Pseudo-first-order inhibition constant

The pseudo-first-order inhibition constant, k (s ), will have different meanings, depending on the exact inhibition mechanism (see below). Four different phenomenological irreversible inhibition mechanisms are discussed in turn. 

Fig. 20 A plot of the observed pseudo-first-order rate constants (kobs) for the methanolysis of HPNPP (4 x 10 5moldm ) as a function of [35 2Zn(II)] in the presence of 1 equivalent of added CH30 per complex giving jpH = 9.5, T = 25 + 0.1 °C. Dotted line is presented as a visual aid directed through all actual data collected at 280 nm ( ) or 320 nm (O) which are the wavelengths for disappearance of HPNPP and appearance of /j-nitrophenol solid line is a linear fit of the data corrected for inhibition by triflate counterions at 280 nm ( ) or 320 nm ( ). Reproduced with permission from ref. 95.

The active-site-directed inhibitor tosylphenylalanine chloromethyl ketone that specifically and irreversibly inhibits chymotrypsin. This chloroketone inhibitor relies on its toluene sulfonyl (or tosyl) group for binding into the aromatic binding pocket of chymotrypsin s active site. Inactivation occurs by alkylation of histidine-57 (pseudo-first order rate constant 0.2 min ). See Chymo-trypsin... 

Pseudo-first-order rate constants for carbonylation of [MeIr(CO)2l3]" were obtained from the exponential decay of its high frequency y(CO) band. In PhCl, the reaction rate was found to be independent of CO pressure above a threshold of ca. 3.5 bar. Variable temperature kinetic data (80-122 °C) gave activation parameters AH 152 (+6) kj mol and AS 82 (+17) J mol K The acceleration on addition of methanol is dramatic (e. g. by an estimated factor of 10 at 33 °C for 1% MeOH) and the activation parameters (AH 33 ( 2) kJ mol" and AS -197 (+8) J mol" K at 25% MeOH) are very different. Added iodide salts cause substantial inhibition and the results are interpreted in terms of the mechanism shown in Scheme 3.6 where the alcohol aids dissociation of iodide from [MeIr(CO)2l3] . This enables coordination of CO to give the tricarbonyl, [MeIr(CO)3l2] which undergoes more facile methyl migration (see below). The behavior of the model reaction closely resembles the kinetics of the catalytic carbonylation system. Similar promotion by methanol has also been observed by HP IR for carbonylation of [MeIr(CO)2Cl3] [99]. In the same study it was reported that [MeIr(CO)2Cl3]" reductively eliminates MeCl ca. 30 times slower than elimination of Mel from [MeIr(CO)2l3] (at 93-132 °C in PhCl). 

Figure 2 Determination of irreversible inhibition constants for erythromycin and CYP3A4 microsomes. Microsomes (1 mg/mL microsomal protein) were incubated with erythromycin (0-100 pM) in the presence of NADPH for differing incubation times. The pseudo-first-order rate constant for enzyme inactivation was plotted versus erythromycin concentration to estimate Ki and inact (14.4 pM and 0.045 min-1, respectively). The curve represents the line of best fit. Source From Ref. 32.

Figure 16. Inhibition of the reaction between p-nitrophenyl acetate and HSA by inorganic anions. Solutions of each anion, triethanolamine, and 3.5 X 10 5M HSA were prepared at the appropriate concentrations and pH 8.1. Logarithms of the observed pseudo-first-order rate constants are plotted vs. a function of ionic strength, jjl, for triethylammonium phosphate (O), fluoride (D), sulfate (%), chloride (M), iodide (A), and perchlorate ( A).

The spectra of alkene selenides persists for several minutes after flashing. A spectrum observed in flashed COSe and ethylene mixture is identical to that produced in flashed CSe2 and ethylene mixture. In Ar or N2, flash photolysis of COSe produces Se2 but no CSe. An added alkene inhibits Se2 formation in experiments either with COSe or CSe2. In flashed CSe2, the rate of decay of Se (4 P) is identical to the rate of appearance of the far ultraviolet bands, within an experimental scatter of + 20% in the pseudo first-order rate constant. Therefore the absorption in the far... 

The induced aquation of [Co(NHs)6N3] + ion in the presence of nitrous acid and Hg2+ ion has also been investigated in aqueous perchlorate solutions. In this case, the pseudo-first-order rate constant A oi)s = [H+] [NOa ]totai/ ([H+]-f-5[Hg +]), where A and B are constants. The Hg + ion inhibits attack of NO+ ion by competing with H+ ion for the nitrite which is present. In mixed acetonitrile-aqueous solutions, formation of [NgNOal is more complete, fi[Hg +] >[H+], and then / obs = [H+ ][N02 ]totai/[Hg +]. For the Hg + ion-induced aquation of [CoCNHaisCl] ion in nitrate media, A obs = (A o+ i[N03"])-[Hg +], with two pathways postulated involving [CoClHg] +and [CoClHgNOs] precursors. It is concluded from competition experiments that if the five-co-ordinate, [Co(NH3)6] +, intermediate is formed in the reaction of [Co(NH3)6Ns] + with NO+ ion, this intermediate is not formed in either of the Hg + ion-induced pathways. ... 

The thermolysis was studied over the range of 100 to 140°C in mixtures of benzene and cyclohexane. It was found that the reaction rate is inhibited by added cyclohexane, but unaffected by added PMej. The pseudo-first-order rate constant is given by... 

The acid catalysed degradation of penicillins is inhibited in cationic micelles of cetyltrimethylammonium bromide (Tsuji et al., 1982) and, as expected, neither anionic micelles of sodium dodecylsulphate nor polyoxyethylene lauryl ether promote the hydroxide-ion catalysed hydrolysis of benzylpenicillin (Gensmantel and Page, 1982a). In the presence of cetyltrimethylammonium bromide (CTAB) the pseudo first-order rate constants for the alkaline hydrolysis increase rapidly with surfactant concentration once... 

FIGURE 5 Plots of the apparent pseudo first-order rate constants for the N-ethylmaleimide inhibition of the condensation reaction using 16 0 CoA ( ), 6,9-18 2 CoA (o), and 6,9,12-18 3 CoA (A) as substrates. 

If the inhibitor concentration is sufiiciently greater than the total enzyme concentration ([I]/[E] > 10-20), it can be shown that the decrease in E - - E I concentration in the inhibition mixture follows pseudo-first-order kinetics at any fixed value of I. The pseudo-first-order rate constant can easily be measured by periodically drawing an aliquot from the inhibition mixture and assaying for residual enzyme activity. Dilution of the inhibitor concentration in the assay mixture will likely result in the absence of E-I in the assay mixture, so that the enzyme concentration obtained will represent the total enzyme (E- -E-I) present in the aliquot. A semilog plot of enzyme activity or concentration vs time will then give directly. It can be shown that fcobs is related to Ki by Eq. (2) and fcj by Eq. (3)... 

The lack of product inhibition on rate of catalyzed cleavage of amide bond is attributed to probable free diffusion of product 22 out of the binding pocket of antibody. The value of the pseudo-first-order rate constant (k) for hydrolysis of 22 in the buffer employed (k = 2.0 x 10 min at pH 8.0) is nearly 10 times larger than the pseudo-first-order rate constant (kjj,) for catalyzed reaction of phenol with 21. Thus, the present antibodies with external phenol cofactor catalyzes the acylation step (i.e., reaction between phenol and 21). But these catalysts have no effect on the deacylation step (i.e., hydrolysis of 22), simply because 22 probably has no productive binding affinity with antibody catalysts. 

Pseudo-first-order rate constants (k s) for the reaction of n-nonanoyloxyben-zenesulfonate and hydrogen peroxide are strongly inhibited by C12E23 micelles. The observed data (k bs vs. [C,2E23]x) were treated with a kinetic equation similar to Equation 3.11 (Chapter 3)."° The micellar binding constants for reactants, obtained kinetically, are mentioned in Table 4.1. The plots of pseudo-first-order rate constants (k bs) for the reaction of pemonanoic acid and n-nonanoyloxyben-... 

The common problems with those metallomicelles may be summarized as follows (1) Most of these complexes were prepared in situ and often were not isolated. Hence, the intended structures of the metallomicelles in solution or in the solid state were not verified. (2) The metal complexes in solution were not identified or characterized in rigorous thermodynamic senses by potentiometric pH titration, etc. The complexation constants and possible species distribution at various pH s were totally unknown. (3) Possible catalytically active species L-Mn+—OH were not identified by means of the thermodynamic pvalues. Those described were all obtained merely in kinetics. (4) The product (phosphate anion) inhibition was not determined. Accordingly, it often was not clear whether it was catalytic or not. (5) Often, the substrates studied were limited. (6) The kinetics was complex, probably as a result of the existence of various species in solution. Thus, in most of the cases only pseudo-first-order rates (e.g., with excess metal complexes) were given. No solid kinetic studies combined with thermodynamic studies have been presented. It is thus impossible to compare the catalytic efficiency of these metallomicelles with that of the natural system. Besides, different... 

This reaction results in light emission between 540 and 600 nm. Luciferase is activated by divalent magnesium, so experiments are carried out in the presence of excess Mg2+ (1 mM). This reaction does not yield a constant light output under pseudo-first-order conditions, as shown in Figure 3.5, which is thought to be due to product inhibition of luciferase. Figure 3.5 also shows the effect of hydro-phobic and amphipathic species on light output these species may be quantitated by their inhibitory effect on the luciferase reaction. 

The rate constants are independent of initial concentration of the dye, atleast upto 100 ppm. Thus, the photodegradation of RO 84 follows pseudo-first order kinetics at initial COD levels <100 ppm. The significant decrease in the rate constant at higher initial COD levels (>200 ppm) may be attributed to strongly inhibited direct excitation of Ti02 semiconductor due to diminished penetration depth of UV light in these highly colored solutions. 

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