Herbicidal conjugates, compositions comprising the same and uses thereof

Abstract

The present disclosure relates to a plant-protective conjugate comprising a herbicide chemically linked to a photoprotective moiety through a photocleavable bond. The conjugate is capable of accumulating within a plant, wherein the bond is cleavable upon exposure to light, thereby releasing the herbicide. The conjugate exhibits a herbicidal effect significantly greater than the herbicide in its free form upon light exposure. The disclosure further provides an agricultural composition comprising the conjugate and a suitable vehicle, as well as a method for delivering the conjugate to plants under conditions that allow for its accumulation and activation by light exposure.

Description

[0001] HERBICIDAL CONJUGATES, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF

[0002] TECHNOLOGICAL FIELD

[0003] The present disclosure relates to agriculture and specifically to herbicides.

[0004] BACKGROUND ART

[0005] References considered to be relevant as background to the presently disclosed subject matter are listed below:

[0006] - Hayashi, K. I.; Kusaka, N.; Yamasaki, S.; Zhao, Y.; Nozaki, H. Development of 4-Methoxy-7-Nitroindolinyl (MNI)-Caged Auxins Which Are Extremely Stable in Planta. Bioorganic Med. Chem. Lett. 2015, 25 (20), 4464-4471.

[0007] Gao, C.; Huang, Q.; Lan, Q.; Feng, Y.; Tang, F.; Hoi, M. P. M.; Zhang, J.; Lee, S. M. Y.; Wang, R. A User-Friendly Herbicide Derived from Photo- Responsive Supramolecular Vesicles. Nat. Commun. 2018 91 2018, 9 (1), 1- 13.

[0008] Acknowledgement of the above references herein is not to be inferred as meaning that these are in any way relevant to the patentability of the presently disclosed subject matter.

[0009] BACKGROUND

[0010] Hayashi et. al., describe the synthesis and application of highly stable caged auxins, 4-methoxy-7-nitroindolinyl (MNI)-caged auxins. Natural auxin, indole 3-acetic acid, and two synthetic auxins, 1-NAA and 2,4-D were caged by MNI caging group. MNI-caged auxins showed a high stability in planta and a rapid release the original auxin when photolyzed.

[0011] Gao e.t al., report photo-responsive paraquat-loaded supramolecular vesicles, prepared via one-pot self-assembly of amphiphilic, ternary host-guest complexes between cucurbit[8]uril, paraquat, and an azobenzene derivative. In this vesicle formulation, paraquat is only released upon UV or sunlight irradiation. Additionally, the PQ-loaded vesicles’ herbicidal activity against a model of invasive weed is nearly identical to that of free paraquat under natural sunlight.

[0012] GENERAL DESCRIPTION

[0013] The present disclosure is based on the development of photoactivatable herbicide conjugates that provide a herbicidal effect greater than the effect achieved by the herbicide when delivered in free form. A unique feature of the presently disclosed conjugates resides in the accumulation of the conjugate within a plant as a result of delivery during a dark period. When exposed to light, the herbicide is released in a burst effect. As a result, a lower amount of herbicide needs to be delivered (in comparison to free herbicide), for achieving a desired herbicidal effect.

[0014] Thus, in accordance with a first aspect of the presently disclosed subject matter there is provided a plant-protective conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, wherein said conjugate is accumulable within a plant; and said chemical bond is a photocleavable bond upon exposure to light, including natural light, when said conjugate is within said plant.

[0015] For achieving the burst effect of the herbicide released from the conjugate, it has been found that there is a need to deliver the conjugate during dark periods. Thus, in accordance with a second aspect of the presently disclosed subject matter there is provided a herbicidal method, the method comprises delivery to a plant a conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, the conjugate being accumulable within a plant; and the chemical bond is a photocleavable bond, when said conjugate is within said plant, wherein said delivery is in absence of light effective to cause cleavage of said photocleavable bond and under conditions allowing accumulation of said conjugate in said plant.

[0016] Finally, in accordance with a third aspect of the presently disclosed subject matter there is provided an agricultural composition comprising an agriculturally acceptable vehicle and a conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, the conjugate being accumulable within a plant; and the chemical bond is a photocleavable bond, when said conjugate is within said plant.

[0017] BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

[0019] Figure 1 provides a graphical representation of the Bromilov model for predicting mobility and application characteristics of pesticides, in plants. The figure categorizes the compounds based on their chemical properties, particularly their pKa (acid dissociation constant) and logP (partition coefficient) values, which in accordance with some examples determine their transport characteristics within plant tissues.

[0020] Figure 2 is a flow diagram showing schematic illustration of the process of application and activation of PPH's in plants according to some examples of the presently disclosed subject matter.

[0021] Figure 3A - Figure 3B are plots showing high resolution NMR spectra of MNI- 2,4-D (12) according to some examples of present disclosure: Figure 3A shows 'H-NMR spectrum, Figure 3B shows °C-NMR spectrum.

[0022] Figure 4A - Figure 4B are plots showing high resolution NMR spectra of MNI- 2,4,5TP (13) according to some examples of present disclosure: Figure 4A shows 'H- NMR spectrum, Figure 4B shows13C-NMR spectrum.

[0023] Figure 5A - Figure 5B are scatter plots (Figure 5A - Figure 5B) showing photoactivation kinetics and chemical structures of MNI-protected herbicides according to some examples of present disclosure: Figure 5A is a scatter plot showing photoactivation reaction progress (photolysis rate) from MNI-2,4-D (12) to release 2,4-D, Figure 5B is a scatter plot showing photo-activation reaction progress (photolysis rate) from MNI-2,4,5-TP (13) to release 2,4,5-TP.

[0024] Figure 6A - Figure 6C are plots depicting the chromatographic data of photorelease of 2,4-D (2) from MNI-2,4-D (12) under the artificial UV irradiation according to some examples of present disclosure: Figure 6A shows full-range HPLC chromatogram representing the overall separation profile of the reaction mixture, Figure 6B shows a zoomed-in chromatogram focusing on the elution peak of MNI-2,4-D (12), Figure 6C shows a zoomed-in chromatogram focusing on the elution peak of 2,4-D (2).

[0025] Figure 7A - Figure 7C are plots depicting the chromatographic data of photorelease of 2,4,5TP from MNI-2,4,5-TP (13) under the artificial UV irradiation according to some examples of present disclosure: Figure 7A shows full-range HPLC chromatogram representing the overall separation profile of the reaction mixture, Figure 7B shows a zoomed-in chromatogram focusing on the elution peak of MNI-2,4,5-TP (13), Figure 7D shows a zoomed-in chromatogram focusing on the elution peak of 2,4,5-TP.

[0026] Figure8A - Figure 8B are scatter plots showing photolysis progress (photolysis rate) of MNI-protected herbicides under sunlight irradiation according to some examples of present disclosure: Figure 8A shows photolysis progress of, MNI-2,4-D, Figure 8B shows photolysis progress of MNI-2,4-5-TP.

[0027] Figure 9A - Figure 9C are plots depicting the chromatographic data of photorelease of 2,4-D (2) from MNI-2,4-D (12) under the sun light irradiation according to some examples of present disclosure: Figure 9A shows full-range HPLC chromatogram representing the overall separation profile of the reaction mixture, Figure 9B shows a zoomed-in chromatogram focusing on the elution peak of MNI-2,4-D (12), Figure 9C shows a zoomed-in chromatogram focusing on the elution peak of 2,4-D (2).

[0028] Figure 10A - Figure 10C are plots depicting the chromatographic data of photorelease of 2,4, 5TP from MNI-2,4,5-TP (13) under the sun light irradiation according to some examples of present disclosure: Figure 10A shows full-range HPLC chromatogram representing the overall separation profile of the reaction mixture, Figure 10B shows a zoomed-in chromatogram focusing on the elution peak of MNI-2,4,5-TP (13), Figure 10C shows a zoomed-in chromatogram focusing on the elution peak of 2,4,5-TP.

[0029] Figure 11 is a box plot showing root elongation of WT Arabidopsis seedlings with no herbicidal conjugates present, under different exposure times to UV light according to some examples of present disclosure.

[0030] Figure 12A - Figure 12B are box plots showing the effect of 2,4-D and 2,4,5-TP on root elongation with and without UV light exposure according to some examples of present disclosure: Figure 12A shows the effect of MNI-2,4-D, Figure 12B shows the effect of MNI-2,4,5-TP.

[0031] Figure 13A - Figure 13F are box plots showing the effect of 2,4-D and 2,4,5-TP on root elongation with and without UV light exposure according to some examples of present disclosure: Figure 13A - Figure 13C show the effect of MNI-2,4-D, Figure 13D - Figure 13F show the effect of MNI-2,4,5-TP.

[0032] Figure 14 is a scatter plot showing the normalized photon count of transgenic DR5: luciferase expressing Arabidopsis seedlings treated with 2,4-D or MNI-2,4-D with or without light irradiation according to some examples disclosed herein.

[0033] DETAILED DESCRIPTION

[0034] Herbicides are mainly used for growth control by inhibiting or eliminating the growth of undesired plants. Compared to human manual control of weeds, chemicals provide more efficient solutions, saving labor costs and making it possible, through an informed choice, to solve multiple problems in one application round. Yet, there are various challenges when using herbicides in their free form.

[0035] Herbicides include large groups of compounds with a variance in their physical properties. Figure 1 illustrates how the hydrophilicity (LogP) and acid dissociation constant (pKa) of herbicides determine their mobility and delivery characteristics within plant tissues.

[0036] Plants can develop tolerance to herbicides:

[0037] Differential response of plant species to specific herbicides like glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) was observed very early after their commercial use began. For example, soybean is susceptible to dicamba during the flowering stage but tolerant to 2,4-D during all growth stages, while cotton is tolerant to dicamba but extremely sensitive to 2,4-D. Such differential responses to herbicides allow farmers to selectively and controllably eliminate specific weeds in the presence of crops. Due to the extensive use of herbicides, previously susceptible plants started evolving resistance mechanisms. This is mainly a result of the drift of herbicides via various routes (wind, large-scale spray methods, seepage through the grounds, transfer by animals, and more) from the application area to other areas, exposing plants to sub-lethal amounts of the herbicides, thus allowing them to evolve resistance mechanisms (mostly via improved or more rapid metabolism). The emergence of resistance in many common weeds significantly decreased the effectiveness of herbicides, leading to the use of ever- increasing amounts.

[0038] The development of resistance in biological systems is more common during exposure to sub-lethal concentrations; under those conditions, natural selection encourages the survival of the more tolerant individuals. Resistance to popular herbicides is known today in many common weeds, and new resistances (new mechanisms, new weeds, or against new herbicides) are being discovered yearly. An example of resistance development against compounds comes from peppermint, in which some species acquired resistance to bromoxynil, requiring the use of a ten-times higher dose to get the same results compared to wild-type peppermint. Therefore, there is a need for increasing the herbicidal effect of herbicides.

[0039] Herbicide pollution

[0040] Herbicides can be toxic substances. Their most significant undesired impact actually stems from their intended role - harming vegetation. When herbicides are applied, they often affect the entire local ecosystem, restricting growth and reproduction of all plants. On the molecular level, they lead to decreased photosynthesis, cell division, and / or amino acid production in plants. Fish and other aquatic life forms also suffer from those effects, often because of the many pathways that lead herbicides to reach the ground and underground water bodies.

[0041] Thus, developing more efficient herbicides that can be used at lower amounts in the field is crucial and reducing the amounts of herbicides, through conjugation as disclosed herein, can also prevent the emergence of resistance mechanisms in weeds.

[0042] In response to agricultural challenges, such as those described below, herbicidal conjugates have been developed, providing a herbicidal effect that is greater than the effect achieved by the same amount of herbicide, when delivered in free form.

[0043] Specifically, and in accordance with the presently disclosed subject matter, there is provided, in accordance with first of its aspects, a plant-protective conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, wherein said conjugate is accumulable within a plant; and said chemical bond is a photocleavable bond upon exposure to natural light, when said conjugate is within said plant.

[0044] As used herein, the term “z z free form” refers to a state of the herbicide in which the herbicide is not chemically bonded to a photoprotective moiety. The term “z z free form” encompasses the herbicide in any conventional formulation, including but not limited to solutions, dispersions, emulsions, or other formulations containing carriers, solvents, surfactants, adjuvants, or other conventional additives.

[0045] The conjugate is composed, in principle, of a herbicide, or herbicide precursor (e.g. chemical modification of the herbicide to allow its eventual conjugation) that is chemically linked (conjugated) to a photochemical protection group also known by the term photoremovable protecting groups (PPGs).

[0046] Generally, herbicides can be divided into two groups of compounds based on, for example, chemical structure, chemical properties, and mode of action. Herbicide resistance action committee (HRAC) modes of action (MoA) classification scheme summarizes the different herbicides in current use and their known MoA. This classification can be found in hracelobal.com / files / HRAC Revised MOA Classification Herbicides Poster. pdf).

[0047] Herbicides, chemical classifications thereof and modes of action thereof in accordance with some examples disclosed herein are summarized inter alia in Table 2.

[0048] In some examples of the presently disclosed subject matter, herbicide, in its non- conjugated / free form, is a compound having a mode of action selected from the group consisting of light activation of reactive oxygen species (ROS), inhibition of cellular metabolism, inhibition of cell division and growth. ACCase inhibition, ALS inhibition, inhibition of microtubule assembly, auxin mimics, photosynthesis inhibition, inhibition of EPSP synthase, inhibition of glutamine synthetase, inhibition of PDS, inhibition of DOXP synthase, inhibition of PPO, inhibition of VLCFAs, DHP inhibition, auxin transport inhibition, PS I electron diversion, inhibition of microtubule organization, uncoupling, inhibition of HPPD, inhibition of dihydroorotate dehydrogenase, inhibition of cellulose synthesis, inhibition of fatty acid thioesterase, inhibition of serine threonine protein phosphatase, inhibition of solanesyl diphosphate synthase, inhibition of homogentisate solanesyltransferase, inhibition of lycopene cyclase.

[0049] A common feature of all herbicides within the scope of the presently disclosed subject matter is that they include, when in free (non-conjugated) at least one functional group, namely, chemically reactive group that can play part in the conjugation with the photoprotective entity.

[0050] In the context of the presently disclosed subject matter, a chemically reactive group of the herbicide is selected from the group consisting of hydroxyl (-OH), carboxyl (-COOH), primary amine (-NH2), secondary amine (-NH), amide ( NHO), azide (-N3), vinyl (-CH=CH2), ethynyl (-CCH), aldehyde (-CHO), ketone (-CO), thiol (-SH), isocyanate (-NCO), epoxide (oxirane, -C2H4O), hydrazine (-NH-NH2), halogen, nitro (-NO2), acryloyl (CH2=CH-C0-), cyanate (-OCN), cyanide (-CN), hydroxymethyl (-CH2OH), thioester (-COSR).

[0051] In some examples of the presently disclosed subject matter, the herbicide comprises at least a hydroxyl group.

[0052] In some examples of the presently disclosed subject matter, the herbicide comprises at least a carboxyl group.

[0053] In some examples of the presently disclosed subject matter, the herbicide comprises at least an amine group.

[0054] In some examples of the presently disclosed subject matter, the herbicide comprises at least an aldehyde group.

[0055] In some examples of the presently disclosed subject matter, the herbicide comprises at least a ketone group.

[0056] In some examples of the presently disclosed subject matter, the herbicide comprises at least a thiol group.

[0057] In some examples of the presently disclosed subject matter, the herbicide comprises, in free form, two or more chemically reactive groups.

[0058] The chemically reactive group can be inherently present in the herbicide or the herbicide can be chemically modified to carry such reactive group. In some examples the herbicide is selected from the group consisting of Alkylazines, Amides, Aryl-carboxylates, Aryloxphenoxy-propionates, Azolyl- carboxamides, Benzofuranes, Benzoates, Benzyl ethers, Carbamates, Cyclohexanediones, Dinitroanilines, Dinitrophenols, Diphenyl ethers, Diphenyl heterocycles, Imidazolinone, Isoxazolines, Isoxazolidinones, N-Phenyl-imides, N- Phenyl-oxadiazolones, N-Phenyl-triazolinones, Nitriles, Oxiranes, Phenoxycarboxylates, Phenyl-ethers, Phenylcarbamates, Phosphinic acids, Phosphoroamidates, Pyridine-carboxylates, Pyridiniums, Pyridines, Pyridyloxy-carboxylates, Pyrimidinyl benzoates, Pyrazoles, Quinoline-carboxylates, Sulfonanilides, Thiocarbamates, Triazines, Triazolopyrimidines, Triazinones, Triketones, Ureas, Uracils, a- Chloroacetamides, a-Oxyacetamides, a-Thioacetamides, chemical derivatives, salts and prodrugs thereof.

[0059] In some examples of the presently disclosed subject matter, the herbicide, in free form, is a compound selected from the group consisting of 2,4-D, 2,4-D-B, 2,4,5-T, Aclonifen, Acetochlor, Acifluorfen, Alachlor, Amicarbazone, Amidosulfuron, Amitrole, Aminocyclopyrachlor, Aminopyralid, Ammetryne, Anilofos, Atrazine, Azafenidin, Azimsulfuron, Barban, Beflubutamid, Benazolin, Benfuresate, Benefin / benfluralin, Bensulide, Bensulfuron-methyl, Bentazon, Benzobicyclon, Benzofenap, Benthiocarb, Bialaphos / bilanafos, Bifenox, Bifenthrin, Bispyribac-Na, Bixlozone, Bromacil, Bromobutide, Butachlor, Butafenacil, Butralin, Cafenstrole, Carbetamide, Carfentrazone-ethyl, Chlorthal-dimethyl / DCPA, Chlorthiamid, Chloranocryl / dicryl, Chloramben, Chloridazon / pyrazon, Chlorimuron-ethyl, Chlorotoluron, Chlorpropham, Chlorsulfuron, Clodinafop-propargyl, Clomazone, Clomeprop, Cloransulam-methyl, Clethodim, Cinosulfuron, Cinmethylin, Cinidon-ethyl, Cycloxydim, Cyclopyrimorate, Cyflufenamid, Cyhalofop-butyl, Cinosulfuron, Cumyluron, Cypermethrin, Cyanazine, Cycloate, Cyclosulfamuron, Difenzoquat, Difenzoquat-methyl, Diflufenican, Diflufenzopyr, Dimethachlor, Dimethenamid, Dimethametryn, Dimepiperate, Diquat, Dichlobenil, Dichlorprop, Diclosulam, Diclofop-methyl, Dicamba, Dimethachlor, Dimethametryn, Dinitramine, Dithiopyr, DNOC, Dinoseb, Diphenamid, Diuron, DMPA, Dymron / daimuron, DSMA, Endothall, Enoxaprop, Ethalfluralin, Ethametsulfuron- methyl, Ethofumesate, Ethoxysulfuron, Esprocarb, EPTC, Etobenzanid, Fenoxaprop- ethyl, Fenoxasulfone, Fenquinotrione, Fenoxaprop-P-ethyl, Fenoxaprop, Fenthiaprop, Fentrazamide, Fentrazamide, Flazasulfuron, Flamprop-m, Florasulam, Florpyrauxifen, Flucarbazone-Na, Flucetosulfuron, Flumetsulam, Flufenacet, Flumiclorac-pentyl, Flumioxazin, Flumioxazin, Fluometuron, Flumioxazin, Fluopyram, Fluopyram, Fluoxastrobin, Fluoroacetate, Flurochloridone, Fluroxypyr, Fluridone, Flurtamone, Fluthiacet-methyl, Foramsulfuron, Fosamine, Fomesafen, Glufosinate-ammonium, Glyphosate, Halauxifen, Halosulfuron-methyl, Haloxyfop-methyl, Hexazinone, Imazaquin, Imazaquin, Imazamox, Imazapic, Imazapyr, Imazapyr, Imazapyr, Imazethapyr, Imazosulfuron, Imidacloprid, Indaziflam, Indanofan, Isoproturon, Isoxaflutole, Isoxaben, Lactofen, Lenacil, Linuron, MCPA, MCPB, Mecopr op -ethyl, Mesosulfuron-methyl, Mesotrione, Metamitron, Metamifop, Metazachlor, Metamifop, Methabenzthiazuron, Methiozolin, Metolachlor, Metazachlor, Metazachlor, Metsulfuron-methyl, Metribuzin, Molinate, Monuron, MSMA, Napropamide, Naproanilide, Naptalam, Niclofen, Nicosulfuron, Norflurazon, Orbencarb, Orthosulfamuron, Oxyfluorfen, Oxadiargyl, Oxadiazon, Oxyfluorfen, Pelargonic acid, Penoxsulam, Pentoxazone, Pendimethalin, Pethoxamid, Picloram, Picolinafen, Pinoxaden, Primisulfuron-methyl, Profoxydim, Prodiamine, Prometon, Prometryne, Propanil, Propachlor, Propazine, Propisochlor, Propoxycarbazone-Na, Propyzamide / pronamide, Prosulfocarb, Prosulfuron, Propanil, Pyraclonil, Pyrasulfotole, Pyribenzoxim, Pyributicarb, Pyriftalid, Pyrithiobac-Na, Pyridate, Pyridate, Pyrimisulfan, Pyriminobac-methyl, Pyraflufen-ethyl, Pyrazoxyfen, Pyrazolynate, Pyroxsulam, Quinclorac, Quinmerac, Quizalofop-ethyl, Rimsulfuron, Saflufenacil, Sethoxydim, Simazine, Sulcotrione, Sulfentrazone, Sulfometuron-methyl, Sulfosulfuron, Tefuryltrione, Tebuthiuron, Terbacil, Terbuthylazine, Terbutryne, Thiazopyr, Thiazopyr, Thenylchlor, Thifensulfuron-methyl, Thiobencarb / Benthiocarb, Tiafenacil, Tiafenacil, Tritosulfuron, Tralkoxydim, Tribenuron-methyl, Triaziflam, Triaziflam, Triafamone, Triafamone, Triafamone, Tri-allate, Trifludimoxazin, Trifluralin, Trifluralin, Triflusulfuron-methyl, Trinexapac-ethyl, Vernolate, Quizalofop-ethyl, Triclopyr, Topramezone, Tolpyralate, chemical derivatives, salts and prodrugs thereof.

[0060] In some examples of the presently disclosed subject matter, herbicide is a compound, when in free form, being selected from the group consisting of Imazapyr, Pyrithiobac, Haloxyfop-methyl, Chlorthal-dimethyl, Clopyralid, Halauxifen, Dicamba, chemical derivatives, salts and prodrugs thereof. In some examples of the presently disclosed subject matter, the herbicide, when in free form, is 2,4-dichlorophenoxyacetic acid (2,4-D), having the following chemical structure:

[0061] In some examples of the presently disclosed subject matter, the herbicide, when in free form, is 2-(2,4,5-trichlorophenoxy)propionic acid (2,4,5-TP) having the following chemical structure:

[0062] Photochemical protection groups

[0063] In the context of the presently disclosed subject matter, photoremovable protecting groups (PPGs) are organic or inorganic molecules, preferably but not exclusively, small molecules, that can be cleaved by photo-irradiation at specific wavelengths. The photochemical reaction of cleavage, using light as active agent (typically and at times, preferably the sole active agent), is utilized to release bioactive compounds. It has been envisaged that the availability of light fluxes at wavelengths ranging from the lower ultra-violet (UV) to far infra-red (IR) in the field makes PPGs excellent candidates for controlled release of herbicides in amounts that would be less effective, if applied in free form.

[0064] Specifically, it has been found and disclosed herein that the conjugation of the herbicide to a photoprotective group improves herbicidal effect, by enhancing its absorbency and allowing the herbicide to accumulate in a plant. One effect achieved from the conjugation is associated with an improved control of the bioactivity due to the conjugation to the protecting group, and / or improved yield and / or decreased loss of the molecule to the environment.

[0065] The conjugation, as disclosed herein, also allows higher concentration inside the cells, leading to lower quantities needed to get the same results. Lower quantities mean more efficient molecules, which might also easily give lethal concentration that prevents one of the biggest problems in agriculture - tolerance.

[0066] Without being limited thereto, some principles of operating with the photoprotective herbicide (PPH) according to the presently disclosed subject matter, can be understood in view of the illustration provided in Figure 2.

[0067] To allow conjugation between the herbicide and the PPG, it is required that also the PPG carry at least one chemically reactive group that can form a chemical bond with the herbicidal reactive group.

[0068] Hence, the herbicide in free form has a first chemical reactive group, and photoprotective moiety, has, in free form, a second chemically reactive group, and the first chemical reactive group and second chemical reactive group are chemically linkable or linked.

[0069] As noted above, the term “zzz free form" used with respect to the herbicide, refers to a state of the herbicide in which the herbicide is not chemically bonded to a photoprotective moiety. The term “zzz free form" encompasses the herbicide in any conventional formulation, including but not limited to solutions, dispersions, emulsions, or other formulations containing carriers, solvents, surfactants, adjuvants, or other conventional additives.

[0070] With respect to the photoprotective moiety, the term “zzz free form" is to be understood to encompass any chemically linkable molecule that, once chemically conjugated to another molecule, such as an herbicide, can be cleaved by photo-irradiation at specific wavelengths (as discussed above).

[0071] As used herein, the term “chemically linkable" refers to the capacity of two or more chemical entities to form a stable chemical bond through a chemical reaction under suitable conditions. Specifically, the term indicates that a first chemical reactive group of one molecule and a second chemical reactive group of another molecule are capable of undergoing a chemical reaction that results in a direct chemical bond between them, which may be of any type, including but not limited to covalent, ionic, hydrogen, or coordination bonds. Without being limited thereto, it is appreciated that the conditions facilitating such linkage may include the presence of a catalyst, specific temperature ranges, pH adjustments, the use of clickable moieties or other reaction-favoring factors. The term “chemically linkable" encompasses both the scenario in which the reactive groups are linked by a chemical bond and the scenario in which they possess the potential to be linked under suitable reaction conditions.

[0072] In some examples of the presently disclosed subject matter, the photoreactive moiety comprises, when in free form (as a PPG) has a chemically reactive group selected from the group consisting of hydroxyl (-OH), carboxyl (-COOH), primary amine (-NH2), secondary amine (-NH), amide ( NHO), azide (-N3), vinyl (-CH=CH2), ethynyl (-CCH), aldehyde (-CHO), ketone (-CO), thiol (-SH), isocyanate (-NCO), epoxide (oxirane, -C2H4O), hydrazine (-NH-NH2), halogen, nitro (-NO2), acryloyl (CH2=CH- CO-), cyanate (-OCN), cyanide (-CN), hydroxymethyl (-CH2OH), thioester (-COSR).

[0073] In some examples of the presently disclosed subject matter, the photoreactive moiety comprises, when in free form, a hydroxyl chemically reactive group.

[0074] In some examples of the presently disclosed subject matter, the photoreactive moiety comprises, when in free form, a carboxyl chemically reactive group.

[0075] In some examples of the presently disclosed subject matter, the photoreactive moiety comprises, when in free form, an amine chemically reactive group.

[0076] In some examples of the presently disclosed subject matter, the photoreactive moiety comprises, when in free form, an aldehyde chemically reactive group.

[0077] In some examples of the presently disclosed subject matter, the photoreactive moiety comprises, when in free form, a ketone chemically reactive group.

[0078] In some examples of the presently disclosed subject matter, the photoreactive moiety comprises, when in free form, a thiol chemically reactive group.

[0079] In some examples of the presently disclosed subject matter, the photoreactive moiety is o-nitrobenzyl and any chemical derivative of same capable of forming a photocleavable bond with the hereindefined herbicides. In some examples of the presently disclosed subject matter, the photoreactive moiety (Coumarin-4-yl) and any chemical derivative of same capable of forming a photocleavable bond with the hereindefined herbicides.

[0080] In some examples of the presently disclosed subject matter, the photoreactive moiety is arylmethyl and any chemical derivative of same capable of forming a photocleavable bond with the hereindefined herbicides.

[0081] In some examples of the presently disclosed subject matter, the photoreactive moiety is arylcarbonylmethyl and any chemical derivative of same capable of forming a photocleavable bond with the hereindefined herbicides.

[0082] In some examples of the presently disclosed subject matter, the photoreactive moiety benzothiadiazol-6 / 7-yl)methyl and any chemical derivative of same capable of forming a photocleavable bond with the hereindefined herbicides.

[0083] In some examples of the presently disclosed subject matter, the photoreactive moiety p-hydroxyphenacyl (pHP) and any chemical derivative of same capable of forming a photocleavable bond with the hereindefined herbicides.

[0084] In some examples of the presently disclosed subject matter, the photoreactive moiety is a quinone and any chemical derivative of same capable of forming a photocleavable bond with the hereindefined herbicides.

[0085] In some examples of the presently disclosed subject matter, the photoreactive moiety is 4-methoxy-7-nitroindolinyl (MNI) and any derivative thereof.

[0086] In some examples of the presently disclosed subject matter, the conjugate is MNI- 2,4-D, having the following chemical structure: For illustrative purposes and not by way of limitation, when a herbicide in a free form is auxin mimicking herbicide, e.g. 2,4-D, the activity can comprise activation of DR5 promoter.

[0087] In some examples of the presently disclosed subject matter, the conjugate is MNI- 2,4, 5-TP, having the following chemical structure:

[0088] In some examples of the presently disclosed subject matter, the conjugate is selected based on structural and / or physical criteria that allow its penetration and accumulation within the plant.

[0089] In some examples of the presently disclosed subject matter, the conjugate fulfills at least one, at times at least two, at least three, or even all four of the following criteria: it has a molecular weight of less than 600Da; at times, of or below 500Da; at times of or below 400Da. it has no more than 5 hydrogen bond donors; it has no more than 10 hydrogen bond acceptors; and it has a partition coefficient (referred to at times as LogP) not greater than 5; at times, not greater than 4, at times not greater than 3.

[0090] The presently disclosed conjugate is accumulable within a plant.

[0091] In the context of the presently disclosed subject matter, the term "accumulable" is intended to mean the tendency of the conjugate to persist and build up within the plant tissues rather than being rapidly degraded, metabolized or removed out of the plant. In other words, this term refers to the characteristic of a conjugate, to be absorbed, retained, and concentrated in one or more tissues of the plant (such as leaves, stems, and roots) over time following its application. In some examples of the presently disclosed subject matter, the conjugate is accumulable during dark periods.

[0092] In the context of present disclosure, the term "dark period, "darkness" , "in the dark" or "in absence of light" refers to conditions where the level of light irradiation applied onto the plant, or to which the conjugate is exposed, is insufficient to cause photocleavage of the photoreactive chemical bond between the herbicide and the PPG.

[0093] In some preferred examples, it is to be appreciated that during such dark periods, the presently disclosed conjugates have no detectable or statistically insignificant herbicidal activity.

[0094] The presently disclosed conjugate, method and composition, are intended for weed control in agriculture. Hence, in accordance with some examples, the conjugate is delivered and accumulable in a weed plant.

[0095] For the sake of simplicity, all terms and definitions provided in connection with the conjugate, according to the presently disclosed first aspect, also apply to the method according to the presently disclosed second aspect, and / or to the agricultural composition according to the presently disclosed third aspect, mutatis mutandis.

[0096] As used herein, the term "weed plant" or "weed" is intended to encompass any undesired plant species that adversely affects the growth of cultivated crops or desired vegetation.

[0097] In some examples of the presently disclosed subject matter, the conjugate is delivered, accumulable and herbicidal effective in a weed plant selected from the group consisting of the following genera: Amaranthus, Amaranthus, Brachypodium, Bassia, Chenopodium, Convolvulus, Cynodon, Cyperus, Echinochloa, Elymus, Fallopia, Glycine, Lolium, Setaria, Solanum, Sorghum, Stellar ia, Xanthium.

[0098] In some examples of the presently disclosed subject matter, the conjugate is delivered, accumulable and herbicidal effective in a weed plant selected from the group consisting of the following species: Amaranthus palmeri, Amaranthus retrojlexus, Brachypodium distachyon, Bassia indica, Chenopodium album, Convolvulus arvensis, Cynodon dactylon, Cyperus rotundus, Echinochloa crus-galli, Elymus repens, Fallopia convolvulus, Glycine max, Lolium perenne, Lolium multijlorum, Setaria viridis, Setaria faberi, Solanum nigrum, Sorghum halepense, Stellar ia media, Xanthium strumarium. In some examples of the presently disclosed subject matter, the weed plant is Brachypodium distachyon.

[0099] In some examples of the presently disclosed subject matter, the weed plant is Bassia indica.

[0100] The chemical linkage between the herbicide and the PPG in the conjugate is a photocleavable bond, particularly when the conjugate is within cell tissue, and preferably after accumulation. Release of the herbicide from the conjugate, is upon exposure to light, which as a result, the conjugate undergoes photolysis. Thus, in the context of the present disclosure, "photolysis" is intended to mean a process whereby the herbicide is released from the conjugate upon exposure to light.

[0101] In the context of the presently disclosed subject matter, the term "light" means any form of irradiation that would result in the photolysis of the conjugate, when the conjugate is within plant tissue.

[0102] In some examples, the light is natural light, e.g. sunlight.

[0103] In some examples, light is artificial light.

[0104] In accordance with the presently disclosed subject matter, the light comprises at least a wavelength or wavelength band within a wavelength range of about 280 nm and about 800 nm, at times within a wavelength range of about 280 nm and about 350 nm, at times within a wavelength range of about 350 nm and about 450 nm, at times within a wavelength range of about 450 nm and about 600 nm, at times within a wavelength range of about 600 nm and about 800 nm.

[0105] Upon exposure to light, photocleavage takes place, and the herbicide is released to perform its herbicidal activity on the plant.

[0106] It has been surprisingly found that upon exposure to light of the plant holding the accumulated conjugate, the conjugate exhibits a herbicidal effect that is statistically significantly greater than the herbicidal effect of the herbicide when administered to said plant in free form.

[0107] When assessing the herbicidal effect of a herbicide, several parameters can be evaluated to determine its impact on plant growth and development. These include root elongation, shoot height, biomass, leaf area, chlorophyll content, leaf number, root-to- shoot ratio, germination rate, leaf chlorosis, necrosis, plant vigor, root density, leaf senescence, branching pattern, flowering time, seed production and any combination of same.

[0108] In some examples of the presently disclosed subject matter, the herbicidal activity or effect is determined at least by assessing the effect on root elongation as compared to a control.

[0109] In some examples of the presently disclosed subject matter, the herbicidal activity of conjugate in dark and upon activation with light has a profile substantially similar or substantially the same as that shown in the expression profile of DR5: luciferase in Figure 14 (Figure 14 shows expression of DR5: luciferase following treatment with 2,4-D or MNI-2,4-D, with or without light irradiation and is postulated to be in correlation with any herbicidal activity).

[0110] Herbicidal activity may depend on the kinetics of herbicide released upon exposure to light.

[0111] In some examples of the presently disclosed subject matter, upon exposure to light, the presently disclosed subject matter has a herbicide release kinetics that can be defined as a sharp release peak, namely, a relatively sudden and rapid increase in herbicide concentration / activity following light exposure, characterized by a steep rise in the release rate also referred herein as “burst effect” .

[0112] As used herein the term “burst release” or “burst effect” is intended to mean substantially immediate release of the herbicide from the conjugate upon exposure to light, characterized by a sharp increase in free herbicide concentration within the plant tissue.

[0113] The characteristic burst release kinetics according to the presently disclosed conjugate can be quantitatively measured by any one of, for example, Peak Concentration (Cmax, the maximum concentration of herbicide released); Time to Peak (Tmax, the time taken to reach the peak concentration after light exposure; Release Rate (dC / dt, the rate of herbicide release over time, particularly around the peak period; Half-Life (t 1 / 2, the time required for the released herbicide concentration to decrease by half after reaching the peak. In some examples of the presently disclosed subject matter, the burst release (and as such, sharp increase) is demonstrated by an immediate increase in peak concentration to at least 60% of the total amount of herbicide delivered (once released) to the plant; at times, of at least 70%; at times, at least 80%; of at times, at least 90%.

[0114] In some examples of the presently disclosed subject matter, the time to peak (Tmax), namely, the immediate increase, is within a range of less than 1 minute. In some examples, Tmax is within a range of about 1 to 2 minutes, at times about 2 to 5 minutes, at times about 5 to 10 minutes, or at times about 10 to 20 minutes following exposure to light.

[0115] Based on these findings, a similar burst effect will be expected in plants, and this can be controlled by the amount of exposure to light. While the time to peak may be different, the release profile will be exhibited as a burst release profile.

[0116] In some examples of the presently disclosed subject matter, upon exposure to light, the presently disclosed subject matter has a herbicide release kinetics similar to or substantially as depicted in any one of Figure 5A - Figure 5B or Figure 8A - Figure 8B

[0117] In some examples of the presently disclosed subject matter upon exposure to light the herbicidal effect of the presently disclosed PPG-herbicide conjugates is at least 2- times greater, at times at least 2.5 times greater, at times at least 3 times greater, at times at least 5 times greater and at times at least 10 times greater than the herbicidal effect of a herbicide in free form.

[0118] The delivery of the conjugate to the plant can be by any method known in the art. In some examples, the delivery method comprises any one of foliar application, soil application, drip irrigation, and others, as known in the art.

[0119] The delivery of the conjugate, as detailed hereinabove, is during dark period / darkness. This allows the herbicide to stay inactive. During the rest of the night, the PPH is absorbed in the plant allowing the material to accumulate inside the plant. From sunrise onwards, the sunlight that contains UV would initiate the chemical reaction that releases the herbicide and activate it, which will damage different systems in the plant (according to the mode of action) and finally cause damage to the plant and death. The PPH accumulates in the desired area and thus produces a strong effect on the plant. As used herein, the term “ dark period' / “ darkness" is intended to mean conditions where the intensity of light is insufficient to cause photocleavage of the photocleavable bond in the herbicidal conjugate, thereby preventing the release of the free active herbicide.

[0120] In some examples, “dark period" / “darkness” is defined as an environment where light intensity is below a specified threshold and where said light intensity cannot initiate photo-release of the herbicide. Such conditions may be achieved during nighttime, when natural sunlight is absent, or in a controlled environment where light exposure is intentionally excluded, such as a greenhouse with blackout curtains or a growth chamber without any active light source.

[0121] In some examples, the terms “dark period" / “darkness” encompasses the absence of light in specific wavelengths capable of activating the photoprotective moiety of the conjugate, including absence of ultraviolet (UV) light or absence of visible light in the range of 280-800 nm.

[0122] In some examples, the terms “dark period" / “darkness” refers to the period between sunset and sunrise, but may also extend to any condition where light is actively prevented from reaching the applied conjugate.

[0123] The delivery of the conjugate to the plant or parts of the plant can be validated by LC / MS.

[0124] In some examples of the presently disclosed subject matter, the delivery to a plant involves applying the conjugate to the plant or to a target area of the plant after the cessation of daylight hours.

[0125] In some examples of the presently disclosed subject matter, the delivery to a plant involves applying the conjugate to the target area at dawn.

[0126] The release of the herbicide is thus controlled by the exposure of the plant to which the conjugate has been delivered, to light. The controlling may involve timing of exposure (e.g. after a sufficient duration of delivery of the conjugate to the plant), duration of exposure, wavelength or wavelength band of exposure, type of light (natural or artificial), intensity of light, duration of delivery and any combination of same. In some examples of the presently disclosed subject matter, the release of herbicide, and as such the sharp herbicidal activity is as a result of exposure of the plant to natural light, e.g. sunlight.

[0127] The delivery of the conjugate involves also formulating the conjugate within a delivery vehicle. Thus, according to a third aspect, there is provided an agricultural composition comprising an agriculturally acceptable vehicle and a conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, the conjugate being accumulable within a plant; and the chemical bond is a photocleavable bond, when said conjugate is within said plant.

[0128] In some examples, the agricultural composition is formulated for applying onto the soil and / or onto the plant in liquid form.

[0129] In some examples, the the agricultural composition is formulated for applying onto the soil and / or onto the plant in solid / particulate form.

[0130] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0131] The term "about" as used herein indicates values that may deviate up to 1%, more specifically 5%, more specifically 10%, more specifically 15%, and in some cases up to 20% higher or lower than the value referred to, the deviation range including integer values, and, if applicable, non-integer values as well, constituting a continuous range. In some embodiments, the term "about" refers to ± 10 %.

[0132] The indefinite articles “a” and “an” as used herein in the description and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one” . It must be noted that, as used in this description and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise.

[0133] The clause “and / or” as used herein in the description and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified.

[0134] As used herein in the description and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of or “exactly one of” or, when used in the claims, “consisting of” will refer to the inclusion of exactly one element of a number or list of elements.

[0135] As used herein in the specification and in the claims, the phrase “at least one” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified.

[0136] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

[0137] Throughout this description (including the Examples) and claims which follow, all transitional phrases such as “comprising” , “including” , “carrying” , “having”, “containing” , “involving”, “holding”, “composed of and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Specifically, it should be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. Only the transitional phrases “consisting of and “consisting essentially of shall be closed or semiclosed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures. More specifically, the terms "comprises" , "comprising" , "including" , “having” and their conjugates mean "including but not limited to". The term “ consisting of' means “including and limited to". The term "consisting essentially of' means that the composition, method or structure may include additional ingredients, steps and / or parts, but only if the additional ingredients, steps and / or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

[0138] It should be noted that various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range. Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases "ranging / ranges between" a first indicate number and a second indicate number and "ranging / ranges from" a first indicate number "to" a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals there between.

[0139] As used herein the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

[0140] It is appreciated that certain features of the presently disclosed subject matter, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub combination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

[0141] Various embodiments and aspects of the present invention as delineated herein above and as claimed in the claims section below find experimental support in the following examples.

[0142] Disclosed and described, it is to be understood that the presently disclosed subject matter is not limited to the particular examples, process steps, and compositions disclosed herein as such methods steps and compositions may vary somewhat. It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only and not intended to be limiting since the scope of the presently disclosed subject matter will be limited only by the appended claims and equivalents thereof.

[0143] The following examples are representative of techniques employed by the inventors in carrying out aspects of the present invention. It should be appreciated that while these techniques are exemplary of preferred embodiments for the practice of the invention, those of skill in the art, in light of the present disclosure, will recognize that numerous modifications can be made without departing from the spirit and intended scope of the presently disclosed subject matter.

[0144] DESCRIPTION OF SOME NON-LIMITING EXAMPLES

[0145] Materials and Methods

[0146] Chemical Methods

[0147] General chemical materials and methods

[0148] All chemicals were purchased from Sigma-Aldrich, TCI, or CombiBlocks and used as received unless otherwise stated. Anhydrous solvents and reagents (THF, DMF, DCM) were obtained as SureSeal bottles from Sigma-Aldrich. Thin-layer chromatography and flash chromatography were performed using Merck KGaA precoated silica gel 60 F-254 plates and Silicycle silica gel 40-63 (230-400 mesh), respectively. UV absorbance spectra were recorded on Agilent Cary 60 UV-Vis Spectrophotometer. Low-resolution ESI mass spectrometry was performed on LC / MS Acquity QDa detector coupled with Waters HPLC. High-resolution ESI mass spectrometry was performed on a Waters SYNAPT system. 1H and 13C NMR spectra were collected in CDC13 or DMS0-d6 unless stated differently (Cambridge Isotope Laboratories, Cambridge, MA) at 25°C using a Bruker Advance III spectrometer at 400 MHz and 100 MHz, respectively, at the Department of Chemistry NMR Facility at Tel Aviv University. All chemical shifts are reported in the standard 5 notation of parts per million using the TMS or residual solvent peak as an internal reference. Abbreviations: MeCN: acetonitrile, EtOH: ethanol, EtsN: trimethylamine, DIPEA:

[0149] N,Ndiisopropylethylamine, DMF: dimethylformamide, THF: tetrahydrofuran, MeOH: methanol, DCM: dichloromethane, HATU: hexafluorophosphate azabenzotri azole tetramethyl uronium, EDC HC1: l-ethyl-3 -(3 -dimethylaminopropyl) carbodiimide hydrochloride, HOBT: hydroxybenzotriazole, TFA: trifluoroacetic acid, EtOAc: ethyl acetate, NaHCCE: sodium bicarbonate, HC1: hydrogen chloride, NH4CI: ammonium chloride, Li OH:, lithium hydroxide.

[0150] Synthetic procedures

[0151] The synthesis of molecules 12 and 13 was according to an existing procedure for synthesizing 12. 2,4,5-TP was used to synthesize 13 without additional modification to the procedure. In brief, to a solution of MNI (11) 15 mg (0.077 mmol) and acetic acid (auxin, 2 or 3) 30 mg (2 eq, 0.154 mmol) in toluene (1 mL), thionyl chloride (50 pL) was added and then stirred overnight at 75 °C. The resulting solution was added dropwise to an aqueous sodium carbonate solution and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, and evaporated in vacuo. A silica gel purified the residue.

[0152] 12: white with pale yellow powder. 47 mg, 57% yield. 'H- NMR(CDCh,400MHz) 5 (ppm) (Figure 3A): 7.82 (d, J= 8.2 Hz, 1H), 7.39 (d, J= 2.1 Hz, 1H), 7.29 (d, J= 2.1 Hz, 1H), 7.04 (d, J= 8.8 Hz, 1H), 6.69 (d, J= 9.2 Hz, 1H), 4.91 (s, 2H), 4.39 (t, J= 7.9 Hz, 2H), 3.93 (s, 3H), 3.11 (t, J= 7.9 Hz, 2H). °C-NMR (CDCh, 100 MHz) 5 (ppm) (Figure 3B): 167.3, 159.0, 151.4, 136.3, 130.0, 127.9, 127.1, 125.6, 114.4, 106.7, 69.0, 59.9, 50.2, 26.6. HRMS (El): calculated for CnHuNiChNaCh 419.0177 (M+), found 419.0175.

[0153] 13: pale yellow powder, 78 mg, 50% yield. ^-NMR (CDCh, 400 MHz) 5 (ppm) (Figure 4A): 7.77 (d, J= 8.8 Hz, 1H), 7.46 (s, 1H), 7.16 (s, 1H), 6.67 (d, J =92 Hz, 1H), 4.99 (dd, J= 13.7, 6.8 Hz, 1H), 4.04 (dd, J= 20, 10 Hz,lH), 3.01-3.13 (m, 2H), 1.71 (m, 3H). °C-NMR (CDCh, 100 MHz) 5 (ppm) (Figure 4B): 169.2, 158.9, 151.3, 136.4, 131.7, 131.0, 130.8, 125.5, 122.9, 121.9, 116.5, 116.2, 106.8, 74.0, 55.9, 49.6, 26.8, 18.1, 17.8.

[0154] HRMS (El): calculated for Ci8Hi5N2O5NaCh 466.9944 (M+), found 466.9949.

[0155] Biological and Spectral Methods:

[0156] Plant growth and conditioning

[0157] Arabidopsis Thaliana seeds Col-0 (Columbia) ecotype was used as a model plant. Marashige and Skoog (MS) medium was used as a growth medium for the seedlings, containing 1% of sucrose and agar (w / v) in vertical plates. Seedlings were stratified for two days in a 0-4 °C freezer and then moved to a growth chamber (Percival CU41L5).

[0158] U.E Growth conditions were 22 °C, and the light intensity claimed by the producer is 120—^ With a long day cycle (16 hrs light, 8 hours dark). In vivo activation experiments used the same Percival with a complete cycle of dark conditions (24 hrs dark).

[0159] In vitro PPHs activation and photolysis

[0160] The system used for the in vitro activation included a stirrer, Prizmatix Ultra high- power collimated LED with UHP-T-365-LA22 filter for UV light source, quartz cuvette with 3mL volume, and a certified cuvette holder; the system did not change parts or settings during the experiment period.

[0161] Calibration curves for each molecule were prepared by measuring the spectra at various concentrations (2,25,50,75,100 ^M). The photo-activation system was designed with constant experimental conditions, using a 25 cm distance between the cuvette and light sources, with the same intensity of light (10%, which is 30 mW, the company states the max capability of the light source is 300 mW) power from the light source (measured at 4.15 mW). A magnetic stirrer is placed into the cuvette to stir the sample efficiently so the photo-activation process would be as efficient and homogenous as possible. The sample is dissolved in 80% DMSO and 20% H2O to a final concentration of 100 .M.

[0162] The UV light activates the reaction, and the herbicide's active compounds accumulate in the solution. For 6 minutes, every 30 seconds, a sample is taken to the LC- MS to track the reaction progress. Due to the calibration curves, we can monitor the reaction and understand how the PPHs react to UV light, which allows us to estimate the rate and efficacy of the photo-cleavable mechanism of every one of the molecules synthesized for the project. All the compounds- including the standards (samples of the free herbicides), were analyzed with this procedure, providing a simple, fast method to evaluate the kinetic properties of every PPH available for the project.

[0163] Sunlight In vitro activation

[0164] The LC-MS was used to measure the sunlight activation in the same manner it was used in the in vitro experiments (light Activation with a UV-light source with a controlled intensity).

[0165] The sunlight in vitro experiments were done in a cuvette exposed directly to sunlight. All the cuvettes were exposed to sunlight simultaneously, place and tools to avoid variance. After specific periods, identical between the samples, a small volume (50 pL) was taken from every sample for further HPLC analysis. From HPLC, the desired product yields, the amount of PPH that has not reacted, and the side product formation were studied. All the samples were made with the compound in 80% DMSO and 20% water solution into a final 100 pM concentration of PPH.

[0166] Root elongation assay as an In vivo experiment in plates

[0167] Arabidopsis Thaliana WT (col-0) plants were grown in MS-Agar for six days for those experiments and maintained and sterilized them with the conditions mentioned above. After six days, the plants were transferred to new plates with MS-Agar and a known concentration of Herbicide or PPH. They stayed on those plates for two hours, allowing the seedling to absorb the active ingredient. After this treatment, the plant was transferred again to a clean MS-Agar and then treated with UV light (0.523 mW) for 2 hours. After the treatment, the seedlings grow in a Percival for six days, and their growth is tracked and monitored. Plates spoiled due to contamination or technical reasons (moist, MS-Agar quality issues, and more) were eliminated by lab protocol. Plants were scanned on day six (after treatment), and the Fiji add-on on image J was used to measure their root elongation. The exposure to UV light was done in a UV light growth chamber made inhouse. This system fits plates and sprout pots.

[0168] Analysis conditions

[0169] HPLC-MS analysis was performed on Waters HPLC with XB ridge C18 column (100 X 3 mm, 5 pm) using a water-acetonitrile gradient of 0% to 100% solvent B for 17 minutes, then 3 minutes at 100% solvent B at a flow rate of 1 mL / min (solvent A = water, solvent B = acetonitrile, both contain 0.1% TFA as an additive). Mass spectrometry was performed on LC / MS Acquity QDa detector coupled with Waters HPLC.

[0170] Preparative HPLC purification conditions

[0171] Preparative HPLC was performed on Waters 2545 HPLC with XB ridge Cl 8 column (100 X 19 mm, 5 pm) using water (solvent A) and acetonitrile (solvent B) gradient of 10-90% solvent B for 25 minutes, then 5 minutes at 100% solvent B at a flow rate of 15 mL / min (solvent A and B both containing 0.1% TFA as an additive).

[0172] EXAMPLE 1 - Synthesis of PPG-herbicide conjugates

[0173] Two herbicides were selected, shown in Scheme 1 : 2,4-dichlorophenoxyacetic acid (2,4-D, 2), and 2-(2,4,5-trichlorophenoxy)propionic acid (2,4,5-TP, 3). . 2,4-D and 2,4,5-TP (also known as fenoprop or silvex) are synthetic auxin mimics; both compounds cause uncontrolled and unsustainable growth that causes plant death.

[0174] 2 3

[0175] Scheme 1. Herbicides used for PPHs synthesis. Synthesis of MNI-Based PPHs

[0176] Activation of the carboxylate with thionyl chloride or oxalyl chloride was applied to conjugate 2,4-D, and 2,4,5-TP, to MNI in this work (compounds 12, and 13, Scheme 3).

[0177] Scheme 3: MNI conjugation reactions with carboxylic acids. 2,4-D and 2,4,5-TP were activated using SOCh and further reacted with MNI to form 12 and 13 with -50% yield.

[0178] EXAMPLE 2 - PPHs evaluation

[0179] The evaluation of the PPHs efficacy comprises several stages, including in vitro evaluation, in vivo evaluation and soil in vivo evaluation, with the goal of each stage to assess critical characteristics of the compound’s performance. These include, for example, the release rate, efficiency and yields under lab conditions, and efficiency in the soil leading to the conclusion of potential future use in other plant species.

[0180] MNI-Protected Herbicides

[0181] Without being bound by theory, the mechanism of photo release from MNI derivatives may include any one of cyclization (CP) and migration (MP). These mechanisms may highlight several essential points regarding the photolysis reaction; first, the mechanism proceeds through several steps that might result in the formation of side products. Second, the MNI nitro group is converted into nitroso, while the indoline is converted into an indole (VI) or a 3H-indole (VII).

[0182] Scheme 4: General mechanisms for photorelease from MNI PPG. The results of in vitro evaluation of the MNI-protected herbicide's photolyze kinetics are shown in Figure 5A - Figure 5B.

[0183] The results show a relatively fast photolysis rate for MNI-2,4-D (12) and MNI- 2,4,5-TP (13). At the same time, a high yield of auxin release (93% and 86%, respectively, after 6 minutes of photolysis) was also observed. The HPLC analysis of the reactions 12 (Figure 6A - Figure 6C) and 13 (Figure 7A - Figure 7C) shows clean traces with the product and the reactant without side products. It was thus concluded that the fast and efficient release from MNI-2,4-D and MNI-2,4,5-TP might be suitable for applications in planta. In vitro photoactivation via sunlight

[0184] The performance of the compounds when irradiated by sunlight was then tested. This in vitro experiment was designed to evaluate the molecules' potential to be activated under field conditions before adding the variables related to plants themselves. It was assumed that low yields at this stage would result in even lower and impractical yields inside the plant. For this experiment, solutions of the compounds were prepared as in the in vitro experiments described above and then exposed side-by-side to direct sunlight (a clear day in February, Israel). The results are shown in Figure 8A - Figure 8B.

[0185] The results of this experiment resonate with those observed for photoactivation by UV light (Figure 5 A - Figure 5B) but with several differences. The MNI-protected synthetic auxins (12 and 13) showed fast activation kinetics (Figure 8A - Figure 8B), decomposing almost entirely after five minutes and reaching almost full release of the auxin after 10 min (chemical yields of 86% and 91%, respectively). The HPLC traces showed that side products were not formed - only the reactant and the expected products for 12 (Figure 9A - Figure 9C) and 13 (Figure 10A - Figure 10C) were observed. MNI- based PPHs fast (burst) release is excellent for the desired PPH design namely, burst effect.

[0186] EXAMPLE 3 - in vivo experiments

[0187] The in vivo evaluation focused on establishing an assay for quantitively comparing the efficacy of photocaged herbicides to that of the original herbicides. Thus, the in vivo efficacy of the compounds was evaluated on seedlings of the model plant Arabidopsis thaliana grown on plates under controlled conditions, and root elongation was monitored as readout.

[0188] First, the effect of UV on seedlings was evaluated to determine irradiation parameters. In the field, the catalyst of the reaction will be the sunlight, mainly the UV part of it. Under lab conditions, an irradiation chamber was designed where plants can be irradiated with UV under controlled conditions. Whole plants or seedlings in plates can be fitted into the chamber. Since plate covers are not permeable to UV, they must be removed before irradiation. The chamber itself is covered in aluminum foil to protect the user. The procedure is explained in more detail in the "Root elongation assay as an in vivo experiment in plates" section in the Methods section. To test for a possible irradiation window in which UV exposure does not lead to observable damage (with no herbicidal conjugates present), seedlings (approx. 6 days old) were exposed to UV in the irradiation chamber with different exposure times (4.15 mW cm'1s'1). Roots length was measured after 7 days and normalized to untreated plants. No significant effect was observed in the tested time frames (up to 2.5 hours) (Figure 11). In conclusion, in the time periods and light intensity used in the experiment, UV light does not significantly affect root elongation.

[0189] The MNI-protected synthetic auxin PPHs produce results with a generally clear trend (Figure 12A - Figure 12B).

[0190] 2,4-D experiment (Figure 12A): The effect of free 2,4-D was comparable in the absence and presence of light. This can be observed consistently in every concentration, providing additional evidence for the assumption that UV does not affect plant growth under these conditions. It also suggests that 2,4-D is not susceptible to photodegradation under our experimental conditions. In the absence of light, MNI-2,4-D (12) shows a slight decrease in root elongation with a wide variance, which appears in all concentrations tested for this group (MNI-2,4-D -UV). Without being bound by theory, the reason for the wide variance may emanate from a high variance of growth between the 3 experimental repetitions (Figure 13A - Figure 13F). The initial hypothesis was that MNI-2,4-D activated by UV would show efficacy at least as good as free 2,4-D. Surprisingly, the MNI-2,4-D group activated by UV light shows a significant decrease in root elongation but is much stronger in all tested concentrations than free 2,4-D. Log P measurements (Table 1) for 2 and 12 suggest the compounds are xylem mobile.

[0191] 2,4,5-TP experiment (Figure 12B): Without being bound by a theory, it is expected that free 2,4,5-TP in the presence or absence of light (+UV, -UV) would lead to a similar effect in plants. The experiment confirmed this expectation, suggesting that

[0192] 2,4,5-TP is not prone to photodegradation under these experimental conditions. For MNI-

[0193] 2,4,5-TP (13), in the absence of light, a wide variance in the effect was observed, in the same ranges of root elongation.

[0194] For the UV activated MNI-2,4,5-TP, a strong effect at 500 nM and 1 pM was observed, completely inhibiting elongation. UV activated MNI-2,4,5-TP shows higher efficacy than free 2,4,5-TP at all concentrations, even as low as 100 nm. The Log P measurements calculated by ChemDraw version 20.1 (Table 1) for 3 and 13 suggest that 3 is xylem mobile while 13 might be borderline too lipophilic and non-mobile in plants, but as seen in the results, it is not raised as an issue in those experiments.

[0195] Table 1. Log p values of PPHs in accordance with some examples disclosed herein.

[0196] Generally, 2,4-D and 2,4, 5-TP -based PPHs showed significantly better inhibition of root elongation in the model plants than their parent, commercially available herbicides.

[0197] EXAMPLE 4 - Bioactivity profile of a PAH compared to a free herbicide

[0198] Arabidopsis seedlings expressing the auxin reporter DR5: luciferase were used to evaluate the bioactivity profile of a PAH compared to a free herbicide. Thus, transgenic seedlings were exposed to either MNI-2,4-D or its parent 2,4-D (10 mM) for 9 hours in the absence of light, then moved to a clean plate and exposed to light (365 / 20 nm) for 2h. Luciferase signal was measured at time points throughout the experiment. The results (Figure 14) show that the bioactivity (measured as auxin signaling) of 2,4-D increases consistently from the time of application. In contrast, MNI-2,4-D shows no bioactivity until light irradiation, which is followed by a sharp increase in bioactivity, higher than that of 2,4, -D.

[0199] EXAMPLE 5 - Synthesis and in vitro evaluation of PPHs diverse modes-of-action

[0200] In order to evaluate the breadth of applicability of the strategy beyond auxin mimics, additional PPHs representing structures with different MOAs will be synthesized. As representative herbicides those presented in Scheme 5 were chosen. These herbicides cover multiple MOAs and structural families. All new PPHs will be first characterized in vitro for photoreaction rate and efficiency, as described hereinabove. PPHs with different rates of herbicide release will be tested, to evaluate the importance of this parameter to functionality in planta. The rate and efficiency of the photoreaction will also be examined in response to sunlight at different levels in order to assess the effects of light availability in field conditions. Thus, samples of PPHs in a cuvette will be exposed for Ih to sunlight in different conditions of times of year (seasons) and day (morning, afternoon, evening, night), cloud coverage and UV index levels. The storage stability of the PPHs (dark, room temperature, using HPLC-MS) over a long period, even one-year period will be monitored. ase

[0201] Inhibition of Microtubule Assembly Auxin Mimics

[0202] Scheme 5: Exemplary herbicides that will be used for synthesis of PPHs

[0203] EXAMPLE 6 - Efficacy evaluation and functional characterization of PPHs in model plants

[0204] PPHs will be evaluated for their efficacy in the model plant Arabidopsis thaliana, as described hereinabove.

[0205] Firstly, efficacy on seedlings grown in plates following brief exposure (2-8h) to either a PPH or its corresponding free herbicide (0.01-10 pM, herbicide dependent), will be evaluated.

[0206] In parallel, the efficacy on mature plants (4 weeks old) with administration via spray will be evaluated. Root length or plants size, respectively, will be measured for a period of 4-8 days to assess effect. The criterion for these evaluations will be outperforming the corresponding free herbicide by a factor of 2. PPHs meeting this criterion will be similarly evaluated on cotton or tomato seedlings and young plants in order to establish cross-species efficacy. The type of plant will be decided based on its sensitivity to the herbicide.

[0207] Subsequently, select PPHs will be studied for parameters such as uptake, translocation and metabolism rate. Uptake and metabolism will be measured jointly in the absence of light to prevent triggered photorelease of the herbicide. Arabidopsis seedlings will be exposed to PPHs and the respective free herbicides for a fixed amount of time (2-9h) in the absence of light and then the seedlings content will be analyzed by HPLC-MS / MS at different time points. To study basipetal or acropetal translocation, PPHs will be applied only to root or shoot tissue (via a split-dish assay) of DR5: luciferase transgenic seedlings. At different time points (12h-48h), the seedlings will be imaged on an IVIS imaging system and samples will be taken for HPLC-MS / MS analysis of content, quantifying PAH and free herbicide levels.

[0208] Separately, in this example, the depiction of bioactivity profile for 2,4-D-MNI (12) will be completed. Especially, focus on measuring later time points (15h-8d) will be given in order to characterize the peak bioactivity level and its expected decline rate in comparison to free 2,4-D.

[0209] EXAMPLE 7 - efficacy evaluation of select derivatives in two common weed types under simulated field conditions

[0210] PPHs using two common weed species: Brachypodium distachyon (monocot) and Bassia indica (dicot) will be evaluated.

[0211] First, experiments will be performed in a greenhouse, evaluating the effective concentrations of free herbicides and comparing them to those of the respective PPHs using spray as an application method (none treated plants will serve as control). A formulation of 5% EtOH in water with 0.02% surfactant will be used and plants will be 2-4 weeks old. PPHs that will show higher efficacy than their respective free herbicides will be promoted for evaluation in simulated field conditions in two setups:

[0212] Setup 1 : Using a single-nozzle track sprayer. This setup simulates field conditions application to mature, potted plants. Plants (4-8 weeks old, 10 in each experimental group) will be sprayed with either a free herbicide or its respective PAH at 3 different concentration based on results from greenhouse experiment and monitored in the greenhouse for 14 days for herbicidal effects.

[0213] Setup 2: Small-scale field testing in a test plot. In this setup, we will explore application in small scale but in field conditions. Small plots (2 m2) densely seeded with weeds (2-4 weeks old) will be treated with either a free herbicide or its respective PAH at 3 different concentrations based on results from greenhouse experiment. Application will be performed at dusk, images of plots will be taken daily and image analysis will be used to assess weeds coverage in each plot and their color.

[0214] Table 2. Herbicides and their mode of action.

[0215] Alipid synthesis inhibitors;Binhibitors of ALS (branched chain amino acid synthesis);cinhibitors of photosynthesis at PS II;Einhibitors of protoporphyrinogen oxidase;Finhibitors of pigment synthesis;Ginhibitors of EPSP synthase;Hinhibitors of glutamine synthetase;1DHP -inhibitors;Kainhibitors of microtubule assembly;Kbinhibitors of microtubule organization;Linhibitors of cellulose synthesis;Muncouplers (membrane disruption);Nlipid synthesis inhibitors (not ACCase);1sulfonylureas;2imidazolinones;3triazolopyrimidines;4pyrimidinyl (thio) benzoates;5sulfonylaminocarbonyl -triazolinones;6pyridazinone;7triazolinones;8phenylcarbamates;9triazinones;10nitriles;11phenyl-pyridazines;12diphenyl ethers;13thiadiazoles;14N-phenyl- phthalimides;15Pyrimidinediones;16F2-inhibitors of HPPD;17glycines;18phosphinic acids;19carbamates;20benzoic acids;21dinitroanilines;22arylaminopropionic acids;23alkylazines;24triazolocarboxamides;25dinitrophenols;26chlorocarboxylic acids.

Claims

CLAIMS:

1. A plant-protective conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, wherein said conjugate is accumulable within a plant; and said chemical bond is a photocleavable bond upon exposure to natural light, when said conjugate is within said plant.

2. The conjugate of claim 1, wherein upon exposure of said plant to light, the conjugate exhibits a herbicidal effect that is statistically significantly greater than the herbicidal effect of the herbicide when administered to said plant in free form.

3. The conjugate of claim 2, wherein upon exposure of said plant to said light, the conjugate exhibits a herbicidal effect that is at least twice greater than the herbicidal effect of the herbicide when administered to said plant in free form.

4. The conjugate of any one of claims 1 to 3, wherein said herbicide in free form has a first chemical reactive group, and said photoprotective moiety, has, in free form, a second chemically reactive group, and the first chemical reactive group and second chemical reactive group are chemically linkable.

5. The conjugate of any one of claims 1 to 4, wherein said herbicide comprise, in free form, a chemically reactive group selected from the group consisting of hydroxyl (-OH), carboxyl (-COOH), primary amine (-NH2), secondary amine (-NH), amide (-NHO), azide (-N3), vinyl (-CH=CH2), ethynyl (-CCH), aldehyde (-CHO), ketone (-CO), thiol (-SH), isocyanate (-NCO), epoxide (oxirane, -C2H4O), hydrazine (-NH-NH2), halogen, nitro (-NO2), acryloyl (CH2=CH-C0-), cyanate (-OCN), cyanide (-CN), hydroxymethyl (-CH2OH), and thioester (-COSR).

6. The conjugate of any one of claims 1 to 5, wherein said photoprotective moiety comprises, in free form, a chemically reactive group selected from the group consisting of hydroxyl (-OH), carboxyl (-COOH), primary amine (-NH2), secondary amine (-NH), amide (-NHO), azide (-N3), vinyl (-COCH2), ethynyl (-CCH), aldehyde (-CHO), ketone (-CO), thiol (-SH), isocyanate (-NCO), epoxide (oxirane, -C2H4O), hydrazine (-NH-NH2), halogen, nitro (-NO2), acryloyl (CH2=CH-C0-), cyanate (-OCN), cyanide (-CN), hydroxymethyl (-CH2OH), and thioester (-COSR).

7. The conjugate of any one of claims 1 to 6, wherein said photoprotective moiety is selected from the group consisting of o-nitrobenzyl, (Coumarin-4-yl)methyl, arylmethyl, arylcarbonylmethyl, benzothiadiazol-6 / 7-yl)methyl, / 2-hydroxy phenacyl (pHP), quinones and any chemical derivative of same.

8. The conjugate of claim 7, wherein said photoprotective moiety is o-nitrobenzyl and any derivative thereof.

9. The conjugate of claim 8, wherein said photoprotective moiety is 4-methoxy-7- nitroindolinyl (MNI).

10. The conjugate of claim 7, wherein said photoprotective moiety is (Coumarin-4- yljmethyl and any derivative thereof.

11. The conjugate of claim 7, wherein said photoprotective moiety is p- hydroxyphenacyl and any derivative thereof.

12. The conjugate of any one of claims 1 to 11, wherein said herbicide is a compound having a mode of action selected from the group consisting of light activation of reactive oxygen species (ROS), inhibition of cellular metabolism and inhibition of cell division and growth.

13. The conjugate of any one of claim 1 to 12, wherein said herbicide is selected from the group consisting of 2,4-D, 2,4-DB, 2,4,5-T, Aclonifen, Acetochlor, Acifluorfen, Alachlor, Amicarbazone, Amidosulfuron, Amitrole, Aminocyclopyrachlor, Aminopyralid, Ammetryne, Anilofos, Atrazine, Azafenidin, Azimsulfuron, Barban, Beflubutamid, Benazolin, Benfuresate, Benefin / benfluralin, Bensulide, Bensulfuron- methyl, Bentazon, Benzobicyclon, Benzofenap, Benthiocarb, Bialaphos / bilanafos, Bifenox, Bifenthrin, Bispyribac-Na, Bixlozone, Bromacil, Bromobutide, Butachlor, Butafenacil, Butralin, Cafenstrole, Carbetamide, Carfentrazone-ethyl, Chlorthal- dimethyl / DCPA, Chlorthiamid, Chloranocryl / dicryl, Chloramben, Chloridazon / pyrazon, Chlorimuron-ethyl, Chlorotoluron, Chlorpropham, Chlorsulfuron, Clodinafop-propargyl, Clomazone, Clomeprop, Cloransulam-methyl, Clethodim, Cinosulfuron, Cinmethylin, Cinidon-ethyl, Cycloxydim, Cyclopyrimorate, Cyflufenamid, Cyhalofop-butyl, Cinosulfuron, Cumyluron, Cypermethrin, Cyanazine, Cycloate, Cyclosulfamuron,Difenzoquat, Difenzoquat-methyl, Diflufenican, Diflufenzopyr, Dimethachlor, Dimethenamid, Dimethametryn, Dimepiperate, Diquat, Dichlobenil, Dichlorprop, Diclosulam, Diclofop-methyl, Dicamba, Dimethachlor, Dimethametryn, Dinitramine, Dithiopyr, DNOC, Dinoseb, Diphenamid, Diuron, DMPA, Dymron / daimuron, DSMA, Endothall, Enoxaprop, Ethalfluralin, Ethametsulfuron-methyl, Ethofumesate, Ethoxysulfuron, Esprocarb, EPTC, Etobenzanid, Fenoxaprop-ethyl, Fenoxasulfone, Fenquinotrione, Fenoxaprop-P-ethyl, Fenoxaprop, Fenthiaprop, Fentrazamide, Fentrazamide, Flazasulfuron, Flamprop-m, Florasulam, Florpyrauxifen, Flucarbazone- Na, Flucetosulfuron, Flumetsulam, Flufenacet, Flumiclorac-pentyl, Flumioxazin, Flumioxazin, Fluometuron, Flumioxazin, Fluopyram, Fluopyram, Fluoxastrobin, Fluoroacetate, Flurochloridone, Fluroxypyr, Fluridone, Flurtamone, Fluthiacet-methyl, Foramsulfuron, Fosamine, Fomesafen, Glufosinate-ammonium, Glyphosate, Halauxifen, Halosulfuron-methyl, Haloxyfop-methyl, Hexazinone, Imazaquin, Imazaquin, Imazamox, Imazapic, Imazapyr, Imazapyr, Imazapyr, Imazethapyr, Imazosulfuron, Imidacloprid, Indaziflam, Indanofan, Isoproturon, Isoxaflutole, Isoxaben, Lactofen, Lenacil, Linuron, MCPA, MCPB, Mecoprop-ethyl, Mesosulfuron-methyl, Mesotrione, Metamitron, Metamifop, Metazachlor, Metamifop, Methabenzthiazuron, Methiozolin, Metolachlor, Metazachlor, Metazachlor, Metsulfuron-methyl, Metribuzin, Molinate, Monuron, MSMA, Napropamide, Naproanilide, Naptalam, Niclofen, Nicosulfuron, Norflurazon, Orbencarb, Orthosulfamuron, Oxyfluorfen, Oxadiargyl, Oxadiazon, Oxyfluorfen, Pelargonic acid, Penoxsulam, Pentoxazone, Pendimethalin, Pethoxamid, Picloram, Picolinafen, Pinoxaden, Primisulfuron-methyl, Profoxydim, Prodiamine, Prom eton, Prometryne, Propanil, Propachlor, Propazine, Propisochlor,Propoxycarbazone-Na, Propyzamide / pronamide, Prosulfocarb, Prosulfuron, Propanil, Pyraclonil, Pyrasulfotole, Pyribenzoxim, Pyributicarb, Pyriftalid, Pyrithiobac-Na,Pyridate, Pyridate, Pyrimisulfan, Pyriminobac-methyl, Pyraflufen-ethyl, Pyrazoxyfen, Pyrazolynate, Pyroxsulam, Quinclorac, Quinmerac, Quizalofop-ethyl, Rimsulfuron, Saflufenacil, Sethoxydim, Simazine, Sulcotrione, Sulfentrazone, Sulfometuron-methyl, Sulfosulfuron, Tefuryltrione, Tebuthiuron, Terbacil, Terbuthylazine, Terbutryne, Thiazopyr, Thiazopyr, Thenylchlor, Thifensulfuron-methyl, Thiob encarb / Benthiocarb, Tiafenacil, Tiafenacil, Tritosulfuron, Tralkoxydim, Tribenuron-methyl, Triaziflam, Triaziflam, Triafamone, Triafamone, Triafamone, Tri-allate, Trifludimoxazin, Trifluralin, Trifluralin, Triflusulfuron-methyl, Trinexapac-ethyl, Vernolate, Quizalofop-ethyl, Triclopyr, Topramezone, Tolpyralate, chemical derivatives, salts and prodrugs thereof.

14. The conjugate of any one of claims 1 to 13, wherein said herbicide is 2,4- dichlorophenoxyacetic acid (2,4-D), having the following chemical structure:

15. The conjugate of claim 14, being MNI-2,4-D, having the following chemical structure16. The conjugate of any one of claims 1 to 13, wherein said herbicide is 2-(2,4,5- trichlorophenoxyjpropionic acid (2,4,5-TP) having the following chemical structure:

17. The conjugate of claim 14, being MNI-2,4,5-TP, having the following chemical structure:

18. A method comprising delivery to a plant a conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, the conjugate being accumulable within a plant; and the chemical bond is a photocleavable bond, when said conjugate is within said plant, wherein said delivery is in absence of light effective to cause cleavage of said photocleavable bond and under conditions allowing accumulation of said conjugate in said plant.

19. The method of claim 18, wherein said conjugate is as defined in any one of claims 1 to 17.

20. The method of claim 18 or 19, comprising at least a period of exposure of said plant to light.

21. The method of claim 20, wherein said light can be natural light and / or artificial light.

22. The method of claim 20 or 21, wherein said light comprises a wavelength or wavelength band within a wavelength range of 280 nm and about 800 nm.

23. The method of any one of claims 18 to 22, comprising delivery of a conjugate amount that is statistically significantly below an amount of the free herbicide required for achieving a same herbicidal effect on same plant.

24. The method of any one of claims 18 to 23, wherein said conditions allowing accumulation of said conjugate in said plant comprise duration of delivery, amount of conjugate, and / or conjugate delivery vehicle.

25. An agricultural composition comprising an agriculturally acceptable vehicle and a conjugate comprising a herbicide linked to a photoprotective moiety with a chemical bond, the conjugate being accumulable within a plant; and the chemical bond is a photocleavable bond, when said conjugate is within said plant.

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