Multiple catalytic cycles

Basran J, RJ Harris, MJ Sutcliffe, NS Scrutton (2003) H-tuneling in the multiple H-transfers of the catalytic cycle of morphinone reductase and in the reductive half-reaction of the homologous pentaerythritol tetranitrate reductase. J Biol Chem 278 43973-43982. 

The catalytic cycle of laccase includes several one-electron transfers between a suitable substrate and the copper atoms, with the concomitant reduction of an oxygen molecule to water during the sequential oxidation of four substrate molecules [66]. With this mechanism, laccases generate phenoxy radicals that undergo non-enzymatic reactions [65]. Multiple reactions lead finally to polymerization, alkyl-aryl cleavage, quinone formation, C> -oxidation or demethoxylation of the phenolic reductant [67]. 

In the field of responsive agents, enzyme targeting has specific advantages. A small concentration of the enzyme can convert a relatively high amount of the probe in multiple catalytic cycles which considerably decreases the detection limit for the enzyme as compared to other biomolecules. Moreover, enzymatic reactions are usually highly specific therefore, the observed change... 

Reaction conditions permitting a catalyst to pass through many catalytic rounds. Multiple-turnover conditions are usually obtained by maintaining the substrate concentration in excess over the concentration of active catalyst. This technique usually allows one the opportunity to evaluate the catalytic rate constant ka,t, which is the first-order decay rate constant for the rate-determining step for each cycle of catalysis, and one can evaluate the magnitude of other parameters such as the substrate s dissociation constant or Michaehs constant. 

None of these difficulties arise when hydrosilylation is promoted by metal catalysts. The mechanism of the addition of silicon-hydrogen bond across carbon-carbon multiple bonds proposed by Chalk and Harrod408,409 includes two basic steps the oxidative addition of hydrosilane to the metal center and the cis insertion of the metal-bound alkene into the metal-hydrogen bond to form an alkylmetal complex (Scheme 6.7). Interaction with another alkene molecule induces the formation of the carbon-silicon bond (route a). This rate-determining reductive elimination completes the catalytic cycle. The addition proceeds with retention of configuration.410 An alternative mechanism, the insertion of alkene into the metal-silicon bond (route b), was later suggested to account for some side reactions (alkene reduction, vinyl substitution).411-414... 

Multinuclear (isocyanide)gold complexes, reactivity, 2, 287 Multi-phase organometallic catalysis, in ionic liquids, 1, 856 Multiple-quantum MAS, half-integer spin quadrupolar nuclei central transition NMR studies, 1, 466 Multistate magnetization transfer, in dynamic NMR magnetization, 1, 410 Multistep catalytic cycles... 

Enzymes often require multiple substrates to complete their catalytic cycle. This may involve combining two compounds into one molecule or transferring atoms or electrons from one substrate to another. The substrates may both bind to an enzyme and react collectively, or each substrate might bind, react, and release sequentially. With two substrates, if both bind to the enzyme, a ternary complex (ES S2) will form (Scheme 4.8). The order of substrate addition may be important (ordered) or not (random order). Cases in which the two substrates react sequentially follow a double-displacement, or ping-pong, mechanism (Scheme 4.9). Enzymes requiring more than two substrates have more complicated complexation pathways. 

It is worthy to note here that the methylidene complex 11 is a poor initiator for olefin metathesis reactions at room temperature. Although this complex can undergo multiple catalytic turnovers, if it is intercepted by free phosphine ligand, it becomes incapable of reentering the metathesis catalytic cycle.32... 

Nature accomplishes many syntheses-even those of complex molecules-by sequences of elementary steps. In the last few decades, the blueprint of catalyzed cascade reactions has found fertile soil through the advent of transition metal catalysis in laboratories. Scrutinizing catalytic cycles and mechanistic insight has paved the way for designing new sequential transformations catalyzed by transition metal complexes in a consecutive or domino fashion. In particular, transition metal-catalyzed sequences considerably enhance structural complexity by multiple iterations of organometalhc elementary steps. All this has fundamentally revolutionized synthetic strategies and conceptual thinking. 

Metal complexes act as "n acids" (10) and are powerful tools for the activation of C—C multiple bonds—the key step for the initiation of many catalytic cycles involving C—C imsaturation. This process is facilitated by a more electrophilic metal center with an enhanced tendency to bind with the nucleophilic monomer. 

The electrophilic activation of a C—C multiple bond as a result of coordination to an electron-deficient metal ion is fundamental to much of organometallic chemistry, both conceptually and in synthetic applications (11). The Wacker process, a classic example of an efficient catalytic oxidation, is an important industrial reaction, used for the conversion of ethylene into acetaldehyde. The catalytic reaction begins with the coordination of ethylene to a Pd(ll) center, leading to activation of the ethylene moiety. The key step is the reaction of the metal-olefin complex with a nucleophile to give substituted metal-alkyl species (12). The integration of this reaction into a productive catalytic cycle requires the eventual cleavage of the newly generated M—C bond. 

In networks with loops or multiple catalytic cycles, the use of (loop) or T (collective) instead of A coefficients may provide further simplification (see Sections 6.4 and 8.8). A detailed example will illustrate the procedure. 

From a mechanistic point of view the first steps of the catalytic cycle should be similar to the telomerization of butadiene itself (Scheme 2). The catalytic precursor generates the Pd(0) species A that reacts to the bis-(ri -allyl) complex C. The C,C bond formation between two C4 units is followed by insertion of carbon dioxide into a Pd,C bond affording the carboxylate intermediate D. Different pathways have been discussed to describe the multiple product formation (refer to ). Interestingly, a bis-(carboxylato) complex may be prepared directly from the reaction of lactone 1, palladium acetate and P(i-Pr)3. This complex was structurally characterized by Behr and co-workers and shows good activity as catalyst. Reviewing the literature, there are some remarkable facts and open questions of theoretical and technical interest ... 

In this Scheme, pC stands for pro-catalyst, C for catalyst, CS for a complex between catalyst and substrate, CP for a complex between catalyst and product, I for an initiator. S for a structural variation of the substrate, R for an added reagent. In cases 1.1 and 1.2 the catalysis is based on a coordinative interaction between catalyst and substrate in case 1.1 the product is released to regenerate C (for example by reductive elimination) whereas in case 1.2 the regeneration of CS results from a substitution of the complexed product by S. It should be clear that cases 1.1 and 1.2 do not exhaust the formal possibilities offered to photogenerated catalysis. One may actually imagine a photogeneration of catalyst from a selected pro-catalyst for any of the multiple catalytic cycles identified in homogeneous catalysis centered on transition metal complexes [12]. 

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