Tautomerism in 7-hydroxyquinoline: a combined experimental and theoretical study in water

Tautomerism in the ground and excited states of 7-hydroxyquinoline (7HQ) was studied in different solvents using steady-state and lifetime spectroscopic measurements, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Equilibrium between the enol and the keto/zwitterion tautomers exists in 7HQ, which is solvent-dependent. Of the solvents used in this study, only in water does the absorbance spectrum of 7HQ show absorption from both the enol and zwitterion tautomers. In addition, in aqueous media, fluorescence is observed from the zwitterion tautomer only, which is attributed to self-quenching of the enol fluorescence by energy transfer to the ground-state zwitterion tautomer and energetically favorable excited-state proton transfer. Solvation of the hydrogen bonding sites of 7HQ was studied in binary mixtures of 1,4-dioxane and water, and three water molecules were estimated to connect the polar sites and induce intermolecular proton transfer. The results are confirmed by DFT calculations showing that three water molecules are the minimum number required to form a stable solvent wire. Mapping the water density around the polar sites using MD simulations shows well-defined hydrogen bonds around the amino and hydroxyl groups of the enol tautomer and slightly less well-defined hydrogen bonds for the zwitterion tautomer. The presence of three-member water wires connecting the polar centers in 7HQ is evident in the MD simulations. The results point to the unique spectral signatures of 7HQ in water, which make this molecule a potential probe to detect the presence of water in nanocavities of macromolecules.     

Dynamics of protein and peptide hydration

Biological processes often involve the surfaces of proteins, where the structural and dynamic properties of the aqueous solvent are modified. Information about the dynamics of protein hydration can be obtained by measuring the magnetic relaxation dispersion (MRD) of the water (2)H and (17)O nuclei or by recording the nuclear Overhauser effect (NOE) between water and protein protons. Here, we use the MRD method to study the hydration of the cyclic peptide oxytocin and the globular protein BPTI in deeply supercooled solutions. The results provide a detailed characterization of water dynamics in the hydration layer at the surface of these biomolecules. More than 95% of the water molecules in contact with the biomolecular surface are found to be no more than two-fold motionally retarded as compared to bulk water. In contrast to small nonpolar molecules, the retardation factor for BPTI showed little or no temperature dependence, suggesting that the exposed nonpolar residues do not induce clathrate-like hydrophobic hydration structures. New NOE data for oxytocin and published NOE data for BPTI were analyzed, and a mutually consistent interpretation of MRD and NOE results was achieved with the aid of a new theory of intermolecular dipolar relaxation that accounts explicitly for the dynamic perturbation at the biomolecular surface. The analysis indicates that water-protein NOEs are dominated by long-range dipolar couplings to bulk water, unless the monitored protein proton is near a partly or fully buried hydration site where the water molecule has a long residence time.     

Hydration-induced changes of structure and vibrational frequencies of methylphosphocholine studied as a model of biomembrane lipids

The chemical characteristics of the polar parts of phospholipids as the main components of biological membranes were investigated by using infrared (IR) spectroscopy and theoretical calculations with water as a probe molecule. The logical key molecule used in this study is methylphosphocholine (MePC) as it is not only a representative model for a polar lipid headgroup but itself has biological significance. Isolated MePC forms a compact (folded) structure which is essentially stabilized by two intramolecular C-H...O type hydrogen bonds. At lower hydration, considerable wavenumber shifts were revealed by IR spectroscopy: the frequencies of the (O-P-O)- stretches were strongly redshifted, whereas methyl and methylene C-H and O-P-O stretches shifted surprisingly to blue. The origin of both red- and blueshifts was rationalized, on the basis of molecular-dynamics and quantum-chemistry calculations. In more detail, the hydration-induced blueshifts of C-H stretches could be shown to arise from several origins: disruption of the intramolecular C-H...O hydrogen bonds, formation of intermolecular C-H...O(water) H-bonds. The stepwise disruption of the intramolecular hydrogen bonds appeared to be the main feature that causes partial unfolding of the compact structure. However, the transition from a folded to extended MePC structure was completed only at high hydration. One might hypothesize that the mechanism of hydration-driven conformational changes as described here for MePC could be transferred to other zwitterions with relevant internal C-H...O hydrogen bonds.     

Solvent dependent excited state spectral properties of 4-hydroxyacridine: Evidence for only water mediated excited state proton transfer process

The possibility of ground and excited state proton transfer reaction across the five member intramolecular hydrogen bonded ring in 4-hydroxyacridine (4-HA) has been investigated spectroscopically and the experimental results have been correlated with quantum chemical calculations. The difference in the emissive behaviour of 4-HA in different types of solvents is due to the presence of different species in the excited state. In non-polar solvents, the species present is non-fluorescing in nature, whereas 4-HA molecule shows normal emission from intramolecularly hydrogen bonded closed conformer in polar aprotic solvents. In polar protic solvents like MeOH, EtOH, etc. (except water), a single broad emission band is attributed to the hydrogen bonded solvated form of 4-HA. However, in case of water, fluorescence from the tautomeric form of 4-HA is observed apart from emission from the solvated form. Emission from the tautomeric form may arise due to double proton transfer via a single water molecule bonded to 4-HA. Evaluation of the potential energy surfaces by quantum chemical calculations using density functional theory (DFT) and time dependent density functional theory (TDDFT), however, points towards the possibility of proton transfer—both intrinsic intramolecular as well as water mediated in the first excited state of 4-HA.     

Water inside a hydrophobic cavitand molecule

The structure and dynamics of water inside a water-soluble, bowl-shaped cavitand molecule with a hydrophobic interior are studied using molecular dynamics computer simulations. The simulations find that the number of inside water molecules is about 4.5, but it fluctuates from being completely empty to full on a time scale of tens of nanoseconds. The transition from empty to full is energetically favorable and entropically unfavorable. The water molecules inside have fewer hydrogen bonds than the bulk and in general weaker interactions; the lower energy results from the nearest-neighbor interactions with the cavitand atoms and the water molecules at the entrance of the cavitand, interactions that are lost upon dewetting. An analysis of translational and rotational motion suggests that the lower entropy of the inside water molecules is due to decreased translational entropy, which outweighs an increased orientational entropy. The cavitand molecule acts as a host binding hydrophobic guests, and dewetting can be induced by the presence of a hydrophobic guest molecule about 3 A above the entrance. At this position, the guest displaces the water molecules which stabilize the inside water molecules and the empty cavitand becomes more stable than the full.     

Different Catalytic Effects of a Single Water Molecule: The Gas‐Phase Reaction of Formic Acid with Hydroxyl Radical in Water Vapor

The effect of a single water molecule on the reaction mechanism of the gas‐phase reaction between formic acid and the hydroxyl radical was investigated with high‐level quantum mechanical calculations using DFT–B3LYP, MP2 and CCSD(T) theoretical approaches in concert with the 6‐311+G(2df,2p) and aug‐cc‐pVTZ basis sets. The reaction between HCOOH and HO has a very complex mechanism involving a proton‐coupled electron transfer process (pcet), two hydrogen‐atom transfer reactions (hat) and a double proton transfer process (dpt). The hydroxyl radical predominantly abstracts the acidic hydrogen of formic acid through a pcet mechanism. A single water molecule affects each one of these reaction mechanisms in different ways, depending on the way the water interacts. Very interesting is also the fact that our calculations predict that the participation of a single water molecule results in the abstraction of the formyl hydrogen of formic acid through a hydrogen atom transfer process (hat).     

Study of molecular behavior in a water nanocluster: size and temperature effect

Temperature and size effects on the behavior of nanoscale water molecule clusters are investigated by molecular dynamics simulations. The flexible three-centered (F3C) water potential is used to model the inter- and intramolecular interactions of the water molecule. The differences between the structural properties for the surface region and those for the interior region of the cluster are also investigated. It is found that as the temperature rises, the average number of hydrogen bonds per water molecule decreases, but the ratio of surface water molecules increases. After comparing the water densities in interior regions and the average number of hydrogen bonds in those regions, we find there is no apparent size effect on water molecules in the interior region, whereas the size of the water cluster has a significant influence on the behavior of water molecules at the surface region.     

Solution structure of the aqueous model peptide N-methylacetamide

Classical molecular dynamics simulations of aqueous N-methylacetamide (NMA) have been performed across a concentration range at 308 K. This peptidic fragment molecule is a useful model for investigating water/peptide hydrogen bond competition. The simulations predict considerable NMA self-association even at low concentrations with a concentration-dependent increase in the ratio of branched to linear clusters. Water-mediated NMA contacts are a feature of this regime, manifested by an unexpected increase in the number of short NMA oxygen contacts arising from water bridge motifs. In contrast, bulk water structure is significantly disrupted by the addition of even small quantities of NMA. With increases in NMA concentration water molecules become progressively more isolated, forming dimers and trimers hydrogen-bonded to NMA. The mixture in this concentration regime may therefore offer a minimal model system for certain structural properties of interior water buried in protein cavities and hydrogen-bonded to mainchain peptide groups.     

Hydrogen bond lifetime dynamics at the interface of a surfactant monolayer

The dynamics of water near the polar headgroups of surfactants in a monolayer adsorbed at the air/water interface is likely to play a decisive role in determining the physical behavior of such organized assemblies. We have carried out an atomistic molecular dynamics (MD) simulation of a monolayer of the anionic surfactant sodium bis(2-ethyl-1-hexyl) sulfosuccinate (aerosol-OT or AOT) adsorbed at the air/water interface. The simulation is performed at room temperature with a surface coverage of that at the critical micelle concentration (78 Angstrom(2)/molecule). Detailed analyses of the lifetime dynamics of surfactant-water (SW) and water-water (WW) hydrogen bonds at the interface have been carried out. The nonexponential hydrogen bond lifetime correlation functions have been analyzed by using the formalism of Luzar and Chandler, which allowed identification of the bound states at the interface and quantification of the dynamic equilibrium between bound and quasi-free water molecules, in terms of time-dependent relaxation rates. It is observed that the water molecules present in the first hydration layer form strong hydrogen bonds with the surfactant headgroups and hence have longer lifetimes. Importantly, it is found that the overall relaxation of the SW hydrogen bonds is faster for those water molecules which form two hydrogen bonds with the surfactant headgroups than those forming one such hydrogen bond. Equally interestingly, it is further noticed that water molecules beyond the first hydration layer form weaker hydrogen bonds than pure bulk water.     

Special features of the hydration of siderophores of the ferrichrome family

An investigation of the hydration of the siderophore ferrichrome A has been carried out by the Monte-Carlo method. It has been shown that the ligands and the iron atom interact weakly with water. The four carbonyl groups of the peptide ring of the molecule, with which hydrogen bonds are formed by six water molecules, and the side-chain carboxyl groups, with each of which a hydrogen bond is formed by one water molecule, interact most strongly with the aqueous phase. Evaluations of the free energy of hydration of the molecule have been carried out. The different activities of the siderophores of the ferrichrome family have been explained on the basis of the calculations. It has been postulated that the bonding of ferrichromes to a membrane receptor is effected by means of the peptide ring of the molecule. The transport of ferrichrome A through the interior of a membrane is energetically considerably more difficult than that of ferrichrome, since it is associated with dehydration of the side-chain carboxyl groups of the molecule.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 24, No. 2, pp. 167–172, March–April, 1988.     

Chiral Encapsulation by Directional Interactions

The complexation of chiral guests in the cavity of dimeric self‐assembled chiral capsule 1 ₂ was studied by using NMR spectroscopy and X‐ray crystallography. Capsule 1 ₂ has walls composed of amino acid backbones forming numerous directional binding sites that are arranged in a chiral manner. The polar character of the interior dictates the encapsulation preferences towards hydrophilic guests and the ability of the capsule to extract guests from water into an organic phase. Chiral discrimination towards hydroxy acids was evaluated by using association constants and competition experiments, and moderate de values were observed (up to 59 %). Complexes with one or two guest molecules in the cavity were formed. For 1:1 complexes, solvent molecules are coencapsulated; this influences guest dynamics and makes the chiral recognition solvent dependent. Reversal of the preferences can be induced by coencapsulation of a nonchiral solvent in the chiral internal environment. For complexes with two guests, filling of the capsule’s internal space can be very effective and packing coefficients of up to 70 % can be reached. The X‐ray crystal structure of complex 1 ₂?((S) ‐6 )₂ with well‐resolved guest molecules reveals a recognition motif that is based on an extensive system of hydrogen bonds. The optimal arrangement of interactions with the alternating positively and negatively charged groups of the capsule’s walls is fulfilled by the guest carboxylic groups acting simultaneously as hydrogen‐bond donors and acceptors. An additional guest molecule interacting externally with the capsule reveals a possible entrance mechanism involving a polar gate. In solution, the structural features and dynamic behavior of the D₄‐symmetric homochiral capsule were analyzed by variable‐temperature NMR spectroscopy and the results were compared with those for the S₈‐symmetric heterochiral capsule.     

Molecular dynamics simulations and quantum chemical calculations on β-cyclodextrin spironolactone complex

Molecular dynamics simulations on β-cyclodextrin in vacuo, with water and complexed with spironolactone (SP) were performed at a temperature of 300 K over a period of 1 ns. Two different orientations of SP in the cavity were considered. Along with conformational parameters, the formation of hydrogen bonds has been monitored during the whole simulation time. Cyclodextrins have the capability to form hydrogen bonds with the surrounding water molecules or intramolecular ones. The incorporation of ligands into the hydrophobic interior of β-cyclodextrin changes the preference of hydrogen bonds significantly and results in a contribution to the decrease of flexibility. Quantum chemical calculations on SP β-CD inclusion complex were performed to determine the interaction energy and to prove the applicability of various methods. Although all applied methods describe reasonable geometries for the association complex, higher level methods (e.g., B3LYP/6-31G(d,p)) seem to be necessary to determine reliable interaction energies.     

The shape of the potential energy curves for NHN(+) hydrogen bonds and the influence of non-linearity

The potential energy curves for proton motion in NHN(+) hydrogen bonds have been calculated to investigate whether different methods of evaluation give different results: for linear H bonds most curves calculated along the NH direction are, as expected, identical with those along NN; for intramolecular H bonds it is very important to take into account the non-linearity and the potential energy curve calculated along the NH direction can be very far from the curve correctly describing the proton transfer. Other factors which influence the proton-transfer process are steric hindrance and presence of anions which modify the proton motion. In the analysis of the proton transfer process it is very important to take changes in the structure of the rest of the molecule into account, which is connected with exchange of energy with the surroundings. Comparison of adiabatic and non-adiabatic curves shows that they are significantly different for very bent hydrogen bonds and for hydrogen bonds with steric constraints for which the proton transfer process must be accompanied with relaxation of the whole molecule. Comparison of the potential-energy curves for compounds with very short H bonds emphasizes that the term 'strong H bond' needs to be qualified. For intermolecular H bonds shortening of the bond is connected with linearization. But for intramolecular H bonds the NN distance cannot be used as the only measure of H bond strength.     

The spectroscopic signature of the "all-surface" to "internally solvated" structural transition in water clusters in the n = 17-21 size regime

The existence of a transitional size regime where preferential stabilization alternates between "all-surface" (all atoms on the surface of a cluster) and "internally solvated" (one water molecule at the center of the cluster, fully solvated) configurations with the addition or the removal of a single water molecule, predicted earlier with the flexible, polarizable (many-body) Thole-type model interaction potential (TTM2-F), has been confirmed from electronic structure calculations for (H2O)n, n = 17-21. The onset of the appearance of the first "interior" configuration in water clusters occurs for n = 17. The observed structural alternation between interior (n = 17, 19, 21) and all-surface (n = 18, 20) global minima in the n = 17-21 cluster regime is accompanied by a corresponding spectroscopic signature, namely, the undulation in the position of the most redshifted OH stretching vibrations according to the trend: interior configurations exhibit more redshifted OH stretching vibrations than all-surface ones. These most redshifted OH stretching vibrations form distinct groups in the intramolecular region of the spectra and correspond to localized vibrations of donor OH stretches that are connected to neighbors via "strong" (water dimer-like) hydrogen bonds and belong to a water molecule with a "free" OH stretch.     

Self-Assemblies of Extended Hydrogen-Bonded Arrays Using 1,4-Butanebisphosphonic Acid as a Versatile Building Block

Two organic salts of 1,4-butanebisphosphonic acid, bis(ethylenediammonium) butanebisphosphonate hydrate ( 1 ) and bis(hexamethylenediammonium) butanebisphosphonate hydrate ( 2 ), have been structurally characterized using single-crystal x-ray diffraction analyses. Compound 1 exhibits a H-bonded pillared bilayered structure, in which etheylenediammonium cation acts as a spacer between the anions resulting in the formation of two types of cavities. The larger cavity is filled by four water molecules though having hydrophobic character. Thus, the material behaves as a nanoporous organic solid. Compound 2 shows a multidimensional hydrogen bonding networks: one-dimensional arrays parallel to the b axis and two-dimensional sheets parallel to the ab plane. The N--H·;·;·;O--P hydrogen bonds, forming H-bonded supramolecular networks, are regarded to be strong and directional hydrogen bonds.     

Structure and dynamics of methanol in water: a quantum mechanical charge field molecular dynamics study

An ab initio quantum mechanical charge field molecular dynamics simulation was carried out for one methanol molecule in water to analyze the structure and dynamics of hydrophobic and hydrophilic groups. It is found that water molecules around the methyl group form a cage-like structure whereas the hydroxyl group acts as both hydrogen bond donor and acceptor, thus forming several hydrogen bonds with water molecules. The dynamic analyses correlate well with the structural data, evaluated by means of radial distribution functions, angular distribution functions, and coordination number distributions. The overall ligand mean residence time, τ identifies the methanol molecule as structure maker. The relative dynamics data of hydrogen bonds between hydroxyl of methanol and water molecules prove the existence of both strong and weak hydrogen bonds. The results obtained from the simulation are in excellent agreement with the experimental results for dilute solution of CH(3)OH in water. The overall hydration shell of methanol consists in average of 18 water molecules out of which three are hydrogen bonded.     

The structure of water in p-sulfonatocalix[4]arene

Tetrasodium p-sulfonatocalix[4]arene exists as a hydrate with approximately 14 water molecules and has three polymorphic modifications, all of which contain a water molecule in the molecular cavity that is engaged in OH···π interactions. Single-crystal neutron structures are reported for two of these three forms and reveal a "compressed" water molecule with short OH bonds. Partial atomic charges and hardness analysis (PACHA) calculations based on the neutron coordinates give an OH···π interaction energy of 6.9-7.5 kJ mol(-1). The PACHA analysis also reveals the dominance of the charge-assisted hydrogen bonds from the Na(+)-coordinated water molecules. The instability of the crystal towards dehydration can be traced to an uncoordinated lattice water site. The remarkable calixarene-Na(+)-hydrate motif is conserved almost unchanged across all three polymorphs. A single-crystal neutron structure is also reported for pentasodium p-sulfonatocalix[4]arene·12H(2)O, which exhibits an intracavity water molecule that is engaged in both OH···π and OH···O hydrogen bonding. The shorter covalent bond to the hydrogen atom that forms the interaction with the aromatic ring is again apparent.     

Entropy drives an attached water molecule from the C- to N-terminus on protonated proline

Results from infrared photodissociation (IRPD) spectroscopy and kinetics of singly hydrated, protonated proline indicate that the water molecule hydrogen bonds preferentially to the formally neutral carboxylic acid at low temperatures and at higher temperatures to the protonated N-terminus, which bears the formal charge. Hydration isomer populations obtained from IRPD kinetic data as a function of temperature are used to generate a van't Hoff plot that reveals that C-terminal binding is enthalpically favored by 4.2-6.4 kJ/mol, whereas N-terminal binding is entropically favored by 31-43 J/(mol K), consistent with a higher calculated barrier for water molecule rotation at the C-terminus.