GB1571814A - Water-soluble antimicrobial agents and compositions containing them - Google Patents

Abstract

An antimicrobial composition is prepared containing an aryl compound carrying an oleophilic substituent and a hydrophilic substituent, and an antimicrobial agent coordinated to the hydrophilic substituent. The oleophilic substituent is a straight alkyl radical from 6 to 24 carbon atoms and the hydrophilic substituent is a sulpho or hydroxyl group. The antimicrobial agent is an imidazole, a benzimidazole, a thiazole or a metallic chelate of oxine. This composition is useful for controlling microbial development and for protecting timber from termites and other insects.

Description

(54) WATER-SOLUBLE ANTIMICROBIAL AGENTS AND COMPOSITIONS CONTAINING THEM (71) We, CHAPMAN CHEMICAL COMPANY, of 416 East Brooks Road, Memphis, Tennesee 38109, United States of America, a corporation of the State of Illinois, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The object of this invention is to provide an antimicrobial agent that is effective against broad groups of microorganisms and, in a preferred embodiment, one that has low toxicity for animal and plant life.Essentially, this object is accomplished by formulating a disubstituted aryl compound in which the first substituent is an oleophilic group adapted to penetrate the lipoid layers of microcells and the second substituent is a hydrophilic group to which an antimicrobial compound is coordinated. By coordinating the antimicrobial component with the disubstituted aryl compound, a synergistic effect is observed in which there is a marked increase in the microbicidal activity of the antimicrobial compound far greater than can be accounted for by the contribution of any antimicrobial properties of the disubtituted aryl compound. Since the antimicrobial compound is coordinated with the hydrophilic substituent, the antimicrobial compound is solubilized on a molecular basis.By coordinating the antimicrobial compound with the aryl compound, the antimicrobial compound can be carried along with tlle aryl compound and so be poised to enter a cell when its protective membrane is breached by the combined attack of hydrophilic and oleophilic substituents of the aryl compound.

The coordinate bond between the disubstituted aryl compound and the antimicrobial compound may be broken by conventional means such as formation of an insoluble or nonionizable compound from either of the two components of the coordinate bond. It is desirable at times to guard against such bond-breaking by means such as pH adjustment or chelation of undesirable ions.

For the protection of certain substrates, it actually may be desirable, however, to allow the coordinate bond to break during or after treatment of the substrate. This happens in the treatment of wood, for example, so that once deposited in the wood, the antimicrobial compound changes from a water-soluble to a water-insoluble form, thereby retaining high residual activity. In this case, the initial coordinate bond has served a very useful purpose in allowing the antimicrobial compound to be deposited within and on the wood on a molecular basis.

The Oleophilic Substituent The oleophilic substituent of the aryl compound should have a degree of stereochemical compatibility with the structure of the semipermeable membrane of the cell. A common structure of the semipermeable membrane of the cell. A common structure meeting this criterion is an essentially unsubstituted straight-chained hydrocarbon having a length that is significant with respect to the thickness of the cell wall. This generally requires, as a minimum, an alkyl chain with six carbon atoms in it. On the other hand, the alkyl chain should not be too long. Since the freedom of mobility of an alkyl chain increases with increasing chain length, alkyl chains begin to coil if a certain length is exceeded. When the coiling is significant, it can cause steric hindrance and make permeation of the cell wall difficult.While the maximum length of the alkyl chain can only be determined with respect to a given environment and a specific cell structure, it is believed to be a fair generalization to suggest that an alkyl chain much longer than 18 carbon atoms and, more especially, one longer than 24 carbon atoms, will lose its effectiveness in penetrating the cell wall.

The preferred alkyl groups of this invention are not excessively branched or substituted to the extent that they lead to steric hindrance. Nonetheless, some substitutes along the hydrocarbon chain, such as chlorine, may improve the oleophilic properties of the "shaped charge" and may be used to advantage. It has also been observed that chlorine substitution may permit the use of shorter alkyl chains.

It can be understood that no rigid definition can be given as to the length, composition and configuration of the oleophilic group as these parameters necessarily must be adjusted for the microbal species of the bacteria and fungi that are to be attacked.

The Hydrophilic Substituent The hydrophilic substituent of the aryl compound must be capable of forming a strong coordinate bond with the antimicrobial compound. There are not too many hydrophilic substituents to choose from that will coordinate well with a compound having antimicrobial properties, and two of the most effective and chemically accessable are the sulfo and the hydroxyl radicals.

The Aryl Compound A preferred aryl compound is benzene which is believed to be most effective and, perhaps to a lesser extent, naphthalene. Aryl compounds comprised of more than two ring structures may lose their effectiveness for several reasons, among them being the fact that their size becomes large as compared with the oleophilic substituent and will tend to cause steric hindrance to the oleophilic substituent in penetrating the wall of the microorganism. While not essential in the practice of this invention, secondary substituents of the aryl group may sometimes prove desirable, particularly if they are capable of withdrawing electrons to increase the strength of the coordination bond between the hydrophilic substituent and the antimicrobial compound. Substituents which function in this manner are, for example, -NO2, -CN and -CHO.Electron-withdrawing substituents should be used sparingly and with discretion if overloading of the ring structure of the aryl compound is to be avoided.

The Antimicrobial Compound As set forth above, the antimicrobial compound must coordinate with the hydrophilic substituent to form a reasonably stable bond if it is to be solubilized and be effective in the practice of this invention.

One particular advantage of this invention lies in the fact that antimicrobial compounds that have known low toxicity toward plant and animal life may be made more effective by formulating them in accordance with this invention, thus greatly increasing their utility. Of these, for example, the metal chelates of 8-hydroxy quinolinol (oxine) are quite prominent, particularly copper-8-quinolinolate (hereinafter called "Cu-8-Q"). The following is a listing taken from literature references of the relative effectiveness of several metal quinolinolates in descending order of activity: mercury copper cadmium nickel lead cobalt zinc iron calcium.

Aluminium and tin have also proved useful.

Other groups of compounds which have been found effective as antimicrobial compounds when coordinated with substituted aryl compounds in accordance with this invention include the imidazoles and thiazoles. One of particularly good microbicidal activity is a benzimidazole marketed by Riedel-de-Haen AG of Seelze/Hanover, West Germany, under its product designation ' Mergal BCM", which is believed to be 2 (me thosy-carbamoyl) -benzimidazol.

The antimicrobial agents of the invention preferably comprise an alkyl [C6 to C18j benzene sulphonic acid co-ordinated with a metal chelate of oxine or an alkyl [C6 to C18] substituted phenol co-ordinated through the hydroxyl group with a metal chelate of oxine.

The agents of the invention may be produced merely by mixing together the ingredients in any desired order in a suitable diluent so as to obtain a co-ordination compound.

The agents are preferably produced as concentrates which can be diluted preferably with water prior to use. Dilution by amounts of up to 1:2000 are possible. Preferred concentrates comprise 1-10 parts by weight of antimicrobial compound; 5-83 parts by weight of disubstituted aryl compound; and 1-50 parts of a polar diluent.

The agents of the invention may be used to control for example, the growth of bacteria, algae, fungi, viruses, yeasts and protozoa.

The following Examples are given to show the effectiveness of one of the preferred antimicrobial agents of this invention in which dodecylbenzene sulfonic acid (DDBSA) is selected as the disubstituted aryl compound and Cu-8-Q is selected as the antimicrobial. The oleophilic substituent on the benzene ring of DDBSA is the 1 2-carbon-membered (approximately) alkyl chain and the hydrophilic substituent is the sulfo group. The oleophilic hydrocarbon chain on the DDBSA is essentially a tetramer of propylene and usually will vary, as commercially available, from between 11 and 13 carbon atoms. Most DDBSA commonly available is straight-chained, but some is branched (the so-called "soft" and "hard" DDBSA's) and both have proved effective in the practice of this invention.

The Cu-8-Q used in the Examples is prepared by the reaction of 8-hydroxy quinolinol with a copper compound such as copper hydrate (cupric hydroxide).

A diluent is used with the mixture of DDBSA and Cu-8-Q which not only serves as a viscosity-reducing agent, but also, it is believed, permits ionization of the alkyl benzene sulfonic acid to achieve complete solubility of the compound. It has been found that complete solubilization is effected most easily through the use of a highly polar organic solvent which is water miscible. A partial list of suitable diluents for use in the present invention is given below: Methanol Ethanol Isopropanol n-Butanol Dimethylformamide N-methyl -2-pyrrolidone Ethyl glycol Water propylene glycol stoddard solvent Toluene Broadly speaking, for every part by weight of the metal -8-quinolinolate, it is preferred to include from 5 to 50 parts by weight DDBSA and 1 to 50 parts by weight of the polar diluent.

The most preferred agent according to the present invention contains from 2 to 10 parts by weight of Cu-8-Q, 25 to 83 parts by weight of the alkyl benzene sulfonic acid, and 15 to 35 parts by weight of the diluent per 100 parts by weight of the concentrate. One specific agent produced according to the present invention contains about 5 parts by weight of Cu-8-Q, coordinatly bonded will about 64 parts by weight of DDBSA, and about 31 parts by weight of methanol. Additionally, it has been found useful to add minor amounts, e.g., 5%by weight, of ethylene glycol to improve shelf life.

One method of producing the agents of the present invention is to mix the diluent with the DDBSA and stir in the quinolinolate. The mixing may be accompanied by liberation of exothermic heat of reaction which speeds up the solution of all components.

Another suitable process for preparing a concentrate consists in first reacting copper hvdroxide with a mixture of methanol and DDBSA to form a metal salt. Then 8-hydroxy quinoline is stirred in to form the metal chelate.

Concentrates prepared as above are diluted, preferably with water, prior to use and essentially may be diluted to any degree. Other diluents may be used, including xylene, isopropanol. ethylene glycol and naphtha. The diluted solutions can be applied by a known technique. such as brushing. spraying, dipping or wiping.

In the Examples that follow, the effectiveness of the various formulations was determined by treating freshly cut pine boards by dip immersion for 10 seconds in the formulation to be tested. The boards, along with an untreated control, were placed in a chamber for the period of time indicated and maintained at a temperature of about 80"F and a humidity of about 70inc.

U'hen the boards were removed from the chamber, they were visually compared with the control. The results of the effectiveness of the fungicide is expressed as the percentage of the total surface area of the board covered by stain and mold. Thus, the lower the percentage, the better the activity as a fungicide.

All parts given in the Examples are parts by weight.

Examples Examples I to III To establish the inherent fungicidal properties of Cu-8-Q. it was dissolved in a strong mineral acid and in maleic acid and the results compared with a solution of similar Cu-8-Q concentrate made in accordance with this invention. Each Example was diluted 1:400 with water for use.

Cu-8-Q Solubilizing Agent Diluent and % Stain Example Amount and Amount Amount 42 Days I 10 DDBSA/50 Methanol/40 29 II 10 98NoH2SO4/20 Water/70 53 III 10 maleic acid/50 water/40 58 As can be seen, dissolving Cu-8-Q in sulfuric and maleic acids is not nearly as effective as solubilizing it with a disubstituted aryl compound of the instant invention.

Examples IV to VIII In these Examples, Cu-8-Q was dissolved in compounds closely related to DDBSA save for the fact that they did not have the oleophilic substituent or "shaped charge" as described in this specification.

In the following Examples IV to VIII, the data given in the table is for the concentrate. In all case, this concentrate was diluted by 400 parts water to 1 part concentrate prior to treating the test specimen.

Cu- 8- Q Solubilizing Agent Diluent and % Stain Example Amount and Amount Amount 42 Days IV 5 DDBSA/64 Methanol/31 17 V 5 p-toluene sulfonic Methanol/31 52 acid/64 VI 5 l-naphthalene sul- Methanol/31 74 fonic acid/64 VII 5 Benzene sulfonic Methanol/31 92 acid/64 VIII 5 Methane sulfonic Methanol/31 62 acid/64 From the foregoing, It can be seen that compounds formed by the substitution of a sulfonic group on an otherwise unsubstituted aryl compound is quite ineffective as a fungicide. Some improvement is noted by additionally substituting a methyl group, but a most dramatic improvement is noted if the second substituent is a 12-carbon alkyl group that is an oleophilic shaped charge within the scope of this invention. Tridecylbenzene sulfonic acid also proved very effective, too. However, 4-dodecylated oxydibenzene sulfonic acid proved less effective under these conditions although it is considered useful in certain instances.

Examples IX to XI In order to prove the effectiveness of a fungicide made in accordance with this invention, the composition of Example IV was diluted 1:200 with water and treated boards compared with those treated with three of the standard fungicidal compositions now in common use.

% Stain and Mold 28 Days Example Test I Test 2 IX Sodium tetrachlorphenate 16.40% 20 7 Other sodium chlorophenates 4.43% Phenyl mercuric lactate 0.40% Inerts 65.11% Methanol 13.66% Dilution: 1:100 in water %Stain and Mold 28 Days Example Test 1 Test 2 DDBSA 50% X Tetrachlorophenol 34.23% 21 12 2,4,5 trichlorophenol 1.90% Other chlorinated phenols 9.25% Inerts 4.62% Dilution: 1:250 in water XI Borax 57.0% 20 0 Sodium pentachlorophenate 31.6% Other sodium chlorophenates 4.4% Inerts 7.0% Dilution: 10 lbs./100 gal. water In contrast to the foregoing, the control treated with the composition of Example IV evidenced 17% stain and mold in Test 1 and 0% in Test 2.

Example XII The following composition was prepared in accordance with previously stated techniques: Copper hydrate 1.70 8-hydroxy quinoline 4.44 DDBSA 64.81 Methanol 15.05 Isopropanol 14.00 This composition was diluted with water and tested, in comparison with a sodium tetrach lorophenate (23So) liquid concentrate, also diluted in water, against organisms on three species of green lumber Douglas fir, Amabilis fir and Ponderosa pine. The organisms were: a fragrans a brown mold that infests Cephaloascus fragrans certain wood species Trichoderma virgatum a common mold Mixed spores a combination of two molds (Penicillium sp. and Aspergillis niger) and a fungus (Ceratocystis pilifera) that causes blue stain in wood.

The freshly cut wood samples were dip treated (15-second immersion) with the test fungicides and then innoculated with spore suspensions of the above described fungi. The test boards plus untreated control boards were then placed in a warm, humid chamber for four weeks. The results are set forth in the table below in which: A = Douglas fir 0 = no growth B = Amabilis fir 1 = no growth for 2 weeks C = Ponderosa pine 2 = medium growth 3 = heavy growth in 4 weeks 4 = heavy growth in 2 weeks Use C T Mixed Dilution fragrans virgatum spores ABC ABC ABC Tetrachloroprophenol composition 1:100 4 4 4 0 0 3 3 4 4 Example XII composition 1:240 2 0 1 3 0 4 4 3 4 Tetrachlorophenol composition 1:50 2 0 4 0 0 1 3 2 4 Example XII composition 1:120 0 0 1 3 0 1 2 2 2 Tetrachlorophenol composition 1:25 2 2 3 0 0 1 0 0 3 Example XII composition 1::60 0 0 0 1 0 0 0 0 0 Tetrachlorophenol composition 1:12.5 0 1 0 0 0 0 0 0 2 Example XII composition 1:30 0 0 0 0 0 0 0 0 0 Controls (no treatment) 4 4 4 3 4 4 4 4 4 The chlorophenol composition above is typical of the type employed to control sap stain and mold in green lumber. In the case of the tested wood species, the chlorophenol types are noted, however, for poor control of C. fragrans, the result of which is common use of mercury-based fungicides (such as phenyl mercuric acetate) in combination with the chlorophenol to achieve needed control. The composition of Example XII, however, does exhibit superior control of C. fragrans.

Examples XIII to XVII To demonstrate the fungicidal properties of various metal-8-quinolinolates, solutions were prepared using 5 parts of the indicated metal-8-quinolinolate, 64 parts DDBSA and 31 parts methanol.

Metal Quino- % Stain Example linolate 28 Days XIII Copper 17 XIV Tin 20 XV Aluminium 28 XVI Nickel 39 XVII Zinc 46 The foregoing metal -8-quinolinolates also may be prepared by in situ reacting oxine with an appropriate metal in the DDBSA/methanol reaction medium.

Example XVIII A Cu-8-Q fungicidal formulation was prepared utilizing substituted aryl compounds of the alkyl phenol type to demonstrate the effectiveness of a hydroxyl group replacement for the sulfo group as the hydrophilic substituent in the practice of this invention.

Copper hydrate 1.4 8-hydroxy quinoline 4.1 Nonyl phenol 74.5 Heavy aromatic naphtha 20.0 The above mixture of ingredients was heated at 1 800F until solution of the Cu-8-Q, formed in situ, was complete. This composition then was reduced from 5 % Cu-8-Q content to 0.25 % by dilution with mineral spirits.

Cotton duck cloth (10 oz.) was treated to refusal by dip immersion in the test solution, dried and buried in sheep manure saturated with water. At the same time, control cloth was buried as well as cloth treated with a commercial Cu-8-Q composition (Cunilate 2174) solubilized in nickel acetate and 2-ethyl hexoic acid containing 0.25 % Cu-8-Q in a mineral spirits carrier.At the end of 28 days at 75"F, the cloth was removed from the sheep manure, washed and checked for loss in strength, with these results: Strength Loss Untreated cotton duck Very high Example XVIII composition Zero to very low Cunilate 2174 Moderate Example XIX Another test evaluation illustrates the considerable effectiveness of the composition of Example XVIII against Lenzites trabea, a widespread fungus causing destructive wood decay, especially in above-ground locations where very few types of decay fungi can withstand the elevated temperatures encountered. The test method employed is an industry standard -- the National Woodwork Manufacturers' Association M-1-70 Soil Block Test. It consists of treating, by impregnation to saturation, of Ponderosa pine blocks with the test fungicide solution in a toluene carrier.After drying, the blocks are subjected to a severe water leaching procedure, after which the blocks are redried and inoculated with a Lenzites trabea fungus cultrue. At the end of the test period, the blocks are measured for weight loss which indicates the degree of wood decay.

% Weight Loss Example XVIII 0.028% Cu-8-Q 15.0 Example XVIII 0.065% Cu-8-Q 5.6 Cunilate 2174 0.093% Cu-8-Q 21.9 It is plainly evident that the composition of this invention used in this test provides superior protection to the wood.

Xylene, benzene, toluene, Stoddard solvent, heavy petroleum oils and naphthas are suitable for diluting this class of compositions of this invention. Generally, solvents with higher aromaticity provide longer solution stability -- i.e., no precipitation of Cu-8-Q.

Greater solution stability is achieved by increasing the ratio of alkyl phenol to Cu-8-Q and/or by increasing the ratio of alkyl phenol/Cu-8-Q composition to petroleum solvent and/or diluent.

Generally preferred are the alkyl phenols which are liquid at room temperature, particularly nonyl and dodecylphenol because of low cost and commercial availability.

To impart additional water repellency to this class of compositions, waxes and certain resins, including certain silicone and rosm ester resins, may be incorporated, as may other means well known to the art.

Examples XX to XXII To demonstrate the very real synergistic effect achieved in the practice of this invention, Cu-8-Q and DDBSA were tested alone and combined to determine their effectiveness in controlling mold and sap stain on freshly cut lumber.

Example Formulation %Mold 28 Days XX 0.025% Cu-8-Q aqueous 89 dispersion XXI 0.035% DDBSA aqueous 49 solution XXII Mixture* of the solutions 6 of Examples XX and XXI (*agitated for 30-60 minutes before use to allow formation of coordinate bond between Cu-8-Q and DDBSA) Examples XXIII to XXXI As further evidence of the effectiveness of anti-microbicial agents prepared in accordance with this invention, a number of tests were conducted utilizing DDBSA as the substituted aryl compound of this invention coordinated with the blow-listed microbial compounds. A 1:200 use dilution in water was prepared from concentrates containing 65 parts DDBSA, 30 parts methanol, and 5 parts of the anti microbial compound.Fresh-cut green pine test boards were dip-treated and evaluated for stain and mold after 30 days in the aforementione constant atmosphere test chamber: example Microbial Compound %Mold & Stain XXIII Cu-8-Q 3 XXIV 2-(4 -thiazolyl) benzimidazole 14 XXV cis-N -(trichloromethyl) thio 23 4-cyclohexane- 1,2 -dicarboximde XXVI diiodomethyl-para-tolyl sulfone 8 XXVII para-chlorophenol diiodomethyl sulfone 6 XXVIII 2-n-octyl -4-isothiazolin-3-one 10 XXIX 2-benzisothiazolin -3-one 14 XXX 2-(methoxy-carbamoyl) -benzimidazol 2 XXXI 8-hydroxy quinoline 10 In some instances, it may prove advantageous to include other anti microbical compounds in a given formulation to increase the over-all spectrum of antimicrobial activity. Such additional microbical agents need not necessarily be of the type thus far described in this specification.For example, when treating green lumber to inhibit sap stain or mold, it is sometimes desirable, to get broader protection, to include a chlorophenol such as pentachlorophenol, tetrachloropheol, or 2,4,5-trichiorophenol, in the composition of this invention.

It is also within the scope of this invention to include insecticides. Surprisingly, it has been found that when a number of well-known insecticides are added to water-soluble agents of this invention, the insecticide is solubilized and remains so when diluted with water for use.

Insecticides exhibiting such unusual behavior include: 0,0-Dimethyl-S -(1,2-dicarbethoxyethyl) phosphorodithionate; 1,2,4,5,6,7,8,8 -Octochloro -2,3,3a,4,7,7a -hexahydro -4,7-methanoindane; 1,1,1-Trichioro -2,2-bis(p -methoxyphenyl) ethanol; and 1-napthyl N-methylcarbamate.

These widely used insecticides have heretofore been available only in non-water-soluble forms such as dusts, wettable powders and emulsifiable concentrates. Availability as true water solutions offers considerable advantage in handling, mixing, stability and application uniformity.

Example XIII Some of the agents of this invention exhibit unexpected insecticidal activity when compared to a known insecticide (pentachlorophenol). Against termites in a soil burial test in Memphis, Tennessee, the following compositions were evaluated: a Example XII, diluted with water to a 0.25% Cu-8-Q content; b Example XVIII, diluted with mineral spirits to a 0.25% Cu-8-Q content; and (c Cunilate 2174 diluted with mineral spirits to a 0.25% Cu-8-Q content; and (d) A 5.0%pentachlorophenol solution in mineral spirits containing 4% propylene glycol ether to provide sufficient pentachlorophenol solubility and to prevent sublimation from the wood.

Dry southern yellow pine stakes, 3/4" square x 24" long, were dip-impregnated with the test solutions, allowed to dry for one week, and then buried to a depth of 12" in the ground for 15 months, at which time these results were observed: Solution Pickup Termite Treatment (lbs/ft3) Rating* None (Control stakes) -- 36 Example XII 1.79 83 Example XVIII 1.13 80 5% pentachlorophenol 1.28 84 solution Cunilate 2174 1.26 56 (Termite Rating: 0 = stakes totally destroyed; 100 = stakes unattacked) Both agents of this invention exhibited termite control essentially equal to that of the pentachlorophenol solution and definitely superior to both the untreated control stakes and those treated with Cunilate 2174.

Example XXXHI The composition set forth below was prepared by previously described procedures: Copper hydrate 0.70 8-hydroxy quinoline 2.08 Isopropanol 32.00 DDBSA 40.00 Water, demineralized 25.22 When evaluated as a germicide by the A.O.A.C. Use Dilution Method (12th Edition, 1975), use dilution in distilled water, 10 ring carriers per organism (incubated at 270C for 48 hours), the results set forth in the table below were obtained after 10 minutes contact time at 20"C. In the table, A = subculture and B = resubculture.

Negative Positive Use Dilution A B A B Staphylococcus aureus 1:500 10 10 0 0 Salmonella cholerasuis 1:500 10 10 0 0 Pseudomonas aeruginosa 1:400 10 10 0 0 Aerobacter aerogenes 1:500 10 10 0 0 [The calculated acute LD50 Of the foregoing formulationpriorto dilution with water for use is 4160 mg. per kilogram of body weight (rat, oral adminstration)]. A 10-minute kill is required by the Environmental Protection Agency (an agency of the United States government) against the first three pathogens for sale as a hospital germicide. The fourth organism is a major cause of slime in recirculated cooling water systems and pulp and paper mills, thereby indicating the usefulness of the composition as a slimicide.

Example XXXIV Using approved A.O.A.C. methods for fungal evaluation, the composition of Example XXXIII was evaluated as a fungicide againstAspergillis niger (a widespread black mold) and Trichophyton mentagrophytes (known as a cause of "athlete s foot" Aspergillis niger -1:200 use dilution in distilled water - no growth after 10 minutes exposure; Trichophyton mentagrophytes - 1:750 use dilution in distilled water - no growth after 10 minutes exposure.

Similar results are obtained by substituting zinc-8 -quinolinolate or aluminium-8quinolinolate in the composition of this Example; zinc oxide and aluminium hydroxide are reacted respectively with 8-hydroxy quinoline instead of copper hydrate.

Example XXXV Copper hydrate 0.70 8-hydroxy quinoline 2.08 Nonyl phenol-EO surfactant* 20.00 DDBSA 45.00 Isopropanol 15.00 Water, distilled 17.22 (*1 mol nonyl phenol to 6 mols ethylene oxide) The composition was prepared by the procedure already described and evaluated for efficacy against ciliated protozoan and two types of viruses with these results: Hemaglutination Assays HA Titre Virus Untreated Treated (1:50) * Treated (:2OO) * Adenovirus 128 0 0 Newcastle Disease 512 0 0 virus (*1:5 and 1:200 use dilutions of composition in water in contact with virus suspensions for 15 minutes) The HA titre is a measure of the number of infectious virus particles present in the test suspension.Plaque Assays Plaque Assays Via the same procedure as above, the untreated virus suspensions contained 6.4 x 104 pfu/ml of Adenovirus virus particles and 21 x 105 pfu/ml Newcastle Disease virus particles respectively. After treatment with the 1:50 and 1:200 use dilutions, readings of 0 pfu/ml were obtained. Each pfu represents one infectious virus particle. A zero pfu reading represents total inactivation of the infectious virus.

Protozoan Inhibition Inhibition of growth of ciliated protozoan (Tetrahymena) in pond water was obtained at a 6 ppm concentration of test composition after 6 hour and 72 hour contact times. The 6 ppm represents the MIC (Minimum Inhibitory Concentration).

These data illustrate the high efficacy of the composition against the microorganisms tested.

Example XXXVI The agents of this invention exhibit control of a number of plant and crop diseases, as illustrated by using the following composition: Copper hydrate 1.70 8-hydroxy quinoline 4.44 Isopropanol 35.00 DDBSA 58.86 A. Valencia oranges Tested on harvested fruit against Phomopsis stem-end rot and Diplodis rot, at a 1:100 use dilution in water, 2-minute dip application. After 3 weeks at 700F, the following percentages of decay were noted: Control (untreated) organges - 9.5% decay Treated oranges - 5.3% decay B. Sugar Cane An agar seeding test against Ceratocystis paradoxa (causes rotting at the seed pieces) at a 1:10,000 (100 ppm) use dilution in water. At 100 ppm concentration, a 3.0 mm inhibition zone resulted.

C. Peach trees Tested against Taphrina deformans (causes leaf curl disease). Four test trees were sprayed twice, two weeks apart, with a 1:400 use dilution in water. Three months later, 100 leaves on each test tree were rated for leaf curl: Treated leaves 13.5% leaf curl Control (untreated) leaves 100 % leaf curl D.Cotton Effectiveness against six fungi and one bacterium (Xanthomonas malvecearum) that are associated with disease of cottonseed or seedlings and other plants was evaluated in vitro, using the following compositions, #1 and #2: Composition #1 Copper hydrate 1.70 8-hydroxy quinoline 4.44 Methanol 4.00 Isopropanol 30.86 DDBSA 59.00 Composition #2 Copper hydrate 2.80 8-hydroxy quinoline 8.20 Methanol 4.00 Isopropanol 26.00 DDBSA 59.00 Both compositions were prepared in accordance with procedures stated in previous Examples.

The following results were obtained, expressed in terms of parts per million (ppm) of test composition in water and the relative growth inhibition provided at each test strength on each tested organism. In the table below: 0 = no apparent inhibition 1 = some inhibition 2 = considerable inhibition (little growth) 3 = total inhibition (no growth) Composition #1 Concentrations (ppm) Test Organisms 0 1 5 25 100 500 1000 Pythium ultimum (41B) 0 0 0 1 2 3 3 Rhizoctonia solani (1D) 0 0 0 1 2 3 3 Fusarium (4A) 0 0 0 3 3 3 3 Fusarium (4D) 0 1 1 2 2 2 3 Fusarium roseum (4C) 0 0 0 1 2 2 3 Collectotrichum gossypii (35A) 0 0 0 1 2 2 2 Xanthomonas malvacearum (2A) 0 0 0 0 2 2 3 Composition #;2 Concentrations (ppm) Test Organisms 0 1 5 25 100 500 1000 Pythium ultimum (41B) 0 0 1 2 2 2 2 Rhizoctonia solani (1D) 0 0 1 2 2 2 2 Fusarium 4A) 0 0 1 1 1 2 2 Fusarium 4D) 0 0 1 1 2 2 2 Fusarium roseum (4C) 0 0 2 2 2 2 2 Collectotrichum gossypn (35A) 0 0 0 2 2 2 2 Xanthomonas malvacearum (2A) 0 0 0 1 1 2 2 *** Concentrations (ppm) 10 25 50 100 200 500 1000 2000 Aspergillissp. - 0 - 0 - 1 1 Helminthosporium - - - 0 - 2 2 oryzae Mucormucedo - - - 0 - 1 1 Penicilliumsp. - - - 0 - 1 1 Rhizopussp. - - - 0 1 1 It is within the scope of this invention to modify the disclosed compositions to improve performance or alter physical properties to meet the needs of specific end uses. For example, in addition to varying the relative amounts of materials used, modifications for specific end uses can be made as by adding thixotropes, cleansing agents, detergents, soil anti redepositing agents, film-forming agents, and other useful additives.

At high use concentration, some of the agents of the invention, particularly those using the aryl sulfonic acids, may cause skin irritation, but it has been found that this can largely be prevented by variously incorporating minor amounts of a polyvinyl pyrrolidone or a nonyl phenol-ethylen oxide product in the agents of this invention.

Discoloration of substrates may occur, but this frequently can be avoided by contacting the treated substrate, such as wood, with a water solution of monoammonium phosphate.

Darkening may also occur from a chemical reaction, as with iron, and corrosion inhibitors may usefully be included in the agents of this invention.

WHAT WE CLAIM IS: 1. A substituted aryl antimicrobial agent which is water-soluble comprising: an aryl neucleus biasing an olephilic substituent and a hydrophilic substituent; and an antimicrobial compound coordinated with the hydrophilic substituent.

2. An agent according to Claim 1 wherein the olephilic substituent is an alkyl group compatible with the semipermeable membrane of the microbe to be controlled.

3. An agent according to Claim 2 wherein the alkyl group is substantially straightchained and contains between six and twenty-four carbon atoms.

4. An agent according to Claim 2 wherein the alkyl group has six or less carbon atoms and includes a chlorine substituent.

5. An agent according to any of the preceding claims wherein the hydrophilic substituent is water-soluble in the ionizable sense.

6. An agent according to Claim 5 wherein the hydrophilic substituent is a sulfo or hydroxyl group.

7. An agent according to any of the preceding claims wherein the aryl neucleus is a phenyl or naphthyl neucleus.

8. An agent according to any of the preceding claims wherein the antimicrobial compound is a metal chelate of oxine.

9. An agent according to Claim 8 wherein the chelating metal is mercury, copper, cadmium, nickel, tin, aluminium or zinc.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (16)

1. **WARNING** start of CLMS field may overlap end of DESC **.

   Composition #2 Concentrations (ppm) Test Organisms 0 1 5 25 100 500 1000 Pythium ultimum (41B) 0 0 1 2 2 2 2 Rhizoctonia solani (1D) 0 0 1 2 2 2 2 Fusarium 4A) 0 0 1 1 1 2 2 Fusarium 4D) 0 0 1 1 2 2 2 Fusarium roseum (4C) 0 0 2 2 2 2 2 Collectotrichum gossypn (35A) 0 0 0 2 2 2 2 Xanthomonas malvacearum (2A) 0 0 0 1 1 2 2 *** Concentrations (ppm)

   10 25 50 100 200 500 1000 2000 Aspergillissp. - 0 - 0 - 1 1 Helminthosporium - - - 0 - 2 2 oryzae Mucormucedo - - - 0 - 1 1 Penicilliumsp. - - - 0 - 1 1 Rhizopussp. - - - 0 1 1 It is within the scope of this invention to modify the disclosed compositions to improve performance or alter physical properties to meet the needs of specific end uses. For example, in addition to varying the relative amounts of materials used, modifications for specific end uses can be made as by adding thixotropes, cleansing agents, detergents, soil anti redepositing agents, film-forming agents, and other useful additives.

   At high use concentration, some of the agents of the invention, particularly those using the aryl sulfonic acids, may cause skin irritation, but it has been found that this can largely be prevented by variously incorporating minor amounts of a polyvinyl pyrrolidone or a nonyl phenol-ethylen oxide product in the agents of this invention.

   Discoloration of substrates may occur, but this frequently can be avoided by contacting the treated substrate, such as wood, with a water solution of monoammonium phosphate.

   Darkening may also occur from a chemical reaction, as with iron, and corrosion inhibitors may usefully be included in the agents of this invention.

   WHAT WE CLAIM IS: 1. A substituted aryl antimicrobial agent which is water-soluble comprising: an aryl neucleus biasing an olephilic substituent and a hydrophilic substituent; and an antimicrobial compound coordinated with the hydrophilic substituent.
2. 2. An agent according to Claim 1 wherein the olephilic substituent is an alkyl group compatible with the semipermeable membrane of the microbe to be controlled.
3. 3. An agent according to Claim 2 wherein the alkyl group is substantially straightchained and contains between six and twenty-four carbon atoms.
4. 4. An agent according to Claim 2 wherein the alkyl group has six or less carbon atoms and includes a chlorine substituent.
5. 5. An agent according to any of the preceding claims wherein the hydrophilic substituent is water-soluble in the ionizable sense.
6. 6. An agent according to Claim 5 wherein the hydrophilic substituent is a sulfo or hydroxyl group.
7. 7. An agent according to any of the preceding claims wherein the aryl neucleus is a phenyl or naphthyl neucleus.
8. 8. An agent according to any of the preceding claims wherein the antimicrobial compound is a metal chelate of oxine.
9. 9. An agent according to Claim 8 wherein the chelating metal is mercury, copper, cadmium, nickel, tin, aluminium or zinc.
10. 10. An antimicrobial agent comprising an alkyl (C6 to Cl8) benzene sulfonic acid coor

    dinated with a metal chelate of oxine.
11. 11. An antimicrobial agent comprising an alkyl (C6 to Cl8) substituted phenol coordinated through the hydroxyl group with a metal chelate of oxine.
12. 12. An agent according to any of claims 1 to 7 wherein the active antimicrobial compound is an imidazole, a benzimidazole or a thiazole.
13. 13. An agent according to any of Claims 1 to 7 wherein the active antimicrobial compound is 2-(4 -thiazolyl) benzimidazole; diiodomethyl -para-tolyl sulfone; para -chloro-phenol diiodomethyl sulfone; 2-n -octyl4 -isothiazolin -3-one; 2 -benziisothiazolin -3-one; or 8-hydroxy quino ine.
14. 14. A method for controlling microbial growth which comprises coordinating an antimicrobial compound with a disubstituted phenyl or naphthyl in which one of the substituents is oleophilic and the other substituent is hydrophilic, and treating a desired area with the resulting agent.
15. 15. A method according to Claim 14 wherein the growth controlled is baceteria, algae, fungi, viruses, yeasts or protozoa.
16. 16. An antimicrobial agent according to Claim 1 substantially as hereinbefore described.