Chlorine-substituted Derivatives Research Articles

Morphostructural damage to bacterial cells exposed to chlorine-containing derivatives of 5-,6-,7-aminoindoles assessed by scanning electron microscope

The cell wall and membranes of Gram-positive and Gram-negative bacteria provide a physical, osmotic, and metabolic barrier between the internal contents of the bacterial cell and the external environment. Observation of changes in the integrity of the bacterial structure using a scanning electron microscope (SEM) can help elucidate the detailed mechanisms of cell death. The aim of the study was to analyze the morphological changes in microbial cells exposed to new compounds with antimicrobial activity chlorine-containing derivatives of 5-,6-,7-aminoindoles using SEM. Methods. The present study was carried out using strains of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli obtained from patients with nonspecific diseases of the respiratory, urinary tract, and intestines with different sensitivities to traditionally used antimicrobial drugs. Results. As a result, the studied chloromethyl-containing compounds of the indole series showed own biological activity, namely antimicrobial. Control cells were morphologically correct and typical. Statistical analysis of cell surface morphometry in control and experimental samples did not reveal significant changes in size after exposure to compounds with laboratory codes T1, T4, T7 and T12. At the same time, compared with control untreated cells of P. aeruginosa, S. aureus and E. coli, treatment with chlorine-substituted derivatives of 5-,6-,7-aminoindoles caused obvious morphological changes, which indicates a deteriorated state of the cell wall. Filamentous cells were observed in P. aeruginosa exposure to T7 and T12. The appearance of long filaments may be associated with the stress experienced by the cell after exposure to the compounds under study. It is believed that the formation of such filaments in bacteria under stress conditions results from defects in cell division, especially in the separation of daughter cells. There are data according to which, when DNA synthesis is suppressed, a bacterium changes its morphology, becomes longer, without reaching cell division. Treatment with T1, T7 and T12 resulted in degradation of the P. aeruginosa cell wall, while treatment with T4 caused the formation of pores on the cell surface. In this study, microscopy showed marked morphological changes in the cell walls of S. aureus, which led to deformation of the cell wall under the influence of T1, T4, T7 and T12. Treatment of E. coli T1, T4, T7 and T12 cells at a concentration of 500 g/ml caused cell lysis, although normal cells were also found. The appearance of cellular debris around whole E. coli cells indicates membrane damage, which probably leads to a change in osmotic pressure. Conclusion. The results using SEM confirmed the data on the antimicrobial activity of chlorine-substituted derivatives of 5-,6-,7-aminoindoles.

Pharmacokinetics of Two Chlorine-Substituted Bis-Pyridinium Mono-Aldoximes with Regenerating Effect on Butyrylcholinesterase.

Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare their pharmacokinetics to their parent compound, K-203. White male Wistar rats were intramuscularly injected with K-203, K-867 or K-870. Serum, brain, kidneys, liver, lung, eyes, and testes tissues were taken after 5, 15, 30, 60, and 120 min and analyzed using reversed-phase high-performance liquid chromatography. K-203, K-867, or K-870 was present in every tissue that was analyzed, including the serum, the eyes, testes, liver, kidneys, lungs, and the brain. The serum levels of K-867 and K-870 (chlorine-substituted derivatives of K-203) were nearly constant between 15 and 30 min, while their parent compound (K-203) showed peak level at 15 min after the administration of 30 µmol/rat. Neither K-203, nor K-867 or K-870 were toxic at a dose of 100 µmol/200 g in rats. Chlorine-substitution of K-867 and K-870 produced limited absorbance and distribution compared to their parent compound, K203.

Discotic liquid crystals of transition metal complexes, 55: Novel chlorine-substituted phthalocyanine derivatives showing mesomorphism and low HOMO energy level

We have synthesized a series of novel phthalocyaninato copper(II) (abbreviated as PcCu) compounds, 1,4,8,11,15,18,22,25-octakisalkoxy-2,3,9,10,16,17,23,24-octachloro-phthalocyaninato copper(II) (abbreviated as ([Formula: see text]-C[Formula: see text]O)[Formula: see text]-Cl)[Formula: see text]PcCu (4a–4d): [Formula: see text] 6 (a), 8 (b), 10 (c) and 12 (d)) and, for comparison, another series of PcCu compounds, 1,4,8,11,15,18,22,25-octakisalkoxyphthalocyaninato copper(II) (abbreviated as ([Formula: see text]-C[Formula: see text]O)[Formula: see text]PcCu (1a–1d)). The PcCu derivatives 1a–1d are substituted by alkoxy chains only at the [Formula: see text] positions (1,4,8,11,15,18,22,25). On the other hand, the PcCu derivatives 4a–4d are substituted by alkoxy chains at the [Formula: see text] positions and chlorine atoms at the [Formula: see text] positions (2,3,9,10,16,17,23,24). We have investigated the influence of chlorine atoms substituted at the [Formula: see text] positions of the Pc ring on mesomorphism, spectroscopic and electronic properties for these two series of PcCu derivatives 1 and 4 by using a polarizing optical microscope, DSC, temperature-variable small angle X-ray diffractometer, a UV-Vis spectrophotometer and cyclic voltammetry. Each of the derivatives 1a–1d is crystalline without showing mesomorphism. On the other hand, each of the chlorine-substituted PcCu derivatives 4a–4d shows plural phase transitions, and the longer chain-substituted PcCu derivatives 4c–4d show a rectangular ordered columnar [Col[Formula: see text](P2m)] mesophase. Furthermore, we have revealed that each of the PcCu derivatives 4a–4d shows a Q-band in the near-infrared region and a lower HOMO energy level than conventional phthalocyanine derivatives.

Substituent Effects on the Reactivity of Benzoquinone Derivatives with Thiols

Benzoquinone (BQ) is an extremely potent electrophilic contact allergen that haptenates endogenous proteins through Michael addition (MA). It is also hypothesized that BQ may haptenate proteins via free radical formation. The objective of this study was to assess the inductive effects (activating and deactivating) of substituents on BQ reactivity and the mechanistic pathway of covalent binding to a nucleophilic thiol. The BQ binding of Cys34 on human serum albumin was studied, and for reactivity studies, nitrobenzenethiol (NBT) was used as a surrogate for protein binding of the BQ and benzoquinone derivatives (BQD). Stopped flow techniques were used to determine pseudofirst order rate constants (k) of methyl-, t-butyl-, and chlorine-substituted BQD reactions with NBT, whereas electron pair resonance (EPR) studies were performed to investigate the presence of the free radical mediated binding mechanism of BQD. Characterization of adducts was performed using mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). The rate constant values demonstrated the chlorine-substituted (activated) BQD to be more reactive toward NBT than the methyl and t-butyl-substituted (deactivated) BQD, and this correlated with the respective EPR intensities. The EPR signal, however, was quenched in the presence of NBT suggesting MA as the dominant reaction pathway. MS and NMR results confirmed adduct formation to be a result of MA onto the BQ ring with vinylic substitution also occurring for chlorine-substituted derivatives. The binding positions on BQ and NBT/BQ(D) stoichiometric ratios were affected by whether the inductive effects of the substituents on the ring were positive or negative. The reactivity of BQ and BQD is discussed in terms of the potential relationship to potential allergenic potency.

Temporary anion states and dissociative electron attachment to nitrobenzene derivatives

The nitrobenzene derivatives 1,2-nitrotoluene, 1,3-nitrotoluene, 1,2-fluoronitrobenzene, 1,3-fluoronitrobenzene, 1,4-fluoronitrobenzene, 1,2-chloronitrobenzene, 1,3-chloronitrobenzene and 1,4-chloronitrobenzene are investigated by means of electron transmission spectroscopy (ETS), dissociative electron attachment spectroscopy (DEAS) and negative ion mass spectrometry (NIMS). The observed energies of electron attachment to π* MOs were interpreted with the support of the empty level structures of the neutral molecules supplied by HF/6-31G and B3LYP/6-31G* calculations. In the chlorine-substituted derivatives three main long-lived negative ions (NIs) (M −, Cl −, and NO 2 −) are observed, only M − and NO 2 − in the other investigated compounds. The detection of the metastable NIs corresponding to the process M* − → R − + (M–R) suggests that the molecular NIs formed near thermal electron energy dissociate on a microsecond timescale. Mean autodetachment lifetimes of the molecular NIs as a function of electron energy are evaluated.

Spectral and luminescent properties of chlorine-substituted derivatives of aniline

The effect of the position and number of chlorine atoms on spectral, geometrical, and photophysical characteristics of individual molecules of chlorine-substituted derivatives of aniline is studied by electronic spectroscopy and quantum-chemical calculations. It is shown that the long-wavelength absorption band of these compounds is formed by several electronic transitions of different nature and intensity. It is ascertained that electronically excited π σ* states involve C-Cl bonds, which weaken upon excitation. According to quantumchemical calculations, the quenching of fluorescence of chlorine-substituted derivatives of aniline is determined by the fact that intersystem crossing is more effective than radiative decay of the S 1 state.

Velnacrine thiaanalogues as potential agents for treating alzheimer's disease

The only therapeutic drugs for combating dementia disease are acetylcholine esterase inhibitors (AChEI). However, the use of tacrine, the first AChEI to be launched as an Alzheimer's disease (AD) drug, has been limited by serious side effects. Therefore, efforts to search for more potent and selective inhibitors of AChE still remain highly significant in the therapeutic treatment of AD. In this work we modified the cyclohexyl ring of velnacrine, a less toxic analogue of tacrine, by synthesizing a series of thiopyranoquinolines in which the C-3 methylene unit was replaced by a sulphur atom. The anti-AChE data show that the activity was maintained with the bioisosteric substitution carried out. The introduction of a chlorine atom at different positions of the aromatic ring resulted in an array of different activities. In an attempt to understand the different behaviours displayed by the chlorine-substituted derivatives, a molecular docking study was performed.

Discovery of novel N-phenylglycine derivatives as potent and selective beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence.

With a novel assay using isolated ferret detrusor to estimate beta(3)-adrenoceptor agonistic activity, we found that a series of glycine derivatives of ritodrine, a beta(2)-adrenoceptor agonist, are potent beta(3)-adrenoceptor agonists, with excellent selectivity versus beta(1) and beta(2) subtypes. Substitution of halogens in the phenyl ring increased potency and selectivity for the beta(3)-adrenoceptor, and this was dependent upon the position of the halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta(3)-adrenoceptor-mediated relaxation of ferret detrusor (EC(50) = 0.93, 11, 14, and 160 nM) and higher potency at beta(3)-adrenoceptors than at beta(1) or beta(2). The intravenous administration of 3h significantly reduced the urinary bladder pressure in anesthetized male rats (ED(50) = 48 microg/kg) without cardiovascular side effects. This article is the first report of structure-activity relationships (SAR) concerning beta(3)-adrenoceptor agonists as agents for the treatment of urinary frequency and incontinence.

Halogenation and toxicity of the biodegradation products of a nonionic surfactant, nonylphenol ethoxylate

We simulated the formation of halogenated by-products of biodegradation products of a nonionic surfactant, nonylphenol ethoxylate (NPE), and evaluated the toxicity of these by-products. Most NPE derivatives bearing shortened ethylene oxide (EO) chains (abbreviated as NPnEO) and nonylphenol carboxylate (NPnEC) disappeared within 24 h. In both NPnEO and NPnEC, benzene rings are substituted by monobromine. In contrast, chlorine-substituted derivatives were scarcely detected. However, the stoichiometrical bromination of NPnEO and NPnEC was not found. Total amounts of NPnEO, NPnEC, and their bromine-substituted products (BrNPnEO and BrNPnEC, respectively) tended to diminish with increasing level of residual chlorine concentration. Hence, it was suggested that both NPnEO and NPnEC were transformed to unknown by-products. The optimum pH for the formation of both BrNPnEO and BrNPnEC was approximately 7, and these formations decreased remarkably at higher pH. The formation of both BrNPnEO and BrNPnEC was shown to be dependent on the bromide anion concentration but independent of the level of residual chlorine. In the umu assay, a mutagenicity test that uses genetically engineered Salmonella bacteria, neither BrNPnEO nor BrNPnEC showed significant mutagenicity irrespective of metabolic activation by S9-mix. However, both BrNPnEO and BrNPnEC showed higher acute toxicity to Daphnia magna than their nonbrominated precursors, NPnEO and NPnEC. The toxicity of BrNPnEO to Daphnia was higher than that of BrNPnEC.

Reaction of Ozone with Ethene and Its Methyl- and Chlorine-Substituted Derivatives in Aqueous Solution

Byproduct formation in ozonation processes is of interest, especially in the area of drinking water, similar to the concerns regarding the health effects of disinfection byproducts generated by chlorine and other oxidants used for that purpose. Chlorinated olefins increasingly contaminate our drinking water resources, and the byproducts formed by ozone were determined here. For a better understanding of the underlying mechanisms, some other olefins were included in this study. The rate constants of the reaction of ozone with ethene and some of its methyl- and chlorine-substituted derivatives in aqueous solution have been measured by stopped-flow (rate constants in units of dm3 mol-1 s-1): tetramethylethene, >106; propene, 8 × 105; ethene, 1.8 × 105; buten-3-ol, 7.9 × 104; vinyl chloride, 1.4 × 104; trans-1,2-dichloroethene, 6.5 × 103; 1,1-dichloropropene, 2.6 × 103; cis-1,2-dichloroethene, 540; 1,1-dichloroethene, 110; trichloroethene, 14. From these data, it is concluded that the rate of reaction is mai...

Photochemical reactions of biphenyl and its chlorinated derivatives on the surfaces of γ-alumina and silica–alumina

Photochemical reactions of biphenyl and its chlorine-substituted derivatives on the surfaces of γ-alumina and silica–alumina have been investigated. Diffuse reflectance spectra show that biphenyl molecules adsorbed on activated surfaces (Ta > 350 °C) form chemical products and charge-transfer complexes. The existence of the latter is also confirmed via observation of an EPR signal on photoirradiation into the CT band. Photoirradiation of the adsorbed organic molecules leads to a redox process on the surface, radical cations are formed, and dechlorination takes place. The coadsorption of persulfate and dinitrobenzene significantly influences the electron-transfer processes. The photochemical products on both activated and non-activated surfaces were separated by HPLC, and the collected fractions were studied spectroscopically. The important reaction of radical cations is hydrolysis resulting in hydroxybiphenyl, the radical BP(OH)˙ is suggested as a key intermediate in hydrolysis.

Determination of the charge state of heteroatoms in organic compounds of group III elements by x-ray fluorescence spectroscopy. Communication 1. Charge values at the sulfur atom in arylalkyl and aryl perfluoroalkyl sulfides and sulfones, and at chlorine in their chlorine-substituted derivatives

1. Quantitative dependences of the charge values at S and Cl atoms on their Kα shifts have been found. Values of q(S) and q(Cl) were determined for a variety of aryl alkyl sulfides and sulfones. 2. In contrast to the aryl alkyl sulfides, in the respective slufones the charge at the S atom stays practically constant for any substitution in the alkyl or aryl segments. 3. In p-chlorosubstituted aryl alkyl sulfides and sulfones the charge values at the Cl atom varies over quite a narrow range, ∼0.1 e; the dependence of q(Cl) on the electronic properties of the p-substituent is complicated.

Preparation and photochemistry of some chlorine-substituted derivatives of deoxybenzoin and bibenzyl

A series of aryl p-chlorobenzyl ketones has been prepared and converted into the corresponding 1-aryl-2-p-chlorophenylethane derivatives (1). U.v. irradiation of two of the latter compounds (1a, b) in benzene results in replacement of the chlorine atom by a phenyl group, whereas other related compounds (1c, e, f) are stable. Irradiation of two isomeric chlorodeoxybenzoins (2a, b) gives the corresponding 1,2,3,4-tetra-arylbutane-1,4-diones (3).

Gas chromatographic separation of chlorine-substituted benzene derivatives

All positional chlorosubstituted derivatives of benzene were separated on stainless steel open tubular column (0,25 mm i.d., 10 m long) coated with diethyleneglycolsuccinate at the temperature programmed (4°C/min.) from 50 to 150°C. Isotherme relative Netretentiondata are tabulated.

Synthesis of new chlorine-substituted derivatives of 2-tetralone

Synthesis of new chlorine-substituted derivatives of 2-tetralone

Effects of chloro substitutions on aliphatic acid inhibitors of pantothenate metabolism in Escherichia coli

The pantothenate-synthesizing enzyme and growing cultures of Escherichia coli were used to study antimetabolite relations involved in inhibitions by salts of aliphatic acids and their chlorine-substituted derivatives. Protection of the enzyme against these inhibitors followed two different patterns. β-Alanine protected the enzyme against inhibition by unchlorinated aliphatic acids, monochloroacetic acid, and β-chloropropionic acid. Pantoate protected the enzyme against inhibition by α-chloropropionic and di- or trichloro-substituted acids of the acetic and propionic series. Chloro-substituted compounds in the first group were less inhibitory to the enzyme than the unchlorinated compounds. However, toxicity to the enzyme increased with additional chlorine substitutions on chloro-substituted compounds antagonized by pantoate. Growing cultures of Escherichia coli strains with reduced capacity for pantoate or β-alanine synthesis were protected from inhibitions due to propionate or its chloro-substituted derivatives by addition of the deficient substrate rather than the substrate effective in protections at the enzyme level.