Studies on predicting reactive sites of 3,9-diazatetraasteranes by conceptual density functional theory and experiment

Theoretical studies on predicting potential reactive sites of attractive compounds are of significance, which are capable of providing deeper insight into their chemical behaviors as well as foundations for discovering new drug molecules. The 3,9-diazatetraasterane derivatives are a kind of cage compounds equipping with potent biological activities. In this paper, predication of reactive sites of 3,9-diazatetraasteranes bearing phenyl and ester groups (6,12-diphenyl-3,9-diazahexacyclo[6.4.0.0^2.7.0^4.11.0^5.10]-dodecane-1,5,7,11-tetracarboxylate) was carried out by the conceptual density functional theory. Firstly, a conformational search of 3,9-diazatetraasterane was performed by molecular dynamics simulations associating with Quantum Mechanics calculations in order to obtain relative stable conformers. And then the reactive site prediction of 3,9-diazatetraasterane was carried out by the Fukui function and condensed Fukui function. The results exhibited that the potentially chemical reactive site is the N atom of 3,9-diazatetraasterane scaffold, which is readily attacked by electrophilic agent. Meanwhile, the calculated results were validated by experimental outcomes in the derivation of 3,9-diazatetraasteranes.

     

A Novel Route to <Emphasis Type="Italic">trans</Emphasis>-Epoxidation of Terpinen-4-ol

Summary. Pure (1S,2R,4S)-1,2-epoxy-p-menthan-4-ol and (1R,2S,4R)-1,2-epoxy-p-menthan-4-ol (trans-epoxides of (4S)-terpinen-4-ol and (4R)-terpinen-4-ol) were prepared and certain reactions of these compounds with nucleophilic reagents were studied. It was shown that the Fürst-Plattner rule regarding the trans-diaxial opening of cyclohexene epoxides predicts the predominant products in all cases studied.     

A Novel Route to trans-Epoxidation of Terpinen-4-ol

Pure (1S,2R,4S)-1,2-epoxy-p-menthan-4-ol and (1R,2S,4R)-1,2-epoxy-p-menthan-4-ol (trans-epoxides of (4S)-terpinen-4-ol and (4R)-terpinen-4-ol) were prepared and certain reactions of these compounds with nucleophilic reagents were studied. It was shown that the Fürst-Plattner rule regarding the trans-diaxial opening of cyclohexene epoxides predicts the predominant products in all cases studied.     

Molecular and Crystal Structure of (1R)-2-arylidene-p-(4-menthen)-3-ones

The molecular structure of chloro-, methoxy-, and methoxyphenyl-substituted (1R)-arylidene-p-(4-menthen)-3-ones was studied by X-ray diffraction. The cyclohexenone ring in the compounds has a sofa conformation with a virtually planar geometry of the s-trans-enone fragment. Based on the experimental data and AM1 calculations it is shown that the electronic effects of substituents do not affect the conformational characteristics of the benzylidene-menthenone fragment, but change the bond lengths in the conjugate system. The endocyclic double bond in the molecules causes pronounced flattening of the exocyclic s-cis-enone and benzylidene groups compared to the corresponding derivatives of p-menthan-3-one. The structural peculiarities of the compound with a biphenylyl group are interpreted as the consequence of intermolecular interactions in crystal.     

Theoretical Study on Co^3＋ in Aqueous Solution in Terms of ABEEM/MM Model

A detailed theoretical investigation on Co^3＋ hydration in aqueous solution has been carded out by means of molecular dynamics （MD） simulations based on the atom-bond electronegativity equalization method fused into molecular mechanics （ABEEM/MM）. The effective Co^3＋ ion-water potential has been constructed by fitting to ab initio structures and binding energies for ionic clusters. And then the ion-water interaction potential was applied in combination with the ABEEM-7P water model to molecular dynamics simulations of single Co^3＋（aq.） solution, managing to reproduce many experimental structural and dynamical properties of the solution. Here, not only the common properties （radial distribution function, angular distribution function and solvation energy） obtained for Co^3＋ in ABEEM-7P water solution were in good agreement with those from the experimental methods and other molecular dynamics simulations but also very interesting properties of charge distributions, geometries of water molecules, hydrogen bond, diffusion coefficients, vibrational spectra are investigated by ABEEM/MM model.     

Synthesis of 4-[(1<Emphasis Type="Italic">R</Emphasis>,4<Emphasis Type="Italic">R</Emphasis>)-3-Oxo-<Emphasis Type="Italic">p</Emphasis>-menthan-2-ylidenemethyl]benzoic Acid and Its Esters

Carbonylation of (E)-2-(4-halobenzylidene)-p-menthan-3-ones, catalyzed by PdCl₂(PPh₃)₂, gave a distereometric mixure of 4-[(1R,4R)- and (1R,4S)-3-oxo-p-menthan-2-ylidenemethyl]benzoic acids, whose reaction with phenols gave 1R,4R diastereomers of the corresponding esters.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 4, 2005, pp. 659–664.Original Russian Text Copyright © 2005 by Drushlyak, Kutulya, Pivnenko, Vashchenko.     

How polarization damping affects ion solvation dynamics

In a recent paper (Sala et al. in J Chem Phys 133:234101, 2010), static properties of chloride in water have been addressed using a polarizable force field and by adding screening functions to damp short-range electrostatic interactions. In this contribution, we further explore the impact of damping polarizable interactions on system dynamics. To this end, results from Car–Parrinello molecular dynamics simulations have been used as benchmark for assessing the impact of damping schemes on the ion solvation dynamics of chloride in water. The results are of general validity, and the methodology could be easily implemented in all methods used to include polarization.     

Rearrangement products of some 1R,4R-2-arylidene-p-menthan-3-ones in acidic media, their structures, and conformational analysis

1R,4R-2-(4-Phenylbenzylidene)-p-menthan-3-one in acidic media undergoes rearrangement with migration of the exocyclic double bond to the cyclohexane ring to form three 2-(4-phenylbenzyl) derivatives ofp-menthen-3-ones. The reaction products differ in the location of the endocyclic double bond (Δ¹ or Δ⁴) and in the configuration of the new chiral C(2) center in the resultingp-menth-4-en-3-ones. The configurations of the 1R,2R- and 1R,2S-2-(4-phenylbenzyl)-p-menth-4-en-3-ones were established based on analysis of their¹H NMR spectra in combination with calculations by molecular mechanics. The molecular conformations of these compounds as well as of some racemic 2-benzyl-p-menth-1-en-3-one derivatives were studied.     

Calculated and experimental NMR chemical shifts of p-menthane-3,9-diols. A combination of molecular dynamics and quantum mechanics to determine the structure and the solvent effects

NMR chemical shifts have been experimentally measured and theoretically estimated for all the carbon atoms of (1R,3S,4S,8S)-p-menthane-3,9-diol in chloroform solution. Theoretical estimations were performed using a combination of molecular dynamics simulations and quantum mechanical calculations. Molecular dynamics simulations were used to obtain the most populated conformations of the (1R,3S:4S,8S)-p-menthane-3,9-diol as well as the distribution of the solvent molecules around it. Quantum mechanical calculations of NMR chemical shifts were performed on the most relevant conformations employing the GIAO-DFT formalism. A special emphasis was put in evaluating the effects of the surrounding solvent molecules. For this purpose, supermolecule calculations were performed on complexes constituted by the solute and n chloroform molecules, where n ranges from 3 to 16. An excellent agreement with experimental data has been obtained following this computational strategy.     

Unusual pathway of alkylation of 2-(4-bromobenzylidene)-<Emphasis Type="Italic">p</Emphasis>-menthan-3-one with ethyl bromoacetate

Reaction of enolate carbanion, generated from 2-(4-bromobenzylidene)-p-menthan-3-one, with ethyl bromoacetate proceeds selectively as the O-alkylation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2420–2423, December, 2007.     

The COMPASS force field: parameterization and validation for phosphazenes

A new, condensed-phase optimised ab-initio force field, COMPASS, has been developed recently. In this paper, the validation of COMPASS for phosphazenes is presented. The functional forms of this force field are of the consistent force field (CFF) type. Charges and bonded terms were derived from HF/6–31G1 calculations, while the nonbonded parameters (L-J 9-6 vdW potential) were initially transferred from the polymer consistent force field, pcff, and optimised using MD simulations of condensed-phase properties. As a validation of COMPASS, molecular mechanics calculations and molecular dynamics simulations have been made on a number of isolated molecules, liquids, and crystals. The calculated molecular structure, vibration frequencies, conformational properties for isolated molecules, crystal cell parameters and density, liquid density, and heat of evaporation agreed favourably with most experimental data. The special conformational properties of the tetracyclophosphazenes, (NPCI₂)₄ and (NPF₂)₄, in the solid state are discussed based on molecular mechanics and CASTEP ab-initio calculations. The effect of nonbonded cutoff distance and different algorithms for pressure control in NPT simulation was also investigated. Finally, molecular dynamics using the COMPASS force field was used to predict properties of three isomers of high-molecular-weight amorphous poly(dibutoxyphosphazenes). In this case, excellent agreement was achieved between densities and glass transition temperatures obtained from dynamics and experimental data.     

Influence of Intermolecular Vibrations on the Electronic Coupling in Organic Semiconductors: The Case of Anthracene and Perfluoropentacene

We have performed classical molecular dynamics simulations and quantum‐chemical calculations on molecular crystals of anthracene and perfluoropentacene. Our goal is to characterize the amplitudes of the room‐temperature molecular displacements and the corresponding thermal fluctuations in electronic transfer integrals, which constitute a key parameter for charge transport in organic semiconductors. Our calculations show that the thermal fluctuations lead to Gaussian‐like distributions of the transfer integrals centered around the values obtained for the equilibrium crystal geometry. The calculated distributions have been plugged into Monte‐Carlo simulations of hopping transport, which show that lattice vibrations impact charge transport properties to various degrees depending on the actual crystal structure.     

Influence of electrostatic interactions on the properties of cyanobiphenyl liquid crystals predicted from atomistic molecular dynamics simulations

The influence of force field details in all-atom molecular dynamics (MD) simulations on the predicted thermodynamic, structural, and dynamic properties of bulk 4-cyano-4?-pentylbiphenyl (5CB) systems have been investigated in the 292–368 K temperature range. The effect of the molecular dipole moment and the details of dihedral potential for biphenyl unit were investigated using both polarisable (POL) and non-polarisable (NP) versions of the quantum chemistry-based force field. The predicted densities for the nematic and isotropic phases of bulk 5CB were found to be in excellent agreement with available experimental data. The nematic-isotropic transition temperature (T_NI) showed strong sensitivity to the force field details, MD simulations with partial atomic charge distributions and molecular dipole moment corresponding to high-level quantum chemistry calculations predicted an overestimation of the T_NI by about 30 K. Rescaling the charges to allow the molecular dipole to be closer to experimentally reported values of 5CB dipole in condensed phases, significantly improved the prediction of T_NI as well as other thermodynamic and dynamic properties of 5CB. We also discuss how the structural, thermodynamic, and dynamic properties of bulk 5CB are affected by the flexibility of the central biphenyl dihedral and the inclusion of induced polarisation effects.     

All-atom and united-atom simulations of guanidinium-based ionic liquids

Ionic liquids (ILs) have been widely used in separation, catalysis, electrochemistry, etc., and one of the most outstanding characteristics is that ILs can be tailored and tuned for specific tasks. In order to design and make better use of ionic liquids, the structures and properties relationship is indispensable. Both molecular dynamics and Monte Carlo simulations have been proved useful to understand the behavior of molecules at the microscale and the properties of the system. However, the quality of such simulations depends on force field parameters describing the interactions between atoms. All-atom (AA) or the united-atom (UA) force fields will be chosen because of the demand for more exact results or the lower computational cost, respectively. In order to make a systematic comparison of the two force fields, molecular simulations for four kinds of acyclic guanidinium-based ionic liquids (cations: (R2N)2C=N+<, anion: nitric or perchloric acid) were performed based on the AA and the UA force fields in this work. AA force field parameters were derived from our previous work (Fluid Phase Equilib., 2008, 272: 1-7), and the UA parameters were proposed in this work. Molecular dynamics simulation results for the AA and UA force fields were compared. Simulation densities are very similar to each other. Center of mass radial distribution functions (RDFs), site to site RDFs and spatial distribution functions (SDFs) were also investigated to depict the microscopic structures of the ILs.     

Atomistic hybrid particle‐field molecular dynamics combined with slip‐springs: Restoring entangled dynamics to simulations of polymer melts

In hybrid particle‐field (hPF) simulations (J. Chem. Phys., 2009 130, 214106), the entangled dynamics of polymer melts is lost due to chain crossability. Chains cross, because the field‐treatment of the nonbonded interactions makes them effectively soft‐core. We introduce a multi‐chain slip‐spring model (J. Chem. Phys., 2013 138, 104907) into the hPF scheme to mimic the topological constraints of entanglements. The structure of the polymer chains is consistent with that of regular molecular dynamics simulations and is not affected by the introduction of slip‐springs. Although slight deviations are seen at short times, dynamical properties such as mean‐square displacements and reorientational relaxation times are in good agreement with traditional molecular dynamics simulations and theoretical predictions at long times.     

Enzyme‐Mediated Preparation of Enantiomerically Pure p‐Menthan‐ 3,9‐diols and Their Use for the Synthesis of Natural p‐Menthane Lactones and Ethers

The diastereoselective preparation of the p‐menthane‐3,9‐diols (±)‐ 12 , (±)‐ 13a , (±)‐ 13b , and (±)‐ 18 and the study of their enzymic resolution is described (Scheme 1). The corresponding enantiomer‐enriched diols obtained by means of the lipase‐mediated kinetic acetylation of the racemic diols are suitable synthetic precursors of many relevant p‐menthane monoterpenes. Their usefulness is shown in the preparation of different natural products of this class that are interesting for industrial purposes because of their odor qualities, i.e., of the enantiomeric form of 3‐hydroxy‐p‐menthan‐9‐oic acid lactone 1 , of mintlactone 2 , of the 3,9‐epoxy‐p‐menth‐1,8(10)‐diene 10 , and of the pheromone vesperal 11 (Schemes 2 and 3).     

Molecular Dynamics Simulation Study of ClF in Water: Halogen Bonding Interaction in Liquid

Does the halogen bonding interaction co-exist in liquid when it competes with the hydrogen bonding interaction? The classical molecular dynamics simulations for the solvation properties of ClF molecule in water are performed with the Lennard-Jones plus Coulomb electrostatic potential parameters that are optimized with ab initio interaction energy calculations for the pre-reactive H₂O…ClF complex. We find that the halogen bonding interactions occur between O and Cl atoms and have the comparable strength and population with respect to the hydrogen bonding interactions of Cl…H.     

Reparameterizations of the χ Torsion and Lennard‐Jones σ Parameters Improve the Conformational Characteristics of Modified Uridines

The currently available force field parameters for modified RNA residues in AMBER show significant deviations in conformational properties from experimental observations. The examination of the transferability of the recently revised torsion parameters revealed that there was an overall improvement in the conformational properties for some of the modifications but the improvements were still insufficient in describing the sugar pucker preferences (J. Chem. Inf. Model. 2014, 54, 1129–1142). Here, we report an approach for the development and fine tuning of the AMBER force field parameters for 2‐thiouridine, 4‐thiouridine, and pseudouridine with diverse conformational preferences. The χ torsion parameters were reparameterized at the individual nucleoside level. The effect of combining the revised γ torsion parameter and modifying the Lennard‐Jones σ parameters were also tested by directly comparing the conformational preferences obtained from our extensive molecular dynamics simulations with those from experimental observations. © 2016 Wiley Periodicals, Inc.     

Mass spectrometric studies of cycloalkane-α-glycols

The mass spectral fragmentations of stereoisomeric cyclohexane-1,2-diols, p-menthane-2,3-diols, 1-hydroxycarvomenthols and 4-hydroxymenthols are discussed.     

A polarizable empirical force field for molecular dynamics simulation of liquid hydrocarbons

Electronic polarizability is usually treated implicitly in molecular simulations, which may lead to imprecise or even erroneous molecular behavior in spatially electronically inhomogeneous regions of systems such as proteins, membranes, interfaces between compounds, or mixtures of solvents. The majority of available molecular force fields and molecular dynamics simulation software packages does not account explicitly for electronic polarization. Even the simplest charge‐on‐spring (COS) models have only been developed for few types of molecules. In this work, we report a polarizable COS model for cyclohexane, as this molecule is a widely used solvent, and for linear alkanes, which are also used as solvents, and are the precursors of lipids, amino acid side chains, carbohydrates, or nucleic acid backbones. The model is an extension of a nonpolarizable united‐atom model for alkanes that had been calibrated against experimental values of the density, the heat of vaporization and the Gibbs free energy of hydration for each alkane. The latter quantity was used to calibrate the parameters governing the interaction of the polarizable alkanes with water. Subsequently, the model was tested for other structural, thermodynamic, dielectric, and dynamic properties such as trans/gauche ratios, excess free energy, static dielectric permittivity, and self‐diffusion. A good agreement with the experimental data for a large set of properties for each considered system was obtained, resulting in a transferable set of polarizable force‐field parameters for CH₂, CH₃, and CH₄ moieties. © 2014 Wiley Periodicals, Inc.