Catalytic diads

The cleavage mechanism of the caspases is shown schematically in Fig. 15.5. They use a typical protease mechanism with a catalytic diad for cleavage of the peptide bond. The nucleophilic thiol of an essential Cys residue forms a covalent thioacyl bond to the substrate during the catalysis. The imidazole ring of an essential histidine is also involved in catalysis and this facilitates hydrolysis of the amide bond in the sense of an acid/base catalysis. 

The active site structure of peroxidases (Fig. 16-13) is quite highly conserved. As in myoglobin, an imidazole group is the proximal heme ligand, but it is usually hydrogen bonded to an aspartate carboxylate as a catalytic diad (Fig. 16-13).223 In cytochrome c peroxidase... 

Early studies desalbe the transesterilication between an active ester and a nucleophile like water catalyzed by amino alcohols [37-46]. For the hydrolysis of active p-nitrophenyl acetates, amino alcohol catalysts served as models for the catalytic diad of serine proteases. Kinetic studies show that the hydrolysis catalyzed by an amino alcohol proceeds via an acylation-deacylation mechanism. 

The 3-methyl- and 3-phenyl-l,2,3-oxadiazolinium salts 96 and 97 are capable of oxidizing thiols to disulfides <1995MI817>. New dihydro-1,2,3-benzoxadiazoles, prepared by the reaction of 1,2-benzoquinones with diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) in the presence of triphenylphosphine (Section 5.03.9.4), have been shown to undergo catalytic hydrogenolysis to give phenols (Equation 12) <20050L5139>. 

The possible occurrence of a back-skip of the chain for catalytic systems based on C2-symmetric metallocenes would not change the chirality of the transition state for the monomer insertion and hence would not influence the corresponding polymer stereostructure. On the contrary, for catalytic systems based on Cs-symmetric metallocenes, this phenomenon would invert the chirality of the transition state for the monomer insertion, and in fact it has been invoked to rationalize typical stereochemical defects (isolated m diads) in syndiotactic polypropylenes.9 376 60 This mechanism of formation of stereoerrors has been confirmed by their increase in polymerization runs conducted with reduced monomer concentrations.65 In fact, it is reasonable to expect an increase in the frequency of chain back-skip by reducing the monomer concentration and hence the frequency of monomer insertion. 

Steric defects in isotactic polypropylene, which involve the appearance of isolated r diads or pairs of r diads, may be considered on a pentad level (Figures 3.45a and b respectively). The 13C NMR signals associated with occasional stereoerrors in the propylene isotactic polymers produced by chiral metallocene-based catalysts (pairs of r diads) indicate that the polymerisation stereochemistry is governed by the enantiomorphism of catalytic sites an error pentad distribution close to mmmr.mmrr.mmrm-.mrrm = 2 2 0 1 is observed... 

The possible origin of the low stereoselectivity for the chain-end-controlled catalytic systems based on metallocenes including two cyclopentadienyl rings has been discussed by Corradini, Guerra, and co-workers.2 The two possible diastereomeric preinsertion intermediates for si and re coordinations of the monomer for the case of a si chain—that is, a growing chain in which the last monomeric unit has been obtained by addition of a si-coordinated propene—are shown in Figure 24, parts A and B, respectively. These models would lead to a si—si and re—si propene enchainments, that is, to an isotactic and syndiotactic diad, respectively. 

The catalytic machinery involves a diad composed of the sulfhydryl group of Cys285 in close proximity to the imidazole group of His237, both from the large subunit. 

There are four possible combinations of regiochemistry and stereochemistry within diad units. The olefins can join in a head-to-head or head-to-tail fashion. Most polyolefins formed by early metal catalyts are formed by strict head-to-tail enchainment, but this head-to-tail enchainment can occur by a series of 1,2-insertions in which the a-olefin substituent is located P to the metal in tihe insertion product or 2,1-insertions in which the a-olefin substituent is located a to the metal in the insertion product. In addition, the olefins can join to give rise to a diad unit containing identical (meso, m) or opposite (racemo, r) stereochemical relationships to the last inserted monomer unit. Site control of polymerization to form isotactic polymer gives rise to rr-defects m the polymer from stereoerrors, but cham-end control of polymerization to form isotactic polymer gives rise to r-defects from stereoerrors. 

Brocklehurst, K., Malthouse, J.P.G. Shipton, M. (1979). Evidence that binding to the S2-subsite of papain may be coupled with catalytically relevant structural change involving the cysteine-25-histidine-159 diad. Kinetics of the reaction of papain with a two-protonic-state reactivity probe containing a hydrophobic side chain. Biochem. J., Vol. 183, No.2, pp. 223-231... 

The same group also reported that dendrimers built by interaction of Dap-His-Ser display a strong effect for the catalytic hydrolysis with enzyme-like kinetics in aqueous medium [34], The rate enhancement of the catalyzed reaction versus the uncatalyzed one is 90,(X)0-fold employing 2.5 mol% of catalyst 40 (Scheme 7.8) which displays His-Thr diad elements. 

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