Kinetics half-life

The duration of action is short, except for lacidipine and lercanidi-pine (high lipophilicity) and amlodipine (long kinetic half-life) extended-release formulations have been developed to ensure once- daily oral administration for many of these agents. 

Although the U02 ion is extremely unstable towards disproportionation (Section 20-4), its aqueous chemistry has been much studied by stopped-flow methods. In DMSO it is more stable, both thermodynamically and kinetically (half-life, 0.5 h). 

Decomposition of organic peroxides to free radicals follows first order kinetics. Half life (t ) is defined as the time required for half of the organic peroxide to decompose at a certain temperature. Half-life is an important parameter in... 

Fluoroacetate is rapidly absorbed by the gastrointestinal tract but not well absorbed dermally. Fluoroacetate is converted to the ultimate toxicant, fluorocitrate. Fluoroacetate is distributed to lipid-rich organs, such as the liver, brain, and kidneys. Fluoroacetate is primarily eliminated through urine. Up to 50% of the fluoroacetate is excreted unchanged in the urine by 72 h following administration. The kinetic half-life for sodium fluoroacetate is species dependent. Reported half-lives in rabbits, goats, and sheep are 1.1, 4-7, and 13.3 h, respectively. 

How long do radioactive isotopes last This is measured by a quantity familiar to anyone who has studied chemical kinetics. You should recall studying first-and second-order reactions and discussing the concept of half-life in each case. (Incidentally, radioactive decay follows flrst-order kinetics.) Half-life is defined as the time required for the concentration of a reactant to decrease to half its initial concentration. Figure 10.3 shows the concentration of a radioactive isotope as a function of time. Note that after one half-life, one-half of the isotope remains after two half-lives, there is one-quarter of the original remaining and so forth. 

The rate of the uncatalysed reaction in all four solvents is rather slow. (The half-life at [2.5] = 1.00 mM is at least 28 hours). However, upon complexation of Cu ion to 2.4a-g the rate of the Diels-Alder reaction between these compounds and 2.5 increases dramatically. Figure 2.2 shows the apparent rate of the Diels-Alder reaction of 2.4a with 2.5 in water as a lunction of the concentration of copper(II)nitrate. At higher catalyst concentrations the rate of the reaction clearly levels off, most likely due to complete binding of the dienophile to the catalyst. Note that in the kinetic experiments... 

In addition to the initial reaction between nitric acid and acetic anhydride, subsequent changes lead to the quantitative formation of tetranitromethane in an equimolar mixture of nitric acid and acetic anhydride this reaction was half completed in 1-2 days. An investigation of the kinetics of this reaction showed it to have an induction period of 2-3 h for the solutions examined ([acetyl nitrate] = 0-7 mol 1 ), after which the rate adopted a form approximately of the first order with a half-life of about a day, close to that observed in the preparative experiment mentioned. In confirmation of this, recent workers have found the half-life of a solution at 25 °C of 0-05 mol 1 of nitric acid to be about 2 days. ... 

An important characteristic property of a radioactive isotope is its half-life, fj/2, which is the amount of time required for half of the radioactive atoms to disintegrate. For first-order kinetics the half-life is independent of concentration and is given as... 

Anhydrous, monomeric formaldehyde is not available commercially. The pure, dry gas is relatively stable at 80—100°C but slowly polymerizes at lower temperatures. Traces of polar impurities such as acids, alkahes, and water greatly accelerate the polymerization. When Hquid formaldehyde is warmed to room temperature in a sealed ampul, it polymerizes rapidly with evolution of heat (63 kj /mol or 15.05 kcal/mol). Uncatalyzed decomposition is very slow below 300°C extrapolation of kinetic data (32) to 400°C indicates that the rate of decomposition is ca 0.44%/min at 101 kPa (1 atm). The main products ate CO and H2. Metals such as platinum (33), copper (34), and chromia and alumina (35) also catalyze the formation of methanol, methyl formate, formic acid, carbon dioxide, and methane. Trace levels of formaldehyde found in urban atmospheres are readily photo-oxidized to carbon dioxide the half-life ranges from 35—50 minutes (36). 

Linear alkylbenzenesulfonate showed no deleterious effect on agricultural crops exposed to this material (54,55). Kinetics of biodegradation have been studied in both wastewater treatment systems and natural degradation systems (48,57,58). Studies have concluded that linear alkylbenzenesulfonate does not pose a risk to the environment (50). Linear alkylbenzenesulfonate has a half-life of approximately one day in sewage sludge and natural water sources and a half-life of one to three weeks in soils. Aquatic environmental safety assessment has also shown that the material does not pose a hazard to the aquatic environment (56). 

Sotalol is rapidly and almost completely (>90%) absorbed. Bioavahabhity of absorbed dmg is 89—100%. Peak plasma levels are achieved in 2—4 h. Sotalol is 50% bound to plasma proteins. Plasma half-life of the compound is about 5.2 h. No metabolites of sotalol have been identified indicating littie metabolism. The dmg is excreted mainly by the kidneys (80—90%) and about 10% is eliminated in the feces. The plasma half-life is prolonged in patients having renal failure. Kinetics of the compound are not affected by changes in liver function (1,2). Sotalol has ah the adverse effects of -adrenoceptor blockers including myocardial depression, bradycardia, transient hypotension, and proarrhythmic effects (1,2). 

Discrimination between exposed and unexposed areas in this process requires the selection of thia zolidine compounds that do not readily undergo alkaline hydrolysis in the absence of silver ions. In a study of model compounds, the rates of hydrolysis of model /V-methyl thia zolidine and A/-octadecyl thiazolidine compounds were compared (47). An alkaline hydrolysis half-life of 33 min was reported for the /V-methyl compound, a half-life of 5525 min (3.8 days) was reported for the corresponding V/-octadecyl compound. Other factors affecting the kinetics include the particular silver ligand chosen and its concentration (48). Polaroid Spectra film introduced silver-assisted thiazolidine cleavage to produce the yellow dye image (49), a system subsequentiy used in 600 Plus and Polacolor Pro 100 films. 

One of the most important parameters of an immobilized-carrier complex is stability of its activity. Catalytic activity of the complex diminishes with time because of leakage, desorption, deactivation, and the like. The half-life of the complex is often used to describe the activity stabihty. Even though there may be frequent exceptions, hn-ear decay is often assumed in treating the kinetics of activity decay of an immobilized complex. 

This compound is less stable than 5 and reverts to benzene with a half-life of about 2 days at 25°C, with AH = 23 kcal/mol. The observed kinetic stability of Dewar benzene is surprisingly high when one considers that its conversion to benzene is exothermic by 71 kcal/mol. The stability of Dewar benzene is intimately related to the orbital symmetry requirements for concerted electrocyclic transformations. The concerted thermal pathway should be conrotatory, since the reaction is the ring opening of a cyclobutene and therefore leads not to benzene, but to a highly strained Z,Z, -cyclohexatriene. A disrotatory process, which would lead directly to benzene, is forbidden. ... 

Entry 3 has only alkyl substituents and yet has a significant lifetime in the absence of oxygen. The tris(/-butyl)methyl radical has an even longer lifetime, with a half-life of about 20 min at 25°C. The steric hindrance provided by the /-butyl substituents greatly retards the rates of dimerization and disproportionation of these radicals. They remain highly reactive toward oxygen, however. The term persistent radicals is used to describe these species, because their extended lifetimes have more to do with kinetic factors than with inherent stability." Entry 5 is a sterically hindered perfluorinated radical and is even more long-lived than similar alkyl radicals. 

In addition to the elimination rate constant, the half-life (T/i) another important parameter that characterizes the time-course of chemical compounds in the body. The elimination half-life (t-1/2) is the time to reduce the concentration of a chemical in plasma to half of its original level. The relationship of half-life to the elimination rate constant is ti/2 = 0.693/ki,i and, therefore, the half-life of a chemical compound can be determined after the determination of k j from the slope of the line. The half-life can also be determined through visual inspection from the log C versus time plot (Fig. 5.40). For compounds that are eliminated through first-order kinetics, the time required for the plasma concentration to be decreased by one half is constant. It is impottant to understand that the half-life of chemicals that are eliminated by first-order kinetics is independent of dose. ... 

When we carry out conventional studies of solution kinetics, we initiate reactions by mixing solutions. The time required to achieve complete mixing places a limit on the fastest reaction that can be studied in this way. It is not difficult to reduce the mixing time to about 10 s, so a reaction having a half-life of, say, 10 s is about the fastest reaction we can study by conventional techniques. (See Section 4.4 for further discussion of this limit.) The slowest reaction accessible to study depends upon analytical sensitivity and patience let us say that the half-life of a graduate student, 2-2 years, sets an approximate limit. This corresponds to roughly 7 x 10 s. Thus, a range of half-lives of about 10 can be studied by conventional techniques. 

First, let us consider batch mixing processes, as exemplified by ordinaiy laboratory practice in solution kinetics. A portion of one solution (say, of the substrate) is added by pipet to a second solution (containing the reagent) in a flask, the flask is shaken to achieve homogeneity, and then samples are withdrawn at known times for analysis, or the solution is subjected to continuous observation as a function of time, for example, by spectrophotometry. For reactions on a time scale (measured by the half-life) of hours or even several minutes, the time consumed in these operations is a negligible portion of the reaction time, but as the half-life of the reaction decreases, it becomes necessary to consider these preliminary steps. Let us distinguish three stages ... 

Ta 1.5 X 10 2, K3 2.1 X 10 and 2.4 x and the corresponding negative logarithms are pA" 1.0, pA"2 1.8, pA"3 6.57 and pA"4 9.62. The P—O—P linkage is kinetically stable towards hydrolysis in dilute neutral solutions at room temperature and the reaction half-life can be of the order of years. Such hydrolytic breakdown of polyphosphate is of considerable importance in certain biological systems and has been much studied. Some factors which affect the rate of degradation of polyphosphates are shown in Table 12.10. 

The most prominent chemical property of HOF is its instability. It decomposes spontaneously (sometimes explosively) to HF and O2 with a half-life of ca. 30 min in a Teflon apparatus at room temperature and lOOmmHg. It reacts rapidly with water to produce HF, H2O2 and O2 in dilute aqueous acid H2O2 is the predominant product whereas in alkaline solution O2 is the principal O-containing product. The kinetics of these processes have been studied and, by use of 0-enriched H2O2, it has... 

The rearrangement has been investigated kinetically. Hawthorne and Strahm found a reaction of the first order at 100°C in diethyl carbitol with k — 5.45 X 10", corresponding to a half-life of 212 min. The activation energy was 28 kcal, the activation entropy —3 1... 

On the basis of the general reaction scheme (see p. 248) the kinetic dependence is caused by the fact that the rate of the 8 2 reaction, Eq. (7), is dependent on the concentration of diazomethane but that the rate of the SkI reaction, Eq. (6), is not. (For unimolecular reactions, the half-life does not depend on the concentration but it does in the case of bimolecular reactions. We have, assuming fast pre-equilibrium ... 

There is a restriction on this simple model for the C0-N02 reaction. According to the kinetic theory of gases, for a reaction mixture at 700 K and concentrations of 0.10 M, every CO molecule should collide with about 109 N02 molecules in one second. If every collision were effective, the reaction should be over in a fraction of a second. In reality, this does not happen under these conditions, the half-life is about 10 s. This implies that not every CO-N02 collision leads to reaction. 

The mean residence time (MRT) gives one parameter for the multi-exponential elimination kinetics with more than one half-life. 

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