Patent Application
20230413811
Priority is claimed of European patent application no. 20 199 746.7 that was filed on Oct. 2, 2020 and European patent application no. 20 199 747.5 that was filed on Oct. 2, 2020.
The invention relates to a trialkyl sulfonium chloride, compositions comprising the trialkyl sulfonium chloride, agricultural compositions comprising such compositions and trialkyl sulfonium chloride, respectively, to the use of the trialkyl sulfonium chloride and of the compositions as a pesticide, preferably as a fungicide, and to methods for controlling or combating pests and/or improving plant health by means of the trialkyl sulfonium chloride and compositions. Preferably, the trialkyl sulfonium chloride is octadecyl dimethyl sulfonium chloride.
Fungi are distributed worldwide. Approximately 100 000 different fungal species are known to date. Fungi pose one of the greatest biotic challenges to crop plant health and thus to food security. During the infection of plants by pathogenic fungi, different phases are usually observed. The first phases of the interaction between phytopathogenic fungi and their potential host plants are decisive for the colonization of the plant by the fungus. During the first stage of the infection, the spores become attached to the surface of the plants, germinate, and the fungus penetrates the plant. This may occur at existing ports such as stomata or wounds, but could also involve the formation of specialized penetration structures or the secretion of cell-wall-digesting enzymes. Our most effective strategies to control fungal pathogens on crops are based on the use of fungitoxic chemistries (fungicides). Over the last decades, numerous fungicides have been developed and are commercially available.
Intensive farming practices, such as monoculture cropping—where vast fields of genetically-uniform cultivars, and the rapid generation time foster the development of fungicide resistance in fungal pathogens. This resistance can occur within a few years of fungicide use in the field. Indeed, the rate of emergence of fungicide resistance outpaces the rate of fungicide discovery.
There are currently only a few new fungicides under development and regulatory approval but these are derivatives of commonly-used chemistries, such as those which target ergosterol biosynthesis, cell wall biosynthesis or particular complexes of the mitochondrial respiration chain. However, the fungicides of the prior art are not satisfactory in every respect and there is a demand for improved fungicides.
There is a continuing need for more effective treatments against crop pathogens to secure our future food production. The rapid development of fungicide resistance in market-leader chemistries makes identification of new fungicides a priority. These fungicides should (i) be active against cropdestroying pathogens, (ii) target a fundamental process at multiple sites to reduce resistance development (iii) be of low toxicity to humans and the environment.
One potential target of new fungicides are fungal mitochondria. Fungal mitochondria differ from their mammalian counterpart in the composition and function of respiratory enzymes, which makes them attractive targets for new fungicides. In a canonical respiratory chain in the mitochondria of eukaryotes, there are four basic protein complexes enabling electron transport and proton pumping that result in electrochemical gradient generation and ATP synthesis. In contrast to animals, fungi contain specific types of complexes including the rotenone-insensitive type II NAD(P)H dehydrogenase or alternative NAD(P)H dehydrogenase (NDH-2) and a cyanide-insensitive alternative oxidase (AOX), which all belong to mitochondrial energy-dissipating systems (see e.g. Nina Antos-Krzeminska et al., Protist, Vol. 170, 21-37, February 2019).
Mitochondria are involved in a broad range of cellular processes, but most importantly host the enzymes for oxidative phosphorylation. Oxidative phosphorylation depends on a proton gradient over the inner mitochondrial membrane, which is maintained by electron transfer through the membrane-bound mitochondrial respiration chain complexes. During this process, mitochondria produce reactive oxygen species (mROS), which in fungi was shown to occur at complex I and complex III (Murphy, M. P. How mitochondria produce reactive oxygen species. Biochem. J. 417, 1-13 (2009). These mROS seem to serve intracellular signaling roles and, if deregulated, damage proteins and lipids in the inner mitochondrial membrane and trigger apoptotic cell death. Increasing evidence suggests that such a programmed cell death pathway exists in fungi and targeting this pathway is a promising strategy to develop novel antifungals. (Li, D. et al. Enzymatic dysfunction of mitochondrial complex I of the Candida albicans goal mutant is associated with increased reactive oxidants and cell death. Eukaryot. Cell 10, 672-682 (2011)
Electron-transfer through the respiration chain triggers proton transport across the inner mitochondrial membrane. This leaves the matrix negatively charged and, as such, it becomes a target for lipophilic cations. These molecules, which combine a cationic head group with a lipophilic moiety pass through cellular membranes and accumulate in the inner membrane of the mitochondrion and expose their cationic moiety towards the matrix. This behavior allows delivery of therapeutics into mitochondria, but can also inhibit the respiratory enzymes. Whilst such effect on mitochondria function challenges use of lipophilic cations in medicine, it could be key for the use of lipophilic cations as plant fungicides/antifungals (G. Steinberg et al. A lipophilic cation protects crops against fungal pathogens by multiple modes of action. Nature Communications 11:1608 (2020)). However, the amphiphilic structure of these molecules also suggests that they are inserted into the plasma membrane. Indeed, until recently, antifungal lipophilic n-alkyl chain cations (=cationic surfactants) were thought to kill fungal cells by altering permeability or function of the plasma membrane. However, a recent publication convincingly demonstrated that lipophilic n-alkyl chain cations, namely the fungicide dodine, a C18-sulfonium, and a C18-ammonium salt inhibit fungal oxidative phosphorylation (G. Steinberg et al.).
The best-studied lipophilic n-alkyl chain cations is dodecyl guanidinium, which carries a positively charged guanidinium group and is currently used as the fungicide Syllit (dodine).
FR 1 182 709 A relates to salts of dodecyl-guanidine as fungicides. U.S. Pat. No. 2,867,562 A relates to monocarboxylic acid salts of dodecylguanidine which are highly effective in controlling fungus organisms injurious to the fruit and foliage of fruit trees, and with fungicidal compositions containing these compounds. U.S. Pat. No. 3,143,459 A relates to nonfoaming wettable powder compositions containing active fungicides such as dodecylguanidine acetate and to methods of preparing such compositions. U.S. Pat. No. 3,157,695 A relates to cyclododecylguanidine and its organic and inorganic salts which are said to have parasiticidal, in particular fungicidal properties.
Dodine is a protectant fungicide that is widely used to control fruit scab and foliar diseases in orchards. Dodine's mode of action is controversial, with results supporting a permeabilizing effect in fungal cells, while others reported the inhibition of vital metabolic enzymes. A recent study has demonstrated that the primary mode of action of dodine is the inhibition of mitochondrial respiration (G. Steinberg et al.). While dodine is useful as a fungicide, it has some issues with toxicity in aquatic organisms. Thus, it may cause environmental problems if it is used as a fungicide on crops or soil as this may result in water run-off to bodies of water such as lakes and rivers, for example.
A trialkyl sulfonium iodide salt (n-octadecyl dimethyl sulfonium iodide) was shown to provide increased protection against fungal diseases (namely Septoria tritici blotch in wheat and rice blast disease; G. Steinberg et al.). This trialkyl sulfonium iodide salt blocked oxidative phosphorylation, but also induced mROS development at respiratory complex 1, which in turn induces fungal cell death (apoptosis; G. Steinberg et al.). Moreover, this compound also induces the innate plant defense system (G. Steinberg et al.). In almost all aspects tested, n-octadeyl dimethyl sulfonium iodide is superior in performance and shows less toxicity than dodecyl guanidinium. Salts of n-octadecyl dimethyl sulfonium other than the iodide salt are not disclosed.
Trialkyl sulfonium salts are also known from the prior art for various purposes.
Certain trialkyl sulfonium salts have been used in textile industry. FR 2 256 278 A1 relates to trialkylsulphonium salts as fabric softeners. U.S. Pat. Nos. 3,666,403 and 3,826,609 relate to methods of dyeing a textile fiber in the presence of sulfonium salts such as dimethylstearylsulfonium salts.
A number of sulfonium salts have been found to inhibit specific cellular enzymes and prevent them from carrying out their normal physiological functions. Triphenylsulfonium chloride has been found to inhibit oxidative phosphorylation and adenosine triphosphate activity in addition to the electron-transfer system in the NAD-cytochrome b region of the respiratory chain. Several alkylsulfonium and alkyl disulfonium salts, such as decamethylene bis(dimethylsulfonium) and n-octadecyl dimethyl sulfonium bromides are potent inhibitors of phospholipase. Sulfonium compounds of similar structure can also inhibit cholinesterase (S. Mitchell, Biological Interactions of Sulfur Compounds, Taylor & Francis, 1996, pp. 208-210; P. R. Young et al., Lipids, 26(11), 1991, 957-959).
U.S. Pat. No. 3,235,356 discloses a method of controlling the growth and propagation of plants by applying thereto alkyl dimethyl sulfonium salts such as octadecyl dimethyl sulfonium methosulfate. U.S. Pat. No. 4,475,941 A relates to a process for the destruction or/and inhibition of the growth of microorganisms by means of organic derivatives of tin to which is added a sulfonium function bearing compound such as tetradecyl dimethyl sulfonium methosulfate. U.S. Pat. No. 4,753,961 A discloses bactericidal compositions comprising a trialkyl sulfonium salt, such as tetradecyl dimethyl sulfonium methosulfate (TDSM).
Certain trialkyl sulfonium salts have been reported to exhibit fungicidal activity. FR 2 467 547 A1 relates to sulfonium compounds such as tetradecyl dimethyl sulfonium halides or methosulfates that are said to be useful as bactericides, fungicides, algicides and corrosion inhibitors. U.S. Pat. No. 4,088,781 A relates to sulphonium compounds having a sulfur atom bearing a 2-hydroxy-ethyl group which in addition to their advantageous surface-active properties have a fungicidal activity which can be utilized without harm to plants.
U.S. Pat. No. 4,542,023 A relates to fungicidal salts of organophosphorous derivatives. The cations of these salts can be trialkyl sulfonium cations.
U.S. Pat. No. 4,464,194 A relates to mixed alkylsulfonium salts of N-phosphonomethylglycine such as dimethyl octadecyl sulfonium salt of N-phosphonomethylglycine.
P. R. Young et al., Lipids, Springer, vol. 26(11), 1991, 957-959 discloses that cetyl trimethyl ammonium and n-octadecyl dimethyl sulfonium bromides inhibit the Clostridium perfrigens phospholipase C-catalyzed hydrolysis of 1-S-phosphocholine-2-O-hexadecanoyl-1-mercapto-2-ethanol at pH 7.5, 37° C., μ=0.15 with KCl.
JP S45 36830 B relates to cellulose acetate fibers that may contain 1-30% diethylstearyl-sulfonium chloride.
J. Feihua et al., synthesis of new cationic surfactant containing sulfur and study on their physico-chemical properties, chemical abstracts service, 1994; 194520, 1-2 discloses that sulfine cation surfactants were prepared from high fatty alcohols. e.g. octadecanol, with high yield. The products had good antibacterial effect for staphylococcus and colon bacillus.
FR 810 437 relates to antimicrobial sulfonium salts such as octadecyl dimethyl sulfonium methosulfate.
WO 93/17723 relates to biodegradable surface disinfectants including methyl sulfate of dimethyl octadecyl sulfonium cations.
K. Negoro et al., journal of the Japan oil chemists' society, 27(1), 1978, 47-51 relates to the preparation of alkyl ethyl methyl sulfonium iodide and their physico-chemical, antimicrobial properties. One synthesized species is alkyl: C18H37, i.e. ethyl methyl octadecyl sulfonium iodide.
K. Yamanauchi et al., J. Am. Chem. Soc. 1983, 105, 538-545 relates to a three-phase model of micellar reactions and methylation of thymidine by (long-vhain-alkyl)dimethylsulfonium iodide.
However, the fungicides of the prior art are not satisfactory in every respect and there is a demand for improved fungicides having improved properties, especially with regard to any one of the following properties or combinations thereof: (a) pesticidal, preferably fungicidal activity; (b) biological activity; (c) compatibility with the environment and toxicity; (d) weathering properties such as resistance against UV radiation and solubility in runoff water; (e) compatibility with agricultural additives; (f) solubility in water and in aqueous media under various pH values; (g) dissolution rate in water and in aqueous media; (h) behavior in the solid state such as crystallinity and polymorphism; (i) physical properties such as density; (j) chemical properties such as degradation; (k) spectral and optical properties; (l) thermal properties such as melting point and boiling point; (m) olfactory properties; (n) electrical properties and ionic strength; (o) mechanical properties such as hardness; (p) surface tension; (q) hygroscopicity; (r) pH value; (s) salt character, cation anion interaction, covalent character; (t) ageing; (u) traceability; (v) processability; (w) storage stability and shelf-life; (x) synthetic obtainability; and/or (y) economic aspects.
It would be advantageous to provide cationic surfactant-based antifungal compounds, which improve upon the efficacy of known cationic surfactant-based antifungal compounds against specific fungi or against a wide range of fungi. It would also be advantageous to provide further cationic surfactant-based antifungal compounds with environmental toxicity. It would furthermore be advantageous to provide more effective cationic surfactant-based antifungal compounds, compositions and treatments which target the metabolism of fungi at multiple sites in one or more metabolic pathways. Such fungicides would ideally employ a novel multi-site mode of action, which targets fundamental processes in the pathogenic cell.
Further, it would be advantageous to provide cationic surfactant-based antifungal compounds which are easy to prepare at limited costs, have a good compatibility with additives that are typically contained in compositions, and that contribute to the overall fungicidal performance not only with regard to biological activity, efficacy and potency, but also with regard to applicability, release kinetics, weatherability, and the like.
Furthermore, it would be advantageous to provide cationic surfactant-based antifungal compounds in form of highly concentrated formulations that can be diluted to agricultural formulations by adding suitable diluting agents such as water shortly before use. The highly concentrated formulations may then be shipped at reduced costs. However, the highly concentrated formulations should exhibit sufficient stability of the ingredients contained therein at high concentrations.
It is an object of the invention to provide pesticides, particularly fungicides that have advantages compared to the prior art. They should be benign to the environment, specific for pests to be treated or prevented, suitable for treating a large variety of different plants and combating a large variety of different harmful pests, particularly fungi. Further, they should have a prolonged eradicating persistent effect such that a certain while after treatment the pests, particularly fungi do not retain their original harmful effect.
This object has been achieved by the subject-matter of the patent claims.
A first aspect of the invention relates to a trialkyl sulfonium chloride according to general formula (A)
wherein
Thus, the trialkyl sulfonium salts according to the invention differ from n-octadecyl dimethyl sulfonium iodide according to G. Steinberg et al. cited above in the counter anion (chloride vs. iodide).
Four alternative NAD(P)H dehydrogenases have been cloned and characterized in the mitochondria of the filamentous fungus N. crassa. One of these enzymes is directed towards mitochondrial matrix (NDI1), while three others are directed externally (NDE1-3). Among these alternative dehydrogenases, NDE2 has been suggested to play a major role in ROS generation in the N. crassa mitochondria (see e.g. Nina Antos-Krzeminska et al., Protist, Vol. 170, 21-37, February 2019). However, recent work in Z. tritici indicates that respiratory complex I is another main source of mROS in fungi (G. Steinberg et al.).
Unexpectedly, the trialkyl sulfonium chlorides, preferably octadecyl dimethyl sulfonium chloride according to the invention are superior over the respective bromides and iodides. While with respect to depolarization of mitochondria and ability to induce mitochondrial ROS formation no significant differences could be observed for the chlorides, bromides and iodides, the chlorides according to the invention provide significant benefit with respect to inducing apoptotic cell death compared to the respective bromides and iodides.
Furthermore, it has been surprisingly found that trialkyl sulfonium salts having a minimum alkyl chain length C18 (octadecyl, stearyl) at residue R3 are capable of suppressing mitochondrial activity, whereas comparative trialkyl sulfonium salts having shorter alkyl chain length at residue R3 show no corresponding effect, irrespective of the counter anion.
There is experimental indication that certain salts of trialkyl sulfonium, particularly the trialkyl sulfonium chlorides, are more stable than others, especially under UV-light.
When the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is present in form of a solvate, the type and stoichiometry of the solvate is not particularly limited. In preferred embodiments, the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is a hydrate, preferably selected from hemihydrate, monohydrate and dihydrate. In other preferred embodiments, the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is an anhydrite, preferably an ansolvate.
Preferably, the trialkyl sulfonium chloride according to the invention is selected from n-octadecyl dimethyl sulfonium chloride, n-octadecyl methyl ethyl sulfonium chloride, n-octadecyl diethyl sulfonium chloride, n-octadecyl methyl propyl sulfonium chloride, n-octadecyl ethyl propyl sulfonium chloride, n-octadecyl dipropyl sulfonium chloride; n-eicosyl dimethyl sulfonium chloride, n-eicosyl methyl ethyl sulfonium chloride, n-eicosyl diethyl sulfonium chloride, n-eicosyl methyl propyl sulfonium chloride, n-eicosyl ethyl propyl sulfonium chloride, n-eicosyl dipropyl sulfonium chloride; n-docosyl dimethyl sulfonium chloride, n-docosyl methyl ethyl sulfonium chloride, n-docosyl diethyl sulfonium chloride, n-docosyl methyl propyl sulfonium chloride, n-docosyl ethyl propyl sulfonium chloride, and n-docosyl dipropyl sulfonium chloride.
Preferably, the trialkyl sulfonium chloride according to the invention is n-octadecyl dimethyl sulfonium chloride:
In a preferred embodiment, the trialkyl sulfonium chloride, preferably the n-octadecyl dimethyl sulfonium chloride, is a solid, preferably amorphous, crystalline or semi-crystalline.
In another preferred embodiment, the trialkyl sulfonium chloride, preferably the n-octadecyl dimethyl sulfonium chloride, is a liquid or a semi-solid.
It is contemplated that the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, according to general formula (A) may be present in admixture with one or more other trialkyl sulfonium chlorides according to general formula (A).
Another aspect of the invention relates to a composition comprising a trialkyl sulfonium chloride according to the invention as described above or a solvate thereof.
It is contemplated that the composition according to the invention may contain two or more trialkyl sulfonium chlorides according to general formula (A).
Preferably, the composition according to the invention comprises an agriculturally acceptable carrier, wherein the content of the carrier is at least 1.0 wt.-%, relative to the total weight of the composition.
In preferred embodiments of the composition according to the invention, the content of the carrier is at least 2.5 wt.-%; preferably at least 5.0 wt.-%, preferably at least 7.5 wt.-%, preferably at least 10 wt.-%, preferably at least 15 wt.-%, preferably at least 20 wt.-%, preferably at least 25 wt.-%, preferably at least 30 wt.-%, preferably at least 40 wt.-%, preferably at least 50 wt.-%, preferably at least 60 wt.-%, preferably at least 70 wt.-%, preferably at least 80 wt.-%, preferably at least 90 wt.-%; in each case relative to the total weight of the composition.
In preferred embodiments, the content of the carrier is at most 97.5 wt.-%, preferably at most 95 wt.-%, preferably at most 92.5 wt.-%, preferably at most 90 wt.-%, preferably at most 87.5 wt.-%, preferably at most 85 wt.-%, preferably at most 82.5 wt.-%, preferably at most 80 wt.-%, in each case relative to the total weight of the composition.
In preferred embodiments, the content of the carrier is within the range of 10±5.0 wt.-%, preferably 20±15 wt.-%, preferably 20±10 wt.-%, preferably 20±5.0 wt.-%, preferably 30±25 wt.-%, preferably 30±20 wt.-%, preferably 30±15 wt.-%, preferably 30±10 wt.-%, preferably 30±5.0 wt.-%, preferably 40±35 wt.-%, preferably 40±30 wt.-%, preferably 40±25 wt.-%, preferably 40±20 wt.-%, preferably 40±15 wt.-%, preferably 40±10 wt.-%, preferably 40±5.0 wt.-%, preferably 50±45 wt.-%, preferably 50±40 wt.-%, preferably 50±35 wt.-%, preferably 50±30 wt.-%, preferably 50±25 wt.-%, preferably 50±20 wt.-%, preferably 50±15 wt.-%, preferably 50±10 wt.-%, preferably 50±5.0 wt.-%, preferably 60±35 wt.-%, preferably 60±30 wt.-%, preferably 60±25 wt.-%, preferably 60±20 wt.-%, preferably 60±15 wt.-%, preferably 60±10 wt.-%, preferably 60±5.0 wt.-%, preferably 70±25 wt.-%, preferably 70±20 wt.-%, preferably 70±15 wt.-%, preferably 70±10 wt.-%, preferably 70±5.0 wt.-%, preferably 80±15 wt.-%, preferably 80±10 wt.-%, preferably 80±5.0 wt.-%, preferably 90±5.0 wt.-%, in each case relative to the total weight of the composition.
In preferred embodiments of the composition according to the invention, especially when the composition is a liquid, the carrier is selected from the group consisting of
and combinations thereof.
In preferred embodiments of the composition according to the invention, the carrier is or comprises water.
In preferred embodiments of the composition according to the invention, the carrier is a solvent. Preferably, the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is completely dissolved in the carrier.
In preferred embodiments of the composition according to the invention, especially when the composition is a solid, the carrier is selected from the group consisting of
The constitution of the composition according to the invention is not particularly limited. Preferably, the composition is selected from solutions, suspensions, emulsions, gels, mousses, pastes, powders and granules. Aqueous suspensions are preferred.
In preferred embodiments, the composition according to the invention is a liquid or a paste.
Preferably, the composition according to the invention has a dynamic viscosity at 23° C. of at least 0.5 mPa·s; preferably at least 0.6 mPa·s, preferably at least 0.7 mPa·s, preferably at least 0.8 mPa·s, preferably at least 0.9 mPa·s, preferably at least 1.0 mPa·s.
Preferably, the composition according to the invention has a dynamic viscosity at 23° C. of at most 10,000 mPa·s; preferably at most 9,000 mPa·s, preferably at most 8,000 mPa·s, preferably at most 7,000 mPa·s, preferably at most 6,000 mPa·s, preferably at most 5,000 mPa·s, preferably at most 4,000 mPa·s, preferably at most 3,000 mPa·s, preferably at most 2,000 mPa·s, preferably at most 1,000 mPa·s, preferably at most 900 mPa·s, preferably at most 800 mPa·s, preferably at most 700 mPa·s, preferably at most 600 mPa·s, preferably at most 500 mPa·s, preferably at most 400 mPa·s, preferably at most 300 mPa·s, preferably at most 200 mPa·s, preferably at most 100 mPa·s, preferably at most 90 mPa·s, preferably at most 80 mPa·s, preferably at most 70 mPa·s, preferably at most 60 mPa·s, preferably at most 50 mPa·s, preferably at most 40 mPa·s, preferably at most 30 mPa·s, preferably at most 20 mPa·s, preferably at most 10 mPa·s.
The dynamic viscosity is preferably determined in accordance with EN ISO 3104 or ASTM D7042.
Preferably, the composition according to the invention is aqueous and has a pH value that provides a satisfactory balance of solubility of trialkyl sulfonium chloride, stability of trialkyl sulfonium chloride, and compatibility with the environment, typically after dilution of a composition having a comparatively high concentration of trialkyl sulfonium chloride to an agricultural composition having the desired lower concentration of trialkyl sulfonium chloride to be used for agricultural purposes, i.e. to be contacted with crops. The pH dependency of the solubility of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, may play an important role. It is principally desirable that the solubility of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, on the one hand is comparatively high when it is provided in a form suitable to be deployed in the fields, and on the other hand is comparatively low when it is subsequently subjected to weathering in the fields thereby preventing that it is quickly taken away and rinsed off by rain and other runoff waters.
It has been surprisingly found that the water solubility of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, has a minimum around pH 7.0, i.e. its water solubility increases at pH values below 7.0 and likewise at pH values above 7.0. This solubility behavior is particularly advantageous because highly concentrated compositions to be deployed in the fields can be prepared at pH values below 7.0 or above 7.0. Once such compositions have been deployed in the fields, the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is exposed to environmental conditions altering the pH value towards neutral pH value, e.g. by rain. The resultant pH shift relatively reduces the water solubility of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, thereby decreasing its tendency to be rinsed off.
Preferably, the composition according to the invention is aqueous and has a pH value within the range of from 2 to 14; preferably 3 to 13; more preferably 8 to 13.
In preferred embodiments, the composition according to the invention has a pH value of at least 1.0; preferably at least 1.5, preferably at least 2.0, preferably at least 2.5, preferably at least 3.0, preferably at least 3.5, preferably at least 4.0, preferably at least 4.5, preferably at least 5.0, preferably at least preferably at least 6.0, preferably at least 6.5, preferably at least 7.0, preferably at least 7.5, preferably at least 8.0, preferably at least 8.5, preferably at least 9.0, preferably at least 9.5, preferably at least preferably at least 10.5, preferably at least 11.
In preferred embodiments, the composition according to the invention has a pH value of at most 14, preferably at most 13.5, preferably at most 13, preferably at most 12.5, preferably at most 12, preferably at most 11.5, preferably at most 11.0, preferably at most 10.5, preferably at most 10.0, preferably at most 9.5, preferably at most 9.0, preferably at most 8.5, preferably at most 8.0, preferably at most 7.5.
In preferred embodiments, the composition according to the invention has a pH value within the range of 2.0±1.0, preferably 3.0±2.0, preferably 3.0±1.0, preferably 4.0±3.0, preferably 4.0±2.0, preferably 4.0±1.0, preferably 5.0±4.0, preferably 5.0±3.0, preferably 5.0±2.0, preferably 5.0±1.0, preferably 6.0±5.0, preferably 6.0±4.0, preferably 6.0±3.0, preferably 6.0±2.0, preferably 6.0±1.0, preferably 7.0±6.0, preferably 7.0±5.0, preferably 7.0±4.0, preferably 7.0±3.0, preferably 7.0±2.0, preferably 7.0±1.0, preferably 8.0±5.0, preferably 8.0±4.0, preferably 8.0±3.0, preferably 8.0±2.0, preferably 8.0±1.0, preferably 9.0±4.0, preferably 9.0±3.0, preferably 9.0±2.0, preferably 9.0±1.0, preferably preferably 10±2.0, preferably 10±1.0, preferably 11±2.0, preferably 11±1.0, preferably 12±1.0.
In a preferred embodiment, the composition according to the invention has a pH value within the range of 3.0±2.5, more preferably 3.0±2.0, still more preferably 3.0±1.5, yet more preferably 3.0±1.0, even more preferably 3.0±0.5. In another preferred embodiment, the composition according to the invention has a pH value within the range of 4.0±3.5, more preferably 4.0±3.0, still more preferably 4.0±2.5, yet more preferably 4.0±2.0, and most preferably 4.0±1.0. In still another preferred embodiment, the composition according to the invention has a pH value within the range of 5.0±4.0, more preferably 5.0±3.0, still more preferably 5.0±2.0, and most preferably 5.0±1.0. In yet another preferred embodiment, the composition according to the invention has a pH value within the range of 6.0±5.0, more preferably 6.0±4.0, still more preferably 6.0±3.0, even more preferably 6.0±2.0, and most preferably 6.0±1.0. In a preferred embodiment, the composition according to the invention has a pH value within the range of 7.0±6.0, more preferably 7.0±5.0, still more preferably 7.0±4.0, yet more preferably 7.0±3.0, even more preferably 7.0±2.0, and most preferably 7.0±1.0. In another preferred embodiment, the composition according to the invention has a pH value within the range of 8.0±5.0, more preferably 8.0±4.0, still more preferably 8.0±3.0, yet more preferably 7.0±2.0, and most preferably 8.0±1.0. In still another preferred embodiment, the composition according to the invention has a pH value within the range of 9.0±4.0, more preferably 9.0±3.0, still more preferably 9.0±2.0, and most preferably 9.0±1.0. In yet another preferred embodiment, the composition according to the invention has a pH value within the range of 10±4.0, more preferably 10±3.0, still more preferably 10±2.0, and most preferably 10±1.0. In another preferred embodiment, the composition according to the invention has a pH value within the range of 11±3.0, more preferably 11±2.0, still more preferably 11±1.0. In still another preferred embodiment, the composition according to the invention has a pH value within the range of 12±2.0, more preferably 12±1.0.
In preferred embodiments, the composition according to the invention has a pH value below 7.0, preferably of at most 6.5.
In other preferred embodiments, the composition according to the invention has a pH value above 7.0, preferably of at least 7.5.
Preferably, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is more than 0.1 wt.-%, relative to the total weight of the composition.
In preferred embodiments, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is at least 0.5 wt.-%, preferably at least 1.0 wt.-%, preferably at least 2.5 wt.-%, preferably at least 5 wt.-%, preferably at least 7.5 wt.-%, preferably at least 10 wt.-%, preferably at least 12.5 wt.-%, preferably at least 15 wt.-%, preferably at least 17.5 wt.-%, preferably at least 20 wt.-%, in each case relative to the total weight of the composition.
In preferred embodiments, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is at most 97.5 wt.-%, preferably at most 95 wt.-%, preferably at most 92.5 wt.-%, preferably at most 90 wt.-%, preferably at most 87.5 wt.-%, preferably at most 85 wt.-%, preferably at most 82.5 wt.-%, preferably at most 80 wt.-%, in each case relative to the total weight of the composition.
Preferably, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is within the range of from 10 to 80 wt.-%, relative to the total weight of the composition.
In preferred embodiments, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is within the range of 10±5.0 wt.-%, preferably 20±15 wt.-%, preferably 20±10 wt.-%, preferably 20±5.0 wt.-%, preferably 30±25 wt.-%, preferably 30±20 wt.-%, preferably 30±15 wt.-%, preferably 30±10 wt.-%, preferably 30±5.0 wt.-%, preferably 40±35 wt.-%, preferably 40±30 wt.-%, preferably 40±25 wt.-%, preferably 40±20 wt.-%, preferably 40±15 wt.-%, preferably 40±10 wt.-%, preferably 40±5.0 wt.-%, preferably 50±45 wt.-%, preferably 50±40 wt.-%, preferably 50±35 wt.-%, preferably 50±30 wt.-%, preferably 50±25 wt.-%, preferably 50±20 wt.-%, preferably 50±15 wt.-%, preferably 50±10 wt.-%, preferably 50±5.0 wt.-%, preferably 60±35 wt.-%, preferably 60±30 wt.-%, preferably 60±25 wt.-%, preferably 60±20 wt.-%, preferably 60±15 wt.-%, preferably 60±10 wt.-%, preferably 60±5.0 wt.-%, preferably 70±25 wt.-%, preferably 70±20 wt.-%, preferably 70±15 wt.-%, preferably 70±10 wt.-%, preferably 70±5.0 wt.-%, preferably 80±15 wt.-%, preferably 80±10 wt.-%, preferably 80±5.0 wt.-%, preferably 90±5.0 wt.-%, in each case relative to the total weight of the composition.
In other preferred embodiments, the composition according to the invention is a solid.
In preferred embodiments of the composition according to the invention, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is at least 2.5 μg/g; preferably at least 5.0 μg/g, preferably at least 7.5 μg/g, preferably at least 10 μg/g, preferably at least 15 μg/g, preferably at least 20 μg/g, preferably at least 25 μg/g, preferably at least 30 μg/g, preferably at least 40 μg/g, preferably at least 50 μg/g, preferably at least 60 μg/g, preferably at least 70 μg/g, preferably at least 80 μg/g, preferably at least 90 μg/g, in each case relative to the total weight of the composition.
In preferred embodiments of the composition according to the invention, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is at most 200 μg/g, preferably at most 190 μg/g, preferably at most 180 μg/g, preferably at most 170 μg/g, preferably at most 160 μg/g, preferably at most 150 μg/g, preferably at most 140 μg/g, preferably at most 130 μg/g, preferably at most 120 μg/g, preferably at most 110 μg/g, preferably at most 100 μg/g, preferably at most 90 μg/g, preferably at most 80 μg/g, preferably at most 70 μg/g, preferably at most 60 μg/g, preferably at most μg/g, preferably at most 40 μg/g, preferably at most 30 μg/g, preferably at most 20 μg/g, preferably at most 10 μg/g, in each case relative to the total weight of the composition.
Besides the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, and the preferably present agriculturally acceptable carrier, the composition according to the invention may further comprise one or more additives. Preferred additives include but are not limited to pH buffering agents, thickening agents, deposition agents (stickers), water conditioning agents, wetting agents, spreading agents, humectants, leaf cuticle and/or cell membrane penetration aids, surfactants, plant growth enhancers, foaming agents, defoaming agents, drift control agents, spray drift reducing agents, evaporation reducing agents, dyes, UV absorbents, and combinations thereof. Such additives are known to the skilled person and commercially available, as individual compounds or as mixtures (masterbatches). They may be contained in the composition according to the invention in usual amounts.
The additives may be in the form of a crop protectant spray additive and/or surfactants. The additives may increase the permeability of plant cuticles and/or cell membranes. The additives may be non-ionic spreading and penetration aids; and/or act to reduce surface tension of the composition.
The additives may enhance the fungicidal activity of the trialkyl sulfonium chloride, for example by increasing permeability of cuticles and/or cell membranes. The additives may enhance the fungicidal activity of the trialkyl sulfonium chloride, for example by increasing permeability of plant cuticles and/or cell membranes.
In preferred embodiments, the composition according to the invention further comprises a surfactant in addition to the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, according to the invention, which may be regarded as a cationic surfactant itself. Surfactants reduce surface tension in the spray droplets of the composition, when the composition is applied to a material (such as a surface, plant leaf, etc.), which aids the composition to spread out and cover the target material with a thin film, leading to more effective or quicker absorption of the composition into the material. Surfactants may also affect the absorption of the composition when sprayed on stems or leaves of a plant, by changing the viscosity and crystalline structure of waxes on leaf and stem surfaces, so that they are more easily penetrated by the trialkyl sulfonium chloride. The surfactant may be chosen to enhance the antifungal properties of the composition, through any one or more of:
It is contemplated that the composition according to the invention comprises a single surfactant in addition to the trialkyl sulfonium chloride, or a combination of two or more surfactants. Each surfactant may independently be selected from non-ionic surfactants, ionic surfactants, amphoteric surfactants, a zwitterionic surfactants, and combinations thereof.
Non-ionic surfactants are generally biodegradable and are compatible with many fertilizers. Some non-ionic surfactants are waxy solids and require a liquid carrier (co-solvent such as alcohol or glycol) to solubilize into liquids. Glycol carriers are generally preferred over alcohols, as the latter are flammable, evaporate quickly, and may increase the number of fine spray droplets (making the formulation likely to drift when sprayed). Preferred non-ionic surfactants include silicone surfactants (such as siloxanes and organosiloxanes). Silicone surfactants significantly reduce surface tension of the composition, enabling the composition, in use, to form a thin layer on a leaf or stem surface of a plant. Silicone surfactants also decrease surface tension and may allow the composition to penetrate the stomates of a plant leaf. Silicone surfactants also provide a protective effect to the compositions of the invention by making the compositions very difficult to wash off after they are applied. Silicone surfactants can also influence the amount/rate of absorption of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, through the cuticle of a leaf. Preferred non-ionic surfactants further include carbamide surfactants (urea surfactants). The carbamide surfactants may comprise monocarbamide dihydrogen sulfate, for example.
Suitable ionic surfactants may be selected from cationic surfactants and anionic surfactants. Preferred cationic surfactants include tallow amine ethoxylates. Preferred anionic surfactants include sulfates, carboxylates, and phosphates attached to lipophilic hydrocarbons, including linear alkylbenzene sulfonates, for example.
Amphoteric surfactants typically function similarly to non-ionic surfactants. Preferred amphoteric surfactants include lecithin (phosphatidylcholine) and amidopropylamines, for example.
Wetting agents or spreading agents lower surface tension in the compositions, and allow the compositions to form a large, thin layer on the leaves and stems of a target plant. Preferred wetting agents or spreading agents include non-ionic surfactants that are preferably diluted with water, alcohol, or glycols; polyglycerol fatty esters; and polyglycols.
Drift control agents or spray drift control agents are preferably used to reduce spray drift of the composition, for example when the composition is sprayed onto a plant, which most often results when fine spray droplets (<150 μm diameter) are carried away from the target area by air currents. Drift control agents alter the viscoelastic properties of the spray solution, yielding a coarser spray with greater mean droplet sizes and weights, and minimizing the number of small, easily-airborne droplets. Suitable drift control agents include polymers such as polyacrylamides, polysaccharides and gums.
Preferred deposition agents (stickers) include film-forming vegetable gels, emulsifiable resins, emulsifiable mineral oils, waxes, and water-soluble polymers, for example. Deposition agents may be used to reduce losses of composition from the target plant, due to the evaporation of the composition from the target surface, or beading-up and falling off of the composition. Deposition agents are particularly suitable for compositions of the invention in the form of dry (wettable) powder and granule formulations.
De-foaming and antifoam agents reduce, suppress or destroy the formation of foam in containers in which the compositions of the invention may be contained. Preferred de-foaming agents include oils, polydimethylsiloxanes and other silicones, alcohols, stearates and glycols, for example.
The composition according to the invention may comprise one or more further antifungal agents.
Preferred further antifungal agents are independently of one another selected from
Preferred further antifungal agents are independently of one another selected from azoles; amino-derivatives; strobilurins; specific anti-oidium compounds; aniline-pyrimidines; benzimidazoles and analogues; dicarboximides; polyhalogenated fungicides; systemic acquired resistance (SAR) inducers; phenylpyrroles; acylalanines; anti-peronosporic compounds; dithiocarbamates; arylamidines; phosphorous acid and its derivatives; fungicidal copper compounds; plant-based oils (botanicals); chitosan; sulfur-based fungicides; fungicidal amides; and nitrogen heterocycles; or any combination thereof.
The composition according to the invention as described above is preferably a pre-mix concentrate, more preferably a pre-mix suspension concentrate, still more preferably an aqueous pre-mix suspension concentrate.
Before use, the pre-mix concentrate according to the invention is preferably diluted, preferably with water, by between 2 and 500 times, such as 10 times, preferably 20 times, preferably 50 times, preferably 100 times, preferably 200 times, preferably 250 times.
Another aspect of the invention relates to an agricultural composition, preferably a ready-to-use aqueous composition comprising:
Thus, carrier and diluent may both be water. For the purpose of the specification different terms are used, while in the agricultural composition thus prepared, depending upon the individual situation, it may not be possible any more to distinguish between diluent and carrier.
Another aspect of the invention relates to a method for the preparation of an agricultural composition, preferably a ready-to-use aqueous composition comprising adding a diluent, preferably water to the composition according to the invention as described above.
All preferred embodiments of the composition according to the invention as described above analogously apply to the agricultural composition according to the invention. The essential difference between the composition according to the invention, i.e. preferably the pre-mix concentrate, more preferably a pre-mix suspension concentrate, still more preferably an aqueous pre-mix suspension concentrate as described above on the one hand, and the agricultural composition according to the invention on the other hand is the content of the ingredients, relative to the total weight of the composition and relative to the total weight of the agricultural composition. While adding diluent increases the total weight of the agricultural composition, the content of its ingredients is relatively decreased. When the diluent is identical to the carrier or to one of the constituents of the carrier, the content of carrier is relatively increased by adding further carrier (i.e. diluent).
In preferred embodiments of the agricultural composition according to the invention, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is at least 2.5 μg/ml; preferably at least 5.0 μg/ml, preferably at least 7.5 μg/ml, preferably at least 10 μg/ml, preferably at least 15 μg/ml, preferably at least 20 μg/ml, preferably at least 25 μg/ml, preferably at least 30 μg/ml, preferably at least 40 μg/ml, preferably at least 50 μg/ml, preferably at least 60 μg/ml, preferably at least 70 μg/ml, preferably at least 80 μg/ml, preferably at least 90 μg/ml, in each case relative to the total weight of the agricultural composition.
In preferred embodiments of the agricultural composition according to the invention, the content of the trialkyl sulfonium chloride, preferably octadecyl dimethyl sulfonium chloride, is at most 200 μg/ml, preferably at most 190 μg/ml, preferably at most 180 μg/ml, preferably at most 170 μg/ml, preferably at most 160 μg/ml, preferably at most 150 μg/ml, preferably at most 140 μg/ml, preferably at most 130 μg/ml, preferably at most 120 μg/ml, preferably at most 110 μg/ml, preferably at most 100 μg/ml, preferably at most 90 μg/ml, preferably at most 80 μg/ml, preferably at most 70 μg/ml, preferably at most 60 μg/ml, preferably at most 50 μg/ml, preferably at most 40 μg/ml, preferably at most 30 μg/ml, preferably at most 20 μg/ml, preferably at most 10 μg/ml, in each case relative to the total weight of the agricultural composition.
Another aspect of the invention relates to the use of a composition according to the invention as described above as a pesticide, preferably as a fungicide. The use according to the invention preferably encompasses contacting the pests, their habitat, materials or plants to be protected against attack by the pests, the soil, the lotus where the plant is growing, the lotus where the plant is to grow or propagation material with a pesticidally effective amount of a composition according to the invention.
Another aspect of the invention relates to a method for controlling or combating pests and/or improving plant health comprising contacting the pests, their habitat, materials or plants to be protected against attack by the pests, the soil, the lotus where the plant is growing, the lotus where the plant is to grow or propagation material with a pesticidally effective amount of a composition according to the invention as described above.
Preferably, the pests are fungi; preferably harmful fungi; preferably phytopathogenic harmful fungi.
In preferred embodiments, the fungi are selected from the group consisting of
Preferred plant pathogenic fungi and oomycete species against which the composition according to the invention can be used include Basidiomycetes, Ascomycetes, Deuteromycetes or imperfect fungi, Chytridiomycetes, Zygomycetes, Microspolidia and Oomycetes. Amongst these, but not exclusively, are Puccinia spp., Ustilago spp, Tilletia spp., Uromyces spp., Phakopsora spp., Rhizoctonia spp., Erysiphe spp., Sphaerotheca spp., Podosphaera spp., Uncinula spp., Helminthosporium spp., Rhynchosporium spp., Pyrenophora spp., Monilinia spp., Sclerotinia spp., Septoria spp. (Mycosphaerella spp., Zymoseptoria spp.), Venturia spp., Botrytis spp., Alternaria spp., Fusarium spp., Cercospora spp., Cercosporella herpotrichoides, Colletotrichum spp., Pyricularia oryzae, Sclerotium spp., Phytophthora spp., Pythium spp., Plasmopara viticola, Peronospora spp., Pseudoperonospora cubensis, Bremia lactucae.
In preferred embodiments, the fungi belong to division Ascomycota, preferably to class Dothideomycetes, more preferably to order Capnodiales, still more preferably to family Mycosphaerellaceae, yet more preferably to genus Septoria, and most preferably are species Septoria tritci.
In preferred embodiments, the fungi belong to Glade SAR, preferably to phylum Oomycota, more preferably to order Peronosporales, still more preferably to family Peronosporaceae. Preferably, the fungi belong to genus Plasmopara, preferably are species Plasmopara viticola. Preferably, the fungi belong to genus Phytophthora, preferably are species Phytophthora infestans.
Specific fungal species infections, against which the composition according to the invention can be used include: Ensiphe graminis in cereals, Zymoseptoria tritici in cereals (especially wheat), Magnaporthe oryzae in cereals (especially rice), Erysiphe cichoracearum and Sphaerotheca fuliginea in cucurbits, Podosphaera leucotricha in apples, Uncinula necator in vines, Venturia inaequalis (scab) in apples, Helminthosporium species in cereals, Septoria nodorum in wheat, Botrytis cinerea (gray mold) in strawberries and grapes, Cercospora arachidicola in groundnuts, Pseudocercosporella herpotrichoides in wheat and barley, Pyricularia oryzae in rice, Fusarium and Verticillium species in various plants, and Alternaria species in fruit and vegetables.
Examples of plant fungal diseases against which the composition according to the invention can be used include, but are not limited to: blotch (particularly wheat blotch), rot, Fusarium wilt disease, canker rot, black root rot, Thielaviopsis root rot, blast (particularly rice blast), cottony rot, smuts, soybean rust, cereal rust, potato blight, mildew, clubroot, anthracnose, damping-off, Rhizictonia rot, bottom rot, cavity spot, target spot, leaf blight, septoria spot, ling spot, black leg, stem blight, black knot, ergot, leaf blister, scab, snow mold, sooty mold and Verticillium wilt.
The use according to the invention and the method according to the invention preferably encompasses treatment of a plant pathogenic disease which is preferably caused by a fungal disease. The plant pathogenic disease may be fungal disease of a plant or its seeds, such as, for example cereals (wheat, barley, lye, oats, rice, maize, sorghum, etc.), fruit trees (apples, pears, plums, peaches, almonds, cherries, bananas, grapes, strawberries, raspberries, blackberries, etc.), citrus trees (oranges, lemons, mandarins, grapefruit, etc.), legumes (beans, peas, lentils, soybean, etc.), vegetables (spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, eggplants, peppers, etc.), cucurbitaceae (pumpkins, zucchini, cucumbers, melons, watermelons, etc.), oleaginous plants (sunflower, rape, peanut, castor, coconut, etc.), tobacco, coffee, tea, cocoa, sugar beet, sugar cane, cotton, or horticultural plants.
Preferably, the plant is selected from the group consisting of agricultural plants, horticultural plants, ornamental plants, and silvicultural plants. Preferably, the plant is a field crop.
For the purpose of the specification, the term “plant” is synonymous to the term “crop” which is to be understood as a plant of economic importance and/or a men-grown plant. The term “plant” as used herein includes all parts of a plant such as germinating seeds, emerging seedlings, herbaceous vegetation as well as established woody plants including all belowground portions (such as the roots) and aboveground portions.
In preferred embodiments, the plant is an agricultural plant. For the purpose of the specification, “agricultural plants” are plants of which a part (e.g. seeds) or all is harvested or cultivated on a commercial scale or which serve as an important source of feed, food, fibers (e.g. cotton, linen), combustibles (e.g. wood, bioethanol, biodiesel, biomass) or other chemical compounds. Preferred agricultural plants are for example a) cereals, e.g. wheat, rye, barley, triticale, oats, sorghum or rice, beet, e.g. sugar beet or fodder beet; b) fruits, such as pomes, stone fruits or soft fruits, e.g. apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, blackberries or gooseberries; leguminous plants, such as lentils, peas, alfalfa or soybeans; c) oil plants, such as rape, oil-seed rape, canola, linseed, mustard, olives, sunflowers, coconut, cocoa beans, castor oil plants, oil palms, ground nuts or soybeans; d) cucurbits, such as squashes, cucumber or melons; e) fiber plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruits or mandarins; g) vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, cucurbits or paprika; h) lauraceous plants, such as avocados, cinnamon or camphor; i) energy and raw material plants, such as corn, soybean, rape, canola, sugar cane or oil palm; j) tobacco; k) nuts; l) coffee; m) tea; n) bananas; o) vines (table grapes and grape juice grape vines); p) hop; q) turf; and r) natural rubber plants.
Preferred agricultural plants are field crops such as potatoes, sugar beets, cereals such as wheat, rye, barley, oats, sorghum, rice, corn, cotton, rape, oilseed rape and canola, legumes such as soybeans, peas and field beans, sunflowers, sugar cane, vegetables such as cucumbers, tomatoes, onions, leeks, lettuce and squashes. Preferred agricultural plants are selected from soybean, sunflower, corn, cotton, canola, sugar cane, sugar beet, pome fruit, barley, oats, sorghum, rice and wheat. Preferred agricultural plants are selected from soybean, sunflower, corn, cotton, canola, sugar cane, sugar beet, pome fruit, barley, oats, sorghum, rice and wheat. Preferred agricultural plants are selected from wheat, barley, corn, soybean, rice, canola and sunflower. Preferred agricultural plants are selected from wheat, barley, oats, rice, sorghum, plantain, maize, potatoes, vegetables and fruits.
In preferred embodiments, the plant is a horticultural plant. For the purpose of the specification, “horticultural plants” are plants which are commonly used in horticulture, e.g. the cultivation of ornamentals, vegetables and/or fruits. Examples for ornamentals are turf, geranium, pelargonia, petunia, begonia and fuchsia. Examples for vegetables are potatoes, tomatoes, peppers, cucurbits, cucumbers, melons, watermelons, garlic, onions, carrots, cabbage, beans, peas and lettuce and more preferably from tomatoes, onions, peas and lettuce. Examples for fruits are apples, pears, cherries, strawberry, citrus, peaches, apricots and blueberries.
In preferred embodiments, the plant is an ornamental plant. For the purpose of the specification, “ornamental plants” are plants which are commonly used in gardening, e.g. in parks, gardens and on balconies. Examples are turf, geranium, pelargonia, petunia, begonia and fuchsia.
In preferred embodiments, the plant is a silvicultural plant. For the purpose of the specification, “silvicultural plants” are trees, more specifically trees used in reforestation or industrial plantations. Industrial plantations generally serve for the commercial production of forest products, such as wood, pulp, paper, rubber tree, Christmas trees, or young trees for gardening purposes. Examples for silvicultural plants are conifers, like pines, in particular Pinus spec., fir and spruce, eucalyptus, tropical trees like teak, rubber tree, oil palm, willow (Salix), in particular Salix spec., poplar (cottonwood), in particular Populus spec., beech, in particular Fagus spec., birch, oil palm and oak.
The trialkyl sulfonium chlorides, preferably octadecyl dimethyl sulfonium chloride according to the invention may be synthesized along standard routes for the synthesis of sulfonium compounds which are described in the literature. For example, a fatty alcohol having the desired chain length of residue R3 (C18-32-alkyl-OH) may be converted into the corresponding alkyl chloride C18-32-alkyl-Cl e.g. by reaction with SOCl2 or SO2Cl2. The thus obtained alkyl chloride may be reacted with an alkylthiol (C1-3-alkyl-SH) yielding the thioether C18-32-alkyl-S—C1-4-alkyl. Subsequently, the thus obtained thioether may be alkylated by reaction with a suitable alkylating agent such as C1-3-alkyl-1 yielding the sulfonium iodide C18-32-alkyl-S+(C1-4-alkyl)2I−. The corresponding chloride salt can be obtained by metathesis with an excess of a suitable salt such as NaCl.
The following examples further illustrate the invention but are not to be construed as limiting its scope:
The protective potential of octadecyl dimethyl sulfonium chloride (ODS-Cl) according to the invention against Septoria tritci (Zymoseptoria tritici, Z. tritici) blotch on wheat was investigated and compared to that of comparative octadecyl dimethyl sulfonium iodide (ODS-I) which is known from G. Steinberg et al. A lipophilic cation protects crops against fungal pathogens by multiple modes of action. Nature Communications 11:1608 (2020).
The species Septoria tritci belongs to the genus Septoria within family Mycosphaerellaceae within order Capnodiales within class Dothideomycetes within division Ascomycota within kingdom Fungi.
Fungicide resistant mutants were generated according to the following procedure using UV mutagenesis. Z. tritici IPO323 cells were harvested from 5 day-old Yeast Extract Peptone Dextrose (YPD) agar plates grown at 18° C. and conidial cells were suspended in sterile water. The cell numbers were determined using a Cellometer Auto 1000 cell counter (Nexcelom Biosciences, Lawrence, USA) and the cell density was adjusted to 1·107/ml. 2 million cells (200 μl of 1·107/ml) per plate were spread on to fungicide amended YPD agar plates (5×IC100, 10×IC100, 50×IC100, 100×IC100 of each fungicide) and mutagenized using Uvitec cross linker CL-508 (Uvitec, Cambridge, UK) with UV wave length 254 nm, 50 mJ cm−2 to produce lethality of ˜50%. Selection plates were incubated in the dark at 18° C. for 14 days. Visible colonies were picked from the selection plates and confirmed on fungicides amended plates (Azoxystrobin: 5×IC100: 1.5 μg/ml; Fluxapyroxad: 5×IC100: 3.0 μg/ml). In total 4 million cells were plated for each experiment (2 plates per experiment) and each experiment was repeated 5 times. For the controls including DMSO (0.8% final concentration) and methanol (0.3% final concentration), 1000 Z. tritici cells were spread per plate (2 plates per experiment; 5 experiments) and the plates were incubated as described above.
The visible colonies were counted and survival rate was determined. The protocol was modified from G. Scalliet et al. 2012, PLoS ONE 7(4): e35429). It was found that octadecyl dimethyl sulfonium chloride (ODS-Cl) according to the invention inhibits effectively plate growth and is ˜2.5-times better than comparative octadecyl dimethyl sulfonium iodide (ODS-I).
Thus, the antifungal effects of the sulfonium compounds according to the invention that are present as salts with chloride counter anions are superior compared to the respective compounds forming salts with iodine counter anions. While this superior antifungal activity has been demonstrated against Septoria tritci blotch on wheat, it will likewise exist with regard to other fungi.
The experimental results with regard to determining the IC100 value for Z. tritici are shown in
It was investigated whether octadecyl dimethyl sulfonium chloride (ODS-Cl) according to the invention can provide a significant level of protection towards P. viticola on detached leaves of grapevine compared to the two reference fungicides, namely Folpet 80WG and Dodine (Technical product). For that purpose, a dose effect curve and the ED50 were determined.
The species Plasmopara viticola belongs to genus Plasmopara within family Peronosporaceae within order Peronosporales within phylum Oomycota within Glade SAR.
Materials and methods: As fungal strain (pathogen), Plasmopara viticola, strain name PvS was used. This strain had been isolated from French untreated vine leaves in 2007. It is known to be susceptible to all fungicides used towards grape downy mildew.
The following fungicide formulations were used:
The formulations were prepared in a volume of water corresponding to 300 L/ha. No surfactant such as Tween or any other compound improving retention on leaves was used.
The timeline of in planta experiments was as follows:
Step (a)—preventive treatment: Grapevine leaves (var. Chardonnay) were taken from young plants and surface disinfected. The abaxial face of each leaf was treated with the fungicide preparations or distilled water (Control) with a hand-sprayer (2 bars) calibrated to deliver 300 L/ha. Two to three leaves were treated for each tested condition. One day post-treatment, leaf discs were cut on untreated or treated grapevine leaves (3 replicates each including at least 7 leaf-discs). Leaf discs were transferred on Petri dishes with the abaxial face up.
Step (b)—P. viticola inoculation of grapevine leaf discs: Each leaf disc was inoculated on its abaxial face with a calibrated sporangia suspension of P. viticola strain PvS. After inoculation, Petri dishes were placed in a climatic chamber: Temperature of 20° C. day/16° C. night—Photoperiod of 16 h light/8 h dark and controlled Relative Humidity (RH).
Step (c)—disease assessment: intensity of infection and analysis: Disease assessments were carried out 7 dpi by using the following arbitrary disease rating:
Disease Severity Index (DSI) was determined using the formula:
The DSI was converted into observed efficiency (OE) by using the formula:
OE=(β−α)/β)×100,
wherein a corresponds to the DSI of treated plants (%) and β to the DSI of the untreated (control) plants (%)). The values were compared by using a appropriated statistical test using the Xlstat software of statistic test (threshold α=5%).
The Disease Severity Index (DSI) was determined using the distribution of the discs and the DSI values were converted into observed efficiency (OE) for each tested product. Treatments were applied preventively one day before inoculation with P. viticola strain PvS on grapevine leaf discs in controlled condition. For comparison of the fungicide DSI %, in the DSI assessment of ODS-Cl 6 rates between 1 mga.i./L (ppm) and 1000 ppm were tested. The reference fungicide Folpet 80WG was tested at 3333 ppm and the reference fungicide Dodine was tested at the field homologated rate of 2267 ppm. All fungicides were used straight preventively 24 h against P. viticola strain PvS on grapevine leaves discs. The statistical test used was the Fischer LSD parametric test (a=5%).
Results are shown in
As demonstrated, the octadecyl dimethyl sulfonium chloride (ODS-Cl) based fungicide tested straight in this study was efficient to protect grapevine leaf towards downy mildew (EC 50=70 ppm or 21 g a.i./ha). A robust dose effect was observed against Plasmopara viticola. The two references that were used at their field recommended rate also showed a full protection against P. viticola symptoms development. Both, Folpet 80WG (3333 ppm) and Dodine (2267 ppm) showed a full control towards Downy Mildew, but at a significantly higher dose.
It was further investigated whether other oomycete can also be controlled by ODS-Cl, namely Phytophthora infestans which is the causal agent of potato (and tomato) late blight.
The species Phytophthora infestans belongs to genus Phytophthora within family Peronosporaceae within order Peronosporales within phylum Oomycota within Glade SAR.
P. infestans is an oomycete, a distinct Glade from the fungal genius, which spores can be spread by wind and water. Within the asexual cycle Sporangia are released from infected tissue and can, under certain circumstances, germinate and infect the plant tissue (referred as indirect germination). Sporangia can also release the contained zoospores that will germinate and infect the tissue (referred as direct germination). The zoospores are flagellated which permits a greater mobility in water conditions either at leaf surface or in soil. Spores generated from asexual life cycle have high mobility but low viability, on the other hand the sexual reproduction generates oospores that are not mobile by themselves but can persist up to several years in soil under a latent physiological state. At the end of the season the frost will eliminate infected residual plant materials but oospores remain viable being a starting point for a new epidemiological cycle when environmental conditions are more favorable.
Once inside the tissue, the first symptoms start appearing after few days at the foliage levels. Symptoms are often obviously visible at the leaf level but other organs can be infected such as stem, fruits (tomato) or tuber. When infecting the tuber, the disease can sometimes remain latent at harvest and being expressed later during storage. Infected leaves release zoospores under humid conditions which can rapidly spread all over the parcel.
Because the use of fungicide is a major strategy to constrain P. infestans spread, the pathogen has developed resistances to some active ingredient in which the mode of action is restricted to a unique cellular target (so-called unisite active ingredients). The use of multisite active ingredients can present a great benefit since their mode of action is less suspected to allow apparition of resistances.
Materials and methods: As fungal strain (pathogen), Phytophthora infestans, strain name Pi96 was used. This strain had been isolated from untreated potato European sample. It is known to be susceptible to all fungicides.
The following fungicide formulations were used:
The timeline of in planta experiments was as follows:
Step (a)—preventive treatment: Potato leaves (var. Bintje) were taken from young plants and surface disinfected. The adaxial face of each detached leaf was treated with the fungicide preparations or distilled water (Control) with a hand-sprayer (2 bars) calibrated to deliver 300 L/ha (Preventive treatment). A minimum of three leaves or at least 18 inoculated leaflets were treated for each tested condition. Preventive treatment 24 h: One day post-treatment, leaflets were cut on untreated or treated potato leaves (3 replicates each including at least 5 to 7 leaflets). Leaflets were transferred on Petri dishes with the abaxial face down.
Step (b)—P. infestans inoculation of potato leaflets: The inoculation occurred on the detached treated or untreated leaflets with a droplet of a calibrated sporangia suspension of P. infestans strain Pi96. After inoculation, potato leaves were transferred in saturated humidity atmosphere in a climatic chamber under the following conditions: 18° C.-14 h day/15° C.-10 h night.
Step (c)—disease assessment: intensity of infection and analysis: Disease assessments were carried out in accordance with Example 2.
With regard to the evaluation of disease severity (DSI) and efficacy of the treatments, the evolution of the DSI (Disease Severity Index) obtained from preventively treated potato leaves inoculated with P. infestans 24 h after treatment was determined. DSI is the surface of diseased leaflet. The results are compiled in the table here below:
Results are also shown in
For comparison of the fungicide DSI %, the fungicide efficacy obtained from preventively treated potato leaves inoculated with P. infestans 24 h after treatment was calculated from DSI values at the final assessment timing (10 dpi).
Results are also shown in
As demonstrated, octadecyl dimethyl sulfonium chloride (ODS-Cl) based fungicide tested straight in this study is efficient to protect potato leaves against late blight at dose starting from 100 ppm. When used at 1000 ppm, ODS-Cl is able to generate a full control of the disease similar to what is obtained from both references Dithan Neotec (Mancozeb) and SYLLIT MAX (Dodine) used at this same dose.
The water solubility of octadecyl dimethyl sulfonium chloride (ODS-Cl) according to the invention and octadecyl dimethyl sulfonium iodide (ODS-I) was determined at different pH values. The results are compiled in the table here below:
Results are shown in
As demonstrated, octadecyl dimethyl sulfonium chloride (ODS-Cl) has a higher solubility in water than octadecyl dimethyl sulfonium iodide (ODS-1). Further, the solubility of ODS-Cl depends on the pH value: while at pH 7 only 0.28 g/L ODS-Cl are soluble in water, the solubility of ODS-Cl significantly increases with higher pH values (0.94 g/L at pH 10) and with lower pH values (1.65 g/L at pH 2.2).
| Number | Date | Country | Kind |
|---|---|---|---|
| 20199746.7 | Oct 2020 | EP | regional |
| 20199747.5 | Oct 2020 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2021/077115 | 10/1/2021 | WO |
