Potentiometric studies of mixed complexes of cobalt(II) and copper(II) with l‐Asparagine and adenine

A potentiometric titration technique has been used to determine the stability constants for the various complexes of Co(II) and Cu(II) with L‐asparagine and from DNA base, e.g. adenine. Stability constants of ternary systems have been evaluated by the method suggested by Irwing‐Rossotti. In addition, the conditional constants were calculated as a function of pH. The maximum values of the conditional formation constants were found to be in accordance with the mixed‐ligand complex formation constants in a determined pH region. Furthermore, the molar fractions of different species from mixed complexes were calculated by means of formation constants. The values of stability constants of mixed‐ligand complexes at 25°C are as follows: log K= 5.25 for Co(II)‐L‐asparagine‐adenine; log K= 9.30 for Cu(II)‐L‐asparagine‐adenine. The ionic strength was kept constant at I = 0.20 with NaClO₄.     

New O,O‐dimethyl (2,2,2‐trichloro‐1‐carbamoyloxy)‐ethyl phosphonates and their biological activity

A series of fifteen carbamoyl derivatives of O,O‐dimethyl (2,2,2‐trichloro‐l‐hydroxy) ethyl phosphonate (trichlorphon) was synthesized. A number of them showed higher insecticidal activity, having at the same time lower toxicity than the starting biologically active structure. A waste‐free technology for the production of the more promising representatives of this series could possibly be developed in the future.     

Synthesis and antithyroid activity of 6‐n‐propyl‐5‐arylazo‐2‐thiouracils †

The synthesis of several 6‐n‐propyl‐5‐arylazo‐2‐thiouracil derivatives was achieved. The antithyroid activity of these derivatives has been determined using iodine‐125‐thiocyanate discharge technique in rats, and 6‐n‐propyl‐2‐thiouracil (PTU) as a standard. None of the 5‐arylazo‐2‐thiouracil analogs showed antithyroid activity as compared to PTU. The structure‐activity relationships (SAR) of position 5 in the PTU molecule and the requirements for better binding to the proposed receptor are discussed.     

Voltammetric study on the interaction of the heavy metals Cd(II) and Mn(II) with transfer‐RNA,DNA and other polynucleotides

Small amounts of bivalent cations, usually provided by Mg²⁺, are in the living cell necessary for the biological activity of t‐RNA as these bivalent cations influence the tertiary and secondary structure of this globular polynucleotide.

In context with the discussed possibility of carcinogenic actions of ingested Cd it is of particular interest to check whether there exist specific strong interactions of this toxic heavy metal with nucleic acids.

Therefore, the binding of the toxic heavy metal ion Cd²⁺ and the essential heavy metal ion Mn²⁺ to t‐RNA and for comparison to DNA and the polynucleotides poly‐U, poly‐A and poly‐A‐poly‐U has been studied. Free metal ion concentrations have been determined by differential pulse polararography. Association constants and the number of binding sites have been evaluated by the Scatchard method and alternatively according to a simple electrostatic model of the polyelectrolytes. With the Scatchard method for t‐RNA and all polynucleotides with helical structure two different binding sites of different strength are observed. Those with higher association constants are assigned to the helical parts of t‐RNA. Interaction sites with low association constants correspond to the parts with no ordered tertiary structure, as their exclusive occurrence for poly‐U, having a completely stochastic coil structure, reflects. The values of the association constants for the stronger and weaker association sites are in the respective polynucleotides for both investigated bivalent metal ions of comparable magnitude. This emphasizes that the interaction is essentially of electrostatic nature and depends primarily on the charge of the interacting species.

Thus the specific strong interaction of Cd by the intercalation into the tertiary structure of nucleic acids or by chelation of their base units can be ruled out as one possibility for carcinogenity of Cd.

Moreover, under physiological conditions the high excess of competitive Mg²⁺ will suppress the interaction of Cd based on electrostatic forces.     

Antimutagenic and bacteriostatic activities of Schiff‐base compounds derived from aminoguanidine,semicarbazone and thiosemicarbazone and a copper(II)‐coordination complex

The Schiff‐base aminoguanidine compounds including a resorcylidene aminoguanidine copper(II) complex that were synthesized at our laboratory posses non‐mutagenic properties when tested with Ames test using Salmonella typhimurium TA97, TA100 and TA102 bacterial strains. These compounds were tested as possible pharmacological agents in preventing a wide array of illnesses. Additionally, some of these compounds exhibit strong antimutagenic and bacteriostatic activity. Nitrovin, a known mutagen, was used in the antimutagenicity tests as the inducer. A three‐dimensional projection of the copper(II) complex was derived by the semi‐empirical method ZINDO/1 to obtain additional information about its structure, and to help elucidate a possible mechanism of action.     

Photodecomposition of Isofenphos (O‐ethyl‐O(2‐isopropoxycarbonyl)‐phenyl)‐Isopropylphos‐Phoramidothioate)

Photodecomposition of the organophosphorus insecticide isofenphos (O‐ethyl‐O‐(2‐isopropoxy‐carbonyl)‐phenyl)‐N‐isopropylphosphoremidothioate) has been studied in solution, on glass and soil surfaces. Isofenphos underwent oxidation from P = S to the P = O group and deesterification on irradiation in hexane and methanol. Photoproducts were isolated and identified by spectroscopic methods.     

The relation between chemical structure and mutagenic activity of some polycyclic aromatic sulfur heterocycles (s‐pah)

Results of Hückel Molecular Orbital (HMO) calculations strongly suggest identical metabolic activation routes for the mutagen benzo[2,3]phenanthro[4,5‐bcd]thiophene and its homocyclic parent, benzo[a]pyrene.     

Alkylation of metals and the activity of metal‐alkyls†

The biochemical basis for resistance to metal ion toxicity is emerging though it is complicated by the different resistance mechanisms. Several strategies for resistance to toxic metal ions have been identified:

1. The development of energy driven efflux pumps which keep toxic element levels low in the interior of the cell. Such mechanisms have been described for Cd(II) and As(V).

2. Oxidation (e.g. AsO^2‐ to AsO₄ ^3‐) or reduction (e.g. Hg²⁺ to Hg⁰) can enzymatically and intracellularly convert a more toxic form of an element to a less toxic form.

3. The biosynthesis of intracellular polymers which serve as traps for the removal of metal ions from solution such as traps have been described for cadmium, calcium, nickel and copper.

4. The binding of metal ions to cell surfaces.

5. The precipitation of insoluble metal complexes (e.g. metal sulfides and metal oxides) at cell surfaces.

6. Biomethylation and transport through cell‐membranes by diffusion controlled processes.

In this short review I shall discuss the implications of biomethylation as a detoxification mechanism for microorganisms as well as for certain higher organisms.     

Investigation of the hemolytic effects of various organophosphoric acid triesters (OPEs) and their structure‐activity relationship

The hemolytic effects of various organophosphonc acid triesters (OPEs) were investigated and they showed strong hemolyic toxicity except triethyl phosphate and tris(chloroethyl)phosphate. 2‐Ethylhexyl diphenyl phosphate (EHDP) showed the strongest toxicity. By quantitative structure‐activity relationship (QSAR) study, one‐parameter regression equation to estimate hemolysis was not obtained. But, two‐parameter regression equations were obtained which were enought to estimate EC₅₀ and EC₂₀. The correlation coefficients with the two‐parameter regression equations were 0.939 for log(l/EC₅₀) and 0.946 for log(l/EC₂₀).     

Toxicity of substituted benzaldehydes to photobacterium phosphoreum and quantitative structure‐activity relationship

Acute toxicities (15min‐EC₅₀) of 21 substituted benzaldehydes to Photobacterium phosphoreum were determined. A quantitative structure‐activity relationship (QSAR) was developed using molecular connectivity indices and quantum chemical parameters, which show that the toxicity is influenced mainly by the difference of the simple and valence‐corrected fourth path molecular connectivity, polarizability, dipole moment, and the most negative net atomic charge on an atom. This study further shows that benzaldehydes are reactive chemicals, which exhibit bioreactive toxicity.     

Light‐induced changes in rabbit pineal gland n‐acetyltransferase activity

N‐acetyltransferase (NAT) activity was determined in different ages of New Zealand White rabbit pineal gland using 2‐aminofluorene and p‐aminobenzoic acid as substrates and it was assayed by high pressure liquid chromatography. Rabbits of different ages were either sacrificed during the light phase, exposed to darkness or light for 1 min during the dark phase of the lighting cycle, returned to their cages in darkness for 30 min and then sacrificed. Pineal gland NAT activity in animal nocturnally exposed to 1 min of light was inhibited in animals 1 ‐day‐old of age. Nocturnal light exposure did not inhibit enzyme activity in 1‐day‐old rabbit, even though these animal displayed clear light : dark differences in pineal gland NAT activity. Nocturnal light exposure also did not inhibit night time levels of NAT activity in 1‐day‐old animals who had been bilaterally enucleated. The result suggested that this effect is retinally mediated. Pre‐treatment of 1‐day‐old and 60‐day‐old animals with the isoproterenol (beta‐noradrenoreceptor agonist drug), prevented the nocturnal light‐induced inhibition of NAT activity. The different sensitivity of 60‐day‐old and 1‐day‐old animals to different illuminances or durations of nocturnal light exposure, was that the duration or intensity of light exposure was enable to inhibit nocturnal NAT activity. The NAT activity was at least 3.2‐ to 4.6‐fold greater in 1‐day‐old rabbits compared to 60‐day‐old rabbits. Kinetic constants for arylamine NAT activity in pineal gland from rabbits were determined. K_m and F_max values for 2‐aminofluorene were 2.6‐fold higher for light exposure than for no light exposure rabbits. This is the first demonstration of the retina‐pineal gland pathway appears light‐induced changes in pineal glands of animals in 1‐day‐old of ages or older; but this pathway does not function in 60‐day‐old rabbits like manner in 1‐day‐old rabbits.     

Photolysis of 3‐(3,4‐dichlorophenyl)‐1, 1 ‐Dimethylurea (Diuron) in dilute aqueous solution

Diuron samples at 40mg/L concentration were photolyzed with ultraviolet lamps and with natural sunlight to determine if data from ultraviolet lamp photolysis could be used to predict results from sunlight photolysis. Seven photoproducts were identified from the photolysis experiments. The identified photoproducts and the photoproduct yields were essentially the same for the two light sources.     

Effects of the Ellagic acid on the N‐Acetyltransferase activity and Acetylation of 2‐aminofluorene in the rat

The effects of the ellagic acid on the in vitro and in vivo acetylation of 2‐aminofluorene were investigated in male Sprague‐Dawley rats. For in vitro examination, cytosols with or without ellagic acid co‐treatment showed different percentage of 2‐aminofluorene acetylation. For in vivo examination, pre‐treatment of male rats with ellagic acid (10 mg/kg) 24h prior to the administration of 2‐aminofluorene (50 mg/kg) resulted in a 26% and 29%, respectively, decrease in the urinary and fecal recovery of N‐acetyl‐2‐aminofluorene, and a 37% decrease in the metabolic clearance of 2‐aminofluorene to N‐acetyl‐2‐aminofluorene. This is the first demonstration that ellagic acid decrease the N‐acetylation of carcinogens in vitro and in vivo.     

Polychlorinated dibenzo‐p‐dioxins and dibenzofurans (PCDD/Fs) in dated environmental samples,and their connection to known sources

This article investigates available environmental data from measurements of the everywhere present contaminants polychlorinated dibenzo‐p‐dioxins and dibenzofurans (PCDD/F) in dated trends in sediment, soil and herbage from locales in Europe and North America. The PCDD/F data are examined in relation to potential major PCDD/F sources based on volume: wood and coal, example of natural combustion; pentachlorophenol (PnCP), example of chlorinated aro‐matics; and polyvinyl chloride (PVC) pyrolysis, example of chlorinated aliphatic. Collected PCDD/F data of congener sums and 2, 3, 7, 8‐substituted congener (PCDD/F profiles) have been investigated with multivariate methods: principal component analysis (PCA) and partial least squares projection to latent structures model (PLS). The results show that PCDD/F data from 12 locales can be separated in one to three independent profiles. Normally one profile is related to the PCDD/F found in PnCP and another to combustion. A subtype of the ‘PnCP’ and ‘combustion’ profiles indicates PCDD/F contributions from PVC‐related combustions. The environmental profiles exhibit some differences from the suggested sources. The relatively unprotected PCDD/F related to PnCP is suggested to have passed photolytic and/or thermal dechlorinations. Lower‐chlorinated congeners in environmental profiles related to combustion appear to have been influenced by environmental distribution processes. PCDD/F data before industrial production of chlorinated organics have only limited similarity to PCDD/F in technical PnCP profiles; an average 4.6% of the PCDD/F is related to PnCP. This suggests that PnCP similarity in recent deposition profiles cannot be a result of environmental transformation. The average proportion of PnCP‐related PCDD/F profile in recent depositions is 35% with North America high (average 57%) and Europe low (average 24%).     

PCB and PCT levels in cultivated and free‐living mussels of galicia (North west Spain)

PCB and PCT residues were measured in free‐living (FM) and cultivated mussels (CM) from ten sites in Galicia by gas chromatography with electron capture detector and capillary column. The level of PCB₁₂₆₀ and PCT₅₄₆₀ in FMs increases going from Muros‐Noya to Vigo estuarine bay. There was a trend of increase from north to south.     

Approaching the binding between Cu(II) and aerobic granules by a modified titration and µ-XRF

Interactions between metals and activated sludge can substantially affect the fate and transport of heavy metals in wastewater treatment plants. Therefore, it is important to develop a simple, fast and efficient method to elucidate the interaction. In this study, a modified titration method with a dynamic mode was developed to investigate the binding of Cu(II), a typical heavy metal, onto aerobic granules. The titration results indicated that pH and ionic strength both had a positive effect on the biosorption capacity of the granular sludge. The µ-XRF results demonstrated that the distribution of metals on the granular surface was heterogeneous, and Cu showed strong correlations and had the same “hot spots” positions with other metal ions (e.g., Ca, Mg, Fe etc.). Ion exchange and complexing were the main mechanisms for the biosorption of Cu(II) by aerobic granules. These results would be beneficial for better understanding of Cu(II) migration and its fate in wastewater treatment plants.     

Synthesis of 2,5‐diaryl‐2,4‐pentadienenitriles and their spectral,fluorescence and mutagenic properties

The condensation of substituted cinnamaldehydes and arylacetonitriles using sodium ethoxide in ethanol at room temperature afforded 2,5‐diaryl‐2,4‐pentadienenitriles in good yield. The structure of the reaction products was established on the basis of their infrared, nuclear magnetic resonance and elemental analysis data. Two representative compounds were studied for their mutagenic activity. One of them showed a weak mutagenicity while the second showed a high mutagenic activity in TA97a Salmonella strain. Both were negative in TA100. Some of these pentadienenitriles showed fluorescence in solutions.     

Quantitative structure‐activity relationships of hydrophobic organic chemicals 1

Quantitative structure‐activity relationships of hydrophobic organic chemicals were studied based on equations we established. Results showed that observed toxicity of hydrophobic organic chemicals were correlated to two physical‐chemical parameters: reaction equilibrium constant of target molecule‐organic chemical; octanol/water partition coefficient. Regression results showed that the molecular connectivity index of first‐order was an ideal parameter instead of the equilibrium constant. Good relationships between toxicity data and the two parameters were found for three aquatic organisms with a wide range of chemicals.     

Relationships between octan‐1‐ol/water partition coefficients,aqueous activity coefficients and reversed phase HPLC capacity factors of alkylbenzenes,chlorobenzenes, chloronaphthalenes and chlorobiphenyls

Linear relationships between logarithms of octan‐1‐ol/water partition coefficients (K_d,oct), aqueous activity coefficients (y_aq) and extrapolated RP HPLC capacity factors (k‘_w) are found for four types of aromatic hydrocarbons (alkylbenzenes and poly‐chlorinated benzenes, ‐naphthalenes and ‐biphenyls).

Both log K,_d,oct and logk‘_w increase with the increasing number of chlorine or methyl‐ene substituents. These increases of log K,_d,oct and log k‘_w are proportional and almost independent of the parent compound. In addition, these increases are linear to increases of logy_aq. The slopes of logk‘_w‐logy_aq and log K,_d,oct‐logv_aq relationships deviate significantly from 1.0. This suggests that the activity coefficients of the test compounds in both octan‐1‐ol and in the stationary phase of the RP column increase after substitution of aromatic compounds with methylene or chlorine.     

Crystallization and X‐ray structure of 3,3’,4‐trichlorobiphenyl (PCB 35)∗

A method for the preparation of single crystals of PCB 35 suitable for single crystal X‐ray structure determination was developed. This method has already been proven suitable for 2,4'‐dichlorobiphenyl and may prove useful for other PCBs or related compounds. The crystals of PCB 35 are orthorhombic, spacegroup P2₁22₁ (a= 10.665(8), 6 = 3.825(3), c= 14.086(9) Å) and the structure was refined to R = 0.094 for 156 unique observed reflections and 43 parameters. Although the crystals were of poor quality, the structure determination unequivocally confirmed the substitution pattern of the biphenyl moiety by Cl atoms inferred previously from spectroscopic methods. The dihedral angle between the planes of the two phenyl rings is 33(2)°.