Axial Chair Research Articles

Conformational Analysis of 5-Methyl-1,3-oxathiane

Computer simulation of conformational transformations of 5-methyl-1,3-oxathiane at the DFT PBE/3ζ, RI-MP2/λ2, and HF/6-31++G(d,p) levels of theory has shown that the interconversion between the equatorial (global minimum) and axial chair conformers occurs along several independent pathways through five flexible forms. Nine transition states corresponding to different half-chair forms, as well as symmetrical and unsymmetrical boat conformers, have been localized on the potential energy surface. The free conformational energy of the methyl group has been estimated at 0.9–1.0 kcal/mol by comparison of the calculated and experimental vicinal coupling constants in the 1H NMR spectra.

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube: A Molecular Dynamics Simulation Study.

The transport behavior of glucose through a cyclic peptide nanotube (CPN), composed of 8 × cyclo[-(Trp-d-Leu)4-Gln-d-Leu-] rings embedded in DMPC lipid bilayers was examined using all-atom molecular dynamics (AAMD) simulations. Two conformational isomers of β-d-glucose, equatorial (4C1) and axial (1C4) chair conformers, were used to examine conformational effects on the hydrogen bond network, energetics, and diffusivity of glucose transport through the CPN. Calculations of the number of hydrogen bonds of the two glucose conformers with water molecules and with the CPN illustrate that the total number of hydrogen bonds of the conformers decreases inside the channel compared to bulk water due to the confinement characteristics of the interior of the CPNs although new hydrogen bonds between the hydroxyl and hydroxymethyl hydrogens of glucose and the carbonyl oxygens in the CPN backbone are formed. Despite the decrease of the number of hydrogen bonds inside the CPN, intramolecular hydrogen bonds of 1C4 are maintained during permeation of 1C4 through the CPN. The retention of intramolecular hydrogen bonds and the spherical shape of 1C4 give rise to considerably weaker orientational preferences and higher diffusion coefficients for 1C4 than those of 4C1 inside and outside the CPN. Due to larger dipole moments induced by the alignment of hydroxyl and hydroxymethyl groups, 1C4 has more favorable interactions with the CPN backbone at the channel entrances and inside the channel than 4C1. In the middle of the CPN channel, entropic gains originating from higher orientational and translational degrees of freedom of 1C4 than those of 4C1 also contribute to lower free energy wells for 1C4 inside the CPN. This work reveals that the conformational variation and intramolecular hydrogen bond formation of β-d-glucose can have important effects on the energetics and dynamics of glucose transport through CPNs, providing insight into the translocation mechanism of d-glucose into the cell through glucose transporters (GLUTs) and the dynamics of glucose confined in silica nanochannels. It is also demonstrated that CPNs can indeed facilitate the permeation of small hydrophilic molecules such as glucose and can be utilized as a novel carrier system for hydrophilic drug compounds into the cell.

Complexation and Structure Elucidation of the Axial Conformers of Mono- and (±)-trans-1,2-Disubstituted Cyclohexanes by Enantiopure Alleno-Acetylenic Cage Receptors.

Single crystal X-ray diffraction is a powerful method to unambiguously characterize the structure of molecules with atomic resolution. Herein, we review the molecular recognition of the (di)axial conformers of Mono- and (±)-trans-1,2-disubstituted cyclohexanes by enantiopure alleno-acetylenic cage receptors in solution and in the solid state. Single crystals of the host-guest complexes suitable for X-ray diffraction allow for the first time to study the dihedral angles of a series of Mono- and (±)-trans-1,2-disubstituted cyclohexanes in their (di)axial chair conformation. Theoretical studies indicate negligible influence of the host structure on the guest conformation, suggesting that the structural information obtained from the host-guest complexes give insight into the innate structures of Mono- and (±)-trans-1,2-disubstituted cyclohexanes. Strong deviation of the dihedral angles a,a(X-C(1)-C(2)-X) from the idealized 180° are observed, accompanied by substantial flattening of the ring dihedral angles ρ(X-C(1)-C(2)-C(3)).

Vibrational Sum-Frequency Generation Study of Morpholine at Air–Liquid and Air–Solution Interfaces

The structure and orientation of interfacial morpholine molecules have been investigated, using vibrational sum-frequency generation (VSFG) spectroscopy—a nonlinear surface specific technique. The VSFG spectra with SSP and PPP polarizations have been measured in the CH (2800–3000 cm–1) and the OH (3000–3750 cm–1) stretch regions at the air–morpholine and air–solution interfaces. The vibrational frequencies in the CH stretch region could be observed in VSFG spectra, implying presence of morpholine molecules at the interfaces with net polar orientation. The intensities of the CH stretch bands get enhanced at the air–solution interface of morpholine solution in millimolar concentration, in comparison to that at the air–morpholine interface which is attributed to increase in polar orientation of interfacial morpholine molecules induced by water molecules. In pure morpholine, the most predominant conformation of molecules is equatorial chair, both in the bulk and at the air–morpholine interface. But in aqueous solution of morpholine, the contribution from axial chair conformer is known to increase. This effect, and also a probable change from the chair to the boat/twist boat conformation at the air–solution interface, may contribute to the enhanced intensity of VSFG peaks of CH stretch bands in solution. The VSFG intensities of the OH stretching frequencies of interfacial water molecules are also enhanced in the presence of morpholine, suggesting an increase in net polar orientation of water molecules induced by morpholine molecules. The VSFG spectra were also measured in the presence of 300 mM HCl, which showed indications of protonation of the interfacial morpholine molecules. Addition of HCl to aqueous solution of morpholine alters the orientation of interfacial water molecules significantly, and the enhanced VSFG intensities in the OH region induced by morpholine molecules are almost completely obliterated. The result suggests that orientation of interfacial water molecules in the presence of HCl gets random. However, the effects of HCl in the CH region of the VSFG spectra differ for different stretching bands. In presence of readily ionizable HCl molecules, a large number of ions are generated, which are probably responsible for changing the surface orientation of both water and morpholine molecules.

Structure and conformational behavior of N-phenylpiperidine studied by gas-phase electron diffraction and quantum chemical calculations

Molecular structure and conformational behavior of N-phenylpiperidine (NPhP) were investigated by synchronous gas-phase electron diffraction/mass spectrometry (GED/MS) and quantum chemistry. Due to influence of steric repulsion and hyperconjugation, NPhP may exist in two conformers, equatorial and axial chair forms. Both experiment and theoretical calculations suggest a C1 symmetry of the conformers, with the plane perpendicular to the phenyl group turned by ca. 30–40° (equatorial) and 0–20° (axial) about the plane perpendicular to the piperidine ring symmetry plane. According to the QC calculations, NPhP may exist as two conformers, equatorial and axial, with a ratio of Eq:Ax = 92:8 (B3LYP), 87:13 (B3LYP-GD3), 84:16 (M06-2X), 83:17 (MP2/6-311G**) and 76:24% (MP2/cc-pVTZ). Except for the latter, these values are in good agreement with the experimental GED data of 90(10):10(10)%.A comparative analysis of similar compounds, phenylcyclohexane and 1-phenylheterocyclohexanes, was performed. Conformational properties depend on the CPhX bond distance and hyperconjugation between the phenyl ring and the lone pair on the heteroatom. The contribution of the axial form of 1-phenylcyclohexane derivatives increases in the series of the heteroatom X in the cyclohexane ring: C → N → Si → P.

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.

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

Conformational analysis of 2,2-dimethyl-5-alkyl-1,3-dioxa-2-silacyclohexanes

Study of conformational isomerization of 2,2-dimethyl-5-alkyl-1,3-dioxa-2-silacyclohexanes using quantum-chemical HF/6-31G(d) and PBE/3z approximations showed that its route involves an equilibrium between the chair conformers with different orientation of substituent at C5 ring atom and proceeds through a transition state corresponding to the 2,5-twist conformation. Molecular dynamics method showed that at room temperature this conformation transforms into the equatorial or axial chair conformers through 1,4-twist or sofa forms. Based on the experimental and theoretical values of vicinal 1H NMR coupling constants we determined quantitative conformational composition of the molecules of these compounds and the values of ΔG0 of the conformational equilibrium.

Conformational analysis of 5-methyl- and 2,2,5-trimethyl-1,3-dithianes

Conformational isomerization of 5-methyl- and 2,2,5-trimethyl-1,3-dithianes was studied using quantum-chemical HF/6-31G(d), HF/pVDZ, and PBE/3z approximations. The potential energy surface of molecules of both compounds is shown to contain the main minimum corresponding to the equatorial chair conformer C-5e. The calculated potential barriers of the conformational isomerization were found. Based on the experimental (1H NMR) and theoretical vicinal coupling constants the ΔG 0 values were determined of the methyl group at the ring C5 atom. The reasons for the distinctions between the values of this parameter from the ΔG 0, obtained by energy minimizations of the equatorial and axial chair conformers are discussed.

Conformational Behaviors of 2-Substituted Cyclohexanone Oximes: An AB Initio, Hybrid Dft Study, and NBO Interpretation

The impacts of the generalized anomeric effect (GAE) and gauche effect (GE) associated with donor–acceptor electron delocalizations and dipole–dipole interactions on the conformational properties of 2-methoxy- (1), 2-methylthio- (2), 2-methylseleno- (3), 2-fluoro- (4), 2-chloro- (5), and 2-bromocyclohexanone oxime (6) have been studied by means of hybrid density functional theory (B3LYP/6–311+G**) and ab initio molecular orbital (HF/6–311+G**)-based methods and natural bond orbital (NBO) interpretation. Both methods used showed that the above compounds exist predominantly in the axial chair conformation and the axial conformation stability increased from 2-methoxy- (1) to 2-methylselenocyclohexanone oxime (3) and also from 2-fluoro- (4) to 2-bromocyclohexanone oxime (6). The NBO analysis showed that the GAE increases from compound 1 to compound 3 and also from compound 4 to compound 6. GE does not have significant impact on the conformational behaviors of compounds 1–6 and GAE succeeds in accounting qualitatively for the increase of the axial preferences in both series of compounds. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Table S1. Supporting Information Available. The structures optimized and thermodynamic functions of the axial and equatorial conformations of compounds 1–6. This material is available free of charge via the Internet.

Conformational analysis of 2-substituted 5,5-bis(chloromethyl)-1,3-dioxanes

Quantum-chemical study on stationary points on the potential energy surfaces of 2-alkyl-, 2-phenyl-, and 2-methyl-2-phenyl-5,5-bis(chloromethyl)-1,3-dioxanes in terms of HF/6-31G(d), B3PW91/6-31G(d,p), and B3PW91/LanL2Dz nonempirical approximations revealed only one pathway for conformational isomerization of the equatorial and axial chair conformers through intermediate energy minimum corresponding to the 2,5-twist conformer.

Conformational analysis of 5-substituted 1,3-dioxanes

Quantum-chemical study on the potential energy surface of 5-alkyl- and 5-phenyl-1,3-dioxanes at the RHF/6-31G(d) level of theory revealed two pathways for conformational isomerizations of the equatorial and axial chair conformers. Potential barriers to this process were estimated. The Gibbs conformational energies ΔG° of substituents at C5 in the 1,3-dioxane ring were determined on the basis of experimental (1H NMR) and theoretical vicinal coupling constants, which turned out to be consistent with published data.

Pathways of conformational isomerization of 4-phenyl-1,3-dioxane

A study of the potential energy surface of 4-phenyl-1,3-dioxane by non-empirical quantum chemical RHF/STO-3G and 6-31G(d) approximations reveals six energetically inequivalent pathways of conformational isomerization of equatorial and axial chair forms.

Conformational analysis of 4-trifluoromethyl-1,3-dioxane

The interest to the structural investigation of 1,3-dioxanes, six-membered heteroanalogs of cyclohexane, originates from the features of their structure (the presence of two heteroatoms separated by sp3-carbon atoms), from their valuable pharmacological properties, and also from the application to the fine organic synthesis [1–5]. In the last decade computer simulations play an important role in conformationsl studies of such compounds. It was shown in particular that the conformational isomerization of unsubstituted 1,3-dioxane and also of 2,2-, 4,4-, and 5,5-dimethyl-1,3-dioxanes occurred between two degenerate in energy invertomers of chair (C and C*), and of 2-methyl-1,3-dioxane, between the conformers of equatorial and axial chair (Ce and Ca) along two materially equivalent paths [6–9]. This study is dedicated to the computer simulation of the paths of conformational isomerization of 4-trifluoromethyl-1,3-dioxane (I) by nonempirical quantum-chemical approximations RHF//STO-3G and 6-31G(d,p) in the framework of software HyperChem [10] under the conditions simulating the behavior of the molecules of this substance in the gas phase. It follows from the data of 1H NMR spectra of individual stereoisomers of 4-trifluoromethyl-5-methyl1,3-dioxane that the molecules of 1,3-dioxane I exist at room temperature prevailingly in the conformation of equatorial chair (Ce) [11].

Conformational isomerization of 4-methyl-1,3-dioxane

The whole possible course of conformational isomerization of 4-methyl-1,3-dioxane has been established using empirical (MM+) and nonempirical [STO-3G, 3-21G, 6-31G(d) and 6-31G(d,p)] approximations within the limits of the Hartree-Fock method. It was shown that the potential energy surface of this compound contains a principal (equatorial chair conformer) and local minima corresponding to the axial chair conformer and series flexible forms.

Adsorption changes of cyclohexyl isothiocyanate on gold surfaces

The adsorption and structure of cyclohexyl isothiocyanate (CHIT) on gold surfaces has been investigated by surface-enhanced Raman scattering (SERS) and scanning tunneling microscopy (STM). Depending on the concentration, the spectral changes of the NCS stretching vibration on gold nanoparticles appeared to be more conspicuous than those of cyclohexyl ring modes. Both equatorial and axial chair conformers of CHIT were found to exist at low bulk concentrations near the monolayer coverage limit, whereas the equatorial chair conformer appeared to be dominant at high bulk concentrations. It was also observed that the ring conversion of equatorial to axial conformers can easily occur at higher temperatures, and the mole fraction of the axial form is assumed to increase with increasing temperature from 30 to 60 °C. Alternatively, STM imaging revealed that the adsorption of CHIT molecules on Au(1 1 1) leads to the formation of disordered SAMs with a few vacancy islands, as opposed to the formation of well-ordered self-assembled monolayers (SAMs) by cyclohexanethiols.

Nonempirical study on the potential energy surface of 5-methyl-1,3-dioxane

Quantum-chemical study on the potential energy surface of 5-methyl-1,3-dioxane at the nonempirical RHF//STO-3G, RHF//3-21G, RHF//6-31G(d), RHF//6-31G(d,p), and MP2//6-31G(d,p) levels of theory revealed two energy-equivalent paths of conformational transformation of the equatorial and axial chair conformers. Potential barriers to these processes were estimated. The δG° value for the methyl substituent on C5 in 1,3-dioxane ring, determined on the basis of the experimental (NMR) and calculated vicinal 1H-1H coupling constants, was very consistent with published data

Study of supercooled orientationally disordered binary solid solutions II: cyclohexyl derivatives, neopentanol and neopentylglycol

The main aim of the present investigation is to see how various relaxation processes including the chair-chair transformation (as found by earlier researchers at room temperature in mechanical relaxation spectroscopy) in cyclohexane derivatives evolve as the temperature is lowered. For this purpose, four remarkable (two-component) solid solutions that are orientationally disordered are investigated, where the first three systems are hydrogen (H-) bonded pairs, and the fourth is a non-H bonded pair. The former group is the two-component system of cyclohexanol (CHXOL) + 2,2-dimethyl-1-propanol or neopentanol (NPOL); cyclohexanol (CHXOL) + cycloheptanol (CHPOL) & neopentanol (NPOL) + neopentylglycol (NPGOL) systems, and the lone non H-bonded pair that has been studied is cyanocyclohexane (CNCH) and cyclohexylchloride (CHC). In all these cases, the liquid mixtures on cooling form orientationally disordered phases which are a solid solution of the corresponding pure phases. The feature is common to all the four systems studied here, but in CHXOL + CHPOL, the phase I of CHXOL beyond x(m) > or = 0.1 only forms a solid solution (designated as S(I')) with the phase I of CHPOL. In CNCH + CHC the solid phase is stable for the concentration range 0 < or = x(m) < or = 0.4 (without transition to any other phase). The above solid phase I (or I') has been investigated at low temperatures and for several concentrations, by means of dielectric spectroscopy and differential scanning calorimetry (DSC). Depending upon the concentration, this phase reveals a glass transition in the temperature range 116-150 K and associated with this is a pronounced relaxation process identifiable with the so called alpha-process. The dielectric spectra of this process is found to follow the Havriliak-Negami (HN) equation. In context of the binary system study here, the analysis of the various parameters obtained show an isomorphic relationship between the phases of the pure components through a continuous change of parameters. Another process of much smaller magnitude designated as the alpha'-process was also found in systems consisting of cyclohexyl derivatives above the glass transition temperature T(g) which kinetically freezes around 170 K. This process interestingly, is also non-Arrhenius in nature, becomes increasingly weaker with increase in the second component, and may be identified with (axial) chair-(equatorial) chair transformation. In addition in all these systems, a weak high-frequency process and a clear sub-T(g) process, are found which are designated as the beta- & gamma-processes respectively. The beta-process may be identified with Johari-Goldstein (JG) or beta(JG) process as it is found to follow the predictions of the coupling model proposed by Ngai. However, the identification of the gamma-process with internal degrees of freedom are fraught with some problems in the interpretation of the experimental data that are highlighted. The kinetic freezing of the various dielectric processes have been critically examined in relation to the T(g) found in the DSC experiments.

Concentration‐ and temperature‐dependent conformation change of cyclohexyl isocyanide on gold nanoparticle surfaces

AbstractThe conformational changes of cyclohexyl isocyanide (CHNC) on gold nanoparticle surfaces were investigated by means of concentration‐ and temperature‐dependent surface‐enhanced Raman scattering (SERS). The equatorial chair conformer appeared to be dominant at high‐bulk concentrations or low temperatures, whereas both the equatorial and axial chair conformers of CHNC were found to exist at low‐bulk concentrations or high temperatures as in the previous reports of cyclohexanethiol (CHT). Depending on concentrations and temperatures, the spectral changes of the NC stretching vibration on gold nanoparticles appeared to be more conspicuous than those of the cyclohexyl ring modes. A density functional theory (DFT) calculation was performed at the level of B3LYP/6‐31G + + (d,p) to compare the energetic stability of the various conformers of CHT and CHNC. The energy differences between the equatorial and axial chair conformers were predicted to be smaller for CHNC than for CHT by ∼3 kJ mol−1 from the DFT calculation. Copyright © 2008 John Wiley &amp; Sons, Ltd.

Conformational changes of cyclohexanethiol adsorbed on gold surfaces

The conformational changes of cyclohexanethiol (CHT) on gold nanoparticles and gold plate surfaces were investigated by means of surface-enhanced Raman scattering. The equatorial chair conformer appeared to be dominant at high bulk concentrations, whereas, both the equatorial and axial chair conformers of CHT were found to exist at low bulk concentrations corresponding to a near monolayer coverage limit. Molecular-scale scanning tunneling microscopy imaging revealed the existence of two axial and equatorial conformers in the CHT monolayer on an Au(1 1 1) surface as well as the existence of the meta-stable conformer, which may be due to dynamic conformational changes of the cyclic ring. It was also found that the peaks corresponding to the axial bands disappeared below room temperature, indicating the equatorial conformer is dominant at low temperatures. From this result, we found that the conformation of CHT on an Au surface was easily changed by surface temperature.