A graph-theoretic method to identify candidate mechanisms for deriving the rate law of a catalytic reaction.

Stoichiometrically, exact candidate pathways or mechanisms for deriving the rate law of a catalytic or complex reaction can be determined through the synthesis of networks of plausible elementary reactions constituting such pathways. A rigorous algorithmic method is proposed for executing this synthesis, which is exceedingly convoluted due to its combinatorial complexity. Such a method for synthesizing networks of reaction pathways follows the general framework of a highly exacting combinatorial method established by us for process-network synthesis. It is based on the unique graph-representation in terms of P-graphs, a set of axioms, and a group of combinatorial algorithms. In the method, the inclusion or exclusion of a step of each elementary reaction in the mechanism of concern hinges on the general combinatorial properties of feasible reaction networks. The decisions are facilitated by solving linear programming problems comprising a set of mass-balance constraints to determine the existence or absence of any feasible solution. The search is accelerated further by exploiting the inferences of preceding decisions, thereby eliminating redundancy. As a result, all feasible independent reaction networks, i.e. pathways, are generated only once; the pathways violating any first principle of either stoichiometry or thermodynamics are eliminated. The method is also capable of generating those combinations of independent pathways directly, which are not microscopically reversible. The efficiency and efficacy of the method are demonstrated with the identification of the feasible mechanisms of ammonia synthesis involving as many as 14 known elementary reactions.

Comparative evaluation of new synergists containing a butynyl-type synergophore group and piperonyl butoxide derivatives.

Cross-substituted derivatives of piperonyl butoxide (PBO) and MB-599 (proposed common name: verbutin) were synthesized and investigated as carbofuran and permethrin synergists against housefly, Musca domestica L. The majority of PBO and MB-599 derivatives were significantly more potent synergists for carbofuran than for permethrin. PBO, the most important representative of this series was not the most potent synergist for carbofuran or for permethrin. Cleavage of the methylenedioxy ring of methylenedioxyphenyl (MDP) polyether compounds resulted in complete loss of synergistic activity with both insecticides, but it could be restored or even improved by incorporating an alkynyl ether moiety into the molecule. The improved synergistic activity was found to be closely associated with the 2-butynyloxymethyl side-chain, suggesting that this can be regarded as a characteristic synergophore group. MB-599, one of the most promising compounds bearing this group showed considerably higher activity with carbofuran (synergist ratio, SR = 37.8) than with PBO (SR = 6.4). There was no significant difference between synergistic activities of MB-599 (SR = 4.6) and PBO (SR = 4) for permethrin.

Chemical models of cytochrome P450 catalyzed insecticide metabolism. Application to the oxidative metabolism of carbamate insecticides.

Cytochrome P450 (CP450) catalyzed oxidative metabolism of carbofuran (1), carbaryl (2), and pirimicarb (3) has been modeled using biomimetic oxidations catalyzed by iron(III) tetraarylporphyrins. Oxidation products of 1 were identified by comparison of HPLC retention times measured under standardized conditions for metabolites synthesized and characterized by (1)H and (13)C NMR spectroscopy. Comparison of product distributions to in vivo metabolic profiles revealed that the H(2)O(2)/meso-tetrakis(pentafluorophenyl)porphyrin iron(III) chloride [Fe(TF(20)PP)] system mimics the action of insect CP450s against carbofuran. The effectiveness of this system was further demonstrated by the biomimetic oxidation of other carbamate insecticides (2 and 3) monitored by HPLC/electrospray MS. The predictive power of this biomimetic model was compared to that of knowledge-based expert systems. Although similar models were recently applied in pharmaceutical research, the usefulness of this approach has first been demonstrated for the prediction of metabolic profiles of agrochemicals.

Is a complete recovery of diabetes mellitus possible?

Serum contains a factor that can normalize streptozotocin induced blood sugar elevation. This normalization can last for a long period. Thus an elimination of elevated diabetic blood sugar values takes place. This means that an euglycemic factor may have the ability to an eventual curing of diabetes. Normal, starving rats are not influenced by the euglycemic factor. An other factor even aggravates diabetic blood sugar level.