Effect of metal ions on the in vitro availability of enoxacin, its in vivo implications, kinetic and antibacterial studies

The present paper describes the effect of metals ions on the in vitro availability of enoxacin (a second generation quinolone antibiotic) owing to drug-metal interaction. These interaction studies were performed at 37 °C in different pH environments simulating human body compartments and were studied by UV spectroscopic technique. In order to determine the probability of these reactions different kinetic parameters (dissolution constants (K) and free energy change (ΔG)) for these reactions were also calculated. It is proposed that the structure of enoxacin contains various electron donating sites which facilitate its binding with metallic cations forming chelates. Hence taking food products, nutritional supplements or multivitamins containing multivalent cations at the same time as enoxacin, could reduce the absorption of the drug into the circulation and thus would decrease the effectiveness of the drug. In addition, the MIC of enoxacin for various microorganisms before and after interaction with metal ions was calculated which in most cases was increased which possibly could impair the clinical efficacy of the drug.

Retrieval of kinetic rates in reactions with semi batch liquid phase using ill-posed inverse problem theory

A neural network procedure to solve inverse chemical kinetic problems is discussed in this work. Rate constants are calculated from the product concentration of an irreversible consecutive reaction: the hydrogenation of Citral molecule, a process with industrial interest. Simulated and experimental data are considered. Errors in the simulated data, up to 7% in the concentrations, were assumed to investigate the robustness of the inverse procedure. Also, the proposed method is compared with two common methods in nonlinear analysis; the Simplex and Levenberg-Marquardt approaches. In all situations investigated, the neural network approach was numerically stable and robust with respect to deviations in the initial conditions or experimental noises.

Kinetic, thermodynamic properties, and optimization of barley hydration

The hydration kinetics of five barley cultivars was studied at six different temperatures ranging from 10 to 35 ºC for 32 hours applying the Peleg model. Response Surface was used to describe dynamic of the process and identify the hydration time for each cultivar. The activation energy (Ea), enthalpy (ΔH*), entropy (ΔS*), and Gibbs free energy (ΔG*) were estimated from the adjusted parameters and Arrhenius equation. Temperature had significant effect on the hydration of the five cultivars. At low temperatures, the stabilization time for hydration was faster. Peleg constants K1 and K2 decreased with increasing temperature. The cultivar BRS BRAU showed the lowest value of initial absorption rate (R0 = 0.149 kg.h-1) at 10 ºC, while the cultivar BRS BOREMA had the highest value of R0 (0.367 kg.h-1 at 35 ºC). The equilibrium moisture content (Me) increased with increasing temperature. The cultivars BRS CAUE and BRS BRAU showed the lowest values of Ea, ΔH*, ΔS* showed negative values, and ΔG* increased with increasing temperature, confirming the effect of temperature on hydration.

Kinetic and mechanistic studies for the molybdenum- catalyzed oxidation of organic sulfides and olefins by t- DuO2H

This research was focussed on the effects of light, solvent and substituents in the molybdenum-catalyzed oxidation of phenylmethyl sulfides with t-Bu02H and on the effect of light in the molybdenum-catalyzed epoxidation of l-octene with t-Bu02H. It was shown that the Mo(CO)6-catalyzed oxidation of phenylmethyl sulfide with t-Bu02H~ at 35°C, proceeds 278 times faster underUV light than under laboratory lighting, whereas the Mo02(acac)2-catalyzed oxidation proceeds only 1.7 times faster under UV light than under normal laboratory lighting. The difference between the activities of both catalysts was explained by the formation of the catalytically active species, Mo(VI). The formation of the Mo(VI) species, from Mo(CO)6 was observed from the IR spectrum of Mo(CO)6 in the carbonyl region. The Mo(CO)6-catalyzed epoxidation of l-octene with t-Bu02H showed that the reaction proceeded 4.6 times faster under UV light than in the dark or under normal laboratory lighting; the rates of epoxidations were found to be the same in the dark and under normal laboratory lighting. The kinetics of the epoxidations of l-octene with t-Bu02H, catalyzed by Mo02(acac)2 were found to be complicated; after fast initial rates, the epoxidation rates decreased with time. The effect of phenylmethyl sulfide on the Mo(CO)6-catalyzed epoxidation of l-octene waS studied. It was shown that instead of phenylmethyl sulfide, phenylmethyl sulfone, which formed rapidly at 85°C, lowered the reaction rate. The epoxidation of l-octene was found to be 2.5 times faster in benzene than in ethanol. The substituent effect on the Mo02(acac)2-catalyzed oxidations of p-OH, p-CHgO, P-CH3' p-H, p-Cl, p-Br, p-CHgCO, p-HCO and P-N02 substituted phenylmethyl sulfides were studied. The oxidations followed second order kinetics for each case; first order dependency on catalyst concentration was also observed in the oxidation of p-CHgOPhSMeand PhSMe. It was found that electron-donating groups on the para position of phenylmethyl sulfide increased the rate of reaction, while electronwithdrawing groups caused the reaction rate to decrease. The reaction constants 0 were determined by using 0, 0- and 0* constants. The rate effects were paralleled by the activation energies for oxidation. The decomposition of t-Bu02H in the presence of M.o (CO)6, Mo02 (acac)2 and VO(acac)2 was studied. The rates of decomposition were found to be very small compared to the oxidation rates at high concentration of catalysis. The relative rates of the Mo02(acac)2-catalyzed oxidation of p-N02PhSMe by t-Bu02H in the presence of either p-CH30PhSMe or PhSMe clearly show that PhSMe and p-CHgOPhSMe act as co-catalysts in the oxidation of p-N02PhSMe. Benzene, mesity1ene and cyclohexane were used to determine the effect of solvent in the Mo02 (acac)2 and Mo(CO)6-catalyzed oxidation of phenylmethyl sulfide. The results showed that in the absence of hydroxylic solvent, a second molecule of t-Bu02H was involved in the transition state. The complexation of the solvent with the catalyst could not be explained.The oxidations of diphenyl sulfoxide catalyzed by VO(acac)2, Mo(CO)6 and Mo02(acac)2 showed that VO(acac)2 catalyzed the oxidation faster than Mo(CO)6 and Mo02 (acac)2_ Moreover, the Mo(CO)6-catalyzed oxidation of diphenyl sulfoxide proceeded under UV light at 35°C.

Laboratory kinetic studies of the reactions of Cl atoms with species of biogenic origin: δ3-Carene, isoprene, methacrolein and methyl vinyl ketone

The rate coefficients for the reaction between atomic chlorine and a number of naturally occurring species have been measured at ambient temperature and atmospheric pressure using the relative rate technique. The values obtained were (4.0 ± 0.8) × 10-10, (2.1 ± 0.5) × 10-10, (3.2 ± 0.5) × 10-10, and (4.9 ± 0.5) × 10-10 cm3 molecule-1 s-1, for reactions with isoprene, methyl vinyl ketone, methacrolein and δ3-carene, respectively. The value obtained for isoprene compares favourably with previously reported values. No values have been reported to date for the rate constants of the other reactions.

Surprisingly slow reaction of dimethylsilylene with dimethylgermane: time-resolved kinetic studies and related quantum chemical calculations

Time-resolved studies of silylene, SiH2, and dimethylsilylene, SiMe2, generated by the 193 nm laser flash photolysis of appropriate precursor molecules have been carried out to obtain rate constants for their bimolecular reactions with dimethylgermane, Me2GeH2, in the gas phase. SiMe2 + Me2GeH2 was studied at five temperatures in the range 299-555 K. Problems of substrate UV absorption at 193 nm at temperatures above 400 K meant that only three temperatures could be used reliably for rate constant measurement. These rate constants gave the Arrhenius parameters log(A/cm(3) molecule(-1) s(-1)) = -13.25 +/- 0.16 and E-a = -(5.01 +/- 1.01) kJ mol(-1). Only room temperature studies of SiH2 were carried out. These gave values of (4.05 +/- 0.06) x 10(-10) cm(3) molecule(-1) s(-1) (SiH2 + Me2GeH2 at 295 K) and also (4.41 +/- 0.07) x 10(-10) cm(3) molecule(-1) s(-1) (SiH2 + MeGeH3 at 296 K). Rate constant comparisons show the surprising result that SiMe2 reacts 12.5 times slower with Me2GeH2 than with Me2SiH2. Quantum chemical calculations (G2(MP2,SVP)//B3LYP level) of the model Si-H and Ge-H insertion processes of SiMe2 with SiH4/MeSiH3 and GeH4/MeGeH3 support these findings and show that the lower reactivity of SiMe2 with Ge-H bonds is caused by a higher secondary barrier for rearrangement of the initially formed complexes. Full details of the structures of intermediate complexes and the discussion of their stabilities are given in the paper. Other, related, comparisons of silylene reactivity are also presented.

An investigation of the germylene addition reaction, GeH2+C2H2: Time-resolved gas-phase kinetic studies and quantum chemical calculations of the reaction energy surface

Time resolved studies of germylene, GeH2, generated by laser flash photolysis of 3,4-dimethylgermacyclopentene-3, have been carried out to obtain rate constants for its bimolecular reaction with acetylene, C2H2. The reaction was studied in the gas-phase over the pressure range 1-100 Tort, with SF6 as bath gas, at 5 temperatures in the range 297-553 K. The reaction showed a very slight pressure dependence at higher temperatures. The high pressure rate constants (obtained by extrapolation at the three higher temperatures) gave the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1)) (-10.94 +/- 0.05) + (6.10 +/- 0.36 kJ mol(-1))/RTln10. These Arrhenius parameters are consistent with a fast reaction occurring at approximately 30% of the collision rate at 298 K. Quantum chemical calculations (both DFT and ab initio G2//B3LYP and G2//QCISD) of the GeC2H4 potential energy surface (PES), show that GeH2 + C2H2 react initially to form germirene which can isomerise to vinylgermylene with a relatively low barrier. RRKM modelling, based on a loose association transition state, but assuming vinylgermylene is the end product (used in combination with a weak collisional deactivation model) predicts a strong pressure dependence using the calculated energies, in conflict with the experimental evidence. The detailed GeC2H4 PES shows considerable complexity with ten other accessible stable minima (B3LYP level), the three most stable of which are all germylenes. Routes through this complex surface were examined in detail. The only product combination which appears capable of satisfying the (P-3) + C2H4.C2H4 was confirmed as a product by GC observed lack of a strong pressure dependence is Ge(P-3) + C2H4. C2H4 was confirmed as a product by GC analysis. Although the formation of these products are shown to be possible by singlet-triplet curve crossing during dissociation of 1-germiranylidene (1-germacyclopropylidene), it seems more likely (on thermochernical grounds) that the triplet biradical, (GeCH2CH2.)-Ge-., is the immediate product precursor. Comparisons are made with the reaction of SiH2 with C2H2.

Time-resolved gas-phase kinetic and quantum chemical studies of the reaction of silylene with oxygen

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by laser flash photolysis of phenylsilane, have been carried out to obtain rate constants for its bimolecular reaction with O-2. The reaction was studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas, at five temperatures in the range 297-600 K. The second order rate constants at 10 Torr were fitted to the Arrhenius equation: log(k/cm(3) molecule(-1) s(-1)) = (-11.08 +/- 0.04) + (1.57 +/- 0.32 kJ mol(-1))/RT ln10 The decrease in rate constant values with increasing temperature, although systematic is very small. The rate constants showed slight increases in value with pressure at each temperature, but this was scarcely beyond experimental uncertainty. From estimates of Lennard-Jones collision rates, this reaction is occurring at ca. 1 in 20 collisions, almost independent of pressure and temperature. Ab initio calculations at the G3 level backed further by multi-configurational (MC) SCF calculations, augmented by second order perturbation theory (MRMP2), support a mechanism in which the initial adduct, H2SiOO, formed in the triplet state (T), undergoes intersystem crossing to the more stable singlet state (S) prior to further low energy isomerisation processes leading, via a sequence of steps, ultimately to dissociation products of which the lowest energy pair are H2O + SiO. The decomposition of the intermediate cyclo-siladioxirane, via O-O bond fission, plays an important role in the overall process. The bottleneck for the overall process appears to be the T -> S process in H2SiOO. This process has a small spin orbit coupling matrix element, consistent with an estimate of its rate constant of 1 x 10(9) s(-1) obtained with the aid of RRKM theory. This interpretation preserves the idea that, as in its reactions in general, SiH2 initially reacts at the encounter rate with O-2. The low values for the secondary reaction barriers on the potential energy surface account for the lack of an observed pressure dependence. Some comparisons are drawn with the reactions of CH2 + O-2 and SiCl2 + O-2.

Time-resolved gas-phase kinetic and quantum chemical studies of the reaction of silylene with nitric oxide

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by laser flash photolysis of phenylsilane, have been carried out to obtain rate constants for its bimolecular reaction with NO. The reaction was studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas at five temperatures in the range 299-592 K. The second-order rate constants at 10 Torr fitted the Arrhenius equation log(k/cm(3) molecule(-1) s(-1)) = (- 11.66 +/- 0.01) + (6.20 +/- 0.10 kJ mol(-1))IRT In 10 The rate constants showed a variation with pressure of a factor of ca. 2 over the available range, almost independent of temperature. The data could not be fitted by RRKM calculations to a simple third body assisted association reaction alone. However, a mechanistic model with an additional (pressure independent) side channel gave a reasonable fit to the data. Ab initio calculations at the G3 level supported a mechanism in which the initial adduct, bent H2SiNO, can ring close to form cyclo-H2SiNO, which is partially collisionally stabilized. In addition, bent H2SiNO can undergo a low barrier isomerization reaction leading, via a sequence of steps, ultimately to dissociation products of which the lowest energy pair are NH2 + SiO. The rate controlling barrier for this latter pathway is only 16 kJ mol(-1) below the energy of SiH2 + NO. This is consistent with the kinetic findings. A particular outcome of this work is that, despite the pressure dependence and the effects of the secondary barrier (in the side reaction), the initial encounter of SiH2 with NO occurs at the collision rate. Thus, silylene can be as reactive with odd electron molecules as with many even electron species. Some comparisons are drawn with the reactions of CH2 + NO and SiCl2 + NO.

Investigation of the prototype silylene reaction, SiH2+H2O(and D2O): time-resolved gas-phase kinetic studies, isotope effects, RRKM calculations, and quantum chemical calculations of the reaction energy surface

Time-resolved kinetic studies of the reaction of silylene, SiH2, with H2O and with D2O have been carried out in the gas phase at 296 and at 339 K, using laser flash photolysis to generate and monitor SiH2. The reaction was studied over the pressure range 10-200 Torr with SF6 as bath gas. The second-order rate constants obtained were pressure dependent, indicating that the reaction is a third-body assisted association process. Rate constants at 339 K were about half those at 296 K. Isotope effects, k(H)/k(D), were small averaging 1.076 0.080, suggesting no involvement of H- (or D-) atom transfer in the rate determining step. RRKM modeling was undertaken based on a transition state appropriate to formation of the expected zwitterionic donoracceptor complex, H2Si...OH2. Because the reaction is close to the low pressure (third order) region, it is difficult to be definitive about the activated complex structure. Various structures were tried, both with and without the incorporation of rotational modes, leading to values for the high-pressure limiting (i.e., true secondorder) rate constant in the range 9.5 x 10(-11) to 5 x 10(-10) cm(3) molecule' s(-1). The RRKM modeling and mechanistic interpretation is supported by ab initio quantum calculations carried out at the G2 and G3 levels. The results are compared and contrasted with the previous studies.

Reactions of silylene with unreactive molecules. 2. nitrogen: gas-phase kinetic and theoretical studies

Time-resolved studies of the reaction of silylene, SiH2, with N-2 have been attempted at 296, 417, and 484 K, using laser flash photolysis to generate and monitor SiH2. No conclusive evidence for reaction could be found even with pressures of N-2 of 500 Torr. This enables us to set upper limits of ca. 3 x 10(-15) cm(3) molecule(-1) s(-1) for the second-order rate constants. A lower limit for the activation energy, E-a, of ca. 47 kJ mol(-1) is also derived. Ab initio calculations at the G3 level indicate that the only SiH2N2 species of lower energy than the separated reactants is the H2Si...N-2 donor-acceptor (ylid) species with a relative enthalpy of -26 kJ mol(-1), insufficient for observation of reaction under the experimental conditions. Ten bound species on the SiH2N2 surface were found and their energies calculated as well as those of the potential dissociation products: HSiN + NH((3)Sigma(-)) and HNSi + NH((3)Sigma(-)). Additionally two of the transition states involving cyclic-SiH2N2 (siladiazirine) were explored. It appears that siladiazirine is neither thermodynamically nor kinetically stable. The findings indicate that Si-N-d bonds (where N-d is double-bonded nitrogen) are not particularly strong. An unexpected cyclic intermediate was found in the isomerization of silaisocyanamide to silacyanamide.

Time-resolved gas-phase kinetic and quantum chemical studies of reactions of silylene with chlorine-containing species. 1. HCl

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by laser flash photolysis of phenylsilane, have been carried out to obtain rate constants for its bimolecular reaction with HCL The reaction was studied in the gas phase at 10 Torr total pressure in SF6 bath gas, at five temperatures in the range of 296-611 K. The second-order rate constants fitted the Arrhenius equation: log(k/cm(3) molecule(-1) s(-1)) = (-11.51 +/- 0.06) + (1.92 +/- 0.47 kJ mol(-1))/RTIn10 Experiments at other pressures showed that these rate constants were unaffected by pressure in the range of 10-100 Torr, but showed small decreases in value of no more than 20% ( +/- 10%) at I Toff, at both the highest and lowest temperatures. The data are consistent with formation of an initial weakly bound donor-acceptor complex, which reacts by two parallel pathways. The first is by chlorine-to-silicon H-shift to make vibrationally excited chlorosilane, SiH3Cl*, which yields HSiCl by H-2 elimination from silicon. In the second pathway, the complex proceeds via H-2 elimination (4-center process) to make chlorosilylene, HSiCl, directly. This interpretation is supported by ab initio quantum calculations carried out at the G3 level which reveal the direct H-2 elimination route for the first time. RRKM modeling predicts the approximate magnitude of the pressure effect but is unable to determine the proportions of each pathway. The experimental data agree with the only previous measurements at room temperature. Comparisons with other reactions of SiH2 are also drawn.

Time-resolved gas-phase kinetic and quantum chemical studies of reactions of silylene with chlorine-containing species. 2. CH3Cl

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by laser flash photolysis of both silacyclopent-3-ene and phenylsilane, have been carried out to obtain second-order rate constants for its reaction with CH3Cl. The reaction was studied in the gas phase at six temperatures in the range 294-606 K. The second-order rate constants gave a curved Arrhenius plot with a minimum value at T approximate to 370 K. The reaction showed no pressure dependence in the presence of up to 100 Torr SF6. The rate constants, however, showed a weak dependence on laser pulse energy. This suggests an interpretation requiring more than one contributing reaction pathway to SiH2 removal. Apart from a direct reaction of SiH2 with CH3Cl, reaction of SiH2 with CH3 (formed by photodissociation of CH3Cl) seems probable, with contributions of up to 30% to the rates. Ab initio calculations (G3 level) show that the initial step of reaction of SiH2 with CH3Cl is formation of a zwitterionic complex (ylid), but a high-energy barrier rules out the subsequent insertion step. On the other hand, the Cl-abstraction reaction leading to CH3 + ClSiH2 has a low barrier, and therefore, this seems the most likely candidate for the main reaction pathway of SiH2 with CH3Cl. RRKM calculations on the abstraction pathway show that this process alone cannot account for the observed temperature dependence of the rate constants. The data are discussed in light of studies of other silylene reactions with haloalkanes.

Experimental and theoretical evidence for homogeneous catalysis in the gas-phase reaction of SiH2 with H2O (and D2O): a combined kinetic and quantum chemical study

Time-resolved kinetic studies of the reaction of silylene, SiH2, with H2O and with D2O have been carried out in the gas phase at 297 K and at 345 K, using laser flash photolysis to generate and monitor SiH2. The reaction was studied independently as a function of H2O (or D2O) and SF6 (bath gas) pressures. At a fixed pressure of SF6 (5 Torr), [SiH2] decay constants, k(obs), showed a quadratic dependence on [H2O] or [D2O]. At a fixed pressure of H2O or D2O, k(obs) Values were strongly dependent on [SF6]. The combined rate expression is consistent with a mechanism involving the reversible formation of a vibrationally excited zwitterionic donor-acceptor complex, H2Si...OH2 (or H2Si...OD2). This complex can then either be stabilized by SF6 or it reacts with a further molecule of H2O (or D2O) in the rate-determining step. Isotope effects are in the range 1.0-1.5 and are broadly consistent with this mechanism. The mechanism is further supported by RRKM theory, which shows the association reaction to be close to its third-order region of pressure (SF6) dependence. Ab initio quantum calculations, carried out at the G3 level, support the existence of a hydrated zwitterion H2Si...(OH2)(2), which can rearrange to hydrated silanol, with an energy barrier below the reaction energy threshold. This is the first example of a gas-phase-catalyzed silylene reaction.

Kinetic studies of reactions of the nitrate radical (NO3) with peroxy radicals (RO2): an indirect source of OH at night?

A discharge-flow system, coupled to cavity-enhanced absorption spectroscopy (CEAS) detection systems for NO3 at lambda = 662 nm and NO2 at lambda = 404 nm, was used to investigate the kinetics of the reactions of NO3 with eight peroxy radicals at P similar to 5 Torr and T similar to 295 K. Values of the rate constants obtained were (k/10(-12) cm(3) molecule(-1) s(-1)): CH3O2 (1.1 +/- 0.5), C2H5O2 (2.3 +/- 0.7), CH2FO2 (1.4 +/- 0.9), CH2ClO2 (3.8(-2.6)(+1.4)), c-C5H9O2 (1.2(-0.5)(+1.1)), c-C6H11O2 (1.9 +/- 0.7), CF3O2 (0.62 +/- 0.17) and CF3CFO2CF3 (0.24 +/- 0.13). We explore possible relationships between k and the orbital energies of the reactants. We also provide a brief discussion of the potential impact of the reactions of NO3 with RO2 on the chemistry of the night-time atmosphere.