A conformational dynamics study of alpha-l-Rhap-(1-->2)[alpha-l-Rhap-(1-->3)]-alpha-l-Rhap-OMe in solution by NMR experiments and molecular simulations

The conformational preference of alpha-l-Rhap-(1-->2)[alpha-l-Rhap-(1-->3)]-alpha-l-Rhap-OMe in solution has been studied by NMR spectroscopy using one-dimensional (1)H,(1)H T-ROESY experiments and measurement of trans-glycosidic (3)J(C,H) coupling constants. Molecular dynamics (MD) simulations with a CHARMM22 type of force field modified for carbohydrates were performed with water as the explicit solvent. The homonuclear cross-relaxation rates, interpreted as effective proton-proton distances, were compared to those obtained from simulation. Via a Karplus torsional relationship, (3)J(C,H) values were calculated from simulation and compared to experimental data. Good agreement was observed between experimental data and the MD simulation, except for one inter-residue T-ROE between protons in the terminal sugar residues. The results show that the trisaccharide exhibits substantial conformational flexibility, in particular along the psi glycosidic torsion angles. Notably, for these torsions, a high degree of correlation (77%) was observed in the MD simulation revealing either psi(2)(+) psi(3)(+) or psi(2)(-)psi(3)(-) states. The simulations also showed that non-exoanomeric conformations were present at the phi torsion angles, but to a limited extent, with the phi(3) state populated to a larger extent than the phi(2) state. Further NMR analysis of the trisaccharide by translational diffusion measurements and (13)C T(1) relaxation experiments quantified global reorientation using an anisotropic model together with interpretation of the internal dynamics via the "model-free" approach. Fitting of the dynamically averaged states to experimental data showed that the psi(2)(+)psi(3)(+) state is present to approximately 49%, psi(2)(-) psi(3)(-) to approximately 39%, and phi(3) (non-exo) to approximately 12%. Finally, using a dynamic and population-averaged model, (1)H,(1)H T-ROE buildup curves were calculated using a full relaxation matrix approach and were found to be in excellent agreement with experimental data, in particular for the above inter-residue proton-proton interaction between the terminal residues.     

A conformational study of the trisaccharide beta-D-Glcp-(1-->2)[beta-D-Glcp-(1-->3)]alpha-D-Glcp-OMe by NMR NOESY and TROESY experiments, computer simulations, and X-ray crystal structure analysis

Proton-proton cross-relaxation rates have been measured for the trisaccharide beta-D-Glcp-(l --> 2)[beta-D-Glcp-(1 --> 3)]alpha-D-Glcp-OMe in D2O as well as in D2O/[D6]DMSO 7:3 solution at 30 degrees C by means of one-dimensional NMR pulsed field gradient 1H,1H NOESY and TROESY experiments. Interatomic distances for the trisaccharide in D2O were calculated from the cross-relaxation rates for two intraresidue and three interglycosidic proton pairs, using the isolated spin-pair approximation. In the solvent mixture one intraresidue and three interglycosidic distances were derived without the use of a specific molecular model. In this case the distances were calculated from the cross-relaxation rates in combination with "model-free" motional parameters previously derived from 13C relaxation measurements. The proton-proton distances for interglycosidic pairs were compared with those averaged from Metropolis Monte Carlo and Langevin Dynamics simulations with the HSEA, PARM22, and CHEAT95 force fields. The crystal structure of the trisaccharide was solved by analysis of X-ray data. Interresidue proton pairs from the crystal structure and those observed by NMR experiments were similar. However, the corresponding proton-proton distances generated by computer simulations were longer. For the (1 --> 2) linkage the glycosidic torsion angles of the crystal structure were found in a region of conformational space populated by all three force fields, whereas for the (1 --> 3) linkage they occupied a region of low population density, as seen from the simulations.     

Application of paramagnetic NMR-validated molecular dynamics simulation to the analysis of a conformational ensemble of a branched oligosaccharide

Oligosaccharides of biological importance often exhibit branched covalent structures and dynamic conformational multiplicities. Here we report the application of a method that we developed, which combined molecular dynamics (MD) simulations and lanthanide-assisted paramagnetic NMR spectroscopy, to evaluate the dynamic conformational ensemble of a branched oligosaccharide. A lanthanide-chelating tag was attached to the reducing end of the branched tetrasaccharide of GM2 ganglioside to observe pseudocontact shifts as the source of long distance information for validating the conformational ensemble derived from MD simulations. By inspecting the results, the conformational space of the GM2 tetrasaccharide was compared with that of its nonbranched derivative, the GM3 trisaccharide.     

Conformational analysis of a tetrasaccharide based on NMR spectroscopy and molecular dynamics simulations

The conformational preference of the human milk oligosaccharide lacto-N-neotetraose, beta-d-Galp-(1 --> 4)-beta-d-GlcpNAc-(1 --> 3)-beta-d-Galp-(1 --> 4)-d-Glcp, has been analyzed using (1)H,(1)H T-ROESY and (1)H,(13)C trans-glycosidic J coupling experiments in isotropic solution and (1)H,(13)C residual dipolar couplings (RDCs) obtained in lyotropic liquid crystalline media. Molecular dynamics simulations of the tetrasaccharide with explicit water as the solvent revealed that two conformational states are significantly populated at the psi glycosidic torsion angle, defined by C(anomeric)-O-C-H, of the (1 --> 3)-linkage. Calculation of order parameters, related to the molecular shape, were based on the inertia tensor and fitting of experimental RDCs to different conformational states showed that psi(+) > 0 degrees is the major and psi(-) < 0 degrees is the minor conformation in solution, in complete agreement with a two-state analysis based on the T-ROESY data. Attention was also given to the effect of salt (200 mM NaCl) in the anisotropic medium, which was a ternary mixture of n-octyl-penta(ethylene glycol), n-octanol, and D(2)O.     

Interpreting NMR data for beta-peptides using molecular dynamics simulations

NMR is one of the most used techniques to resolve structure of proteins and peptides in solution. However, inconsistencies may occur due to the fact that a polypeptide may adopt more than one conformation. Since the NOE distance bounds and (3)J-values used in such structure determination represent a nonlinear average over the total ensemble of conformers, imposition of NOE or (3)J-value restraints to obtain one unique conformation is not an appropriate procedure in such cases. Here, we show that unrestrained MD simulation of a solute in solution using a high-quality force field yields a conformational ensemble that is largely compatible with the experimental NMR data on the solute. Four 100 ns MD simulations of two forms of a nine-residue beta-peptide in methanol at two temperatures produced conformational ensembles that were used to interpret the NMR data on this molecule and resolve inconsistencies between the experimental NOEs. The protected and unprotected forms of the beta-peptide adopt predominantly a 12/10-helix in agreement with the qualitative interpretation of the NMR data. However, a particular NOE was not compatible with this helix indicating the presence of other conformations. The simulations showed that 3(14)()-helical structures were present in the ensemble of the unprotected form and that their presence correlates with the fulfillment of the particular NOE. Additionally, all inter-hydrogen distances were calculated to compare NOEs predicted by the simulations to the ones observed experimentally. The MD conformational ensembles allowed for a detailed and consistent interpretation of the experimental data and showed the small but specific conformational differences between the protected and unprotected forms of the peptide.     

Lanthanide-assisted NMR evaluation of a dynamic ensemble of oligosaccharide conformations

A novel methodology is presented for evaluating a dynamic ensemble of oligosaccharide conformations by lanthanide-assisted NMR spectroscopy combined with molecular dynamics (MD) simulations. The results obtained using the GM3 trisaccharide demonstrated that pseudocontact shift measurements offer a valuable experimental tool for the validation of MD simulations of highly flexible biomolecules.     

Interaction of a tripeptide with cesium perfluorooctanoate micelles

The interaction of alanyl-phenylalanyl-alanine (Ala-Phe-Ala) with the micelles formed by cesium perfluorooctanoate (CsPFO) in water was studied in the isotropic phase by means of 1H NMR and by molecular dynamics (MD) simulations. Information on the location of the peptide was experimentally obtained from selective variations in Ala-Phe-Ala chemical shifts and from differential line broadening in the presence of the paramagnetic ion Mn2+. The peptide-micelle association constant was estimated analyzing the chemical shift variations of the most sensitive Ala-Phe-Ala resonances with the peptide concentration. MD simulations of Ala-Phe-Ala in the micellar environment confirmed the experimental observations, identifying the hydrogen bonding interactions of the different peptide moieties with the micelle, yielding a binding constant close to the experimental one. NOESY experiments suggest that the peptide in the micellar environment does not adopt a preferred conformation but is mainly unstructured. Details on the conformational behavior of the peptide in the micellar solution observed through MD were consistent with a different conformational equilibrium in the proximity of the micelle. Information on Ala-Phe-Ala dynamics was obtained from 1H T1 data and compared to MD simulation results on the overall tumbling motion.     

Experimental (NMR) and Theoretical (MD Simulations) Studies on the Conformational Preference of Three Cycloalkanols when Included in β-Cyclodextrin

The inclusion complexes between three cycloalkanols (cyclopentanol, cyclohexanol and cycloheptanol) and β-cyclodextrin (β-CD) have been studied by NMR experiments, and by molecular dynamics (MD) simulations. Complexes present medium to small association constants. All experimental data show the equatorial conformer as the most stable after complexation because no changes were detected in the coupling constants of the H1 protons. Intermolecular ROE experiments suggest that while cyclopentanol is deeply included into the β-CD cavity, cyclohexanol and cycloheptanol occupy mainly the wider entrance. The MD simulations agree with the experimental data (equatorial conformers are always the most stable), and average geometries coincide with those deduced from the ROE experiments.     

RNA unrestrained molecular dynamics ensemble improves agreement with experimental NMR data compared to single static structure: a test case

Nuclear magnetic resonance (NMR) provides structural and dynamic information reflecting an average, often non-linear, of multiple solution-state conformations. Therefore, a single optimized structure derived from NMR refinement may be misleading if the NMR data actually result from averaging of distinct conformers. It is hypothesized that a conformational ensemble generated by a valid molecular dynamics (MD) simulation should be able to improve agreement with the NMR data set compared with the single optimized starting structure. Using a model system consisting of two sequence-related self-complementary ribonucleotide octamers for which NMR data was available, 0.3 ns particle mesh Ewald MD simulations were performed in the AMBER force field in the presence of explicit water and counterions. Agreement of the averaged properties of the molecular dynamics ensembles with NMR data such as homonuclear proton nuclear Overhauser effect (NOE)-based distance constraints, homonuclear proton and heteronuclear ¹H–³¹P coupling constant (J) data, and qualitative NMR information on hydrogen bond occupancy, was systematically assessed. Despite the short length of the simulation, the ensemble generated from it agreed with the NMR experimental constraints more completely than the single optimized NMR structure. This suggests that short unrestrained MD simulations may be of utility in interpreting NMR results. As expected, a 0.5 ns simulation utilizing a distance dependent dielectric did not improve agreement with the NMR data, consistent with its inferior exploration of conformational space as assessed by 2-D RMSD plots. Thus, ability to rapidly improve agreement with NMR constraints may be a sensitive diagnostic of the MD methods themselves.     

HMGB1–Carbenoxolone Interactions: Dynamics Insights from Combined Nuclear Magnetic Resonance and Molecular Dynamics

The interplay of protein dynamics and molecular recognition is of fundamental importance in biological processes. Atomic‐resolution insights into these phenomena may provide new opportunities for drug discovery. Herein, we have combined NMR relaxation experiments and residual dipolar coupling (RDC) measurements with molecular dynamics (MD) simulations to study the effects of the anti‐inflammatory drug carbenoxolone (CBNX) on the conformational properties and on the internal dynamics of a subdomain (box A) of high‐mobility group B protein (HMGB1). ¹⁵N relaxation data show that CBNX binding enhances the fast pico‐ to nanosecond motions of a loop and partially removes the internal motional anisotropy of the first two helices of box A. Dipolar wave analysis of amide RDC data shows that ligand binding induces helical distortions. In parallel, increased mobility of the loop upon ligand binding is highlighted by the essential dynamics analysis (EDA) of MD simulations. Moreover, simulations detect two possible orientations for CBNX, which induces two possible conformations of helix H3, one being similar to the free form and the second one causing a partial helical distortion. Finally, we introduce a new approach for the analysis of the internal coordination of protein residues that is consistent with experimental data and allows us to pinpoint which substructures of box A are dynamically affected by CBNX. The observations reported here may be useful for understanding the role of protein dynamics in binding at atomic resolution.     

Comparison of properties of Aib-rich peptides in crystal and solution: a molecular dynamics study.

In order to study the differences of the structural properties of Aib-rich peptides in solution and in the crystalline state, molecular dynamics (MD) simulations of the Aib-containing peptide II (pBrBz-(Aib)5-Leu-(Aib)2-OMe) were performed in the crystalline state, starting from two different conformers obtained experimentally by X-ray diffraction. The structural properties as derived from X-ray crystallography (e.g., torsional angles and hydrogen bonds) are well-reproduced in both constant-volume and constant-pressure simulations, although the force-field parameters used result in a too-high density of the crystals. Through comparison with the results from previous MD and nuclear magnetic resonance (NMR) studies of the very similar peptide I (Z-(Aib)s-Leu-(Aib)2-OMe) in dimethylsulfoxide (DMSO) solution, it is found that, in the crystal simulation, the conformational distribution of peptide II is much narrower than that in the solution simulation of peptide. I. This leads to a significant difference in 3 [symbol: see text] (HN, HC alpha) coupling constant values, in agreement with experimental data, whereas the NOE intensities or proton-proton distance bounds appear insensitive to the difference in conformational distribution. For small peptides the differences between their conformational distribution in the crystalline form and in solution may be much larger than for proteins, a fact which should be kept in mind when interpreting molecular properties in the solution state by using X-ray crystallographic data.     

Conformational study of a guaiacyl beta-O-4 lignin model compound by NMR. Examination of intramolecular hydrogen bonding interactions and conformational flexibility in solution

Intramolecular H-bonding interactions were investigated in solution for the threo and erythro diastereomeric forms of a guaiacyl beta-O-4 lignin model compound by using the NMR data obtained from hydroxyl protons. Temperature coefficients of the chemical shifts (ddelta/dT) and coupling constants (3J(HCOH)) were measured in aprotic and protic solutions: DMSO-d6, acetone-d6 and acetone-d6-water. The NMR parameters do not support the existence of strong and persistent intramolecular H-bonds that could participate in the stabilization of the guaiacyl beta-O-4 structure in solution, but instead indicate that intermolecular H-bonds to solvent predominate. 1D NOE experiments nevertheless revealed the presence of a direct chemical exchange between the hydroxyl protons, suggesting the possible existence of weak and transient intramolecular H-bonding interactions. The conformational flexibility of the threo structure was also investigated in acetone solution from the measurement of long-range 1H, 1H and 1H, 13C coupling constants and from NOESY experiments. The NMR data are not consistent with any single conformation, indicating that different conformers co-exist in solution. The experimental results support the conformational flexibility predicted by molecular dynamics simulations performed in a previous study. Finally, both experimental and theoretical approaches indicate that weak intramolecular H-bonds can exist transiently in solution, breaking and reforming as the beta-O-4 molecule undergoes conformational interconversion, but cannot be invoked as possible means of conferring rigidity to the beta-O-4 structure.     

Fluorescent charge-assisted halogen-bonding macrocyclic halo-imidazolium receptors for anion recognition and sensing in aqueous media

The synthesis and anion binding properties of a new family of fluorescent halogen bonding (XB) macrocyclic halo-imidazolium receptors are described. The receptors contain chloro-, bromo-, and iodo-imidazolium motifs incorporated into a cyclic structure using naphthalene spacer groups. The large size of the iodine atom substituents resulted in the isolation of anti and syn conformers of the iodo-imidazoliophane, whereas the chloro- and bromo-imidazoliophane analogues exhibit solution dynamic conformational behavior. The syn iodo-imidazoliophane isomer forms novel dimeric isostructural XB complexes of 2:2 stoichiometry with bromide and iodide anions in the solid state. Solution phase DOSY NMR experiments indicate iodide recognition takes place via cooperative convergent XB-iodide 1:1 stoichiometric binding in aqueous solvent mixtures. (1)H NMR and fluorescence spectroscopic titration experiments with a variety of anions in the competitive CD(3)OD/D(2)O (9:1) aqueous solvent mixture demonstrated the bromo- and syn iodo-imidazoliophane XB receptors to bind selectively iodide and bromide respectively, and sense these halide anions exclusively via a fluorescence response. The protic-, chloro-, and anti iodo-imidazoliophane receptors proved to be ineffectual anion complexants in this aqueous methanolic solvent mixture. Computational DFT and molecular dynamics simulations corroborate the experimental observations that bromo- and syn iodo-imidazoliophane XB receptors form stable cooperative convergent XB associations with bromide and iodide.     

Conformational analysis of L-prolines in water

The results of the ring conformational analysis of L-proline, N-acetyl-L-proline, and trans-4-hydroxy-L-proline by NMR combined with calculations using density functional theory (DFT) and molecular dynamics (MD) are reported. Accurate values of 1H-1H J-couplings in water and other solvents have been determined. Using a two-site equilibrium model, the Cgamma-endo conformer of L-proline in water has been identified as intermediate between gammaTdelta [twist(Cgamma-endo, Cdelta-exo)] and gammaE [envelope(Cgamma-endo)] and the Cgamma-exo conformer as betaTgamma. Both conformers were equally populated at room temperature. The N-acetyl [cis-rotamer gammaTbeta(80%)/gammaE(20%) and trans-rotamer gammaTbeta(61%)/gammaE(39%)] and 4-hydroxy (gammaEpsilon) derivatives showed significant changes in both the population and the geometries of the preferred ring conformers. The combination of NMR predicted populations with the DFT B3LYP/6-311+G(2d,p)/IEFPCM calculations proved successful, resulting in fairly accurate predictions of J-couplings. Simulations using MD were mostly in favor of the two-site equilibrium model between Cgamma-endo and Cgamma-exo conformers, similar to that used for the analysis of NMR J-couplings. Various force fields examined for MD simulations failed to reproduce the ring conformational geometries and populations of L-proline in water accurately, while significantly better agreement with NMR was found for trans-N-acetyl-L-proline using GROMOS and AMBER force fields.     

Chemoenzymatic iterative synthesis of difficult linkages of oligosaccharides on soluble polymeric supports

[reaction: see text]. A trisaccharide donor containing a cis-Galpalpha(1-->4)Galp linkage was prepared using a synthetic strategy based on chemoenzymatic oligosaccharide synthesis on a soluble polymeric support. Significantly, only retaining glycosyltransferases gave complete reactions, whereas inverting enzymes showed little or no activity with poly(ethylene glycol) (MPEG)-bound lactose as an acceptor. The MPEG-attached trisaccharide was shown to bind to Verotoxin-1 by transfer NOE studies through the Galpalpha(1-->4)Galp portion of the molecule.     

Large oligosaccharide-based glycodendrimers

Carbohydrate-based dendritic structures composed of 21 and 27 monosaccharide residues have been synthesized in a convergent manner from trisaccharide building blocks. The oligosaccharide AB2 monomers are based on a maltosyl beta(1-->6)galactose structure, which has been modified to include two methylamino groups at the primary positions of the glucosyl residues. Reductive alkylation of the secondary amino groups, with the innate formyl function of a second oligosaccharide monomer, allows for the chemoselective construction of dendritic wedges, while employing a minimal number of protecting groups. The first-generation dendron can be coupled either to another AB2 monomer, to give a second-generation dendron, or to a tris[2-(methylamino)ethyl]amine-based core moiety, to provide a carbohydrate-based dendrimer. Alternating alpha- and beta-glucosyl residues in the monomers and dendrons, simplifies 1H NMR spectra as a consequence of spreading out the anomeric proton signals. Monomers and dendrons were characterized by extensive one- and two-dimensional NMR spectroscopy in addition to FAB, electrospray, and MALDI-TOF mass spectrometry. Molecular dynamics simulations revealed similar conformations in the dendrons as in the isolated trisaccharide repeating units.     

Post-transition state dynamics for propene ozonolysis: Intramolecular and unimolecular dynamics of molozonide

A direct chemical dynamics simulation, at the B3LYP6-31G(d) level of theory, was used to study the post-transition state intramolecular and unimolecular dynamics for the O3 + propene reaction. Comparisons of B3LYP6-31G(d) with CCSD(T)/cc-pVTZ and other levels of theory show that the former gives accurate structures and energies for the reaction's stationary points. The direct dynamics simulations are initiated at the anti and syn O3 + propene transition states (TSs) and the TS symmetries are preserved in forming the molozonide intermediates. Anti<-->syn molozonide isomerization has a very low barrier of 2-3 kcalmol and its Rice-Ramsperger-Kassel-Marcus (RRKM) lifetime is 0.3 ps. However, the trajectory isomerization is slower and it is unclear whether this anti<-->syn equilibration is complete when the trajectories are terminated at 1.6 ps. The syn (anti) molozonides dissociate to CH3CHO + H2COO and H2CO + syn (anti) CH3CHOO. The kinetics for the latter reactions are in overall good agreement with RRKM theory, but there is a symmetry preserving non-RRKM dynamical constraint for the former. Dissociation of anti molozonide to CH3CHO + H2COO is enhanced and suppressed, respectively, for the trajectory ensembles initiated at the anti and syn O3 + propene TSs. The dissociation of syn molozonide to CH3CHO + H2COO may also be enhanced for trajectories initiated at the syn O3 + propene TS. At the time the trajectories are terminated at 1.6 ps, the ratio of the trajectory and RRKM values of the CH3CHO + H2COO product yield is 1.6 if the symmetries of the initiation and dissociation TSs are the same and 0.6 if their symmetries are different. There are coherences in the intramolecular energy flow, which depend on molozonide's symmetry (i.e., anti or syn). This symmetry related dynamics is not completely understood, but it is clearly related to the non-RRKM dynamics for anti<-->syn isomerization and anti molozonide dissociation to CH3CHO + H2COO. Correlations are found between the stretching motions of molozonide, indicative of nonchaotic and non-RRKM dynamics. The non-RRKM dynamics of molozonide dissociation partitions vibration energy to H2COO that is larger than statistical partitioning. Though the direct dynamics simulations are classical, better agreement is obtained using quantum instead of classical harmonic RRKM theory. This may result from the neglect of anharmonicity in the RRKM calculations, the non-RRKM dynamics of the classical trajectories, or a combination of these two effects. The trajectories suggest that the equilibrium syn/anti molozonide ratio is approximately 1.1-1.2 times larger than that predicted by the harmonic densities of state, indicating an anharmonic correction.     

Vibrational spectra, crystal structures, constitutional and rotational isomerism of FC(O)SCN and FC(O)NCS

Fluorocarbonyl thio- and isothiocyanate, FC(O)SCN and FC(O)NCS, were fully characterized by IR (gas, Ar and N(2) matrixes), Raman (liquid and solid), UV (gas), and (13)C NMR (liquid) spectroscopy, as well as single-crystal X-ray diffraction. Their vibrational and conformational properties were analyzed using matrix isolation techniques guided by quantum chemical calculation at the ab initio [MP2 and CCSD(T)], density functional theory B3LYP, and CBS-QB3 levels of theory. A complete assignment of the fundamental modes of FC(O)SCN was performed. In both the gas and liquid states, FC(O)SCN and FC(O)NCS were found to exist as two conformers (C(s) symmetry), in which the carbonyl double bond (C═O) adopts a synperiplanar (syn) and an antiperiplanar (anti) orientation with respect to either the SCN or NCS group. For FC(O)SCN, the conformational enthalpy difference, ΔH° = H°(anti) - H°(syn), was determined by matrix IR experiments to be 0.9 ± 0.2 kcal mol(-1). The conformational equilibria were evaluated by fast-cooling gaseous samples highly diluted in argon at different temperatures as cryogenic matrixes. The conformational properties of both molecules were analyzed in terms of the hyperconjugative electronic effect applying the natural bond orbital method. The kinetics of the thermal conversion of the high-energy anti into the syn FC(O)NCS conformer was studied in Ar and N(2) matrixes at cryogenic temperatures. The reversed syn → anti photoisomerization was observed using UV-vis light. Rearrangement of FC(O)SCN into FC(O)NCS was observed in the neat liquid and in solution. Under 193 nm (ArF excimer laser) irradiation, FC(O)NCS isolated in cryogenic Ar matrixes forms FC(O)SCN. At low temperature, single crystals of the two constitutional isomers were obtained using a miniature zone melting procedure. According to X-ray diffraction, they exclusively crystallize in their syn forms (C(s) symmetry) in the orthorhombic crystal system.     

Anomalous conformational change in 1-butyl-3-methylimidazolium tetrafluoroborate-D2O mixtures

We have investigated the effect of deuterated water on the conformational equilibrium between the gauche and trans conformers of the [bmim] cation in mixtures of water and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)]), an ionic liquid, at room temperature. A comparison of the results obtained from solutions made with H(2)O and with D(2)O highlights an anomalous conformational change in the D(2)O solution showing an extended N-shaped behavior. The gauche conformer of the [bmim] cation in D(2)O increased up to x = ~50 (D(2)O mol %); however, it decreased up to higher water concentrations of x = ~85 before again increasing drastically toward x = ~100. We provide spectroscopic evidence that the anomalous conformational dynamics of the [bmim] cation in D(2)O is directly related to the H/D exchange reaction of the C-H group at position 2 of the imidazolium ring.     

Validation of the GROMOS 54A7 Force Field Regarding Mixed α/β‐Peptide Molecules

A molecular‐dynamics (MD) simulation study of two heptapeptides containing α‐ and β‐amino acid residues is presented. According to NMR experiments, the two peptides differ in dominant fold when solvated in MeOH: peptide 3 adopts predominantly β‐hairpin‐like conformations, while peptide 8 adopts a 14/15‐helical fold. The MD simulations largely reproduce the experimental data. Application of NOE atom? atom distance restraining improves the agreement with experimental data, but reduces the conformational sampling. Peptide 3 shows a variety of conformations, while still agreeing with the NOE and ³J‐coupling data, whereas the conformational ensemble of peptide 8 is dominated by one helical conformation. The results confirm the suitability of the GROMOS 54A7 force field for simulation or structure refinement of mixed α/β‐peptides in MeOH.