Comparative computational studies of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives as potential antinociceptive agents

In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a-i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds. The most active compounds were 3,4-dihydro-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-4-oxo-pyrimidine-5-carbonitrile (5b) and 3,4-dihydro-2,6-diphenyl-4-oxo-pyrimidine-5-carbonitrile (5i), which inhibited the number of abdominal constrictions, at 50 mg/kg dose, in 88.6% and 88% of the sample, respectively. A preliminary SAR study demonstrated that halogen replacement in the phenyl rings of the compounds under study reduces the antinociceptive activity. DFT calculations showed that there is a high correlation between the ionization potentials and the analgesic properties of the compounds. It was found that compounds with a positive ionization potential (compounds 5b and 5i) were found to be the best analgesic drugs in this series.     

Quantum-chemical Modeling of the Reaction of 3-Pyridinecarbaldehyde with 3-Cyano-4,5,5-trimethyl-2(5H)-furanone

The condensation of pyridinecarbaldehydes with 3-cyano-4,5,5-trimethyl-2(5H)-furanone and 3-cyano-4,6,6-trimethyl-5,6-dihydro-2(2H)-pyranone leads to the formation of the products of crotonic condensation and compounds of the Michael adduct type. A model investigation of the mechanism by the semiempirical AM1 quantum-chemical method for the case of the reaction of 3-pyridinecarbaldehyde with 3-cyano-4,5,5-trimethyl-2(5H)-furanone showed that the products can be formed in parallel from one and the same intermediate compound.     

Encapsulation of Tetraazaannulenato Compounds in Matrix by Sol-Gel Process

The hybrid organic-inorganic catalyst constituted by {5,7,12,14-tetramethyldibenzo[b,i]-1,4,8,11-tetraaza[14]annulenato} nickel (II), NiTMTAA, encapsulated in an alumina matrix has been prepared. NiTMTAA was synthesized by the reaction of nickel acetate with o-phenylenediamine in the presence of 2,4-pentanedione under argon atmosphere. The alumina hybrid material was obtained by a non hydrolytic sol-gel route, through the condensation of aluminum chloride with diisopropylether in the presence of NiTMTAA. The material has been prepared through precipitation from a gel. Characterization of the alumina hybrid material has been performed by ultra violet-visible spectroscopy, electron spectroscopic imaging, surface area, atomic absorption, infrared spectroscopy, and thermogravimetric analysis. The ultra violet-visible absorption spectrum of the hybrid material has bands characteristic of the NiTMTAA compound showing that the structure of NiTMTAA has been preserved in the hybrid material. The new material has a surface area of 300 m²/g. The electron image was that of a non-crystalline microstructure. Comparison between the leaching of NiTMTAA from NiTMTAA adsorbed on commercial neutral alumina confirm that in the non-hydrolytic materials the NiTMTAA is entrapped and not only adsorbed on the alumina surface. The use of conventional hydrolytic sol-gel process leads to the complete leaching of NiTMTAA from matrix, underlining the importance of the non-hydrolytic alumina gel process in the matrix preparation. The new catalysts prepared were tested for their ability to catalyze the epoxidation of (Z)-cyclooctene using iodosylbenzene as oxygen donor, giving moderate yields in the epoxidation (40%), while the homogeneous NiTMTAA is inactive due to NiTMTAA bleaching. These results emphasize the effect of the non-hydrolytic alumina matrix to prevent chemical degradation of NiTMTAA.     

Non-collinear multi-wave mixing in a Doppler-broadened two-level medium

Received: 8 April 1998/Revised version: 3 June 1998     

Synthesis and Characterization of the β-BaB2O4 Phase Obtained by the Polymeric Precursor Method

A modified polymeric precursor method based on the Pechini process was used to synthesize -BaB₂O₄ (-BBO) crystalline phase. D-sorbitol (C₆H₁₄O₆) was used as a polymerizing agent to avoid the loss of boron during the samples' calcination and crystallization. The -BBO stoichiometric crystalline phase was only obtained when sorbitol was added to the solution. The results of Raman spectroscopy show that the amorphous phase is only completely eliminated when the samples are heat-treated at 750°C for 20 h. Thin films of -BBO phase displaying a preferred orientation were obtained when crystallized at 750°C for 2 h and deposited on sapphire substrate.     

An optimized protocol for anthraquinones isolation from Rhamnus frangula L.

Different from works described in the literature, which use expansive analytical methods to separation of anthraquinones derivatives (AQs), this communication reported a simple and inexpensive methodology to get them. In this way, the expensive commercial AQs: Chrysophanol, physcione and emodine were extracted from plant material (Rhamnus frangula L.) and isolated by classical column chromatography technique under optimised binary mobile phase gradients (CHCl₃ : AcOEt(a), a = 1 to 5%) in excellent yields.     

Synthesis and characterization of Al2O3/Cr2O3-based ceramic pigments

The synthesis and the characterization of Al₂O₃-based nanocrystalline inorganic pigments are reported. The pigments were synthesized by the polymeric precursor (Pechini method) using Cr₂O₃ as chromophore. XRD results only evidenced the corundum phase. The average particle size was about 34 nm. The samples were also characterized by differential scanning calorimetry (DSC) and thermogravimetry (TG), and CIE-L*a*b* calorimetry. The pigments obtained in this work presented different colors, ranging from green to rose. This revised version was published online in August 2006 with corrections to the Cover Date.     

Quantum-chemical investigation of the mechanism of cyclocondensation of 4-hydroxy-4-methylpentan-2-one with cyanoacetamide using the AM1 method

The mechanism of formation of 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile from 4-hydroxy-4-methylpentan-2-one and cyanoacetamide in the presence of ammonium acetate has been studied by the AM1 method. It was found that, under the reaction conditions, the amide is readily converted to an iminol tautomeric form which takes part in subsequent reaction. It was shown that the reaction is a cascade process forming two intermediates. The final product 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile is formed from the product of a Knoevenagel condensation via an intramolecular nucleophilic substitution mechanism. On the basis of the activation energies obtained it can be deduced that the limiting stage is the deprotonation process of the cyanoacetiminol. Dedicated to Professor L. I. Belen’kii with gratitude and deep respect. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 209–216, February, 2006.