Patent Application
20100314318
The invention relates to biocidal compounds and methods of use for the control of microorganisms in water systems that have a pH of 5 or greater.
Water systems provide fertile breeding grounds for algae, bacteria, viruses, fungi, and other pathogens. Microbial contamination can create a variety of problems, including aesthetic unpleasantries such as slimy green water, serious health risks such as fungal, bacterial, or viral infections, and clogging or corrosion of equipment.
Biofouling of water systems susceptible to microbial contamination is typically controlled through the use of biocidal agents. For instance, 2,2-dibromo-3-nitrilopropionamide (“DBNPA”) is a commercially available biocide that is particularly desirable because it is a fast acting, low cost material that exhibits efficacy against a broad spectrum of microorganisms.
It is known, however, that various physical and/or chemical conditions in the water system can result in the premature deactivation of the biocide, thus rendering the biocide essentially ineffective before the desired microbial control has been achieved. As an example, while DBNPA is stable under acidic conditions, it undergoes rapid hydrolytic degradation in neutral to basic solution. Its rate of disappearance increases by a factor of about 450 in going from pH 6, essentially neutral, to pH 8.9, slightly basic. See, Exner et al., J. Agr. Food. Chem., 1973, 21(5), 838-842 (“Exner”). At pH 8, DBNPA's half life is 2 hours. (Exner, Table 1). At pH 11.3, its half life is only 25 sec, essentially instantaneous degradation. (Exner, page 839, left column). DBNPA, therefore, is not an attractive biocide for use in non-acidic water systems.
It would be a significant advance in the art to provide biocides, for treatment of water systems, that are fast acting, long lasting, and that are stable when subjected to deactivating conditions in the water system, such as increased pH.
In one aspect, the invention provides a method for controlling microorganisms in a water system having a pH of 5 or greater. The method comprises treating the water system with an effective amount of a compound of formula I:
wherein X, R and R1 are as defined herein.
In another aspect, the invention provides biocidal compounds. The compounds are of formula (II):
wherein X and R2 are as defined herein.
As noted above, in one aspect the invention relates to methods for controlling microorganisms in water systems having pH of 5 or greater. The method comprises treating such a water system with an effective amount of a compound of formula (I). The inventors have surprisingly discovered that compounds of formula (I) are more resistant to hydrolysis at near-neutral-to-alkaline pH than other biocides, including the commercial compound DBNPA. For instance, the Examples below demonstrate that at pH 6.9 (and a temperature of 30° C.), 2,2-dibromomalonamide (DBMAL), an exemplary compound of the invention, is remarkably more stable than DBNPA (a comparative biocide). No loss of DBMAL is detected over 96 hours whereas 84% the DBNPA is lost in this same time frame at identical conditions.
The compounds of formula (I) have the following chemical structure:
wherein X is halogen; and R and R1 are, respectively, hydroxyalkyl and a cyano radical (—C≡N), or R and R1 are, respectively, hydrogen and an amido radical of the formula:
Preferably, X in the compounds of formula I is bromo, chloro, or iodo, more preferably it is bromo.
A preferred compound of formula (I) is 2,2-dibromo-2-cyano-N-(3-hydroxypropyl)acetamide.
A further preferred compound of formula (I) is 2,2-dibromomalonamide. The term “2,2-dibromomalonamide” means a compound of the following formula:
Compounds of formula (I) can be prepared by those skilled in the art using well known literature techniques.
The compounds of formula I are useful for controlling microorganisms in water systems having a pH of 5 or greater. Such water systems include, but are not limited to cooling tower water, metal working fluids, oil and gas field injection or fracturing or produced water or fluids, oil and gas field water-based fluids, paper and pulp mill process water, oil and gas field operation system, oil and gas field transportation system, oil and gas field separation and storage systems, air washers, boiling water, wastewater, ballast water, filtration systems, paint, polymer emulsions, coatings, aqueous-based slurries and dispersed pigments, adhesives, inks, tape joint compounds, household and personal care, or aqueous-based fluids used in leather tanning applications. Preferred water systems are metal working fluids, cooling tower water, paper and pulp mill process water, membrane-based filtration systems, polymer emulsions and aqueous based mineral slurries, such as kaolin, and calcium carbonate slurries.
Representative membrane-based filtration systems include those comprising one or more semi-permeable membranes, including but not limited to: microfiltration, ultrafiltration, nanofiltration, reverse osmosis and ion-exchange membranes. Applicable systems include those comprising a single type of membrane (e.g. microfiltration) and those comprising multiple types of membranes (e.g. ultrafiltration and reverse osmosis). For example, a membrane-based filtration system may comprise an upstream microfiltration or ultrafiltration membrane and a downstream nanofiltration or reverse osmosis membrane.
The subject biocidal compounds may be added to a feed solution prior to filtration, (e.g. added to a storage tank or pond containing feed solution to be treated) or during filtration, (e.g. dosed into a pressurized feed solution during filtration). Moreover, the subject biocidal compounds may be added to cleaning or storage solutions which contact the membrane. For purposes of this description, any aqueous solution (e.g. raw feed water, cleaning solution, membrane storage solution, etc.) contacting a membrane of a system is referred to as a “feed solution.”
When used within a system having both micro or ultrafiltration and nanofiltration or reverse osmosis membranes, the subject biocidal compounds provide biocidal effect to each membrane (e.g. both upstream and downstream membranes). Membranes and operating conditions may be chosen to allow the majority of the subject biocidal compounds in a feed solution to permeate (i.e. pass through) the microfiltration and ultrafiltration membranes and be rejected, (i.e. concentrated) by the nanofiltration and reverse osmosis membranes.
In some applications, such as when producing drinking water, it may be advantageous that membranes and operating conditions be selected to pass less than 5%, and more preferably less than 1%, of the subject biocidal compounds into the permeate solution.
The portion of biocidal compound rejected by a membrane(s) may be recovered from the concentrate stream and recycled for use in subsequent treatments, (e.g. directed back to a storage tank or dosed within incoming feed). The recycle of biocidal compounds may be part of an intermittent or continuous process. When the subject biocidal compounds are added to a cleaning solution, membranes within the system may be static soaked in the solution or the solution may flow across the membrane. In the latter case, the solution is preferably recycled to a storage tank. In either case, the intermittent cleaning operation preferably lasts less than 24 hours.
In many membrane-based filtration systems, the pH of the feed solution is at least 7, often at least 8 and in some embodiments the pH of the feed solution is increased to at least 9, and in other embodiments at least 10. Examples of such membrane-based systems are described U.S. Pat. No. 6,537,456 and U.S. Pat. No. 7,442,309. Moreover, membranes of many systems are commonly cleaned or stored with feed solutions having pH values of that have been increased to at least 11 and in some embodiments at least 12. Unlike DBNPA (as described in WO 2008/091453), the subject biocidal compounds remain effective under such neutral and alkaline conditions. As a consequence, the subject biocidal compounds may be added to a wider breath of feed solutions (e.g. pH adjusted aqueous feeds, aqueous cleaning solutions, aqueous storage solutions) used in connection with membrane-based filtration systems.
Modules containing a semipermeable membrane may also be stored for more than a week in the presence of an aqueous solution comprising one of the subject biocidal compounds. The modules and biocidal solution may be contained in bags or tanks. Alternatively, during times when a filtration system is not used, modules may be stored within the filtration system, in contact with the subject biocidal compounds.
The type of membranes used in such systems are not particularly limited and include flat sheet, tubular and hollow fiber. One preferred class of membranes include thin-film composite polyamide membranes commonly used in nanofiltration and reverse osmosis applications, as generally described in U.S. Pat. No. 4,277,344; US 2007/0251883; and US 2008/0185332. Such nanofiltration and/or reverse osmosis membranes are commonly provided as flat sheets within a spiral wound configuration. Non-limiting examples of microfiltration and ultrafiltration membranes include porous membranes made from a variety of materials including polysulfones, polyethersulfones, polyamides, polypropylene and polyvinylidene fluoride. Such micro and ultrafiltration membranes are commonly provided as hollow fibers.
As noted, the pH of water systems in which the compounds of the invention are used have a pH of 5 or greater. In some embodiments, the pH is 6 or greater. In some embodiments, the pH is 7 or greater. In still other embodiments, the pH is 8 or greater.
A person of ordinary skill in the art can readily determine, without undue experimentation, the effective amount of the compounds of formula I that should be used in any particular application. For example, an amount of between 1 and 1000 ppm, or 5 and 500 ppm, or 5 and 100 ppm by weight is generally adequate. By way of further illustration, for cooling tower water, a typical active dosage of the biocidal compound is 5 ppm to 50 ppm, or 10 ppm to 25 ppm, twice a week or as needed, depending, for instance, on water conditions including biological contamination, chemical water additives, pH, temperature, salinity, and the like. By way of additional illustration, for metal working fluids, a typical active dosage for the biocidal compound is between 20 ppm and 100 ppm, or between 30 ppm and 50 ppm and a frequency of twice a week or as needed, depending on the degree of biological contamination.
The compounds of formula I can be used in the water system with other additives such as, but not limited to, surfactants, ionic/nonionic polymers and scale and corrosion inhibitors, oxygen scavengers, and/or additional biocides.
The compounds of formula I are useful for controlling a wide variety of microorganisms. In one embodiment, the microorganism are the Legionella species of bacteria, including Legionella residing within amoeba. A preferred biocide for this Legionella embodiment is 2,2-dibromomalonamide.
Legionella have been implicated as the cause of Legionnaires' disease and Pontiac fever, collectively known as legionellosis. Many outbreaks of legionellosis have been attributed to evaporative cooling systems providing infectious doses. Legionella exhibit the relatively unique survival ability of parasitizing and residing within amoeba, eventually lysing their host cells to emerge as mature infectious forms. This mechanism has been suggested as the major means of amplification of Legionella numbers in natural and man made water systems and their increased virulence. A biocide that can effectively control Legionella, including forms of Legionella species rendered more virulent by passage through amoeba, is highly desirable. As demonstrated by the examples, compounds of formula I, such as 2,2-dibromomalonamide, are effective for such bacterial control.
In a second aspect, the invention provides novel compounds that are useful as biocides for controlling microorganisms. The compounds are of the formula II:
wherein X is halogen and R2 is hydroxyalkyl.
In one embodiment, X in the compound of formula (II) is bromo.
In one embodiment, R2 is hydroxypropyl.
In one embodiment, the compound is 2,2-dibromo-2-cyano-N-(3-hydroxypropyl)acetamide.
The compounds described herein are surprisingly resistant to hydrolysis at near-neutral-to-alkaline pH than other biocides, including the commercial compound DBNPA. The compounds consequently are useful for controlling microorganisms in a broader range of water systems than currently known biocides and therefore represent a significant advance in the industry.
For the purposes of this specification, “microorganism” means bacteria, algae, and viruses. The words “control” and “controlling” should be broadly construed to include within their meaning, and without being limited thereto, inhibiting the growth or propagation of microorganisms, killing microorganisms, disinfection, and/or preservation.
By “hydroxyalkyl” is meant an alkyl group (i.e., a straight and branched chain aliphatic group) that contains 1 to 6 carbon atoms and is substituted with a hydroxyl group. Examples include, but are not limited to, hydroxymethyl, hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, and the like.
“Halogen” refers to fluoro, chloro, bromo, or iodo.
Unless otherwise indicated, ratios, percentages, parts, and the like used herein are by weight.
The following examples are illustrative of the invention but are not intended to limit its scope.
The following compositions are evaluated in the Examples:
2,2-Dibromo-3-nitrilopropionamide (“DBNPA”) is obtained from The Dow Chemical Company.
2,2-Dibromomalonamide (“DBMAL”) is obtained from Johnson Mathey.
2,2-Dibromo-2-cyano-N-(3-hydroxypropyl)acetamide (“DBCHA”) is prepared as shown in Example 1.
CMIT/MIT (5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one) is obtained from The Dow Chemical Company.
Glutaraldehyde is obtained from The Dow Chemical Company.
Dioctyl dimethyl ammonium chloride and didecyl dimethyl ammonium chloride are obtained from Lonza Inc.
1-Bromo-3-chloro-5,5-dimethylhydantoin (“BCDMH”) is obtained from Lonza Inc.
Triazine (1,3,5-triethylhexahydro-1,3,5-triazine) is obtained from Clariant Corporation.
0.1 mole of 3-amino-1-propanol (7.51 grams) is added to a solution of 0.1 moles methyl cyanoacetate (10.1 grams) in methanol (40 grams). The mixture is stirred and heated to 60° C. for 30 minutes. The methanol solvent is vacuum stripped from the reaction product. The reaction product, without any further purification necessary, is dissolved in water and reacted with 0.1 mole of bromine (16.0 grams) and 0.03 mole of sodium bromate (5.0 grams), The reaction temperature is kept below 30° C. After the bromine and sodium bromate addition is complete the reaction mixture is allowed to stir for 30 minutes before neutralizing to pH 3 to 4 with dilute sodium hydroxide. Yield is 0.09 mole of 2,2-dibromo-2-cyano-N-(3-hydroxypropyl)acetamide (28 grams).
Dilute solutions (less than 0.5 wt %) of DBMAL and DBNPA are prepared at three different pHs. The pH is set and maintained, by using standard buffer solutions, at pH 6.9, 8.0 and 9.0. These solutions are then held at constant temperature at either −1° C. or 30° C. Periodically, aliquots are analyzed by HPLC to determine the level of DBMAL or DBNPA remaining. Results are shown in Table 1.
Table 1 shows that even at near-neutral conditions (pH=6.9) and a temperature of 30° C., DBMAL is remarkably more stable than DBNPA (a comparative biocide). No loss of DBMAL is detected over 96 hours whereas 84% the DBNPA is lost in this same time frame at identical conditions.
DBMAL and DBNPA are added to 50 ml of a cooling tower water sample (at about pH 8.3) in a 125 ml flask containing about 107 CFU/mL of bacteria, at final active concentration of 50 ppm, 25 ppm and 12.5 ppm. The same contaminated cooling tower water sample without biocide is used as control. The mixtures are incubated at 30° C. with shaking (175 RPM) for 96 hrs. At 1 hr, 3 hrs, 24 hrs, 48 hrs, 72 hrs and 96 hrs after the biocide addition, the viable bacteria in the mixtures are enumerated using a serial dilution method. Starting from 24 hrs after the sampling, the mixtures are re-inoculated with about 106 CFU/mL of bacteria isolated from the cooling water sample. Table 2 shows the efficacy of DBMAL and DBNPA at different time points, expressed as reductions in numbers of bacteria. Numbers presented are logarithm (base 10) transformations of bacterial counts.
As indicated in Table 2, DBMAL exhibits a relative slower killing action than the comparative compound DBNPA, however, DBMAL's effectiveness (>3 log10 killing) lasts for two days more than that of DBNPA at the same active concentration of 50 ppm and 25 ppm, and lasts for one day more than DBNPA at the same active concentration of 12.5 ppm.
Sterile artificial Cooling Tower water (0.2203 g of CaCl2, 0.1847 g of MgSO4, and 0.2033 g of NaHCO3 in 1 L water, approximately pH 8.5) is contaminated with field isolated bacteria at about a 107 CFU/mL concentration. The aliquots of this contaminated water are then treated with eight dosage levels of DBMAL and five other commonly used biocides in cooling water application. The same contaminated water sample without biocide is used as control. After incubating at 30° C. for 1 hr, 3 hrs, 24 hrs, 48 hrs, 72 hrs and 96 hrs, the valid bacteria in the aliquots were enumerated using serial dilution method. Starting from 24 hrs after the sampling, all water samples are reinoculated with about 106 CFU/mL of bacteria. Table 3 compares the efficacy of the six biocides at different time points, expressed by bacterial log10 reduction. DBMAL shows high and long lasting efficacy in this comparison study.
A semi-synthetic metal working fluid (MWF) (55.35% of deionized water, 20.00% of oil, 15% of sodium sulfonate, 4% of ALKATERGE™ T-IV (surfactant), 3% of oleic acid, 2% of glycol ether, 0.65% of AMP™-95 (neutralizing amine)) is contaminated with field isolated bacteria at about a 106 CFU/mL concentration. The aliquots of this contaminated MWF are treated with four biocides at 8 dosage levels. The same contaminated MWF sample without biocide is used as control. After incubating at room temperature for 2 hr, 4 hrs, 24 hrs, 48 hrs, 72 hrs and 96 hrs, the viable bacteria in the aliquots are enumerated using serial dilution method. Table 4 shows the efficacy of DBMAL and three other biocides against bacteria in MWF. Again, DBMAL shows high and long lasting efficacy in this study. No re-inoculation of field isolates is performed in this example.
A sterile synthetic salts water is prepared and inoculated with Pseudomonas aeruginosa ATCC 10145 at about 107 CFU/mL. The synthetic water is prepared to contain (in 1 liter deionized water) the following: CaCl2, 0.2203 g; MgSO4, 0.1847 g; and NaHCO3, 0.2033 g. The final pH of the synthetic cooling water is adjusted to 8.5. Aliquots of the cell suspension are then treated with biocides at selected dosage levels. The same contaminated water sample without biocide is used as control. After incubating at 37° C. for different time intervals, numbers of surviving bacteria are enumerated using a serial dilution method. After incubating for 24 hr, all cell suspensions are reinoculated with Pseudomonas aeruginosa ATCC 10145 at ˜106 CFU/mL.
The efficacy results for DBMAL (inventive), DBCHA (inventive) and DBNPA (comparative) are shown in Table 5. The data are expressed as the dosage required to achieve a 3 log10 bacterial reduction in water samples after each incubation period.
P. aeruginosa ATCC 10145 at different contact time intervals
The bactericidal efficacy of DBMAL starts slightly later than that of DBNPA, however, its efficacy increases with time and is better than DBNPA after 48 hour incubation and when rechallenged with P. aeruginosa cells. DBCHA also shows better long term efficacy than DBNPA.
Since Legionella are amplified in natural and man made systems, such as cooling towers, by passage through amoeba, eradication of such amoeba fed Legionella, is more important and relevant. This example uses amoeba (Acanthamoeba polypohaga) fed Legionella pneumophila (AfLp) in evaluating suitable biocides.
The Legionella are allowed to infect and grow inside amoeba starting with a low multiplicity of infection (1 Legionella to 100 amoeba cells). Such a passage is repeated one more time allowing for establishment of the more virulent form as their dominant physiology, prior to exposure to various concentrations of biocides. The evaluations are conducted after two and twenty four hours of exposure. Appropriate neutralization of the biocides is carried out prior to enumeration of survivors. Table 6 below compares effectiveness of various biocides against both AfLp and free normally grown Legionella cells.
Legionella
The data shows that for every biocide tested the amount needed to kill AfLp is greater than the amounts needed to kill free Legionella. However the amounts of DBMAL required for Legionella control is much lower than those needed for other tested biocides, including DBNPA. This is an unexpected and surprising finding. The levels of DBMAL needed for providing 6 log kills are only about twice that needed for controlling free cells at the corresponding time points. DBMAL provides a means of controlling the more virulent form of AfLp at low dosages when compared to other commonly used biocides.
Samples of a generic acrylic polymer emulsion (49.9% [w/v] solids, pH 8.2) are inoculated with approximately equal numbers (ca. 1×106 per ml) of cells of Pseudomonas aeruginosa, Klebsiella pneumoniae, Bacillus subtilis, and Staphylococcus aureus. The cell inocula are evenly dispersed in the emulsion samples by vigorous agitation. Samples are then sampled to measure the initial inoculum size. The acrylic polymer emulsions are then amended with selected concentrations of DBMAL (from 2.5 to 500 ppm [or mg/l]). The biocide-treated emulsions are incubated at room temperature (ca. 23° C.) on a rocker platform to provide gentle agitation. Samples for enumerating surviving bacteria are collected after 2, 24, and 48 hr of incubation, serially diluted in phosphate-buffered saline, and plated onto Tryptic Soy Agar (TSA) plates.
Results. As illustrated in
In this study, a set of samples of the acrylic polymer emulsion are prepared as described above and treated with DBMAL (0 to 50 ppm) and a second set treated with DBNPA (0 to 50 ppm). After a 48-hr contact time, samples are collected for plate counts.
Results. As illustrated in
Two samples of kaolin slurries (Kaolux HS [particle size finer than 2 microns, 83.4%; 64.9% solids; pH 6.6] and Kaogloss [particle size finer than 2 microns, 90.7%; 70.1% solids; pH 6.3]), are obtained from Thiele Kaolin Company, Sandersville, Ga. Samples of the two slurries are inoculated with four bacterial species (described in Example 8), sampled to confirm the initial size of the bacterial community, and treated with selected concentrations of DBMAL. Samples for bacterial enumeration are collected after 24 hr and 48 hr incubation periods.
Results. The bacteria inoculated into the Kaolux samples treated with DBMAL are sensitive to the presence of the biocidal active and the response is concentration dependent. For example, as illustrated in
Kaogloss. Samples of Kaogloss are treated as described above with DBMAL and sampled after 24 hr and 48 hr of contact time. The results (see
Suspensions of analytical grade (Sigma-Aldrich) calcium carbonate are prepared using deionized water. The pH of the suspensions are adjusted to 7.0, 8.0, and 9.0 with solutions of HCl or NaOH, as appropriate, immediately before the mixed species consortium of bacteria is added (see above for details). Each suspension is vigorously agitated and sampled to determine the initial numbers of bacteria. After sampling for bacterial enumeration, the suspensions are treated with 10 ppm DBMAL, agitated to ensure proper mixing of the biocide and placed on a platform rocker to provide constant agitation. Samples for bacterial enumeration (via plate counts) are collected after 2-hr and 24 hr contact times.
Results. As illustrated in
Aliquots of a sample of the commercially available calcium carbonate slurry, Hydrocarb 90 (Omya), are inoculated with the bacterial consortium as previous described. After agitating to disperse the inoculum, the samples are amended with 5 ppm and 10 ppm DBNPA or DBMAL. The samples are incubated on a rocker platform to provide constant agitation and sampled after 24 hr to determine numbers of bacteria. The initial concentrations of bacteria are higher than in previous examples because of the amount of bacteria present in the sample before the mixed species consortium is added.
Results. The populations of bacteria in samples treated with 5 ppm of DBNPA or DBMAL decrease relatively little during the 24-hr contact (
This study is carried out as previously described except the efficacy of DBMAL is compared to that of DBNPA and CMIT/MIT. For this study, efficacies of the actives are compared using single doses that are typical single dose treatments for products under field conditions.
Results. The results (
While the invention has been described above according to its preferred embodiments, it can be modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the invention using the general principles disclosed herein. Further, the application is intended to cover such departures from the present disclosure as come within the known or customary practice in the art to which this invention pertains and which fall within the limits of the following claims.
This application claims the benefit of U.S. Provisional Application Ser. No. 61/179,157, filed May 18, 2009, which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61179157 | May 2009 | US |
