New lead structures in the isoxazole system: relationship between quantum chemical parameters and immunological activity.

Potential immunological activities of three compounds: RM54 and its two derivatives RM55 and RM56, were evaluated in several, selected in vitro and in vivo tests such as: mitogen-induced lymphocyte proliferation, cytokine production, the humoral immune response in vitro and carrageenan test. Leflunomide served as a reference drug. The studied compounds showed differential, generally immunosuppressive properties. RM56 exhibited stronger suppressive activities as compared to RM54 and RM55. In particular, RM56 displayed the strongest activity in suppression of the carrageenan inflammation that was correlated with strong suppression of the humoral immune response in vitro and lymphocyte proliferation. Density Functional Theory (DFT) was employed to shed a light on molecular properties of the investigated compounds. The geometrical parameters of the studied molecular structures were fully optimized at the B3LYP/6-311G(d,p) level. The atomic charges distribution derived on the base of the Mulliken population analysis was correlated with immunological activity of RM54, RM55 and RM56. The obtained relationships show that the isoxazole ring plays an important role in the observed immunological activities. We also suggest that due to strong anti-inflammatory and anti-proliferative properties of RM-56, potential therapeutic applications of this derivative can be broad.

Theoretical study of the kinetics of chlorine atom abstraction from chloromethanes by atomic chlorine.

Ab initio calculations at the G3 level were used in a theoretical description of the kinetics and mechanism of the chlorine abstraction reactions from mono-, di-, tri- and tetra-chloromethane by chlorine atoms. The calculated profiles of the potential energy surface of the reaction systems show that the mechanism of the studied reactions is complex and the Cl-abstraction proceeds via the formation of intermediate complexes. The multi-step reaction mechanism consists of two elementary steps in the case of CCl4 + Cl, and three for the other reactions. Rate constants were calculated using the theoretical method based on the RRKM theory and the simplified version of the statistical adiabatic channel model. The temperature dependencies of the calculated rate constants can be expressed, in temperature range of 200-3,000 K as [Formula: see text]. The rate constants for the reverse reactions CH3/CH2Cl/CHCl2/CCl3 + Cl2 were calculated via the equilibrium constants derived theoretically. The kinetic equations [Formula: see text] allow a very good description of the reaction kinetics. The derived expressions are a substantial supplement to the kinetic data necessary to describe and model the complex gas-phase reactions of importance in combustion and atmospheric chemistry.

Theoretical study of the kinetics of reactions of the monohalogenated methanes with atomic chlorine.

Ab initio calculations at the G2 level were used in a theoretical description of the kinetics and mechanism of the hydrogen abstraction reactions from fluoro-, chloro- and bromomethane by chlorine atoms. The profiles of the potential energy surfaces show that mechanism of the reactions under investigation is complex and consists of two - in the case of CH3F+Cl - and of three elementary steps for CH3Cl+Cl and CH3Br+Cl. The heights of the energy barrier related to the H-abstraction are of 8-10 kJ mol(-1), the lowest value corresponds to CH3Cl+Cl and the highest one to CH3F+Cl. The rate constants were calculated using the theoretical method based on the RRKM theory and the simplified version of the statistical adiabatic channel model. The kinetic equations derived in this study[Formula: see text]and[Formula: see text]allow a description of the kinetics of the reactions under investigation in the temperature range of 200-3000 K. The kinetics of reactions of the entirely deuterated reactants were also included in the kinetic analysis. Results of ab initio calculations show that D-abstraction process is related with the energy barrier of 5 kJ mol(-1) higher than the H-abstraction from the corresponding non-deuterated reactant molecule. The derived analytical equations for the reactions, CD3X+Cl, CH2X+HCl and CD2X+DCl (X = F, Cl and Br) are a substantial supplement of the kinetic data necessary for the description and modeling of the processes of importance in the atmospheric chemistry.

Mechanism of the gas-phase decomposition of trifluoro-, trichloro-, and tribromomethanols in the presence of hydrogen halides.

Ab initio calculations at the G2 level were used in a theoretical analysis of the kinetics of the decomposition of trifluoro-, trichloro-, and tribromomethanols. The high-pressure limiting rate coefficients k(diss,∞) for the thermal dissociation of CF(3)OH, CCl(3)OH, and CBr(3)OH were calculated using the conventional transition state theory. The results of potential surface calculations show that in the presence of the hydrogen halides HX (X = F, Cl, and Br), considerably lower energy pathways are accessible for the decomposition of CF(3)OH, CCl(3)OH, and CBr(3)OH. The mechanism of the reactions appears to be complex and consists of three consecutive elementary processes with the formation of pre- and post-reaction adducts. The presence of hydrogen halides considerably decreases the energy barrier for the bimolecular decomposition of the alcohols CF(3)OH, CCl(3)OH, and CBr(3)OH. Results of this study indicate that hydrogen halides can considerably accelerate the homogeneous decomposition of perhalogenated methanols when they are present in the reaction area at sufficiently high concentrations. However, the atmospheric concentrations of hydrogen halides are too small for efficient removal of atmospheric CF(3)OH, CCl(3)OH, and CBr(3)OH.

Theoretical kinetic study of the formation reactions of methanol and methyl hypohalites in the gas phase.

CH(3)OX molecules (X = H, F, Cl and Br) can be formed in the atmosphere by the CH(3) + OX and CH(3)O + X recombination reactions. In the present study the results of a theoretical analysis of the kinetics and thermochemistry of this class of reactions are presented. The molecular properties of the reactants and products were derived from ab initio calculations. The high-pressure limiting rate constants for the recombination reactions were evaluated using a version of the statistical adiabatic channel model. The kinetic equations derived in this study allow a description of the kinetics of the reactions under investigation in the temperature range of 200-500 K.

Theoretical study of the kinetics and mechanism of the decomposition of trifluoromethanol, trichloromethanol, and tribromomethanol in the gas phase.

Ab initio calculations at the G2 level were used in a theoretical analysis of the kinetics of unimolecular and water-accelerated decomposition of the halogenated alcohols CX(3)OH (X = F, Cl, and Br) into CX(2)O and HX. The calculations show that reactions of the unimolecular decomposition of CX(3)OH are of no importance under atmospheric conditions. A considerably lower energy pathway for the decomposition of CX(3)OH is accessible by homogenous reactions between CX(3)OH and water. It is shown that CX(3)OH + H(2)O reactions proceed via the formation of intermediate complexes. The mechanism of the reactions appears to be complex and consists of three consecutive elementary processes. The calculated values of the second-order rate constants are of 2.5 x 10(-21), 2.1 x 10(-19), and 1.2 x 10(-17) cm(3)molecule(-1)s(-1) at 300 K for CF(3)OH + H(2)O, CCl(3)OH + H(2)O, and CBr(3)OH + H(2)O, respectively. The theoretically derived atmospheric lifetimes of the CX(3)OH molecules indicate that the water-mediated decomposition reactions CX(3)OH + H(2)O may be the most efficient process of CF(3)OH, CCl(3)OH, and CBr(3)OH loss in the atmosphere.