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Simultaneous degradation of chloro- and methyl-substituted aromatic compounds: competition between Pseudomonas strains using the ortho and meta pathway or the ortho pathway exclusively.

Pseudomonas sp. D7-4 and Pseudomonas sp. B13 FR1(pFRC20P) degraded mixtures of chloro- and methyl-substituted benzoates exclusively via an extended ortho pathway, whereas in Pseudomonas putida WR 201 both ortho and meta fission were induced by mixtures of 3-chloro- and 3-methylbenzoate or even by 3-chloro-benzoate alone. The competition behaviour of these strains was compared in batch and in chemostat cultures.. Despite misrouting of metabolites, strain WR201 was competitive, in a lot of the competition experiments, with mixtures of these substrates. Only in a narrow range of the mixing ratio of chloro- and methylbenzoate was the presence of both the meta and ortho pathways a disadvantage for competitiveness. Outside these ranges other attributes, such as high growth rates or short lag periods, or a respective strain were even more essential for one strain to outcompete another.

Benzoates↗

The aspartic acid metabolic pathway, an exciting and essential pathway in plants.

Aspartate is the common precursor of the essential amino acids lysine, threonine, methionine and isoleucine in higher plants. In addition, aspartate may also be converted to asparagine, in a potentially competing reaction. The latest information on the properties of the enzymes involved in the pathways and the genes that encode them is described. An understanding of the overall regulatory control of the flux through the pathways is undisputedly of great interest, since the nutritive value of all cereal and legume crops is reduced due to low concentrations of at least one of the aspartate-derived amino acids. We have reviewed the recent literature and discussed in this paper possible methods by which the concentrations of the limiting amino acids may be increased in the seeds.

Aspartic Acid↗

Partial construction of apoptotic pathway in PBMC obtained from active SLE patients and the significance of plasma TNF-alpha on this pathway.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects various organs and systems. Increased apoptosis, together with defects in the uptake of apoptotic bodies, are thought to have a pathogenic role in SLE. By detection of chromatin condensation, 30% of apoptosis was detected in peripheral blood mononuclear cells (PBMC) from Thai patients with active SLE. Therefore, understanding of the molecular processes in PBMC apoptosis may allow us to gain insight into pathophysiology of SLE. Thus, genes involved in the apoptosis of PBMC from these patients were investigated ex vivo by cDNA array analysis. Seventeen apoptosis-related genes were stimulated in active SLE, more than twofold higher than in inactive SLE. These genes are classified into six groups, namely death receptors, death ligands, caspases, bcl-family, and neutral proteases and genes involved in endoplasmic reticulum stress-mediated apoptosis, such as caspase-4 and GADD153. Among those stimulated genes, tumor necrosis factor (TNF) and the TNF-receptor family were drastically up-regulated 60- and 19-fold higher than in healthy controls, respectively. Moreover, the degree of apoptosis correlated with the level of TNF-alpha in plasma, suggesting that the TNF family plays a role in the induction of apoptosis in SLE. To verify this hypothesis, PBMC from healthy individuals were treated with plasma from active SLE patients in the presence or absence of etanercept, a TNF inhibitor. In the presence of etanercept, active SLE plasma reduced the level of apoptosis to 26.43%. In conclusion, massive apoptotic death of PBMC occurred during the active stage of SLE. The molecular pathway of SLE-PBMC apoptosis was mediated at least via TNF/TNFR signaling pathway, which was confirmed by functional test of TNF-alpha in SLE patients' plasma.

Adult↗

A comparative study on the effects of inhibitors of the lipoxygenase pathway on neutrophil function. Inhibitory effects on neutrophil function may not be attributed to inhibition of the lipoxygenase pathway.

The effects of five inhibitors of the lipoxygenase pathway were evaluated on oxygen radical production, degranulation, chemotaxis, leukotriene B4 (LTB4) production by neutrophils. The lipoxygenase inhibitors tested were nordihydroguaiaretic acid (NDGA), esculetin, eicosatetraynoic acid (ETYA), 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone (AA-861), and 6,9-deepoxy-6, 9-(phenylimino)-delta 6.8-prostaglandin I1 (U-60,257). Neutrophils were activated by n-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA), A23187, or platelet activating factor (PAF). The effects of these inhibitors on NADPH oxidase activity and phospholipase A2 activity of isolated particulate fraction of neutrophils were also evaluated. ETYA inhibited neutrophil function induced by all the stimulators except PMA. AA-681 was unique in that it did not inhibit PAF-induced neutrophil activation. U-60,257 had virtually no effect on oxygen radical production and degranulation, but chemotaxis was moderately suppressed. NDGA effectively inhibited neutrophil function, except for chemotaxis. Esculetin inhibited only oxygen radical production, but this was due to inhibition on NADPH oxidase activity of neutrophil membrane. The inhibitory effect on neutrophil function and that of LTB4 production were not closely correlated. It is suggested that lipoxygenase inhibitors may modify neutrophil function by the mechanism not involving the lipoxygenase pathway. It is also suggested that LTB4 may not be a mediator in neutrophil oxygen radical production and degranulation induced by the stimulators used in the present study.

5,8,11,14-Eicosatetraynoic Acid↗

An alternative metabolic pathway of 11-deoxycorticosterone in bovine adrenal in vitro: evidence for the presence of a pathway of 11-deoxycorticosterone oxidation at 19-position.

Comparative studies of 11 beta-, 18-, and 19-hydroxylation activities of 11-deoxycorticosterone (DOC) by bovine adrenal mitochondria revealed that an appreciable level of hydroxylation rate was observed in 19-hydroxylation (0.32 nmol/min/mg mitochondrial protein), as well as in 11 beta- and 18-hydroxylations (4.7 and 0.27 nmol/min/mg mitochondrial protein, respectively), at saturated substrate concentration in vitro. Also, the rates of the oxidation reactions of 19-hydroxy-11-deoxycorticosterone (19-OH-DOC) and 19-oxo-11-deoxycorticosterone (19-oxo-DOC) at the 19-position were about 5 times higher than the 19-hydroxylation rate of DOC. Although the affinities of 19-OH-DOC and 19-oxo-DOC for the enzyme(s) involved in the C-19 oxidation were about one-fifth those of DOC, these results strongly suggest the presence of the following pathway in bovine adrenal in vitro: DOC----19-OH-DOC----19-oxo-DOC----19-oic-DOC. This was further confirmed by a dynamic study of the formation and subsequent decay of the C-19 oxidized metabolites produced from DOC. At maximum concentrations of 19-OH-DOC and 19-oxo-DOC, the rates of production of, respectively, 19-oxo-DOC and 19-oic-DOC reached maximum. Furthermore, at the beginning of the incubation (1-4 min), an induction period in the formation of 19-oxo-DOC and 19-oic-DOC was observed and the formation of 19-oxo-DOC always preceded the appearance of 19-oic-DOC. These observations strongly support the existence of the pathway of the C-19 oxidation of DOC as mentioned above. It was also established that reduced pyridine nucleotide (NADPH) and molecular oxygen were required for these oxidation reactions. In addition, these three oxidation reactions were uniformly inhibited by the presence of carbon monoxide or metyrapone (0.01-1.0 microM), which is known to bind specifically with cytochrome P-450, while potassium cyanide (0.01-0.1 mM) did not affect them. These results suggest the possibility of the involvement of cytochrome P-450 in the C-19 oxidation reactions of DOC, 19-OH-DOC, and 19-oxo-DOC. We also showed that 19-oic-DOC is not further metabolized to other steroids such as 19-nor-11-deoxycorticosterone in bovine adrenal cortex.

Adrenal Glands↗

Strategies for representing metabolic pathways within biochemical systems theory: reversible pathways.

The search for systematic methods to deal with the integrated behavior of complex biochemical systems has over the past two decades led to the proposal of several theories of biochemical systems. Among the most promising is biochemical systems theory (BST). Recent comparisons of this theory with several others that have recently been proposed have demonstrated that all are variants of BST and share a common underlying formalism. Hence, the different variants can be precisely related and ranked according to their completeness and operational utility. The original and most fruitful variant within BST is based on a particular representation, called an S-system (for synergistic and saturable systems), that exhibits many advantages not found among alternative representations. Even within the preferred S-system representation there are options, depending on the method of aggregating fluxes, that become especially apparent when one considers reversible pathways. In this paper we focus on the paradigm situation and clearly distinguish the two most common strategies for generating an S-system representation. The first is called the "reversible" strategy because it involves aggregating incoming fluxes separately from outgoing fluxes for each metabolite to define a net flux that can be positive, negative, or zero. The second is the "irreversible" strategy, which involves aggregating forward and reverse fluxes through each reaction to define a net flux that is always positive. This second strategy has been used almost exclusively in all variants of BST. The principal results of detailed analyses are the following: (1) All S-system representations predict the same changes in dependent concentrations for a given change in an independent concentration. (2) The reversible strategy is superior to the irreversible on the basis of several criteria, including accuracy in predicting steady-state flux, accuracy in predicting transient responses, and robustness of representation. (3) Only the reversible strategy yields a representation that is able to capture the characteristic feature of amphibolic pathways, namely, the reversal of nets flux under physiological conditions. Finally, the results document the wide range of variation over which the S-system representation can accurately predict the behavior of intact biochemical systems and confirm similar results of earlier studies [Voit and Savageau, Biochemistry 26: 6869-6880 (1987)].

Biochemical Phenomena↗

Independent pathways in the modulation of osteoclastic resorption by intermediates of the mevalonate biosynthetic pathway: the role of the retinoic acid receptor.

Geranylgeranyl pyrophosphate (GGPP) and geranylgeraniol (GGOH) are used for the prenylation of GTP binding proteins and can reverse the antiresorptive action of nitrogen-containing bisphosphonates which inhibit farnesyl pyrophosphate synthase, an enzyme of the mevalonate pathway involved in the formation of GGPP. Previously, in cultures of fetal mouse long bones, we showed that GGOH stimulates osteoclastic bone resorption, but the cellular and molecular mode of action is not known. In cell homogenates, it has been found that GGOH can be metabolized to geranylgeranoic acid (GGA) which, like retinoic acid (RA), is a stimulator of retinoic acid receptor (RAR) expression. For this, we examined the involvement of the RAR in the action of GGOH on bone resorption. We show here that RA, GGOH, GGPP and GGA stimulate osteoclastic bone resorption and that this action is reversed by the RAR antagonist AGN-193109. These findings indicate the functional involvement of the RAR in the action of these polyisoprenoids. Moreover, RA, GGOH and GGA all stimulated RARbeta mRNA expression in bone explants. However, in contrast to GGOH and GGPP, GGA was not able to reverse the antiresorptive action of ibandronate, a nitrogen-containing bisphosphonate, suggesting that GGA is not involved in protein prenylation. In conclusion, our studies show that both GGOH and GGPP, independent of protein prenylation, stimulate osteoclastic bone resorption via RAR, probably via metabolism into GGA. Identification of such mechanism can help in the better understanding of the role of this metabolic pathway in the regulation of the activity and survival of osteoclasts.

Animals↗

The folding pathway of T4 lysozyme: an on-pathway hidden folding intermediate.

T4 lysozyme has two easily distinguishable but energetically coupled domains: the N and C-terminal domains. In earlier studies, an amide hydrogen/deuterium exchange pulse-labeling experiment detected a stable submillisecond intermediate that accumulates before the rate-limiting transition state. It involves the formation of structures in both the N and C-terminal regions. However, a native-state hydrogen exchange experiment subsequently detected an equilibrium intermediate that only involves the formation of the C-terminal domain. Here, using stopped-flow circular dichroism and fluorescence, amide hydrogen exchange-folding competition, and protein engineering methods, we re-examined the folding pathway of T4-lysozyme. We found no evidence for the existence of a stable folding intermediate before the rate-limiting transition state at neutral pH. In addition, using native-state hydrogen exchange-directed protein engineering, we created a mimic of the equilibrium intermediate. We found that the intermediate mimic folds with the same rate as the wild-type protein, suggesting that the equilibrium intermediate is an on-pathway intermediate that exists after the rate-limiting transition state.

Bacteriophage T4↗

A G protein-associated ERK pathway is involved in LPS-induced proliferation and a PTK-associated p38 MAPK pathway is involved in LPS-induced differentiation in resting B cells.

We, previously, showed that PKC-dependent ERK/p38 MAPK activation was inhibited by treating the resting B cell line 38B9 with an anti-MHC class II antibody. Further studies in this work demonstrated that PKA was involved in lipopolysaccharide (LPS)-induced proliferation of the cells, such that the PKC inhibitor activated PKA with concomitant LPS-induced proliferation but not IgG secretion. Consequently, the PKA inhibitor down-regulated ERK and p38 MAPK, and decreased cell proliferation. In addition, the treatment of LPS-stimulated 38B9 cells with PTK inhibitor reduced PKC- and PKA-dependent p38 MAPK activation and reduced the level of IgG secretion rather than the level of proliferation. However, the treatment of LPS-stimulated 38B9 cells with pertussis toxin (PTX), an inhibitor for the G protein-coupled receptor, inhibited the activation of both PKC- and PKA-dependent ERK and significantly reduced LPS-induced proliferation but not IgG secretion. Furthermore, ERK and p38 MAPK inhibitors reduced LPS-induced proliferation and differentiation, respectively, in 38B9 cells in a dose-dependent manner. These results suggest that LPS-induced proliferation of resting B cells is mainly mediated through a G protein-associated PKA/PKC-dependent ERK pathway and that a PTK-associated PKC/PKA-dependent p38 MAPK pathway is mostly involved in LPS-induced differentiation of the resting B cells.

Animals↗

15-Hydroperoxyeicosapentaenoic acid, but not eicosapentaenoic acid, shifts arachidonic acid away from cyclooxygenase pathway into acyl-CoA synthetase pathway in rabbit kidney medulla microsomes.

Under physiological conditions, small amounts of free arachidonic acid (AA) are released from membrane phospholipids, and cyclooxygenase (COX) and acyl-CoA synthetase (ACS) competitively act on this fatty acid to form prostaglandins (PGs) and arachidonoyl-CoA (AA-CoA). In the present study, we investigated the effects of eicosapentaenoic acid (EPA) and 15-hydroperoxyeicosapentaenoic acid (15-HPEPE) on the PG and AA-CoA formations from high and low concentrations of AA (60 and 5 microM) in rabbit kidney medulla microsomes. The kidney medulla microsomes were incubated with 60 or 5 microM [(14)C]-AA in 0.1M Tris/HCl buffer (pH 8.0) containing cofactors of COX (reduced glutathione and hydroquinone) and cofactors of ACS (ATP, MgCl(2) and CoA). After incubation, PG (as total PGs), AA-CoA and residual AA were separated by selective extraction using petroleum ether and ethyl acetate. EPA reduced the PG and AA-CoA formations from both 60 and 5 microM AA. In contrast, 15-HPEPE decreased the PG formation without affecting the AA-CoA formation from 60 microM AA, and increased the AA-CoA formation at the expense of PG formation when 5 microM AA was used as substrate concentration. The experiments utilizing Fe(2+) and an electron spin resonance (ESR) revealed that 15-HPEPE elicits these effects in the form of hydroperoxy adduct. These results suggest that 15-HPEPE, but not EPA, has the potential to shift AA away from COX pathway into ACS pathway at low substrate concentration (close to the physiological concentration of AA).

Animals↗

Control analysis of biochemical pathways: a novel procedure for calculating control coefficients, and an additional theorem for branched pathways.

A novel method for calculating control coefficients of individual enzymes on fluxes and concentrations in metabolic pathways is presented. This method is derived by applying the theorem on implicit functions to the equations defining the steady state metabolite concentrations; it allows verification of the existing summation theorems and connectivity relations, and leads to a novel theorem for flux control coefficients in branched pathways. The method and the novel theorem are illustrated by several examples.

Mathematics↗

Examination of signal transduction pathway of stimulated B1 and B2 kinin receptors; MAP kinase pathway to AP-1 translocation in HEK 293 cells.

B1 or B2 kinin receptor-overexpressing HEK293 cells were stimulated with des-Arg9-BK or BK, respectively. Each agonist induced translocation of AP-1 into the nuclear fraction as well as activation of MAP kinases in each cells. MAP kinase inhibitor PD98059 suppressed translocation of AP-1 and agonist-induced MAP kinase activation in both cells. These results indicate that stimulation of B1 or B2 receptor expresses a feature of the signal transduction pathway of MAP kinase activation to translocation of AP-1. This signal transduction pathway of HEK cells through B1 and B2 receptors may be similar in response to respective agonists.

Animals↗

The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau.

In Pick disease and progressive supranuclear palsy (PSP), accumulations of phosphorylated tau are associated with oxidative stress, although the mechanism linking these features remains unknown. However, we suspected that the oxidative stress-induced activation of mitogen-activated protein kinases might lead to tau phosphorylation and accumulation as characteristic inclusion bodies. To test this notion, we investigated whether the activation of mitogen-activated protein kinases is involved in the pathogenesis of Pick disease and PSP. Our results show that the lesions of both Pick disease and PSP are associated with the activation of the p38 pathway (phospho-MKK6 and phospho-p38), one of the best characterized of the mitogen-activated protein kinase pathways. Based on these findings, we propose that the phosphorylation of tau is a direct consequence of the oxidative stress-induced activation of mitogen-activated protein kinases, including p38.

Calcium-Calmodulin-Dependent Protein Kinases↗

Effects of 50-Hz magnetic fields on the signalling pathways of fMLP-induced shape changes in invertebrate immunocytes: the activation of an alternative "stress pathway".

N-formyl-Meth-Leu-Phe (fMLP)-induced immunocyte shape changes in the mussel Mytilus galloprovincialis through both the phosphatidylinositol and the cAMP pathways are studied. Fifteen- and thirty-minute exposures of mussels to 50-Hz magnetic fields (MFs) at intensities of 300 and 400 microT do not provoke permanent cell damage, since immunocytes maintain the capacity to respond to fMLP. This avoidance of external insult seems to be achieved through the activation of a "stress pathway" which is not functionally detectable in nonexposed animals and which involves mitogen activated protein (MAP) kinase members. This phenomenon is clearly evident at 400 microT. Contemporaneously, a different expression of Jun transcriptional regulatory proteins is also found.

Animals↗

Heterogeneity of anterograde fast-pathway and retrograde slow-pathway conduction patterns in patients with the fast-slow form of atrioventricular nodal reentrant tachycardia: electrophysiologic and electrocardiographic considerations.

OBJECTIVES: This study sought to define the electrophysiologic and electrocardiographic characteristics of fast-slow atrioventricular nodal reentrant tachycardia (AVNRT). BACKGROUND: In fast-slow AVNRT the retrograde slow pathway (SP) is located in the posterior septum, whereas the anterograde fast pathway (FP) is located in the anterior septum; however, exceptions may occur. METHODS: Twelve patients with fast-slow AVNRT were studied. To determine the location of the retrograde SP, atrial activation during AVNRT was examined while recording the electrograms from the low septal right atrium (LSRA) on the His bundle electrogram and the orifice of the coronary sinus (CS). Further, to investigate the location of the anterograde FP, single extrastimuli were delivered during AVNRT both from the high right atrium and the CS. RESULTS: The CS activation during AVNRT preceded the LSRA in six patients (posterior type); LSRA activation preceded the CS in three patients (anterior type), and in the remaining three both sites were activated simultaneously (middle type). In the anterior type, CS stimulation preexcited the His and the ventricle without capturing the LSRA electrogram (atrial dissociation between the CS and the LSRA), suggesting that the anterograde FP was located posterior to the retrograde SP. In the posterior and middle types, high right atrial stimulation demonstrated atrial dissociation, suggesting that the anterograde FP was located anterior to the SP. In the posterior and middle types, retrograde P waves in the inferior leads were deeply negative, whereas they were shallow in the anterior type. CONCLUSIONS: Fast-slow AVNRT was able to be categorized into posterior, middle and anterior types according to the site of the retrograde SP. The anterior type AVNRT, where an anteriorly located SP is used in the retrograde direction and a posteriorly located FP in the anterograde direction, appears to represent an anatomical reversal of the posterior type which uses a posterior SP for retrograde and an anterior FP for anterograde conduction. Anterior type AVNRT should be considered in the differential diagnosis of long RP (RP > PR intervals) tachycardias with shallow negative P waves in the inferior leads.

Adult↗

Circular dichroism spectroscopy of the intermediates that precede the rate-limiting step of the refolding pathway of bovine pancreatic trypsin inhibitor. Relationship of conformation and the refolding pathway.

Circular dichroism spectra of the partially folded trapped intermediates were measured in order to aid in the elucidation of the conformational forces which determine a nonrandom, nonsequential pathway of disulfide bond formation upon refolding of bovine pancreatic trypsin inhibitor. Whatever conformation was responsible for the kinetic rates of the intermediates should be stabilized by the presence of their trapped disulfide bonds. The near-ultraviolet spectra provide considerable information about the environments of the aromatic and disulfide side chains. The predominant single-disulfide intermediate has significant nonrandom conformation not present in the fully reduced protein, with aromatic rings and the disulfide bond in stabilized asymmetric environments. Forming either of the two nonnative, but kinetically important, second disulfides in this intermediate does not produce unequivocably different conformations. Forming a second native, but kinetically unproductive, disulfide produces a substantial decrease in randomness, which may hinder formation of the third disulfide. The largest conformational changes occur upon disulfide rearrangement to the stable, correctly refolded, two- and three-disulfide species. Interpretation of the far-ultraviolet spectra in terms of the secondary structure of the intermediates is uncertain, due to the atypical spectra of the folded forms of the protein. Consequently, we are unable to determine unambiguously the secondary structure of the intermediates. However, all the spectra show that nonrandom conformations of the polypeptide chain gradually appear as disulfide bond formation progresses, as expected from the nonrandom pathway of the latter.

Animals↗

Overexpression of the endoplasmic reticulum 60 protein ER-60 downregulates apoB100 secretion by inducing its intracellular degradation via a nonproteasomal pathway: evidence for an ER-60-mediated and pCMB-sensitive intracellular degradative pathway.

Co- and posttranslational regulation of apolipoprotein B (apoB) has been postulated to involve degradation by both proteasomal and nonproteasomal pathways; however, nonproteasomal mechanisms of apoB degradation are currently unknown. We have previously demonstrated an intracellular association of newly synthesized apoB with endoplasmic reticulum (ER)-60, an ER-localized protein, possessing both proteolytic and chaperone activities. In the present paper, adenoviral expression vectors containing rat ER-60 cDNA were used to achieve dose- and time-dependent overexpression of ER-60 to investigate its role in apoB100 turnover. Overexpressed ER-60 accumulated in the microsomal lumen of HepG2 cells and was associated with apoB100 in dense lipoprotein particles. Overexpression of ER-60 in HepG2 cells significantly reduced both intracellular and secreted apoB100, with no effect on the secretion of a control protein, albumin. Similar results were obtained in McA-RH7777 rat hepatoma cells. ER-60-stimulated apoB100 degradation and inhibition of apoB100 secretion were sensitive to the protease inhibitor, p-chloromercuribenzoate (pCMB), in a dose-dependent manner but were unaffected by the proteasomal or lysosomal protease inhibitors, N-acetyl-leucinyl-leucinyl-nor-leucinal, E64, and leupeptin. Interestingly, enhanced expression of ER-60 induced apoB100 fragmentation in permeabilized HepG2 cells and resulted in detection of a unique 50 kDa degradation intermediate, a process that could be inhibited by pCMB. Intracellular stability and secretion of apoB100 in primary hamster hepatocytes were also found to be sensitive to pCMB. When taken together, the data suggest an important role for ER-60 in promoting apoB100 degradation via a pCMB-sensitive process in the ER. ER-60 may act directly as a protease or may be involved indirectly as a chaperone/protein factor targeting apoB100 to this nonproteasomal and pCMB-sensitive degradative pathway.

Adenoviridae↗

Novel pathways for oxygen insertion into unactivated C-H bonds by dioxiranes. Transition structures for stepwise routes via radical pairs and comparison with the concerted pathway.

The oxygen insertion into C-H bonds (of methane, isobutane, and acetone) by dioxiranes (parent dioxirane and dimethyldioxirane) to give alcohols was studied with the DFT theory, using both restricted and unrestricted B3LYP methods, and 6-31G(d) and 6-311+G(d,p) basis sets to evaluate the feasibility of stepwise mechanisms and their competition with the concerted counterpart. Confirming previous results by other authors, we have located, with the RB3LYP method, concerted TSs in which the oxygen bound to be inserted interacts very strongly with the hydrogen atom and very weakly with the carbon atom of the C-H bond. These TSs nicely explain all the experimental observations (e.g., configuration retention at the chiral centers), but all of them exhibit an RHF --> UHF wave function instability that preclude considering them as genuine transition structures. We also were able to characterize, with UB3LYP methods, two alternative two-step processes that can lead to final products (alcohol + carbonyl compound) via singlet radical pair intermediates. For the first step of both processes we located genuine diradicaloid TSs, namely, TSs rad,coll and TSs rad,perp, that have stable wave functions. In TSs rad,coll the alkane C-H bond tends to be collinear with the breaking O(1)- - -O(2) bond while in TSs rad,perp the alkane C-H bond is almost perpendicular to the O(1)- - -O(2) bond. The first step, of both processes, can represent an example of a "molecule induced homolysis" reaction: collision between alkane and dioxirane brings about the homolytic cleavage of the dioxirane O-O bond and the hydrogen abstraction follows afterward to produce the diradicaloid TS that then falls down to a singlet radical pair. This hypothesis was fully confirmed by IRC analysis in the case of TSs rad,coll. The possible pathways that lead from the intermediate radical pair to final products are discussed as well as the hypothesis that the radical collinear TSs may collapse directly to products in a "one-step nonconcerted" process. However, diradical mechanisms cannot explain the experimental data as satisfactorily as the concerted pathway does. As for computational predictions about competition of diradical vs concerted mechanisms, they strongly depend (i) on the alkane C-H type, (ii) on whether gas phase or solution is considered, and (iii) on the basis set used for calculations. In short, the concerted TS benefits, with respect to the corresponding diradicaloid TSs, of alkyl substitution at the C-H center, solvation effects, and basis set extension. Actually, in the case of DMD reactions with methane and acetone, the diradicaloid TSs are always (both in gas phase and in solution and with both the basis sets used) strongly favored over their concerted counterpart. In the case of DMD reaction with isobutane tertiary C-H bond the large favor for the diradicaloid TSs over the concerted TS, predicted in gas phase by the B3LYP/6-31G(d) method, progressively decreases as a result of basis set extension and introduction of solvent effects: the higher theory level [B3LYP/6-311+G(d,p)] suggests that in acetone solution TS conc has almost the same energy as TS rad,perp while TS rad,coll resides only 2 kcal/mol higher.

Journal Article↗