Equatorial Conformers Research Articles

Matrix‐isolation IR spectroscopy of R‐(+)‐3‐methylcyclopentanone in para‐hydrogen crystal

High‐resolution infrared (IR) spectra of R‐(+)‐3‐methylcyclopentanone (R3MCP) in para‐hydrogen (pH2) crystal were recorded and compared with the corresponding IR spectra of R3MCP in Argon (Ar) isolation matrix as well as the IR spectra of the neat crystalline R3MCP at low deposition temperature of 4 ± 0.05 K. Moreover, IR spectra of R3MCP, hosted in pH2 crystal, were recorded using a high‐resolution Fourier transform IR spectrometer as a function of sample concentration and over the range 10–300 ppm. Furthermore, density functional theory calculations of simulated IR spectra for the optimized geometries of R3MCP equatorial‐methyl and axial‐methyl conformers are compared with experimental spectra for the purpose of investigating molecular conformation. Upon comparison between theoretical and experimental IR spectra, vibrational modes arising from equatorial and axial conformers have been successfully assigned and related to the individual conformer's structure. Copyright © 2015 John Wiley & Sons, Ltd.

Conformational analysis of morpholine studied using Raman spectroscopy and density functional theoretical calculations

Morpholine is a very interesting cyclic compound which is an ether as well as a secondary amine. The relative distribution of different conformations of morpholine depends on the medium. Using Raman spectroscopy and theoretical calculations, we found that, equatorial chair conformer is predominant in the pure liquid, but in aqueous solution, contribution from the axial conformer increases. The surface-enhanced Raman scattering (SERS) studies in presence of silver nanoparticles showed change in relative intensities of different vibrational modes of morpholine. It was found that the axial chair conformer is preferentially adsorbed vertically through the NAg bond on the nanoparticle surface.

Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients

The purpose of this study was to evaluate the performance of a commercially available CyberKnife system with a multileaf collimator (CK‐MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity‐modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK‐MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK‐MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK‐MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%–3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25 min for the whole pelvis plans and 19 min for the intracranial cases. The CK‐MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while maintaining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (>100 cm3) were generated that achieved high prescription isodose levels. The CK‐MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments.PACS numbers: 87.56.nk, 87.56.bd

The Role of CH···O Coulombic Interactions in Determining Rotameric Conformations of Phenyl Substituted 1,3-Dioxanes and Tetrahydropyrans.

The rotameric conformations of the phenyl ring in both the axial and the equatorial conformers of phenyl substituted 1,3-dioxanes and tetrahydropyrans are compared with those of the corresponding phenylcyclohexanes at the MP2/6-311+G* level. The compounds with an axial phenyl commonly adopt a conformation in which the plane of the aromatic ring is perpendicular to the benzylic C-H bond. However, axial 5-phenyl-1,3-dioxane adopts a "parallel" conformation that allows an ortho hydrogen to be proximate to the two ring oxygens, leading to attractive CH···O interactions. Stabilizing Coulombic interactions of this sort are found with many of the oxygen-containing six-membered rings that were investigated.

High-resolution structures of the d-alanyl carrier protein (Dcp) DltC from Bacillus subtilis reveal equivalent conformations of apo- and holo-forms

d-Alanylation of lipoteichoic acids plays an important role in modulating the properties of Gram-positive bacteria cell walls. The d-alanyl carrier protein DltC from Bacillus subtilis has been solved in apo- and two cofactor-modified holo-forms, whereby the entire phosphopantetheine moiety is defined in one. The atomic resolution of the apo-structure allows delineation of alternative conformations within the hydrophobic core of the 78 residue four helix bundle. In contrast to previous reports for a peptidyl carrier protein from a non-ribosomal peptide synthetase, no obvious structural differences between apo- and holo-DltC forms are observed. Solution NMR spectroscopy confirms these findings and demonstrates in addition that the two forms exhibit similar backbone dynamics on the ps–ns and ms timescales.

Clathrates of TETROL: Further Aspects of the Selective Inclusion of Methylcyclohexanones in Their Energetically Unfavorable Axial Methyl Conformations.

(+)-(2R,3R)-1,1,4,4-Tetraphenylbutane-1,2,3,4-tetraol (TETROL) functions as a highly efficient host for the inclusion of cyclohexanone and 2-, 3-, and 4-methylcyclohexanone, all with 1:1 host/guest ratios. Most extraordinarily, the 3- and 4-methyl isomers are uniquely included in their higher energy axial methyl conformations rather than as their more energetically favorable equatorial analogues. In contrast, 2-methylcyclohexanone is included more conventionally in the equatorial methyl conformation. During recrystallization of TETROL from racemic 2- and 3-methylcyclohexanone, some preference is shown by the host for the (R)-enantiomer. In the latter case, this is attributed to a much stronger H-bond between a hydroxyl group of TETROL and the carbonyl group of the (R)-enantiomer (O···O 2.621(2) Å) compared with a significantly weaker H-bond to the (S)-enantiomer (3.125(8) Å). In the former instance, hydrogen-bond strengths to both enantiomers are similar, but the (R)-enantiomer engages in three (guest)CH···π(host) and three (guest)H···Car(host) contacts, whereas fewer interactions of these types are observed for the (S)-enantiomer. Calculations of geometries of the guest cyclohexanones were determined at the MP2/6-311++G(2df,2p) level and compared with those obtained at the G3(MP2) level. Finally, an interesting correlation between crystal packing indices for the three methylcyclohexanone clathrates and their respective desolvation onset temperatures was identified.

Conversion of aminodeoxychorismate synthase into anthranilate synthase with Janus mutations: mechanism of pyruvate elimination catalyzed by chorismate enzymes.

The central importance of chorismate enzymes in bacteria, fungi, parasites, and plants combined with their absence in mammals makes them attractive targets for antimicrobials and herbicides. Two of these enzymes, anthranilate synthase (AS) and aminodeoxychorismate synthase (ADCS), are structurally and mechanistically similar. The first catalytic step, amination at C2, is common between them, but AS additionally catalyzes pyruvate elimination, aromatizing the aminated intermediate to anthranilate. Despite prior attempts, the conversion of a pyruvate elimination-deficient enzyme into an elimination-proficient one has not been reported. Janus, a bioinformatics method for predicting mutations required to functionally interconvert homologous enzymes, was employed to predict mutations to convert ADCS into AS. A genetic selection on a library of Janus-predicted mutations was performed. Complementation of an AS-deficient strain of Escherichia coli grown on minimal medium led to several ADCS mutants that allow growth in 6 days compared to 2 days for wild-type AS. The purified mutant enzymes catalyze the conversion of chorismate to anthranilate at rates that are ∼50% of the rate of wild-type ADCS-catalyzed conversion of chorismate to aminodeoxychorismate. The residues mutated do not contact the substrate. Molecular dynamics studies suggest that pyruvate elimination is controlled by the conformation of the C2-aminated intermediate. Enzymes that catalyze elimination favor the equatorial conformation, which presents the C2-H to a conserved active site lysine (Lys424) for deprotonation and maximizes stereoelectronic activation. Acid/base catalysis of pyruvate elimination was confirmed in AS and salicylate synthase by showing incorporation of a solvent-derived proton into the pyruvate methyl group and by solvent kinetic isotope effects on pyruvate elimination catalyzed by AS.

A Computational Study of the Contributions to the Relative Stability of the α and β Conformers of D‐Glucopyranose

In order to better evaluate the contributors to the conformational energy of D‐Glucopyranose, the geometry‐energy relationships for a sequence of model compounds was determined. The conformational energies of 1‐Hydroxy (equatorial) 3‐Hydroxymethylcyclohexane and 2‐Hydroxy 6‐ Hydroxymethyltetrahydro‐2H‐pyran were used to model D‐Glucopyranose. The conformational energies were determined at the B3LYP/6‐311G++(d,p) and MP2/6‐311++(d,p) levels in the gas phase and solution. The relative B3LYP energy as a function of the orientation of the substituents were determined by relaxed scans as the –CH2‐OH at C5 was rotated about the OCCO and HOCC dihedrals and the –OH at C1 was rotated about the HOCO dihedral. The lowest energy rotamers for the axial (α) and equatorial (β) conformers were used to calculate the conformational energy. Because solute‐solvent interactions have significant effects on the relative stability of the axial and equatorial conformers, the energy versus dihedral scans were repeated using a continuum solvent model with water (ε = ~80), acetone (ε = ~20) and cyclohexane (ε = ~2) selected as the solvent.

Comparison of dose distributions hippocampus in high grade gliomas irradiation with linac-based imrt and volumetric arc therapy: a dosimetric study.

The aim of this study was to assess the feasibility of sparing contralateral hippocampus during partial brain radiotherapy in high grade gliomas. 20 previously treated patients were replanned to 60 Gy in 30 fractions with sparing intensity-modulated radiotherapy (IMRT) and volumetric modulated arctherapy (VMAT) using the following planning objectives: 100 % of PTV covered by 95% isodose without violating organs at risk (OAR) and hot spot dose constraints. For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as sparing IMRT and VMAT plans which spared contralateral (hemispheric cases) hippocampus. When the three plans were compared, there was equivalent PTV coverage, homogeneity, and conformality. Sparing IMRT significantly reduced maximum, mean, V20, V30 and V40 hippocampus doses compared with standart IMRT and VMAT (p < 0.05). VMAT significantly reduced maximum left lens and mean eye doses compared with standart IMRT and sparing IMRT (p < 0.05). Brainstem, chiasm, left and right optic nerves, right eyes and lens doses were similar. VMAT significantly reduced monitor units compared with standart IMRT and sparing IMRT (p < 0.05). It is possible to spare contralateral hippocampus during PBRT for high grade gliomas using IMRT. This approach may reduce late cognitive sequelae of cranial radiotherapy.

Revealing halogen bonding interactions with anomeric systems: An ab initio quantum chemical studies

A computational study has been performed using MP2 and CCSD(T) methods on a series of O⋯X (X=Br, Cl and I) halogen bonds to evaluate the strength and characteristic of such highly directional noncovalent interactions. The study has been carried out on a series of dimeric complexes formed between interhalogen compounds (such as BrF, BrCl and BrI) and oxygen containing electron donor molecule. The existence and consequences of the anomeric effect of the electron donor molecule has also been investigated through an exploration of halogen bonding interactions in this halogen bonded complexes. The ab initio quantum chemical calculations have been employed to study both the nature and directionality of the halogen molecules toward the sp3 oxygen atom in anomeric systems. The presence of anomeric nO→σ*CN interaction involves a dominant role for the availability of the axial and equatorial lone pairs of donor O atom to participate with interhalogen compounds in the halogen-bonded complexes. The energy difference between the axial and equatorial conformers with interhalogen compounds reaches up to 4.60kJ/mol, which however depends upon the interacting halogen atoms and its attaching atoms. The energy decomposition analysis further suggests that the total halogen bond interaction energies are mainly contributed by the attractive electrostatic and dispersion components. The role of substituents attached with the halogen atoms has also been evaluated in this study. With the increase of halogen atom size and the positive nature of σ-hole, the halogen atom interacted more with the electron donor atom and the electrostatic contribution to the total interaction energy enhances appreciably. Further, noncovalent interaction (NCI) studies have been carried out to locate the noncovalent halogen bonding interactions in real space.

Conformer-resolved quantum dynamics study of the photodissociation of 3-pyrroline.

A model Hamiltonian based on the vibronic coupling model is developed to describe the excited state dynamics of 3-pyrroline. With the use of the method of improved relaxation in conjunction with the MCTDH wavepacket propagation algorithm, vibrational eigenstates corresponding to both the axial and equatorial conformers of 3-pyrroline are calculated and subsequently used in a conformer-resolved study of the photodissociation of 3-pyrroline following excitation to its S1(3s/πσ*) and S2(3px) states. In analogy with ammonia, the excited state dynamics of both conformers of 3-pyrroline are found to be dominated by the (quasi-) planarization of the molecule in its electronically excited states and predominantly diabatic behavior of dissociation mediated by a conical intersection between the S1 and S0 states.

Conformational analysis of 3-methyltetrahydro-1,3-oxazine

Conformational analysis of 3-methyltetrahydro-1,3-oxazine has been performed using HF/6-31G(d), PBE/3z, and RI-MP2/λ2 simulation approximations. The potential energy surface contains eight minima. Interconversion of the axial and equatorial chair conformers (main minima) occurs via several independent pathways involving six twist forms. The preferred path presumes direct chair-chair transition via pyramidal inversion of the nitrogen atom.

Conformational properties of 1-tert-butyl-1-silacyclohexane, C5H10SiH(t-Bu): gas-phase electron diffraction, temperature-dependent Raman spectroscopy, and quantum chemical calculations

The conformational preference of the t-butyl group in 1-t-Bu-1-silacyclohexane was studied experimentally by means of gas-phase electron diffraction (GED), and temperature-dependent Raman spectroscopy as well as by quantum chemical calculations applying density functional theory and ab initio methods. According to the GED experiment at 283 K, the vapor of the title compound contains only the equatorial conformer. At 99.5 % level of confidence, up to 4 % of axial conformer cannot be completely excluded, however. The Raman spectroscopy experiment in the temperature range of 295–375 K of the neat liquid indicated that the equatorial conformer is favored over the axial one by 0.56 (15) kcal mol−1 (ΔH values). The experimental values are fairly well reproduced by the calculations. CCSD(T) calculations predict the equatorial conformer to have a 1.19 kcal mol−1 lower Gibbs free energy (corresponding to about 89 % equatorial preference) and a 0.99 kcal mol−1 lower enthalpy than the axial conformer at 300 K. According to natural bond orbital analysis, the equatorial conformer of the title compound is an example of a molecular stabilization, which is not favored by steric and conjugation effects but favored by electrostatic interactions. Results from dynamic NMR experiments were inconclusive.

Endocyclic oxygen in 3-fluorodihydro-2H-pyran-4(3H)-one that does not induce the gauche effect.

2-Fluorocyclohexanone undergoes chair inversion, giving rise to axial and equatorial conformers, with the equatorial form being highly preferred in solution, for example, 87% in chloroform and 93% in methylene chloride. Modifications in the conformational preferences can modify macroscopic properties of 2-fluoro ketones. The introduction of an endocyclic oxygen in 2-fluorocyclohexanone to give 3-fluorodihydro-2H-pyran-4(3H)-one would be expected to create a gauche effect in the axial conformer along with the O-C-C-F moiety, inducing an increase of its population. However, small changes were verified in the conformational populations both in the gas phase and solution because the carbonyl group plays an important role for the hyperconjugation in the equatorial conformer, despite experiencing strong dipolar repulsion with the fluorine atom. These data were obtained theoretically and by NMR spectroscopy, while the nature of the interactions governing these conformational shifts were investigated on the basis of natural bond orbital analysis.

Conformational equilibria and large-amplitude motions in dimers of carboxylic acids: rotational spectrum of acetic acid-difluoroacetic acid.

We report the rotational spectra of two conformers of the acetic acid-difluoroacetic acid adduct (CH3COOH-CHF2COOH) and supply information on its internal dynamics. The two conformers differ from each other, depending on the trans or gauche orientation of the terminal -CHF2 group. Both conformers display splittings of the rotational transitions, due to the internal rotation of the methyl group of acetic acid. The corresponding barriers are determined to be V3(trans)=99.8(3) and V3(gauche)=90.5(9) cm(-1) (where V3 is the methyl rotation barrier height). The gauche form displays a further doubling of the rotational transitions, due to the tunneling motion of the -CHF2 group between its two equivalent conformations. The corresponding B2 barrier is estimated to be 108(2) cm(-1). The increase in the distance between the two monomers upon OH→OD deuteration (the Ubbelohde effect) is determined.

SU‐F‐BRD‐05: Dosimetric Comparison of Protocol‐Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed‐ Beam IMRT

Purpose:The purpose of this study is to inter‐compare and find statistically significant differences between flattened field fixed‐beam (FB) IMRT with flattening‐filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT.Methods:SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parameters of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum‐ and volumetric‐dose limits.Results:For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t‐test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p&lt;0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans.Conclusions:FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs‐at‐risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.

Investigating (R)-3-Methylcyclopentanone Conformers Using Temperature-Dependent Raman Spectroscopy

Recorded temperature-dependent Raman spectra of neat (R)-3-methylcyclopentanone (R3MCP) over the Raman active C–H stretch region (2850–3000 cm–1) are being employed to determine conformer energy difference (ΔH° = 4.83 ± 0.45 kJ/mol) between R3MCP equatorial-methyl and axial-methyl isomers. Upon comparison with spectra obtained at room temperature, crystalline R3MCP Raman spectra recorded at liquid nitrogen temperature (~77 K) are being utilized to assist identifying Raman vibrational modes a rising due to R3MCP equatorial and axial conformers. Correspondingly, density functional theory calculations (correlation function type B3LYP using a moderate 6-31G* and large aug-cc-pVDZ basis sets) are also manipulated to obtain highly resolved Raman spectra for the optimized geometries of equatorial and axial conformers, which are also used to help identify vibrational modes a rising due to each conformer. Reported calculated spectra of the individual R3MCP conformers are shown to have good agreement with corresponding experimental Raman spectra.

Experimental and Theoretical Studies of Intramolecular Hydrogen Bonding in 3-Hydroxytetrahydropyran: Beyond AIM Analysis

The conformational preferences of 3-hydroxytetrahydropyran (1) were evaluated using infrared and nuclear magnetic resonance spectroscopic data in solvents of different polarities. Theoretical calculations in the isolated phase and including the solvent effect were performed, showing that the most stable conformations for compound 1 are those containing the substituent in the axial and equatorial orientations. The axial conformation is more stable in the isolated phase and in a nonpolar solvent, while the equatorial conformation is more stable than the axial in polar media. The occurrence of intramolecular hydrogen-bonded O-H···O in the axial conformer was detected from infrared spectra in a nonpolar solvent at different concentrations. Our attempt to evaluate this interaction using population natural bond orbital and topological quantum theory of atoms in molecules analyses failed, but topological noncovalent interaction analysis was capable of characterizing it.

Conformational preference of perhydro-1,3,2-dioxazine inside nanotubes

Conformational changes of perhydro-1,3,2-dioxazine in open single-walled carbon nanotubes have been studied by hybrid DFT PBE/3z method. It was established that relative stability of equatorial and axial chair conformers of encapsulated molecule has been inverted, the latter form becoming favorable. In this case the barrier of pyramidal inversion of nitrogen atom has been slightly de

Molecular structure and polymorphism of a cyclohexanediol: trans-1,4-cyclohexanedimethanol

The methoxy substituent intrans-1,4-cyclohexanedimethanol stabilizes equatorial conformations, whose two polymorphs were found and characterized by DSC, FTIR, and XRD.