János Csanádi

Photocatalytic oxidation of the fungicide metalaxyl dissolved in water over TiO2

Abstract Metalaxyl ( N -(2,6-dimethylphenyl)- N -(methoxy-acetyl)- d , l -alanine methyl ester, C 15 H 21 NO 4 ) is extensively used as fungicide, and the resulting water contamination is a potential health hazard. The photocatalytic decomposition of this fungicide in aqueous suspensions containing TiO 2 yields its complete mineralization. The intermediates formed during the photomineralization and the reaction pathways were analyzed by recording proton NMR spectra. On the basis of the measurements of total organic carbon it was concluded that the rate of metalaxyl decomposition can be explained in terms of the Langmuir–Hinshelwood kinetic model and the values of the resulting constants were compared with those of some other organic compounds reported in the literature.

New D-modified androstane derivatives as aromatase inhibitors☆

Starting from a 16-oximino derivative of 5-androstene the newly-synthesized 16-oximino-17-hydroxy-17-substituted derivatives 2-4 gave by the Beckmann fragmentation reaction the corresponding D-seco derivatives 6-9. Besides, in the case of the 17-hydroxy-17-methyl-16-oximino derivative 2, as a result of the rearrangement, the hydrolysis product 5 of the 16-oximino group with the opposite configuration at the C-17 was obtained. By the Oppenauer oxidation and/or by dehydration of 7 with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), the corresponding derivatives 12, 13, and 14 were obtained. The structures of 6 and 12 were unambiguously proved by the appropriate X-ray structural analysis. Kinetic analysis for anti-aromatase activity showed that compound 12 expressed the highest inhibition in the denucleated rat ovarian fraction in comparison to other androstene derivatives (IC(50) was 0.42 microM). In comparison to aminoglutethimide (AG) activity, it was 3.5 times lower. The inhibition was competitive, with K(i) of 0.27 microM. Introduction of additional units of unsaturation (compounds 13 and 14) in D-seco derivatives did not increase anti-aromatase activity.

Formation of hydrogen-bonded complexes between bile acids and lidocaine in the lidocaine transfer from an aqueous phase to chloroform.

Bile acids are amphiphilic molecules, which, in addition to their physiological role, have also acquired increasingly more important pharmacological applications. It has been shown that these compounds have a promoting effect on the transport of many drugs through the cell membrane. Pharmacodynamic studies showed that they exerted a significant effect on the analgesic action of lidocaine. This study is concerned with the determination of the constants of hydrogen-bonded complexes formed between the investigated bile acids and lidocaine. It was found that a prerequisite for forming such a complex is the existence of at least two OH groups or one OH group and one keto group in the bile acid molecule at an appropriate mutual distance. If a keto group is involved in lidocaine binding, the resulting complex has a larger equilibrium constant. A model--multiple linear regression equation--was constructed, relating the molecular descriptors to the equilibrium constant of hydrogen-bonded complex. It was also shown how the complex formed between lidocaine and bile acid influences the rate constant of the decrease of lidocaine concentration in the aqueous phase during its transfer to the chloroform solution of a bile acid. It was found that the complex formed between lidocaine and bile acids plays an important role in the appearance of the depot effect of lidocaine.

The synthesis and biological evaluation of A-ring substituted steroidal p-quinones

Abstract The preparation of A-ring steroidal 1,4-quinones involves m -CPBA/(BzO) 2 O/ hv oxidation of estrone (or estradiol 17-acetate), acid rearrangement of the obtained quinol, and oxidation. A detailed NMR analysis of 1,4-quinones and their derivatives, as well as the results of preliminary antibacterial and cytotoxicity tests is presented.

Photocatalytic degradation of the insecticide acetamiprid on TiO2 catalyst

The work is concerned with the photocatalytic degradation of acetamiprid, a widely used pyridine-based neonicotinoid insecticide, in UV-irradiated aqueous suspensions of O2/TiO2. The rate of degradation was studied by HPLC/DAD and UV spectrophotometry. It was found that the reaction in the investigated concentration range (0.5-2.0 mg cm-3) is of a pseudo-first order. The 1H NMR analysis indicated that beside acetaldehyde, formic and acetic acid, pyridine-containing intermediates (e.g. 6-chloronicotinic acid) formed during the process. The HPLC/MS measurements also proved the presence of aromatic degradation intermediates. During the photocatalytic process the pH changed by even three units, from 5 to 2. In contrast to the photocatalytic results in the photolytic experimental conditions, acetamiprid appeared to be stable. To get a deeper insight into the complex photocatalytic process of acetamiprid, the photocatalytic degradation of 6-chloronicotinic acid, the detected pyridine-based degradation product, was also investigated.

Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives

New 17-picolyl and 17-picolinylidene androstane derivatives, 3-10, 15, 18, 19, 22 and 23, were synthesized starting from 17α-picolyl-androst-5-en-3β,17β-diol (1) and 17(Z)-picolinylidene-androst-5-en-3β-ol (2). Reaction of 1 with m-chloroperoxybenzoic acid gives 5α,6α-epoxy N-oxide derivative 3, or, with Jones reagent, 3,6-dione derivative 4; while 17α-picolyl-androst-5-en-3β,4α,17β-triol (5) or 3β,4β,17β-triol (6) derivatives are obtainable from 1 using SeO(2) in dioxane. Base-catalyzed tosyl group elimination from 7 or 9 affords AB conjugated derivatives 8 and 10. Oppenauer oxidation of 1 and 2 yields 4-en-3-one derivatives 11 and 12, which, with H(2)O(2) in 4 M NaOH, affords 4α,5α and 4β,5β-epoxides 13, 14, 16 and 17. New 4-methoxy-3-keto derivatives 15 and 18 were obtained from 13 and 14, or, with methanol in 4 M NaOH, from 16 and 17. Reduction of 11 with NaBH(4) gives 22, which was then acetylated to obtain 23. All new derivatives were screened for antitumor activity against human breast adenocarcinoma ER+, MCF-7; human breast adenocarcinoma ER-, MDA-MB-231; prostate cancer AR-, PC-3; human cervix carcinoma, HeLa; and colon cancer, HT-29 cells; as well as one human non-tumor cell line, MRC-5. Compounds 3, 5, 6, 8, 10, 18, 19 and 22 exhibited significant antitumor activity against MDA-MB-231 breast cancer cells; while 5, 6 and 10 also showed strong cytotoxicity against HT-29. Only compound 19 exhibited significant activity against MCF-7 breast cancer cells. No compounds displayed cytotoxicity against non-tumor MRC-5 cells.

Photocatalytic degradation of the herbicide clomazone in natural water using TiO2: kinetics, mechanism, and toxicity of degradation products.

The photocatalytic degradation of the herbicide clomazone (0.05mM) in aqueous suspensions of TiO2 Degussa P25 was examined as a function of the different operational parameters. The optimum concentration of the catalyst was found to be 0.50mgmL(-1) under UV light at the pH 10.3. In the first stage of the reaction, the photocatalytic degradation of clomazone followed the pseudo-first order kinetics, with and the heterogeneous catalysis proceeding via OH radicals. The results also showed that the disappearance of clomazone led to the formation of a number of organic intermediates and ionic byproducts, whereas its complete mineralization occurred after about 55min. Tentative photodegradation pathways were proposed and discussed. A comparison of the evolution of toxicity that was evaluated in vitro in rat hepatoma (H-4-II-E) and human fetal lung (MRC-5) cell lines with the degradation kinetics indicates that the irradiation contributed to the decrease of the toxicity of the mixture that is no longer dominated by the parent compound. The study also encompassed the effect of the quality of natural water on the rate of removal of clomazone.

Spectroscopic monitoring of photocatalytic degradation of the insecticide acetamiprid and its degradation product 6-chloronicotinic acid on TiO2 catalyst

Two spectroscopic methods, 1H NMR and FTIR, were developed for the monitoring of the photocatalytic degradation of acetamiprid, a widely used pyridine-based neonicotinoid insecticide, in UV-irradiated aqueous suspensions of O2/TiO2. The 1H NMR method allowed also the identification of the intermediates such as 6-chloronicotinic and formic acids, as well as separate monitoring of the kinetics of degradation of acyclic and aromatic moieties based on the different chemical shifts of the protons belonging to the methyl group of the acyclic and selected proton of the heterocyclic aromatic moiety. The FTIR procedure enabled the monitoring of the kinetics of degradation of the cyano group of the compound. The obtained results are in good agreement with the comparative HPLC-DAD and HPLC-MS/MS measurements, which also enabled the identification of certain intermediates. To get a deeper insight into the complex photocatalytic process, the photocatalytic degradation of 6-chloronicotinic acid, a stable degradation intermediate of acetamiprid, was also investigated by 1H NMR and HPLC-DAD methods. Based on the obtained data, a tentative reaction mechanism was proposed for the photocatalytic degradation of acetamiprid.

Determination of critical micellar concentrations of two monoketo derivatives of cholic acid

Critical micellear concentrations (CMC) were determined for two novel promoters of membrane permeability-7-monoketocholic acid (7-MKC) and 12-monoketocholic acid (12-MKC), using two non-invasive ((1)H NMR relaxation experiment and conductometry) and two invasive (spectral shift and partition coefficient of the probe molecule) methods. Studies by the former methods suggest the different aggregation abilities of the investigated bile acid derivatives. In an aqueous solution, 7-MKC has a somewhat lower CMC value (43 mM) than 12-MKC (50 mM). Further, it was found that, in addition to primary micelles, 7-MKC forms also secondary micelles. In the experiments with probe (hydrophobic) molecules, the aggregation properties of investigated bile acids did not differ in water, whereas the presence of urea altered the aggregation of 7-MKC. Based on the CMC value, 7-MKC is more hydrophobic than 12-MKC. The apparent hydrophobicity of 7-MKC is a consequence of the formation of secondary micelles, shifting the monomer equilibrium to the direction of primary micelles, which is manifested as a decrease in the CMC value.

A novel route to 2-deoxy-2-iodo-d-mannopyranose derivatives

1,5-Anhydro-2-deoxy-D-hex-1-enitols are versatile synthons’*2. Various functional groups, such as chloro3, fluoro4-7, bromo8, or iodo’-I’, may be introduced at position 2 by either direct or indirect addition of suitable agents across the double bond. Iodination of o-glucal triacetate, using iodine and silver benzoate in dry benzene9*10, iodine and silver acetate in methanol’, N-iodosuccinimide in dry methanol’*, or iodonium bis(2,4,6-trimethylpyridine)perchlorate12, have been described, corresponding to the formal addition of alkyl or acyl hypoiodite across the double bond. However, the formation of free 2-deoxy-2-iodo sugars has not been described hitherto. We now report a formal electrophilic addition of “hypoiodous acid” to 3,4,6-tri0-acetyl-o-glucal’3 (1) and 3,4-di-0-acetyl-6-0-tosyl-D-glucal’4 (2). Depending on the buffer system used and the pH, a mixture of the 2-deoxy-2-iodo esters 3 of 5 together with the corresponding 2-deoxy-2-iodo sugars 4 or 6, or only 4 or 6, were obtained. The compounds obtained could be used for the preparation of 2-deoxy sugars or Brigl’s anhydrides. Thus, treatment of 1 or 2 with iodine in tert-butyl alcohol in the presence of acetate buffer (pH 5, room temperature, 3 h) gave a mixture of the 2-deoxy-2iodo-manno-esters 3 or 5 together with the corresponding Zdeoxy-Ziodo-a-o-mannopyranose derivatives 4 or 6, in the ratio 3 : 1. However, when this reaction was carried out in the presence of a phosphate or carbonate buffer (pH 6-7, room temperature, 3 h), the 2-deoq&iodo-a-D-mannopyranose derivatives 4 or 6 were the only isolable products (50-60%). The structures of 3-6 were confirmed by the NMR data (Table I> and [cu], values. The above procedure for the preparation of the 2-deoxy-2-iodo-cu-D-manno-