Biological activity of 4-hydroxyisophthalic acid derivatives. Hydrazones with antimicrobial activity

The following hydrazono derivatives (I-XIX) of type (A) (sequence in text) where Rn = (sequence in text ) (I-XVII); (sequence in text) (XVIII); -CCl3 (XIX); and Xn = H (I); 2-Cl (II); 3-Cl (III); 4-Cl (IV); 2-NO2 (V); 3-NO2 (VI); 4-NO2 (VII); 2-OH (VIII); 3-OH (IX); 4-OH (X); 4-F (XI); 3,4-OCH3,OH (XII); 3,4,5-OCH3,OH,J (XIII); 3,4-OCH3,OCH3 (XIV); 2,4-Cl2 (XV); 3,4-Cl2 (XVI); 2,6-Cl2 (XVII); were prepared and characterized in an attempt to make available for testing a representative selection of hitherto unreported 4-hydroxyisophthalic acid derivatives. The new compounds in question were obtained in satisfactory yield by condensation of 4-hydroxyisophthalic acid hydrazide with the appropriate aldehydes. The prepared compounds were tested for their possible activity against Gram-positive (S. epidermidis, B. subtilis, B. anthracis) and Gram-negative bacteria (P. aeruginosa, B. melitensis, S. typhi O, S. typhi H, S. infantis, S. paratyphi B, E. coli Bb, E. coli 7075), and fungi (C. albicans, A. niger, S. cerevisiae). The "in vitro" antimicrobial assays were carried out using the paper disk technique (Kirby-Bauer modified). The influence of certain structural modifications on the antimicrobial activity was evaluated.     

Biological activity of 4-hydroxyisophthalic acid derivatives. II. Anilides with antimicrobial activity

A series of 1,3 -bis-anilides of 4-hydroxyisophthalic acid was prepared and tested for antibacterial and antifungal activity. The prepared compounds (I-XVIII), of general structure (A), (Formula: see text) where Xn = H (I); 2-F (II); 3-F (III); 4-F (IV); 2-Cl (V); 3-Cl (VI); 4-Cl (VII); 2-Br (VIII); 3-Br (IX); 4-Br (X); 2-J (XI); 3-J (XII); 4-J (XIII); 2,5-Cl2 (XIV); 2,4-Br2 (XV); 2,3,4-Cl3 (XVI), 2,4,5-Cl3 (XVII); 2,4,6-Cl3 (XVIII), were investigated for the purpose of determining the effect of halogen-substitution on the aniline rings of (A). All of these compounds were prepared in satisfactory hield by reaction of 4-hydroxyisophthalic acid with the appropriate aromatic amine at 175 degrees for 3 hours. The 1,3-bis-anilides prepared in this investigation were screened for antimicrobial activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were laboratory cultures of S. aureus, B. subtilis, B. anthracis, M. paratuberculosis 607, E. coli Bb, S. typhi, S. typhimurium, S. paratyphi B, Pr. vulgaris, Kl. pneumoniae, Ps. aeruginosa, C. albicans, and A. niger. The results of this investigation indicated that most of the 1,3-bis-(halogen-anilides) of 4-hydroxyisophthalic acid had little or no antifungal activity "in vitro", while showed significant activity against Gram+ and Gram- bacteria. Some fluoro-derivatives showed inhibitory activity especially toward S. aureus and M. paratuberculosis. Iodo-derivatives showed broad-spectrum "in vitro" antimicrobial activity, and had some antifungal activity.     

Structure-activity relationships of hydrazono derivatives of biological interest

The following hydrazono derivatives (I-XXIII) of type (A), (formula; see text) where: X = NO2 (II, IV, VI, VIII, X, XIV-XXIII), X = H (I, III, V, VII, IX, XI, XII, XIII), and Y = H (I, II); 3-Cl (III, IV); 4-Cl (V, VI); 3,4-Cl2 (VII, VIII); 2,6-Cl2 (IX, X); 2-NO2 (XI); 3-NO2 (XII); 4-NO2 (XIII, XIV); 2-F (XV); 3-F (XVI); 4-F (XVII); 2-OH (XVIII); 4-OH (XIX); 2,4-(OH)2(XX); 2,4,6-(OH)3(XXI); 2,3-(OH,NO2) (XXII); 2,4-(NO2)2 (XXIII), were prepared and tested for antibacterial and antifungal activity. All of these compounds were prepared in satisfactory yield by reaction of aromatic aldehydes with 2-furoyl and 5-nitro-2-furoyl hydrazide. The hydrazono derivatives I-XXIII prepared in this investigation were screened for antimicrobial activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were laboratory cultures of S. aureus, S. -haemoliticus, B. subtilis, M. paratuberculosis, E. coli, S. typhi, Ps. aeruginosa, K1. pneumoniae, A. niger, S. cerevisiae, C. albicans. The results of this study showed that a number of the prepared hydrazono derivatives exhibited varying degrees of activity against Gram-positive and Gram-negative bacteria. Compounds IV and XV possessed broad spectrum "in vitro" against Gram-positive and Gram-negative bacteria. Compounds XII greater than IV greater than XV showed inhibitory activity especially toward S. aureus. Compounds IV greater than XV greater than XVI were especially active against E. coli. Compounds XV greater than IV were especially inhibitory toward S. typhi and most of the prepared compounds inhibited considerably Ps. aeruginosa and K1. pneumoniae.     

Studies on heterocyclic compounds: spiro [indole-3,2'-thiazolidine] derivatives. Antimicrobial activity of monohalogenated 3'-phenylspiro 3H-indole-3,2'-thiazolidine-2,4' (1H)-diones

The following halogenated 3'-phenyl [3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI); Y = H (I, II), 3-F (III, IV), 2-Cl (V, VI), 3-Cl (VII, VIII), 4-Cl (IX, X), 2-Br (XI, XII), 3-Br (XIII, XIV), 4-Br (XV, XVI). The synthetic approach involves the preparation of variously substituted Schiff-bases of indol-2,3-dione, which then are subjected to cyclocondensation with alpha-mercaptoalkanoic acids, to give spirothiazolidinones of type (A). The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, S. typhi, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified. The results of the antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. 3-Fluoro-derivative (III) showed inhibitory activity especially toward S. aureus and C. albicans. Chloroderivatives (VII) and (VIII) showed broad-spectrum "in vitro" antimicrobial activity, and were especially inhibitory toward S. aureus, E. coli, and S. Typhi. Fluoro-derivative (IV) and bromo-derivatives (XIII) and (XIV) possessed marked antimicrobial activity against M. paratuberculosis.     

Studies on heterocyclic compounds: 1,3-thiazolidin-4-one derivatives. IV. Biological activity of variously substituted 2,3-diaryl-1,3-thiazolidin-4-ones

The following 2,3-diaryl-1,3-thiazolidin-4-ones of general formula (A) were synthesized and screened for antimicrobial activity. (formula; see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV, XVII, XIX, XXI, XXIII), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI, XVIII, XX, XXII, XXIV); R = H (I, II, V, VI, VII, VIII, XI, XIII), 4-CH3 (XXI, XXII, XXIII, XXIV), 4-Br (III, IV, IX, X), 2-NO2 (XIII, XIV), 3-NO2 (XV, XVI), 4-NO2 (XVII, XVIII), 4-OCH3 (XIX, XX); R' = H (I, II, III, IV, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII), 4-CH3 (XXIII, XXIV), 3-Br (V, VI), 4-Br (VII, VIII, IX, X), 4-J (XI, XII). These compounds were prepared by the general synthetic procedure previously reported for the 1,3-thiazolidin-4-one derivatives already prepared and screened in this SARs program. The synthetic approach involves the cyclocondensation of the appropriate Schiff bases with alpha-mercaptoalkanoic acids. The prepared compounds were screened against S. aureus, S. beta-haemolititicus, B. subtilis, M. paratuberculosis 607, S. typhi, Kl. pneumoniae, E. coli Bb, Ps, aeruginosa, C. albicans, A. niger, S. cerevisiae by a disk-diffusion assay (Kirby-Bauer modified). The results obtained in this investigation showed that the prepared compounds exhibited varying degrees of antimicrobial activity. They were especially inhibitory toward Gram-positive bacteria, and fungi. 4-Nitroderivatives (XVII), (XVIII), and 2-nitroderivatives (XIV) and (XIII) possessed marked antimicrobial activity against S. aureus, S. beta-haemoliticus, and B. subtilis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on heterocyclic compounds: 1,3-thiazolidin-4-one derivatives. III. Biological activity of halogenated 2,3-diaryl-1,3-thiazolidin-4-ones

In previous communications from these laboratories, thiazolidinone derivatives of general formula (A) were synthesized and screened for antimicrobial activity. (formula; see text) where: X = H, CH3 Ar = phenyl Ar' = fluorinated or chlorinated phenyl The present communication is in part concerned with further extension of these studies to variously halogenated thiazolidinones of general formula (B). (formula; see text) where: X = H, CH3 R = H, 2-F, 3-F, 4-F, 3-Cl, 4-Cl R' = H, 4-F, 4-Cl These compounds were prepared by the general synthetic procedure previously reported for the 1,3-thiazolidin-4-one derivatives already prepared and screened in this SARs program. The general synthetic approach involves the cyclocondensation of the appropriate Schiff bases with alpha-mercaptoalkanoic acids such as thioglycolic and thiolactic acid. The prepared compounds were tested for their possible activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were: S. aureus, S. beta-haemoliticus, B. subtilis, M. paratuberculosis 607, S. typhi, Kl. pneumoniae, E. coli Bb, Ps. aeruginosa, C. albicans, A. niger, S. cerevisiae. The results of this antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. The second half of this report deals with the structure-activity relationships in all the compounds prepared and studied in this research program. For comparison of antimicrobial activity, the growth inhibitory activity of all the halogenated thiazolidinones of type (A) and (B), prepared and screened in this SARs study, were tabulated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Specificity of reductive dehalogenation of substituted ortho-chlorophenols by Desulfitobacterium dehalogenans JW/IU-DC1.

Resting cells of Desulfitobacterium dehalogenans JW/IU-DC1 growth with pyruvate and 3-chloro-4-hydroxyphenylacetate (3-Cl-4-OHPA) as the electron acceptor and inducer of dehalogenation reductively ortho-dehalogenate pentachlorophenol (PCP); tetrachlorophenols (TeCPs); the trichlorophenols 2,3,4-TCP, 2,3,6-TCP, and 2,4,6-TCP; the dichlorophenols 2,3-DCP, 2,4-DCP, and 2,6-DCP; 2,6-dichloro-4-R-phenols (2,6-DCl-4-RPs, where R is -H, -F, -Cl, -NO2, -CO2, or -COOCH3; 2-chloro-4-R-phenols (2-Cl-4-RPs, where R is -H, -F, -Cl, -Br, -NO2, -CO2-, -CH2CO2, or -COOCH3); and the bromophenols 2-BrP, 2,6-DBrP, and 2-Br-4ClP [corrected]. Monochlorophenols, the dichlorophenols 2,5-DCP, 3,4-DCP, and 3,5-DCP, the trichlorophenols 2,3,5-TCP, 2,4,5-TCP, and 3,4,5-TCP, and the fluorinated analog of 3-Cl-4-OHPA, 3-F-4-OHPA ("2-F-4-CH2CO2- P"), are not dehalogenated. A chlorine substituent in position 3 (meta), 4 (para), or 6 (second ortho) of the phenolic moiety facilitates ortho dehalogenation in position 2. Chlorine in the 5 (second meta) position has a negative effect on the dehalogenation rate or even prevents dechlorination in the 2 position. In general, 2,6-DCl-4-RPs are dechlorinated faster than the corresponding 2-Cl-4-RPs with the same substituent R in the 4 position. The highest dechlorination rate, however, was found for dechlorination of 2,3-DCP, with a maximal observed first-order rate constant of 19.4 h-1 g (dry weight) of biomass-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimation of the hydrophobicity of 2,4-diphenyl-1,3-oxazoline analogs and QSAR analysis of their ovicidal activity against Tetranychus [corrected] urticae

Partition coefficients of six 2-phenyl-1,3-oxazoline congeners containing 2-I, 2-NO2, 2-CF3, 2,6-(CH3)2, 2,6-F2, and 2-F-6-Cl substitutions on the phenyl moiety were measured in a 1-octanol/water system using the flask-shaking method. The effect on the hydrophobicity (LogP) of substituents on the phenyl moiety of 2-phenyl-1,3-oxazolines linearly correlated with that of benzamide congeners. logP values of other 2-(substituted phenyl)-1,3-oxazoline analogs were empirically estimated from the corresponding substituted benzamides. The ovicidal activity of 2-(substituted phenyl)-4-phenyl-1,3-oxazoline analogs against the two-spotted spider mite Tetranychus [corrected] urticae was quantitatively analyzed using the classical QSAR (Hansch-Fujita) method. Results showed that ovicidal activity increases with hydrophobicity. The introduction of inductive electron-withdrawing groups at ortho-positions increased ovicidal activity, but addition of steric bulk was unfavorable. Substitution at either the meta- or para-position was detrimental to the acaricidal activity.     

Synthesis and biological activity of Schiff and Mannich bases bearing 2,4-dichloro-5-fluorophenyl moiety

A series of 2,4-dichloro-5-fluorophenyl bearing Mannich base (4 and 5) was prepared from triazole Schiff bases (3) by aminomethylation with formaldehyde and secondary/substituted primary amines. All newly synthesized compounds were screened for their antimicrobial activity. Compounds 3c, 4c, 4e and 4f exhibited promising antibacterial and compounds 3c, 5c, 5e and 5f showed good antifungal activity.     

Relaxant activity of 2-(substituted phenyl)-1H-benzimidazoles on isolated rat aortic rings: design and synthesis of 5-nitro derivatives

The relaxant activity of 2-(o, p-substituted phenyl)-1H-benzimidazole derivatives with various 5- and 6-position substituents (-H, -CH3, -NO2, -CF3), namely 1-7, was recorded using the in vitro rat aorta ring test. Compounds 3 and 6 [2-(5-nitro-1H-benzimidazol-2-yl)phenol and 2-(4-methoxyphenyl)-5-nitro-1H-benzimidazole] were prepared using a short route, and were the most potent compounds of the series, showing IC50 value of 0.95 and 1.41 (with endothelium) and 2.01 and 3.61 microM (without endothelium), respectively. Studying further structure-activity relationships through the use of bioisosteric substitution in these benzimidazole derivatives should provide novel vasorelaxant leads and possibly against hypertensive diseases.     

Polynuclear diorganotin(IV) complexes with arylhydroxamates: Syntheses, structures and in vitro cytotoxic activities

Series of polynuclear diorganotin(IV) complexes with di-halogenbenzohydroxamate ligands (substituents=2,4-Cl(2), 2,4-F(2), 3,4-F(2), 2,5-F(2), 2,6-F(2)), formulated as the polymeric [R(2)SnL](n)a (1:1) and the tetranuclear [R(4)Sn(2)(HL)(2)(L)](2)b (2:3) (HL=arylhydroxamate), were prepared and characterized by FT-IR, (1)H, (13)C, (119)Sn NMR spectroscopies, elemental analyses and melting point measurements. X-ray diffraction analyses were also carried out for the representative complexes [Me(2)Sn{2,4- F(2)C(6)H(3)C(O)NO}](n)2a and [n-Bu(4)Sn(2){2,4- F(2)C(6)H(3)C(O)NHO}(2) {2,4-F(2)C(6)H(3)C(O)NO}] (2)1b and show that the ligated mono- and di-basic forms, HL and L, of the arylhydroxamic acid (H(2)L) display the oxamic and oximic tautomeric forms, respectively. These compounds exhibit in vitro cytotoxicities toward human leukemic promyelocites HL-60, BGC-823, BEL-7402 and KB cell lines which, in some cases, are identical to, or even higher than, that of "cisplatin". The polymeric diorganotin/hydroxamato complexes a containing the long carbon chain butyl ligands are the most active ones, and the dependence of the antitumor activity of the complexes on various factors, namely the nuclearity, the organic ligand, the type, position and number of the X ring substituents, is also discussed.     

Studies on heterocyclic compounds: 1,3-thiazolidin-4-one derivatives. V. Pharmacological activity of substituted 2-phenyl-3-(N,N-dimethylaminoprophyl)-1,3-thiazolidin-4-one .

The following 2-substituted phenyl-3-(N,N-dimethylaminopropyl)-1,3-thiazolidin-4-one of general formula (A): [formula: see text] where: X = H (I), 3-F (II), 3-Cl (III), 3-Br (IV), 3-CH3 (V), 3-OCH3 (VI), 3-NO2 (VII), 4-F (VIII), 4-Cl (IX), 4-Br (X), 4-CH3 (XI), 4-OCH3 (XII), 4-NO2 (XIII) were prepared and tested for antihistamine activity. The synthetic procedure involves the cyclocondensation of the appropriate Schiff base with thioglycolic acid in refluxing dry benzene. The compounds herein presented were tested for their ability to inhibit the contraction inducted by histamine 5.10(-7) M "in vitro", on guinea pig ileum. The results are reported as contraction of test compound causing 50% of submaximal contraction induced by histamine (IC50), and related to mepyramine as control. The results of the antihistamine tests showed an interesting degree of activity of some of the new thiazolidinone-derivatives. Compounds II, III, V, X, and XI showed IC50 values near the value of the control, compound XI being the most active. These compounds seem to be worthy of further investigation.     

Structure-activity relationship of linear peptide Bu-His6-DPhe7-Arg8-Trp9-Gly10-NH2 at the human melanocortin-1 and -4 receptors: DPhe7 and Trp9 substitution

A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Nal and Bta) were identified in this study.     

Synthesis of novel Schiff base analogues of 4-amino-1,5-dimethyl-2-phenylpyrazol-3-one and their evaluation for antioxidant and anti-inflammatory activity

4-Aminoantipyrine (4-amino-1,5-dimethyl-2-phenylpyrazole-3-one) and its analogues have been found to be compounds of interest for their anti-inflammatory, analgesic, antiviral, antipyretic, antirheumatic and antimicrobial activities. In the present study, Schiff base analogues of 4-aminoantipyrine were synthesized by the condensation reaction with substituted benzaldehydes and then evaluated for their antioxidant and anti-inflammatory activities. From among the synthesized compounds (3a-m, 4 and 5), 3 k and 3f exhibited the highest antioxidant activity followed by 3g, 3l, 3c, 3i, 5, 3m and 3h. The IC(50) values for compounds 3 k and 3f were found to be 0.44 and 0.93 μM, respectively, comparable to that of ascorbic acid (IC(50) 0.41 μM), a standard antioxidant agent. From the comparisons between the hydroxylated and methoxylated compounds, the rank order of antioxidant activity for the products resulting from benzylidene phenyl ring substitution was 2,4,6-OH>3,4-OH>3-OMe-4-OH>3,5-OMe-4-OH>2,4-OH>3-Me-4-OMe>3,4-OMe>4-OMe>4-OH. The structure-activity relationship study revealed that the position and nature of the substituted group on the benzylidene phenyl ring of the Schiff base analogues of 4-aminoantipyrine play an important role in their antioxidant activity. The anti-inflammatory activity of 3f, which also exhibited excellent antioxidant activity, was evaluated in terms of its inhibition of NO production, an inflammatory modulator, in LPS pretreated RAW 264.7 cells using the Griess method. We also examined whether or not this compound had effect on iNOS and COX-2 mRNA expression in RAW 264.7 cells. It was observed that compound 3f significantly reduced NO production and inhibited LPS-stimulated iNOS and COX-2 mRNA levels in a dose-dependent manner. Overall, 3f showed promising antioxidant and anti-inflammatory activities and may be used as the lead compound in a future study.     

Half-sandwich Ru II[9]aneS3 complexes structurally similar to antitumor-active organometallic piano-stool compounds: preparation, structural characterization and in vitro cytotoxic activity

The preparation, structural characterization, and chemical behavior in aqueous solution of a series of new Ru[9]aneS3 half-sandwich complexes of the type [Ru([9]aneS3)Cl(NN)][CF3SO3] and [Ru([9]aneS3)(dmso-S)(N-N)][CF3SO3]2 (5-15, NN=substituted bpy or 2x1-methylimidazole) are described. The X-ray structures of [Ru([9]aneS3)Cl(3,3'-H2dcbpy)][CF3SO3] (9) (3,3'-H2dcbpy=3,3'-dicarboxy-2,2'-bipyridine), [Ru([9]aneS3)Cl(4,4'-dmobpy)][CF3SO3] (13) (4,4'-dmobpy=4,4'-dimethoxy-2,2'-bipyridine), and [Ru([9]aneS3)Cl(1-MeIm)2][CF3SO3] (15) (1-MeIm=1-methylimidazole) were also determined. The new compounds are structurally similar to anticancer-active organometallic half-sandwich complexes of formula [Ru(eta6-arene)Cl(NN)][PF6]. Three chloro compounds (5, 9, 15) were tested in vitro for cytotoxic activity against two human cancer cell lines in comparison with the previously described [Ru([9]aneS3)Cl(en)][CF3SO3] (1, en=ethylenediamine), [Ru([9]aneS3)Cl(bpy)][CF3SO3] (2), and with their common dmso precursor [Ru([9]aneS3)Cl(dmso-S)2][CF3SO3] (3). Only the ethylenediamine complex 1 showed some antiproliferative activity, ca. one order of magnitude lower than the reference organometallic half-sandwich compound RM175 that contains biphenyl instead of [9]aneS3. This compound was further tested against a panel of human cancer cell lines (including one resistant to cisplatin).     

Inhibition of Src kinase activity by 4-anilino-7-thienyl-3-quinolinecarbonitriles

Based on a screening lead from a yeast-based assay to identify Src family kinase inhibitors, a series of 4-anilino-7-thienyl-3-quinolinecarbonitriles was prepared. When the thiophene ring was substituted with a water-solubilizing group in a 2,5-, 3,5- or 2,4-pattern, potent inhibition of Src kinase activity was observed.     

Synthesis and structure-antifungal activity relationships of 3-aryl-5-alkyl-2,5-dihydrofuran-2-ones and their carbanalogues: further refinement of tentative pharmacophore group

Two series of 3-(substituted phenyl)-5-alkyl-2,5-dihydrofuran-2-ones related to a natural product, (-)incrustoporine, were synthesized and their in vitro antifungal activity evaluated. The compounds with halogen substituents on the phenyl ring exhibited selective antifungal activity against the filamentous strains of Absidia corymbifera and Aspergillus fumigatus. On the other hand, the influence of the length of the alkyl chain at C(5) was marginal. The antifungal effect of the most active compound against the above strains was higher than that of ketoconazole, and close to that of amphotericin B. In order to verify the hypothesis about a possible relationship between the Michael-accepting ability of the compounds and their antifungal activity, a series of simple carbanalogues, 2-(substituted phenyl)cyclopent-2-enones, was prepared and subjected to antifungal activity assay as well.     

Anaerobic biodegradation of chlorophenols in fresh and acclimated sludge.

We investigated the anaerobic biodegradation of mono- and dichlorophenol isomers by fresh (unacclimated) sludge and by sludge acclimated to either 2-chlorophenol, 3-chlorophenol, or 4-chlorophenol. Biodegradation was evaluated by monitoring substrate disappearance and, in selected cases, production of 14CH4 from labeled substrates. In unacclimated sludge, each of the monochlorophenol isomers was degraded. The relative rates of disappearance were in this order: ortho greater than meta greater than para. For the dichlorophenols in unacclimated sludge, reductive dechlorination of the Cl group ortho to phenolic OH was observed, and the monochlorophenol compounds released were subsequently degraded. 3,4-Dichlorophenol and 3,5-dichlorophenol were persistent. Sludge acclimated to 2-chlorophenol cross-acclimated to 4-chlorophenol but did not utilize 3-chlorophenol. This sludge also degraded 2,4-dichlorophenol. Sludge acclimated to 3-chlorophenol cross-acclimated to 4-chlorophenol but not to 2-chlorophenol. This sludge degraded 3,4- and 3,5-dichlorophenol but not 2,3- or 2,5-dichlorophenol. The specific cross-acclimation patterns observed for monochlorophenol degradation demonstrated the existence of two unique microbial activities that were in turn different from fresh sludge. The sludge acclimated to 4-chlorophenol could degrade all three monochlorophenol isomers and 2,4- and 3,4-dichlorophenol. The active microbial population in this sludge appeared to be a mixture of populations present in the 2-chlorphenol- and 3-chlorophenol-acclimated sludges, both of which could utilize 4-chlorophenol. Experiments with 14C-radiolabeled p-chlorophenol, o-chlorophenol, and 2,4-dichlorophenol demonstrated that these compounds were converted to 14CH4 and 14CO2.     

Chlorodifluoromethyl-substituted monosaccharide derivatives--radical activation of the carbon-chlorine-bond

The dithionite-mediated addition of BrCF(2)Cl to 3,4-di-O-pivaloyl-D-xylal (1) generated preferably 1-CF(2)Cl-substituted products, that is, (2-bromo-2-deoxy-3,4-di-O-pivaloyl-beta-D-xylopyranosyl)-chlorodifluoromethane and (2-deoxy-3,4-di-O-pivaloyl-beta-D-threo-pentopyranosyl)-chlorodifluoromethane. Selected chlorodifluoromethyl-substituted monosaccharide derivatives were hydrodechlorinated or alkylated at the CF(2)Cl-group using tin reagents under radical reaction conditions. Thus, hydrodechlorinations of (2,3,4-tri-O-acetyl-6-deoxy-alpha-L-galactopyranosyl)-chlorodifluoromethane and of methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-2,6-dideoxy-alpha/beta-L-glucopyranoside are reported using tri-n-butyltin hydride initiated by AIBN. UV-initiated allylations are reported for reactions of (2-deoxy-3,4-di-O-pivaloyl-beta-D-threo-pentopyranosyl)-chlorodifluoromethane, (2,3,4-tri-O-acetyl-6-deoxy-alpha-L-galactopyranosyl)-chlorodifluoromethane, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha-D-glucopyranose, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha-D-mannopyranose and methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-alpha/beta-D-rabinopyranoside with allyltri-n-butyltin.     

Synthesis, structural characterization and antimicrobial activities of 4- and 6-coordinate nickel(II) complexes with three thiosemicarbazones and semicarbazone ligands

To investigate the relationship between antimicrobial activities and the molecular structures of nickel(II) complexes with thiosemicarbazone and semicarbazone ligands, nickel(II) complexes with ligands Hmtsc, Hatsc, Hasc and H2dmtsc, were prepared and characterized by elemental analysis, FT-IR, 1H and 13C NMR spectroscopies, magnetic susceptibility measurements, UV-Vis absorption spectra, TG/DTA and single-crystal X-ray analysis. Their antimicrobial activities were evaluated by the MIC against four bacteria (B. subtilis, S. aureus, E. coli and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A. niger and P. citrinum). The 4-coordinate, diamagnetic nickel(II) complexes showed antimicrobial activities which were different from those of free ligands or the starting nickel(II) compounds; [Ni(mtsc)(OAc)] 1 showed selective and effective antimicrobial activities against two Gram-positive bacteria (B. subtilis and S. aureus) and modest activities against a yeast (S. cerevisiae), [Ni(mtsc)Cl] 3 exhibited moderate activities against a Gram-positive bacterium (S. aureus), and [Ni(atsc)(OAc)] 5 showed modest activities against two Gram-positive bacteria (B. subtilis and S. aureus). On the other hand, the 6-coordinate, paramagnetic nickel(II) complexes with two protonated or deprotonated ligands ([Ni(mtsc)2] 2, [Ni(atsc)(mtsc)] 4, [Ni(atsc)2] 6, [Ni(Hatsc)2](NO3)(2)7, [Ni(Hatsc)2]Cl(2)8 and [Ni(Hasc)2](OAc)(2)9) and the sterically crowded 4-coordinate, diamagnetic nickel(II) complex ([Ni(dmtsc)] 10) did not inhibit the growth of the test organisms. The structure-activity correlation in this series of nickel(II) complexes was discussed based on their ligand-replacement abilities.