Photolysis of chloral hydrate in water with 254 nm ultraviolet: Kinetics, influencing factors, mechanisms, and products.

Chloral hydrate (CH) is a common disinfection by-product found in treated water, and its effective control is important to human health. This study evaluated the effects of some environmental factors (e.g., pH, CH dosage, typical ions) and operational variables (e.g., lamp power, irradiation time) on CH photolysis efficiency via low-pressure mercury lamp-induced ultraviolet (LPUV) at 254 nm. The results demonstrated that the photolysis rate increased significantly with increasing pH from 7.0 to 10.5 and lamp power from 6 to 12 W. Meanwhile, the presence of nitrate, iodide, or free chlorine facilitated CH photolysis, whereas the existence of natural organic matter hindered the process. Together, these factors may help explain varying CH photolysis in different types of waters: seawater > ultrapure water > tap water > lake water. In addition, the initial CH dosage also played an important role, with higher CH being degraded more slowly. Mechanistically, although no catalyst or oxidant was added, CH photolysis was to some extent inhibited by a hydroxyl radical quencher, tert-butyl alcohol, suggesting that indirect photolysis was also responsible for CH loss. In terms of reaction products, the CH photolysis yielded primarily chloride ions and carbon dioxide, thus supporting mineralization as the key pathway. The results may help better understand the control of CH in water using UV.

Stability of regularly prescribed oral liquids formulated with SyrSpend® SF.

The purpose of this research was to evaluate the stability of 12 oral liquid formulations frequently compounded in hospital and community settings formulated in a specific vehicle: SyrSpend® SF. The stability of melatonin, glycopyrrolate, ciclosporin, chloral hydrate, flecainide acetate, tiagabine HCl, labetalol HCl, ciprofloxacin HCl, spironolactone/hydrochlorothiazide, hydrocortisone, itraconazole and celecoxib in SyrSpend SF PH4 (liquid) was investigated at 0, 30, 60 and 90 days and stored at both controlled room temperature and refrigerated. Itraconazole samples were also investigated at 15 and 45 days. No change in odor, color or appearance was observed in the formulations during the test period. Based on the results, a beyond-use date of 30 days can be assigned to tiagabine HCl 1.0 mg/ml in SyrSpend SF when stored at controlled room temperature, and 90 days under refrigeration, improving stability data previously published using other vehicles. A beyond-use date of 60 days can be assigned to chloral hydrate 100.0 mg/ml. In this case, stability is not enhanced by refrigeration. With the rest of the formulations, less than 10% API loss occurred over 90 days at either controlled room temperature or under refrigeration. Including for example itraconazole 20.0 mg/ml, thus providing extended stability compared to simple syrup and other oral liquid vehicles. The findings of this study show that SyrSpend SF is an appropriate suspending vehicle to be used for personalized formulations of the APIs studied here.

Assessing the genotoxicity of two commonly occurring byproducts of water disinfection: Chloral hydrate and bromal hydrate.

Water disinfection treatments result in the formation of disinfection byproducts (DBPs) that have been linked to adverse human health outcomes including higher incidence of bladder and colorectal cancer. However, data about the genotoxicity of DBPs is limited to only a small fraction of compounds. Chloral hydrate (CH) and bromal hydrate (BH) are two trihaloacetaldehydes commonly detected in disinfected waters, but little is known about their genotoxicity, especially BH. We investigated the genotoxicity of CH and BH using a test battery that includes three in vitro genotoxicity assays. We conducted the Ames test using Salmonella bacterial strains TA97a, TA98, TA100 and TA102, and the alkaline comet assay and the micronucleus test both using Chinese hamster ovary cells. We carried out the tests in the absence and presence of the metabolic fraction S9 mix. CH did not exhibit statistically significant genotoxic effects in any of the three assays. In contrast, BH exhibited mutagenic activity in the Salmonella strain TA100 and induced statistically significant DNA lesions in CHO cells as appeared in the comet assay. The genotoxic potential of BH in both assays decreased in the presence of the metabolic fraction S9 mix. BH did not induce chromosomal damage in CHO cells. Our results show that BH exhibited genotoxic activity by causing mutations and primary DNA damage while CH did not induce genotoxic effects. Our findings highlight concerns about the higher genotoxicity of brominated DBPs in comparison to their chlorinated analogues.

Toward better understanding of chloral hydrate stability in water: Kinetics, pathways, and influencing factors.

Chloral hydrate (CH) is a disinfection byproduct commonly found in disinfected water, and once formed, CH may undergo several transformation processes in water distribution system. In order to understand its fate and occurrence in water, this study examined several factors that may affect the stability of CH in water, including pH, temperature, initial CH concentration, typical anions, and the presence of free chlorine and monochloramine. The results indicated that CH was a relatively stable compound (half-life ∼7 d for 20 µg/L) in ambient pH (7) and temperature (20 °C) conditions. However, the hydrolysis rate can be greatly facilitated by increasing pH (from 7 to 12) and temperature (from 20 to 60 °C) or decreasing initial CH concentration (from 10 mg/L to 20 µg/L). To quantify the influences of these factors on the CH hydrolysis rate constant (k, 1/h), which spans five orders of magnitude, this study developed a multivariate model that predicts literature and this study's data well (R(2) = 0.90). In contrast, the presence of chloride, nitrate, monochloramine, and free chlorine exhibited no significant impacts on the degradation of CH, while the CH loss in non-buffered waters spiked with sodium hypochlorite was driven by alkaline hydrolysis. In terms of reaction products, CH hydrolysis yielded mostly chloroform and formic acid and a few chloride, which confirmed decarburization as a dominant pathway and dehalogenation as a noticeable coexisting reaction.

[Influence of Chemical Pre-oxidation on Chloral Hydrate Formation of Threonine].

The influences of different chemical pre-oxidants, including sodium hypochlorite (NaClO), chlorine dioxide (ClO2), permanganate (KMnO4), hydrogen peroxide (H2O2), ozone (O3) and ozone/hydrogen peroxide (O3/H2O2), on chloral hydrate (CH) formation were studied for threonine that has the highest special chloral hydrate formation potential (SCHFP). Suitable pre-oxidants and corresponding optimal doses were determined to provide guidance for controlling chloral hydrate (CH) formation during drinking water treatment. The results indicated that the pre-oxidants that could decrease CH formation for one day incubation time (CH1d) were H2O2, ClO2, KMnO4 and NaClO, and the corresponding suitable doses were 3, 0.5, 0.6 and 0.5 mg·L-1, and the corresponding CH1d removal rates were 61.54%, 47.63%, 29.77% and 10.94%, respectively. The pre-oxidants that could decrease CH formation potential (CHFP) were KMnO4, NaClO, H2O2 and ClO2, and the corresponding suitable doses were 0.6 mg·L-1, 0.5 mg·L-1, 3 mg·L-1 and 0.5 mg·L-1, and the corresponding CHFP removal rates were 41.01%, 33.38%, 8.36% and 2.40%, respectively. In addition, O3 and O3/H2O2 were not suitable for controlling CH in the conventional treatment process because they could increase CH1d and CHFP.

Formation Pathways and Trade-Offs between Haloacetamides and Haloacetaldehydes during Combined Chlorination and Chloramination of Lignin Phenols and Natural Waters.

In vitro bioassays have indicated that haloacetamides and haloacetaldehydes exhibit the highest cytotoxicity among DBP classes. Previous research has focused on their potential formation from the chlorination or chloramination of aliphatic compounds, particularly nonaromatic amino acids, and acetaldehyde. The present work found that acetaldehyde served as a relatively poor precursor for trichloroacetaldehyde and dichloroacetamide, generally the most prevalent of the haloacetaldehydes and haloacetamides, during chlorination or chlorination/chloramination. Using phenolic model compounds, particularly 4-hydroxybenzoic acid, as models for structures in humic substances, we found significantly higher formation of trichloroacetaldehyde and dichloroacetamide from prechlorination followed by chloramination. Evaluation of the stoichiometry of chlorine reactions with 4-hydroxybenzoic acid and several intermediates indicated that seven successive Cl[+1] transfers, faster with chlorination than chloramination, can form 2,3,5,5,6-pentachloro-6-hydroxy-cyclohexa-2-ene-1,4-dione via chlorophenol and chlorobenzoquinone intermediates. Formation of 2,3,5,5,6-pentachloro-6-hydroxy-cyclohexa-2-ene-1,4-dione may serve as a key branching point, with chloramines promoting the formation of dichloroacetamide and chlorination promoting the formation of trichloroacetaldehyde. The behavior of 4-hydroxybenzoic acid with respect to yields of dichloroacetamide and trichloroacetaldehyde during chlorination followed by chloramination was similar to the behavior observed for model humic acids and several surface waters, suggesting that phenolic structures in natural waters may serve as the predominant, and common pool of precursors for haloacetamides and haloacetaldehydes. Experiments with natural waters indicated that the branching point is reached over prechlorine exposures (100-500 mg-min/L) relevant to drinking water utilities using chlorine as a primary disinfectant and chloramines for maintenance of a distribution system residual.

Controlled Burning of Forest Detritus Altering Spectroscopic Characteristics and Chlorine Reactivity of Dissolved Organic Matter: Effects of Temperature and Oxygen Availability.

Forest fires occur with increasing frequency and severity in the western United States, potentially altering the chemistry and quantity of dissolved organic matter (DOM) and disinfection byproduct (DBP) precursors exported from forested watersheds. However, little is known concerning effects of the fire triangle (heat, oxygen, and fuel) on DOM alteration. Using detritus from Pinus ponderosa and Abies concolor (dominant species in forests in the western United States), we prepared DOM from unburned and burned detritus under hypoxic (pyrolysis) and oxic conditions (thermal oxidation) at 250 and 400 °C. DOM characteristics and chlorine reactivity were evaluated by absorption and fluorescence spectroscopy and chlorination-based DBP formation potential tests. Spectroscopic results suggest that burned-detritus extracts had lower molecular weight (reflected by increased E2:E3 and fluorescence index) and divergent aromaticity (reflected by SUVA254) depending on oxygen availability. Temperature and oxygen availability interacted to alter the chlorine reactivity of fire-affected DOM. Increasing temperature from 50 to 400 °C resulted in decreased reactivities for trihalomethane and chloral hydrate formation and divergent reactivities for haloacetonitrile formation (unchanged for pyrolysis and increased for oxidation) and haloketone formation (increased for pyrolysis and decreased for oxidation). We demonstrate that DBP precursors in fire-affected forest detritus are highly dependent on temperature and oxygen availability.

[Effect of Three Typical Disinfection Byproducts on Bacterial Antibiotic Resistance].

The effect of typical disinfection byproducts (DBPs) on bacterial antibiotic resistance was investigated in this study. chlorodibromomethane (CDBM), iodoacetic acid (IAA) and chloral hydrate (CH) were selected, which belong to trihalomethanes (THMs), haloacetic acids (HAAs) and aldehydes, respectively. After exposure to the selected DBPs, the resistance change of the tested strains to antibiotics was determined. As a result, all of the three DBPs induced Pseudomonas aeruginosa PAO1 to gain increased resistance to the five antibiotics tested, and the DBPs ranked as IAA > CH > CDBM according to their enhancement effects. Multidrug resistance could also be enhanced by treatment with IAA. The same result was observed in Escherichia coli K12, suggesting that the effect of DBPs on antibiotic resistance was a common phenomenon. The mechanism was probably that DBPs stimulated oxidative stress, which induced mutagenesis. And the antibiotic resistance mutation frequency could be increased along with mutagenesis. This study revealed that the acquisition of bacterial antibiotic resistance might be related to DBPs in drinking water systems. Besides the genotoxicological risks, the epidemiological risks of DBPs should not be overlooked.

The Sihler staining study of the infraorbital nerve and its clinical complication.

The infraorbital nerve (ION) is a cardinal cutaneous nerve that provides general sensation to the mid face. Its twigs are vulnerable to iatrogenic damage during medical and dental manipulations. The aims of this study were to elucidate the distribution pattern of the ION and thus help to prevent nerve damage during medical procedures and to enable accurate prognostic evaluation where complications do occur. This was achieved by treating 7 human hemifaces with the Sihler modified staining protocol, which enables clear visualization of the course and distribution of nerves without the accidental displacement of these structures that can occur during classic dissection. The twigs of the ION can be classified into the usual 5 groups: inferior palpebral, innervating the lower eyelid in a fan-shaped area; external and internal nasal, reaching the nosewing and philtrum including the septal area between the nostrils, respectively; as well as medial and lateral superior labial, supplying the superior labial area from the midline to the mouth corner. Of particular note, the superior labial twigs fully innervated the infraorbital triangle formed by the infraorbital foramen, the most lateral point of the nosewing, and the mouth corner. In the superior 3-quarter area, the ION twigs made anastomoses with the buccal branches of the facial nerve, forming an infraorbital nervous plexus. The infraorbital triangle may be considered a dangerous zone with respect to the risk for iatrogenic complications associated with the various medical interventions such as implant placement.

Synthesis, characterization and non-isothermal decomposition kinetic of a new galactochloralose based polymer.

A glycopolymer, poly(3-O-methacroyl-5,6-O-isopropylidene-1,2-O-(S)-trichloroethylidene-α-d-galactofuranose) (PMIPTEG) was synthesized from the sugar-carrying methacrylate monomer, 3-O-methacroyl-5,6-O-isopropylidene-1,2-O-(S)-trichloroethylidene-α-d-galactofuranose (MIPTEG) via conventional free radical polymerization with AIBN in 1,4-dioxane. The structures of glycomonomer and their polymers were confirmed by UV-vis, FT-IR, (1)H NMR, (13)C NMR, GPC, TG/DTG-DTA, DSC, and SEM techniques. SEM images showed that PMIPTEG had a straight-chain length structure. On the other hand, the thermal decomposition kinetics of polymer were investigated by means of thermogravimetric analysis in dynamic nitrogen atmosphere at different heating rates. The apparent activation energies for thermal decomposition of the PMIPTEG were calculated using the Kissinger, Kim-Park, Tang, Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS) and Friedman methods and were found to be 100.15, 104.40, 102.0, 102.2, 103.2 and 99.6 kJ/mol, respectively. The most likely process mechanism related to the thermal decomposition stage of PMIPTEG was determined to be a Dn deceleration type in terms of master plots results.

Stability evaluation of 7 % chloral hydrate syrup contained in mono and multi-dose bottles under room and refrigeration conditions.

PURPOSE: To evaluate the stability of an extemporaneously prepared 7% chloral hydrate syrup under different conditions of storage and dispensing. METHODS: Three batches of 7% chloral hydrate syrup were prepared. Each batch was stored in 50 light-resistant glass containers of 60 mL with child-resistant caps and in two bottles of 1000 mL to simulate two forms of dispensing, mono and multi-dose, respectively. Twenty five mono-dose bottles and a multi-dose bottle of each batch were stored under room conditions (20 ± 1 °C) and the rest of the samples were stored in the fridge (5 ± 2 °C). The physical, chemical and microbiological stability was evaluated for 180 days. Stability was defined as retention of at least 95% of the initial concentration of chloral hydrate, the absence of both visible particulate matter, or color and/or odor changes and the compliance with microbiological attributes of non-sterile pharmaceutical products. RESULTS: At least 98% of the initial chloral hydrate concentration remained throughout the 180-day study period. There were no detectable changes in color, odor, specific gravity and pH and no visible microbial growth. These results were not affected by storage, room or refrigeration conditions or by the frequent opening or closing of the multi-dose containers. CONCLUSIONS: Extemporaneously compounded 7% chloral hydrate syrup was stable for at least 180 days when stored in mono or multi-dose light-resistant glass containers at room temperature and under refrigeration.

Adsorption and hydrolysis of alcohols and carbonyls on ice at temperatures of the upper troposphere.

The uptake of gaseous ethanol, 1,1,1-trifluoroethanol, acetone, chloral (CCl(3)CHO), and fluoral (CF(3)CHO) on ice films has been investigated using a coated-wall flow tube at temperatures 208-228 K corresponding to the upper troposphere (UT), with a mass spectrometric measurement of gas concentration. The uptake was largely reversible and followed Langmuir-type kinetic behavior, i.e., surface coverage increased with the trace gas concentration approaching a maximum surface coverage at a gas phase concentration of N(max) ∼ (2-4) × 10(14) molecules cm(-3), corresponding to a surface coverage of ∼30% of a monolayer (ML). The equilibrium partition coefficients, K(LinC), were obtained from the experimental data by analysis using the simple Langmuir model for specific conditions of temperature and concentration. The analysis showed that the K(LinC) depend only weakly on surface coverages. The following expressions described the temperature dependence of the partition coefficients (K(LinC)) in centimeters, at low coverage for ethanol, trifluoroethanol, acetone, chloral, and fluoral: K(LinC) = 1.36 × 10(-11) exp(5573.5/T), K(LinC) = 3.74 × 10(-12) exp(6427/T), K(LinC) = 3.04 × 10(-9) exp(4625/T), K(LinC) = 7.52 × 10(-4) exp(2069/T), and K(LinC) = 1.06 × 10(-2) exp(904/T). For acetone and ethanol the enthalpies and entropies of adsorption derived from all available data showed systematic temperature dependence, which is attributed to temperature dependent surface modifications, e.g., QLL formation. For chloral and fluoral, there was an irreversible component of uptake, which was attributed to hydrate formation on the surface. Rate constants for these surface reactions derived using a Langmuir-Hinshelwood mechanism are reported.

Production of various disinfection byproducts in indoor swimming pool waters treated with different disinfection methods.

In this study, the concentrations of disinfection byproducts (DBPs), including trihalomethanes (THMs; chloroform, bromodichloromethane, dibromochloromethane, and bromoform), haloacetic acids (HAAs; dichloroacetic acid and trichloroacetic acid), haloacetonitriles (HANs; dichloroacetonitrile, trichloroacetonitrile, bromochloroacetonitrile, and dibromoacetonitrile), and chloral hydrate (CH) were measured in 86 indoor swimming pools in Seoul, Korea, treated using different disinfection methods, such as chlorine, ozone and chlorine, and a technique that uses electrochemically generated mixed oxidants (EGMOs). The correlations between DBPs and other environmental factors such as with total organic carbon (TOC), KMnO(4) consumption, free residual chlorine, pH, and nitrate (NO(3)(-)) in the pools were examined. The geometric mean concentrations of total DBPs in swimming pool waters were 183.1±2.5µg/L, 32.6±2.1µg/L, and 139.9±2.4µg/L in pools disinfected with chlorine, ozone/chlorine, and EGMO, respectively. The mean concentrations of total THMs (TTHMs), total HAAs (THAAs), total HANs (THANs), and CH differed significantly depending on the disinfection method used (P<0.01). Interestingly, THAAs concentrations were the highest, followed by TTHMs, CH, and THANs in all swimming pools regardless of disinfection method. TOC showed a good correlation with the concentrations of DBPs in all swimming pools (chlorine; r=0.82, P<0.01; ozone/chlorine; r=0.52, P<0.01, EGMO; r=0.39, P<0.05). In addition, nitrate was positively correlated with the concentrations of total DBPs in swimming pools disinfected with chlorine and ozone/chlorine (chlorine; r=0.58; ozone/chlorine; r=0.60, P<0.01), whereas was negative correlated with the concentrations of total DBPs (r=-0.53, P<0.01) in the EGMO-treated pools.

Disinfection byproduct formation and fractionation behavior of natural organic matter surrogates.

While natural organic matter (NOM) surrogates are established in disinfection byproduct (DBP) research, their use in fractionation studies is rare. To understand how surrogates relate to drinking waters, a range of NOM surrogates were fractionated with XAD resins. Their trihalomethane (THM), haloacetic acid (HAA), haloacetaldehyde, haloacetonitrile, and haloketone formations after chlorination were recorded. While compounds with higher log K(ow) values behaved as hydrophobic acids, fractionation of the more hydrophilic compounds did not clearly correlate to the log K(ow). High HAA formation from ferulic and aspartic acids and 1,1,1-trichloropropanone (1,1,1-TCP) formation from 3-oxopropanoic acid were notable. Three amino acids, asparagine, aspartic acid, and tryptophan, formed significant levels of dichloroacetonitrile (DCAN) and trichloroacetaldehyde (TCA). Formation of DBPs did not correlate to any compound physical property; however, there were several correlations between DBP groups. The most significant were between dichloroacetic acid (DCAA) and dichloroacetonitrile (DCAN), DCAN and TCA, and dichloroacetaldehyde (DCA) and trichloroacetaldehyde, indicating the possibility of similar relationships in natural waters.

Controversies about the occurrence of chloral hydrate in drinking water.

Besides trihalomethanes (THMs) and haloacetic acids (HAAs), chloral hydrate (CH) is the next most prevalent disinfection by-product (DBP) in drinking water, formed as a result of the reaction between chlorine and natural organic matter (NOM). Chloral hydrate (trichloroacetaldehyde) should be limited in drinking water because of its adverse health effect. The controversies concerning the appearance of CH in disinfected water found in literature are discussed in the present paper. According to some authors the CH yield during chlorination of water depends only on TOC. However, there are other data available that do not confirm this relationship. Another fact requiring clarification is the dependence of CH formation on pH. In the present study, CH formation is analysed in different types of water disinfected with different doses of chlorine. Formation of CH is correlated with the dose of Cl(2) and the contact time. The formation of chloral hydrate takes place as long as chlorine is available in the water. Total organic carbon (TOC) is not considered the main factor influencing the production of chloral hydrate in water treated with Cl(2) as the production depends also on the nature of NOM. Higher levels of CH are observed at alkaline conditions (pH>7). A significant correlation (R(2)>0.9) between the concentrations of chloral hydrate and chloroform has been observed. The preozonation increases significantly the chloral hydrate formation potential in the water treated. Biofiltration process does not remove all of CH precursors and its efficiency depends strongly on the contact time. Chloral hydrate was analyzed by gas chromatography with electron capture detector with the detection limit 0.1 microg L(-1).

False-positive ethyl glucuronide immunoassay screening associated with chloral hydrate medication as confirmed by LC-MS/MS and self-medication.

BACKGROUND: Urine-ethyl glucuronide (EtG) concentrations are considered as a specific marker of recent alcohol consumption. We describe false-positive EtG screening results by the DRI ethyl glucuronide enzyme immunoassay caused by chloral hydrate intake. METHODS: Urine-EtG-screening: DRI EtG enzyme immunoassay (Thermo Fisher Scientific Microgenics) on a Hitachi 912 analyzer. EtG- and ethyl sulfate (EtS) confirmatory analysis: LC-MS/MS with an ESI source in the negative ionization, selective reaction monitoring mode. PATIENT: ethanol-abstaining women under buprenorphine-treatment (medication with levetiracetam, gabapentin, clomethiazol and chloral hydrate). Proband: self-medication with 500 mg chloral hydrate after a 5-day ethanol abstinence. EtG analysis for both in subsequent urines. Check for cross reactions of the pharmaceuticals with the EtG immunoassay by addition of pure substance (2 g/L each) to EtG-free urine. RESULTS: EtG concentrations up to 8.0 mg/L or 7.0 mg/g creatinine (cut-off 0.5 mg/L or mg/g) for the patient and up to 0.28 mg/L or 0.35 mg/g for the control subject (after 500 mg chloral hydrate) were obtained by the immunoassay. LC-MS/MS could not confirm these EtG results. In fact, EtG and/or EtS were not detectable in any of the urine samples by LC-MS/MS (lower limit of detection 0.01 mg/L). Cross reactions of the pharmaceuticals, incl. the chloral hydrate metabolites trichloroethanol and trichloroacetic acid, with the DRI EtG immunoassay results were ruled out (by spiking experiments) as the underlying cause for the false-positive EtG immunoassay results. CONCLUSIONS: Trichloroethyl glucuronide as an important chloral hydrate metabolite remains the most probable cross reacting substance with the DRI EtG immunoassay (unproven because of lack in pure standard). The chloral hydrate self-medication experiment clearly points to an association of the false-positive EtG immunoassay results and chloral hydrate intake. Chloral hydrate medication has to be considered as a cause for false-positive EtG screening results by the DRI EtG immunoassay even in cases with regular chloral hydrate treatment (250-1000 mg) and the more in patients with chloral hydrate tolerance (taking g/day). It is recommended that positive EtG immunoassay results always be confirmed by a more specific technique such as LC-MS/MS, including ethyl sulfate as a second minor ethanol metabolite.

Development and interpretation of disinfection byproduct formation models using the Information Collection Rule database.

Multiple linear regression models were used to examine relationships between water quality, treatment, and disinfection byproduct (DBP) formation in Information Collection Rule field data. Finished water models were specified using a cross-validation approach based on data for 225 free chlorine treatment plants. Turbidity, bromide, temperature, alkalinity, total organic carbon, ultraviolet absorbance at 254 nm, pH, chlorine residual, chlorine consumed, and chlorine contact time were employed as independent variables. Important trends within the trihalomethane, dihaloacetic acid, and trihaloacetic acid classes were observed. Bromide was a significant predictor for all DBP species and its influence changed in sign and magnitude with the extent of bromine substitution. A similar pattern followed by alkalinity suggested it plays an important role as an indicator of natural organic matter hydrophobicity and reactivity. Chlorine consumed and organic precursor variables were significant predictors in almost all DBP species models, exhibiting trends opposite to those for alkalinity and bromide. Temperature was the most significant variable in chloroform and chloral hydrate models and its significance declined with increasing bromine substitution within the trihalomethane class. pH had a strong positive influence on chloroform formation, a negative influence on trihaloacetic acid formation, and no influence on dihaloacetic acid formation.

Trichloroacetaldehyde modified oligonucleotides.

Some commercial batches of dichloroacetic acid (DCA) contain traces of chloral (trichloroacetaldehyde). Using such DCA to effect detritylation during solid-phase oligonucleotide synthesis results in the formation of a family of process impurities in which the atoms of chloral (Cl3CCHO) are incorporated between the 5'-oxygen and phosphorus atoms of an internucleotide linkage. The structure was elucidated by HPLC with UV and MS detection, digestion of the oligonucleotide, synthesis of model compounds, and 1H and 31P NMR spectroscopy. By understanding the chemistry behind its formation, we are now able to limit levels of this impurity in synthetic oligonucleotides by limiting chloral in DCA.

Photolysis of chloral under atmospheric conditions.

The photolysis of chloral under atmospheric conditions was studied at the large outdoor European Photoreactor (EUPHORE) in Valencia, Spain. The photodissociation rate coefficient, J(chloral), was measured directly under different sunlight conditions during April 1999. Values in the range of J(chloral) = (4.61-6.11) x 10(-5) s(-1) were obtained, yielding an average value of J(chloral)/J(NO2) = (6.15 +/- 0.62) x 10(-3). This corresponds to a photolysis lifetime of 4.5-6 h under conditions appropriate to the solar flux during summer months and confirms that atmospheric photolysis is the major degradation pathway for chloral. The overall quantum efficiency of photolysis under atmospheric conditions was determined to be 1.00 +/- 0.05. The atmospheric photolysis of chloral produced phosgene, CO, and Cl atoms with molar yields of 0.83 +/- 0.04, 1.01 +/- 0.05, and 1.18 +/- 0.06, respectively. The product yield data are consistent with a mechanism in which the primary photolysis channel produces a Cl atom and a CCl2CHO radical. The latter species is converted to the oxy radical OCCl2CHO,which decomposes by both C-C and C-Cl bond fission. A chemical mechanism for the photolysis of chloral by sunlight is proposed, and the atmospheric implications are discussed.

Practical asymmetric synthesis of beta-trichloromethyl-beta-hydroxy ketones by the reaction of chloral or chloral hydrate with chiral imines.

[reaction: see text] Chloral or its hydrate undergoes the carbon-carbon bond-formation reaction with various optically active imines in the absence of any additive, followed by hydrolysis, to produce the corresponding beta-trichloromethyl-beta-hydroxy ketones in good yields with high enantioselectivities. In addition, the products with higher ee values were obtained by a simple recrystallization process.