Diversity of potential hydrogen bonds in cellulose I revealed by molecular dynamics simulation

We have performed molecular dynamics calculations using a revised version of the Gromos56A_carbo force field to understand the consequences of the different potential hydrogen bonding patterns on the structural stability and thermal behavior of the I_α and I_β forms of native cellulose. For each allomorph, we considered three patterns of hydrogen bonds: two patterns obtained from neutron diffraction data refinement and a regular mixture of the two. Upon annealing, the hydrogen bonding schemes of cellulose I_β, irrespective of the starting structure, re-arranged into the main hydrogen bond pattern experimentally observed (pattern A). On the other hand, the I_α structures, irrespective of the starting hydrogen bonding pattern, converged to a non-experimental structure where the adjacent chains are shifted along the chain direction by 0.12 nm in the hydrogen-bonded plane, and the hydroxymethyl group conformation alternates between gt and tg along the chain. The exotic structure in I_α might be a consequence of a deficiency in force field parameters and/or potential molecular arrangement in less crystalline cellulose.     

Molecular dynamics simulations of conserved Hox protein hexapeptides. I. Folding behavior in water solution

Molecular dynamics simulations of hexapeptides TFDWMK and LFPWMR; the highly conserved regions of Hox proteins Hox B1 and Hox B8, respectively, are carried out starting from extended structures to investigate their conformational space in water solution. In addition, we have studied TADWMK and TADAMK, where the aromatic residues Phenylalanine and Tryptophan were successively substituted for Alanine to investigate effects from the presence/absence of aromatic amino acids and interactions between them to folding behavior. The backbone of the hexapeptides in all simulations folds to a similar conformation found in experimental studies in solution. Intramolecular, hydrophobically driven interactions between the aromatic residues and internal hydrogen bonds are found to stabilize the conformations.     

Do aurophilic interactions compete against hydrogen bonds? Experimental evidence and rationalization based on ab initio calculations

[M(C6F5)(N(H)=CPh2)] (M = Ag (1) and Au (2)) complexes have been synthesized and characterized by X-ray diffraction analysis. Complex 1 shows a ladder-type structure in which two [Ag(C6F5)(N(H)=CPh2)] units are linked by a Ag(I)-Ag(I) interaction in an antiparallel disposition. The dimeric units are associated through hydrogen bonds of the type N-H...F(ortho). On the other hand, gold(I) complex 2 displays discrete dimers also in an antiparallel conformation in which both Au(I)-Au(I) interactions and N-H.F(ortho) hydrogen bonds appear within the dimeric units. The features of these coexisting interactions have been theoretically studied by ab initio calculations based on four different model systems in order to analyze them separately. The interactions have been analyzed at HF and MP2 levels of theory showing that, in this case, even at larger distances. The Au(I)-Au(I) interaction is stronger than Ag(I)-Ag(I) and that N-H.F hydrogen bonding and Au(I)-Au(I) contacts have a similar strength in the same molecule, which permits a competition between these two structural motifs giving rise to different structural arrangements.     

Conformation-changing aggregation in hydroxyacetone: a combined low-temperature FTIR, jet, and crystallographic study

Aggregation in hydroxyacetone (HA) is studied using low-temperature FTIR, supersonic jet expansion, and X-ray crystallographic (in situ cryocrystallization) techniques. Along with quantum chemical methods (MP2 and DFT), the experiments unravel the conformational preferences of HA upon aggregation to dimers and oligomers. The O-H···O═C intramolecular hydrogen bond present in the gas-phase monomer partially opens upon aggregation in supersonic expansions, giving rise to intermolecular cooperatively enhanced O-H···O-H hydrogen bonds in competition with isolated O-H···O═C hydrogen bonds. On the other hand, low-temperature IR studies on the neat solid and X-ray crystallographic data reveal that HA undergoes profound conformational changes upon crystallization, with the HOCC dihedral angle changing from ~0° in the gas phase to ~180° in the crystalline phase, hence giving rise to a completely new conformation. These conclusions are supported by theoretical calculations performed on the geometry derived from the crystalline phase.     

Helix-forming carbohydrate amino acids

[reaction: see text] The solution-phase conformational properties of tetrameric and octameric chains of C-glycosyl alpha-d-lyxofuranose configured tetrahydrofuran amino acids (where the C-2 and C-5 substituents on the tetrahydrofuran ring are trans to each other) were examined using NMR and IR and CD in organic solvents. Studies by NMR and IR demonstrated that in chloroform solution, the tetramer 7 does not adopt a hydrogen-bonded conformation whereas the octamer 10 populates a well-defined helical secondary structure stabilized by 16-membered (i, i - 3) interresidue hydrogen bonds, similar to a pi-helix. Circular dichroism studies in trifluoroethanol are consistent with this conformation for the octamer 10, and also indicate that the tetramer 7 adopts a rigid conformation not stabilized by hydrogen bonds.     

A novel intramolecular hydrogen bonding between a side-chain pyridine ring and an amide hydrogen of the peptide backbone in tripeptides containing the new amino acid, alpha,alpha-di(2-pyridyl)glycine

Four tripeptides (Z-AA1-2Dpy-AA3-OMe; AA1, AA3 = Gly, Aib) containing a novel amino acid, alpha, alpha-di(2-pyridyl)glycine (2Dpy), were synthesized by the modified Ugi reaction. NMR analysis clearly indicated that the 2Dpy-containing tripeptides except the peptide in which AA1, AA3 = Aib, adopt a unique conformation with two intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen and between AA3-NH and another pyridine nitrogen. This conformation has so far not been reported. On the other hand, the peptide Z-Aib-2Dpy-Aib-OMe probably adopts a beta-turn structure which is stabilized by two intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen and between AA3-NH and the C=O of the Z group.     

Probing the dependence of the properties of cellulose acetates and their films on the degree of biopolymer substitution: use of solvatochromic indicators and thermal analysis

Although cellulose acetates, CAs, are extensively employed there is scant information about the systematic dependence of their properties on their degree of substitution, DS; this is the subject of the present work. Nine CAs samples, DS from 0.83 to 3.0 were synthesized; their films were prepared. The following solvatochromic probes have been employed in order to determine the empirical polarity, E _T(33); “acidity, α”; “basicity, β”, and “dipolarity/polarizability, π*” of the casted films: 2,6-dichloro-4-(2,4,6-triphenyl-pyridinium-1-yl) phenolate, WB; 4-nitroaniline; 4-nitroanisole; 4-nitro-N,N-dimethylaniline; 2,6-diphenyl-4-(2,4,6-triphenyl-pyridinium-1-yl)phenolate, RB. Additionally, two systems, ethanol plus ethyl acetate (EtOH–EtAc), and cellulose plus cellulose triacetate, CTA, were employed as models for CAs of different DS. Regarding the model systems, the following was observed: (i) For EtOH–EtAc, the dependence of all solvatochromic parameters on the “equivalent-DS” of the binary mixture was non-linear because of preferential solvation; (ii) The dependence of E _T(33) on equivalent DS of the cellulose–CTA films is linear, but the slope is smaller than that of the corresponding plot for CAs. This is attributed to the more efficient hydrogen bonding in the model system, a conclusion corroborated by IR measurements. The dependence of solvatochromic parameters of CAs on their DS is described by the simple equations; a consequence of the substitution of the OH by the ester group. The thermal properties of bulk CAs samples were investigated by DSC and TGA; their dependence on DS is described by simple equations. The relevance of these data to the processing and applications of CAs is briefly discussed.     

Hydrocarbon chain conformation in an intercalated surfactant monolayer and bilayer

Cetyl trimethyl ammonium (CTA) ions have been confined within galleries of layered CdPS₃ at two different grafting densities. Low grafting densities are obtained on direct intercalation of CTA ions into CdPS₃ to give Cd_0.93PS₃(CTA)_0.14. Intercalation occurs with a lattice expansion of 4.8 ? with the interlamellar surfactant ion lying flat forming a monolayer. Intercalation at higher grafting densities was effected by a two-step ion-exchange process to give Cd_0.83PS₃(CTA)_0.34, with a lattice expansion of 26.5 ?. At higher grafting densities the interlamellar surfactant ions adopt a tilted bilayer structure.¹³C NMR and orientation-dependent IR vibrational spectroscopy on single crystals have been used to probe the conformation and orientation of the methylene ‘tail’ of the intercalated surfactant in the two phases. In the monolayer phase, the confined methylene chain adopts an essentially all-trans conformation with most of the trans chain aligned parallel to the gallery walls. On lowering the temperature, molecular plane aligns parallel, so that the methylene chain lies flat, rigid and aligned to the confining surface. In the bilayer phase, most bonds in the methylene chain are in trans conformation. It is possible to identify specific conformational sequences containing a gauche bond, in the interior and termini of the intercalated methylene. These high energy conformers disappear on cooling leaving all fifteen methylene units of the intercalated cetyl trimethyl ammonium ion in trans conformational registry at 40 K.     

Comparison of aqueous molecular dynamics with NMR relaxation and residual dipolar couplings favors internal motion in a mannose oligosaccharide.

An investigation has been performed to assess how aqueous dynamical simulations of flexible molecules can be compared against NMR data. The methodology compares state-of-the-art NMR data (residual dipolar coupling, NOESY, and (13)C relaxation) to molecular dynamics simulations in water over several nanoseconds. In contrast to many previous applications of residual dipolar coupling in structure investigations of biomolecules, the approach described here uses molecular dynamics simulations to provide a dynamic representation of the molecule. A mannose pentasaccharide, alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->2)-D-Manp, was chosen as the model compound for this study. The presence of alpha-linked mannan is common to many glycopeptides, and therefore an understanding of the structure and the dynamics of this molecule is of both chemical and biological importance. This paper sets out to address the following questions. (1) Are the single structures which have been used to interpret residual dipolar couplings a useful representation of this molecule? (2) If dynamic flexibility is included in a representation of the molecule, can relaxation and residual dipolar coupling data then be simultaneously satisfied? (3) Do aqueous molecular dynamics simulations provide a reasonable representation of the dynamics present in the molecule and its interaction with water? In summary, two aqueous molecular dynamics simulations, each of 20 ns, were computed. They were started from two distant conformations and both converged to one flexible ensemble. The measured residual dipolar couplings were in agreement with predictions made by averaging the whole ensemble and from a specific single structure selected from the ensemble. However, the inclusion of internal motion was necessary to rationalize the relaxation data. Therefore, it is proposed that although residual dipolar couplings can be interpreted as a single-structure, this may not be a correct interpretation of molecular conformation in light of other experimental data. Second, the methodology described here shows that the ensembles from aqueous molecular dynamics can be effectively tested against experimental data sets. In the simulation, significant conformational motion was observed at each of the linkages, and no evidence for intramolecular hydrogen bonds at either alpha(1-->2) or alpha(1-->3) linkages was found. This is in contrast to simulations of other linkages, such as beta(1-->4), which are often predicted to maintain intramolecular hydrogen bonds and are coincidentally predicted to have less conformational freedom in solution.     

Partially O-alkylated thiacalix[4]arenes: synthesis, molecular and crystal structures, conformational behavior

NMR spectroscopy, X-ray diffraction analysis, and quantum chemical calculations were used for conformational behavior study of partially alkylated thiacalix[4]arenes bearing methyl (1), ethyl (2), or propyl (3) groups at the lower rim. The conformational properties are governed by two basic effects: (i) stabilization by intramolecular hydrogen bonds, and (ii) sterical requirements of the alkoxy groups at the lower rim. While the monosubstituted derivatives 1a and 3a adopt the cone conformation in solution, distally disubstituted compounds 1b, 1'b, 2b, 2'b, 3b, and 3'b exhibit several interesting conformational features. They prefer pinched cone conformation in solution, and, except for 3'b, they form also 1,2-alternate conformation, which is flexible and undergoes rather fast transition between two identical structures. The crystal structures of the compounds 1b, 2b, 2'b, and 3b revealed yet quite rare 1,2-alternate conformation forming molecular channels held together by pi-pi interactions. Different channels-with hexagonal symmetry, 0.26 nm wide-are formed in the crystal structure of the pinched cone conformation of 3b. An uncommon hydrogen bonding pattern was found in dimethoxy and dipropoxy derivatives 1'b and 3'b that adopt distorted cone conformations in crystal. Trialkoxy-substituted compounds 1c and 3c adopt the partial cone conformation in solution. A higher mobility of methyl derivative 1c enables also existence of the cone conformer.     

Conformational switching between carboxylic acid and carboxylate anion states by NH-O hydrogen bonding

Biologically important Ca-proteins and Ca-biominerals as metal-polymer complexes are often regulated by the complexation and demetalation with the biopolymers. Metal-oxygen bond is supported by NH···O hydrogen bonds between coordinating oxyanion and neighboring amide NH and by the successive hydrogen bonding networks. Carboxylate anion under hydrophobic conditions has a high basicity that leads to a covalent Ca-O bond character that is significantly affected by the NH···O hydrogen bond. The hydrogen bonds in Asp-containing tripeptide fragments in Ca-proteins presumably control coordination/dissociation of metal-oxygen bonds. Our systematic studies of carboxylate, sulfonate and phosphate Ca(II) complexes demonstrate a relationship between the basicity of oxyanion in carboxylate and hydrogen bonds as cooperating with the oligopeptide conformation in Asp-containing Ca(II) complexes. Hydrogen bonds between carboxylate oxyanion and amide NH, controlled by a conformational switching of oligopeptide fragments, seem to be one of essential factors for the regulatory formation of Ca-proteins and nano-architectures in connection with the interface structure of inorganic and organic phases in biominerals.     

Structural Micro-heterogeneities of Crystalline Iβ-cellulose

The crystal structure of the native Iβ-allomorph of cellulose [Nishiyama et al. 2002. J. Am. Chem. Soc. 124: 9074–9082] reveals subtle but significant conformational differences between the two different chains and also a multiplicity of positions of the hydrogen atoms of the HO₂ and HO₆ hydroxyl groups. Two structures differing in the hydrogen bonding networks were then proposed, however, the static or dynamic origin of the observed disorder remains to be specified. Molecular modelling was used to address this question: 18 minicrystal and 2 macrocrystal models of cellulose were generated differing by the initial orientations of the HO₂ and HO₆ hydroxyl groups; among which the two proposed structures (called N1 and N16) together with a random structure which respect the experimental percentage of hydroxyl hydrogen orientations. Results showed that only 10 of the studied combinations were stable, the major structure (N1) defined by crystallographers was estimated viable whereas not the minor one (N16). All the calculated data from the retained crystals, which describe the solid dimensions, the individual chain conformations and the supermolecular organisation, 1/ remained stable at their equilibrium value during the dynamics and 2/ were sensitive to the initial positions of the hydrogen atoms. Analysis of the hydrogen bonds revealed that sheet stacking might be stabilised by unexpected hydrogen bonds in addition to hydrophobic interactions. Our results thus favoured local disorders which involve a limited number of chains; they revealed the structural microheterogeneity of the Iβ-phase of cellulose and a complex disorder of its corresponding hydrogen bonding networks.     

Structure of dilignol,β-O-4-[1-(4-hydroxyphenyl)-2-(2-methoxyphenoxy)-1-ethanol] in crystal and in solution

The structure of dilignol, 1-(4-hydroxyphenyl)-2-(2-methoxyphenoxy)-1-ethanol was studied by x-ray diffraction structural analysis and¹H PMR spectroscopy. The dilignol molecules crystallize in an extended conformation with trans-Ar-C-C-O and trans-C-C-O-Ar structures: the angle between the plane of the aromatic systems was 74.0°. This conformation was stabilized by intermolecular hydrogen bonds, which linked the molecules into chains. Weak Y-shaped hydrogen bonds were found between molecules of adjacent chains. These results were compared with the literature data on the crystal structure of -O-4 dilignols. A similar conformation of dilignol stabilized by an intramolecular hydrogen bond, whose existence was indicated by IR spectroscopy, was found to predominate in acetone and chloroform solutions. A conclusion was drawn concerning the conformational mobility of -O-4 dilignols and the factors determining the conformational composition of dilignols in solution were discussed.S. M. Kirov Leningrad Forest Technology Institute, Institute of Wood Chemistry, Academy of Sciences of the Latvian SSR. Institute of Organic Synthesis, Academy of Sciences of the Latvian SSR. Translated from Zhurnal Strukturnoi Khimii, Vol. 30, No. 5, pp. 135–141, September–October, 1989.     

Synthesis and Crystal Structure of N-Benzyl-N'-(2-pyridyl)urea and Its Mononuclear Cu(II) Complex

A new ligand of N-benzyl-N'-(2-pyridyl)urea L and its self-assembly product with CuCl2, [Cu(II)LCl2]∞ 1, have been synthesized and structurally characterized by IR, 1H NMR and single-crystal X-ray diffraction analysis. In the structure of L, the urea groups adopt Z,E conformation to form dimers through intermolecular hydrogen bonds; while in complex 1, it assumes Z,Z conformation to fit for the coordination sphere of the Cu(II) ions. The coordinated units are connected through intermolecular N-H…Cl hydrogen bonds to form an extended 2D framework. Finally, a 3D structure is obtained via π-π stacking interactions between pyridyl rings.     

Two polymorphs of N1,N4‐bis(5‐hydroxypenta‐1,3‐diynyl)‐N1,N4‐diphenylbenzene‐1,4‐diamine

The title compound, C₂₈H₂₀N₂O₂, forms two conformational polymorphs, (I) and (II), where the molecular structures are similar except for the orientation of the two hydroxy groups. In (I), which was obtained by slow evaporation from chloroform, the two hydroxy groups have an anti conformation. The molecules form a sheet structure within the ac plane, where the hydroxy groups form zigzag hydrogen bonds. In (II), which was obtained by slow evaporation from acetonitrile, the two hydroxy groups have a syn conformation. The molecules form a double‐sheet structure within the ab plane, where the hydroxy groups form 4‐helix hydrogen bonds.     

Synthesis and Crystal Structure of N-Benzyl-N＇-（2-pyridyl）urea and Its Mononuclear Cu（Ⅱ） Complex

A new ligand of N-benzyl-N＇-（2-pyridyl）urea L and its self-assembly product with CuCl2, [Cu（Ⅱ）LCl2]∞ 1, have been synthesized and structurally characterized by IR, 1H NMR and single-crystal X-ray diffraction analysis. In the structure of L, the urea groups adopt Z,E conformation to form dimers through intermolecular hydrogen bonds; while in complex 1, it assumes Z,Z conformation to fit for the coordination sphere of the Cu（Ⅱ） ions. The coordinated units are connected through intermolecular N-H...Cl hydrogen bonds to form an extended 2D framework. Finally, a 3D structure is obtained via π-π stacking interactions between pyridyl rings     

Modification of the structure of cellulose triacetate films in the course of solvent vapor sorption

Intermolecular interaction and structure of cellulose triacetate films in the course of sorption of dimethylsulfoxide, nitromethane, and tetrachloroethane vapors were studied by Fourier IR spectroscopy, X-ray diffraction analysis, and polarization microscopy. Quantitative ratio of different types of intra- and intermolecular hydrogen bonds in polymer films was estimated. Changes in the structure of cellulose triacetate films in the course of solvent vapor sorption were discussed from the viewpoint of competition between the interchain interactions via OH and C=O groups of the macromolecules and their solvation with the solvent molecules.     

Rotational isomerism and physical properties of long-chain molecules in solid states

Rotational isomerism occurring in solid state of organic long-chain compounds, including synthetic linear polymers, have been concerned in connection with the macroscopic physical properties of bulk materials. The conformational order in the non-crystalline part of polyethylene has been investigated by Raman spectra, and related to the elastic behaviors of bulk samples. In the solid-state phase transition induced by mechanical forces of poly(butylene terephthalate) the macroscopic strain has been related directly to the conformational conversion of the molecules. Concerning the piezoelectric and pyroelectric activities of poly(vinylidene fluoride), polymorphism, phase transition, and structural change on the poling process have been investigated. A ferroelectric-paraelectric phase transition has been found for a series of copolymers of vinylidene fluoride and trifluoroethylene. On the phase transition a great change in molecular conformation is accompanied with the scrambling of the dipolar orientation. This is the characteristic of polymer ferroelectrics in which the dipolar units are linked with each other by covalent bonds in a molecular chain. Spectroscopic evidences are presented indicating that the thermodynamic stability of polymorphs of n-fatty acids is closely related to the rotational isomerism occurring in the carboxyl groups.     

Synthesis of jasplakinolide analogues containing a novel omega-amino acid

The synthesis of the omega-amino acid 4 is described utilizing a two-dimensional synthesis strategy combined with an enzymatic differentiation of homotopic ester groups. The amino acid 4 features two non-bonded interactions that result in conformational constraints on a cyclic construct. This amino acid was incorporated into the four macrolactams 17, 22, 31, and 37. The ring in 17 and 22 is 18-membered, whereas 31 and 37 have a 19-membered ring. The pairs with the same ring size differ in a N-methyl group. For the larger macrolactams (31 and 37) conformational analysis showed that the macrocyclic rings are somewhat more rigid than in the natural lead, the depsipeptide jasplakinolide. Nevertheless, their conformations are comparable to the natural product. There are no intramolecular hydrogen bonds, neither is the cis-rotamer populated in the N-methyl compound 37. Due to the increased flexibility of the smaller macrolactams 17 and 22 and signal overlap, a distinct solution structure could not be obtained for these compounds. The amino acid 4 should be useful for restricting the conformation of other small peptides.     

"Union is strength": how weak hydrogen bonds become stronger

Recently reported rotational spectroscopic studies on small dimers and oligomers bound by weak hydrogen bonds show that the driving forces, the spatial arrangement and the dynamical features displayed are very different from those involved in stronger and conventional hydrogen bonds. The very small binding energies (similar to those of van der Waals interactions) imply that the stabilization of the dimer is often obtained by networks of weak hydrogen bonds. Even in the presence of multiple bonds the partner molecules show a high degree of internal freedom within the complex. This paper analyses several examples of molecular adducts bound by weak hydrogen bonds formed in free jet expansions and recently characterized by rotational spectroscopy. They include weakly bound complexes of weak donors with strong acceptors (C-H···O,N, S-H···O,N), strong donors (O-H, N-H) with weak acceptors such as the halogen atoms and π systems but also the elusive interactions between weak donors and weak acceptors (C-H···π and C-H···halogen). Examples are also given where rotational spectroscopy highlights that weak hydrogen bonds are extremely important in chiral recognition phenomena and as driving forces of the conformational landscape of important biomolecules.