Orientation Of Phenyl Rings Research Articles

Single crystal, conformational, quantum reactivity, hirshfeld surface, molecular interactions, ADMET, and molecular docking investigations on HIV-1 site of 3-isopropyldiphenyl-1-(2-(thiophen-2yl)acetyl)piperidin-4-one

The 3-isopropyl-2,6-diphenyl-1-(2-(thiophen-2yl)acetyl)piperidin-4-one (IPTP) single crystals were grown by slow evaporation method and the structure is confirmed through FT-IR, 1H NMR, and 13C NMR spectral analyses. Single crystal X-ray diffraction revealed that the title compound having chair conformation of the piperidine ring, with an axial orientation of phenyl rings at C-2 and C-6 positions and an isopropyl group at C-3. Hirshfeld surface analysis was employed to examine intermolecular contacts and strong and weak attractive, repulsive, and van der Waals interactions in the molecule were determined using the reduced density gradient method (RDG). The geometrical parameters obtained through Density Functional Theory are compared with experimental values and also conducted to optimize structural parameters, frontier molecular orbitals (FMOs), and molecular electrostatic potential surface analysis (MEPS). NBO calculations were employed to investigate intermolecular and intramolecular charge movement, as well as the molecule's stability. Vibrational Energy Distribution Analysis (VEDA) software facilitated potential energy decomposition (PED) analysis using FT-IR wave numbers. The title compound molecular docking data were compared with the markedly available FDA-approved anti-HIV drug of Nelfinavir and their results were discussed, ADME analysis studies were discussed concerning FDA-approved anti-HIV drugs, including Nelfinavir, Betulinic Acid, Haloperidol, and Donepezil.

Syntheses and Structure-Activity Relationship Studies of Antitumor Bicyclic Hexapeptide RA-VII Analogues

A series of antitumor bicyclic hexapeptide RA-VII analogues modified at residue 2, 3, or 6 were prepared by the chemical transformation of the hydroxy, methoxy, or carboxy groups or the aromatic rings of natural peptides RA-II, III, V, VII, and X. Analogues with modified side chains or peptide backbones, which cannot be prepared by the chemical transformation of their natural peptides, and newly isolated peptides from Rubia cordifolia roots were synthesized by using protected cycloisodityrosines prepared by the degradation of bis(thioamide) obtained from RA-VII or the diphenyl ether formation of boronodipeptide under the modified Chan-Lam coupling reaction conditions. Studies of the conformational features of the analogues and the newly isolated peptides and their relationships with cytotoxic activities against the HCT-116, HL-60, KATO-III, KB, L1210, MCF-7, and P-388 cell lines revealed the following: the methoxy group at residue 3 is essential for the potent cytotoxic activity; the methyl group at Ala-2 and Ala-4 but not at D-Ala-1 is required to establish the bioactive conformation; the N-methyl group at Tyr-5 is necessary for the peptides to adopt the active conformation preferentially; and the orientation of Tyr-5 and/or Tyr-6 phenyl rings has a significant effect on the cytotoxic activity.

Nanostructuring Polystyrene in a Melt

The melts of four fractions of polystyrene are investigated by the method of electric birefringence. It is found that the electro-optical properties of the melt greatly depend on the length of the polymer chain. The fractions with the highest molecular weight showed an increase in the Kerr constant K at temperatures above 120°C. The anomalous nature of the temperature dependence of the form K ∝ T is explained by the fact that at high temperatures the flexibility of the polymer chain begins to grow rapidly. This process is called the liquid-liquid transition. As a result, the short-range orientational order increases, which is associated with a change in the mutual orientation of phenyl rings.

Collective Solvation and Transport at Tetrahydrofuran-Silica Interfaces for Separation of Aromatic Compounds: Insight from Molecular Dynamics Simulations.

We have performed umbrella sampling molecular dynamics simulations to study the separation mechanism of aromatic compounds at the tetrahydrofuran (THF)-methanol-silica interface by liquid chromatography. Solute molecules with different polarities (naphthol and naphthalene) are selected as representative aromatic compounds. For the polar solute (naphthol), the free energy profile shows a deep minimum near the THF-silica interface, suggesting strong interactions with the polar surface. When methanol is added to the interface, there is a sharp increase in naphthol's free energy minimum, and the corresponding diffusion dynamics also undergoes a dramatic change. These findings explain the fast separation mechanism in recent experiments of separating fused ring compounds in asphaltenes with liquid chromatography. Further solvation structure and orientation analysis suggest that apolar and polar solutes may find their own comfort zones several angstroms away from the interface, and their phenyl ring's orientations would undergo a parallel-to-perpendicular transition as the solute molecule moves away from the surface. Extending our simulation studies to systems with different solute concentrations reveals that there is a decrease in the adsorption free energy accompanied by enhanced surface diffusion as the solute concentration increases, which is related to the crowding in the interfacial layers. Our simulation analysis gives a detailed microscopic description of solute solvation and transport at the THF-silica chromatography interface and will be helpful for improving separation protocols in future applications.

Crystal Structure, Hirschfeld Surface Analysis, and Absorption Spectra of a New Polymorph of Highly Symmetric Tetraphenylporphyrinato Zn(II), ZnTPP

The crystal and molecular structure of a new polymorph of four-coordinated Zn(II) tetraphenylporphyrin, with formula ZnTPP (TPP = 5,10,15,20-tetraphenyl porphyrin) has been determined from 3D X-ray diffraction data. The new polymorph crystallizes in the tetragonal space group, I4/m with cell dimensions a = 13.4206(9), c = 9.7210(16) A, V = 1750.9(3) A3, and Z = 4. The previous polymorph was crystallized in triclinic space group, P $$\bar {1}$$ . The single crystal of toluene solvate, a pseudopolymorph of tetraphenylporphinatozinc(II), ZnTPP ⋅ 2C7H8 was also crystallized in the triclinic space group, P $$\bar {1}$$ . The porphyrin cores of all the three centrosymmetric crystalline forms adopt a planar conformation which is attributed to the equivalent size of Zn2+ cations and that of porphyrin cores. In contrast to the two previous triclinic structures, which have two crystallography unique pyrrole rings, the tetragonal structure in the present form has all the pyrrole rings symmetric in nature. Further the symmetric orientations of phenyl rings about the mean N4 plane in the present form, unlike the two previous triclinic forms in which phenyl rings makes two types of dihedral angles with mean N4 plane reflects that the tetragonal structure of ZnTPP is the highly ordered geometry. All the four Zn–N bond distances in the present form are equal i.e., 2.048(2) A and is slightly longer than the average Zn–N bond distances found in the previous triclinic forms. The 3D packing of present form features sandwich type or face to face stacked layers that are bridged by a body centred molecule. The crystal packing is mainly stabilised by C–H⋅⋅⋅C and H⋅⋅⋅H intermolecular forces. Further the role and nature of various intermolecular interactions were quantitatively analysed by 3D Hirschfeld surface analysis and associated 2D fingerprint plots. The optical absorption spectra of ZnTPP and its free base analog, H2TPP have been further analysed in pure organic solvents of CH2Cl2 and CH3OH at different ionic strengths of the media and their results have been discussed in detail.

Fabrication and Characterization of Anthracene Doped P-terphenyl Thin Films By Spin Coating Technique; Investigation of Fluorescence Properties.

Thin films of p-terphenyl luminophors doped by varying amounts of anthracene were prepared by using spin coating technique. The morphological, structural, and photophysical investigation of thin films of p-terphenyl as a function of anthracene concentration is studied by using scanning electron microscopy (SEM), X-ray diffraction (XRD), fluorescence spectroscopy and fluorescence microscopy. The results of XRD and SEM studies indicated that the doped p-terphenyl thin film is homogeneous as compared with a bare p-terphenyl thin film. The fluorescence spectroscopy results indicate complete quenching of p-terphenyl fluorescence and simultaneous sensitization of blue anthracene like emission towards the red side of the spectrum with maximum intensity at 410 nm. The blue intense emission of anthracene seen in fluorescence microscopy images is in agreement with observed fluorescence spectral results. A suitable mechanism of excitation energy transfer (EET) from p-terphenyl to anthracene molecules is proposed and discussed on the basis of energy level diagram. The efficient EET is believed to occur by the orientation of phenyl rings of p-terphenyl in excited state. As the concentration of doped anthracene increases, the fluorescence intensity of doped p-terphenyl and Full Width at Half Maximum (FWHM) found to be increased. The p-terphenyl film containing 0.65 moles of anthracene is of FWHM as low as 28.51 nm. Such narrow band blue emitting doped luminophors are of demand in light emitting diodes (OLED) and scintillation applications.

Enhanced Thermal Stability of Polystyrene by Interfacial Noncovalent Interactions

The local conformation of polystyrene (PS) and deuterated PS at the interface with quartz substrates, which were covered with phenyl groups using phenyltrimethoxysilane (PTS) under various conditions, was examined by sum frequency generation spectroscopy. As evidenced by the red-shift of the wavenumber of the v2 vibration mode for phenyl groups, it was claimed that PTS phenyl groups standing vertically from the quartz surface induced the perpendicular orientation of PS phenyl rings by energetically favorable parallel-displaced π–π interactions at the interface. The local conformation of PS chains strongly anchored onto the substrate by the π–π interactions remained almost unchanged for 48 h even at a temperature 60 K higher than the bulk glass transition temperature. That is, the interfacial π–π interactions facilitated the adsorption of PS chains on the substrate to attain a large enthalpic gain, resulting in significantly slower dynamics of PS chains at the interface. Our results illustrate the importan...

Flipped Phenyl Ring Orientations of Dopamine Binding with Human and Drosophila Dopamine Transporters: Remarkable Role of Three Nonconserved Residues.

Molecular modeling and molecular dynamics simulations were performed in the present study to examine the modes of dopamine binding with human and Drosophila dopamine transporters (hDAT and dDAT). The computational data revealed flipped binding orientations of dopamine in hDAT and dDAT due to the major differences in three key residues (S149, G153, and A423 of hDAT vs A117, D121, and S422 of dDAT) in the binding pocket. These three residues dictate the binding orientation of dopamine in the binding pocket, as the aromatic ring of dopamine tends to take an orientation with both the para- and meta-hydroxyl groups being close to polar residues and away from nonpolar residues of the protein. The flipped binding orientations of dopamine in hDAT and dDAT clearly demonstrate a generally valuable insight concerning how the species difference could drastically affect the protein-ligand binding modes, demonstrating that the species difference, which is a factor rarely considered in early drug design stage, must be accounted for throughout the ligand/drug design and discovery processes in general.

Polymorphism and Modulation of Para-Substituted l-Phenylalanine.

The crystal structure of para-methyl-l-phenylalanine at 230 K resembles that of the para-fluorinated analogue from the literature but is commensurately modulated with seven molecules in the asymmetric unit (Z′ = 7). At 100 K, the superstructure loses its modulation, leading to a unit cell with Z′ = 1, with clear disorder in the phenyl ring orientations. The methyl-substituent in para-methyl-l-phenylalanine has, in contrast to fluorine, no polar interactions with protons of neighboring molecules, which might allow for the well-defined modulation of the crystal structure at 230 K.

Depth-resolved local conformation and thermal relaxation of polystyrene near substrate interface.

By means of sum-frequency generation spectroscopy, we report a depth-resolved measurement of the local conformation and chain relaxation of polystyrene (hPS) located at different distances from the quartz interface. To control the distance from the quartz interface, deuterated polystyrene (dPS) layers with thicknesses of 3.4, 7.5, and 20 nm were coated on the quartz substrates. The hPS chains in direct contact with the substrate surface predominantly orient their phenyl rings in a direction normal to the substrate. This conformation was found to be barely relaxed when the film was annealed for 24 h at 423 K, higher than the bulk glass transition temperature. In contrast, for the hPS chains supported on the dPS layer, the orientation of phenyl rings of hPS became weaker with the annealing and this trend was more significant with increasing distance from the quartz substrate. In particular, the orientation of phenyl rings of hPS after annealing vanished at a distance of 20 nm. These results might provide an important evidence of the difference in the relaxation dynamics of the PS chains located at different distances from the quartz interface.

Distribution of glass transition temperatures Tg in polystyrene thin films as revealed by low-energy muon spin relaxation: A comparison with neutron reflectivity results.

In a previous paper [Phys. Rev. E 83, 021801 (2011)] we performed neutron reflectivity (NR) measurements on a five-layer polystyrene (PS) thin film consisting of alternatively stacked deuterated polystyrene (dPS) and hydrogenated polystyrene (hPS) layers (dPS/hPS/dPS/hPS/dPS, ∼100 nm thick) on a Si substrate to reveal the distribution of Tg along the depth direction. Information on the Tg distribution is very useful to understand the interesting but unusual properties of polymer thin films. However, one problem that we have to clarify is if there are effects of deuterium labeling on Tg or not. To tackle the problem we performed low-energy muon spin relaxation (μSR) measurements on the above-mentioned deuterium-labeled five-layer PS thin film as well as dPS and hPS single-layer thin films ∼100 nm thick as a function of muon implantation energy. It was found that the deuterium labeling had no significant effects on the Tg distribution, guaranteeing that we can safely discuss the unusual thin film properties based on the Tg distribution revealed by NR on the deuterium-labeled thin films. In addition, the μSR result suggested that the higher Tg near the Si substrate is due to the strong orientation of phenyl rings.

To be or not to be butterfly: New mechanistic insights in the Aza-Michael asymmetric addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide.

The asymmetric Aza-Michael addition of homochiral lithium benzylamides to α,β-unsaturated esters represents an extended protocol to obtain enantioenriched β-amino esters. An exhaustive mechanistic revision of the originally proposed mechanism is reported, developing a quantum mechanics/molecular mechanics protocol for the asymmetric Aza-Michael reaction of homochiral lithium benzylamides. Explicit and implicit solvent schemes were considered, together with a proper account of long-range dispersion forces, evaluated through a density functional theory benchmark of different functionals. Theoretical results showed that the diastereoselectivity is mainly controlled by the N-α-methylbenzyl moiety placing, deriving a Si/Re 99:1 diastereoselective ratio, in good agreement with reported experimental results. The main transition state geometries are two transition state conformers in a "V-stacked" orientation of the amide's phenyl rings, differing in the tetrahydrofuran molecule arrangement coordinated to the metal center. Extensive conformational sampling and quantum-level refinement give reasonable good speed/accuracy results, allowing this protocol to be extended to other similar Aza-Michael reaction systems.

Organic and organometallic derivatives of pentaphenylbenzene, C6Ph5X: correlation of peripheral phenyl ring orientations with the steric bulk of “X”

A series of C6Ph5X compounds, including X = H, Br, CO2H, CO2R, C[Formula: see text]CPh, cis-BrC=C(Br)Ph, 2-bornenyl, and ferrocenyl, have been characterized by use of X-ray crystallography. Also, the first organometallic complexes of pentaphenylbenzene have been prepared by reaction with chromium hexacarbonyl to yield (η6-C6Ph5H)Cr(CO)3 complexes in which the metal tripod is attached either to an ortho peripheral ring or to the central ring. Crystalline pentaphenylbenzoic acid exists as a hydrogen-bonded dimer; however, the steric bulk of the substituents does not allow the carboxylic acid moieties to be linked directly but instead via two bridging methanol molecules. In the solid state, the orientation of the peripheral rings in bulky C6Ph5X systems is very sensitive to the size of the “X” substituents, such that the twist angle of the para ring responds inversely with increasing bulk of “X”, which drives the ortho rings farther out of the plane of the central ring. The relevance of these observations to correlated motion in molecular propellers, and ultimately to molecular machines, is discussed.

Conformational and crystal energetics of a polymorphic cyclized product of Napafenac: The Z′ and crystal stability correlation

We report the single crystal diffraction study of a dimorphic 7-benzoyl-1,3-dihydroindol-2-one system and evaluate its stability relationships through thermal, grinding and slurry methods. Computational methods are invoked to understand the stability relationships. The form I crystallizes in the triclinic space group P1¯ with two molecules in the asymmetric unit (Z′=2), whereas, form II crystallizes in the monoclinic space group P21/c with a single molecule in the asymmetric unit (Z′=1). The molecules exhibit subtle conformational variations along the bond connecting the phenyl and indole rings and adopt different crystal packing. While both polymorphs show similar amide dimer of NH⋯O interactions, they do differ significantly in the way the amide dimers are packed. The Differential Scanning Calorimetry (DSC), phase transformation studies and lattice energy calculations clearly established the greater stability of high Z′ form over low Z′ form, which contradicts the widely accepted notion that Z′>1 structures are usually kinetic (or metastable). The choice of two different orientations of phenyl rings in form I enforces shorter π⋯π interactions and additional CH⋯π contacts to result in the extra stabilization energy over form II crystal packing with a single conformer. The Z′ and stability correlation is established in 83 reported polymorphic systems which indicate that the number of stable crystal structures decrease as the Z′ value increases. However, the polymorphic systems with Z′=1 and 2 combinations are more frequently observed than any other combinations.

Redox-sensitive structural change in the A-domain of HMGB1 and its implication for the binding to cisplatin modified DNA

HMGB1 (high-mobility group B1) is a ubiquitously expressed bifunctional protein that acts as a nuclear protein in cells and also as an inflammatory mediator in the extracellular space. HMGB1 changes its functions according to the redox states in both intra- and extra-cellular environments. Two cysteines, Cys23 and Cys45, in the A-domain of HMGB1 form a disulfide bond under oxidative conditions. The A-domain with the disulfide bond shows reduced affinity to cisplatin modified DNA. We have solved the oxidized A-domain structure by NMR. In the structure, Phe38 has a flipped ring orientation from that found in the reduced form; the phenyl ring in the reduced form intercalates into the platinated lesion in DNA. The phenyl ring orientation in the oxidized form is stabilized through intramolecular hydrophobic contacts. The reorientation of the Phe38 ring by the disulfide bond in the A-domain may explain the reduced HMGB1 binding affinity towards cisplatinated DNA.

Surface Orientation of Polystyrene Based Polymers: Steric Effects from Pendant Groups on the Phenyl Ring

Near edge X-ray absorption fine structure (NEXAFS) coupled with molecular dynamics simulations were utilized to probe the orientation at the exposed surface of the polymer film for polystyrene type polymers with various pendant functional groups off the phenyl ring. For all the polymers, the surface was oriented so that the rings are nominally normal to the film surface and pointing outward from the surface. The magnitude of this orientation was small and dependent on the size of the pendant functional group. Bulky functional groups hindered the surface orientation, leading to nearly unoriented surfaces. Depth dependent NEXAFS measurements demonstrated that the surface orientation was localized near the interface. Molecular dynamics simulations showed that the phenyl rings were not oriented strongly around a particular "average tilt angle". In contrast, simulations demonstrate that the phenyl rings exhibit a broad distribution of tilt angles, and that changes in the tilt angle distribution with pendant functionality give rise to the observed NEXAFS response. The more oriented samples exhibit a higher probability of phenyl ring orientation at angles greater than 60 degrees relative to the plane of the films surface.

Phe233 in the Voltage-Sensor is Rate Limiting for Channel Closure but not for the Opening

During activation, the charged S4 segment in the voltage sensor domain (VSD) of voltage-gated ion channels is required to translate across a hydrophobic zone. This constitutes a thin aperture clearly separating the open/relaxed and closed/resting states. The nature of this barrier is critical for channel function, and has been the focus of much attention. Previously, we identified the single preserved residue F233 (F290 in Shaker) as a structural barrier for the gating charges, that uniquely determines intermediate state and substitutions modulate the deactivation barrier. A fundamental understanding of the S4 activation/deactivation barrier as well as kinetics is an important remaining challenge to decipher gating. Here, we study the free barrier and kinetics of the VSD through combining in-vitro and in-silico experiments. We used site-directed mutagenesis and measured the voltage-dependence in-vitro to study the effect of F290L compared to the wild-type (WT). In parallel, molecular dynamics simulations allowed us to identify residues interacting with the phenyl ring. Through in-silico mutations we show their impact on the barrier, as well as the structural and kinetics effects for the phenyl ring orientation during the first step of deactivation and the (reverse) last step of the activation. Strikingly, the channel closing transition shows a huge speedup from the F290L mutant (1ms, WT 10ms), in contrast to the opening that is completely unaffected. This indicates that F233 is only rate-limiting for the channel closure, but not opening and suggests different kinetics for the activation/deactivation barriers. Additionally the ring is clearly stabilized through vdW interactions with surrounding hydrophobic residues, and appears to always open by upward rotation both for activation/deactivation. This upward rotation suggests a model where the closing is possibly a mostly entropic process, while opening would be largely enthalpic.

Studies of some monocyclic and bicyclic arylacetonitriles

The high-resolution (1)H, (13)C, (1)H-(1)H COSY and (1)H-(13)C COSY NMR spectra have been recorded in CDCl(3) for arylacetonitriles 1-12 and analyzed. The arylacetonitriles 3-7 exist in two isomeric forms E (methyl group is anti to cyano group) and Z (the methyl group is syn to cyano group) in solution. Normal chair conformation with equatorial orientations of phenyl rings at C-2 and C-6 for monocyclic nitriles 1 and 2, epimeric chair structure EC (axial configuration of methyl group at C-3) for both the E and Z isomers of arylacetonitrile derivatives (3-7) and a distorted boat form, B(3), for the N-acylacetonitrile derivatives (8-10) have been proposed based on NMR data. The bicyclic nitriles 11 and 12 exist in twin chair conformations in solution. DFT calculations and chemical shifts also support these conformations. Geometry optimizations for 1-12 were carried out according to density functional theory using B3LYP/6-31G(d,p) basis set and for 1 and 8 the theoretical geometrical parameters have been compared with those of single crystal measurements.

Metal Complexes of a Structurally Embellished Phosphinane Ligand: An Assessment of Stereoelectronic Effects

AbstractThe stereoelectronic features of the pentacyclic phosphane (1S,4R,4aS,5aR,6R,9S,9aS,10aR)‐4,6,11,11,12,12‐hexamethyl‐10‐phenyldodecahydro‐1,4:6,9‐dimethanophenoxaphosphinine (phenop) have been explored through a range of empirical methods including single‐crystal X‐ray structure determinations of the sulfide derivative phenopS (1), the selenide phenopSe (2), [Fe(CO)4(κ1‐phenop)] (3), [W(CO)5(κ1‐phenop)] (4) and trans‐[Rh(κ1‐phenop)(CO)Cl] (5). Cone angles derived from the structural data range from 164–203° with the smaller values being observed for the compounds possessing a phenyl group that is orthogonal to the P–Z bond and the larger values for the compounds expressing a parallel phenyl ring orientation. The cone angle data suggest a moderately bulky phosphane comparable, in steric terms, to PCy3. This is further borne out on inspection of the M–P bond lengths which tend towards the longer end of the known scale. Some flexibility is observed in the central ring which approximates to a boat conformation at one extreme and an envelope at the other depending on the nature of the P‐substituent. The electronic properties of κ1‐phenop have been assessed using a combination of infrared and NMR spectroscopy. The absolute value of the one‐bond coupling constants 1JP‐Se and 1JP‐Rh are very close to those reported for PPh3, suggesting a close analogy between κ1‐phenop and the well known triphenylphosphane. In addition, relevant υ(CO) stretches in the IR spectra of the metal carbonyl complexes also closely mimic those for the analogous complexes containing PPh3. These conclusions are supported by molecular electrostatic potential calculations at the DFT level which place phenop close to PPh3 in terms of lone pair availability.

Conductivity of Styrene Lines on Si(100)-(2×1):H: Effects of Molecular Orientation and Surface Charge

First-principles electronic structure calculations of styrene lines on H-covered Si(100) show that phenyl ring orientations at chain ends are fluxional, favoring structures with the terminal ring a...