Methoxychlor structure

Figure 15.4 Structures of DDT, methoxychlor, and their major metabolites, and toxicological and key physicochemical properties. Data from [132, 135, 141, 210].

Estimate the Ki0Vi values at 25°C of the following compounds based on the experimental Ki0Vi values of the indicated structurally related compounds (a) benzoic acid dimethylaminoethyl ester from benzoic acid ethyl ester (log Kiaw = 2.64), (b) the insecticide methoxychlor from DDT (log Ki0Vi = 6.20), (c) the insecticide fenthion from parathion [log Kiow = 3.83, see 111. Ex. 7.2, Answer (d)], and (d) the hormone estradiol from testosterone [log Ki0Vi = 3.32, see 111. Ex. 7.2, Answer (e)]. 

Many chlorinated hydrocarbon alternatives to DD T have been developed. One of the earliest substitutes was methoxychlor, shown in Figure 15.18. This compound has a much lower toxicity in most animals and, unlike DDT, is not readily stored in animal fat. Look carefully at the structures of methoxychlor and DDT, and you ll see that they are identical except that methoxychlor has two ether groups where DDT has two chlorine atoms. Because the structures are nearly identical, they have nearly the same level of toxicity in insects. In higher... 

The apparent rate of hydrolysis and the relative abundance of reaction products is often a function of pH because alternative reaction pathways are preferred at different pH. In the case of halogenated hydrocarbons, base-catalyzed hydrolysis will result in elimination reactions while neutral hydrolysis will take place via nucleophilic displacement reactions. An example of the pH dependence of hydrolysis is illustrated by the base-catalyzed hydrolysis of the structurally similar insecticides DDT and methoxy-chlor. Under a common range of natural pH (5 to 8) the hydrolysis rate of methoxychlor is invariant while the hydrolysis of DDT is about 15-fold faster at pH 8 compared to pH 5. Only at higher pH (>8) does the hydrolysis rate of methoxychlor increase. In addition the major product of DDT hydrolysis throughout this pH range is the same (DDE), while the methoxychlor hydrolysis product shifts from the alcohol at pH 5-8 (nucleophilic substitution) to the dehydrochlorinated DMDE at pH > 8 (elimination). This illustrates the necessity to conduct detailed mechanistic experiments as a function of pH for hydrolytic reactions. 

As seen from the structural formulas in Figure 16.4, the organochlorine insecticides are of intermediate molecular mass and contain at least one aromatic or nonaromatic ring. They can be placed in four major chemical classes. The first of these consists of the chloroethylene derivatives, of which DDT and methoxychlor are the prime examples. The second major class is composed of chlorinated cyclodiene compounds, including aldrin, dieldrin, and heptachlor. The most highly chlorinated members of this class, such as chloredecone, are manufactured from hexachlorocyclo-pentadiene (see Section 16.3). The benzene hexachloride stereoisomers make up a third class of organochlorine insecticides, and the third group, known collectively as toxaphene, constitutes a fourth. 

The structures of DDT and methoxychlor are given below (left and right, respectively). Given that the log Kow value for DDT is 5.87, what is the log Kow value of methoxychlor By what factor is it more or less lipophilic than DDT ... 

Strategy. The only structural difference between these two molecules is the replacement of two chlorine atoms on DDT with two methoxy (also written as OCH3) moieties on methoxychlor. Thus, we can use the pi-values of these two groups to first remove the two chlorines and then add the two methoxys. 

Methoxychlor is structurally related to DDT, but it is much less persistent and is, therefore, still in use. For example, it can be found in household quality flea dip. 

O-Dealkylation O-Dealkylation of alkyl groups of the ester or ether structures of insecticides occurs frequently, but it also involves an unstable a-hydroxy intermediate as found in N-dealkylation. For example, methoxychlor is O-demethylated by the system (Figure 8.6). O-Dealkylation is known to occur with a wide variety of organophosphates, including certain dimethyl triesters. O-Dealkylation results in detoxification. 

Endocrine disruptors often are structural analogs of endogenous hormones (hormones produced naturally in the host). Hormone analogs may act like the endogenous hormone if the analog-receptor complex in the target cell mimics the function of the hormone-receptor complex. Hydroxy metabolites of both o,p -DDT and methoxychlor bind to estrogen... 

Organochlorine insecticides may be divided into three broad groups dichlorodiphenylethanes, such as DDT and methoxychlor cyclodienes, such as chlor-dane and dieldrin and hexachlorocyclohexanes, such as lindane. Mirex and chlordecone, however, are organochlorine insecticides whose caged structures do not fit well into the previous groups. 

The occurrence of HCP In HA fractions and Its absence In FL fractions suggests that the pollutant was strongly associated with organic matter and was probably deposited In the sediments In bound form. HCP may have been covalently bound to organic matter and released hydrolytically during base treatment. Laboratory studies support these observations Miller et al. (53) demonstrated that HCP covalently binds to rat tissue protein (In vitro) and Mathur and Morley (54) showed that a structurally similar compound, methoxychlor (2,2 -bls(jj-methoxyphenyl)l,l,l-trlchloroethane), strongly associated with a synthetic humic acid. 

Muller himself and other entomologists tested a wide array of compounds similar to DDT in order to reveal the relationship between structure and activity. The most important outcome besides DDT was methoxychlor having p,p -methoxy groups instead of p,p -chloro groups. The methoxy groups have approximately the same size and shape as the chloro groups. 

Methoxychlor is much less stable and became popular when the environmental contamination caused by DDT was recognized. The methoxy groups are easily attacked by oxidative enzymes (CYP enzymes). Ethyl groups in the para position are also possible, as in Perthane. Another DDT analogue, more active as a miticide, is dicofol. The structures of DDT and some of the more important derivatives are shown. 

Further investigations revealed not only the presence of DDT and its metabolites in Teltow Canal sediments but also the occurrence of 2,4 and 4,4 -methoxychlor (MDT) at elevated concentrations (up to 1100 pg/kg) (22). As methoxychlor is structurally related to DDT, MDT-related compounds were also included in the quantitative analyses (see Tab. 6). We detected MDT, MDD, MDE, MDB and MDA in the extracts and partly in the hydrolysis product mixtures of all four sediment samples. The total amounts ranged between 600 and 8000 pg/kg in the extracts and between 1200 and 6000 pg/kg after application of the hydrolysis procedure. In degradation products after BBr3-treatment and RuC -oxidation no MDT-related substances were analysed likely due to the lower concentration level as compared to the DDT-related compounds. 

Methoxychlor. Its chemical structure and properties are similar to those of DDT, but it biodegrades more easily. Aquatic organisms metabolize it and transform it into other less toxic substances and therefore it does not lead to significant bioaccumulation phenomena. 

Methoxychlor [72-43-5], a compound similar to DDT in chemical structure soon replaced DDT after the latter s ban. It is less toxic than DDT and degrades faster in the enviromnent than DDT or its metabolite. Methoxychlor is being used to control biting flies, honseflies and mosquito larvae. Other applications include its use against elm bark-beetle that causes Dutch elm disease and in veterinary medicines to kill parasites that live on the exterior of their host. 

Although the toxic properties are more or less the same for structurally similar compounds, such as Heptachlor and Chlordane, the degree of toxicity may vary significantly with chlorosubstitution in the compound. For example, substitution of chlorine atoms with methoxy group in the aromatic rings in DDT decreases the latter s toxicity. Thus, the methoxy derivative, Methoxychlor, is significantly less toxic than DDT. Similarly, ethyl-substituted Perthane is much less toxic than p,p -DDD. 

The metabolic pathways including stereochemistry of methoxychlor metabolism by liver slices obtained in this study are proposed in Figure 6. When the metabolic pathways are expressed in 2-dimentional molecular structures, mouse and quail show quite similar patterns, since the oxidative mono-O-demethylation and subsequent glucuronidation are the main metabolic pathways for both species. However, once the stereological structures are taken into account, the metabolic pathways in these two species turn out to be different, because of the enantioselectivity of the mono-demethylation reactions. Indeed, when the stereological structures are taken into consideration, it is shown that the metabolic pathways of methoxychlor from the four test animal species are all... 

The OC insecticides, hexachlorobenzene (HCB), HCH, DDE, DDT, and methoxychlor (Fig. 1, structure Lb) were determined in soil and plant samples after extraction with n-hexane, n-pentane, or cyclohexane. Benzo[a]pyrene and other aromatic hydrocarbons were also investigated (47) (Table 2). 

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