Equatorial Conformers Research Articles

Molecular Architecture of Salmonella Typhimurium Virus P22 Genome Ejection Machinery

Bacteriophage P22 is a prototypical member of the Podoviridae superfamily. Since its discovery in 1952, P22 has become a paradigm for phage transduction and a model for icosahedral viral capsid assembly. Here, we describe the complete architecture of the P22 tail apparatus (gp1, gp4, gp10, gp9, and gp26) and the potential location and organization of P22 ejection proteins (gp7, gp20, and gp16), determined using cryo-EM localized reconstruction, genetic knockouts, and biochemical analysis. We found that the tail apparatus exists in two equivalent conformations, rotated by ∼6° relative to the capsid. Portal protomers make unique contacts with coat subunits in both conformations, explaining the 12:5 symmetry mismatch. The tail assembles around the hexameric tail hub (gp10), which folds into an interrupted β-propeller characterized by an apical insertion domain. The tail hub connects proximally to the dodecameric portal protein and head-to-tail adapter (gp4), distally to the trimeric tail needle (gp26), and laterally to six trimeric tailspikes (gp9) that attach asymmetrically to gp10 insertion domain. Cryo-EM analysis of P22 mutants lacking the ejection proteins gp7 or gp20 and biochemical analysis of purified recombinant proteins suggest that gp7 and gp20 form a molecular complex associated with the tail apparatus via the portal protein barrel. We identified a putative signal transduction pathway from the tailspike to the tail needle, mediated by three flexible loops in the tail hub, that explains how lipopolysaccharide (LPS) is sufficient to trigger the ejection of the P22 DNA in vitro.

Noninvasive cardiac radioablation for ventricular tachycardia: dosimetric comparison between linear accelerator- and robotic CyberKnife-based radiosurgery systems

BackgroundFew dosimetric comparisons have been published between linear accelerator (LA)-based systems and CyberKnife (CK)-based robotic radiosurgery systems for cardiac radio-ablation in ventricular tachycardia. This study aimed to compare the dosimetry of noninvasive cardiac radio-ablation deliverable on LA with that on CK.MethodsThirteen patients who underwent noninvasive cardiac radio-ablation by LA were included. The prescribed dose was 25 Gy in 1 fraction, and the average planning target volume was 49.8 ± 31.0 cm3 (range, 14.4–93.7 cm3). CK plans were generated for comparison.ResultsBoth the CK and LA plans accomplished appropriate dose coverage and normal tissue sparing. Compared with the LA plans, the CK plans achieved significantly lower gradient indices (3.12 ± 0.71 vs. 3.48 ± 0.55, p = 0.031) and gradient measures (1.00 ± 0.29 cm vs. 1.17 ± 0.29 cm, p < 0.001). They had similar equivalent conformity indices (CK vs. LA: 0.84 ± 0.08 vs. 0.87 ± 0.07, p = 0.093) and maximum doses 2 cm from the planning target volume (PTV) in any direction (CK vs. LA: 50.8 ± 9.9% vs. 53.1 ± 5.3%, p = 0.423). The dosimetric advantages of CK were more prominent in patients with a PTV of ≤ 50 cm3 or a spherical PTV. In patients with a PTV of > 50 cm3 or a non-spherical PTV, the LA and CK plans were similar regarding dosimetric parameters. CK plans involved more beams (232.2 ± 110.8 beams vs. 10.0 ± 1.7 arcs) and longer treatment times (119.2 ± 43.3 min vs. 22.4 ± 1.6 min, p = 0.007).ConclusionsBoth CK and LA are ideal modalities for noninvasive cardiac radio-ablation. Upfront treatment should be considered based on clinical intent.

Anomeric‐Schleyer hyperconjugative interaction as a convenient avenue for aromaticity enhancement of phospholes

AbstractDue to the insufficient interaction of the phosphorus lone pair with the butadiene moiety, the aromaticity of the phosphole ring is lower than that of its counterpart's pyrrole, furan, and thiophene. Considering the high importance of phosphole core in organic chemistry, increasing its stability through reinforcement its aromaticity can be very valuable. In the present work, the aromaticity of the phosphole on the anomeric carbon in both the axial and equatorial conformers of the unsaturated six‐membered heterocycles, using structural, electronic, energetic, and magnetic indices were investigated by the DFT‐B3LYP/6‐311++G(d,p) computational method. Electron pumping through anomeric and then Schleyer hyperconjugative interaction increase the aromaticity of the phosphole ring in axial conformer of compounds 1–11. Based on various types of aromaticity indices, the results showed that the phosphole ring in the axial position has far higher aromaticity than the equatorial position. The phosphole ring containing cyano groups shows an efficient anomeric effect and, as a result, higher aromaticity. Excellent correlations were observed between aromaticity indices with different backgrounds.

Novel insight on aromaticity enhancement of pyridone heterocycles using the anomeric effect-Schleyer hyperconjugation aromaticity: A DFT and NBO study

Considering the value of 2-pyridone and 4-pyridone heterocyclic groups in organic chemistry, in this study, the anomeric effect and Schleyer hyperconjugation aromaticity for the first time have been used to increase the aromaticity of these heterocycles. The anomeric effect in tetrahydropyrans containing 2-pyridone or 4-pyridone ring on the anomeric carbon in axial and equatorial conformers has been investigated using the DFT-B3LYP/6–311++G(d,p) calculation method. On the other hand, the aromaticity of 2-pyridone and 4-pyridone in the considered conformers was investigated by nucleus-independent chemical shift indices (NICS) and the harmonic oscillator model of electron delocalization index (HOMED). The results illustrate that placing 2-pyridone and 4-pyridone in the axial position increases their aromaticity through the anomeric effect. Furthermore, connecting the ring from the carbon atom to the anomeric position is better than the nitrogen atom for aromaticity increment. Aromaticity indices show that the anomeric effect-Schleyer hyperconjugation interaction is more robust in the presence of nitrogen atoms than oxygen or sulfur atom.

Influence of Internal Noncovalent Bonds on Rotational Dynamics.

While a good deal of information has accumulated concerning the manner in which an intramolecular noncovalent bond can affect the relative energies of various conformers, less is known about how such bonds might affect the dynamics of interconversion between them. A series of molecules are constructed in which symmetrically equivalent conformers containing a noncovalent bond can be interconverted by a bond rotation, the energy barrier to which is computed by quantum chemical methods. The rotation of a CF3 group attached to a phenyl ring is speeded up if a Se··F chalcogen bond can be formed with a SeH or SeF group placed in an ortho position, a bond that is present in and stabilizes the rotational transition state. The analogous SnF3 group can, on the other hand, engage in a Sn··Se tetrel bond in its global minimum. The energetic cost of breakage of this bond is not fully compensated by the appearance of a Se··F chalcogen bond in the rotational transition state. Other systems were designed by placing two phenyl rings on opposite ends of an octahedrally disposed SeF4 group. A high barrier inhibits their rotation with bulky Br atoms in ortho positions, but this barrier is lowered if Br is replaced by groups that can engage in either chalcogen (SeH or SeF) or pnicogen (AsH2) bonds with the F atoms in the rotational transition state. The barrier reduction is closely related to the strength of these noncovalent bonds.

N-N(+) Bond-Forming Intramolecular Cyclization of O-Tosyloxy β-Aminopropioamidoximes and Ion Exchange Reaction for the Synthesis of 2-Aminospiropyrazolilammonium Chlorides and Hexafluorophosphates.

Our research area is related to the spiropyrazolinium-containingcompounds, which are insufficiently studied compared with pyrazoline-containing compounds. Nitrogen-containing azoniaspiromolecules have also been well studied. In drug design and other areas, they are a priori important structures, since rigid spirocyclic scaffolds with the reduced conformational entropy are able to organize a closely spaced area. Azoniaspirostructures are currently of wide practical interest as ionic liquids, current sources (membranes), structure-directing agents in organocatalysis, and in the synthesis of ordered ceramics. Our goal was the synthesis of 2-aminospiropyrazolilammonium chlorides and hexafluorophosphates. Our methodology is based on the tosylation of β-aminopropioamidoximes with six-membered N-heterocycles (piperidine, morpholine, thiomorpholine, and phenylpiperazine) at the β-position. 2-Aminospiropyrazolilammonium chlorides and hexafluorophosphates were obtained by the reaction of double ion substitution in the reaction of toluenesulfonates of 2-aminospiropyrazolinium compounds with an ethereal solution of HCl in ethanol and with ammonium hexafluorophosphate in ethanol in quantitative yields of 55-97%. The physicochemical characteristics of the synthesized compounds and their IR and NMR spectra are presented. The obtained salts were additionally characterized by the single-crystal XRD analysis. The presence of both axial and equatorial conformations of spirocations in solids was confirmed. 2-Aminospiropyrazolilammonium chlorides and hexafluorophosphates have weak in vitro antimicrobial activity on Gram-positive and Gram-negative bacterial lines.

The determination of aggregation size on the emulsion properties of myofibrillar protein

Myofibrillar protein (MP) majorly determines the quality of emulsified meat product. Since MP is sensitive to external stresses, it would easily denature and form aggregates during processing. However, for now, how MP aggregates size affects its emulsion properties is still lacking clarification. In this study, large/small-sized MP aggregate-models with similar structural properties were successfully established through pH-shifting treatment. Specifically, the NaOH–HCl/gluconolactone induced MP aggregates were treated as large aggregate (LA) and small aggregate (SA) models, respectively, which were subsequently validated through transmission electron microscopy (sectional size: LA 282.47 nm2 and SA 104.79 nm2), gel-permeation chromatography (aggregate peak proportion: LA 73.75% and SA 66.86%) and dynamic light scattering (mean volume weight diameter: LA 45.33 μm and SA 26.20 μm). Then, the structural properties were measured to confirm the equivalent conformation for both models, which exhibited similar protein profiles and molecular flexibility values, and same changing trend in the secondary structure as well as protein unfolding level. Under similar spatial conformation, aggregate size could be the dominant factor to determine interfacial behaviors and emulsifying properties of protein aggregate. Smaller aggregates of SA may be beneficial for the higher interfacial diffusion and rearrangement rate, and greater ability to reduce interfacial tension compared with those of LA. Therefore, SA had better emulsion properties than LA with higher emulsifying activity and stability, and lower Turbiscan stability index. These aggregate models have implications for the development of healthy emulsified meat products, which is conducive to more precise control of product quality and sensory.

NMR and FT-IR Investigation Study and Topological Analysis of Various Conformations of 2,5-dimethyl-2,5-dihydroxyl-1,4-dithian using Density Functional Theory Method

Abstract: 1,4-dithian-2,5-dihydroxyl is the major source for the synthesis of sulfur-containing heterocyclic compounds such as thiophene and 1,3-thiazole derivatives, which these compounds are widely used in pharmaceuticals and agricultural industries. Sulfur-containing heterocycles, such as 2-aminothiophene, thiazolidine, oxothiazolidine, and thiazoles, can be comprehensively synthesized from dimerization of the derivatives of 1,4-dithian-2,5- dihydroxyl. FT-IR and NMR spectra of axial and equatorial conformations of 2,5-dimethyl-2,5-dihydroxyl-1,4- dithian compound were investigated by density functional theory (DFT) using B3LYP/6-311++G** and M06- 2X/aug-cc-pVDZ computational methods. The topological properties of the electron charge density were calculated by the quantum theory of atoms in molecules (QTAIM) and non-covalent interactions/reduced electron density gradient (NCI-RDG) theoretical methods. The obtained results of the analyses were also discussed in more detail. The results showed that the steric interactions are more prominent than the van der Waals interactions, and in both conformations, steric interactions are included in the middle of the 1,4-dithian ring and there is hydrogen bonding between hydroxyl groups and 1,4-dithian ring structure heteroatoms in the axial conformation while this interaction is not observed in the case of equatorial conformation. The presence of these interactions was confirmed using NBO analysis.

The conformational behavior and structure of monosubstituted 1,3,5‐trisilacyclohexanes—Part III: 1‐Methyl‐1,3,5‐trisilacyclohexane

Abstract1‐Methyl‐1,3,5‐trisilacyclohexane was synthesized and its structure and conformational properties have been determined by gas‐phase electron diffraction (GED) and quantum chemical (QC) calculations. The molecule may exist in two forms differing from each other by the substituent's position. QC results show that the equatorial conformer is predicted to be slightly more stable than the axial conformer; note that one method (M06‐2X) with basis set 6‐311G** shows an equal amount of Ax and Eq conformers: ratio (Ax/Eq) = (30–50):(70–50)% (depending on the method and basis set). From the GED data, the molar fractions of the conformers were found to be Ax:Eq = 54(10):46(10) at 280(5) K. A temperature‐dependent Raman experiment resulted in an Ax:Eq ratio of 58(4):42(4). Conformational properties are compared in series of analogous 1‐X‐1‐(hetero)cyclohexanes.

Syntheses and crystal structures of three salts of 1-(4-nitro-phenyl)-piperazine.

The crystal structures and Hirshfeld surface analyses of three salts of 1-(4-nitro-phenyl)-piperazine with 2-chloro-benzoic acid, 2-bromo-benzoic acid and 2-iodo-benzoic acid are reported. The chloro-benzoate salt, C10H14N3O2 +·C7H4ClO2 -, contains whole-ion-disordered cations and anions, which were modeled with two equivalent conformations with occupancies of 0.745 (10)/0.255 (10) and 0.563 (13)/0.437 (13), respectively. The bromo-benzoate and iodo-benzoate derivatives are isomorphous and crystallize as hemihydrates, viz. C10H14N3O2 +·C7H4BrO2 -·0.5H2O and C10H14N3O2 +·C7H4IO2 -·0.5H2O, respectively [the water mol-ecule is disordered over two locations with occupancies of 0.276 (3)/0.223 (3) for the iodo-benzoate derivative]. In the extended structures, all three salts feature an R 4 4(12) loop of two anions and two cations linked by N-H⋯O hydrogen bonds.

Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins.

Transitions between the unfolded and native states of the ordered globular proteins are accompanied by the accumulation of several intermediates, such as pre-molten globules, wet molten globules, and dry molten globules. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

Preoperative short-course radiation therapy with PROtons compared to photons in high-risk RECTal cancer (PRORECT): Initial dosimetric experience

Background and purposeNeoadjuvant short-course radiotherapy(SCRT) followed by full-dose systemic chemotherapy is an established treatment modality in locally advanced rectal cancer (LARC). Until recently, SCRT has been exclusively delivered with photons. Proton beam therapy (PBT) may minimize acute toxicity, which in turn likely impacts favorably on the tolerability to subsequent chemotherapy. The aim of this study is a dosimetric comparison between SCRT with photons and protons in the randomized phase II trial PRORECT (NCT04525989). Materials and methodsFrom June 2021 to June 2022, twenty consecutive patients with LARC have been treated according to study protocol. For each patient, both a VMAT and a PBT treatment plans have been generated and compared pairwise. ResultsDose-volume histogram (DVH) analysis revealed that SCRT with protons significantly reduced radiation dose to pelvic organs at risk including bladder, bones, and bowel in comparison to SCRT with photons. Photon and proton treatment plans had equivalent conformity and homogeneity indexes. ConclusionPreoperative SCRT with protons offers a significant reduction of radiation dose to normal tissues compared with current photon-based radiotherapy technique. Demonstrated dosimetric advantages may translate into measurable clinical benefits in patients with LARC. Clinical implications of the dosimetric superiority of SCRT with protons will be presented in the coming reports from the PRORECT trial.

5-(4-Methoxyphenyl)-1-[4-(4-methoxyphenyl)thiazol-2-yl]-3-[4-(prop-2-ynyloxy)phenyl]-4,5-dihydro-1H-pyrazole

The title compound, C29H25N3O3S, crystallizes in the monoclinic space group P21/n. The molecule contains a central four-ring system in which all of the rings are almost coplanar. Both the 4-methoxyphenyl ring and the prop-2-ynyloxy substituent are disordered over two equivalent conformations with occupancy ratios of 0.903 (2):0.097 (2) and 0.776 (5):0.224 (5), respectively. In the crystal, π–π interactions [centroid–centroid distance = 3.7327 (11) Å] between the dihydropyrazole ring and the 4-methoxyphenyl ring link the molecules into centrosymmetric dimers. In addition, there are weak C—H...S, C—H...N and C—H...O interactions, which link the molecules into a complex three-dimensional array.

Cellulose Modification with Maleic Anhydride

Cellulose modification is a challenge due to molecules characteristics – equatorial conformation, hydrogen bonds both withing molecule and among neighboring molecules etc. Esterification of cellulose hydroxyl groups (-OH) with dicarboxylic compounds is challenging. In presented study simple modification with maleic anhydride is performed in an anhydrous environment. Scanning electron microscopy reveals clean fibers of cellulose-maleic anhydride derivatives. FTIR proves unique peak at 1735cm-1 that corresponds to ester carbonyl groups. Titration of carboxylic (-COOH) groups solidifies that one part of anhydride has bonded with cellulose and other carboxylic groups is accessible for further development.

Anion‐Directed Conformation Switching and Trigonal Distortion in Hexakis(methylamine)nickel(II) Cations

AbstractThe homoleptic [Ni(NH2CH3)6]2+ cations have dozens of energetically feasible conformational isomers (conformers), and we herein show their conformation is tunable using counter anions. The reaction of Ni(NO3)2 or NiCl2 with aqueous methylamine in dimethylformamide gave [Ni(NH2CH3)6](NO3)2 (1) or [Ni(NH2CH3)6]Cl2 (2) in which methylamine ligands have axial or equatorial orientation with respect to the three‐fold principal axis, respectively. Interestingly, the conformation of methylamine ligands affects geometry around nickel(II) so that the nickel octahedron is trigonally compressed in 1, whereas it is trigonally elongated in 2, causing different visible light absorption properties between 1 and 2. Density functional theory calculations showed that nitrate anions stabilize the axial conformer through two‐point hydrogen bonding interactions with methylamines, whereas spherical chloride anions promote deformation of the axial conformer into the equatorial conformer through formation of three‐point hydrogen bonding interactions.

Solvent effects on the vibrational modes of (R)-3-methylcyclohexanone conformers

• DFT calculations of IR spectra are reported for ( R )-3-methylcyclohexanone ( R 3MCH) conformers in 11 solvents. • Solvent effects on IR spectra of R 3MCH conformers are investigated. • DFT calculations of the dipole moment components and magnitude of R 3MCH conformers were performed in 11 solvents. • A weak linear correlation was observed between the EQ and AX enthalpy difference as a function of solvent polarity. Quantum chemical calculations of the IR spectra, dipole moments, and enthalpies for the optimized geometries of dominant Equatorial (EQ) and Axial (AX) conformers of R-(+)-3-methylcyclohexanone (R3MCH) were performed in 11 common solvents of different polarity and nature, in the framework of polarizable continuum model (PCM). Density Functional Theory (DFT) involving exchange–correlation functional B3LYP and aug-cc-pVTZ basis set were used. The IR calculations of the individual conformers of R3MCH in CCl 4 yielded two distinct vibrational modes at 1086.13 cm −1 and 1030.86 cm −1 that were identified as unique markers of the EQ and AX conformers, respectively. By monitoring the calculated peaks of these two markers in 11 different solvents, a linear correlation between the EQ and AX markers’ intensities and frequencies with solvent polarity was observed. This correlation was directly related to the dipole moment orientation of each conformer. Upon increasing solvent polarity, the mode frequency of the EQ and AX markers experienced hypsochromic (blue) and bathochromic (red) shifts, respectively. A weak linear correlation was observed between the EQ and AX enthalpy difference as a function of solvent polarity.

The 130–360 GHz rotational spectrum of isocyanocyclobutane (C4H7NC) and cyanocyclobutane (C4H7CN)

The 130–360 GHz rotational spectrum of isocyanocyclobutane is reported herein for the first time. Over 2200 transitions were measured, assigned, and least-squares fit to a partial-octic distorted-rotor Hamiltonian with small deviation (σfit < 50 kHz) for the equatorial conformer. The axial conformer has so far remained elusive. For cyanocyclobutane, we measured the rotational spectra of both equatorial and axial conformers in the same frequency region to allow a direct comparison between the isomers. Transition frequencies for each conformational isomer of cyanocyclobutane were similarly fit to partial octic distorted-rotor Hamiltonians with small deviation. The experimental spectroscopic constants are in very good agreement with the predicted values (B3LYP) for all three species and with those reported in an earlier microwave study of cyanocyclobutane. Measurement of the relative transition intensities provides an updated energy difference of 0.69 (7) kcal/mol between the two conformers, with the equatorial conformation being the more stable one. Analysis of the axial conformation of cyanocyclobutane reveals coupling of its ground state to the vibrationally excited states of the equatorial conformation. Our observations of the vibrationally excited states of the equatorial conformer suggest that there are many Coriolis interactions between these states that were not described previously. Combined with literature values of nuclear quadrupole coupling constants, these spectroscopic constants and reported transition frequencies provide the basis for future astronomical searches for isocyanocyclobutane and cyanocyclobutane.

Conformational landscape and internal dynamics of limona ketone, a key oxidation product of limonene

The rotational spectrum of limona ketone (4-acetyl-1-methyl-1-cyclohexene), a key oxidation product of limonene, was recorded in the gas phase using a Fourier transform microwave spectrometer coupled to a supersonic jet expansion over the 4–20 GHz range. To display a complete view of the conformational landscape of this relatively flexible system, the relative stability and inter-conversion barriers between conformers were explored by electronic structure calculations. The lowest energy equatorial conformer was detected, and its spectroscopic molecular parameters were determined from the analysis of the spectrum. The internal rotation of the methyl group attached to the aldehyde moiety was taken into account in the analysis. The internal dynamics of the methyl group within the acetyl moiety was quantitatively described. Experimental lines of both A and E symmetry were fitted to experimental accuracy, and the experimental barrier height of the methyl group internal rotation is discussed with the support of quantum chemical calculations.

Photoelectron Circular Dichroism as a Signature of Subtle Conformational Changes: The Case of Ring Inversion in 1-Indanol.

Chirality plays a fundamental role in the molecular recognition processes. Molecular flexibility is also crucial in molecular recognition, allowing the interacting molecules to adjust their structures and hence optimize the interaction. Methods probing simultaneously chirality and molecular conformation are therefore crucially needed. Taking advantage of a possible control in the gas phase of the conformational distribution between the equatorial and axial conformers resulting from a ring inversion in jet-cooled 1-indanol, we demonstrate here the sensitivity of valence-shell photoelectron circular dichroism (PECD) to both chirality and subtle conformational changes, in a case where the photoelectron spectra of the two conformers are identical. For the highest occupied orbital, we observe a dramatic inversion of the PECD-induced photoelectron asymmetries, while the photoionization cross-section and usual anisotropy (β) parameter are completely insensitive to conformational isomerism. Such a sensitivity is a major asset for the ongoing developments of PECD-based techniques as a sensitive chiral (bio)chemical analytical tool in the gas phase.

Reversible Self-Assembly of an N-Heterocyclic Carbene on Metal Surfaces.

Self-assembly of cyclohexyl cyclic (alkyl)(amino)carbenes (cyCAAC) can be realized and reversibly switched from a close-packed trimer phase to a chainlike dimer phase, enabled by the ring-flip of the cyclohexyl wingtip. Multiple methods including scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations identified a distinct isomer (axial or equatorial chair conformer) in each phase, and consequently support the conclusion regarding the determination of molecular surface geometry on the self-assembly of cyCAAC. Moreover, various substrates such as Ag (111) and Cu (111) are tested to elucidate the importance of cyCAAC-surface interactions on cyCAAC based nanopatterns. These investigations of patterned surfaces prompted a deep understanding of cyCAAC binding mode, surface geometry and reversible self-assembly, which are of paramount significance in the areas of catalysis, biosensor design and surface functionalization.