4C1 Conformation Research Articles

Cycloparaphenylene Möbius trefoils.

DFT computations (ωB97X-D/6-31G(d)) of eight different cycloparaphenylenes that have three internal linking groups are shown to have two different conformations that express interesting Möbius topologies. The D3 conformers have linking numbers Lk of 3 (three half-twists as a trefoil), and the much more stable C2 conformers have a single half-twist, Lk = 1.

Quantum Chemical Relationship between Generalized Anomeric Effect and Thermodynamic Parameters in M2Cl2 (M = O, S, Se)

Compounds such as dioxygen dichloride (1), disulfur dichloride (2), and diselenium dichloride (3) have been investigated using LC-BLYP, LC-ωPBE and B3LYP with aug-cc-pVmZ basis set (m: 2, 3, 4). Natural Bond Orbital (NBO) analysis has been performed on skew (C2), trans (C2h) and cis (C2v) conformations. The results indicated that the resonance energy associated with electron delocalization in molecules 1 to 3 in C2 conformation is 13.75, 22.76, and 17.99 kcal/mol, respectively, and is directly related to the off-diagonal elements (Fij). In addition, the Generalized Anomeric Effect (GAE) associated with electron delocalization is increased from molecules 1 to 2 and decreased from molecules 2 to 3.

Multiple conformations facilitate PilT function in the type IV pilus

Type IV pilus-like systems are protein complexes that polymerize pilin fibres. They are critical for virulence in many bacterial pathogens. Pilin polymerization and depolymerization are powered by motor ATPases of the PilT/VirB11-like family. This family is thought to operate with C2 symmetry; however, most of these ATPases crystallize with either C3 or C6 symmetric conformations. The relevance of these conformations is unclear. Here, we determine the X-ray structures of PilT in four unique conformations and use these structures to classify the conformation of available PilT/VirB11-like family member structures. Single particle electron cryomicroscopy (cryoEM) structures of PilT reveal condition-dependent preferences for C2,C3, and C6 conformations. The physiologic importance of these conformations is validated by coevolution analysis and functional studies of point mutants, identifying a rare gain-of-function mutation that favours the C2 conformation. With these data, we propose a comprehensive model of PilT function with broad implications for PilT/VirB11-like family members.

The antioxidant activities of balsam pear polysaccharide

The antioxidant activities of polysaccharide from balsam pear were studied. It was determined by gel permeation chromatography that the molecular weight distribution of purified polysaccharide was concentrated near 33582 Da. It indicated that the monosaccharide components were rhamnose, galacturonic acid, galactose, xylose and arabinose. Fourier transform infrared spectroscopy, nuclear magnetic resonance and Congo red experiments showed that there are C1, C2, C3, C5 links, and stable β-triple helix conformation in aqueous solution. It was found that polysaccharide had good scavenging effect on free radicals. So, balsam pear polysaccharide should be a potential antioxidant.

Experimental and DFT studies on 2′,4′-dihydroxychalcone, a product isolated from Zuccagnia punctata Cav. (Fabaceae) medicinal plant

Abstract Here, 2′,4′-dihydroxychalcone (DHC) has been isolated from Zuccagnia punctata Cav. (Fabaceae) medicinal plant and, after that, the FT-IR, UV–Visible, 1H and 13C NMR spectroscopies were combined with the hybrid B3LYP/6–311++G** method to characterize this species. Structural, electronic, topological and vibrational properties of two conformers of DHC in gas phase and in aqueous and in ethanol solutions at the same level of theory were investigated. The most stable C2 conformer of DHC shows an intra-molecular O–H⋯O bond, as observed in the experimental structure reported for DHC by using X-ray diffraction. Force fields for both conformers of DHC in the three media at the same level of theory and their complete vibrational assignments of expected 84 vibration modes are reported for first time. The calculations predicted in the IR spectrum of C2 notable shifting of O–H and C O stretching modes due to intra-molecular H bonds formed. Corrected solvation energy of C1 in water and ethanol are respectively of −101.86 and −94.93 kJ/mol while the values for C2 decrease to −81.06 and −75.85 kJ/mol, respectively. Hence, both forms clearly evidence the higher solubility of DHC in water. The evaluation of molecular electrostatic potentials (MEP) surfaces have suggested that nucleophilic and electrophilic sites of higher reactivity in C1 and C2 of DHC are strongly located on the C O and OH groups while the frontier orbital studies reveal that DHC in the three media are most reactive than other species isolated from plants. The two forms of DHC could be present in solid phase and in solutions, as supported by two bands observed in the UV–Visible spectra of DHC in methanol solution.

Synthesis and Structure of a Strained, Cyclic meta‐Quaterphenylene Acetylene

A strained, cyclic hydrocarbon comprising a meta‐quaterphenyl‐based arc that is clamped by an alkyne tether was synthesized via Yamamoto coupling of a dichloro precursor. DFT calculations (B3LYP/6‐31G*) indicate that the lowest‐energy ground state adopts a twisted, C2 conformation that bears 19.0 kcal/mol of strain energy. X‐ray crystallographic analysis confirms that, in the solid state, the molecule adopts a twisted structure that is similar to the calculated C2 conformation. Exposure of the ortho‐linked dichloro precursor to Yamamoto conditions generates 9,9′‐bisfluorenylidene in high yield.

Conformational Itinerary of Sucrose During Hydrolysis by Retaining Amylosucrase.

By means of QM(DFT)/MM metadynamics we have unraveled the hydrolytic reaction mechanism of Neisseria polysaccharea amylosucrase (NpAS), a member of GH13 family. Our results provide an atomistic picture of the active site reorganization along the catalytic double-displacement reaction, clarifying whether the glycosyl-enzyme reaction intermediate features an α-glucosyl unit in an undistorted 4C1 conformation, as inferred from structural studies, or a distorted 1S3-like conformation, as expected from mechanistic analysis of glycoside hydrolases (GHs). We show that, even though the first step of the reaction (glycosylation) results in a 4C1 conformation, the α-glucosyl unit undergoes an easy conformational change toward a distorted conformation as the active site preorganizes for the forthcoming reaction step (deglycosylation), in which an acceptor molecule, i.e., a water molecule for the hydrolytic reaction, performs a nucleophilic attack on the anomeric carbon. The two conformations (4C1 ad E3) can be viewed as two different states of the glycosyl-enzyme intermediate (GEI), but only the E3 state is preactivated for catalysis. These results are consistent with the general conformational itinerary observed for α-glucosidases.

Stereoselective β-Mannosylation with 2,6-Lactone-bridged Thiomannosyl Donor by Remote Acyl Group Participation.

Stereoselective β-mannosylation has been recognized as one of the greatest challenges of carbohydrate chemistry. Herein, we described a practical method for stereoselective construction of β-mannosides by using a 2,6-lactone-bridged thiomannosyl donor through the remote acyl-group participation as well as the steric effect of O-4 substituent. The two effects are enabled through the conversion of a regular mannopyranosyl 4 C1 conformation into a 2,6-lactone bridged conformation. The lactone donor could be readily prepared in three steps on a gram scale and the β-mannosylation proceeded smoothly with high stereoselectivity for primary, secondary and tertiary alcohol acceptors. In addition, this strategy was successfully applied to the synthesis of a naturally occurring trisaccharide.

2.2.2.2](2,7)‐1‐Bromonaphthalenophane from a Desymmetrized Building Block Bearing Electrophilic and Masked Nucleophilic Functionalities

AbstractIn search of 2,7‐ethylene‐bridged naphthalenophanes with desymmetrized naphthalene cores as inherently chiral cyclophanes, nucleophilic substitution of 1‐bromo‐7‐(bromomethyl)‐2‐[(trimethylsilyl)methyl]naphthalene, a desymmetrized building block bearing an electrophilic group (CH2Br) and a masked nucleophilic functionality (CH2TMS) which can be activated by fluoride anion, was examined. As a result, in contrast to the case of parent naphthalenophanes wherein the smallest [2.2]naphthalenophane was obtained as the major product, only [2.2.2.2](2,7)‐1‐bromonaphthalenophane was obtained albeit in low yields, whereas the corresponding [2.2]‐ or [2.2.2]naphthalenophanes were not obtained. Though the [2.2.2.2]‐1‐bromonaphthalenophane can adopt four idealized geometries of different symmetry, among which three are inherently chiral, theoretical calculations predict that three conformers have almost equal energy and may equilibrate in solution. The X‐ray crystallographic study shows that it adopts a C2 conformation with anti,anti,anti orientation of the C−Br bonds at least as a major component in crystal.

Multiple glass transitions in vapor-deposited orientational glasses of the most fragile plastic crystal Freon 113.

We investigate by fast-scanning nanocalorimetry the formation of Freon 113 films from the vapor phase at deposition temperatures ranging from 50 to 120 K, that is, spanning above and below the transition temperature of the glassy crystal to the plastic crystal (Tgc = 72 K). Analysis of the heat capacity curves indicates that vapor deposition at T < Tgc of the highly fragile Freon 113 yields structural and orientational glasses in the as-deposited state depending on the temperature range of deposition. Interestingly, growing above Tgc produces plastic crystals with a conformational ratio C1/Cs that changes with Tdep above and below 110-120 K, the temperature at which previous works have identified the arrest of the transformations between the C1 and Cs conformers.

Synthesis and Characterization of New Isatin Nucleosides

In this research, a series of new nucleoside analogues 25–36 of substituted isatin as nucleobase were synthesized in three steps. The reaction sequence is started from the condensation of free sugar (D-glucose and L-rhamnose) with different anilines to afford the N-arylglycosylamines 1–12 which subsequently O-acetylated in the presence of acetic anhydride/pyridine. The resulting acetylated N-arylglycosylamines 13–24 were then subjected to an intramolecular cyclization with oxalyl chloride in the presence of anhydrous aluminum chloride to yield the target isatin nucleosides. The synthesized compounds were characterized by the FTIR, 1H-NMR and13 C-NMR spectroscopy. The stereochemistry was established based on the coupling constants observed between vicinal hydrogens of the glycon that confirmed the β-configuration of the synthesized nucleosides with a 4C1 conformation of the glucosides and a 1C4 conformation of the rhamnosides.

Synthesis, spectroscopic and antimicrobial studies of some simple thiomorpholideSchiff`s base congeners

A set of eight thiomorpholide-hydrazone conjugates 6a-g and 7 was prepared in good yield by sequential Willgerodt-Kindler reaction on 4-aminoacetophenone then condensation with the considered aromatic aldehydes. The molecular fragmentation of these conjugates by EIMS was interpreted. Structure elucidation of these derivatives was further studied using 1H NMR, COSY, 13C NMR, Dept135 and HSQC techniques. The preferred conformation of the morpholine ring was assigned as the 4C1 conformation. The COSY spectrum of compound 6c showed abnormal deshielding of the N(CH2)2 over the O(CH2)2 protons which was explained. In vitroantimicrobial screening of these congeners with standard antibiotics disclosed their moderate activity against E. coli, S. aureus and C. albicans.

Synthesis of 5a,5a'-dicarba-d-glucobioses from conformationally restricted carbaglucosyl triflates using SN2-type inversion with carbaglucosyl nucleophiles.

Novel carbohydrate mimics were designed which contain two 5a-carba-d-glucose residues, one each at reducing and nonreducing end, and thus these mimics are 5a,5a'-dicarba-d-glucobioses. Dicarbadisaccharides have attractive features such as stability against endogenous degradative enzymes and being resistant to glycation reactions such as the Maillard reaction. For the synthesis of dicarba-β-d-isomaltose derivatives, the carbaglucosyl triflate locked in 4C1 conformation was synthesized by protecting with butane-2,3-diacetal group or benzylidene group. Then, 5a,5a'-dicarba-β-d-maltose and 5a,5a'-dicarba-α,β-d-trehalose were synthesized by the SN2-type inversion reaction using 4,6-O-benzylidene carbaglucosyl triflate with 4-OH and 1-OH carba-β-d-glucose derivatives, respectively, and similarly 5a,5a'-dicarba-α-d-isomaltose with 6-OH carba-α-d-glucose derivative.

Spectroscopic and theoretical studies of some 2‑(methoxy)‑2‑[(4‑substituted)‑phenylsulfanyl]‑(4'‑substituted) acetophenones.

The conformational analysis of some 2‑(methoxy)‑2‑[(4‑substituted)‑phenylsulfanyl]‑(4'‑substituted) acetophenones was performed through infrared (IR) spectroscopic analysis of the carbonyl stretching band (νCO), supported by B3LYP/6-31+G(d,p) calculations and X-ray diffraction. Five (1-5) of the seven studied compounds (1-7) presented Fermi resonance (FR) on the νCO fundamental transition band. Deuteration of these compounds (1a-5a) precluded the occurrence of FR, revealing a νCO doublet for all compounds in all solvents used. The computational results indicated the existence of three conformers (c1, c2 and c3) for the whole series whose relative abundances varied with solvent permittivity. The higher νCO frequency c1 conformer was assigned to the higher frequency component of the carbonyl doublet, while both c2 and c3 were assigned to the lower frequency one. Anharmonic vibrational frequencies and Potential Energy Distribution (PED) calculations of compound 3 indicated that the combination band (cb) between the methyne δCH and one skeletal mode couples with the νCO mode giving rise to the FR on the c2 conformer in vacuum and on the c1 one in non-polar solvents. The experimental data indicated a progressive increase in c1 conformer stability with the increase of the solvent dielectric constant, which is in good agreement with the polarizable continuum model (PCM) calculations. The higher νCO frequency and the stronger solvation of the c1 conformer is a consequence of the repulsive field effect (RFE) originated by the alignment and closeness of the Cδ+Oδ- and Cδ+Oδ- dipoles. Finally, the balance between orbital and electrostatic interactions dictates the conformational preferences. X-ray single crystal analysis for compound 6 revealed the c1 geometry in the solid state and its stabilization by CH…O hydrogen bonds.

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

The replacement of hydroxyl groups by fluorine atoms on hexopyranose scaffolds may allow access to the discovery of new chemical entities possessing unique physical, chemical and ultimately even biological properties. The prospect of significant effects generated by such multiple and controlled substitutions encouraged us to develop diverse synthetic routes towards the stereoselective synthesis of polyfluorinated hexopyranoses, six of which are unprecedented. Hence, we report the synthesis of heavily fluorinated galactose, glucose, mannose, talose, allose, fucose, and galacturonic acid methyl ester using a Chiron approach from inexpensive levoglucosan. Structural analysis of single-crystal X-ray diffractions and NMR studies confirm the conservation of favored 4C1 conformation for fluorinated carbohydrate analogs, while a slightly distorted conformation due to repulsive 1,3-diaxial F···F interaction is observed for the trifluorinated talose derivative. Finally, the relative stereochemistry of multi-vicinal fluorine atoms has a strong effect on the lipophilicities (logP).

Spectroscopic (FT-IR, Laser-Raman and NMR) and conformational analysis on novel pyrazole β-keto ester compound

Our goal in this study is to submit a comprehensive theoretical study of novel compound. Therefore, we perused and analyzed the experimental (real form) and theoretical (gas form) vibrational frequencies for the most stable conformer of title compound. The crystallographic geometry was used for full geometry optimization, followed by a conformational analysis. The experimental FT-IR and Laser-Raman spectra of the studied molecule were taken in the region (4000-400 cm−1) and (4000-100 cm−1) in gas phase, respectively. For the most stable conformer, the vibrational modes and their assignments and optimized structure parameters (bond lengths, bond angles) were computed by using DFT/B3LYP functional and 6-311++G(d,p) basis set. Gaussian 09W software and GaussView5 interface programs were utilized for all computations. Theoretical mode assignments of the most stable conformer were obtained by using potential energy distribution (PED) with free VEDA 4 software program. The observed FT-IR and Laser-Raman spectra were compared with the calculated theoretical data. The computed vibrational frequencies of C1 conformer were also found in good agreement with the experimental results. The Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) analysis divulge the possibility of charge transfer within the molecule. The proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) chemical shifts were researched for the most stable conformer C1, both experimentally in DMSO-d6 and theoretically in DMSO with integral equation formalism polarizable continuum model (IEFPCM) method.

Influence of inert matrixes on the conformational switching of trimethyl phosphate at low temperatures through thermal effects

The conformational switching of trimethyl phosphate (TMP) in Ne, Ar, Kr and Xe matrixes was studied using infrared spectroscopy under isolated conditions at low temperatures. In all the inert matrixes, the vapor phase population of ground state C3(G±G±G±) and the higher energy C1(TG±G±) conformers of TMP is preserved during the initial deposition. However, on annealing the inert Ar/Kr/Xe matrixes, the conformational composition of TMP was irreversibly altered. In Ar and Kr matrixes, an interconversion from ground state C3(G±G±G±) to higher energy C1(TG±G±) conformer was observed whereas Xe presents an interesting variation. In Xe matrix, the higher energy C1(TG±G±) conformer completely depopulated with a concomitant increase in the population of the ground state C3(G±G±G±) conformer. In Ne matrix notably, no conformational interconversion was observed. Computations on the conformers of TMP were performed using B3LYP and M06-2X levels of theory with 6-311++G(d,p) and aug-cc-pVDZ basis sets. The effect of inert matrixes was modeled using Self-Consistent Reaction Field (SCRF) methods.

Combining pure shift and J-edited spectroscopies: A strategy for extracting chemical shifts and scalar couplings from highly crowded proton spectra of oligomeric saccharides.

We report the application of pure shift and J-edited nuclear magnetic resonance spectroscopies to the structural analysis of a protected maltotrioside synthetic intermediate whose crowded 1 H spectrum displays highly crowded regions. The analytical strategy is based on the implementation of J-edited and TOCSY experiments whose resolution is optimized by the use of broadband homonuclear decoupling and selective refocusing techniques, to assign and measure chemical shifts and homonuclear scalar couplings with high accuracy. The resulting data show a high level of complementarity, providing a detailed insight into each subunit of this oligomeric saccharide, even for proton sites whose nuclear magnetic resonance signals strongly overlap. This approach allowed for fully assigning proton chemical shifts and extracting 80% of the 3 JHH couplings that are in excellent agreement with those expected for D-gluco-pyranosyl units in 4 C1 conformations.

Ribocyclophanes A-E, Glycosylated Cyclophanes with Antiproliferative Activity from Two Cultured Terrestrial Cyanobacteria.

The cell extracts of two cultured freshwater Nostoc spp., UIC 10279 and UIC 10366, both from the suburbs of Chicago, showed antiproliferative activity against MDA-MB-231 and MDA-MB-435 cancer cell lines. Bioassay-guided fractionation led to the isolation of five glycosylated cylindrocyclophanes, named ribocyclophanes A-E (1-5) and cylindrocyclophane D (6). The structure determination was carried out by HRESIMS and 1D and 2D NMR analyses and confirmed by single-crystal X-ray crystallography. The structures of ribocyclophanes A-E (1-5) contain a β-d-ribopyranose glycone in the rare 1 C4 conformation. Among isolated compounds, ribocyclophane D (4) showed antiproliferative activity against MDA-MB-435 and MDA-MB-231 cancer cells with an IC50 value of less than 1 μM.

α-D,L-Sorbose

The racemic title compound, C6H12O6, consisting of C-4 epimers of psicose, was crystallized from an aqueous solution of an equimolar mixture of D- and L-sorboses. It was confirmed that D-sorbose (or L-sorbose) formed α-pyranose with a 4 C 1 (or 1 C 4) conformation where the anomer position was designated as carbon-1. The asymmetric unit comprises two crystallographically independent molecules. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming a three-dimensional framework. The unit-cell volume of the title racemic α-D,L-sorbose is 1450.86 (6) Å3 (Z = 8), which is about 41 Å3 smaller than that of twice the amount of chiral α-L-sorbose [V = 745.942 Å3 (Z = 4)].