Theoretical study of the hydroboration reaction of cyclopropane with borane

The hydroboration of cyclopropane has been investigated using the B3LYP density functional method employing several split-valence basis sets. It is shown that the reaction proceeds via an intermediate weakly bound complex and a three-centered transition state. Calculations at higher levels of theory were also performed at the geometries optimized at the B3LYP level, but only slight changes in the barriers were observed. Structural parameters for the transition state are also reported.     

Theoretical study of the reaction of CH2XO (X = F, Cl, Br) radicals with the NO radical

In this paper, we focus on the multiple-channel reactions of CH₂XO (X = F, Cl, Br) radicals with the NO radical by means of direct dynamic methods. All structures of the stationary points were obtained at the MP2/6-311+G(d,p) level and vibrational frequency analysis was also performed at this level of theory. The minimum energy path (MEP) was obtained via the intrinsic reaction coordinate (IRC) theory at the MP2/6-311+G(d,p) level, and higher-level energetic information was refined by the MC-QCISD method. The rate constants for the three hydrogen abstraction reaction channels over the temperature range 200–1,500 K were calculated by the improved canonical variational transition state theory (ICVT) with a correction for small-curvature tunneling (SCT). The rate constants calculated in this manner were in good agreement with the available experimental data, and the three-parameter rate–temperature formulae for the temperature range 200–1,500 K were $ {k_{1{\text{a}} }}(T)=0.32\times {10^{-18 }}{T^{1.83 }}\exp \left( {1748.54/T} \right) $ , $ {k_{2{\text{a}} }}(T)=0.22\times {10^{-19 }}{T^{2.19 }}\exp \left( {1770.19/T} \right) $ , $ {k_{3{\text{a}} }}(T)=0.88\times {10^{-20 }}{T^{2.20 }}\exp \left( {1513.82/T} \right) $ (in units of cm³ molecule^?1?s^?1).     

The reaction between nitrite and oxyhemoglobin: a mechanistic study

The nitrite anion (NO(-)(2)) has recently received much attention as an endogenous nitric oxide source that has the potential to be supplemented for therapeutic benefit. One major mechanism of nitrite reduction is the direct reaction between this anion and the ferrous heme group of deoxygenated hemoglobin. However, the reaction of nitrite with oxyhemoglobin (oxyHb) is well established and generates nitrate and methemoglobin (metHb). Several mechanisms have been proposed that involve the intermediacy of protein-free radicals, ferryl heme, nitrogen dioxide (NO(2)), and hydrogen peroxide (H(2)O(2)) in an autocatalytic free radical chain reaction, which could potentially limit the usefulness of nitrite therapy. In this study we show that none of the previously published mechanisms is sufficient to fully explain the kinetics of the reaction of nitrite with oxyHb. Based on experimental data and kinetic simulation, we have modified previous models for this reaction mechanism and show that the new model proposed here is consistent with experimental data. The important feature of this model is that, whereas previously both H(2)O(2) and NO(2) were thought to be integral to both the initiation and propagation steps, H(2)O(2) now only plays a role as an initiator species, and NO(2) only plays a role as an autocatalytic propagatory species. The consequences of uncoupling the roles of H(2)O(2) and NO(2) in the reaction mechanism for the in vivo reactivity of nitrite are discussed.     

Theoretical study of the catalytic reaction mechanism of MndD

Manganese-dependent homoprotocatechuate 2,3-dioxygenase (MndD) is an enzyme taking part in the catabolism of aromatic compounds in the environment. It uses molecular oxygen to perform an extradiol cleavage of the ring of the ortho-dihydroxylated aromatic compound homoprotocatechuate. A theoretical investigation of the reaction path for MndD was performed using hybrid density functional theory with the B3LYP functional, and a catalytic mechanism has been suggested. Models of different size were built from the crystal structure of the enzyme and were used in the search for intermediates and transition states. It was found that the substrate first binds at the active site as a monoanion. Next the dioxygen is bound, forming a hydroperoxo intermediate. The O–O bond, activated in this way undergoes homolytic cleavage leading to an oxyl and then to an extra epoxide radical with subsequent opening of the aromatic ring. The lactone ring is then hydrolyzed by the Mn-bound OH group, and the final product is obtained in the last reaction steps. Alternative reaction paths were considered, and their calculated barriers were found to be higher than for the suggested mechanism. The selectivity between the extra- and intra-cleavage pathways was found to be determined by the barriers for the decay of the radical state.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Baker's yeast flavocytochrome b2. A mechanistic study of the dehydrohalogenation reaction

It has been shown that reduced flavocytochrome b2 not only catalyzes reduction of bromopyruvate [P. Urban, P.M. Alliel and F. Lederer (1983) Eur. J. Biochem. 134, 275-281] but also transforms it into pyruvate in a reductive elimination process. The dehydrohalogenation reaction also takes place when oxidized enzyme acts on bromolactate, but the reaction is more difficult to observe under these conditions because of its low efficiency compared to the normal oxidative process. The maximal rates of pyruvate production from bromopyruvate and chloropyruvate differ by a factor of less than 10, whereas elimination from fluoropyruvate cannot be detected. These results support a mechanism in which the dehydrohalogenation reaction takes place from a carbanion intermediate of the normal reductive-oxidative pathway.     

A reaction of the superoxide radical with tetrapyrroles

Bilirubin and biliverdin were bleached during exposure to the aerobic xanthine oxidase reaction. Enzymic scavenging of O₂^?, by Superoxide dismutase, inhibited, whereas enzymic scavenging of H₂O₂, by catalase, did not. Increasing the rate of production of O₂^? without increasing the turnover rate of xanthine oxidase, by increasing pO₂, accelerated the bleaching of the biliverdin. Moreover, a scavenger of OH·, such as benzoate, or an inactivating chelating agent for iron, such as diethylenetriamine pentaacetate or desferrioxamine mesylate, did not inhibit. It follows that O₂^? can directly attack these tetrapyrroles. Kinetic competition between Superoxide dismutase and bilirubin yielded a value for k_{bilirubin, O2^?} = 2.3 × 10⁴ M^?1s^?1 at pH 8.3 and at 23 °C. A similar experiment for biliverdin yielded a value for k_{bilirubin, O2^?} = 7 × 10⁴ M^?1s^?1.     

A multi-component reaction to 5-cyanouracils: synthesis and mechanistic study

Acetonitrile as a solvent, excess of primary amines as general bases, and a reflux condition make the multi-component reactions of (2-cyanoacetyl) carbamate 1, ethyl orthoformate, and primary amines form 5-cyanouracils 4a-c feasibly. Mechanistic studies of the multi-component reaction were carried out by proton NMR spectrometer. Acetonitrile as a solvent makes the reaction of 1 with ethyl orthoformate produce E-ethyl (2-cyano-3-ethoxyacryloyl) carbamate E-2 without a catalyst of acetic anhydride. The reactions of E-2 with primary amines produce the corresponding Z-3a-c as the only stable isomers eventually in CDCl3 or CD3CN. General-base-catalyzed intramolecular cyclizations of Z-3a-c at a reflux condition in CD3CN generated the corresponding 5-cyanouracils 4a-c.     

Theoretical study on primary reaction of photosynthetic bacteria

Theoretical calculation was carried out on the primary electron donor P₈₇₀ of photosynthetic bacteria. The results show that: (i) the bimolecular structure of the primary electron donor is more advantageous in energy than monomolecular structure; (ii) the initial configuration of primary electron donor is no longer stable and changes to the configuration with lower energy and chemical reactivity after the charge separation. In the P₈₇₀, such structural change is completed through the rotation of C₃ acetyl, so the oxygen atom of acetyl interacts with the magnesium atom of another bacterio-chlorophyll molecule, and the total energy and chemical reactivity are reduced evidently. It is suggested that the structural change of the primary electron donor is important in preventing the occurrence of charge recombination during the primary reaction and maintaining the high efficiency of the conversion of sun-light to chemical energy. A new mechanism of primary reaction has been proposed, which can give reasonable explanations to the results of kinetic and site mutation studies.     

Theoretical study on primary reaction of photosynthetic bacteria

Theoretical calculation was carried out on the primary electron donor P_(870) of photosynthetic bacteria. The results show that: (ⅰ) the bimolecular structure of the primary electron donor is more advantageous in energy than monomolecular structure; (ⅱ) the initial configuration of primary electron donor is no longer stable and changes to the configuration with lower energy and chemical reactivity after the charge separation. In the P_(870), such structural change is completed through the rotation of C_3 acetyl, so the oxygen atom of acetyl interacts with the magnesium atom of another bacterio-chlorophyll molecule, and the total energy and chemical reactivity are reduced evidently. It is suggested that the structural change of the primary electron donor is important in preventing the occurrence of charge recombination during the primary reaction and maintaining the high efficiency of the conversion of sun-light to chemical energy. A new mechanism of primary reaction has been proposed, which can give r     

The reaction of superoxide radical with N-acetylcysteine

The interaction of superoxide radicals with N-acetylcysteine (RSH) in an aqueous solution of pH 7 using the technique of steady state radiolysis has been investigated in this paper. The radiolytic yield of the products (G value) of RSH consumption and disulfide of N-acetylcysteine (RSSR) formation has been determined. The G value of the products is not dependent on the concentration of RSH (at the plateau of dilution curve) or on the inverse of the square root of the dose rate (dose rate)(-1/2), from which it is concluded that in this reaction there is no character of chain reaction. The disulfide of N-acetylcysteine is the only sulfur final product. Hydrogen peroxide is not a reaction product, and accordingly the reaction of O(2)(*-) with RSH does not proceed via hydrogen atom abstraction from RSH. A reaction mechanism is proposed, and an overall rate constant of 68 M(-1) s(-1) has been estimated.     

Quantitation of the hydroxyl radical by reaction with dimethyl sulfoxide

This investigation was conducted to validate the use of dimethyl sulfoxide (DMSO) as a quantitative molecular probe for the generation of hydroxyl radicals (HO.) in aqueous systems. Reaction of HO. with DMSO produces methane sulfinic acid as a primary product, which can be detected by a simple colorimetric assay. To evaluate this method for estimating total HO. production, we studied three model systems, including the Fenton reaction, gamma irradiation of water, and ultraviolet photolysis of hydrogen peroxide, for which the theoretical maximum yield of HO. could be calculated and compared to measured DMSO oxidation. The results confirm that 0.05 to 1 M DMSO may be used to capture nearly all of the expected HO. radicals formed. Thus, methane sulfinic acid production from DMSO holds promise as an easily measured marker for HO. formation in aqueous systems pretreated with DMSO.     

Further insights into the reaction of melatonin with hydroxyl radical

Recent interest has focused on the use of exogenous melatonin as an antioxidant, particularly to scavenge the highly cytotoxic hydroxyl radical (HO(z.rad;)) which may be generated in many pathological conditions. However, in vitro and in vivo studies aimed at assessing the antioxidant properties of melatonin have produced conflicting results. While it is known that HO(z.rad;) reacts with melatonin at a diffusion limited rate, very little is known about the products of this reaction. In this investigation it is shown that incubation of melatonin with a Fenton-type HO(z.rad;)-generating system at pH 7.4 forms a complex mixture of primary products. These include 2-hydroxymelatonin, which was isolated as its more stable oxindole tautomer, 4- and 6-hydroxymelatonin, N-acetyl-N(2)-formyl-5-methoxykynurenine and 7,7(')-bi-(5-methoxy-N-acetyltryptamine-4-one). Reaction pathways that might lead to these products are described. The differing biological effects of these products, while currently incompletely understood, might account for the controversy concerning the antioxidant properties of melatonin.     

Theoretical mechanistic study of the formic acid decomposition assisted by a Ru(II)-phosphine catalyst

There is considerable evidence, which we discuss, indicating that compressibility and available free space in the crystal lattice are among the factors that govern the sensitivity of an explosive compound. Expanding and extending earlier work, we demonstrate, for 25 explosives, that there is an overall general tendency for greater impact sensitivity as the estimated free space per molecule increases. More specific relationships can be discerned by looking at subgroups of the compounds. The nitramine sensitivities, most of which are quite high, increase nearly linearly but only very gradually with free space. The nitroaromatics cover a wide range of sensitivities but all have an approximately similar intermediate level of free space. The remaining types of compounds show a reasonable sensitivity–free space relationship with one outlier: FOX-7 (1,1-diamino-2,2-dinitroethylene).     

Kinetic and mechanistic studies on the reaction of melilotate hydroxylase with deuterated melilotate.

Melilotate has been synthesized from melilotate by iodiantion followed by reductive deiodination in the presence of deuterated hydrazine. The deuterated melilotate has been employed in investigations of the reaction mechanism of melilotate hydroxylase. Stopped-flow spectrophotometry has revealed no isotope effect in the formation or decay of the oxygenated intermediate which is observed when reduced melilotate hydroxylase reacts with molecular oxygen. Steady-state analysis has corroborated this result, and in addition shows that there is no isotope effect in the reductive cycle of the enzyme mechanism. This analysis does reveal a reproducible 8% decrease in Vmax for the enzyme when using deuterated melilotate. These observations are compatible with the thesis that the above intermediate is an oxygenated form of the reduced flavine prosthetic group and that the last step of the proposed mechanism is rapid and involves a primary isotope effect. The existence of the NIH shift mechanism has been studied using combined gas chromatography-mass spectrometry. No evidence could be obtained for intramolecular migration of deuterium during the hydroxylation reaction. However, the small amount of migration expected when phenols are hydroxylated precludes elimination of the NIH shift as a possibility.     

Sterol C24-methyltransferase: mechanistic studies of the C-methylation reaction with 24-fluorocycloartenol

The mechanism of the C-methylation reaction was studied with the allylic substrate analog 24-fluorocycloartenol 10 assayed with soybean sterol C24-methyltransferase (SMT). 10 is an effective competitive inhibitor (Ki = 32 microM) of the SMT, and the electron-withdrawing alpha-fluorine substituent was shown to suppress the rate of the C-methylation reaction by one order of magnitude relative to the natural cycloartenol substrate, kcat = 0.02 min(-1) versus 0.6 min(-1); alternately 10 can prevent the critical hydride shift of H24 to C25 to afford time-dependent inactivation of SMT (k(inact) = 0.32 min(-1)).     

Difference between histidine and histamine in the mechanistic pathway of the fluorescence reaction with ortho-phthalaldehyde

Histamine reacts with ortho-phthalaldehyde (OPA) in an alkaline medium to form an unstable fluorescent adduct (Fbase-Hm). Acidification of the solution to pH 2-4 gives a stable and highly fluorescent adduct (Facid-Hm). In contrast, histidine develops a relatively stable fluorescent adduct (Fbase-Hd) with OPA in an alkaline medium. Upon acidification of the solution, however, only trace amounts of the alternative fluorescent adduct (Facid-Hd) are produced although Fbase-Hd disappears similarly to Fbase-Hm. In this paper, the reaction pathway of histidine with OPA was clarified by the kinetic analysis of formation and degradation of Fbase-Hd. In comparing the results of this study with the previous ones for histamine (T. Yoshimura et al., 1987, Anal. Biochem., 164, 132-137), we elucidate the difference between histamine and histidine in the mechanism of fluorescence reaction with OPA. The presence of the carboxyl group in histidine not only stabilizes Fbase-Hd in an alkaline medium but also prevents the formation of a 1:2 adduct of histidine and OPA, the precursor of Facid-Hd.     

Carbenic vs. ionic mechanistic pathway in reaction of cyclohexanone with bromoform

The extensive computation study was done to elucidate the mechanism of formation dibromoepoxide from cyclohexanone and bromoform. In this reaction, the formation of dihaloepoxide 2 is postulated as a key step that determines the distribution and stereochemistry of products. Two mechanistic paths of reaction were investigated: the addition of dibromocarbene to carbonyl group of ketone, and the addition of tribromomethyl carbanion to the same (C=O) group. The mechanisms for the addition reactions of dibromocarbenes and tribromomethyl carbanions with cyclohexanone have been investigated using ab initio HF/6-311++G** and MP2/6-311+G* level of theory. Solvent effects on these reactions have been explored by calculations which included a continuum polarizable conductor model (CPCM) for the solvent (H(2)O). The calculations showed that both mechanisms are possible and are exothermic, but have markedly different activation energies.     

The diffusion-controlled reaction of semioxidized tryptophan with the superoxide radical anion

From pulse radiolysis measurements in oxygenated aqueous solution, the semioxidized tryptophan radical (Trp·— formed by the one-electron oxidation of Trp by Br₂^- radical—has been shown to oxidize the superoxide radical anion with a rate constant of k = 2 × 10⁹ M⁻¹ s⁻¹. Proof of this reaction is found in addition of superoxide dismutase (SOD) to the system, which totally eliminates the contribution of the Trp^· + O₂^- mechanism to Trp^· decay. Little, if any, reaction of molecular oxygen with Trp^· may be observed on the time scale of the pulse radiolysis experiment.