Development of Polar Order in the Liquid Crystal Phases of a 4‐Cyanoresorcinol‐Based Bent‐Core Mesogen with Fluorinated Azobenzene Wings

A bent‐core mesogen consisting of a 4‐cyanoresorcinol unit as the central core and laterally fluorinated azobenzene wings forms four different smectic LC phase structures in the sequence SmA–SmC_s–SmC_sP_AR–M, all involving polar SmC_sP_S domains with growing coherence length of tilt and polar order on decreasing temperature. The SmA phase is a cluster‐type de Vries phase with randomized tilt and polar direction; in the paraelectric SmC_s phase the tilt becomes uniform, although polar order is still short‐range. Increasing polar correlation leads to a new tilted and randomized polar smectic phase with antipolar correlation between the domains (SmC_sP_AR) which then transforms into a viscous polar mesophase M. As another interesting feature, spontaneous symmetry breaking by formation of a conglomerate of chiral domains is observed in the non‐polar paraelectric SmC_s phase.     

Side chain flexibility and the pore dimensions in the GABA<Subscript>A</Subscript> receptor

Permeation of ions through open channels and their accessibility to pore-targeting drugs depend on the pore cross-sectional dimensions, which are known only for static X-ray and cryo-EM structures. Here, we have built homology models of the closed, open and desensitized α₁β₂γ₂ GABA_A receptor (GABA_AR). The models are based, respectively, on the X-ray structure of α₃ glycine receptor (α₃ GlyR), cryo-EM structure of α₁ GlyR and X-ray structure of β₃ GABA_AR. We employed Monte Carlo energy minimizations to explore how the pore lumen may increase due to repulsions of flexible side chains from a variable-diameter electroneutral atom (an expanding sphere) pulled through the pore. The expanding sphere computations predicted that the pore diameter averaged along the permeation pathway is larger by approximately 3 Å than that computed for the models with fixed sidechains. Our models predict three major pore constrictions located at the levels of ?2′, 9′ and 20′ residues. Residues around the ?2′ and 9′ rings are known to form the desensitization and activation gates of GABA_AR. Our computations predict that the 20′ ring may also serve as GABA_AR gate whose physiological role is unclear. The side chain flexibility of residues ?2′, 9′ and 20′ and hence the dimensions of the constrictions depend on the GABA_AR functional state.     

Polymerization of ethylene in the presence of bis(phenoxyimine) complexes of titanium chloride that contain various substituents in a phenoxy group

The kinetic features of ethylene polymerization with six methylaluminoxane-activated bis(phenoxyimine) complexes of titanium chloride that are distinguished by the electronic properties of substituents in the phenoxy group are studied in the temperature range 30–80°C and at an ethylene pressure of 0.3 MPa. It is shown that, in the presence of an electro-donor or electron-acceptor substituent in the phenoxy group, the catalytic systems under study exhibit high activity (up to ～700 t_PE mol _cat ^?1 mol _ethylene ^?1 h^?1) and form high-molecular-mass PE samples (M _η = (500–900) × 10³) with different molecular-mass distributions. In the case of titanium bis(phenoxyimine) complexes containing donor substituents at the para position of the phenoxy group, the polymerization of ethylene follows the living-chain mechanism, while the introduction of acceptor substituents diminishes the contribution of this mechanism to the reaction.     

Donor-acceptor complexes of borazines

Donor-acceptor complexes of borazine (BZ) and its substituted derivatives with Lewis acids (A = MCl(3), MBr(3); M = B, Al, Ga) and Lewis bases (D = NH(3), Py) have been theoretically studied at the B3LYP/TZVP level of theory. The calculations showed that complexes with Lewis bases only are unstable with respect to dissociation into their components, while complexes with Lewis acids only (such as aluminum and gallium trihalides) are stable. It was shown that formation of ternary D→BZ→A complexes may be achieved by subsequent introduction of the Lewis acid (acceptor A) and the Lewis base (donor D) to borazine. The nature of substituents in the borazine ring, their number, and position were shown to have only minor influence on the stability of ternary D→BZ→A complexes due to the compensation effect. Much weaker acceptor properties of borazine are explained in terms of large endothermic pyramidalization energy of the boron center in the borazine ring. In contrast to borazine, binary complexes of the isoelectronic benzene were predicted to be weakly bound even in the case of very strong Lewis acids; ternary DA complexes of benzene were predicted to be unbound. The donor-acceptor complex formation was predicted to significantly reduce both the endothermicity (by 70-95 kJ mol(-1)) and the activation energy (by 40-70 kJ mol(-1)) for the borazine hydrogenation. Thus, activation of the borazine ring by Lewis acids may be a facile way for the hydrogenation of borazines and polyborazines.     

N-(4-(di-tert-butyl[F]fluorosilyl)benzyl)-2-hydroxy-N,N-dimethylethylammonium bromide ([F]SiFANBr): A novel lead compound for the development of hydrophilic SiFA-based prosthetic groups for F-labeling

¹⁸F-labeled compounds play a major role in the development of new in vivo imaging agents for Positron Emission Tomography (PET), a non invasive imaging modality depicting the biodistribution of radioactive compounds in humans. Recently we reported a new method for the introduction of fluorine-18 into a range of organic molecules exploiting the very fast ¹⁸F-¹⁹F isotope exchange of fluorosilanes (termed SiFA compounds). Here, we wish to report the labeling of the first charged SiFA molecule N-(4-(di-tert-butylfluorosilyl)benzyl)-2-hydroxy-N,N-dimethylethylammonium bromide (SiFAN⁺Br⁻) serving as a lead compound in the development of SiFA-based prosthetic groups of reduced lipophilicity for biomolecule labeling. Mild conditions for synthesis of [¹⁸F]SiFAN⁺Br⁻ and an easy purification procedure using simple C-18 solid phase cartridge have been developed yielding the [¹⁸F]SiFAN⁺Br⁻ in radiochemical yields of 34% (non-decay corrected) within 40 min. A series of kinetic experiments were performed that show high isotopic exchange rate constants. Low activation energy (15.7 kcal/mol) and a large preexponential factor (7.9 × 10¹³ M⁻¹ s⁻¹) were calculated for the isotopic exchange reaction from a corresponding Arrhenius plot. For comparison, the ¹⁸F-fluorination of ethyleneglycol-di-p-tosylate via the formation of a carbon-¹⁸F bond showed a 1.3 kcal/mol higher activation energy and a much lower preexponential factor of 2.9 × 10⁹ M⁻¹ s⁻¹. Moderate hydrophilicity (log D = 0.44), stability in aqueous media at pH up to 7.4 and a high specific activity of [¹⁸F]SiFAN⁺Br⁻ (SA = 20.4 GBq/μmol, 0.55 Ci/μmol) make this charged SiFA compound useful for the development of novel SiFA-based ¹⁸F-labeling synthons.     

Infrared spectroscopic studies of transition metal complexes and polarizability effect

The literature data on substituent influence on the CS, CN, NC, NN, and NO stretching frequencies (ν) in the IR spectra and in specific cases on their respective stretching force constants (k) have been analyzed for 28 series of the transition metal complexes. The ν and k values were first established to depend not only on the inductive and resonance effects but on the polarizability of substituents as well. The contribution of the polarizability effect varies from 0 to 57% with the type of series.     

On a relationship between molecular polarizability and partial molar volume in water

We reveal a universal relationship between molecular polarizability (a single-molecule property) and partial molar volume in water that is an ensemble property characterizing solute-solvent systems. Since both of these quantities are of the key importance to describe solvation behavior of dissolved molecular species in aqueous solutions, the obtained relationship should have a high impact in chemistry, pharmaceutical, and life sciences as well as in environments. We demonstrated that the obtained relationship between the partial molar volume in water and the molecular polarizability has in general a non-homogeneous character. We performed a detailed analysis of this relationship on a set of ~200 organic molecules from various chemical classes and revealed its fine well-organized structure. We found that this structure strongly depends on the chemical nature of the solutes and can be rationalized in terms of specific solute-solvent interactions. Efficiency and universality of the proposed approach was demonstrated on an external test set containing several dozens of polyfunctional and druglike molecules.     

A combined effective fragment potential-fragment molecular orbital method. II. Analytic gradient and application to the geometry optimization of solvated tetraglycine and chignolin

The gradient for the fragment molecular orbital (FMO) method interfaced with effective fragment potentials (EFP), denoted by FMO∕EFP, was developed and applied to polypeptides solvated in water. The structures of neutral and zwitterionic tetraglycine immersed in water layers of 2.0, 2.5, 3.0, 3.5, 4.0, and 4.5 A? are investigated by performing FMO∕EFP geometry optimizations at the RHF∕cc-pVDZ level of theory for the solutes. The geometries optimized with FMO-RHF∕EFP are compared to those from the conventional RHF∕EFP and are found to be in very close agreement. Using the optimized geometries, the stability of the hydrated zwitterionic and neutral structures is discussed structurally and in terms of energetics at the second-order M?ller-Plesset theory (MP2)∕cc-pVDZ level. To demonstrate the potential of the method for proteins, the geometry of hydrated chignolin (protein data bank ID: 1UAO) was optimized, and the importance of the inclusion of water was examined by comparing the solvated and gas phase structures of chignolin with the experimental NMR structure.