Number Of Halogen Substituents Research Articles

Studies About the Effect of Halogenated Solvents on the Fluorescence Properties of 9-Aryl-Substituted Isoquinolinium Derivatives - A Case Study.

It was demonstrated that 9-aryl-substituted isoquinolinium derivatives have significantly increased fluorescence quantum yields in halogenated solvents, mostly pronounced in chloroalkanes, which appears to be specific for this type of solvents. Further analysis with selected halogenated solvents revealed that the type and number of halogen substituents and the dielectric constant of the solvent have a distinct impact on the emission quantum yield. The solvent effect is explained by a solvation of the charge shift (CS) state by attractive halogen-π interactions (halogen bond), which impedes the torsional relaxation of the excited state.

Computational insight into biotransformation of halophenols by cytochrome P450: Mechanism and reactivity for epoxidation

Halophenols (XPs) have aroused great interests due to their high toxicity and low biodegradability. Previous experimental studies have shown that XPs can be catalytically transformed into epoxides and haloquinones by cytochrome P450 enzymes (CYPs). However, these metabolites have never been detected directly. Moreover, the effects of the reaction site and the type and number of halogen substituents on the biotransformation reactivity of halophenols still remain unknown. In this work, we performed density functional theory (DFT) calculations to simulate the CYP-mediated biotransformation of 36 XPs with mono-, di-, and tri-halogen (F, Cl, and Br) substitutions to unravel the mechanism and relevant kinetics of XPs epoxidation. The whole epoxidation process consists of initial rate-determining O-addition and subsequent ring-closure steps. The simulation results show that the epoxidation in low-spin (LS) state is kinetically preferred over that in high-spin (HS) state, and the formation of epoxide metabolite is strongly exothermic. For all XPs, the epoxidation reactivity follows the order of ortho/para O-addition > meta O-addition. Moreover, the O-addition with higher energy barriers roughly corresponds to chlorophenols and fluorophenols with more halogen atoms. Compared with dichlorophenols, the additional ortho-Cl substitution on trichlorophenols can slightly increase the energy barriers of meta O-addition. By contrast, the additional inclusion of an ortho-Cl to monochlorophenols enhances the meta O-addition reactivity of dichlorophenols. Overall, the present work clarifies the biotransformation routes of XPs to produce epoxides, and identifies the key factors affecting the epoxidation reactivity, which are beneficial in understanding comprehensively the metabolic fate and toxicity of XPs.

Comparative performance of TiO2-rGO photocatalyst in the degradation of dichloroacetic and perfluorooctanoic acids

Halogenated organic compounds are frequently characterized by their bioaccumulative nature, and long­term effects on human health. Their low biodegradability and their difficult removal by conventional technologies lead to their undesirable persistence in the environment. Titanium dioxide and reduced graphene oxide TiO2-rGO composites have shown promising results with enhanced photocatalytic degradation rates compared to bare TiO2 in the degradation of a good number of persistent pollutants. In this context, this work deepens on the influence of the type and number of halogen substitution on the photocatalytic degradation of halogenated organic compounds (HOCs). For the experimental analysis two HOCs, dichloroacetic acid (DCA) and perfluorooctanoic acid (PFOA), have been selected as both molecules differ in the type of halogen atoms, chlorine and fluorine, the number of halogen atoms, and in the length of the alkyl chain. The results showed that TiO2-rGO catalysts achieved a similar kinetic performance for the removal of the primary contaminant in terms of its degradation rate. Besides, TiO2-rGO composite successfully induced the release of all chlorine atoms from the DCA molecule, achieving its total mineralization. However, PFOA defluorination and mineralization rates were remarkably lower than its degradation rate. Although both contaminants released two halogen atoms step-by-step for the degradation of each molecule, PFOA dehalogenation was slowed down due to the generation of secondary products that retain fluorine. Therefore, we conclude that the composite photocatalysts showed a similar performance in terms of degradation rate of the primary contaminant independent on the length of the alkyl chain and on the number of halogen atoms, however, the mineralization and dehalogenation rates were strongly dependent on the number of halogen substituents and the length of the alkyl chain.

Uptake of Halogenated Phenols by Aquatic Plants

Reclamation of biologically treated wastewaters is frequently enhanced with the use of constructed wetlands and wastewater lagoons that remove nutrients and persistent organic pollutants. To better design systems utilizing uptake of persistent organic contaminants by aquatic plants, a quantitative description of partitioning of contaminants into aquatic plants is required. The uptake of halogenated phenols by Lemna minor was investigated to examine uptake of a family of closely related organic contaminants by a common aquatic plant. Batch experiments with L. minor (52 h) and 14 halogenated phenols were operated at nontoxic concentration levels with >90% of aqueous-phase contaminant in the protonated form. Pseudo-first-order rate coefficients determined using nonlinear regression of time series concentration data described contaminant uptake. Changing halogen substituent or number of halogen substituents did not affect uptake rate, however halogen positioning did affect contaminant uptake rate. Uptake rate...

Comparative Toxicokinetics of Chlorinated and Brominated Haloacetates in F344 Rats

Chloro, bromo, and mixed bromochloro haloacetates (HAs) are by-products of drinking water disinfection and are hepatocarcinogenic in rodents. We compared the toxicokinetics of a series of di-HAs, dichloro (DCA), bromochloro (BCA), dibromo (DBA) and tri-HAs: trichloro (TCA), bromodichloro (BDCA), chlorodibromo (CDBA), and tribromo (TBA) after iv and oral dosing (500 μm/kg) in male F344 rats. The blood concentrations of the HAs after iv injection declined in a bi-exponential manner with a short but pronounced distributive phase. The structural features that had the greatest influence on the disposition of HAs were substitution of a halogen for a hydrogen and the degree of bromine substitution. All di-HAs had blood elimination half-lives of less than 4 h (DCA > DBA, BCA) compared to the tri-HAs, which had half-lives that varied from 0.6 to 8.0 h (TCA > BDCA > CDBA > TBA). The urinary excretion of all di-HAs was low and accounted for less than 3% of the dose in contrast to the tri-HAs, where urinary excretion accounted for at least 30% of the dose. Toxicokinetic analysis indicated the steady-state apparent volume of distribution varied between 301 and 881 ml/kg among the HAs, but the variation was not statistically significant (P > 0.17). The blood concentration–time profiles for all di-HAs after oral dosing was complex and exhibited multiple peaks. This did not appear to be due to enterohepatic recirculation, as bile duct cannulated animals also displayed similar profiles. In contrast, the profiles for the tri-HAs did not exhibit multiple peaking after oral dosing and could be described using a one-compartment pharmacokinetic model. The oral bioavailability of the HAs varied between 30% (DBA) and 116% (TCA), depending on the number of halogen substituents and the degree of bromine substitution. In general, three patterns of elimination for the HAs can be broadly described: low metabolism with moderate renal clearance (TCA), high metabolism and renal clearance (BDCA, CDBA, TBA), and high metabolism, low renal clearance (DCA, BCA, DBA).

Polyhalovinyl Sulfones as Polyfunctional Electrophilic Substrates in Reactions with Nucleophiles

Abstract In the present review the results of investigations of the chemical properties of polyhalovinyl sulfones are summarized. The main accent is made on their ability to react with nucleophiles at different electrophilic sites depending on the nature and the number of halogen substituents as well as on the nucleophile. Special attention is given to the halophilic reduction of these electrophiles by soft nucleophiles. The synthetic potential of polyhalovinyl sulfones as synthons for various heterocycles in reactions with polydentate S- and N-nucleophiles is also demonstrated.

Benzimidazole nucleoside analogues as inhibitors of plant (maize seedling) casein kinases

Halogeno benzimidazole and benzimidazole nucleoside analogues have been screened for inhibitory activity vs. purified plant (maize seedling) casein kinases I, IIA and IIB, and the results compared with those previously reported for some of the compounds as inhibitors of the corresponding mammalian CK-1 and CK-2 (Meggio et al. (1990) Eur. J. Biochem. 187, 89-94). One new analogue, the riboside of 5,7-dibromobenzimidazole, which is sterically constrained to the anti conformation about the glycosidic bond, and is a good inhibitor, exhibited appreciable (5-7-fold) discrimination between the type I and type II enzymes. An increase in the number of halogen substituents on the benzene ring of benzimidazole from two to three led to marked enhancement of inhibitory activity, particularly against the type II enzymes, with a decrease in Ki from 24 to 4 microM. The 2-aza analogue of 5,6-dichlorobenzimidazole, i.e. 5,6-dichlorobenzotriazole, as the free base, even more effectively discriminated between the two types of plant casein kinases, with Ki approximately 100 microM for CK-I, and Ki approximately 9 microM for CK-IIA and CK-IIB. Inhibition in all instances was competitive with respect to ATP (for CK-I), and ATP and GTP (for CK-IIA and CK-IIB). The results are compared with those for halogenated isoquinolinesulfonamide inhibitors reported by Chijiwa et al. (J. Biol. Chem. (1989) 264, 4924-4927), leading to proposals for the synthesis of potentially more effective and more discriminating inhibitors. Attention is drawn to the significant role of the halogen substituents in the mechanism(s) of action of the structurally related benzimidazole, benzotriazole and naphthalene and isoquinoline, inhibitors of protein kinases.

Induction of rat hepatic drug metabolizing enzymes by substituted urea herbicides.

Effects of eight structurally closely related substituted urea herbicides were investigated on the induction of cytochrome P-450 dependent monooxygenase enzyme complex, as well as on two conjugating enzymes after short-term treatment of rats. Liver microsomal cytochrome P-450 content was induced approximately by 50%. Cytochrome P-450 dependent monooxygenase activities showed a great variety depending on the substrate and on the herbicide. Two-18-fold induction was detected with 7-ethoxycoumarin, while up to 8-fold induction was measured with benzo(a)pyrene. Aldrin epoxidase activities were increased up to 3-fold, and aminopyrine N-demethylase activities were only slightly different from the control level. UDP-glucuronyltransferase and glutathione S-transferase activities were enhanced up to 2-fold. The results indicate that chemical structure of the related substituted urea compounds, the number of halogen substituents on their phenyl group exert a strong influence on the induction of monooxygenases.

Residue analysis of methoxuron and its breakdown product (3-chloro-4-methoxyaniline) by thin-layer and high-performance liquid chromatography with fluorescence detection

Dns derivatization prior to fluorescence detection of phenylurea herbicides (after hydrolysis) and their aniline metabolites was further developed for residue analytical purposes with high-performance (HPLC) and thin-layer chromatography (TLC). Metoxuron and 3-chloro-4-methoxyaniline (CMA) were used as model compounds. An increased fluorescence intensity in TLC was obtained by dipping the plates into paraffin-hexane (2:1). A simple derivatization procedure, viz., addition of Dns chloride, evaporation and dissolution, plus overnight reaction, in the acetonitrile-water mixture used as the mobile phase, was developed for HPLC. The fluorescence intensity of Dns-anilines decreases with increase in the number of halogen substituents, and increases if a methoxy substituent is present. The detection limit of Dns-CMA is about 1 ng in both TLC and HPLC. Residue analyses of CMA and metoxuron in water, potato and soil samples involved acetone or dichloromethane extraction, silica gel clean-up, hydrolysis on a TLC plate (for metoxuron), Dns derivatization and HPLC or TLC evaluation. Retention data and recoveries are presented. The detection limits for CMA are 0.001 mg/kg in water, 0.02 mg/kg in potato and 0.2 mg/kg in soil.

Dehalogenation: A Novel Pathway for the Anaerobic Biodegradation of Haloaromatic Compounds

Microorganisms of lake sediment and sewage sludge anaerobically metabolized halobenzoates by a novel pathway. The primary degradative event was loss of the aryl halide without the alteration of the aromatic ring. Dehalogenation required strict anaerobic conditions and depended on the halogen and position, but not the number of halogen substituents. A stable methanogenic bacterial consortium was enriched from sludge and found capable of dehalogenating and often mineralizing a variety of halobenzoates to CH(4) and CO(2). The results suggest that reductive dehalogenation of aromatics could be important in removal of some chlorinated xenobiotics from the environment.

Neurotoxicity of halogenated O-phenyl O-alkyl alkylphosphonothioates.

Twenty-seven halogenated organophosphorus esters were tested for neurotoxicity in adult hens. Fourteen compounds were overtly neurotoxic, including eight of the eleven methylphosphonothioates, three of seven ethylphosphonothioates, and three of six phosphoramidates, one of which was the commercial herbicide DMPA. Neurotoxic activity varied both with the number of halogen substituents on the phenyl group, and with the identity of the 4-phenyl halogen. Neurotoxic activity also varied with the alkyl group involved in the P-C or P-N bond, and with the identity of the O-alkyl group.

Dye-Sensitized Photooxidation in the House Fly, Musca domestica1

A series of 6 xanthene dyes—rose bengal, phloxin B, erythrosin B, eosin yellowish, fluorescein, and rhodamine B—caused a light-dependent toxicity in the house fly, Musca domestica , after oral ingestion. Relative toxicities were described by means of rate constants of photooxidation calculated for each dye which include both the LT50 and the tissue dye level. These values were compared with similar values determined for reactions in the boll weevil, Anthonomus grandis , and with the phosphorescence quantum yields of the dyes, the number of halogen substituents, and the halogen content by weight. Lowered mortality at higher dietary concentrations was due to lowered consumption and was taken as preliminary evidence of feeding inhibition.

Studies on halogen quenching through the Stern-Volmer plot (author's transl)

The quenching effect for halogenated benzenes, methanes and ethanes have been investigated. The halogen quenching was accurately measured using the internal conversion electrons emitted from 113Sn-113mIn. From the quenching constants determined by the Stern-Volmer plots with respect to various halogen quenchers, the following results have been obtained. (1) The quenching constants increase with the number of halogen substituents, so as linearly in halogenated benzenes and exponentially in halogenated methanes and ehtanes. Even the isomers of halogenides have different quenching constants. (2) There is a linearity between logarithm of the quenching constant and a polarographic half-wave reduction potential. (3) Electron excitation provides larger quenching constants than UV excitation for halogenated methames. Based on these results, the mechanism of halogen quenching have been discussed in connection with the exciplex formation.