The effect of electron withdrawing croups on the stability of thiabenzenes

The reactions of p-trifluoromethylphenyllithium with 2,4,6-triarylthiopyrylium perehlorates (Ar = Ph, p-CH₃OC₆H₄, p-NMe₂C₆H₄) have been studied. The initially formed thiabenzenes were not slable enough to he isolated and rearranged readily to their corresponding 4-(p-tri-fluoromethylphenyl)-2,4,6-triarylthiopyrans. The instability of the intermediate thiabenzenes reveals that, in contrast to the stabilization effect of the electron-withdrawing p-chloro- and pentalluorophcnyl groups attached to carbon atoms in sulfur ring, the electron-withdrawing p-lrilluoromethyl group on subsliluenls attached to sulfur decreases the stability of thiabenzenes.     

Inclusion complexation of Itraconazole with β-and 2-hydroxypropyl-β-cyclodextrins in aqueous solutions

The inclusion behavior of Itraconazole (Itra) with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by using phase solubility and molecular mechanics techniques. The effects of pH and temperature on complex stabilit were also explored. The aqueous solubility of Itra was significantly enhanced as CD concentration increased. Itra tends to form 1: 3 complexes with β-and HP-β-CD at pH ≥ 4 and 1: 2 at pH 2. Thermodynamic parameters for Itra/HP-β-CD show that the 1: 1 complex is driven by enthalpy but retarded by entropy changes. In contrast, the formation of 1: 2 and 1: 3 complexes is largely favored by entropy due to higher desolvation induced by total enclosure of Itra with two (or three) favorably interacting CD molecules. The inclusion mode of Itra/β-CD complexes was proved by molecular mechanics technique, which provided a powerful means for understanding inclusion interactions and processes. Published in Russian in Zhurnal Fizicheskoi Khimii, 2006, Vol. 80, No. 7, pp. 1200–1205. The text was submitted by the authors in English.     

Surface active inverse micelles

Surface tension of solutions of a commercial non-ionic surfactant, Laureth 4, and two hydrocarbons, decane and hexadecane, with added water, was determined using a de Nouy ring. The results showed a reduction of surface tension with added water, confirming an earlier suggestion of surface activity of inverse micelles. The surface activity is ascribed to the orientation of the hydrocarbon chains in the inverse micelle, giving a preferential location of the low surface free-energy methyl groups at the surface of the micelle. The location of the micelle at the surface was estimated from calculations of the minimum in the free energy when a solid particle was transferred across the liquid–air interface. This energy showed a distinct minimum indicating the location of the particle. However, the conditions for that minimum to occur were such that no balance of surface tension forces along the liquid surface to air could occur. The reason for that apparent discrepancy is discussed.     

Inclusion Complexation of Loratadine with Natural and Modified Cyclodextrins: Phase Solubility and Thermodynamic Studies

The extent and mode of solubility enhancement exerted by the cyclodextrins (α-, β-, γ-, and HP-β-CDs) on loratadine (Lort) have been experimentally measured under controlled conditions in buffered aqueous solutions. Rigorous nonlinear regression analysis of the phase solubility diagrams obtained in 0.1 mol⋅L⁻¹ phosphate buffer at pH=7.0 and 25 °C revealed the following: neutral Lort (pK _a =4.6) tends to form soluble 1:1 and 1:2 Lort/CD complexes with all four of the examined CDs, where complex stability follows the decreasing order β-CD>HP-β-CD>γ-CD>α-CD. The hydrophobic character of Lort constitutes about 66% of the driving force for complex formation whereas specific interactions contribute 11.2 kJ⋅mol⁻¹ towards the stability of the complexes. Thermodynamic studies showed that Lort/CD complex formation was favored by large enthalpic contributions but was impeded by negative entropic changes. Dissolution studies indicate that the dissolution rate of Lort from the freeze-dried Lort/β-CD complex is significantly higher than that of the corresponding physical mixture. Both DSC studies and molecular mechanical modeling of Lort/β-CD interactions were carried out to explore the possible formation of inclusion complexes.     

Unit cell dimensions and space groups of some liquid crystals

It is now very well established that for a proper understanding and interpretation of several physical properties of liquid crystalline phases, a knowledge of the molecular structure in the crystalline state is very useful, as the molecular conformation in the crystalline state predetermines the molecular organisation inthe mesomorphic state. Also, it is believed that the stabilisation of liquid crystalline phase and hence the micro variations in the physical properties depend strongly on the long side chains and are essentially independent of the central rigid core. In view of this, we communicate the preliminary crystallogrphic data for some liquid crystalline materials, the detailed structure of which has been taken up.     

Crystal Structure of Mesogenic Material III Nematogenic 4–(4′-EthoxyphenyIazo)PhenyI Undecylenate

The crystal structure of 4–(4′-ethoxyphenylazo)phenyl undecylenate has been determined by direct methods. The compound crystallizes in space group P2₁/n with a = 5.914(1), b = 15.143(3), c = 25.819(2)A° and β = 91.450(2)°. The structure was refined to R = 0.0412 for 1998 observed reflections. The molecule is almost linear and planar. The angle between the two phenyl rings is 3.996°. The pairs of molecules related by a centre of symmetry form an imbricated arrangement.     

In Vitro and In Vivo Antidiabetic Potential of Monoterpenoids: An Update

Diabetes mellitus (DM) is a chronic metabolic condition characterized by persistent hyperglycemia due to insufficient insulin levels or insulin resistance. Despite the availability of several oral and injectable hypoglycemic agents, their use is associated with a wide range of side effects. Monoterpenes are compounds extracted from different plants including herbs, vegetables, and fruits and they contribute to their aroma and flavor. Based on their chemical structure, monoterpenes are classified into acyclic, monocyclic, and bicyclic monoterpenes. They have been found to exhibit numerous biological and medicinal effects such as antipruritic, antioxidant, anti-inflammatory, and analgesic activities. Therefore, monoterpenes emerged as promising molecules that can be used therapeutically to treat a vast range of diseases. Additionally, monoterpenes were found to modulate enzymes and proteins that contribute to insulin resistance and other pathological events caused by DM. In this review, we highlight the different mechanisms by which monoterpenes can be used in the pharmacological intervention of DM via the alteration of certain enzymes, proteins, and pathways involved in the pathophysiology of DM. Based on the fact that monoterpenes have multiple mechanisms of action on different targets in in vitro and in vivo studies, they can be considered as lead compounds for developing effective hypoglycemic agents. Incorporating these compounds in clinical trials is needed to investigate their actions in diabetic patients in order to confirm their ability in controlling hyperglycemia.     

Orientational order parameters of nematogenic trans-4-propyl cyclohexyl-4 (trans-4-alkyl cyclohexyl) benzoates

The refractive indices and densities of three members of trans-4-propyl cyclohexyl-4 (trans-4-alkyl cyclohexyl) benzoates are reported as functions of temperature in the nematic and isotropic phases. The principal molecular polarizabilities and order parameters (S) have been evaluated using the anisotropic internal field model (Neugebauer’s approach). Also order parameters have been estimated by studying the dipole-dipole splittings in the wide line proton magnetic resonance (PMR) spectra. The results obtained are in close agreement with those obtained from refractive index measurements.     

Inclusion complexation of diclofenac with natural and modified cyclodextrins explored through phase solubility, 1H-NMR and molecular modeling studies

Guest–host interactions were examined for neutral diclofenac (Diclo) and Diclofenac sodium (Diclo sodium) with each of the cyclodextrin (CD) derivatives: α-CD, β-CD, γ-CD and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), all in 0.05 M aqueous phosphate buffer solution adjusted to 0.2 M ionic strength with NaCl at 20 °C, and with β-CD at different pHs and temperatures. The pH solubility profiles were measured to obtain the acid–base ionization constants (pK _as) for Diclo in the presence and absence of β-CD. Phase solubility diagrams (PSDs) were also measured and analyzed through rigorous procedures to obtain estimates of the complex formation constants for Diclo/CD and Diclo sodium/CD complexation in aqueous solutions. The results indicate that both Diclo and Diclo sodium form soluble 1:1 complexes with α-, β-, and HP-β-CD. In contrast, Diclo forms soluble 1:1 Diclo/γ-CD complexes, while Diclo sodium forms 1:1 and 2:1 Diclo/γ-CD, but the 1:1 complex saturates at 5.8 mM γ-CD with a solubility product constant (pK _sp = 5.5). Therefore, though overall complex stabilities were found to follow the decreasing order: γ-CD > HP-β-CD > β-CD > α-CD, some complex precipitation problems may be faced with aqueous formulations of Diclo sodium with γ-CD, where the overall concentration of the latter exceeds 5.8 mM γ-CD. Both ¹H-NMR spectroscopic and molecular mechanical modeling (MM⁺) studies of Diclo/β-CD indicate the possible formation of soluble isomeric 1:1 complexes in water.