Vanadium Chloroperoxidases: The Missing Link in the Formation of Chlorinated Compounds and Chloroform in the Terrestrial Environment?

It is well established that the majority of chlorinated organic substances found in the terrestrial environment are produced naturally. The presence of these compounds in soils is not limited to a single ecosystem. Natural chlorination is also a widespread phenomenon in grasslands and agricultural soils typical for unforested areas. These chlorinated compounds are formed from chlorination of natural organic matter consisting of very complex chemical structures, such as lignin. Chlorination of several lignin model compounds results in the intermediate formation of trichloroacetyl-containing compounds, which are also found in soils. These decay, in general, through a haloform-type reaction mechanism to CHCl3 . Upon release into the atmosphere, CHCl3 will produce chlorine radicals through photolysis, which will, in turn, lead to natural depletion of ozone. There is evidence that fungal chloroperoxidases able to produce HOCl are involved in the chlorination of natural organic matter. The objective of this review is to clarify the role and source of the various chloroperoxidases involved in the natural formation of CHCl3 .

A study of the properties of chlorine dioxide gas as a fumigant.

Chlorine dioxide (ClO2) is a strong oxidant that possesses an antimicrobial activity. We demonstrated here that ClO2 gas is easily generated by mixing 3.35% sodium chlorite solution (Purogene) and 85% phosphoric acid at a 10:1 volume ratio without using an expensive machine. In a test room (87 m(3)), experiments were carried out using various amounts of sodium chlorite solution (0.25 ml/m(3) to 20.0 ml/m(3)). The gas concentration increased in a sodium chlorite volume-dependent manner and reached peak values of from 0.8 ppm to 40.8 ppm at 2 h-3 h, and then gradually decreased. No differences in gas concentrations were observed between 0.1 and 2.5 m above the floor, indicating that the gas was evenly distributed. Under high-humidity (approximately 80% relative humidity), colony formation of both Staphylococcus aureus and Escherichia coli was completely inhibited by ClO2 gas exposure at 1.0 ml/m(3) sodium chlorite solution (mean maximal concentration of 3.0 ppm). Exposure at 4.0 ml/m(3) sodium chlorite solution (mean maximal concentration of 10.6 ppm) achieved complete inactivation of Bacillus atrophaeus spores. In contrast, without humidification, the efficacy of ClO2 gas was apparently attenuated, suggesting that the atmospheric moisture is indispensable. Delicate electronic devices (computer, camera, etc.) operated normally, even after being subjected to more than 20 times of fumigation. Considering that our method for gas generation is simple, reproducible, and highly effective at decontaminating microbes, our approach is expected to serve as an inexpensive alternative method for cleaning and disinfecting animal facilities.

Potential biodefense model applications for portable chlorine dioxide gas production.

Development of decontamination methods and strategies to address potential infectious disease outbreaks and bioterrorism events are pertinent to this nation's biodefense strategies and general biosecurity. Chlorine dioxide (ClO2) gas has a history of use as a decontamination agent in response to an act of bioterrorism. However, the more widespread use of ClO2 gas to meet current and unforeseen decontamination needs has been hampered because the gas is too unstable for shipment and must be prepared at the application site. Newer technology allows for easy, onsite gas generation without the need for dedicated equipment, electricity, water, or personnel with advanced training. In a laboratory model system, 2 unique applications (personal protective equipment [PPE] and animal skin) were investigated in the context of potential development of decontamination protocols. Such protocols could serve to reduce human exposure to bacteria in a decontamination response effort. Chlorine dioxide gas was capable of reducing (2-7 logs of vegetative and spore-forming bacteria), and in some instances eliminating, culturable bacteria from difficult to clean areas on PPE facepieces. The gas was effective in eliminating naturally occurring bacteria on animal skin and also on skin inoculated with Bacillus spores. The culturable bacteria, including Bacillus spores, were eliminated in a time- and dose-dependent manner. Results of these studies suggested portable, easily used ClO2 gas generation systems have excellent potential for protocol development to contribute to biodefense strategies and decontamination responses to infectious disease outbreaks or other biothreat events.

Formation of chlorinated species through reaction of SO2 with NaClO2 powder and their role in the oxidation of NO and Hg°.

This study examines gaseous chlorinated species generated from the reaction of sulfur dioxide (SO2) with sodium chlorite powder (NaClO2(s)) to obtain insight into the propensity of this process to enhance NO and Hg° oxidation. A packed bed reactor containing NaClO2(s) was used and the reaction temperature was set to 130 °C. Initially, we determined that the presence of SO2 enhances the oxidation of NO and Hg° by reaction with NaClO2(s). We then introduced NO2 into the gas mixture as a radical scavenger and determined that the chlorinated species generated by the reaction of SO2 with NaClO2(s) are OClO, Cl, ClO, and Cl2. Based on these results, we suggest that such gaseous chlorinated ones are responsible for the enhancement of NO and Hg° oxidation.

Occurrences of nitrosamines in chlorinated and chloraminated drinking water in three representative cities, China.

An investigation of the occurrence of nine nitrosamines in drinking water following different water treatment processes was conducted using samples from seven drinking water treatment plants in three cities and tap waters in one city in China. The total nitrosamine levels ranged from not detected (n.d.) to 43.45 ng/L. The species and concentrations of the nine nitrosamines varied with disinfection methods and source waters. N-nitrosodimethylamine (NDMA), which is the nitrosamines of greatest concern, was identified in raw water, disinfecting water, finished water and tap water samples, ranging from 0.8 to 21.6, 0.12 to 24.2, n.d. to 8.8, and n.d. to 13.3 ng/L, respectively. Chloramination alone produced the most significant amounts of NDMA, while ozonation followed by chloramination led to moderately reduced levels. Additionally, chlorination produced relatively less NDMA, while low pressure ultraviolet radiation followed by chlorination could also significantly reduce them. Total organic carbon is one of the most important factors influencing nitrosamines formation in disinfecting water. In contrast, the addition of chlorine following any other disinfection was found to increase the formation of the other eight species of nitrosamines. The three nitrosamines recommended for monitoring by the US EPA were detected in the tap water samples, but most were present at levels below those that pose a risk to human health. Nevertheless, the occurrence and concentration of nitrosamines regulated in the Drinking Water Contaminant Candidate List could cause some potential human effects and therefore warrant attention.

Synthesis and QSPR study on environment-related properties of polychlorinated diphenyl sulfides (PCDPSs).

Twenty-nine congeners of polychlorinated diphenyl sulfide (PCDPS) theoretically possible were synthesized and purified, and their octanol-water partition coefficients (logK(ow)) and high performance liquid chromatography capacity factors (HPLC-logk') were determined. Then the constitutional and structural descriptors were obtained respectively to establish 2D models and comparative molecular similarity indices analysis (CoMSIA) method was used to establish 3D models. All the models were robust and predictive, indicating that the electrostatic effect may be the primary factor influencing the two properties of PCDPS. The logK(ow) and logk' values of all PCDPS congeners were predicted based on these models. The establishment of linear equation on logK(ow) between PCDPS and chlorinated or brominated diphenyl ether (PCDE, PBDE) was attempted, and the hydrophobic differences were considered to relate with the size of the molecules.

Generation and analysis of mixed chlorinated/brominated homologs of the halogenated natural product heptachloro-1'-methyl-1,2'-bipyrrole.

The 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole (Q1, MBP-79) and further halogenated 1'-methyl-1,2'-bipyrroles (MBPs) are a class of marine natural products repeatedly detected in seafood and marine mammals from all over the world. Only Q1 is currently commercially available as reference standard and the full synthesis of mixed brominated-chlorinated compound is rather complicated. For this reason, synthetic Q1 (240 mg) was transferred into bromine-containing MBPs by UV-irradiation in the presence of bromine. Bromine, which rapidly vanished from the solutions, was renewed during the reaction in order to generate higher amounts of Br-containing MBPs. A total of ∼150 mg Q1 was transferred after ∼10 min irradiation with high amounts of Br(2) to give 30.5mg BrCl(6)-MBPs along with lower proportions of Br(2)Cl(5)-, Br(3)Cl(4)-, Br(4)Cl(3)- and traces of Br(5)Cl(2)-MBPs. Longer UV-irradiation in the presence of Br(2) even allowed for the detection of Br(6)Cl-MBPs and traces of Br(7)-MBP. However, this reaction also provided some unknown by-products. A sample stored in the dark and later in in-door light (no UV irradiation) also eliminated Q1 after 76 d in favour of heptahalogenated MBPs with up to three bromine substituents. The irradiation products were separated on silica, and fractions containing only Q1 and BrCl(6)-MBPs were then further fractionated by non-aqueous RP-HPLC. A pure isolate of the major BrCl(6)-MBP (∼1.5mg) was characterized by GC/MS and (13)C NMR to be 2-bromo-3,3',4,4',5,5'-hexachloro-1-methyl-1,2'-bipyrrole (Br-MBP-75). Partial GC enantioseparation of the axially chiral Br-MBP-75 was achieved on a ß-PMCD column. A full enantioseparation was managed by enantioselective HPLC using a NUCLEOCEL DELTA S column. Low amounts of pure BrCl(6)-MBP enantiomers could be trapped.

Using RuO(2) anode for chlorine dioxide production in an un-divided electrochemical cell.

Chlorine dioxide is a well known powerful disinfectant. Although there are several chemical and electrochemical methods developed for on-line chlorine dioxide generation, the details are mostly confined as patents. We studied in this work the electrochemical generation of dissolved chlorine dioxide from an un-buffered solution of sodium chlorite and sodium chloride mixture in an un-divided electrochemical cell set-up with RuO(2)-coated-Ti anode and Pt-coated-Ti cathode under constant current mode. Various process parameters including feed flow rate (10 to 150 ml/min), feed solution pH (2.3 to 9.4), concentration of sodium chloride (0 to 170 mM), concentration of sodium chlorite (0 to 7.7 mM), and the applied current (100 to 1,200 mA) were optimized. Experiments were conducted by performing single pass experiments, with no circulation. The current efficiency and the power consumption were calculated for the optimized conditions, and compared with IrO(2) electrode of our previous investigation.

Synthesis and insect antifeedant activities of some substituted styryl 3,4-dichlorophenyl ketones.

Sixteen substituted styryl 3,4-dichlorophenyl ketones [(2E)-1-(3,4-dichlorophenyl)-3-phenyl-2-propen-1-ones] were synthesized using eco-friendly benign stereoselective crossed-aldol reaction. They are characterized by their analytical, infrared, NMR and mass spectral data. The insect antifeedant activities of these chalcones were evaluated using Caster semilooper and Achoea janata L.

Total synthesis of piericidin A1. Application of a modified Negishi carboalumination-nickel-catalyzed cross-coupling.

A total synthesis of the mitochondrial complex I inhibitor piericidin A1 is described. It features a unique strategy for the key disconnection, highlighting a modified Negishi carboalumination/Ni-catalyzed cross-coupling on a polyenyne precursor.

Studies on process parameters for chlorine dioxide production using IrO2 anode in an un-divided electrochemical cell.

Chlorine dioxide is potentially a powerful oxidant with environmentally compatible application in several strategic areas relating to pollution control typically for water disinfection, and its sustained production is a key factor for its successful application. Although increased attention has been paid for on-line chlorine dioxide generation by several chemical and electrochemical methods, the details are mostly confined as patents. We studied in this work the electrochemical generation of chlorine dioxide from an un-buffered solution of sodium chlorite and sodium chloride mixture in an un-divided electrochemical cell under constant current mode, with a view to optimize various process parameters, which have a direct bearing on the chlorine dioxide formation efficiency under laboratory conditions. The effect of feed flow rate (10-150 ml min(-1)), feed solution pH (2.3-5.0), concentration of sodium chloride (0-169.4mM), concentration of sodium chlorite (0-7.7 mM), and the applied current (100-1200 mA) on the formation of dissolved ClO(2) gas in solution and the pH of the product-containing solution was investigated by performing single pass experiments, with no circulation, in a cell set-up with Ti/IrO(2) anode and Ti/Pt cathode. The current efficiency and the power consumption were calculated for the optimized conditions.

One-pot formation of allylic chlorides from carbonyl derivatives.

An efficient, one-pot method for the conversion of carbonyl electrophiles to allylic chlorides has been developed, by activating magnesium alkoxides in situ using TiCl4.

Highly efficient route for enantioselective preparation of chlorohydrins via dynamic kinetic resolution.

Dynamic kinetic resolution (DKR) of various aromatic chlorohydrins with the use of Pseudomonas cepacia lipase (PS-C "Amano" II) and ruthenium catalyst 1 afforded chlorohydrin acetates in high yields and high enantiomeric excesses. These optically pure chlorohydrin acetates are useful synthetic intermediates and can be transformed to a range of important chiral compounds.

Experimental and computational study of the conrotatory ring opening of various 3-chloro-2-azetines.

A combined experimental and theoretical study is presented on 2-azetines, a class of azaheterocyclic compounds, which are difficult to access but have shown a unique reactivity as strained cyclic enamines. New highly substituted 2-azetines bearing aryl substituents at the 2- and 4-position were synthesized from 3,3-dichloroazetidines. Whereas 2-aryl-3,3-dichloroazetidines gave stable 2-aryl-3-chloro-2-azetines upon treatment with sodium hydride in DMSO, 2,4-diaryl-3,3-dichloroazetidines showed a remarkably different reactivity in that they afforded benzimidoyl-substituted alkynes under similar mild treatment with base. The formation of the alkynes involves electrocyclic ring opening of intermediate 2,4-diaryl-3-chloro-2-azetines and elimination of hydrogen chloride. Ab initio theoretical calculations confirmed the experimental findings and demonstrated that the 4-aryl substituent is responsible for this remarkably enhanced reactivity of 2-azetines toward electrocyclic conrotatory ring opening by a significant decrease in reaction barrier of about 30 kJ/mol. This activation effect by an aryl group in the allylic position toward electrocyclic ring opening of unsaturated four-membered rings is of general importance since a similar increased reactivity of 4-aryloxetes, 4-arylthiete-1,1-dioxides, and 3-arylcyclobutenes has been reported in literature as well.

Synthesis and testing of 2-deoxy-2,2-dihaloglycosides as mechanism-based inhibitors of alpha-glycosidases.

The synthesis of a series of 2-deoxy-2,2-dihaloglycosyl halides as potential alpha-glycosidase inactivators has been achieved via the halogenation of protected 2-fluoroglycal precursors. Direct chlorination of per-O-acetylated 2-fluoro-d-glucal and 2-fluoromaltal followed by basic deprotection yielded the corresponding 2-chloro-2-deoxy-2-fluoroglycosyl chlorides. Reaction of the per-O-acetylated 2-fluoroglycals with acetyl hypofluorite or Selectfluor yielded the 2-deoxy-2,2-difluoroglycosyl derivatives, which were converted to their alpha-chlorides using thionyl chloride and deprotected under basic conditions. Trinitrophenyl glycosides of the 2-deoxy-2,2-difluoro mono- and disaccharides were synthesized by arylation of the hemiacetals with picryl fluoride, then deprotected with HCl in methanol. All three monosaccharide derivatives caused active site-directed, time-dependent inactivation of yeast alpha-glucosidase via the trapping of covalent glycosyl-enzyme intermediates, and kinetic parameters for inactivation by each compound were determined. Surprisingly neither of the 2-deoxy-2,2-dihalomaltosyl chlorides caused time-dependent inactivation of human pancreatic alpha-amylase, despite the fact that the trinitrophenyl 2-deoxy-2,2-difluoromaltoside functioned in that mode. The trinitrophenyl glycosides appear to be approximately 1000-fold more reactive than the corresponding chlorides in the enzyme active sites.

Synthesis, characterization and Stat3 inhibitory properties of the prototypical platinum(IV) anticancer drug, [PtCl3(NO2)(NH3)2] (CPA-7).

This paper describes a reinvestigation of the literature concerning the synthesis and structural characterization of the platinum(IV)-based anticancer drug known as CPA-7 and believed to be the compound fac-[PtCl3(NO2)(NH 3)2]. CPA-7 has previously been extensively investigated for its ability to control tumor cell growth by inhibition of Stat3 signaling, but very little information is available concerning its synthesis or spectroscopic properties. A reproducible synthetic route is shown to produce an active material which is characterized by IR and (1)H, (14)N, (15)N, and (195)Pt NMR spectroscopy, and single crystal X-ray crystallography. The freshly prepared drug is obtained as a single isomer which may in fact be fac- or mer-[PtCl3(NO2)(NH3)2], but recrystallization resulted in a disordered crystal containing approximately equal amounts of the two geometric isomers.

SAR studies of capsazepinoid bronchodilators 3: The thiourea part (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region).

Certain derivatives and analogues of capsazepine are potent in vitro inhibitors of bronchoconstriction in human small airways. During an investigation of the dependency of the potency on the structural features of the capsazepinoids in the thiourea moiety (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region), it was revealed that capsazepinoids with a thiourea or an amide link between the B-ring and the C-region in general have a good bronchorelaxing activity, while urea is a less attractive choice. Further, it was shown that 1,2,3,4-tetrahydroisoquinolines with a 2-(phenyl)ethyl derivative as the C-region are considerably more potent than those with an octyl group, while 2,3,4,5-tetrahydro-1H-2-benzazepines were found to be more insensitive to the nature of the C-region.

A regioselective approach to trisubstituted 2 (or 6)-arylaminopyrimidine-5-carbaldehydes and their application in the synthesis of structurally and electronically unique GlambdaC base precursors.

An efficient regioselective synthesis of trisubstituted 2(or 6)-arylaminopyrimidine-5-carbaldehydes has been developed via an S(N)Ar reaction of 2,4,6-trichloropyrimidine-5-carbaldehyde with aniline, methylamine, and alkoxide nucleophiles using a combination of phase-transfer catalysis and more traditional SNAr reaction conditions. We demonstrate that in a few synthetic steps, highly functionalized fused-bicyclic pyrimidine substrates can be accessed from the trisubstituted 2-arylaminopyrimidine-5-carbaldehydes. Furthermore, these fused-bicyclic compounds are readily derivatized using the Suzuki cross-coupling reaction to generate electronically and structurally unique GlambdaC base precursors.