Chain Torsion Research Articles

Absorption and Excited-State Coherences of Cryogenically Cold Retinal Protonated Schiff Base in Vacuo.

Retinal protonated Schiff base (RPSB), found in its all-trans conformer in Bacteriorhodopsin, undergoes barrier-controlled isomerization upon photoabsorption through polyene- chain torsion. The effects of the protein environment on the active vibrations during photoabsorption and their redistribution are still not understood. This paper reports on femtosecond time-resolved action-absorption measurements of cryogenically cooled gas-phase all-trans RPSB, which exhibit two coherent vibrational oscillations, 167(14) cm-1 and 117(1) cm-1, of the first excited state with dephasing times of ∼ 1 ps. The absence of the high-frequency vibration in solution and the low-frequency vibration in the protein indicates that these vibrations are sensitive to environments. An action-absorption spectrum of cryogenically cold all-trans RPSB, reveals a ∼ 310 cm-1 active vibration when using a hole-burning technique and 1500 cm-1 C=Cstretching modes.

Exploring pH-Triggered Lamellar to Cubic Phase Transition in 2-Hydroxyoleic Acid/Monoolein Nanodispersions: Insights into Membrane Physicochemical Properties.

Self-assembled lipid nanoparticles (LNPs) are essential nanocarriers for drug delivery. Functionalization of LNPs with ionizable lipids creates pH-responsive nanoparticles that change structures under varying pH conditions, enabling pH-triggered drug release. Typically, bicontinuous cubic phase nanoparticles (Cubosomes) and lamellar structured vesicles (Liposomes) differ in lipid packing statuses, affecting drug release and cellular uptake. However, most research predominantly focuses on elucidating lattice structure changes of these LNPs without a deep investigation of lipid-membrane properties. Addressing this gap, our study delves into the lipid-membrane physicochemical property variations during the lamellar-to-cubic phase transition. Here, we prepared pH-responsive LNPs using 2-hydroxyoleic acid/monoolein (2-OHOA/MO) binary components. Small-angle X-ray scattering (SAXS) revealed a phase transition from lamellar vesicles (Lα) to cubosomes (Im3m/Pn3m) with pH reduction. Laurdan and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence probes tracked the lipid-water interfacial polarity and lipid-membrane fluidity variations during the phase transition. Raman spectroscopy provided further insights into lipid-membrane lipid chain packing and chain torsion. We observed that the changes in lipid-membrane properties coincided with the lamellar-to-cubic phase transition, emphasizing the interplay between the phase structure and lipid-membrane behaviors in the 2-OHOA/MO system. This study provides insights into the lipid-membrane properties variation during the pH-triggered phase transition in the 2-OHOA/MO system, guiding future research toward more effective and reliable pH-responsive drug delivery platforms.

DiffBindFR: an SE(3) equivariant network for flexible protein-ligand docking.

Molecular docking, a key technique in structure-based drug design, plays pivotal roles in protein-ligand interaction modeling, hit identification and optimization, in which accurate prediction of protein-ligand binding mode is essential. Conventional docking approaches perform well in redocking tasks with known protein binding pocket conformation in the complex state. However, in real-world docking scenario without knowing the protein binding conformation for a new ligand, accurately modeling the binding complex structure remains challenging as flexible docking is computationally expensive and inaccurate. Typical deep learning-based docking methods do not explicitly consider protein side chain conformations and fail to ensure the physical plausibility and detailed atomic interactions. In this study, we present DiffBindFR, a full-atom diffusion-based flexible docking model that operates over the product space of ligand overall movements and flexibility and pocket side chain torsion changes. We show that DiffBindFR has higher accuracy in producing native-like binding structures with physically plausible and detailed interactions than available docking methods. Furthermore, in the Apo and AlphaFold2 modeled structures, DiffBindFR demonstrates superior advantages in accurate ligand binding pose and protein binding conformation prediction, making it suitable for Apo and AlphaFold2 structure-based drug design. DiffBindFR provides a powerful flexible docking tool for modeling accurate protein-ligand binding structures.

Elucidating the impact mechanism of temperature and water content on thermal conductivity of hydrated Nafion membranes by molecular dynamics simulation

The thermal conductivity of the proton exchange membrane significantly affects the operating performance of the fuel cell. In this work, the impact of water content and temperature on thermal conductivity of hydrated Nafion membranes was investigated via molecular dynamics simulations and the influencing mechanism was explained from the perspective of interchain and intrachain heat transfer. The study shows that the thermal conductivity is mainly positively affected by water content, which is a result of the triple effect of hydrogen bonding acting as interchain heat transfer bridge, the stronger microphase separation allowing water to behave more like bulk water, and the decrease in the degree of chain torsion resulting in less phonon scattering along the chain. Particularly, we emphasized two crucial paths in which hydrogen bonding improves interchain heat transport. Furthermore, the temperature has little and slightly negative effects on thermal conductivity at low and high hydration levels, respectively. That is because, in low hydration levels, the incomplete hydrogen bond network is hardly influenced, but the bridging effect is suppressed and intrachain heat transfer capacity is reduced in high hydration levels. We believe this study can broaden the design basis of high temperature polymer electrolyte membranes.

The exceptional attachment ability of the ectoparasitic bee louse Braula coeca (Diptera, Braulidae) on the honeybee

AbstractBee lice (Braulidae) are small parasitic flies, which are adapted to live on their bee host. As such, the wingless Braula coeca is a parasite of the common honey bee Apis mellifera and it is well adapted to attach to its hairy surface. The attachment system of B. coeca provides a secure grip on the fine setae of the bee. This is crucial for the parasite survival, as detachment from the host is fatal for the bee louse. The feet morphology of B. coeca is well adapted to the challenging bee surface, notably by strongly broadened claws, which are split into a high number of comb‐like teeth, perfectly matching the diameter of the bee hairs. Based on microscopy observations, both the morphology and material composition of the tarsi of B. coeca are characterized in detail. Using high‐speed video analysis, we combine the morphology data on the attachment system with a behavioural context. Furthermore, we directly measured the attachment forces generated by the bee lice in contact with the host. In particular, the claws are involved in attachment to the host, as the interstices between the teeth‐like spines allow for the collection of several hairs and generate strong friction, when the hairs slip to the narrow gap between the spines. The overall morphology of the tarsus produces strong attachment, with average safety factors (force per body weight) around 1130, and stabilizes the tarsal chain with lateral stoppers against overflexion, but also allows for the fast detachment by the tarsal chain torsion.

Aspartate: An interesting model for analyzing dipole-ion and ion pair interactions through its oppositely charged amine and acid groups.

Anionic species of aspartic acid, Asp- , having a zwitterionic backbone and a deprotonated side chain, appears to be a good example for analyzing dipole-ion and ion pair interactions. Density functional theory calculations were herein performed to investigate the low energy conformers of Asp- embedded in a dielectric continuum modeling an aqueous environment, through a scan of the potential energy as a function of the side chain (χ1 , χ2 ) torsion angles. The most energetically favorable conformers having g+ g- and g- g+ side chain orientations are found to be stabilized by charge-enhanced intramolecular H-bonding involving the positively charged ( ) and the two negatively charged (COO- ) groups. These conformers were further used to analyze Asp- + nW clusters (W: water, n = 1 or 3), and Asp- /Asp- pair formation. COO- groups were found to be the most attractive sites for hosting a water molecule (binding energy: -6.0 ± 1.5 kcal/mol), compared to groups (binding energy: -4.7 ± 1.1 kcal/mol). Energy separation between g+ g- and g- g+ conformers increases upon explicit hydration. Asp- /Asp- ion pairs, stabilized by the interaction between the group of a partner and the COO- group of the other, shows a quite constant binding energy (-8.1 ± 0.2 kcal/mol), whatever the pair type, and the relative orientation of the two interacting partners. This study suggests a first step to achieve a more realistic image of intermolecular interactions in aqueous environment, especially upon increasing concentration. It can also be considered as a preliminary attempt to assess the interactions of the Lys+ …Asp- /Glu- ion pairs stabilizing intra- and interchain interactions in proteins.

Characterization of (Boc-Cys/Sec-NHMe)2 and (Boc-Cys/Sec-OMe)2 : Evidence of local conformational difference between disulfide and diselenide.

Conformations of disulfide and diselenide were compared in (Boc-Cys/Sec-NHMe)2 and (Boc-Cys/Sec-OMe)2 using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, density functional theory (DFT), and circular dichroism (CD) spectroscopy. Conformations of disulfide/diselenide in polypeptides are defined based on the sign of side chain torsion angle χ3 (-CH2 -S/Se-S/Se-CH2 -); negative indicates left-handed and positive indicates right-handed orientation. In the crystals of (Boc-Cys-OMe)2 and (Boc-Sec-OMe)2 , the disulfide exhibits a left-handed and the diselenide a right-handed orientation. Characterization of cystine and selenocystine derivatives in solution using 1 H-NMR, natural abundant 77 Se NMR, 2D-ROESY, and chemical shift analysis coupled to DMSO titration has indicated the symmetrical nature and antiparallel orientation of Cys/Sec residues about the disulfide/diselenide bridges. Structural calculations of cystine and selenocystine derivatives using DFT further support the antiparallel orientation of Cys/Sec residues about disulfide/diselenide. The far-ultraviolet (UV) region CD spectra of cystine and selenocystine derivatives have exhibited the negative Cotton effect (CE) for disulfide and positive for diselenide confirming the difference in the conformational preference of disulfide and diselenide. In the previously reported polymorphic structure of (Boc-Sec-OMe)2 , the diselenide has right-handed orientation. In the X-ray structures of disulfide and diselenide analogues of Escherichia coli protein encoded by curli specific gene C (CgsC) retrieved from Protein Databank (PDB), disulfide has left-handed and the diselenide right-handed orientation. The current report provides the evidence for the local conformational difference between a disulfide and a diselenide group under unconstrained conditions, which may be useful for the rational replacement of disulfide by diselenide in polypeptide chains.

Side chain torsion dictates planarity and ionizability of green fluorescent protein’s chromophore leading to spectral perturbations

Spectral characteristics of fluorescent proteins (FPs) are well studied, and through protein engineering, several FP variants constituting entire visible spectrum have been created. One of the most common mechanisms attributed to spectral shifts in FP is excited state proton transfer (ESPT), hydroxyl moiety protonation and deprotonation, along with chromophore cis–trans isomerism. The most widely studied FPs are those derived from avGFP (Aequorea victoria GFP) and Dsred (Discosoma coral). Apart from the above mechanism, certain interacting residues are said to play a vital role in altering the proton transfer pathway leading to numerous spectral variants. Similarly, the hydrogen-bonded networks solely cannot dictate the energy landscape of FPs. Non-bonded interactions also can create secondary harmonic shifts by dipole–dipole inductions. Side chain contacts tend to alter the topological and torsional geometry, thereby disturbing the chromophore’s planarity. Side chain torsional variations have almost been unaccounted for their distortions in FPs. We hypothesize the torsional landscape and altered residual interactions as prominent factors for the spectral shifts. Through our 200 ns molecular dynamics investigation, we prospect that van der Waals packing in Dsred is more compact than that of avGFP, thus creating a low solvent occupiable environment and reduced solvent interactions having higher red spectral shift. The torsional changes of wild avGFP, S65T avGFP and Dsred have been studied to comprehend the inter-residual contact distance and the geometrical descriptors.Communicated by Ramaswamy H. Sarma

Features of spectrum of frequencies of torsional oscillations transmissions of machines

The issue of the strength of machines and mechanisms with intense dynamic loads is given priority. These are different in design, construction, loading conditions of the machine: energy, self-propelled, agricultural, auto and industrial tractors, diesel locomotives, transport and others. They are united by the presence of a powerful source of periodic loads in a wide range of frequencies, the presence of a relatively flexible transmission (crankshafts, elastic couplings, cardan shafts, fusible housing, etc.), the similarity of the nature of dynamic processes, the similarity of research methods. These are machines and constructions that should be considered as the only dynamic system. The theoretical basis and methods of calculations of motor-transmission systems for free and forced oscillations are elaborated in detail. An important step in the study of dynamic processes begins with the idealized reduced equivalent scheme, built on the principle of sampling of inertial and elastic characteristics. Investigation of torsional oscillations in such systems is obligatory. An important part of this analysis is the calculation of the spectrum of eigenfrequencies and forms of oscillation of a multi-mass equivalent transmission scheme. The paper deals with the definition and analysis of the characteristics of the spectrum of frequencies and forms of oscillations of power transmission of transmission machines. For numerical experiments, a 12-mass chain torsion circuit of a typical power transmission of a tractor was selected. Inertia characteristics of the engine, transmission, gearboxes, wheels and others are taken into account. elasticity of the crankshaft, couplings, and others. The approaches to simplify the dynamic model are discussed. It is shown that the spectrum is sufficiently dense; appearance of expected pairs of almost multiple frequencies; some forms of oscillations have a pronounced partial character. The influence on the frequency spectrum of the reduction of the order of equations by combining certain masses is also considered.

Molecular Mechanic Studies on the Zwitterionic and Neutral Conformation Stability of Biological Active Peptide

In this current work the conformational properties of the L-Alanyl-L-Glutamine dipeptide which was biological active dipeptide has been investigated by theoretical conformational analysis method using program which is based on Molecular Mechanic calculations in order to determine the structure function relation. The calculations on zwitterionic and neutral form of Ala-Gln which is formed side and main chain torsion angles let us to define their preferable energetically conformers. The side and main chain status of the stable conformations of Ala-Gln were acquired based on the results of the conformational analysis. By using Ramachandran maps, the global conformation, which has the lowest energy of the dipeptide, has been determined. The goal of this work was to explain structure-activity relationship by investigating the bioactive conformation of biological active peptide.

Vibrational spectroscopic and structural investigations of bioactive molecule Glycyl-Tyrosine (Gly-Tyr)

This study investigated the conformational behavior of biological active molecule Glycyl-Tyrosine (Gly-Tyr) dipeptide and its dimers, by Boltzmann jump and DFT calculations. The energy calculations on Gly-Tyr dipeptide as a function of side chain torsion angles enabled us to determine the preferred conformations. The most stable conformations obtained from the above process were further optimized by the DFT calculations. The geometry optimization and vibrational wavenumbers calculations of Gly-Tyr dipeptide were carried out with the Gaussian03 program by using density functional theory (DFT) with B3LYP functional and 6-31++G (d,p) basis set. The dimeric forms of the dipeptide were also formed and energetically preferred conformations of dimers were investigated using the same method and the same basis set. The results provided a good account of the role of the number and type of inter- or/and intra-molecular H-bond interactions existing in the dimer and monomer forms of the dipeptides. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of monomeric and dimeric forms of the dipeptide were calculated and compared with the experimental vibrational spectra of solid Gly-Tyr dipeptide. Vibrational assignment of the molecule was done using the potential energy distribution analysis. HOMO-LUMO energy has been used to elucidate the reasons for intra molecular charge transfer.

Privileged hydration sites in aromatic side chains: effect on conformational equilibrium.

Water interaction with peptide chains is one of the key structure stabilizing factors in an aqueous environment. Because of its strong polar character, water can bind to both anionic and cationic sites via electrostatic interactions. It can also act as a hydrogen-bond donor or acceptor according to its interactions with different polar groups in the backbone and side chains of peptides and proteins. Based on density functional theory calculations, the present report aims at illustrating the most energetically favorable interaction sites of aromatic side chains of phenylalanine, tyrosine, tryptophan, and histidine (neutral and protonated species) with surrounding water molecules. It was shown that beyond the strong interactions occurring between water and the aromatic ring acceptor/donor sites, such as O-H, N-H and -N[double bond, length as m-dash] groups, weaker interactions with π-electron clouds should also be considered. The latter type of binding, hereafter referred to as Hwπ interaction, involves one of the water hydrogen atoms (Hw) pointing toward the aromatic ring. Upon comparison between the theoretical data obtained from a purely implicit hydration model, i.e. a polarized solvent continuum, and those collected from a mixture of implicit and explicit hydration models, it has been shown that the explicit water molecule binding to aromatic rings affects the relative energies of the rotamers generated by the two side chain torsion angles (χ1 and χ2).

The role of the backbone torsion in protein folding

BackgroundThe set of forces and sequence of events that govern the transition from an unfolded polypeptide chain to a functional protein with correct spatial structure remain incompletely known, despite the importance of the problem and decades of theory development, computer simulations, and laboratory experiments. Information about the correctly folded state of most proteins is likely to be present in their sequences, and yet many proteins fail to attain native structure after overexpression in a non-native environment or upon experimental denaturation and refolding.Presentation of the hypothesisWe hypothesize that correct protein folding in vivo is an active, energy-dependent process that most likely applies torque force co-translationally to all proteins and possibly also post-translationally to many proteins in every cell. When a site on an unfolded polypeptide is rotationally constrained, torsion applied at another site would induce twisting of the main chain, which would initiate the formation of a local secondary structure, such as an alpha-helical turn or a beta-turn/beta-hairpin. The nucleation of structural elements is a rate-limiting, energetically unfavorable step in the process of protein folding, and energy-dependent chain torsion is likely to help overcome this barrier in vivo. Several molecular machines in a cell, primarily ribosomes, but also possibly signal recognition particles and chaperone systems, may play a role in applying torque to an unfolded protein chain, using the energy of GTP or ATP hydrolysis. Lack of such force in the in vitro systems may be the main reason of the failure of many longer proteins to attain the correct functional conformation.Testing the hypothesisThe hypothesis can be tested using single-molecule approaches, by measuring directly the forces applied to polypeptide chains under controlled conditions in vitro, and in bulk, by assessing folding rates and extent of misfolding in proteins that are engineered to experience transient spatial constraint during their synthesis.Implications of the hypothesisLearning about the role of main chain torsion in protein folding will improve our understanding of folding mechanisms and may lead to bioengineering solutions that would enhance the yields of correctly folded proteins in heterologous expression systems.ReviewersThis article was reviewed by Frank Eisenhaber, Igor Berezovsky and Michael Gromiha.

Characterization of Aqueous Oleic Acid/Oleate Dispersions by Fluorescent Probes and Raman Spectroscopy.

Oleic acid (OA) and oleates form self-assembled structures dispersible in aqueous media. Herein, the physicochemical properties of OA/oleate assemblies were characterized using fluorescent probes and Raman spectroscopy, under relatively high dilution (<100 mM of total amphiphile) at 25 °C. Anisotropy analysis using 1,6-diphenyl-1,3,5-hexatriene showed that the microviscosity of the OA/oleate assembly was highest at pH 7.5 (the pH range of 6.9-10.6 was investigated). The fluorescence spectra of 6-lauroyl-2-dimethylaminonaphthalene revealed the dehydrated environments on membrane surfaces at pH < 7.7. The pH-dependent Raman peak intensity ratios, chain torsion (S = I1124/I1096) and chain packing (R = I2850/I2930), showed local maxima, indicating the occurrence of metastable phases, such as dispersed cubic phase (pH = 7.5), vesicle (pH = 8.5), and dispersed cylindrical micelle (pH = 9.7). These results suggest that large-scale OA/oleate assemblies could possess particular membrane properties in a narrow pH region, e.g., at pH 7.5, and 9.7.

TMalphaDB and TMbetaDB: web servers to study the structural role of sequence motifs in α-helix and β-barrel domains of membrane proteins.

BackgroundMembrane proteins represent over 25 % of human protein genes and account for more than 60 % of drug targets due to their accessibility from the extracellular environment. The increasing number of available crystal structures of these proteins in the Protein Data Bank permits an initial estimation of their structural properties.DescriptionWe have developed two web servers—TMalphaDB for α-helix bundles and TMbetaDB for β-barrels—to analyse the growing repertoire of available crystal structures of membrane proteins. TMalphaDB and TMbetaDB permit to search for these specific sequence motifs in a non-redundant structure database of transmembrane segments and quantify structural parameters such as ϕ and ψ backbone dihedral angles, χ1 side chain torsion angle, unit bend and unit twist.ConclusionsThe structural information offered by TMalphaDB and TMbetaDB permits to quantify structural distortions induced by specific sequence motifs, and to elucidate their role in the 3D structure. This specific structural information has direct implications in homology modeling of the growing sequences of membrane proteins lacking experimental structure. TMalphaDB and TMbetaDB are freely available at http://lmc.uab.cat/TMalphaDB and http://lmc.uab.cat/TMbetaDB.

Correct folding of an α-helix and a β-hairpin using a polarized 2D torsional potential.

A new modification to the AMBER force field that incorporates the coupled two-dimensional main chain torsion energy has been evaluated for the balanced representation of secondary structures. In this modified AMBER force field (AMBER032D), the main chain torsion energy is represented by 2-dimensional Fourier expansions with parameters fitted to the potential energy surface generated by high-level quantum mechanical calculations of small peptides in solution. Molecular dynamics simulations are performed to study the folding of two model peptides adopting either α-helix or β-hairpin structures. Both peptides are successfully folded into their native structures using an AMBER032D force field with the implementation of a polarization scheme (AMBER032Dp). For comparison, simulations using a standard AMBER03 force field with and without polarization, as well as AMBER032D without polarization, fail to fold both peptides successfully. The correction to secondary structure propensity in the AMBER03 force field and the polarization effect are critical to folding Trpzip2; without these factors, a helical structure is obtained. This study strongly suggests that this new force field is capable of providing a more balanced preference for helical and extended conformations. The electrostatic polarization effect is shown to be indispensable to the growth of secondary structures.

Coupled two-dimensional main-chain torsional potential for protein dynamics II: performance and validation.

The accuracy of force fields is of utmost importance in molecular modeling of proteins. Despite successful applications of force fields for about the past 30 years, some inherent flaws lying in force fields, such as biased secondary propensities and fixed atomic charges, have been observed in different aspects of biomolecular research; hence, a correction to current force fields is desirable. Because of the simplified functional form and the limited number of parameters for main chain torsion (MCT) in traditional force fields, it is not easy to propose an exquisite force field that is well-balanced among various conformations. Recently, AMBER-compatible force fields with coupled MCT term have been proposed, which show some improvement over AMBER03 and AMBER99SB force fields. In this work, further calibration of the torsional parameters has been conducted by changing the solvation model in quantum mechanical calculation and minimizing the deviation from the nuclear magnetic resonance experiments for some benchmark model systems and a folded protein. The results show that the revised force fields give excellent agreement with experiments in J coupling, chemical shifts, and secondary structure populations. In addition, the polarization effect is found to be crucial for the systems with ordered secondary structures.

A Coupled Two-Dimensional Main Chain Torsional Potential for Protein Dynamics

A new AMBER compatible force field is proposed for balanced representation of secondary structures. In this modified AMBER force field (AMBER2D), the main chain torsion energy is represented by 2-dimensional Fourier expansions with parameters fitted to the potential energy surface generated by quantum mechanical calculations of small peptides in solution at M06 2X/aug-cc-pvtz//HF/6-31G∗∗ level. Solvation model based on solute electron density (SMD) developed in Truhlar's group was considered. The benchmark systems used in the validation of this force field include capped dipeptides (Ace-X-NME, XP), tripeptides (XXX, XA, G, V}; GYG, Y {A, V, F, L, S, E, K, M}), alanine tetrapeptide, Ac-(AAQAA)3 -NH2, and ubiquitin. Besides, we also investigate the folding of two representative proteins (PDB ID 2I9M and 1LE1). The results demonstrated that this 2D main chain torsion is effective in delineating the energy variation associated with main chain torsions. Furthermore, the electrostatic polarization effect is very important for long peptides or proteins. This work also serves as an implication for the necessity of more accurate functional forms for main chain torsions in the future development of force field.

Fast Atomic Charge Calculation for Implementation into a Polarizable Force Field and Application to an Ion Channel Protein

Polarization of atoms plays a substantial role in molecular interactions. Class I and II force fields mostly calculate with fixed atomic charges which can cause inadequate descriptions for highly charged molecules, for example, ion channels or metalloproteins. Changes in charge distributions can be included into molecular mechanics calculations by various methods. Here, we present a very fast computational quantum mechanical method, the Bond Polarization Theory (BPT). Atomic charges are obtained via a charge calculation method that depend on the 3D structure of the system in a similar way as atomic charges ofab initiocalculations. Different methods of population analysis and charge calculation methods and their dependence on the basis set were investigated. A refined parameterization yielded excellent correlation ofR=0.9967. The method was implemented in the force field COSMOS-NMR and applied to the histidine-tryptophan-complex of the transmembrane domain of the M2 protein channel of influenza A virus. Our calculations show that moderate changes of side chain torsion angleχ1and small variations ofχ2of Trp-41 are necessary to switch from the inactivated into the activated state; and a rough two-side jump model of His-37 is supported for proton gating in accordance with a flipping mechanism.

Ring- and side-group conformational properties of di-O-acylated xylopyranosides: A computational study

The conformational properties (4C1, 1C4, and skew ring structures, side chain torsion) of methyl 2,4- (1) and 3,4-O-diacetyl (2) as well as 2,4- (3) and 3,4-O-dibenzoyl (4)-ß-D-xylopyranoside are calculated by dispersion-corrected density functional theory (B3LYP-D3) and LPNO–CEPA/1-def2-TZVPP. Derivatives with acyl groups in positions 2 and 4 (1 and 3) prefer the 1C4 chair conformation of the pyranose chair; 3,4-di-O-acyl compounds 2 and 4 show nearly equal or even dominating amounts of the 4C1 chair. Intramolecular hydrogen bonding of the type O3H⋯O1 (1 and 3) and O2H⋯O4 are characteristic for the lowest energy conformations of 1C4 chairs. With increasing solvent polarity a shift towards 4C1 chair structures is calculated. B3LYP-D3 conformer populations show fairly good agreement with CEPA/1 results (R2=0.992).