Abstract Understanding the molecular-level hydration of fructose tautomers remains a challenge due to their rapid interconversion and structural complexity. A dual-scale approach was employed, combining long-time classical molecular dynamics (MD) and ab initio molecular dynamics (AIMD) to elucidate differences in the hydrogen-bonding networks of both pyranose and furanose tautomers with statistical and electronic accuracy. Our simulations highlight the inherent competition between intra- and intermolecular hydrogen bonds, driven by the limited number of hydroxyl donor and acceptor sites. Crucially, the formation of these internal bonds is driven by ring puckering in the flexible furanoses alongside the spatial orientation of the hydroxymethyl groups in both tautomer families. This structural interplay indirectly influences the entire intermolecular solvation shell, comprising both hydrophilic and hydrophobic regions. By correlating these competing intra- and intermolecular patterns with Bader charges and water dipole moments, we establish a quantitative electronic-structure basis for carbohydrate solvation. These insights provide a comprehensive atomistic framework that deepens our understanding of biologically relevant processes, such as recognition and docking efficiency within metabolic enzymes.

Molecular dynamics computer simulations have been conducted on neat liquid methanol, using three different “united atom” (three site) interatomic potentials: TraPPE [Chen et al., J. Phys. Chem. B 105, 3093 (2001)], UAM-I [García-Melgarejo et al., J. Mol. Liq. 323, 114576 (2021)], and OPLS/2016 [D. Gonzalez-Salgado and C. Vega, J. Chem. Phys. 145, 034508 (2016)]. The effects of pressure, between 1 bar and 6 kbar, have been evaluated on total scattering structure factors, partial radial distribution functions, and on collective characteristics such as ring-size distributions and cluster-size distributions. Agreement with experimental density is nearly quantitative for all three force fields, and major trends observed for recent pressure-dependent neutron diffraction data are reproduced qualitatively. In general, the OPLS/2016 force field generates properties that are markedly different from results originating from the other potentials. Pressure effects are hardly noticeable on most partial radial distribution functions and on the distribution of the number of hydrogen-bonded neighbors. On the other hand, collective structural properties, such as cluster- and ring-size distributions, exhibit significant changes with increasing pressure: larger clusters become more numerous, whereas the number of cyclic clusters, i.e., rings, decreases. The self-diffusion coefficient decreases with increasing pressure, and the same is valid for the average lifetime of hydrogen bonds.

Various theoretical methods were applied and evaluated to determine the dipole moment of polar protic (methanol, ethanol) and aprotic (acetonitrile, pyridine, acetone) dipoles in the crystal phase. In mono-alcohols, the dipole moment is influenced by the hydrogen bonding (H-bonding) environment, similarly to earlier findings with liquid water. Using localization techniques without considering the effect of neighboring molecules gives similar results for the dipole moment of mono-alcohols than those obtained from the polarized continuum model (PCM). However, the PCM for polar aprotic molecules provides significantly different dipole moment values compared to localization methods. Our results clearly show that the magnitude of the dipole moment in the condensed phase cannot be unambiguously determined.

The structural rigidity of cyclodextrin (CD) molecules, which plays a leading role in their ability to form inclusion complexes, is largely due to the hydrogen bonds (HBs) formed within the CD molecule. To describe these intramolecular HB properties we performed Molecular Dynamics (MD) simulations for α-, β-, and γ-CD molecules in an aqueous environment. We scrutinized the role of tumbling phenomenon, that is, the glucopyranose (Glcp) units may rotate around the glycosidic bonds, in formation of intramolecular HBs. As a first step the tumbling of Glcp units were characterized and different water model were applied to monitor their effects on the ratio of rotated cases. The results show that this ratio can highly depend on the applied water model. Small Angle X-ray diffraction experiments were performed. A comparison of the molecular shape factors obtained from MD simulations and SAXS experiments reveals a low probability of tumbling of Glcp units. This result corresponds with the calculated average probability of rotated Glcp unit from MD simulation for α-CD and β-CD. However, it significantly deviates in the case of γ-CD.

Molecular magnetic units capable of Coordination-Induced Spin-State Switching (CISSS) are embedded within a soft porous crystal (SPC) framework, enabling cooperative and bistable spin-state memory at room temperature. The transformation between the open-pore high-spin state [Ni2(hbih)(py)6]pyH2O (CN6) and the closed-pore low-spin state [Ni2(hbih)(py)2] (CN4) leads to pronounced magnetic hysteresis. Crucially, Hill analysis yields a coefficient of n approximate to 12, quantitatively evidencing strong cooperativity in guest-induced switching and indicating a large kinetic barrier (10 726 cm-1 and 13 610 cm-1 for association and dissociation, respectively). Such high cooperativity and the associated energy barriers enable photo-thermal manipulation for reversible, inkless, and non-contact information printing, affording a storage half-life of 289 days. This study highlights a bottom-up strategy to realize framework-level cooperative bistability in molecular magnetic materials through the synergy of CISSS chemistry and SPC architectures.

In this work, comprehensive ab initio quantum chemical calculations using the DFT level of theory were performed to characterize the stabilization interactions (H-bonding and hyperconjugation effects) of two stable symmetrical conformations of α-, β-, and γ-cyclodextrins (CDs). For this purpose, we analyzed the electron density using “Atom in molecules” (AIM), “Natural Bond Orbital” (NBO), and energy decomposition method (CECA) in 3D and in Hilbert space. We also calculated the H-bond lengths and OH vibrational frequencies. In every investigated CD, the quantum chemical descriptors characterizing the strength of the interactions between the H-bonds of the primary OH (or hydroxymethyl) and secondary OH groups are examined by comparing the same quantity calculated for ethylene glycol, α-d-glucose (α-d-Glcp) and a water cluster as reference systems. By using these external standards, we can characterize more quantitatively the properties of these bonds (e.g., strength). We have demonstrated that bond critical points (BCP) of intra-unit H-bonds are absent in cyclodextrins, similar to α-d-Glcp and ethylene glycol. In contrast, the CECA analysis showed the existence of an exchange (bond-like) interaction between the interacting O…H atoms. Consequently, the exchange interaction refers to a chemical bond, namely the H-bond between two atoms, unlike BCP, which is not suitable for its detection.

Ab initio molecular dynamics (AIMD) simulations have been performed on aqueous solutions of four simple sugars, alpha-D-glucose, beta-D-glucose, alpha-D-mannose, and alpha-D-galactose. Hydrogen-bonding (HB) properties, such as the number of donor- and acceptor-type HB-s, and the lengths and strengths of hydrogen bonds between sugar and water molecules, have been determined. Related electronic properties, such as the dipole moments of water molecules and partial charges of the sugar O atoms, have also been calculated. The hydrophilic and hydrophobic shells were characterized by means of spatial distribution functions. beta-D-Glucose was found to form the highest number of hydrophilic and the smallest number of hydrophobic connections to neighboring water molecules. The average sugar-water H-bond length was the shortest for beta-D-glucose, which suggests that these are the strongest such H-bonds. Furthermore, beta-D-glucose appears to stand out in terms of the symmetry properties of both its hydrophilic and hydrophobic hydration shells. In summary, in all aspects considered here, there seems to be a correlation between the distinct characteristics of beta-D-glucose reported here and its outstanding solubility in water. Admittedly, our findings represent only some of the important factors that influence the solubility.

Non-toxic, chemically inert, organic polymers as polyethylene glycol (PEG) and polyoxymethylene (POM) have versatile applications in basic research, industry and pharmacy. In this work, we aim to characterize the hy-dration structure of PEG and POM oligomers by exploring how the solute disturbs the water structure compared to the bulk solvent and how the solute chain interacts with the solvent. We explore the effect of (i) the C-C-O (PEG) versus C-O (POM) constitution of the chain and (ii) chain length. To this end, MD simulations followed by clustering and topological analysis of the hydration network, as well as quantum mechanical calculations of atomic charges are used.We show that the hydration varies with chain conformation and length. The degree of folding of the chain impacts its degree of solvation, which is measurable by different parameters as for example the number of water molecules in the first solvation shell and the solvent accessible surface. Atomic charges calculated on the olig-omers in gas phase are stable throughout conformation and chain length and seem not to determine solvation. Hydration however induces charge transfer from the solute molecule to the solvent, which depends on the degree of hydration.

Ab initio molecular dynamics (AIMD) simulations have been performed on aqueous solutions of four simple sugars, α-D-glucose, e̱ṯa̱-D-glucose, α-D-mannose and α-D-galactose. Hydrogen bonding (HB) properties, such as the number of donor and acceptor type HB-s, and the lengths and strengths of hydrogen bonds between sugar and water molecules, have been determined. Related electronic properties, such as the dipole moments of water molecules and partial charges of the sugar O-atoms, have also been calculated. The hydrophilic and hydrophobic shells were characterized by means of spatial distribution functions. e̱ṯa̱-D-glucose has been found to form the highest number of hydrophilic and the smallest number of hydrophobic connections to neighboring water molecules. The average sugar-water H-bond length was the shortest for e̱ṯa̱-D-glucose, which suggests that these are the strongest such H-bonds. Furthermore, e̱ṯa̱-D-glucose appears to stand out in terms of symmetry properties of both its hydrophilic and hydrophobic hydration shells. In summary, in all aspects considered here, there seems to be a correlation between the distinct characteristics of e̱ṯa̱-D-glucose and its outstanding solubility in water.

A self-consistent scheme is presented that is applicable for revealing details of the microscopic structure of hydrogen-bonded liquids, including the description of the hydrogen-bonded network. The scheme starts with diffraction measurements, followed by molecular dynamics simulations. Computational results are compared with the experimentally accessible information on the structure, which is most frequently the total scattering structure factor. In the case of an at least semiquantitative agreement between experiment and simulation, sets of particle coordinates from the latter may be exploited for revealing nonmeasurable structural details. Calculations of some properties concerning the hydrogen-bonded network are also described, in the order of increasing complexity: starting with the definition of a hydrogen bond, first and second neighborhoods are described via spatial correlations functions. Attention is then turned to cyclic and noncyclic hydrogen-bonded clusters, before cluster size distributions and percolation are discussed. We would like to point out that, as a result of applying the novel protocol, these latter, rather abstract, quantities become consistent with diffraction data: it may thus be argued that the approach reviewed here is the first one that establishes a direct link between measurements and elements of network theories. Applications for liquid water, simple alcohols, and alcohol-water liquid mixtures demonstrate the usefulness of the aforementioned characteristics. The procedure can readily be applied to more complicated hydrogen-bonded networks, like mixtures of polyols (diols, triols, sugars, etc.) and water, and complex aqueous solutions of even larger molecules (even of proteins).

Solvation is essential for the proper structure and functioning of biomolecules. It has a major role in establishing the B-form as the dominant structure of DNA and strongly affects its biological functions. In our genome, two modes of base pairing (Watson-Crick (WC) and Hoogsteen (HG)) exist in equilibrium and are related to the functional properties of the DNA including ligand recognition and gene regulation. Here, we use molecular dynamics simulation along with topological analysis of the H-bond network to investigate the hydration patterns of DNA structure with WC and HG base pairings. We showed that DNA most significantly disturbs the H-bonding properties of the first hydration shell and slightly the second shell compared to bulk water and that the water network is considerably different in the minor and major grooves. We found that HG base pairing leads to increased solvation of the major groove and a less ordered water structure in the minor groove accompanied with increasing hydrophobicity of the minor groove which could also contribute to the site recognition of specific DNA binding proteins. Our newly developed method to selectively study the solvation of the minor and major grooves opens the door to study in finer details the binding between various form of DNA and different ligands such drugs, RNA and proteins.

It is shown that the dipole moment of polar (water, methanol, formamide, acetone and acetonitrile) molecules in the neighborhood of a cation is increased primarily by polarization from the bare electrostatic charge of the cation, although the effective value of the latter is somewhat reduced by "back donation" of electrons from neighbouring polar molecules. In other words, the classical picture may be viewed as if a point charge slightly smaller than the nominal charge of the cation would be placed at the cation site. It was found that the geometrical arrangement of the polar molecules in the first solvation shell is such that their mutual polarization reduces the dipole moments of individual molecules, so that in some cases they become smaller than the dipole moment of the free protic or aprotic molecule. We conjecture that this behavior is essentially a manifestation of the Le Chatellier-Braun principle.

Molecular dynamics simulations of pure ambient liquid water were performed. Hydrogen bond network properties were determined by calculation of eigenvectors and eigenvalues of the Laplace matrix. We investigated how these quantities depend on the system size, the coordination number and periodic boundary conditions taking into account different hydrogen bond definitions. It was found that the first peak of the Laplace spectra contains six eigenvalues. These results suggest that six communities are always formed in our simulated systems independently of the number of molecules in the cubic box. By the help of the spectral clustering method, which is an acceptable indicator of the global properties of H-bonded network, two different H-bonded environments were identified. The tetrahedrality of the water molecules is significantly larger at the surface than inside the clusters. This difference can be related to the coexistence of HDL and LDL domains in liquid water. Furthermore, our work also emphasizes that the periodic boundary conditions always cause clustering in the system.

New X-ray and neutron diffraction experiments have been performed on ethanol-water mixtures as a function of decreasing temperature, so that such diffraction data are now available over the entire composition range. Extensive molecular dynamics simulations show that the all-atom interatomic potentials applied are adequate for gaining insight of the hydrogen bonded network structure, as well as of its changes on cooling. Various tools have been exploited for revealing details concerning hydrogen bonding, like determining H-bond acceptor and donor sites, calculating cluster size distributions and cluster topologies, as well as computing the Laplace spectra and fractal dimensions of the networks. It is found that 5-membered hydrogen bonded cycles are dominant up to an ethanol content of 70% at room temperature, above which concentration ring structures nearly disappear. Percolation has been given special attention, so that it could be shown that at low temperature, close to the freezing point even the mixture with 90% ethanol possesses a 3D percolating network. Moreover, the water sub-network also percolates even at room temperature, with a percolation transition occurring around 50% ethanol.

Synchrotron X-ray diffraction measurements have been conducted on aqueous mixtures of propan-2-ol (a.k.a. isopropanol, or 2-propanol), for alcohol contents between 10 and 90 mol%, from room temperature down to 230 K. Molecular dynamics simulations, by using an all-atom parametrization of the propan-2-ol molecule and the well-known TIP4P/2005 water model, were able to provide semi-quantitative descriptions of the measured total structure factors. Various quantities related to hydrogen bonding, like hydrogen bond numbers, size distribution of cyclic entities and cluster size distributions, have been determined from the particle co-ordinates obtained from the simulations. The percolation threshold at room temperature could be estimated to be between isopropanol concentrations of 62 and 74 mol%, whereas at very low temperature, calculations yielded a value above 90 mol%. (C) 2021 The Authors. Published by Elsevier B.V.

The quantum harmonic model and the two-phase thermodynamics method (2PT) are widely used to obtain quantum corrected properties such as isobaric heat capacities or molar entropies. 2PT heat capacities were calculated inconsistently in the literature. For water the classical heat capacity was also considered, but for organic liquids it was omitted. We reanalyzed the performance of different quantum corrections on the heat capacities of common organic solvents against experimental data. We have pointed out serious flaws in previous 2PT studies. The vibrational density of states was calculated incorrectly causing 39 % relative error in diffusion coefficients and 45 % error in the 2PT heat capacities. The wrong conversion of isobaric isochoric heat capacity also caused about 40 % error but in the other direction. We have introduced the concept of anharmonic correction (AC) which is simply the deviation of the classical heat capacity from that of the harmonic oscillator model. This anharmonic contribution is around +30-40 J/mol/K for water depending on the water model and -8-10 J/mol/K for hydrocarbons and halocarbons. AC is unrealistically large, +40 J/K/mol for alcohols and amines indicating some deficiency of the OPLS force field. The accuracy of the computations was also assessed with the determination of the self-diffusion coefficients.

Corrections for nuclear quantum effects (NQE) have been calculated for classical molecular dynamics (MD) simulation models of light (H2O), heavy (D2O) and ‘null’ [(H2O)0.64(D2O)0.36] water. New path integral molecular dynamics (PIMD) simulations have also been conducted for the same systems. NQEs have somewhat smaller influence on the O-D and D-D partial radial distribution functions of heavy water than on the O-H and H-H ones of light water. After correcting for NQEs the O-‘H’ bondlengths in light and heavy water have become different: the O-D ones are about 0.5% shorter than the O-H ones. Following NQE corrections, the total RDF of ‘null’ water does show hydrogen related features at the position of the intramolecular O-‘H’ peak. Based on a cross-check procedure involving the NQE-corrected total and partial radial distribution functions, it can be stated that concerning the structure of liquid water, the assumption that H and D are equal is valid to a very good approximation for intermolecular correlations. These findings are also supported by our path integral molecular dynamics simulations.

Hydrogen bonding to chloride ions has been frequently discussed over the past 5 decades. Still, the possible role of such secondary intermolecular bonding interactions in hydrogen bonded networks has not been investigated in any detail. Here we consider computer models of concentrated aqueous LiCl solutions and compute the usual hydrogen bond network characteristics, such as distributions of cluster sizes and of cyclic entities, both for models that take and do not take chloride ions into account. During the analysis of hydrogen bonded rings, a significant amount of 'solvent separated anion pairs' have been detected at high LiCl concentrations. It is demonstrated that taking halide anions into account as organic constituents of the hydrogen bonded network does make the interpretation of structural details significantly more meaningful than when considering water molecules only. Finally, we compare simulated structures generated by 'good' and 'bad' potential sets on the basis of the tools developed here, and show that this novel concept is, indeed, also helpful for distinguishing between reasonable and meaningless structural models.