Ligation reactions, kinetics

Peptides typically are prepared for this ligation process using a-alkyl thioesters, because they are simple to make at the time of peptide synthesis. However, due to the relatively slow reaction kinetics of alkyl thioesters, most native chemical ligation processes have been catalyzed through the use of thiol compound additives, such as benzyl mercaptan or thiophenol (Dawson et al., 1997). These compounds react with the initial a-alkyl thioester to form another intermediate, an aryl thioester, which is more reactive toward the N-terminal cysteine on the other peptide to be coupled. A study... 

Very recently, the kinetics and thermodynamics of a variety of axial ligation reactions have been investigated with Fe11 and Co11 porphyrins involving the small molecules CO, 02, and NO as ligands 27-30, 40, 92, 93). These experiments lead to the conclusion that the dynamic trans effects observed in these systems cannot alone be explained by the interaction models D and F (Fig. 1). Especially imidazole and its derivatives do not hold the place in various series of trans effects that they should take on the ground of their proton basicities. Therefore, besides their usual a-donor-tr-acceptor function, these unsaturated molecules are ascribed an additional 7r-donor function. 

Just as in conventional substitution reactions in Cr(III) complexes, there is considerable controversy as to the mechanism of substitution in Cr(III) meso-substituted porphyrins negative AS values suggest associative activation of the axial sites while positive AV values imply dissociative activation. A thorough study of the kinetic and equilibrium properties of the axial ligation reaction between imidazole and pyridine with [Cr(TPPS)(H20)2] " has now been made. Data were analyzed according to Scheme 1 and the rate and equilibrium constants are reported in Table 6.4. Data for the toluene soluble [CrCl(TPP)X] (X = py, quinoline, or PPhj) with 1-methyl imidazole (Meim) are not quite comparable, as the reaction is not first order in Meim. Kinetic parameters for the dissociation of X from [CrCl(TPP)X] in toluene are, in order X, k (s" ), AH, AS, AV py,... 

The replication efficiency is usually characterized by two kinetic parameters e, which reflects the ratio between template-assisted and template-free ligation reactions, and... 

Figure 12 Kinetic profiles of product formation in reactions between E and N in the presence of the caged peptide T in the dark (black dashed line) and after shining light (solid black line). The kinetics of ligation reactions between E and N without any template seeded (blue dashed lines) or seeded with premade T molecules (blue solid line) are shown for comparison.

A rapid reaction between dioxorhenium(VII) and PPh3 was proposed in Eq. (11) for sake of consistency with the kinetic data. For reasons to be presented subsequently, this is shown as the addition of the phosphorus to an oxo oxygen. In effect, this is the reduction of rhenium(VII) with the concomitant creation of a rhenium(V) complex ligated by a phosphine oxide,... 

The carbonic anhydrase (Cam) in M. thermophila cells is elevated several fold when the energy source is shifted to acetate, suggesting a role for this enzyme in the acetate-fermentation pathway. It is proposed that Cam functions outside the cell membrane to convert CO2 to a charged species (reaction A4) thereby facilitating removal of product from the cytoplasm. Cam is the prototype of a new class (y) of carbonic anhydrases, independently evolved from the other two classes (a and P). The crystal structure of Cam reveals a novel left-handed parallel P-helix fold (Kisker et al. 1996). Apart from the histidines ligating zinc, the activesite residues of Cam have no recognizable analogs in the active sites of the a- and P-classes. Kinetic analyses establish that the enzyme has a zinc-hydroxide mechanism similar to that of Cab (Alber et al. 1999). 

A similar carbonylative coupling reaction was applied to the kinetic resolution of secondary alcohols [63]. In the presence of a Pd catalyst ligated by chiral oxazolinylferrocenylphosphine, the pentavalent Ph3Bi(OAc)2 and carbon monoxide effectively benzoylated secondary alcohols, and up to 48% enantiomeric excess (ee) was attained (Scheme 47). Although the enantioselectivity is not satisfactory, this is a unique new procedure for the kinetic resolution. 

In addition of organometallic reagents to some arynes, prior counterion complexation with the substituent can direct the incoming group to the ortho position (kinetic control). Addition of alkyllithiums to oxazolinyl (OXZ) aryne (51) to give the ortho product (52) is explained in this manner. In contrast, lithium dialkylcuprates add to the aryne (51) exclusively at the meta position. This is ascribed to thermodynamic control of the reaction, which results in the formation of the more ligated and stable adduct (S3).i2 Control of nucleophilic addition to arynes by complex-induced proximity effects has not been explored with substituents other than OXZ,83 but has considerable synthetic potential if it can be achieved, say through solvent manipulation. 

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