Improvement in aqueous solubility of achiral symmetric cyclofenil by modification to a chiral asymmetric analog

Decreasing the partition coefficient (LogP) by the introduction of a hydrophilic group is the conventional approach for improving the aqueous solubility of drug candidates, but is not always effective. Since melting point is related to aqueous solubility, we and other groups have developed alternative strategies to improve solubility by means of chemical modification to weaken intermolecular interaction in the solid state, thereby lowering the melting point and increasing the solubility. Here, we show that converting the symmetrical molecular structure of the clinically used estrogen receptor (ER) antagonist cyclofenil (1) into asymmetrical form by introducing an alkyl group enhances the aqueous solubility. Among the synthesized analogs, the chiral methylated analog (R)-4c shows the highest solubility, being 3.6-fold more soluble than 1 even though its hydrophobicity is increased by the methylation. Furthermore, (R)-4c also showed higher membrane permeability than 1, while retaining a comparable metabolic rate, and equivalent biological activity of the active forms (R)-13a to 2. Further validation of this strategy using lead compounds having symmetric structures is expected.

Improving the Stability of Lycopene from Chemical Degradation in Model Beverage Emulsions: Impact of Hydrophilic Group Size of Emulsifier and Antioxidant Polarity

The chemical stability of the lipophilic bioactives encapsulated in emulsions can be influenced by emulsion droplet interfacial characteristics as well as by the ability of antioxidants incorporated in emulsion to prevent the degradation of the encapsulated compounds. Therefore, this study evaluated the effects of the interfacial characteristics of emulsions and the polarity of antioxidants on the storage stability of lycopene in emulsions. Emulsions with 5% (w/w) oil containing lycopene (30 µmol/kg emulsion) were prepared using a series of polyethylene glycol acyl ether-type emulsifiers through microfluidization. Change in lycopene content in emulsions was monitored by high performance liquid chromatography. Our findings show that the hydrophilic group size (or length) of emulsifiers and the emulsifier concentration at the interfacial film play a role, albeit minor, in controlling the storage stability of lycopene encapsulated in emulsions. Lipophilic (tert-butylhydroquinone (TBHQ)) and amphiphilic (lauryl gallate) antioxidants similarly improved the storage stability of lycopene in emulsions from acid- and radical-mediated degradation, independent of the characteristics of interfacial films of emulsions. However, TBHQ inhibited the degradation of lycopene in emulsions more effectively than lauryl gallate under conditions intended to accelerate the acid-mediated degradation of lycopene. Therefore, our findings can provide helpful information about what type of emulsifiers and antioxidants can be chosen for preparing food emulsions capable of maximizing the stability of lycopene encapsulated therein.

Systematically Exploring Molecular Aggregation and Its Impact on Surface Tension and Viscosity in High Concentration Solutions

The aggregation structure of dye molecules has a great influence on the properties of dye solutions, especially in high concentration. Here, the dye molecular aggregation structures were investigated systemically in aqueous solutions with high concentration using three reactive dyes (O-13, R-24:1 and R-218). O-13 showed stronger aggregation than R-24:1 and R-218. This is because of the small non-conjugate side chain and its β-linked position on the naphthalene of O-13. Compared with R-218, R-24:1 showed relatively weaker aggregation due to the good solution of R-24:1. The change of different aggregate distributions in the solutions were also investigated by splitting the absorption curves. Moreover, it is found that the surface tension of solutions can be modified by the combined effect of both aggregation and the position of the hydrophilic group, which, however, also have an effect on viscosity. This exploration will provide guidance for the study of high concentration solutions.

(R)-2-Phenyl-4,5-Dihydrothiazole-4-Carboxamide Derivatives Containing a Diacylhydrazine Group: Synthesis, Biological Evaluation, and SARs

A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated. The antifungal activity result indicated that most title compounds against Cercospora arachidicola, Alternaria solani, Phytophthora capsici, and Physalospora piricola exhibited apparent antifungal activities at 50 mg/L, and better than chlorothalonil or carbendazim. The EC50 values of (R)-N’-benzoyl-2-(4-chlorophenyl)-4,5-dihydrothiazole-4-carbohydrazide (I-5) against six tested phytopathogenic fungi were comparable to those of chlorothalonil. The CoMSIA model showed that a proper hydrophilic group in the R1 position, as well as a proper hydrophilic and electron-donating group in the R2 position, could improve the antifungal activity against Physalospora piricola, which contributed to the further optimization of the structures. Meanwhile, most title compounds displayed good insecticidal activities, especially compound (R)-N’-(4-nitrobenzoyl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carbohydrazide (III-3). The insecticidal mechanism results indicated that compound III-3 can serve as effective insect Ca2+ level modulators by disrupting the cellular calcium homeostasis in Mythimna separata.

Asymmetric Iodoetherification of Isosorbide-Derived Glycals: A Regio- and Stereoselective Access to a Variety of O-Substituted Isosorbide Derivatives

Isosorbide is a competitive starting material for various valuable derivatives by functionalization and/or substitution since it is a renewable and carbon neutral material that is produced on an industrial scale from sorbitol. A set of O-alkyl- or O-arylated beta-iodo ethers has been synthesized from isosorbide. The key step was the iodoetherification of isosorbide-derived glycals with a variety of oxygenated nucleophiles in the presence of N-iodosuccinimide. trans-Iodo ethers and acetate were obtained in good yields and the removal of iodide affords isosorbide derivatives. The usefulness of this new approach is illustrated by the synthesis of a surfactant having a dimer of isosorbide as hydrophilic group and by the preparation of a structurally unusual bicyclic anhydro carbohydrate.

Studies of Thermo-acoustical Properties of Polyoxyethylene (20) cetyl ether (Brij-58) in Presence of Additives at Different Temperatures

The measurement of ultrasonic velocity and density as a function of temperature and concentration of additives were carried out. The variation of ultrasonic velocity and density of micellar solution of Polyoxyethylene (20) cetyl ether (Brij-58, CMC= 0.0086% w/v) in the presence of polymer PVP and PEO were studied at 298.15, 303.15, 308.15 and 313.15K. Various acoustic parameters such as adiabatic compressibility (?ad), molar volume (Vm), intermolecular free length (Lf), acoustic impedance (Z) and surface tension (?) of aqueous solution of Brij-58 and Brij-58-polymer mixed solutions were derived from these data. The results were discussed on the basis of polymer-surfactant interactions and hydrophobic interaction, which in turn depends upon the structural arrangement of the linkages involved and difference in the chain which binds the hydrophobic and hydrophilic group in the studied surfactant molecule. It was noted that the ultrasound velocity decreases with increase in temperature. The decrease in the value of ?ad and Lf with increase in ultrasonic velocity indicates that there is significant interaction between the surfactant molecule and added polymer PVP and PEO.

STUDYING OF CONNECTION OF HYDROCARBON FRAGMENT OF COLLECTOR WITH ITS FLOTATION ACTIVITY

High flotation activity of collector when additional hydrophilic group is implemented in its structure of hydrocarbon fragment does not have explanation in thermodynamic description of the elementary act of flotation. An assumption is made that the presence of hydrophilic group promotes connection establishing of energetic links between hydrocarbon fragment of reagent and water molecules. As a result, speed of spreading of physical form of reagent sorption on “gas-liquid” interface, when flotation complex forms, increases. Connection between flotation activity of collector, its structure and composition and power of surface flow of its physically sorbed forms is established.

20.7% highly reproducible inverted planar perovskite solar cells with enhanced fill factor and eliminated hysteresis

The approach of a hydrophilic group grafted buffer layer (HGGBL) was investigated for perovskite growth to realize highly efficient inverted planar perovskite solar cells with superior reproducibility, negligible hysteresis and improved stability.

Design, synthesis and characterization of bitumen emulsifiers based on molecular simulation

Under the guidance of molecular simulation technology, the Monte Carlo molecular mechanics simulation was used to calculate the compatibility of different lipophilic groups with each component of bitumen, and the compatibility of different hydrophilic groups with water. Based on the calculated results of interaction parameters Chi and mixture energy Emix, the preferred structures of lipophilic and hydrophilic groups of bitumen emulsifier were determined. The target bitumen emulsifier was then synthesized by the reaction of organic acid and polyamine. The molecular simulation results showed that the compatibility of lipophilic group T11 with the bitumen was the best, and the mixing ability of the hydrophilic group H5 with water was excellent. The experimental results show that the preferred structures T11H5 had a good emulsifying performance to prepare emulsified bitumen with good storage stability, consistent with the results of the molecular simulation.