluster (CII) have been found for the first time. Both clusters have a triangular core surrounded by a set of ten Al atoms in the form of a ring. These cationic clusters have substantial aromatic character. The planar CI cluster has local antiaromatic patches within global aromatic sea. It is doubly aromatic having both σ and π aromatic character. The quasi-planar CII cluster is also aromatic but it has more σ-delocalization.

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Graphical abstract Planar and quasi-planar Al₁₃⁺ clusters with triangular core surrounded by a ring of ten atoms.

     

Understanding weakly coordinating anions: tetrakis(pentafluorophenyl)borate paired with inorganic and organic cations

Efficient design of ionic compounds requires a systematic understanding of cation–anion interactions. Weakening of electrostatic attraction is essential to increase the liquid range of the ionic compound and decrease its melting point. Here, we report simulations of the closest-approach cation–anion distances in a variety of ion pairs containing the tetrakis(pentafluorophenyl)borate (TFPB^–) anion. Small alkali cations (Li⁺, Na⁺) penetrate the TFPB^– core, whereas K⁺ and larger organic cations do not. In the latter case, the shortest possible distance from the cations to the boron atom of TFPB^– ranges from 0.50 nm to 0.63 nm. TFPB^– was shown to be substantially rigid, providing a steric hindrance to thermodynamically efficient cation–anion coordination. Our results prove that TFPB^– is more efficient for electrostatic charge confinement than the tetraoctylammonium cation, whereas the perfluorophenyl group is more efficient than linear alkyl chains. These simulations will motivate development of TFPB^–-based ionic liquids with low phase transition points.

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Graphical Abstract Ionic configuration of the equilibrated “TFPB + K”system

     

Hexahydrated Mg2+ Binding and Outer-Shell Dehydration on RNA Surface

The interaction between metal ions, especially Mg²⁺ ions, and RNA plays a critical role in RNA folding. Upon binding to RNA, a metal ion that is fully hydrated in bulk solvent can become dehydrated. Here we use molecular dynamics simulation to investigate the dehydration of bound hexahydrated Mg²⁺ ions. We find that a hydrated Mg²⁺ ion in the RNA groove region can involve significant dehydration in the outer hydration shell. The first or innermost hydration shell of the Mg²⁺ ion, however, is retained during the simulation because of the strong ion-water electrostatic attraction. As a result, water-mediated hydrogen bonding remains an important form for Mg²⁺-RNA interaction. Analysis for ions at different binding sites shows that the most pronounced water deficiency relative to the fully hydrated state occurs at a radial distance of around 11 Å from the center of the ion. Based on the independent 200 ns molecular dynamics simulations for three different RNA structures (Protein Data Bank: 1TRA, 2TPK, and 437D), we find that Mg²⁺ ions overwhelmingly dominate over monovalent ions such as Na⁺ and K⁺ in ion-RNA binding. Furthermore, application of the free energy perturbation method leads to a quantitative relationship between the Mg²⁺ dehydration free energy and the local structural environment. We find that $\text{ΔΔ}{G}_{\text{hyd}},$ the change of the Mg²⁺ hydration free energy upon binding to RNA, varies linearly with the inverse distance between the Mg²⁺ ion and the nearby nonbridging oxygen atoms of the phosphate groups, and $\text{ΔΔ}{G}_{\text{hyd}}$ can reach ?2.0 kcal/mol and ?3.0 kcal/mol for an Mg²⁺ ion bound to the surface and to the groove interior, respectively. In addition, the computation results in an analytical formula for the hydration ratio as a function of the average inverse Mg²⁺-O distance. The results here might be useful for further quantitative investigations of ion-RNA interactions in RNA folding.     

Hydration effect on proton transfer in melamine−cyanuric acid complex

Self-assembly of melamine-cyanuric acid (MC) leads to urinary tract calculi and renal failure. The hydration effects on molecular geometry, the IR spectra, the frontier molecular orbital, the energy barrier of proton transfer (PT), as well as the stability of MC were explored by density functional theory (DFT) calculations. The intramolecular PT breaks the big π-conjugated ring of melamine or converts the p-π conjugation (:N-C'=O) to π-π conjugation (O=C-N=C') of cyanuric acid. The intermolecular PT varies the coupling between melamine and cyanuric acid from pure hydrogen bonds (N_a…HN_d and NH…O) to the cooperation of cation…anion electrostatic interaction (N_aH⁺…N_d ^-) and two NH…O hydrogen bonds. Distinct IR spectra shifts occur for N_a…HN_d stretching mode upon PT, i.e., blue-shift upon intramolecular PT and red-shift upon intermolecular PT. It is expected that the PT would inhibit the generation of rosette-like structure or one-dimensional tape conformer for the MC complexes. Hydration obviously effects the local geometric structure around the water binding site, as well as the IR spectra of NH…O and N…HN hydrogen bonds. Hydration decreases the intramolecular PT barrier from ~45 kcal mol^-1 in anhydrous complex to ~11.5 kcal mol^-1 in trihydrated clusters. While, the hydration effects on intermolecular PT barrier is slight. The relative stability of MC varies slightly by hydration due to the strong hydrogen bond interaction between melamine and cyanuric acid fragments.

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Graphical Abstract Hydration effect on proton transfer in melamine?cyanuric acid complex

     

Characterization of a recombinant Akabane mutant virus with knockout of a nonstructural protein NSs in a pregnant goat model

正Dear Editor,Akabane virus(AKAV),an orthobunyavirus,is transmitted primarily by biting midges and is widely distributed throughout the world except the Europe.AKAV was first isolated from mosquitoes in Japan(Oya et al.,1961).Although pregnant cows,ewes,and goats infected with AKAV exhibit no clinical signs of disease,in utero infections result in abortion,premature birth,stillbirth,and     

Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior,electrostatic and energetic analysis

The dynamic behavior of the HCV IRES IIId domain is analyzed by means of a 2.6-ns molecular dynamics simulation, starting from an NMR structure. The simulation is carried out in explicit water with Na⁺ counterions, and particle-mesh Ewald summation is used for the electrostatic interactions. In this work, we analyze selected patterns of the helix that are crucial for IRES activity and that could be considered as targets for the intervention of inhibitors, such as the hexanucleotide terminal loop (more particularly its three consecutive guanines) and the loop-E motif. The simulation has allowed us to analyze the dynamics of the loop substructure and has revealed a behavior among the guanine bases that might explain the different role of the third guanine of the GGG triplet upon molecular recognition. The accessibility of the loop-E motif and the loop major and minor groove is also examined, as well as the effect of Na⁺ or Mg²⁺ counterion within the simulation. The electrostatic analysis reveals several ion pockets, not discussed in the experimental structure. The positions of these ions are useful for locating specific electrostatic recognition sites for potential inhibitor binding. Figure Superposition of 14 structures representative of the evolution of IRES IIId RNA along 2.6-ns MD simulation     

Density functional study of isoguanine tetrad and pentad sandwich complexes with alkali metal ions

Isoguanine tetraplexes and pentaplexes contain two or more stacked polyads with intercalating metal ions. We report here the results of a density functional study of sandwiched isoguanine tetrad and pentad complexes consisting of two polyads with Na⁺, K⁺ and Rb⁺ ions at the B3LYP level. In comparison to single polyad metal ion complexes, there is a trend towards increased non-planarity of the polyads in the sandwich complexes. In general, the pentad sandwiches have relatively planar polyad structures, whereas the tetrad complexes contain highly non-planar polyad building blocks. As in other sandwich complexes and in metal ion complexes with single polyads, the metal ion-base interaction energy plays an essential role. In iG sandwich structures, this interaction energy is slightly larger than in the corresponding guanine sandwich complexes. Because the base–base interaction energy is even more increased in passing from guanine to isoguanine, the isoguanine sandwiches are thus far the only examples where the base–base interaction energy is larger than the base–metal ion interaction energy. Stacking interactions have been studied in smaller models consisting of two bases, retaining the geometry from the complete complex structures. From the data obtained at the B3LYP and BH&;H levels and with Møller-Plesset perturbation theory, one can conclude that the B3LYP method overestimates the repulsion in stacked base dimers. For the complexes studied in this work, this is only of minor importance because the direct inter-tetrad or inter-pentad interaction is supplemented by a strong metal ion-base interaction. Using a microsolvation model, the metal ion preference K⁺≈Rb⁺?>?Na⁺ is found for tetrad complexes. On the other hand, for pentads the ordering is Rb⁺?>?K⁺?>?Na⁺. In the latter case experimental data are available that agree with this prediction.

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Figure Structures of isoguanine pentad complexes with Rb⁺ at different symmetries.

     

Protonation and electronic structure of 2,6-dichlorophenolindophenolate during reduction. A theoretical study including explicit solvent

Protonation in the two-electron/two-proton reduction processes of 2,6-dichlorophenolindophenolate (DCIP) is investigated combining density functional theory (DFT) and molecular dynamics (MD) methods. DCIP (anion), DCIP^?– (radical anion), and DCIP^2? (dianion) are considered, including the electronic structure analysis from the prospective of quantum theory of atoms and molecules (QTAIM). It is shown that oxygen on the indophenolate moiety and nitrogen are the first and/or the second proton acceptor sites and their energetic order depends on the total charge of the system. MD simulations of differently charged species interacting with the solvent molecules have been performed for methanol, water, and oxonium cation (H₃O⁺). Methanol and water molecules are found to form only hydrogen bonds with the solute irrespective of its charge. The calculated pK_a values show that the imino group of DCIPH^? is a weaker acid than water. While in the case of DCIP (and DCIP^?–) plus oxonium cation, proton transfer from the solvent to the solute was evidenced for both aforementioned acceptor sites. In addition, MD simulations of bulks containing 15 and 43 molecules of water around the DCIP molecule have been performed, revealing the formation of 2–4 hydrogen bonds.

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Graphical Abstract 2,6-Dichlorophenolindophenolate interacts with solvent molecules (water, oxonium cation and methanol). Hydrogen transfer and electronic structure are studied by DFT and molecular dynamics methods

     

Gel electrophoresis measurement of counterion condensation on DNA

We used agarose gel electrophoresis to measure the effective charge neutralization of DNA by counterions of different structure and valence, including Na⁺, Mg²⁺, Co(NH₃), and sperinidine³⁺, which competed for binding with an excess of Tris acetate buffer. Linear DNA molecules ranged in size from 1 to 5 kilobases, and supercoiled plasmid pUC18 was also measured. In all cases, the results were in good agreement with theoretical predict ions from counterion condensation theory for two-counterion mixtures. © 1995 John Wiley & Sons, Inc.     

Salinity-dependence of the properties of gill (Na++K+-ATPase in rainbow trout Oncorhynchus mykiss

• 1.1. The expected higher gill (Na⁺+K⁺)-ATPase activity in rainbow trout adapted to brackish water (BW) with respect to fresh water (FW) is accompanied by some changes in the enzyme kinetics while the enzyme sensitivity to ouabain is unaffected
• 2.2. Maximal activation is attained under the optimal conditions of 4 mM ATP, 7.5 mM Mg²⁺, 50 mM Na⁺, 2.5 mM K⁺, pH 7.0 in FW, and 3 mM ATP, 10 mM Mg²⁺, 100 mM Na⁺, 10 mM K⁺, pH 7.5 in BW.
• 3.3. The change of the enzyme activation kinetics by Mg²⁺, ATP, Na⁺ and K⁺ from simple saturation in FW to cooperativity in BW and other habitat-dependent variations including the pH alkaline shift in BW are hypothetically related to an adaptive significance to the different environmental salinity.
• 4.4. Gill total lipids and phospholipids are 30% lower in BW than in FW while their ratio is constant; some differences in gill total lipid fatty acid composition between FW and BW do not significantly affect the unsaturation parameters.

     

A two-layer ONIOM study of thiophene cracking catalyzed by proton- and cation-exchanged FAU zeolite

A two-layer ONIOM study on the hydrodesulfurization mechanism of thiophene in H-FAU and M-FAU (M?=?Li⁺, Na⁺, and K⁺) has been carried out. The calculated results reveal that in H-FAU, for a unimolecular mechanism, the rate-determining step is hydrogenation of alkoxide intermediate. The assistance of H₂O and H₂S molecules does not reduce the difficulty of the C-S bond cracking step more effectively. A bimolecular hydrodesulfurization mechanism is more favorable due to the lower activation barriers. The rate-determining step is the formation of 2-methylthiophene, not the C-S bond cracking of thiophene. Moreover, the ring opening of thiophene is much easier to occur than the desulfurization step. A careful analysis of energetics indicates that H₂S, propene, and methyl thiophene are the major products for the hydrodesulfurization process of thiophene over H-FAU zeolite, in good agreement with experimental findings. In M-FAU zeolites, both unimolecular and bimolecular cracking processes are difficult to occur because of the high energy barriers. Compared to the case on H-FAU, the metal cations on M-FAU increase the difficulty of occurrence of bimolecular polymerization and subsequent C-S bond cracking steps.

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Graphical abstract Hydrodesulfurization process of thiophene can take place in H-FAU zeolite. Two different mechanisms, unimolecular and bimolecular ones, have been proposed and evaluated in detail. The bimolecular mechanism is more favorable due to lower activation barrier as described in the picture above. Our calculated data indicate that H₂S, propene, and methylthiophene are the major products, in good agreement with experimental observations. The effect of metal cations on the reaction mechanism is also investigated in this work.

     

The mechanisms for N-heterocyclic olefin-catalyzed formation of cyclic carbonate from CO<Subscript>2</Subscript> and propargylic alcohols

The mechanistic details of N-heterocyclic olefin-catalyzed formation of cyclic carbonate from CO₂ and propargylic alcohols were investigated by DFT calculations. Six mechanisms, four for the formation of five-membered cyclic carbonate (M-A, M-B, M-B’ and M-C), and two for six-membered cyclic carbonate (M-D and M-E), were fully investigated. The energy profiles in dichloromethane showed that M-B is the predominant reaction with the lowest barrier of 31.99 kcal mol^?1, while M-C and M-D may be kinetically competitive to M-B. The very high activation energy of 45.37 kcal mol^-1, 57.07 kcal mol^-1 and 59.61 kcal mol^?1 for M-A, M-B’ and M-E, respectively, suggest that they are of lesser importance in the overall mechanism.

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Graphical abstract Formations of five-membered ring product and six-membered ring product are kinetically competitive, but five-membered ring product is thermodynamically more preferable.