Novel modulators of plant nitrate, ammonium, and potassium and methods of using the same

Abstract

Novel methods and compositions for modulating NO3- transporter in a plant are disclosed.

Description

[0001] NOVEL MODULATORS OF PLANT NITRATE, AMMONIUM, AND POTASSIUM AND METHODS OF USING THE SAME

[0002] FIELD OF THE INVENTION

[0003] The invention relates to novel modulators of plant nitrate, ammonium, and potassium and methods of using them in crop protection .

[0004] BACKGROUND OF THE INVENTION

[0005] Nitrogen critically influences plant growth and development. Plants adopt numerous strategies to modulate the uptake capacity of their roots to cope with spatial and temporal fluctuations in N availability. The molecular basis of nitrate uptake by the root has been studied intensively over the past 30 years. Plants employ two different uptake systems depending on how much external nitrate is available: the high-affinity and low- affinity transport systems (HATS and LATS) , operating at low (<1 mM) or high (>1 mM) medium nitrate, respectively.

[0006] Plants' genome has multiple Nitrate Transporter! or Nitrate Transporterl / Peptide Transporter family (NRT1 / NPF) genes and Nitrate Transporter! (NRT2) genes. The NPF family is responsible for LATS, while the NRT2 / NNP ( nitrate-nitrite porter) functions in HATS. Although most NRT2 and NPF transporters have yet to be functionally characterized, four NRT2 transporters (NRT2.1, NRT2.2, NRT2.4, and NRT2.5) and two NPF transporters (NRT1.1 and NRT1.2) are components of root nitrate uptake. NRT1.1 is the only demonstrated dual-affinity nitrate transporter and a putative nitrate sensor (transceptor) .

[0007] Within the NRT2 / NPF family, NRT2.1 predominantly localizes to the plasma membrane of root epidermal and cortical cells, where the bulk of nitrate uptake occurs. Among NPF transporters, 13 have been found to be involved in root-to-shoot transport, seed development, or N storage. NPF2.7, also called NAXT1, is the known root nitrate efflux transporter identified to date. In addition to NPF and NRT2 transporters, CLC and SLAC / SLAH protein family members facilitate nitrate transport inside the plant. SLAC / SLAH is a small protein family encoded by five genes that display a common predicted structure of 10 transmembrane domains. Among them, SLAC1 and SLAH3 are characterized by NO3- / Cl- permeability and appear to be involved in regulating stomatai closure. In contrast, SLAH2 is expressed in the stele of the root and encodes an anion channel that transports nitrate exclusively and may facilitate nitrate transport between root and shoot. Seven CLC genes have been identified in Arabidopsis. CLCa and CLCb proteins are NO3- / H+ antiporters involved in vacuolar nitrate storage and are the only two (out of over 20 nitrate transporters) that do not localize to the plasma membrane (see Vidal et al. , (2020) . The Plant Cell, 32 (7) , 2094- 2119. https: / / doi.org / 10.1105 / tpc.19.00748 for review) .

[0008] The 3D structure of the NRT1.1 protein is known and is represented by atomic coordinates of the structure of NRT1.1 dimer from Arabidopsis Thaliana that has been experimentally determined using X-ray crystallography (PDB codes 4OH3, 5A2O) . In addition, the inward-facing conformation of the nitrate transport channel corresponding to a low-affinity state of the NRT1.1 protein structure has been used as an NRT1.1 model. This structure (A0A178W8F7) is deposited in the AlphaFold DB (https : / / alphafold .ebi.ac.uk / and https : / / alphafold .ebi.ac.uk / entry / A0A178W8F7 ) .

[0009] The outward-facing conformation of the NRT1.1 protein model was determined based on structural similarity and homology within the major facilitator superfamily (MFS) transporters, as referenced in the Transporter Classification Database (TCDB) . To create the model, the outward-facing scaffold of the mammalian peptide transporter HsPepTl / SLC15Al was used, with PDB codes 7PMX, 7PMW, and 7PN1 identified using the NCBI VAST (vector alignment search tool) . Specifically, the N- and C-terminal domains of the NRT1 . 1 inward structure were aligned and overlaid onto the corresponding domains of the homologous proteins in their outward-facing conformations .

[0010] Besides their role as protein constituents , amino acids and their derivatives are also involved in a plethora of cellular reactions . Therefore , they influence several physiological processes such as plant growth and development , intracellular pH control , generation of metabolic energy or redox power , and resistance to both abiotic and biotic stress . Furthermore , amino acids have a role during signaling in plants has recently been discussed . In this context , regulation of amino acid content , fluxes , and transport through the plant are critical for plant adaptation to carbon and nitrogen status , development , and defense .

[0011] Nitrate influx is strongly upregulated by N limitation or N starvation and, on the contrary, downregulated by high N provision . Metabolic processes , photosynthesis , and multiple hormonal signals modulate nitrate transporters . In turn, point mutations in two key residues of NRT1 . 1 ( P492 and T101 ) differentially affect several of the NRT1 . 1-dependent responses to nitrate , and the short-term upregulation of the nitrate- uptake gene NRT2 . 1 , and its longer-term downregulation, at high nitrate concentrations . These mutations have differential effects on genome-wide gene expression . NRT1 . 1 activates four separate signaling mechanisms , which have independent structural bases in the protein . In particular , the phosphorylated and non- phosphorylated forms of NRT1 . 1 at T101 have distinct signaling functions , and the nitrate-dependent regulation of root development depends on the phosphorylated form.

[0012] The early events after nitrate influx are often called the Primary Nitrate Response ( PNR) . It has been proposed that the ornithine-urea cycle (urea cycle ) might constitute an important control point of N metabolism in plants . Excessive nitrate and ammonium are converted into Glu, Gin, and then to Asp, Asn, and N-rich amino acids associated with the urea cycle , such as Arg and ornithine ( Orn) . Activation of the Urea cycle may be used as a marker of the plat overload with nitrate and / or ammonium.

[0013] New compounds effective for controlling the growth of undesired vegetation are in constant demand . In the most common situation, such compounds are sought to selectively control the growth of weeds in useful crops such as cotton, rice , corn / maze , wheat and soybeans , to name a few . Unchecked weed growth in such crops can cause significant losses , reducing profit for the farmer and increasing costs to the consumer . In other situations , herbicides are desired to control all plant growth . Examples of areas in which complete control of all vegetation is desired are areas around railroad tracks , storage tanks , and industrial storage areas . Identifying new compounds having herbicidal activity, which are more effective , less costly, and environmentally safe remains long and unmet need .

[0014] SUMMARY OF THE INVENTION

[0015] It is a principal obj ect of the present invention to provide novel NO3- modulators , that have a beneficial safety profile and potent herbicidal activity .

[0016] According to some embodiments , the invention provides a method of modulating at least one NO3- sensor in a plant , the method comprising applying at least one compound, the compound comprising : ( i ) a substituted or non-substituted 5 -membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by an optionally substituted flexible linker ; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker , and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom ( A) .

[0017] According to some embodiments , the invention further provides a method of modulating at least one NO3- sensor in a plant , the method comprising applying at least one compound, the compound comprising : ( i ) a substituted or non-substituted 6-membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by a flexible linker ; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0018] According to some embodiments , the invention further provides a method of modulating the accumulation of nitrate in a plant , the method comprising applying to the plant at least one compound, the compound comprising : ( i ) a substituted or non-substituted 5 -membered heterocycle , and ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by an optionally substituted flexible linker ; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker , and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0019] According to some embodiments , the invention further provides a method of modulating the accumulation of nitrate in a plant , the method comprising applying to the plant at least one compound, the compound comprising : ( i ) a substituted or non-substituted 6-membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by a flexible linker; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0020] According to some embodiments , the invention further provides a method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, the compound comprising : ( i ) a substituted or non-substituted 5 -membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by an optionally substituted flexible linker ; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker , and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0021] According to some embodiments , the invention further provides a method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, the compound comprising : ( i ) a substituted or non-substituted 6-membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by an optionally substituted flexible linker ; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker , and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0022] According to some embodiments , the invention further provides a herbicidal composition comprising at least one compound, the compound comprising : ( i ) a substituted or non-substituted 6- membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by a flexible linker; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom, and at least one herbicidally acceptable carrier .

[0023] According to some embodiments , the invention further provides a herbicidal composition comprising at least one compound, the compound comprising : ( i ) a substituted or non-substituted 5- membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by a flexible linker; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom, and at least one herbicidally acceptable carrier .

[0024] BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 . Illustrates channel-like scaffold in the inter-subunit interface of the NRT1 . 1 dimer with NO3- . The output is produced by the Membrane Builder (CHARMM-GUI tools ) . A pore with a minimal radius of 4 . 5 A is formed on the extracellular side of the NRT1 . 1 dimer . The radius of the transport channel on the intracellular side ranges from 12 to 15 A.

[0026] DETAILED DESCRIPTION OF THE INVENTION

[0027] The present invention is now described more fully hereinafter with reference to the accompanying examples , in which embodiments of the invention are shown . This invention may, however , be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather these embodiments are provided so that this disclosure will be thorough and complete and will fully convey the scope of the invention to those skilled in the art .

[0028] It is a principal obj ect of the present invention to provide novel , safe and potent herbicides .

[0029] The present application provides new compounds designed using certain scaffolds of amino acid derivatives that selectively bind NRT1 . 1 and thus disrupt the plant ' s NO3“ / NH4+sensing, uptake , and metabolism. Assuming the conservative nature of nitrate sensors , the foregoing embodiments of the invention should be extended to other members of the NRT1 and NRT2 families .

[0030] According to some embodiments , the invention provides a method of modulating at least one NO3- sensor in a plant , the method comprising applying at least one compound or a salt thereof , the compound comprising : ( i ) a substituted or non-substituted 5- membered Heterocycle , ( ii ) an anionic or electronegative group, wherein ( i ) and ( ii ) are interconnected by a flexible li nker , wherein the preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible l inker and an intramolecular distance in the range of

[0031] 3 to 10 Angstrom (A) between the centroid of the heterocycle and acidic or electronegative site / moiety of trie anionic or the electronegative group .

[0032] According to some embodiments , the invention provides a method of modulating at least one NO3- transporter in a plant , the method comprising applying at least one compound characteri zed by having a binding affinity to at least one area of the at least one NO3- transporter , the compound comprising : ( i ) a substituted or non-substituted 5-membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i) and ( ii ) are interconnected by an optionally substituted flexible linker; and wherein a preferred spatial arrangement ( PSA) of the compound has a tors ion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker , and, wherein an intramolecular distance between the centroi d of the heterocycle and the acidic or electronegative site of the anionic or electronegat ive group is in the range of 3 to 10 Angstrom.

[0033] According to some embodiments , the invention provides a method of modulating at least one NO3- transporter in a plant , the method comprising applying at least one compound characterized by having a binding affinity to at least one area of the at leas t oneNO3- transporter, the compound comprising : ( i ) a substituted or non-substituted 6-membered heterocycle , and ( ii ) an anionic or electronegative group comprising an acidic and / or electronegat ive site ; wherein ( i) and ( ii ) are interconnected by a f lexible l inker ; and wherein a prefer red spatial arrangement ( PSA) of the compound has a torsion angle in the range of +25 to + 80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular dis tance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom. According to some embodiments, the invention provides a method of modulating accumulation of nitrate in a plant, the method comprising applying to the plant at least one compound, characterized by having a binding affinity to at least one area of the at least one NO3- transporter, the compound comprising: (i) a substituted or non-substituted 5-membered heterocycle, and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by an optionally substituted flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0034] According to some embodiments, the invention provides a method of modulating the accumulation of nitrate in a plant, the method comprising applying to the plant at least one compound / composition characterized by having a binding affinity to at least one area of the at least one NO3- transporter, the compound comprising: (i) a substituted or non-substituted 6- membered heterocycle, and (ii) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by a flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0035] According to some embodiments, the invention provides a method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, characterized by having a binding affinity to at least one area of the at least oneNO3- transporter, the compound comprising: (i) a substituted or non-substituted 5 -membered heterocycle, and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by an optionally substituted flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0036] According to some embodiments, the invention provides a method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, characterized by having a binding affinity to at least one area of the at least oneNO3- transporter, the compound comprising:

[0037] (i) a substituted or non-substituted 6-membered heterocycle, and

[0038] (ii) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by a flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

[0039] .As used herein, the term ''plant" refers, without limitation, to the whole plant or plant parts, such as roots, leaves, shoots, seeds, fruits, stem, flower, and plant cells. The term "applying to the plant" refers, without limitation, to any suitable application method, including foliar application, soil application, or any other relevant application method. According to some embodiments , the plant can be a harmful plant

[0040] According to some embodiments, the plant can be a crop. According to some embodiments, the plant can be a grass, a cereal, a shrub, an herbaceous plant, or any other relevant organism. plant can be characterized monocotyledons or monocots, or dicotyledons, dicotyls or dicots, eudicotssEudicotidae , or eudicotyledons (tricolpates) . s ome embo d ime nt s , omoound is selective to eudicots,

[0041] Eudicotidae, or eudicotyledons ( tricolpates ) .

[0042] As used herein, the term "flexible linker" refers, without limitation, to any chain having a degree of spatial freedom. The freedom can be characterized as spatial movement or rotation according to any axis in relation to the chain. In some embodiments, the flexible linker is characterized as having multiple spatial arrangements.

[0043] According to some embodiments of the above and foregoing methods, the preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of -50 to -80 degrees.

[0044] According to some embodiments of the above and foregoing methods, the preferred spatial arrangement (PSA) of the compound has a torsion angle of: -25 degrees, -26 degrees, -27

[0045] 28 degrees, -29 degrees, “30 degrees, -31 degrees, “32 degrees

[0046] 33 degrees, ~34 degrees, -35 degrees, -36 degrees, -37 degrees

[0047] 38 degrees, ~39 degrees, -40 degrees, -41 degrees, -42 degrees

[0048] 43 degrees, -44 degrees, -45 degrees, -46 degrees, -47 degrees

[0049] 48 degrees, -49 degrees, -50 degrees, -51 degrees, -52 degrees

[0050] 53 degrees, -54 degrees, -55 degrees, -56 degrees, -57 degrees

[0051] 58 degrees, -59 degrees, -60 degrees, -61 degrees, -62 degrees

[0052] 63 degrees, -64 degrees, -66 degrees, -67 degrees

[0053] 68 degrees, -69 degrees, -71 degrees, -72 degrees

[0054] 73 degrees, -74 degrees, -76 degrees, -77 degrees

[0055] 78 degrees, -79 degrees, According to s ome embodiments of the above and foregoing methods, the preferred spatial arrangement (PSA) of the compound has a torsion angle of: 25 degrees, 26 degrees, 27 degrees, 28 degrees , 29 degrees, 30 degrees, 31 degrees , 32 degrees , 33 degrees , 34 degrees, 35 degrees, 36 degrees , 37 degrees , 38 degrees , 39 degrees, 40 degrees, 41 degrees 42 degrees 43 degrees , 44 degrees, 45 degrees, 4: 6 degrees , 47 degrees , 48 degrees , 49 degrees, 50 degrees, 51 degrees , 52 degrees , 53 degrees , 54 degrees, 55 degrees, 56 degrees , 57 degrees , 58 degrees , 59 degrees, 60 degrees, 61 degrees , 62 degrees , 63 degrees 64 degrees, 65 degrees, 66 degrees, 67 degrees, -68 degrees , 69 degrees, 70 degrees, 71 degrees, 72 degrees, 73 degrees , 74 degrees, 75 degrees, 76 degrees 77 degrees 78 degrees , 79 degrees, and 80 degrees.

[0056] According to s ome emb o d ime n t s of the above and foregoing methods , the flexible linker and an intramolecular distance between the centroid of the heterocycle and acidic orelectronegative site / moiety of the anionic or the electronegative group is 3.0 Angstrom (A) , 3.1 A, 3.2 A 3.3 A,

[0057] 3.4 A, 33..66 AA,, 3.7 A, 3.8 A, 3.9 A, 4.0 A, 4.1 A, 4.2 A, 4.3 A,

[0058] 4.4 A, 44..55 AA,, 4.6 A, 4.7 A, 4.8 A, 4.9 A, 5.0 A, 5.1 A, 5.2 A,

[0059] 5.3 A, 5.4 A, 5.6 A, 5.7 A, 5.8 A, 5.9 A, 6.0 A, 6.1 A, 6.2 A,

[0060] 6.3 A, 6.4 A, 6.5 A, 6.6 A, 6.7 A, 6.8 A, 6.9 A, 7.0 A, 7.1 A,

[0061] 7.2 A, 7.3 A, 7.4 A, 7.6 A 7.7 A, 7.8 A, 7.9 A, 8.0 A, 8.1 A,

[0062] 8.2 A, 8.3 A, 8.4: A, 8.5 A, 8.6 A, 8.7 A, 8.8 A, , 8.9 A, 9.0 A, 9.1 A, 9.2 A, 9.3 A, 9.4 A, 9.6 A, 9.7 A, 9.8 A, 9 : .9 A, and 10.0 A.

[0063] According to s ome emb o d ime n t s of the above and foregoing methods , the flexible linker and an intramolecular distance between the centroid of the heterocycle and acidic orelectronegative site / moiety of the anionic or the electronegative group is in the range of 3 to 10 Angstrom. According to some embodiments of the above method, the at least one compound is an amphoteric compound. As used herein, the term ’'amphoteric'’ refers, without limitation, to compounds that can act as both an acid or a base.

[0064] According to some embodiments ot the above methods, the amphoteric compound may donate an electron.

[0065] According to some embodiments of the above methods, the at least one compound is an amphiphilic compound. In some embodiments, the at least one compound has a Log P is in the range of -1.5 to 3.

[0066] According to some embodiments, the invention provides a method of modulating at least one NO3- sensor in a plant, the method comprising applying at least one compound, the compound comprising: (i) a substituted or non-substituted 6-membered Heterocycle, ( ii ) an anionic / electronegative group, wherein (i) and (ii) are interconnected by a flexible linker, wherein the preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker and an intramolecular distance in the range of 3 to 10 Angstrom between the centroid of a heterocycle and the acidic / electronegative site / moiety .

[0067] As used herein, the term "sensor" is meant to be understood, without limitation, to refer to any cellular protein capable of sensing environmental conditions, serving as a sensor or signal transducer for any environmental stimuli. In the context of the invention the term " NO3- sensor" refers, without limitation, to any protein capable of sensing environment NaOl3- concentrations.

[0068] According to some embodiments of the above methods, the application of the above compounds may lead to increased accumulation (higher levels) of metabolites related to nitrogen assimilation in plants. A non-limiting list of such metabolites includes intracellular Aspartic acid (Asp) , Asparagine (Asn) , amino acids related to the Ornithine cycle, Citrulline (Cit) , Arginine (Arg) , and Ornithine (Orn) -

[0069] According to some embodiments of the above methods, the application of the above compounds may cause accumulation of urea and polyamines (such as agmatine) indicating an increase in nitrate levels within plant cells (Example 7) .

[0070] According to some embodiments of the above methods, the application of the above compounds leads to an increase of plant nitrate, ammonium, and potassium levels / concentration. The non- limited list of plant species includes Lettuce R, Soybeans (Glycine mar) , Basilicum, According to some embodiments, the increase in plant nitrate, ammonium, and potassium levels / concentration is dose-dependent (Example 6) ,

[0071] In the context of the invention, the terms 'anionic' or 'electronegative' group refer, without limitation, to any group that carries an overall full or partial negative charge. Electronegativity is a chemical property of a molecule (such as an atom) or a part of a molecule (such as a moiety or a functional group) that describes the tendency of the atom, the moiety, or the functional group to attract electrons toward itself and thus to obtain a partial negative charge. In some embodimients the anionic or electronegative group is an acidic group or moiety. In some embodiments, anionic groups, e.g., COO- and NO3-, have a full negative charge. In some embodiments, electronegative groups shift electron pairs and get a partial negative charge, e.g. , COOH, NO2, Cl, Br and more.

[0072] In the context of the invention, the term 'torsion angle’ may refer, without limitation, to the angle between the planes formed by the flexible linker; or, to the dihedral angle formed between two planes: (i) plane formed by the heterocycle and (ii) the plane formed by the anionic, acidic, and / or electronegative group (as compared to regular angles, formed between two lines or bonds ) . As used herein, the term 'centroid' , refers, without limitation, to the geometric center of the heterocycle .

[0073] According to some embodiments, the NO3- sensor is Dual affinity Nitrate Transporter.

[0074] According to some embodiments of the above methods, the non- limiting list ofNO3- sensors includes dual-affinity nitrate transporter NRT1.1 -

[0075] According to any embodiments of any of above methods, NO3- transporter is selected from a group consisting, without limitations, of the Transporter family (NRT1 / NPF) and Nitrate Transporterf (NRT2) family, specifically, NPF6.3 (NRT1.1) NPF6.2 (NRT1.4) , and NRT2.1.

[0076] According to any embodiments of any of above methods, at least one area of the at least one NO3- transporter is aNO3- binding site .

[0077] According to some embodiments of the above methods, the compound is characterized as amphoteric.

[0078] According to some embodiments of the above methods, the compound is characterized as amphiphilic.

[0079] According to any embodiments of any of above methods the NO3- transporter is selected from a group consisting of Nitrate T r a n s p o r t e r 1 / P e p t i d e .

[0080] According to any embodiments of any of the above methods the binding affinity is equal to or higher than -4 kcal / mol. According to any embodiments of any of above methods the binding affinity is equal or higher than -8 kcal / mol. In some embodiments of any of above methods the binding affinity is equal or higher than -10 kcal / mol.

[0081] According to any embodiments of any of above methods the leterocycle is at least a partially positively charged or a dipole . According to some embodiments of any of the above methods, the heterocycle comprises at Least one heteroatom. In some embodiments, the heterocycle comprises at least two heteroatoms. In some embodiments, at least one heteroatom is sulfur (S) , nitrogen (N) or oxygen (0) .

[0082] According to any embodiments of any of the above methods, the two heteroatoms are sulfur and nitrogen, nitrogen and oxygen, and nitrogen and nitrogen. In some embodiments, the heterocycle is selected, without limitations, from the group consisting of Pyridine (C5N) , Pyrrole (C4N) , Thiophen (C4S) , 1,2-Thiazole (C3NS) , 1,3-Thiazole (C3NS) , Isothiazole (C3NS) , 1,2-Thiazine (C4NS) , 1,3-Thiazine (C4NS) , 1,4-Thiazine (C4NS) , Oxazole (C3NO) , Isoxazole (C3NO) , 1,2-Oxazines (C4NO) , 1 , 3-Oxazines (C4NO) , and

[0083] 1,4-Oxazines (C4NO) .

[0084] According to any embodiments of any of the above methods, the heterocycle is substituted by at least one molecule. A non- limiting list of the molecules includes -H, -Cl, -Br, -F, -I, - NO2, =O, =S, -CF3, -HC=O, -RC=O, -COOH, -C1CO, -SO3R, and -CN. Preferably, the heterocycle is substituted by -Cl, -Br, -F, -I, — NO2 , =O , = S, — CF3, - CCI3, — SO2F, and — CN .

[0085] According to any embodiments of any of above methods the heterocycle has 1 or 2 substituted carbon atoms.

[0086] According to any embodiments of any of above methods, the heterocycle is characterized as having at least a partial Amphiphilic or as a dipole.

[0087] According to some embodiments of the above methods, the acidic or electronegative group is characterized by having at least a partial negative charge.

[0088] According to some embodiments of any of the above methods, a non-limiting list of the acidic and / or electronegative group includes carboxyl, carbonyl, alkyl chloride, carboxamide, amide, Imide, acid chloride, phosphonate, phosphate, sulfate, sulfonate, nitro, cyano, and nitrate, or an ester thereof, or a salt thereof.

[0089] According to some embodiments of any of the above methods, the ester is selected, without limitations, from an alkane; a phenol; a mono-, di-, or three halides phenol; a pyridine; mono- , di-, or three halides pyridine; an alkyl phenol (aliphatic chain C1-15) ; alkyl pyridine (aliphatic chain C1-15) , an ether, a polyether, a diol, poly-diol, or any combination thereof.

[0090] According to some embodiments of the above methods, the flexible linker comprises up to 12 atoms. In some embodiments, the linker can comprise substituted or non-substituted carbon atoms and heteroatoms. A non-limiting list of heteroatoms in the flexible linker includes oxygen, substituted or non-substituted sulfur, and substituted or non-substituted nitrogen, or any other suitable heteroatom. In some embodiments, the linker can comprise between 0 to 6 heteroatoms. An exemplary embodiment of the flexible linker comprising six heteroatoms is depicted be 1. ow :

[0091] According to some embodiments of any of the above methods the flexible linker comprises at least substituted carbon atoms and 0 or 1 heteroatom selected from oxygen (O), sulfur (S ) , and nitrogen (N) .

[0092] According to some embodiments of the above methods, the flexible linker can be substituted, without limitation, with H, F, Cl,

[0093] Br, or I

[0094] According to some embodiments of any of the above methods, the carbon atom of the flexible linker is substituted, without limitations, with (CH2)nCH3, -O [ (CH2)2O]m(CH2)nCH3, (CH2)nC6H5, - 0 [ (CH2)2O]m(CH2)nC6H5, (CH2)nC5NH4, -O [ (CH2)2O]m(CH2)nC5NH4,

[0095] (CH2) nC5NHsBr, -O [ (CH2)2O]m(CH2)nC5NH3Br, ( CH2)nC5NH2Br F, or

[0096] 0 [ (CH2)2O]m(CH2) nC5NH2BrF; and wherein n = 0 to 15 and m = 0 to 5. According to some embodiments of the above methods, the at least one compound is devoid of any H-bond donors.

[0097] According to some embodiments of the above methods, the at least one compound has a spatial arrangement with the lowest energy minimum among all possible conformers. In some embodiments, the at least one compound has spatial arrangement induced by interaction with the nitrate-sensing binding site of the transceptor molecule NRT1.1 (hereafter PSA) . As used herein, the term "transceptor" refers to a cellular molecule, or protein, dual-affinity nitrate transporter and a putative nitrate sensor capable of both acting as both transporter and a sensor for any environmental stimuli.

[0098] According to some embodiments of the above methods, any one of the binding sites are defined by Amino Acids at positions 110- to-130, 194-to-228, 70-to-84 or 510-to-518.

[0099] The invention further provides the method, according to any of the above, wherein the compound has between 11 and 14 Non- Hydrogen & Polar H atoms (NHPH) .

[0100] According to some embodiments of the above methods, the sensor has 2 binding sites, referred to as nitrate-sensing binding sites 1 and 2. In some embodiments, the sensor has 3 binding sites .

[0101] According to some embodiments of the above methods, the Binding

[0102] Energy (BE) of the amphoteric compound to the nitrate-sensing binding sites 1 and 2 is in the range from -4 to -9 kcal / mol.

[0103] In some embodiments, the Binding Energy (BE) of the amphoteric compound to the nitrate-sensing binding 1 and 2 is -4.0 kcal. / mol , -4 , 1. kcal / mol, -4 2 kcal / mol , -4 3 kcal / mol, -4.4 kcal / mol, -4 5 kcal / mol. -4 6 kcal / mol, -4.7 kcal / mol, -4.8 kcal / mol, -4 9 kcal / mol, -5 0 kcal / mol , -5.1 kcal / mol, -5.2 kcal / mol, -5.3 kcal / mol, -5 4 kcal / mol , -5 5 kcal / mol, -5.6 kcal / mol -5 '7 kcal / mol, „ 5 8 kcal / mol , -5.9 kcal / mol -6.0 kcal / moi, - 6.1 kcal / mol, ... r-. 2 kcal / mol , - 6.3 kcal / mol, -6.4 kcal / mol, -6.5 kcal / mol, -6 6 kcal / mol , -6.7 kcal / mol, -6.8 kcal / mol, -6 9 kcal / mol , -7.0 kcal / mol , -7 1 kcal / mol , -7.2 kcal / mol, -7.3 kcal / mol, -7 4 kcal / mol, -7.5 kcal / mol, -7.6 kcal / mol, -7.7 kcal / mol, -7 8 kcal / mol , -7.9 kcal / mol, -8.0 kcal / mol , -8.1. kcal / mol, -8 2 kcal / mol , -8.3 kcal / mol, -8.4 kcal / mol -8.5 kcal / mol, -8.6 kcal / mol , -8.7 kcal / mol -8.8 kcal / mol, -8.9 kcal / mol, -9.0 kcal / mol, or any number therebetween .

[0104] According to some embodiments of the above methods, wherein the

[0105] Binding Efficacy (BEff) is set equal to or below -0.3t kcal / mol, where the Binding Efficacy is equal to BE divided by the number of Non-Hydrogen & Polar H atoms (NHPH) . In some embodiments , the

[0106] BEff is 0.35 kcal / mol.

[0107] According to some embodiments of the above methods, the docking of nitrate to the NSBSs is assessed using the following metrics:

[0108] (a) "Binding Energy" (BE) , referring to the approximated docking energies [AutoDock] and expressed as kcal / mol.

[0109] (b) The number Non-Hydrogen Atoms & Polar Hydrogen

[0110] Atoms (NHPH) . (c) The "Binding Efficacy (BEff) " . is calculated according to:

[0111] BEff - (BE) / ('NHPH) [Pharm]

[0112] Exemplary embodiments of docking parameters for nitrate are summarized in Table 1.

[0113] Table 1. Docking of nitrate in NSBS 1 and 2 on transceptor NRT1.1

[0114] According to some embodiments, the binding sites for the compounds of the present invention overlap with Nitrate Sensor Binding Sites on NRT1.1

[0115] According to some embodiments, in-siiica docking of the compounds according to the present invention is performed using AutoDock Vina and Gnina programs on structures of NRT1.1 protein dimer and monomer in inward- and outward-facing conformations. According to some embodiments of the above methods, a non- limiting list of compounds of the invention includes:

[0116]

[0117]

[0118]

[0119]

[0120] According to some embodiments, the invention provides a method of modulating at least one NO3- sensor in a plant, the method comprising applying at least one amphoteric compound or a salt thereof, selected from the group consisting of:

[0121]

[0122]

[0123]

[0124]

[0125] According to some embodiments of any of the above methods the compound selected, without limitations , from the group consisting of :

[0126]

[0127]

[0128]

[0129] According to some embodiments of any of the above methods compound selected, without limitations, from the group consisting of:

[0130] According to some embodiments, the invention provides a method of modulating at least oneNO3- transporter in a plant, the method comprising applying at least one compound characterized by having a binding affinity to at least one area of the at least one NO3- transporter, selected, without limitations, from the group consisting of:

[0131]

[0132]

[0133]

[0134]

[0135]

[0136] According to some embodiments , the invention provides a method of modulating accumulation of nitrate in a plant , the method comprising applying to the plant at least one compound / composition characterized by having a binding affinity to at least one area of the at least one NO3- transporter , the compound, selected, without limitations , from the group cons isting of :

[0137]

[0138]

[0139]

[0140]

[0141]

[0142] According to some embodiments , the invention provides a method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, characterized by having a binding af finity to at least one area of the at least one NO3- transporter, the compound, selected, without limitat ions , from the group consisting of :

[0143]

[0144]

[0145]

[0146]

[0147]

[0148] According to some embodiments , the invention provides a method of modul ating accumulation of nitrate in a plant , the method comprising applying to the plant at least one compound / composition characterized by having a binding affinity to at least one area of the at least one NO3- transporter , the compound, selected, without limitations , from the group c o n s i s t i n g of :

[0149] According to some embodiments, the invention provides a method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, characterized by having a binding affinity to at least one area of the at least oneNO3- transporter, the compound, selected, without limitations, from the group consisting of:

[0150]

[0151] According to some embodiments , the invention provides a method of modulating at least one NO3- transporter in a plant , the method comprising applying at leas t one compound characterized by having a binding affinity to at least one area of the at least one NO3- transporter, selected, without limitations , from the group consi sting of :

[0152] According to some embodiments , the above method further comprises a step of applying to a locus of the undesired plant growth at least one crop protection agent .

[0153] According to some embodiments of the above methods , the crop protection agent is selected from the group consisting of herbicides , fungicides , insecticides and plant growth regulators .

[0154] According to some embodiments of the above methods , the crop protection agent is an amino acid synthesis inhibitor herbicide .

[0155] A non-limiting list of amino acid synthesis inhibitor herbicides includes : sulfonylurea herbicide , imidazolinone herbicide , sulfonamide herbicide and amino acid derivatives , imazamox, imazapic, imazethapyr, imazaquin, imazapyr and imazamethabenz ,

[0156] Chlorimuron, Primisulf uron, Thif ensulfuron, Triasulfuron, Nicosulfuron, Metsulfuron, Tribenuron, Rimsulfuron and Trif lusulfuron, and glyphosate .

[0157] According to some embodiments of the above methods , the plant growth regulator is selected from the group consisting of dicamba , 2 , 4 -D, clopyralid and fluroxypyr .

[0158] According to some embodiments the above methods , further comprising applying a third herbicide or a plant growth regulator .

[0159] According to some embodiments of the above methods , the locus of the undesired vegetation is field of a crop .

[0160] According to some embodiments of the above methods , a non- limiting list of crops includes maize , wheat , rice , barley, sorghum, and oats . The invention further provides the method, according to any of the above , wherein the herbicidal composition is applied pre- emergence .

[0161] The invention further provides the method, according to any of the above , wherein the herbicidal composition is applied post- emergence .

[0162] The invention further provides the method, according to any of the above , the regulat ion of cellular nitrogen uptake is characterized by disrupting nitrate- and ammonium- signal t r a n s du c t i o n .

[0163] The invention further provides the method, according to any of the above , wherein the regulat ion of cellular nitrogen uptake i s characterized by disrupting hormona l regu lation in plants associated with nitrate- and ammonium-signaling networks .

[0164] The invention further provides the method, according to any of the above , wherein the regulation of cel lu lar nitrogen uptake is characterized by disrupting cel lul ar uptake and ass imi lation of nitrate , ammonium, and potassium.

[0165] The invention provides a compound for modulating at least one NO3- sensor in a plant , the compound selected from the group consisting of :

[0166] The invention provides a composition for modulating at least one NO3- sensor in a plant, comprising at least one compound according to any of the above.

[0167] According to some embodiments of the above method, the undesired plant growth is a broadleaf weed.

[0168] According to some embodiments, the invention provides a method of controlling growth of plants at least partially resistant to herbicides selected from the HPAC 9 group (Inhibitors of EPSP synthesis) , 2 (Acetolactate Synthase (ALS) inhibitors) , 4 (Plant growth regulators or synthetic auxins) , Paraquat comprising applying to the plant or a plant part thereof, an effective amount of the herbicidal composition or the compound according to one or more of the above embodiments. According to some embodiments , the invention provides a method of controlling the growth of plants with at least partial resistance to herbicides . According to some embodiments , resistance based on an alteration or overexpression of the target site of action .

[0169] According to some embodiments of the above method, the crop is selected from the group consisting of maize , oats , rice , wheat , pearl millet , proso millet , rye , and sorghum .

[0170] According to some embodiments of the above method, the herbicidal composition is applied pre-emergence .

[0171] According to some embodiments of the above method, the herbicidal composition is applied post-emergence .

[0172] According to some embodiments , the invention provides a method of selectively controlling the growth of harmful and / or undesirable weeds , comprising applying to a field of a crop an effective amount of the herbicidal composition or compound, according to one or more of the above embodiments . As used herein, the term "selectively controlling" refers , without limitation, to a situation when the growth of the harmful and / or undesirable weeds is affected by the compositions according to the embodiments of the invention , without affecting growth of desirable vegetation, such as , without limitation, crops . According to some embodiments , the weeds are considered as relevant to maize , oats , rice , wheat , pearl millet , proso millet , rye , and / or sorghum cultivation .

[0173] According to some embodiments of the above methods , the effective amount of the of the herbicidal composition or compound, according to one or more of the above embodiments is in a range of between 50gr / Ha to 2000gr / Ha, when applied pre- emergence . According to some embodiments of the above methods, the effective amount of the of the herbicidal composition or compound, according to one or more of the above embodiments is 50gr / Ha, lOOgr / Ha, 150gr / Ha, 200 gr / Ha, 250 gr / Ha, 300 gr / Ha, 350 gr / Ha, 400 gr / Ha, 450 gr / Ha, 500 gr / Ha, 550 gr / Ha, 600 gr / Ha, 650 gr / Ha, 700 gr / Ha, 750 gr / Ha, 800 gr / Ha, 850 gr / Ha, 900 gr / Ha, 950 gr / Ha, 1000 gr / Ha, 1050gr / Ha, llOOgr / Ha, 1150gr / Ha, 1200 gr / Ha, 1250 gr / Ha, 1300 gr / Ha, 1350 gr / Ha, 1400 gr / Ha, 1450 gr / Ha, 1500 gr / Ha, 1550 gr / Ha, 1600 gr / Ha, 1650 gr / Ha, 1700 gr / Ha, 1750 gr / Ha, 1800 gr / Ha, 1850 gr / Ha, 1900 gr / Ha, 1950 gr / Ha, 2000 gr / Ha, when applied pre-emergence.

[0174] According to some embodiments of the above methods, the effective amount of the of the herbicidal composition or compound, according to one or more of the above embodiments is in a range of between 125gr / Ha to 2000gr / Ha, when applied post- emergence .

[0175] According to some embodiments of the above methods, the effective amount of the of the herbicidal composition or compound, according to one or more of the above embodiments is,

[0176] 125 gr / Ha, 150 gr / Ha, 175 gr / Ha, 200 gr / Ha, 225 gr / Ha, 250 gr / Ha,

[0177] 275 gr / Ha, 300 gr / Ha, 325 gr / Ha, 350 gr / Ha, 375 gr / Ha, 400 gr / Ha,

[0178] 425 gr / Ha, 450 gr / Ha, 475 gr / Ha, 500 gr / Ha, 525 gr / Ha, 550 gr / Ha,

[0179] 575 gr / Ha, 600 gr / Ha, 625 gr / Ha, 650 gr / Ha, 675 gr / Ha, 700 gr / Ha,

[0180] 725 gr / Ha, 750 gr / Ha, 775 gr / Ha, 800 gr / Ha, 825 gr / Ha, 850 gr / Ha,

[0181] 875 gr / Ha, 900 gr / Ha, 925 gr / Ha, 950 gr / Ha, 975 gr / Ha, 1000 gr / Ha, 1025 gr / Ha, 1050 gr / Ha, 1075 gr / Ha, 1100 gr / Ha, 1125 gr / Ha, 1150gr / Ha, 1175 gr / Ha, 1200 gr / Ha, 1225 gr / Ha, 1250 gr / Ha, 1275 gr / Ha, 1300 gr / Ha, 1325 gr / Ha, 1350 gr / Ha, 1375 gr / Ha, 1400 gr / Ha, 1425 gr / Ha, 1450 gr / Ha, 1475 gr / Ha, 1500 gr / Ha, 1525 gr / Ha, 1550 gr / Ha, 1575 gr / Ha, 1600 gr / Ha, 1625 gr / Ha, 1650 gr / Ha, 1675 gr / Ha, 1700 gr / Ha, 1725 gr / Ha, 1750 gr / Ha, 1775 gr / Ha, 1800 gr / Ha, 1825 gr / Ha, 1850 gr / Ha, 1875 gr / Ha, 1900 gr / Ha, 1925 gr / Ha , 1950 gr / Ha , 1975 gr / Ha , 2000 gr / Ha, when applied pre-emergence .

[0182] According to some embodiments , the invention provides a herbicidal composition comprising compound, the compound comprising : ( i ) a substituted or non-substituted 6-membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by a flexible linker ; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom, and at least one herbicidally acceptable carrier .

[0183] According to some embodiments , the invention provides a herbicidal composition comprising compound, the compound comprising : ( i ) a substituted or non-substituted 5 -membered heterocycle , and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by a flexible linker ; and wherein a preferred spatial arrangement ( PSA) of the compound has a torsion angle in the range of -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom, and at least one herbicidally acceptable carrier .

[0184] According to some embodiments , the invention provides a herbicidal composi tion, compri sing at least one compound characte ized by having a binding af finity to at least one area of at least one NOs~ transporter, the compound comprising : ( i ) a substituted or non-substituted 5-membered heterocycle, and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site ; wherein ( i ) and ( ii ) are interconnected by an optiona lly substituted f lexible l inker ; and wherein a pref erred spatial arrangement ( PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anioni c or electronegative group is in the range of 3 to 10 Angstrom and at least one herbicidally acceptable carrier .

[0185] According to some embodiments , the invention provides a herbicida l composition, comprising at least one compound characterized by having a binding affinity to at least one area of at least one NO3- transporter, the compound comprising : ( i ) a substituted or non-substituted 6-membered heterocycle , and ( ii ) an anionic or electronegative group comprising an acidic and / or el ectronegative site ; wherein ( i ) and ( ii ) are interconnected by a flexible linker; and wherein a preferred spatial arrangement ( PSA ) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker , and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom and at least one herbicida lly acceptable carrier .

[0186] According to some embodiments of any of the above herbicidal compositions , the NO3- transporter is selected from a group consist ing of Nitrate Transporterl / Peptide Transporter family (NR.T1 / NPF ) and Nitrate Transporter! (NRT2 ) family, specifically , NPF6 - 3 (NRT1 . 1 ) NPF6 . 2 (NRT1 . 4 ) , and NRT2 . 1 . According to some embodiments of any of the above herbicidal compositions, at least one area of the at least one NO3- transporter is a NO3- binding site.

[0187] According to some embodiments of any of the above herbicidal compositions, the binding affinity is equal or higher than -4 kcal / mol. According to other embodiments of any of above herbicidal composition, the binding affinity is equal or higher

[0188] (larger) than -8 kcal / mol.

[0189] According to some embodiments of any of the above herbicidal compositions, the compound is an amphiphilic compound.

[0190] According to some embodiments of any of the above herbicidal compositions, the heterocycle is at least a partially positively charged or a dipole.

[0191] According to some embodiments of any of the above herbicidal compositions, the heterocycle comprises at least one heteroatom selected from the group consisting of sulfur (S) , nitrogen (N) and oxygen (0) .

[0192] According to some embodiments of any of the above herbicidal compositions, the heterocycle is selected from Pyridine (C5N) , Pyrrole (C4N) , Thiophen (C4S) , 1,2-Thiazole (C3NS) , 1,3-Thiazole (C3NS) , Isothiazole (C3NS) , 1,2-Thiazine (C4NS) , 1,3-Thiazine (C4NS) , 1,4-Thiazine (C4NS) , Oxazole (C3NO) , Isoxazole (C3NO) , 1,2-Oxazines (C4NO) , 1, 3-Oxazines (C4NO) , or 1,4-Oxazines (C4NO) .

[0193] According to some embodiments of any of the above heroic :idal compositions, the heterocycle is substituted by at least one molecule selected from -Cl, -Br, -F, -I, -NO2, =O, =S, -CI

[0194] CCI3, -SO2F, and -CN.

[0195] According to some embodiments of any of the above herbicidal compositions , the heterocycle has 1 or 2 substituted carbon atoms . According to some embodiments of any of the above herbicidal compositions, the anionic or electronegative group is characterized as having at least a partial negative charge.

[0196] According to some embodiments of any of the above herbicidal compositions, the anionic / electronegative group is selected from carboxyl, carbonyl, alkyl chloride, carboxamide, amide. Imide, acid chloride, nitro, cyano, and nitrate phosphonate, phosphate, sulfate, sulfonate, or an ester thereof, or a salt thereof.

[0197] According to some embodiments of any of the above herbicidal compositions, the ester is selected from an alkane; a phenol; a mono-, di-, or three halides phenol; a pyridine; mono-, di-, or three halides pyridine; an alkyl phenol (aliphatic chain C1-15) ; alkyl pyridine (aliphatic chain C1-15) , an ether, a polyether, a diol, poly-diol, or any combination thereof.

[0198] According to some embodiments of any of the above herbicidal compositions, the ester is selected from [ (CH2) 2O]m(CH2) nCHs, [ (CH2) 2O ]m(CH2)nC6H5, [ (CH2)2O]m(CH2)nC5NH4, [ (CH2)2O]m( CH2)nC5NH3Br , or [ (CH2)2O]m(CH2)nC5NH2BrF; and wherein n = 0 to 15 and m = 0 to 5.

[0199] According to some embodiments of any of the above herbicidal compositions, the salt is a Na, K, Ca, NH«+salt.

[0200] According to some embodiments of any of the above herbicidal compositions, the anionic / electronegative group is selected from the group consisting of nitro-, cyano-, and nitrate.

[0201] According to some embodiments of any of the above herbicidal compositions, the flexible linker comprises at least one substituted or non-substituted carbon atom and 0 or 1 heteroatom selected from oxygen (0) , sulfur (S) , and nitrogen (N) .

[0202] According to some embodiments of any of the above herbicidal compositions, a carbon atom of flexible linker substituted with F, Br, Cl, or I. According to some embodiments of any of the above herbicidal c omp o s 1 t i o n s , a. carbon atom of the flexible linker is substituted with (CH2)nCH3, -0[ (CH2)2O]m(CH2)nCH3, (CH2)nC6H5,

[0203] 0 [ (CH2)2O]m(CH2)nC6H5, (CH2)nC5NH4, -0[ (CH2)2O]m(CH2)nC5NH4,

[0204] (CH2)nC5NH3Br, -O[ (CH2)2O]m(CH2)nC5NH3Br, (CH2)nC5NH2BrF, or

[0205] O [ (CH2)2O]m(CH2)nC5NH2BrF; and wherein n 0 to 15 and m 0 to 5.

[0206] According to some embodiments of any of the above herbicidal compositions, the PSA is a spatial arrangement with the lowest energy minimum among all possible conformers for an individual molecule .

[0207] According to some embodiments of any of the above herbicidal compositions , the compound selected from the group consisting of :

[0208]

[0209]

[0210]

[0211]

[0212]

[0213] According to some embodiments of any of the above herbicidal compos itions , the compound selected from the group consisting

[0214]

[0215] According to some embodiments, the invention provides an herbicidal composition, one compound

[0216]

[0217]

[0218]

[0219] According to some embodiments of any of the above herbicidal compos itions , additionally compr isi ng at least one additional plant protection compound . According to some embodiments of any of the above herbicidal composit ions , the at least one additional plant protection agent is selected from the group consisting of herbicides , amino acid synthesis inhibitor herbicides , fungicides , insecticides and plant growth regulators . According to some embodiments of any of the above herbicidal compositions , the amino acid synthesis inhibitor herbicide is selected from the group consisting of sulfonylurea herbicide , imidazolinone herbicide , sulfonamide herbicide and amino acid derivatives , imazamox , imazapic , imazethapyr, imazaquin, imazapyr and imazamethabenz , Chlorimuron, Primisulf uron,

[0220] Thif ensulfuron, Triasulfuron, Nicosulf uron, Metsulfuron,

[0221] Tribenuron, Rimsulfuron, glyphosate and Trif lusulfuron or a combination thereof . According to some embodiments of any of the above herbicidal compositions , the plant growth regulator is selected from the group consisting of dicamba, 2 , 4-D, clopyralid and fluroxypyr .

[0222] According to some embodiments of any of the above herbi cida l compositions , further comprising a third herbicide or a plant growth regulator .

[0223] According to some embodiments , the invention provides an amino- acid sequence Lys218A, Argl26A, Argl29A, Alall OA, Serl l4A, Thrl llA, Leul l8A, Ilel21A, Trp219A, Ala225A, Phe226A, Val229A, and Lys218B, Argl26B, Argl29B , Alall OB, Serl l4B , Thrl llB, Leul l8B , Ilel21B, Trp219B, Ala225B , Phe226B, Val229B side chains from each monomer (where A and B indicating respective subunits forming the dimer of NRT1 . 1 ) , and / or similar and / or homologous sequences and / or related sequences of otherNO3- sensors . According to some embodiments , the amino acid sequence has 85% - 99% homology to the above sequence .

[0224] According to some embodiments , the above amino acid sequences can be used as markers for identifying responder and / or resistant plants to the compounds and compositions of the invention . In the context of the invention, the term "homologous" refers , without limitation, to sequences of shared ancestry in the evolutionary history of life . Homology is defined as a degree of homology and expressed as a percentage of homology and / or percentage of sequence identity, namely number of identical residues over a defined length in a given alignment . In the context of the invention the term "similar" refers , without limitation, to sequences having a certain degree of sequence identity, while conservative substitutions of amino acid residues having similar physicochemical properties over a defined length of a given alignment are also allowed . Sequence similarity is expressed as a percentage of similarity ( degree of similarity) . According to some embodiments , transgenic plants carrying the above sequences and / or carrying mutations in the above sequences can be generated to conf er / eliminate resistance and to allow selectivity .

[0225] According to some embodiments , the invention provides methods for generating transgenic plant or plant parts carrying the above sequences and / or mutations in the above sequences .

[0226] Soi l nitrate levels have a si gnif icant impact on the kinetics and magnitude of nitrate accumulation . When the compound of the invention is applied, plants grown in low nitrate soil (< 1 mM of N03- ) show a significant nitrate accumulati on (p<0 . 05 ) af ter 24 hours . However, the response of plants grown on normal- and high-nitrogen soi l ( 5 to 10 mM NO3- j is delayed and becomes apparent at 48 to 96 HPA.

[0227] As used herein, the term "inward" refers , without limitation, to any part of the protein, transceptor or any amino acids facing the inner part of the transceptor or a channel , or the interface between the monomers .

[0228] As used herein, the term "outward" refers , without limitation, to any part of the protein, transceptor or any amino acids facing the outer part of the transceptor or a channel .

[0229] The outward-facing conformation of the NRT1 . 1 protein model was determined based on structural similarity and homology within the maj or facilitator superfamily (MPS ) transporters , as referenced in the Transporter Classification Database (TCDB ) . To create the model, the outward-facing scaffo ld of the mammalian peptide transporter HsPepTl / SLC15Al was used, with DDB codes 7PMX, 7PMW, and 7PN1 identi fied using the NCBI VAST (vector alignment search tool ) . Specifically, the N- and C-terminal domains of the NRT 1 . 1 inward structure were aligned and overlaid onto the corresponding doma ins of the homologous proteins in their outward-facing conformations . Different positions of transmembrane (TM) helices between the two "inward" and "outward" structures imply a simple rigid-body motion of the N- and C-terminal domains upon the inward-outward conformational transition . During these structural changes, the interface area between the N-terminal and C-termina l domains decreases from 1437 . 6 to 1069 . 5 A2 . The hydrogen bonds / contacts that are broken between TM he lices in the inward-facing structure are listed in Table 3 and the hydrogen bonds / contacts that are formed between TM helices in the outward-facing structure are listed in Table 4 .

[0230] The NRT1 - 1 dimer and monomer protein-membrane systems were constructed by embedding in a DOPC / DDPC ( 1, 2-dioleoyl-sn- g l y c e r o - 3 - p h o s p h o c h o l i n e / l,2-di d e c a n o yl - s n - g l y c e r o - 3 - phosphocholine) membrane (Tables 3—4) using CHARMM-GUI bioinformatics protocol (see Example 1 for more details) .

[0231] Identification of the nitrate-sensing domain on the inter- subunit interface of NRT1.1 was done by analyzing structural analysis of the inter-subunit interface of the NRT1.1 dimer.

[0232] A structural analysis was performed using the Membrane Builder from the CHARMM-GUI tools and revealed a channel-like scaffold in the inter-subunit interface of the NRT1.1 dimer. The scaffold core is symmetrically formed by four parallel TM helices, Hl and H3, from each subunit. The minimum pore radius of this scaffold is approximately 10 Angstroms, as shown in Figure 1.

[0233] The output was produced by the Membrane Builder (CHARMM-GUI tools) . A pore with a minimal radius of 4.5 A is formed on the extracellular side of the NRT1.1 dimer. The radius of the transport channel on the intracellular side ranges from 12 to 15 A.

[0234] The extracellular side of the channels / pores inner surface is lined with the Lys218, Argl26, Argl29, AlallO, Serll4, Thrill, Leull8, Ilel21, Trp219, Ala225, Phe226, and Val229 side chains from each monomer.

[0235] Electrostatic calculations used an adaptive Poisson-Boltzmann solver (APBS) , revealed significant positive electrostatic potential within the inter-subunit dimeric pore or channel. This positive potential is generated by six positively charged side chains, consisting of two Arginine (Arg) and one Lysine (Lys) residue from each subunit, located at the extracellular entrance / gate of the pore. Due to uncompensated electrostatic repulsion between Lys / Arg side chains , the inter-subunit pore remains open, with a radius of ~4 . 5 A ( as explained in Figure 1 ) . The positively charged groups positioned near the surface of the external lipid membrane facilitate the diffusion of anionic molecules , such as NO3- , towards the pore / channel .

[0236] When exposed to the extracellular media, the channel bounds up to six water molecules and interacts with other external molecules . At high concentrations , extracellular nitrate anions diffuse towards the inter-subunit pore entrances and engage in electrostatic interactions with the Lys / Arg side chains . These interactions stabilize the dimeric form and favor the low- affinity state .

[0237] Nitrate-sensing binding site on the inward- and outward monomeric subunits of NRT1 . 1

[0238] Molecular dynamic studies for the compounds of the present inventi on, in in-silico models of NTR1 . 1 (Examples 1 and 2 ) and CIPK23 confirmed and refined previously published ( Rashid et al . , 2018 ) Nitrate Sensor Binding Site (NSBSs ) ( Table 5) .

[0239] Table 5 : nitrate binding sites on NRT1 . 1

[0240] Binding to the nitrate sensing area of the inter-subunit pore (NSBS-1) . Compounds according to trie present invention bind effectively to the nitrate sensing area located in the inter-subunit pore of the NRT1.1 dimer. The binding process involves several electrostatic interactions, such as the ligand anionic carboxy group with the positively charged Argl26, Argl29, and Lys218, hydrogen bonding with Serll4 and Thrill, pi-stacking of the thiazole ring with Trp219 and Phe226, and hydrophobic contacts with Leull8, Ilel21, and Val229.

[0241] More specifically, the compounds were seen to have binding energies in the range of -5 to -9 kcal / mol through multiple contacts with the residues in the NSBS-1. These residues are formed by the sequence comprising Serll4, Thrl'17, Leul'18, Ilel21, Argl26, Argl29, Lys218, Trp219, Phe226, and Val229.

[0242] Binding of the compounds of the present invention in the nitrate sensing area of subunit A in ths inward-facing conformation

[0243] (NSBS-2) .

[0244] In some embodiments, the compounds bind to distinct areas on the internal surface of the NRT1.1 channel in the inward-facing conformation. The most f requent / extensive ligand-protein contacts occur in the nitrate binding region formed by the protein sequence comprising Leu49, Leu78, HIS356, Thr360, Tyr388, Leu504, Leu507, Phe511 (NSBS-2) . The binding affinities of active compounds in this area range from -4 to -9 kcal / mol.

[0245] Binding to the pocket area near ths ThrlOl phosphorylation site

[0246] (ThylOl pocket)

[0247] When the NRT1.1 subunit / monomer is in the inward-facing conformation, the compounds of the present invention bind to the pocket near the ThrlOl phosphorylation site f ormed / created by the sequence comprising Serl66, Serl68, Arg98, Asp93, Thr500, and Ser250. In some embodiments, the compounds have binding energy in the range of -4 to -6 kcal / mol in this specific region relative to the nitrate sensing area. Binding to the distinct areas on the internal surface of the

[0248] NRT1.1 channel in the outward- facing conformation

[0249] In some embodiments, the compounds of the present invention bind to distinct areas on the internal surface of the NRT1.1 channel in the outward-facing conformation. The most frequent, / extensive ligand-protein contacts occur in the interhelical region formed by the protein sequence comprising Arg45, Leu78, Phe82, Lysl64, Ilel97, HIS356, Thr360, Tyr480, Leu504, Leu507, Phe511. The binding affinities to this site are in the range of -4 to -7 kcal / mol -

[0250] In some embodiments, the compounds of the present invention demonstrate significant affinity to the nitrate-sensing binding sites on NRT1.1. (NSBSs) The contacting amino acid residues in the NSBS are listed in Table 6.

[0251] Table 6: Binding sites for the coirpounds of the present invention on NRT1.1

[0252] The asterisk indicates contacting amino acid residues common for the compounds and nitrate .

[0253] Examples :

[0254] Example 1. Models of the NRT1.1 transporter protein

[0255] (a) Dimer., the inward- facing- conformation

[0256] The known 3D geometry of NRT1.1 protein is represented by atomic coordinates of the structure of NRT1.1 dimer from Arabidopsis Tha liana experimentally determined by X-ray crystallography (RDB codes 4OH3 , 5A2O) . Another source used as the NRT1 . 1 model is the structure (A0A178W8F7 ) deposited in the Alpha Fold DB [ref link] . Both structures represent the inward-facing conformation of the nitrate transport channel corresponding to a low-affinity state of the NRT1 . 1 protein .

[0257] (b) Monomer , the outward-facing conformation

[0258] The model of NRT1 . 1 protein in the outward-facing conformation was based on the established structural similarity / homology within the maj or facilitator superfamily (MFS ) transporters [ref to TCDB ( Transporter Classification Database ) ] . The model was built on the outward-facing scaffold of the top-score homology structures of the mammalian peptide transporter HsPepTl / SLC15Al ( PDB codes 7PMX, 7PMW, 7PN1 ) identified using the NCBI VAST ( the vector alignment search tool ) [ref to VAST ] . Specifically, the outward-facing conformation is constructed by aligning and overlaying the N- and C-terminal domains of the NRT1 . 1 inward structure onto the corresponding domains of the homologous proteins in their outward-facing conformations .

[0259] (a) The inward-outward conformational transition

[0260] Dif ferent positions of transmembrane (TM) helices between the two "inward" and "outward" structures imply a simple rigid-body motion of the N- and C-terminal domains upon the inward-outward conformational transition . During these structural changes , the interface area between the N-terminal and C-terminal domains decreases from 1437 . 6 to 1069 . 5 A . The following hydrogen bonds / contacts are broken between TM helices in the inward- facing

[0261] Table 7

[0262] New hydrogen bonds / contacts are formed between TM helices in the o u t w a r d --- f a c i n g s t r u c t u r e :

[0263] Table 8

[0264] (d) The NRT1. 1 protein -membrane system

[0265] The NRT1 . 1 dimer and monomer prote in-membrane systems were constructed by embedding in a DO PC / DD PC ( 1 , 2 -dioleoyl-sn- glycero-3 -phospho choline / 1 , 2 -didecanoy l-sn-glycero-3- phosphocholine ) membrane ( Tables 9-10 ) using CHARMM-GUI bioinformatics protocol [ ref to CHARMM] .

[0266]

[0267] Example 2. Identification of the nitrate sensing area and possible binding sites The structural analysis was performed using the Membrane Builder from the CHARMM-GUI tools, revealing a channel-like scaffold in the inter-subunit interface of the NRT1.1 dimer. The scaffold core is symmetrically formed by four parallel TM helices, Hl and H3, from each subunit. The minimum pore radius of this scaffold is approximately 10 Angstroms, as shown in Figure 1.

[0268] The extracellular side of the pore inner surface is lined with the Lys218A, Argl26A, Argl29A, AlallOA, Serll4A, ThrlliA, Leull8A, Ilel21A, Trp219A, Ala225A, Phe226A, Val229A, and Lys218B, Argl26B, Argl29B, AlallOB, Serll4B, ThrlliB, Leull8B, Ilel21B, Trp219B, Ala225B, Phe226B, Val229B side chains from each monomer (where A and B indicating respective subunits forming the dimer of NRT1.1) The electrostatic calculations were conducted using an adaptive Poisson-Boltzmann solver (APBS , [ref APBS ] ) to unveil the significant positive electrostatic potential within the inter- subunit dimeric pore . The positive potential is generated by six positive charges , consisting of two Arginine (Arg ) and one Lysine (Lys ) residue from each subunit , located at the extracellular entrance / gate of the pore . Near the surface of the external lipid membrane , the positive potential facilitates the diffusion of anionic molecules , such as NOs- , towards the pore .

[0269] Due to uncompensated electrostatic repulsion between Lys / Arg side chains , the inter-subunit pore remains open; its radius is ~4 . 5 A ( as explained in Figure 1 ) . When exposed to the extracellular media , it appeared that it can bind up to six water molecules and can interact with other external molecules . At high concentrations , extracellular nitrate anions diffuse towards the inter-subunit pore entrances and engage in electrostatic interactions with the Lys / Arg side chains . These interactions stabilize the dimeric form and favor the low- affinity state . https : / / apbs . readthedocs . io / en / latest /

[0270] Example 3 . Docking model

[0271] In-siliao multistep docking was conducted using AutoDock Vina and Gnina programs [ ref to AutoDock] into the structures of the NRT1 - 1 protei n dimer and the monomer in the inward- and outward- facing conformations , respectively .

[0272] (a) Binding to the nitrate sensing area of the inter- subunit pore (NSBS-1) . compounds of the present invention were found to effectively bind ni trate sens ing area located in the inter- subunit pore of the NRT1 . 1 dimer . The binding process involved various contacts through electrostatic interactions of the ligand anionic carboxy group with the positively charged Argl26, Argl29, and Lys218, hydrogen bonding with Serll4 and Thrill, pi-stacking of the thiazole ring with Trp219 and Phe226, and hydrophobic contacts with Leull8, Ilel21, and Val229.

[0273] Specifically, active compounds exhibited binding energies within the range of 5 to 7 kcal / mol through multiple contacts with the residues in the NSBS-1 f ormed / created by the sequence comprising Serll4, Thrill, Leull8, Ilel21, Argl26, Argl29, Lys218, Trp219, Phe226, and Val229.

[0274] (b) Binding of to the nitrate sensing area of subunit A in the inward-facing conformation (NSBS-2) .

[0275] Herbicidal compounds of the present invention were shown to bind distinct areas on the internal surface of the NRT1.1 channel in the inward-facing conformation. The most f requent / extensive ligand-protein contacts occur in the nitrate binding region formed by the protein sequence comprising Leu49, Leu78, HIS356, Thr360, Tyr388, Leu504, Leu507, Phe511 (NSBS-2) . The binding affinities of the compounds range from -4 to -7 kcal / mol.

[0276] (c) Binding to the pocket area near the ThrlOl phosphorylation site (Thy 101 pocket)

[0277] When the NRT1.1 subuni t / monomer is in the inward-facing conformation, compounds bound to the pocket near the ThrlOl phosphorylation site f ormed / created by the sequence comprising Serl66, Serl68, Arg98, Asp93, Thr500, and Ser250. Active compounds show a comparable or less efficient binding from -4 to -6 kcal / mol in this specific region relative to the nitrate sensing area.

[0278] (d) Binding to the distinct areas on the internal surface of the NRT1.1 channel in the outward-facing conformation Active compounds bound to distinct areas on the internal surface of the NRT1.1 channel in the outward-facing conformation. The most f requent / extensive ligand-protein contacts occur in the interhelical region formed by the protein sequence comprising Arg45, Leu78, Phe82, Lysl64, Ilel97, HIS356, Thr360, Tyr480, Leu504, Leu507, Phe511. The binding affinities range from -4 to -7 kcal / mol.

[0279] [refs to AutoDock Vina]

[0280] Example 4. Conformational Preferences

[0281] Conformational sampling was conducted around all rotatable bonds, including those in the flexible linker, by systematically varying its torsion angles, followed by geometry optimization and comparative analysis of the calculated conformations with the help of molecular mechanics and quantum chemistry programs [refs QM MM] .

[0282] The scaffold was constructed by superimposing stable low-energy conformations of the active compounds using algorithms implemented in the Python RDKit library [ref RDKit] .

[0283] The scaffold implies that in active compounds, a distance of 3- 10 Angstroms between the basic and acidic / anionic sites, or between the centroid of a heterocycle and the acidic / anionic site, is correlated with the herbicidal activity. This distance was maintained in active compounds through a specific 3D arrangement / conf iguration of atomic groups corresponding to the most energetically stable conformations.

[0284] These preferable conformations were characterized by torsion angles of the rotatable bonds in the range from -25 to ~85 degrees in the flexible links connecting a heterocycle with an anionic / electronegative moiety .

[0285] In the typical compound representing a thiazole derivative, the thiazole carbon atom (CT) adjacent to the thiazole nitrogen atom (NT) , was connected through a linker carbon atom (CL) with the carboxyl carbon atom COO(-) . In this case, the rotatable bond was between the CT and CL atoms, and the preferred "active" conformation was defined by the torsion angle of NT-CT-CL-COO in the range from -25 to -85 degrees (Table 11) . Table 11: "Conformer Energies and Torsion Angles"

[0286] > Conformers, generated for each molecule taken in both protonated (-Hp) and not-protonated / neutral (-np) form of its basic centers, are indicated as cnfl, cnf2, cnf3 ... etc.

[0287] > Total electronic energy calculated for each conformer: E tot, Hartree (the energy unit used in quantum mechanics / chemistry and related codes / programs ) .

[0288] > The energy difference between the lowest-energy (the most stable) conformer and other conformers of a given molecule: E rel, kcal / mol.

[0289] > The torsion angle between a planar heterocyclic ring and an anionic center: Torsion Angle, degrees

[0290] [refs QM MM]

[0291] (open sources only! )

[0292] [ref RDKit]

[0293] RDKit: Open-source cheminformatics, https: / / www.rdkit.org

[0294] Example 6. Effect of FPs on nitrate accumulation and assimilation

[0295] Methods : a. Study of FPs effect on the Nitrate accumulation. Soybean seeds were planted in pots (7x7x6 cm) filled with sandy soil and kept in a growth chamber under controlled conditions with a temperature of 24°C and a 16 / 8 light / dark cycle. At the first trifoliate stage, plants were treated with FPS 666 (125 g a.i. / Ha) and mock (water with neutral detergent, 0.001%) . The test materials were applied as a foliar spray using an airbrush sprayer at a pressure of 20 PSI and a volume of 300 L / Ha. Drench supplementation with nitrate at desired concentrations (KNO3 0.1, 1.0, and 10 mM in tap water) was performed 1 hour after applying the test material (1HPA) . At time points 1-, 4-, and seven days post-application (DPA) , stems (9 plants per treatment / per time point) from treated plants were harvested, chopped into small pieces, and squeezed using a garlic press. The sap from the stems was collected, and 400 uL were placed on a Horiba LAQUAtwin NO3- ion-meter probe. The experiment was performed in triplicates, and each replica was measured three times to reduce the variability of the machine. b. Study of FPs effect on nitrate assimilation. Soybean seeds were planted in a nursery medium and grown as described above. The plants were treated at the stage of first trifolium with the test materials, FP5666 (30, 300, and 400 g a.i. / Ha) , FP7157 (250 g a.i. / Ha) , or mock (water with neutral detergent, 0.001%) . The test materials were applied by foliar spray at a volume of 300 L / Ha using an airbrush sprayer at a pressure of 20 PSI. The samples of the test material or mock were collected 3, 8, 24, 72, 120, and 168 hours post application (HPA) . At each desired time, leaves from treated plants were excised, bulked, and kept at -20° for further analysis.

[0296] LC-MS analysis tubes with fresh tissue were placed in a lyophilizer for 24 hours for cold-drying. Next, the dry tissue was ground to a powder, and the samples were extracted with ACN / W (1:1) solvent acidified with 0.1% formic acid. The extracts were filtered (regenerated cellulose 0.2 um, membrane filters) and spiked with the mixture of internal standards before LC / MS analysis. Quantitative analysis of amino acids was carried out using the LC-MS / MS system Nexera X2 UPLC (Shimadzu) coupled with the QTRAP 6500+ mass spectrometer (Sciex) .

[0297] Calib ration c o n t a i n i n g 34 individual amino acids

[0298] (purchased from Sigma-Aldrich) were prepared at concentrations ranging from 5 ng / ml to 5000 ng / ml. The samples were spiked with a mixture of 20 isotopically labeled amino acids used as internal standards (purchased from Cambridge Isotopes) at a final concentration of 100 ng / ml per sample.

[0299] The results of the test are summarized in Tables 12 and 13. a. The treatment with FP5666 significantly increases the nitrate level in soybeans grown in low and high-nitrate soil. The effect of FP-induced nitrate accumulation was sustained for at least seven days. FP-induced nitrate accumulation was delayed in plants grown in high-nitrate soil . b. The test materials, FP5666 and FP7157, caused a significant accumulation of ammonia metabolites, amino acids, and their derivatives involved in nitrogen assimilation response, such as the urea cycle amino acids, Asp, and Asn. In our experimental set, the effect of FPs is seen as early as 8 hours post application (HPA) and culminated at 72 - 168HPA.

[0300] Discussion and conclusions :

[0301] The nitrogen sources taken up by higher plants are nitrate or ammonium and amino acids under particular conditions of soil composition. Nitrogen assimilation requires the reduction of nitrate to ammonium and then the nitrogen assimilation in the ammonium pathway intermediates, particularly glutamine, arginine, ornithine, putrescine aspartate, and asparagine.

[0302] Ammonium accumulation is toxic for many plant species, leading to physiological and morphological disorders that affect plant growth and development. High-NH4+conditions increased the transcript levels of genes involved in the urea cycle and the content of intermediates of this cycle [Urra et al., (2022) . Journal of Experimental Botany, 73(16) , 5581-5595. https: / / doi.org / 10.1093 / jxb / erac235] .

[0303] Treatment with FPs precipitates a remarkable increase in the plant's nitrate (Table 12) , followed by nitrate assimilation in ammonium pathway intermediates (Table 13) . FPs cause a rise of Arg, Ornithine, Citruline, and Urea taken together with their metabolites to levels more than a hundred times higher than in mock-treated plants. The magnitude of nitrogen assimilation response suggests that NH4+toxicity is a critical factor in the mechanism of action of FPs.

[0304] After treating plants with FPs, there is a significant increase in the nitrate content, which is followed by the assimilation of nitrate into the ammonium pathway. To better understand the extent of this response, we consider the levels of amino acids and their relevant metabolites. It was observed that the treatment with FPs leads to more than a hundred times higher levels of Arg, Ornithine, Citrulline, and Urea, along with their metabolites, compared to the mock-treated plants. This indicates that NH4+toxicity plays a crucial role in the mechanism of action of FPs .

[0305] Table 12. Effect of FP5666 on nitrate content in soybeans shoots. (** p < 0.05; *** p < 0.01) Table 13. Effect of FP5666 on the Nitrate Assimilation in s o yb e a n s leaves.

[0306] The data is represented by Folds of Control calculated as a ratio of the amino acid content in plants treated with FP5666 (125 g / Ha) divided by its content in mock-treated plants

[0307] (rounded numbers) . HPA means hours after the treatment; Bold font indicates p 4 0.5. underlining indicates Folds 4 2.0.

[0308] ADMA - N, N-Dimethylarginine; SDMA - N, N ' -Dimethylarginine

[0309] Example 7. Selection of new potential candidates suitable for control of plants' nitrogen and crop protection.

[0310] The selection rules described in Example 5 were applied to the library of candidates designed using the scaffold A-B-C, where A is an aromatic 5- or 6-member heterocycle, B - is a linker, and C is an anionic / acidic site, where A may include one to 5 heteroatoms selected from N and S and where B and substituting groups on A, B and C were chosen in a way favoring the stereo- arrangement with the distance and torsion angle between A and C 3 to 5 (Angstrom) and -25 to - 85 degrees respectively .

[0311] The list of selected candidates is shown in Table 14 below . Table 14 : Potential plant nitrate modulators with herbicidal activity

[0312] Example 8 : Effect of derivatives of heterocyclic amino acids on germination & early plant development .

[0313] Materials: Seeds of Lettuce R. (Super- Jericho, non-sterilized) were obtained from Ben Shahar Moshe Ltd. , 99% purity. The test compounds listed in Table 15 below were synthesized de novo or purchased from different vendors.

[0314] Filter Paper Bioassays with Lettuce seeds: The protocol follows Bertin et al. 2009 and Movellan et al. 2014 with specified modifications described below.

[0315] Seeds were placed on Whatman no. 1 filter paper (Whatman, Middlesex, U.K. ) in Petri dishes (10 seeds per plate) with 2.0 ml of aqueous solution of a test material in concentration ranging from 0 (control) to 1 mmol / 1 were placed in a tray tilted at 45 degrees. The trays were kept in the dark for 48 hours and then transferred to the growth chamber with a 6 / 18 dark / light cycle for four days. Each experiment was performed at least with two repeats.

[0316] The development of plants' radicles and shoots was visually assessed six days after the beginning of the test to determine the Minimal Effective Concentration (MEC) of a test material. In the context of the invention, MEC is defined as the lowest concentration level of a test material that caused deviation (absence of germination or malformation of radicle or shoots) from the plant's development in the Control group. MEC is expressed in an arbitrary unit as an activity score, as presented in Table 15.

[0317] Table 15: The Herbicidal activity Score (arbitrary units) effect on seeds' germination and early plant development.

[0318] Table 15 : Herbicidal activity of selected compounds on seed germination and early plant development

[0319] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a, " "an" and "the" are intended to include plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" or "comprising, " when used in this specification, specify the presence of stated features, integers, steps, operations, elements components and / or groups or combinations thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or groups or combinations thereof. As used herein the terms "comprises", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to". The term "consisting of" means "including and limited to". As used herein, the term "and / or" includes any and all possible combinations or one or more of the associated listed items , as well as the lack of combinations when interpreted in the alternative ( "or" ) .

[0320] Unless otherwise defined, all terms ( including technical and scientific terms ) used herein have the same meaning as commonly understood by one of ordinary s kill in the art to which this invention belongs . It will be further understood that terms , such as those defined in commonly used dictionaries , should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and claims and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein . Well-known functions or constructions may not be described in detail for brevity and / or clarity .

[0321] It will be understood that , although the terms first , second, etc . , may be used herein to describe various elements , components , regions , layers and / or sections , these elements , components , regions , layers and / or sections should not be limited by these terms . Rather , these terms are only used to distinguish one element , component , region, layer and / or section, from another element , component , region, layer and / or section .

[0322] Throughout this application, 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 subranges 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 subranges 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.

[0323] 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 therebetween.

[0324] Whenever the term "about" is used, it is meant to refer to a measurable value such as an amount, a temporal duration, and the like, and is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

[0325] Certain features of the invention, 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 .

[0326] As used herein the terms "comprises", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to".

[0327] The term "consisting of" means "including and limited to". As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof .

[0328] It will be understood that when an element is referred to as being "on, " "attached" to, "connected" to, "coupled" with, "contacting," etc., another element, it can be directly on, attached to, connected to, coupled with and / or contacting the other element or intervening elements can also be present. In contrast, when an element is referred to as being, for example, "directly on, " "directly attached" to, "directly connected" to, "directly coupled" with or "directly contacting" another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed "adjacent" another feature can have portions that overlap or underlie the adjacent feature .

[0329] It will be understood that, although the terms first, second, etc. , may be used herein to describe various elements, components, regions, layers and / or sections, these elements, components, regions, layers and / or sections should not be limited by these terms. Rather, these terms are only used to distinguish one element, component, region, layer and / or section, from another element, component, region, layer and / or section .

[0330] As will be appreciated by those of skill in the art, the compounds of the various formulas disclosed herein may contain chiral centers, e.g. , asymmetric carbon atoms. Thus, the present disclosure is concerned with the synthesis of both: (i) racemic mixtures of the active compounds, and (ii) enantiomeric forms of the active compounds. The resolution of racemates into enantiomeric forms and racemization of optically active enantiomeric form can be done in accordance with known procedures in the art . Geometric isomers of double bonds and the like may also be present in the compounds disclosed herein, and all such stable isomers are included within the present disclosure unless otherwise specified . Also included in the compounds of the disclosure are tautomers ( e . g . , tautomers of triazole and / or imidazole ) and rotamers . All chains defined by the formulas herein which include three or more carbons may be saturated or unsaturated unless otherwise indicated .

[0331] It is understood that substituents and substitution patterns on the compounds used in the method of the present invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques known in the art from readily available starting materials . If a substituent is itself substituted with more than one group, it is understood that these multiple groups may be on the same carbon or on different carbons , so long as a stable structure results .

[0332] An "optionally substituted" group refers to a functional group in which one or more bonds to a hydrogen atom contained therein are replaced by a bond to non-hydrogen or non-carbon atoms , provided that normal valences are maintained and that the substitution results in a stable compound . Substituted groups also include groups in which one or more bonds to a carbon ( s ) or hydrogen ( s ) atom are replaced by one or more bonds , including double or triple bonds , to a heteroatom . Where multiple substituent moieties are disclosed or claimed, the substituted compound can be independently substituted by one or more of the disclosed or claimed substituent moieties , singly or plurally . By independently substituted, it is meant that the ( two or more ) substituents can be the same or different . In choosing the compounds of the present invention, one of ordinary skill in the art will recognize that the various substituents are to be chosen in conformity with well-known principles of chemical structure connectivity .

[0333] As used herein, "H" refers to a hydrogen atom. "C" refers to a carbon atom. "N" refers to a nitrogen atom. "0" refers to an oxygen atom. "Halo" refers to F, Cl, Br or I. The term "hydroxy," as used herein, refers to an —OH moiety. "Br" refers to a bromine atom. "Cl" refers to a chlorine atom. "I" refers to an iodine atom. "F" refers to a fluorine atom. An "acyl group" is intended to mean a group — C(0)— R, where R is a suitable substituent, for example, an acetyl group, a propionyl group, a butyroyl group, a benzoyl group, or an alkylbenzoyl group. "Alkyl," as used herein, refers to a straight or branched chain hydrocarbon containing from 1 or 2 to 10 or 20 or more carbon atoms (e.g. , C2, C3, C4, C5, C6, C7, C8, C9, CIO, Cll, C12, C13, C14, C15, etc. ) . In some embodiments the alkyl can be a lower alkyl. "Lower alkyl" refers to straight or branched chain alkyl having from 1 to 3, or from 1 to 5 , or from 1 to 8 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert- butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl , 2 , 2-dimethylpentyl, 2 , 3-dimethylpentyl , n-heptyl, n-octyl, n- nonyl, n-decyl, and the like. As used herein, the identification of a carbon number range, e.g., C1-C12 alkyl, is intended to include each of the component carbon number moieties within such range, so that each intervening carbon number and any other stated or intervening carbon number value in that stated range is encompassed, such that sub-ranges of carbon number within specified carbon number ranges may independently be specified. For example, C1-C12 alkyl is intended to include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl, including straight chain as well as branched groups, as noted above, and the carbon number range Cl- C12 alkyl may also be more restrictively specified as sub-ranges such as C1-C4 alkyl, C2-C8 alkyl, C2-C4 alkyl, C3-C5 alkyl, or any other sub-range within the broader carbon number range. In addition, ranges of carbon numbers specifically excluding a carbon number or numbers are contemplated, as are sub-ranges excluding either or both of carbon number limits of specified ranges. As generally understood by those of ordinary skill in the art, "saturation" refers to the state in which all available valence bonds of an atom (e.g. , carbon) are attached to other atoms. Similarly, "unsaturation" refers to the state in which not all the available valence bonds are attached to other atoms; in such compounds the extra bonds usually take the form of double or triple bonds (usually with carbon) . For example, a carbon chain is "saturated" when there are no double or triple bonds present along the chain or directly connected to the chain (e.g., a carbonyl) , and is "unsaturated" when at least one double or triple bond is present along the chain or directly connected to the chain (e.g. , a carbonyl) . Further, the presence or absence of a substituent depending upon chain saturation will be understood by those of ordinary skill in the art to depend upon the valence requirement of the atom or atoms to which the substituent binds (e.g., carbon) . "Alkenyl," as used herein, refers to a straight or branched chain hydrocarbon containing from 1 or 2 to 10 or 20 or more carbons, and containing at least one carbon-carbon double bond, formed structurally, for example, by the replacement of two hydrogens. Representative examples of "alkenyl" include, but are not limited to, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2- heptenyl, 2-methyl-l-heptenyl, 3-decenyl and the like. "Alkynyl," as used herein, refers to a straight or branched chain hydrocarbon group containing from 1 or 2 to 10 or 20 or more carbon atoms, and containing at least one carbon-carbon triple bond. Representative examples of alkynyl include, but are not limited, to acetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl, 1-butynyl and the like. The term "cycloalkyl," as used herein, refers to a saturated cyclic hydrocarbon group containing from 3 to 8 carbons or more .

[0334] As understood in the art , the term "optionally substituted" indicates that the specified group is either unsubstituted or substituted by one or more suitable substituents . A "substituent" that is "substituted" is an atom or group which takes the place of a hydrogen atom on the parent chain or cycle of an organic molecule . "Heterocycle , " as used herein, refers to a monocyclic, bicyclic or tricyclic ring system . Monocyclic heterocycle ring systems are exemplified by any 5 to 9-membered ring containing 1 , 2 , 3 , or 4 heteroatoms independently selected from the group consisting of : 0, N, and S . "Aryl" as used herein refers to a ring system having one or more aromatic rings . Representative examples of aryl include azulenyl , indanyl , indenyl , naphthyl , phenyl , tetrahydronaphthyl , and the like . "Heteroaryl" means a cyclic , aromatic hydrocarbon in which one or more carbon atoms have been replaced with heteroatoms ( e . g . , N, 0 or S ) . If the heteroaryl group contains more than one heteroatom, the heteroatoms may be the same or different . "Alkoxy, " as used herein, refers to an alkyl group, as defined herein, appended to the parent molecular moiety through an oxy group, as defined herein . An "amine" or "amino" is intended to mean the group — NH2 . "Primary amines" have one of three hydrogen atoms replaced by an alkyl or aromatic group . "Secondary amines" have two organic substituents bound to the nitrogen together with one hydrogen . "Tertiary amines" have three organic substituents bound to the nitrogen . An "amide" as used herein, refers to a functional group having a carbonyl group (C=O ) linked to a nitrogen atom (N ) , or an organic compound that contains this group, generally depicted as : wherein, R and R' can independently be any covalently linked atom or atoms. The term "oxo", as used herein, refers to a =O moiety. The term "oxy", as used herein, refers to a — 0— moiety. "Nitro" refers to the organic compound functional group — NO2. "Carbonyl" is a functional group having a carbon atom double- bonded to an oxygen atom (— C=O) . "Carboxy" as used herein refers to a — COOH functional group, also written as — CO2H or — (C=O)— OH.

[0335] It will be understood that the compounds, compositions and methods provided herein may be further specified in some embodiments by provisos or limitations excluding specific substituents, groups, moieties, structures, ingredients, steps, or conditions, as applicable, in relation to various broader specifications and exemplifications set forth herein.

[0336] "Agriculturally acceptable carriers" of the invention include, without limitation, adjuvants, mixers, enhancers, etc. beneficial for application of the chemical formula. Suitable carriers should not be phytotoxic to valuable crops, particularly at the concentrations employed in applying the compositions for selective weed control in the presence of crops and should not react chemically with the compounds of the chemical formula herein or other composition ingredients. Such mixtures can be designed for application directly to weeds or their locus or can be concentrates or formulations which are normally diluted with additional carriers and adjuvants before application. They may include inert or active components and can be solids, such as, for example, dusts, granules, water dispersible granules, or wettable powders, or liquids, such as, for example, emulsifiable concentrates, solutions, emulsions or suspensions. Suitable agricultural carriers useful in preparing herbicidal compositions of the present invention are well known to those skilled in the art. For example, liquid carriers that can be employed include water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, methanol, ethanol, isopropanol, amyl alcohol, ethylene glycol, propylene glycol, glycerine, and the like. Water is generally the carrier of choice for the dilution of concentrates. Suitable solid carriers include talc, pyrophyllite clay, silica, attapulgus clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonire clay, Fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, and the like.

[0337] It is frequently desirable to incorporate one or more surface- active agents into the compositions of the present invention. Such surface-active agents are advantageously employed in both solid and liquid compositions, especially those designed to be diluted with carrier before application. The surface-active agents can be anionic, cationic or nonionic in character and can be employed as emulsifying agents, wetting agents, suspending agents, or for other purposes. Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C . sub .18 ethoxylate; alcohol- alkylene oxide addition products, such as tridecyl alcohol- C. sub.16 ethorylate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di ( 2-ethylhexyl ) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono and dialkyl phosphate esters . Other adjuvants commonly utilized in herbicidal compositions include antifoam agents, compatibilizing agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, dyes, odorants, penetrations aids, spreading agents, sticking agents, dispersing agents, thickening agents, freeze point depressants, antimicrobial agents, and the like. The compositions can also contain other compatible components, for example, other herbicides, plant growth regulants, fungicides, insecticides, and the like and can be formulated with liquid fertilizers or solid, particulate fertilizer carriers such as ammonium nitrate, urea and the like.

[0338] "Agriculturally acceptable salt" is intended to mean a salt that retains the biological effectiveness of the free acids and bases of a specified compound and that is not biologically or otherwise undesirable. Examples of agriculturally acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne- 1,4-dioates, hexyne-1, 6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, xylenesulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, y-hydroxybutyrates , glycollates, tartrates, methane- sulfonates, propanesulfonates, naphthalene-l-sulf onates , naphthalene-2-sulf onates , and mandelates.

[0339] Throughout this application, 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 subranges 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 subranges 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 .

[0340] 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 therebetween .

[0341] Certain features of the invention, 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 .

[0342] 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, agricultural, biological, and biochemical arts.

[0343] As used herein the term "plant growth regulator" refers but not limited to a compound, either natural or synthetic, that modifies or controls one or more specific physiological processes within a plant.

[0344] As used herein the term "plant" refers but not limited to whole plants, ancestors and progeny of the plants and plant parts, including seeds, shoots, stems, roots (including tubers) , and plant cells, tissues and organs. The plant may be in any form including suspension cultures, embryos, meristematic regions, callus tissue, leaves, gametophytes, sporophytes, pollen, and microspores .

[0345] As used herein the term "crop protection agent" refers but not limited to an agent which is a pesticide (or a mixture of more than one pesticide) or a plant growth regulator.

[0346] As used herein the term "pesticide" refers to, but not limited to a chemical or biological agent that deters, incapacitates, kills, or otherwise discourages pests.

[0347] Compounds of this invention will generally be used as a herbicidal active ingredient in a composition. As used herein the term "composition" refers but not limited to a formulation, with at least one additional component selected from the oup consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as oil type, moisture and temperature. Useful compositions may include both liquid and solid formulation. Liquid formulations may include solutions (including emulsifiable concentrates) , suspensions, emulsions (including icroemulsions , oil-in-water emulsions, flowable concentrates and / or suspoemulsions ) and alike, which optionally can be thickened into gels . The general types of aqueous liquid compositions are soluble concentrate , suspension concentrate , capsule suspension, oncentrated emulsion, microemulsion, oil- in-water emulsion, flowable concentrate and uspo-emulsion . The general types of nonaqueous liquid compositions are emulsifiable oncentrate , microemulsif iable concentrate , dispersible concentrate and oil dispersion .

[0348] The general types of solid formulations are dusts , powders , granules , pellets , prills , astilles , tablets , filled films ( including seed coatings ) and the like , which can be ater- dispersible ("wettable" ) or water-soluble . Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment . Active ingredient can be (micro ) encapsulated and further formed into a suspension or solid formulation; alternatively, the entire formulation of active ingredient can be encapsulated ( or "overcoated" ) . Encapsulation can control or delay release of the active ingredient . Sprayable formulations are typically extended in a suitable medium before spraying . Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water , but occasionally another suitable medium like an aromatic or paraffinic hydrocarbon or vegetable oil . Spray volumes can range from about one to several thousand liters per hectare , but more typically are in the range from about ten to several hundred liters per hectare . Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant . Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting .

[0349] The formulations will typically contain effective amounts of active ingredient , diluent and surfactant within the following approximate ranges which add up to 100 percent by eight . The compounds of the invention have (both preemergent and postemergent ) herbicidal activity . As used herein the term "controlling undesired plant growth" refers to killing or inj uring the vegetation or reducing its growth .

[0350] The compounds and compositions of the invention can be usefully applied by a variety of methods involving contacting a herbicidally effective amount of a compound of the invention, or a composition comprising the compound and at least one of a surfactant , a solid diluent or a liquid diluent , to the foliage or other part of the undesired plant or to the environment of the undesired plant growth such as the soil or water in which the undesired plant is growing or which surrounds the seed or other propagule of the undesired plant .

[0351] A herbicidally effective amount of the compounds of this invention is determined by a number of factors : formulation selected, method of application, amount and type of undesired plant growth present , growing conditions , etc . In general , a herbicidally effective amount of compounds of this invention is about 0 . 001 to 20 kg / ha with a preferred range of about 0 . 004 to 1 kg / ha . One skilled in the art can easily determine the herbicidally effective amount necessary for the desired level of weed control .

[0352] The compounds of the invention are applied, typically in a form of formulated composition, to a locus comprising desired vegetation ( e . g . , crops ) and undesired plant growth ( i . e . weeds ) , both of which may be seeds , seedlings and / or larger plants , in contact with a growth medium ( e . g . , soil ) . In this locus , a composition comprising the compounds of the invention can be directly applied to a plant or any part of a plant thereof , particularly of the undesired plant growth, and / or to the growth medium in contact with the plant .

[0353] Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including herbicides , herbicide safeners , fungicides , insecticides , nematocides , bactericides , acaricides , plant growth regulators such as insect molting inhibitors and rooting stimulants , chemosterilants , semiochemicals , repellents , attractants , pheromones , feeding stimulants , plant nutrients , other biologically active compounds or bacteria , virus or fungi to form a multi-component pesticide giving broader spectrum of agricultural protection . Mixtures of the compounds of the invention with other herbicides can broaden the spectrum of activity against additional weed species and suppress the proliferation of any resistant biotypes .

[0354] Throughout this application various publications , published patent applications and published patents are referenced . The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains .

[0355] Certain features of the invention, 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 .

Claims

Claims :

1. A method of modulating at least one NO3- transporter in a plant, the method comprising applying at least one compound characterized by having a binding affinity to at least one area of the at least one NO3- transporter, the compound comprising: (i) a substituted or non-substituted 5-membered heterocycle, and, ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by an optionally substituted flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10Angstrom.

2. A method of modulating at least one NO3- transporter in a plant, the method comprising applying at least one compound characterized by having a binding affinity to at least one area of the at least oneNO3- transporter, the compound comprising: (i) a substituted or non-substituted 6-membered heterocycle, and (ii) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by a flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of theheterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

3. A method of modulating accumulation of nitrate in a plant, the method comprising applying to the plant at least one compound, characterized by having a binding affinity to at least one area of the at least one NO3- transporter, the compound comprising: (i) a substituted or non-substituted 5-membered heterocycle, and, (ii) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by an optionally substituted flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or ”25 to “80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10Angstrom.

4. A method of modulating accumulation of nitrate in a plant, the method comprising applying to the plant at least one compound / composition characterized by having a binding affinity to at least one area of the at least one NO3- transporter, the compound comprising: (1) a substituted or non-substituted 6- membered heterocycle, and ( ii ) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by a flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degreesor -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10Angstrom .

5. A method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, characterized by having a binding affinity to at least one area of the at least one NO3- transporter, the compound comprising: (i) a substituted or non-substituted 5- membered heterocycle, and, (ii) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by an optionally substituted flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom.

6. A method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, characterized by having a binding affinity to at least one area of the at least oneNO3- transporter, the compound comprising: (i) a substituted or non-substituted 6- membered heterocycle, and (ii) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) areinterconnected by a flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10Angstrom .

7. The method of any one of claims 1 to 6, wherein the NO3_transporter is selected from a group consisting of Nitrate Transporterl / Peptide Transporter family (NRT1 / NPF) and Nitrate Transporter! (NRT2) family, specifically, NPF6.3 (NRT1.1) , NPF6.2 (NRT1.4) , andNRT2.1.

8. The method of any one of claims 1 to 7, wherein at least one area of the at least one NO3- transporter is a NO3- binding site.

9. The method of any one of claims 1 to 8, wherein the binding affinity is equal or higher than -4 kcal / mol.

10. The method of any one of claims 1 to 9, wherein the compound is an amphiphilic compound.

11. The method of any one of claims 1 to 10, wherein the heterocycle is at least a partially positively charged or a dipole.

12. The method of any one of claims 1 to 11, wherein the heterocycle compr isesleast one heteroatom selected from the group consisting of sulfur (S) , nitrogen (N) and oxygen (O) -13. The method of any one of claims 1 to 12, wherein the heterocycle is selected from Pyridine (C5N) , Pyrrole(C4N) , Thiophen (C4S) , 1,2-Thiazole (C3NS) , 1,3-Thiazole (C3NS) , Isothiazole (C3NS) , 1,2-Thiazine (C4NS) , 1,3-Thiazine (C4NS) , 1,4-Thiazine (C4NS) , Oxazole (C3NO) , Isoxazole (C3NO) , 1,2-Oxazines (C4NO) , 1 , 3-Oxazines (C4NO ) , or 1,4-Oxazines (C4NO) .

14. The method of any one of claims 1 to 13, wherein the heterocycle is substituted by at least one molecule selected fromand -SO2F.

15. The method of any one of claims 1 to 14, wherein the heterocycle has 1 or 2 substituted carbon atoms .

16. The method of any one of claims 1 to 15, wherein the anionic or electronegative group is characterized as having at least a partial negative charge.

17. The method of any one of claims 1 to 16, wherein the anionic / electronegative group is selected from carboxyl, phosphonate, phosphate, sulfate, sulfonate, or an ester thereof, or a salt thereof.

18. The method of claim 17, wherein the ester is selected from an alkane; a phenol; a mono-, di-, or three halides phenol; a pyridine; mono-, di-, or three halides pyridine; an alkyl phenol (aliphatic chain C1-15) ; alkyl pyridine (aliphatic chain C1-15) , an ether, a polyether, a diol, poly-diol, or any combination thereof .

19. The method of any one of claims 17 or 18, wherein the ester is selected from [ (CH2) 2O]m(CH2)nCH3,20. The method of claim 17, wherein the salt is a Na, K,Ca, NH<r salt.

21. The method of any one of claims 1 to 20, wherein the anionic / electronegative group is selected from the group consisting of nitro-, cyano-, and nitrate.

22. The method of any one of claims 1 to 21, wherein the flexible linker comprises at least one substituted or non-substituted carbon atoms and 0 or 1 heteroatom selected from oxygen (O) , sulfur (S) , and nitrogen23. The method of any one of claims 1 to 22, wherein the carbon atom of the flexible linker is substituted with F, Br, Cl, or I .

24. The method of any one of claims 1 to 23, wherein carbon atom of the flexible linker is substituted25. The method of any one of claims 1 to 24, wherein the PSA is a spatial arrangement with the lowest energy minimum among all possible conformers for an individual molecule.

26. The method of any one of claims 1 to 25, wherein the compound selected from the group consisting ot :

7. The method ot any one of claims 1 to 26, wherein the compound selected from the group consisting of:2- (2-chloro-l, 3-thiazol-4-yl ) -2-fluoro-2- phenyl acet icacid2- (2-chloro-l, 3-thiazol-4-yl ) -2-phenylaceticacid2- (2-chloro-l, 3-thiazol-4-yl)hexanoicacid2- (2-chloro-l, 3-thiazol-4-yl) pent ano icacid2- (4-chloro-l, 3-thiazol-2-yl) -2, 2 -di fluoro acet icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2 -fluoro- 2- phenyl acet icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- fluorobut ano icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- fluorohexanedio icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luorohexanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent anedioicac id2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icacid2- ( 6-bromo-5-f luoropyridin-2-yl (octanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) heptanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) hexanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentane dioic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) propanoic acid2.3 -dibromo- 6- ( 2 -ethoxy- 1 -fluoroethyl ) pyridine2.3-dibromo-6- [l-fluoro-2- (2- methoxyethoxy ) ethyl] pyridine2.3 -dibromo- 6- [l-fluoro-2- (hexyloxy) ethyl] pyridine2-chloro-4- [l-fluoro-2- (2-methoxyethoxy) ethyl] -1, 3- thiazole2-chloro-4- [l-fluoro-2- (pentyloxy) ethyl] -1, 3- thiazole4- ( 2-butoxy-l-f luoroethyl ) -2-chloro-l, 3-thiazole2- (2-chloro-l, 3-thiazol-4-yl ) -2-f luoroacetic acid2- [5- (carboxymethyl) -2-chloro-l, 3-thiazol-4-yl] -2- fluoroacetic acid2- [ 6-bromo-4- ( carboxymethyl ) -5-f luoropyridin-2- yl] acetic acid2- [2-bromo-6- (carboxymethoxy) -3-f luoropyridin-4- yl] acetic acid2-bromo-6- ( carboxymethylsulfanyl ) pyridine-3-carboxylic acid2-bromo-6- ( carboxymethylsulfanyl ) pyridine-4-carboxylic acid2- [ 2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-3- yl] acetic acid2- [ 2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-4- yl] acetic acid2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridine-4- carboxylic acid2- [2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridin-4-yl] acetic acid2- [2- (carboxymethoxy) -6-chloropyridin-4-yl] acetic acid2- [2- (carboxymethylsulfanyl) -6-chloropyridin-4- yl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) oxypropanoic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylpropanoic acid2-bromo-6- (nitromethoxy) pyridine2-bromo-6- (nitromethylsulfanyl) pyridine2-bromo-3-f luoro-6- (nitromethyl) pyridine2- (5-chloro-4-oxopyrrol-2-yl) acetic acid4- (5-chloro-4-oxopyrrol-2-yl) butanoic acid4- ( 5-chloro-4-sulfanylidenepyrrol-2-yl ) butanoic acid4- ( 2-chloro-l-oxo-l , 3-thiazol-4-yl ) butanoic acid2-chloro-5- ( 3-nitropropyl ) pyrrol-3-one2-chloro-5- (3-nitropropyl) pyrrole-3-thione2-chloro-4- (3-nitropropyl) -1, 3-thiazolel-oxide2- ( 5-chloro-4-sulfanylidenepyrrol-2-yl ) acetic acid2- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) acetic acid2-chloro-5- (nitromethyl) pyrrol-3-one2-chloro-5- (nitromethyl) pyrrole-3-thione2-chloro-4- (nitromethyl) -1, 3-thiazolel-oxide2,5-dichloro-4-( nitromethyl )-l, 3- thiazole2-chloro-4- (nitromethyl) -1, 3-thiazole2- (2, 5-dichloro-l, 3-thiazol-4-yl ) acetic acid2- ( 4-oxopyrrol-2-yl ) oxyacetic acid5- ( 4 -chlorophenoxy) -1,2, 4-triazol-3-one4-bromo-2- ( 4-chlorophenoxy) -5-f luoropyrimidine2- ( 6-bromopyridin-2-yl) sulfanylacetic acid2- [ (4-chloro-l, 3-thiazol-2-yl ) sulfanyl] acetic acid ethyl 2- [ ( 6-bromo-5-f luoropyridin-2- yl) sulfanyl] acetate ethyl2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetate2- (3, 6-dibromopyridin-2-yl ) sulfanylacetic acid2- [ (S) - (2, 5-dichloro-l, 3-thiazol-4-yl ) sulfinyl] acetic acid2- [ (2, 5-dichloro-l, 3-thiazol-4-yl ) sulfanyl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid4- (5, 6-dibromopyridin-2-yl ) sulfanylbutanoic acid28. A method of modulating at least one NO3- transporter in a plant, the method comprising applying at leastone compound characterized by having a binding affinity to at least one area of the at least oneN03- transporter , selected from the group consist ing of :29 . A method of modulating accumulation of n itrate in a plant , the method comprising applying to the plant at least one compound / composition characteri zed byhaving a binding affinity to at least one area of the at least one NO3- transporter , the compound , selected from the group consisting of :A method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound, characterized by having a binding affinity t at least one area ot the at least one NO3- transporter , the compound, selected trom the group cons isting of :in a plant, the method comprising applying at least one compound characterized by having a binding affinity to at least one area of the at least one NO3- transporter, selected from the group consisting of:2- ( 2 -chloro- 1 , 3-thiazol-4-yl) -2-fluoro-2- phenylaceticacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl) -2 -phenylacet icac id2- ( 2 -chloro- 1 , 3-thiazol-4-yl) hexanoicacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl)pentanoicacid2- ( 4 -chloro- 1 , 3-thiazol-2-yl) -2, 2-dif luoroaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-fluoro-2- phenylaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-f luorobutanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luorohexanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-f luorohexanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent anedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icac id2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icac id2- ( 6-bromo-5-f luoropyridin-2-yl ) octanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) heptanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) hexanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentane dioic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) propanoic acid2.3 -dibromo- 6- ( 2 -ethoxy- 1-f luoroethyl ) pyridine2.3 -dibromo- 6- [l-fluoro-2 - (2- methoxyethoxy ) ethyl ] pyridine2.3-dibromo-6- [l-fluoro-2- (hexyloxy) ethyl] pyridine2-chloro-4- [l-fluoro-2- ( 2-methoxyethoxy ) ethyl] -1, 3- thiazole2-chloro-4- [l-fluoro-2- (pentyloxy) ethyl] -1, 3-thiazole4- ( 2-butoxy-l-f luoroethyl ) -2-chloro-l, 3-thiazole2- (2-chloro-l, 3-thiazol-4-yl ) -2-f luoroacetic acid2- [5- (carboxymethyl) -2-chloro-l, 3-thiazol-4-yl ] -2- fluoroacetic acid2- [6-bromo-4- (carboxymethyl) -5-f luoropyridin-2- yl] acetic acid2- [2-bromo-6- (carboxymethoxy) -3-f luoropyridin-4- yl] acetic acid2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridine -3 -carboxylic acid2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridine -4 -carboxylic acid2- [2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-3-yl] acetic acid2- [2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-4-yl] acetic acid2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridine-4- carboxylic acid2- [2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridin-4- yl] acetic acid2- [2- (carboxymethoxy) -6-chloropyridin-4-yl] acetic acid 2- [2- (carboxymethylsulfanyl) -6-chloropyridin-4- yl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid3- ( 6 -bromo- 5 -f luoropyridin-2-yl ) oxypropanoic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylpropanoic acid 2-bromo-6- (nitromethoxy) pyridine2 -bromo- 6- ( nitromethyl sulfanyl ) pyridine2-bromo-3-f luoro-6- (nitromethyl) pyridine2- (5-chloro-4-oxopyrrol-2-yl) acetic acid4- (5-chloro-4-oxopyrrol-2-yl) butanoic acid4- ( 5-chloro-4-sulf anylidenepyrrol-2-yl ) butanoic acid4- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) butanoic acid 2-chloro-5- ( 3-nitropropyl ) pyrrol-3-one2-chloro-5- (3-nitropropyl) pyrrole-3-thione2-chloro-4- (3-nitropropyl) -1, 3-thiazolel-oxide2- (5-chloro-4-sulfanylidenepyrrol-2-yl) acetic acid 2- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) acetic acid 2-chloro-5- (nitromethyl) pyrrol-3-one2-chloro-5- (nitromethyl) pyrrole-3-thione2-chloro-4- (nitromethyl) -1, 3-thiazolel-oxide2 , 5 -di chloro- 4- ( nitromethyl )-l, 3- thiazole2-chloro-4- (nitromethyl) -1, 3-thiazole2-(2,5-dichloro-l,3-thiazol-4-yl)acetic acid2- ( 4 -oxopyrrol -2 -yl ) oxyacetic acid5- ( 4-chlorophenoxy) -1, 2, 4-triazol-3-one4-bromo-2- ( 4-chlorophenoxy) -5-f luoropyrimidine2- ( 6-bromopyridin-2-yl ) sulfanylacetic acid2 - [ ( 4 - chloro- 1 , 3-thiazol-2-yl) sulfanyl ] acetic acid ethyl 2- [ ( 6-bromo-5-f luoropyridin-2-yl ) sulfanyl] acetate ethyl2- ( 6-bromo-5-f luoropyridin-2-yl) oxyacetate 2- (3, 6-dibromopyridin-2-yl ) sulfanylacetic acid 2-[ (S)-(2,5-dichloro-l,3-thiazol-4-yl) sulfinyl ] acetic acid2- [ (2, 5-dichloro-l , 3-thiazol-4-yl ) sulfanyl] acetic acid 2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid 2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid4- (5 , 6-dibromopyridin-2-yl ) sulfanylbutanoic acid32. A method of modulating accumulation of nitrate in a plant, the method comprising applying to the plant at least one compound / composition characterized by having a binding affinity to at least one area of the at least one NO;r transporter, the compound, selected from the group consisting of:2- ( 2 -chloro- 1 , 3-thiazol-4-yl) -2-fluoro-2- phenylaceticacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl) -2-phenylaceticacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl) hexanoicacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl)pentanoicacid2- ( 4 -chloro- 1 , 3-thiazol-2-yl) -2, 2-dif luoroaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-fluoro-2- phenylaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-f luorobutanoicacid 2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luorohexanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-f luorohexanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent anedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icac id2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icac id2- ( 6-bromo-5-f luoropyridin-2-yl ) octanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) heptanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) hexanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentane dioic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) propanoic acid2.3 -dibromo- 6- ( 2 -ethoxy- 1-f luoroethyl ) pyridine2.3 -dibromo- 6- [l-fluoro-2- (2- methoxyethoxy ) ethyl ] pyridine2.3-dibromo-6- [l-fluoro-2- (hexyloxy) ethyl] pyridine 2-chloro-4- [l-fluoro-2- ( 2-methoxyethoxy ) ethyl] -1, 3- thiazole2-chloro-4- [l-fluoro-2- (pentyloxy) ethyl] -1, 3-thiazole 4- ( 2-butoxy-l-f luoroethyl ) -2-chloro-l, 3-thiazole2- (2-chloro-l, 3-thiazol-4-yl ) -2-f luoroacetic acid2- [5- (carboxymethyl) -2-chloro-l, 3-thiazol-4-yl ] -2- fluoroacetic acid2- [6-bromo-4- (carboxymethyl) -5-f luoropyridin-2- yl] acetic acid2- [2-bromo-6- (carboxymethoxy) -3-f luoropyridin-4- yl] acetic acid2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridine -3 -carboxylic acid2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridine -4 -carboxylic acid2- [2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-3-yl] acetic acid2- [2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-4-yl] acetic acid2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridine-4- carboxylic acid2- [2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridin-4- yl] acetic acid2- [2- (carboxymethoxy) -6-chloropyridin-4-yl] acetic acid2- [2- (carboxymethylsulfanyl) -6-chloropyridin-4- yl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid3- ( 6 -bromo- 5-f luoropyridin-2-yl ) oxypropanoic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylpropanoic acid2-bromo-6- (nitromethoxy) pyridine2 -bromo- 6- ( nitromethyl sulfanyl ) pyridine2-bromo-3-f luoro-6- (nitromethyl) pyridine2- (5-chloro-4-oxopyrrol-2-yl) acetic acid4- (5-chloro-4-oxopyrrol-2-yl) butanoic acid4- ( 5-chloro-4-sulf anylidenepyrrol-2-yl ) butanoic acid4- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) butanoic acid2-chloro-5- ( 3-nitropropyl ) pyrrol-3-one2-chloro-5- (3-nitropropyl) pyrrole-3-thione2-chloro-4- (3-nitropropyl) -1, 3-thiazolel-oxide2- (5-chloro-4-sulfanylidenepyrrol-2-yl) acetic acid2- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) acetic acid2-chloro-5- (nitromethyl) pyrrol-3-one2-chloro-5- (nitromethyl) pyrrole-3-thione2-chloro-4- (nitromethyl) -1, 3-thiazolel-oxide2 , 5 -di chloro- 4- ( nitromethyl )-l, 3- thiazole2-chloro-4- (nitromethyl) -1, 3-thiazole2-(2,5-dichloro-l,3-thiazol-4-yl)acetic acid2- ( 4 -oxopyrrol -2 -yl ) oxyacetic acid5- ( 4-chlorophenoxy) -1, 2, 4-triazol-3-one4-bromo-2- ( 4-chlorophenoxy) -5-f luoropyrimidine2- ( 6-bromopyridin-2-yl ) sulfanylacetic acid2 - [ ( 4 - chloro- 1 , 3-thiazol-2-yl) sulfanyl ] acetic acidethyl 2- [ ( 6-bromo-5-f luoropyridin-2-yl ) sulfanyl] acetate ethyl2- ( 6-bromo-5-f luoropyridin-2-yl) oxyacetate2- (3, 6-dibromopyridin-2-yl ) sulfanylacetic acid2-[ (S)-(2,5-dichloro-l,3-thiazol-4-yl) sulfinyl ] acetic acid2- [ (2, 5-dichloro-l , 3-thiazol-4-yl ) sulfanyl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid4- (5 , 6-dibromopyridin-2-yl ) sulfanylbutanoic acid33. A method of controlling undesired vegetation comprising applying to the locus of the undesired vegetation at least one compound; characterized by having a binding affinity to at least one area of the at least one NO3- transporter, the compound, selected from the group consisting of:2- ( 2 -chloro- 1 , 3-thiazol-4-yl) -2-fluoro-2- phenylaceticacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl) -2-phenylaceticacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl) hexanoicacid2- ( 2 -chloro- 1 , 3-thiazol-4-yl)pentanoicacid2- ( 4 -chloro- 1 , 3-thiazol-2-yl) -2, 2-dif luoroaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-fluoro-2- phenylaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-f luorobutanoicacid 2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luoroheptanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luorohexanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2-f luorohexanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent anedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icac id2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icac id2- ( 6-bromo-5-f luoropyridin-2-yl ) octanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) heptanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) hexanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentane dioic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) propanoic acid2.3 -dibromo- 6- ( 2 -ethoxy- 1-f luoroethyl ) pyridine2.3 -dibromo- 6- [l-fluoro-2 - (2- methoxyethoxy ) ethyl ] pyridine2.3-dibromo-6- [l-fluoro-2- (hexyloxy) ethyl] pyridine2-chloro-4- [l-fluoro-2- ( 2-methoxyethoxy ) ethyl] -1, 3- thiazole2-chloro-4- [l-fluoro-2- (pentyloxy) ethyl] -1, 3-thiazole4- ( 2-butoxy-l-f luoroethyl ) -2-chloro-l, 3-thiazole2- (2-chloro-l, 3-thiazol-4-yl ) -2-f luoroacetic acid2- [5- (carboxymethyl) -2-chloro-l, 3-thiazol-4-yl ] -2- fluoroacetic acid2- [6-bromo-4- (carboxymethyl) -5-f luoropyridin-2- yl] acetic acid2- [2-bromo-6- (carboxymethoxy) -3-f luoropyridin-4- yl] acetic acid2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridine -3 -carboxylic acid2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridine -4 -carboxylic acid2- [2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-3-yl] acetic acid2- [2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-4-yl] acetic acid2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridine-4- carboxylic acid2- [2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridin-4- yl] acetic acid2- [2- (carboxymethoxy) -6-chloropyridin-4-yl] acetic acid2- [2- (carboxymethylsulfanyl) -6-chloropyridin-4- yl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid3- ( 6 -bromo- 5-f luoropyridin-2-yl ) oxypropanoic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylpropanoic acid2-bromo-6- (nitromethoxy) pyridine2 -bromo- 6- ( nitromethyl sulfanyl ) pyridine2-bromo-3-f luoro-6- (nitromethyl) pyridine2- (5-chloro-4-oxopyrrol-2-yl) acetic acid4- (5-chloro-4-oxopyrrol-2-yl) butanoic acid4- ( 5-chloro-4-sulf anylidenepyrrol-2-yl ) butanoic acid4- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) butanoic acid2-chloro-5- ( 3-nitropropyl ) pyrrol-3-one2-chloro-5- (3-nitropropyl) pyrrole-3-thione2-chloro-4- (3-nitropropyl) -1, 3-thiazolel-oxide2- (5-chloro-4-sulfanylidenepyrrol-2-yl) acetic acid2- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) acetic acid2-chloro-5- (nitromethyl) pyrrol-3-one2-chloro-5- (nitromethyl) pyrrole-3-thione2-chloro-4- (nitromethyl) -1, 3-thiazolel-oxide2 , 5 -di chloro- 4- ( nitromethyl )-l, 3- thiazole2-chloro-4- (nitromethyl) -1, 3-thiazole2-(2,5-dichloro-l,3-thiazol-4-yl)acetic acid2- ( 4 -oxopyrrol -2 -yl ) oxyacetic acid5- ( 4-chlorophenoxy) -1, 2, 4-triazol-3-one4-bromo-2- ( 4-chlorophenoxy) -5-f luoropyrimidine2- ( 6-bromopyridin-2-yl ) sulfanylacetic acid2- [ ( 4 - chloro- 1 , 3-thiazol-2-yl) sulfanyl ] acetic acid ethyl 2- [ ( 6-bromo-5-f luoropyridin-2-yl ) sulfanyl] acetate ethyl2- ( 6-bromo-5-f luoropyridin-2-yl) oxyacetate2- (3, 6-dibromopyridin-2-yl ) sulfanylacetic acid2-[ (S)-(2,5-dichloro-l,3-thiazol-4-yl) sulfinyl ] acetic acid2- [ (2, 5-dichloro-l , 3-thiazol-4-yl ) sulfanyl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid4- (5 , 6-dibromopyridin-2-yl ) sulfanylbutanoic acid34, The method of any one of claims 1 to 33, additionally comprising applying at least one additional plant protect ion compound .

35. The method of claim 34, wherein the at least one additional plant protection agent is selected from the group consisting of herbicides, fungicides, insecticides, plant growth regulators, amino acid synthesis inhibitor herbicide, and any combination thereof .

36. The method of claim 35, wherein the amino acid synthesis inhibitor herbicide is selected from the group consisting of sulfonylurea herbicide, imidazolinone herbicide, sulfonamide herbicide and amino acid derivatives, imazamox, imazapic, imazethapyr, imazaquin, imazapyr and imazamethabenz , Chlorimuron, Primisulf uron, Thif ensulfuron, Triasulfuron, Nicosulf uron, Metsulfuron, Tribenuron,Rimsulfuron, Trif lusulfuron and glyphosate, or a combination thereof.

37. The method of claim 35, wherein the plant growth regulator is selected from the group consisting of dicamba, 2,4-D clopyralid and fluroxypyr, or a combination thereof.

38. The method of any one of claims 33 to 37, further comprising applying a third herbicide or a plant growth regulator.

39. A herbicidal composition, comprising at least one compound characterized by having a binding affinity to at least one area of at least oneNO3- transporter, the compound comprising: (i) a substituted or non-substituted 5-membered heterocycle, and, (ii) an anionic or electronegative group comprising an acidic and / or electronegative site; wherein (i) and (ii) are interconnected by an optionally substituted flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom and at least one herbicidally acceptable40. A herbicidal composition, comprising at least one compound characterized by having a binding affinity to at least one area of at least one NO3- transporter, the compound comprising: (i) a substituted or non-substituted 6-membered heterocycle, and (ii) an anionic or electronegative group comprising an acidic and / or electronegativesite; wherein (i) and (ii) are interconnected by a flexible linker; and wherein a preferred spatial arrangement (PSA) of the compound has a torsion angle in the range of +25 to +80 degrees or -25 to -80 degrees in the flexible linker, and, wherein an intramolecular distance between the centroid of the heterocycle and the acidic or electronegative site of the anionic or electronegative group is in the range of 3 to 10 Angstrom and at least one herbicidally acceptable carrier.

41. The herbicidal composition of either one of claim 39 or claim 40, wherein the NO3- transporter is selected from a group consisting of Nitrate Transporter! / Peptide Transporter family (NRT1 / NPF) and Nitrate Transporter2 (NRT2) family, specifically, NPF6.3 (NRTl.l) , NPF6.2 (NRT1.4) , and NRT2.1.

42. The herbicidal composition of any one of claims 39 to 41, wherein at least one area of the at least one NO3- transporter is a NO3- binding site. herbicidal composition of any one of claims 39 to 42, wherein the binding affinity is equal or higher(larger) than ”4 / 5 kcal / mol. herbicidal composition of any one of claims 39 to 43, wherein the compound is an amphiphilic compound .

45. The herbicidal composition of any one of claims 39 to 44, wherein the heterocycle is at least a partially positively charged or a dipole.

46. The herbicidal composition of any one of claims 39 to 45, wherein the heterocycle comprises at least one heteroatom selected from the group consisting of sulfur (S) , nitrogen (N) and oxygen (0) -47. The herbicidal composition of any one of claims 39 to 46, wherein the heterocycle is selected from Pyridine (C5N) , Pyrrole (C4N) , Thiophen (C4S) , 1,2-Thiazole (C3NS) , 1,3-Thiazole (C3NS) , Isothiazole (C3NS) , 1,2-Thiazine (C4NS) , 1,3-Thiazine (C4NS) , 1,4- Thiazine (C4NS) , Oxazole (C3NO) , Isoxazole (C3NO) , 1,2-Oxazines (C4NO) , 1 , 3-Oxazines (C4NO) , or 1,4-Oxazines (C4NO) .

48. The herbicidal composition of any one of claims 39 to 47, wherein the heterocycle is substituted by at least one molecule selected from -Cl, -Br, -F, -I, =O, =3, -CF3, -CCI3, and -SO2F.

49. The herbicidal composition of any one of claims 39 to 48, wherein the heterocycle has 1 or 2 substituted carbon atoms .

50. The herbicidal composition of any one of claims 39 to 49, wherein the anionic or electronegative group is characterized as having at least a partial negative charge.

51. The herbicidal composition of any one of claims 39 to 50, wherein the anionic / electronegative group is selected from carboxyl, phosphonate, phosphate, sulfate, sulfonate, or an ester thereof, or a salt thereof.

52. The herbicidal composition of claim 51, wherein the ester is selected from an alkane; a phenol; a mono-, di-, or three halides phenol; a pyridine; mono-, di- , or three halides pyridine; an alkyl phenol (aliphatic chain Ci-is) ? alkyl pyridine (aliphatic chain Ci-15) , an ether, a polyether, a diol, poly- diol, or any combination thereof.

53. The herbicidal composition of any one of claims 51 or 52, wherein the ester is selected from [ ( CH2)2O]m(CH2)nCH3, [ (CH2)2O]m(CH2)nC6H5,[ (CH2)2O]m(CH2)nC5NH4, [ ( CH2)20 ]m( CH2) nC5NHsBr , or[ (CH2)2O]m(CH2)nC5NH2BrF; and wherein n = 0 to 15 and m = 0 to 5.

54. The herbicidal composition of claim 53, wherein the salt is a Na, K, Ca, NF h+salt.

55. The herbicidal composition of any one of claims 39 to 54, wherein the anionic / electronegative group is selected from the group consisting of nitro-, cyano- , and nitrate.

56. The herbicidal composition of any one of claims 39 to 55, wherein the flexible linker comprises at least one substituted or non-substituted carbon atom andor 1 heteroatom selected from oxygen (0) , sulfur (S) , and nitrogen (N; .

57. The herbicidal composition of any one of claims 39 to 56, wherein the carbon atom of the flexible linker is substituted with F, Br, Cl, or I.

58. The herbicidal composition of any one of claims 39 to 57, wherein carbon atom of the flexible linker is substituted with (CH2)nCH3, -O [ (CH2)20]m(CH2)nCH3, (CH2)nC6H5, -O [ (CH2)2O]m(CH2)nC6H5, (CH2)nC5NH4,0 [ (CH2)2O]m(CH2)nC5NH4, (CH2)nC5NH3Br,0 [ (CH2)2O]m(CH2)nC5NH3Br, (CH2)nC5NH2BrF, or 0[ (CH2)2O]m(CH2)nC5NH2BrF; and wherein n = 0 to 15 and m = 0 to 5.

59. The herbicidal composition of any one of claims 39 to 58, wherein the PSA is a spatial arrangement with the lowest energy minimum among all possible conformers for an individual molecule.

0. The herbicidal composition of any one of claims 39 to 59, wherein the compound selected from the group consisting of:2- (2-chloro-l, 3-thiazol-4-yl ) -2-fluoro-2- phenylaceticacid2- (2-chloro-l, 3-thiazol-4-yl ) -2-phenylaceticacid2- (2-chloro-l, 3-thiazol-4-yl) hexanoicacid2- (2-chloro-l, 3-thiazol-4-yl) pentanoicacid2- (4-chloro-l, 3-thiazol-2-yl) -2, 2-dif luoroaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2-f luoro-2- phenylaceticacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2-f luorobutanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2- f luoroheptanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2-f luoroheptanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2- f luorohexanedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2-f luorohexanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2- f luor opent anedioicacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2-f luoropentanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl) -2-f luoropentanoicacid2- ( 6-bromo-5-f luoropyridin-2-yl) octanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl) heptanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl) hexanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl) pentanedioic acid2- ( 6-bromo-5-f luoropyridin-2-yl) pentanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl) propanoic acid2.3-dibromo-6- ( 2 -ethoxy- 1 -fluoroethyl ) pyridine2.3-dibromo-6- [l-fluoro-2- (2- methoxyethoxy ) ethyl] pyridine2.3-dibromo-6- [l-fluoro-2- (hexyloxy) ethyl ] pyridine2-chloro-4- [l-fluoro-2- (2-methoxyethoxy) ethyl] -1, 3- thiazole2-chloro-4- [l-fluoro-2- (pentyloxy) ethyl] -1, 3-thiazole4- ( 2-butoxy-l-f luoroethyl ) -2-chloro-l, 3-thiazole2- (2-chloro-l, 3-thiazol-4-yl ) -2-f luoroacetic acid2- [5- (carboxymethyl) -2-chloro-l, 3-thiazol-4-yl] -2- fluoroacetic acid2- [ 6-bromo-4- (carboxymethyl) -5-f luoropyridin-2-yl] acetic acid2- [2-bromo-6- (carboxymethoxy) -3-f luoropyridin-4- yl] acetic acid2-bromo-6- ( carboxymethylsulfanyl ) pyridine-3-carboxylic acid2-bromo-6- ( carboxymethylsulfanyl ) pyridine-4-carboxylic acid2- [ 2 -bromo- 6- ( carboxymethyl sulfanyl )pyridin-3-yl] acetic acid2- [ 2 -bromo- 6- ( carboxymethyl sulfanyl )pyridin-4-yl] acetic acid2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridine-4- carboxylic acid2- [2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridin-4- yl] acetic acid2- [2- (carboxymethoxy) -6-chloropyridin-4-yl] acetic acid2- [2- (carboxymethylsulfanyl) -6-chloropyridin-4-yl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) oxypropanoic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylpropanoic acid2-bromo-6- (nitromethoxy) pyridine2-bromo-6- (nitromethylsulfanyl) pyridine2-bromo-3-f luoro-6- (nitromethyl) pyridine2- (5-chloro-4-oxopyrrol-2-yl) acetic acid4- (5-chloro-4-oxopyrrol-2-yl) butanoic acid4- ( 5 -chloro -4 -sulf anylidenepyrrol-2-yl ) butanoic acid4- ( 2-chloro-l-oxo-l , 3-thiazol-4-yl ) butanoic acid2-chloro-5- ( 3-nitropropyl ) pyrrol-3-one2-chloro-5- (3-nitropropyl) pyrrole-3-thione2-chloro-4- (3-nitropropyl) -1, 3-thiazolel-oxide2- (5-chloro-4-sulfanylidenepyrrol-2-yl) acetic acid2- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) acetic acid2-chloro-5- (nitromethyl) pyrrol-3-one2-chloro-5- (nitromethyl) pyrrole-3-thione2-chloro-4- (nitromethyl) -1, 3-thiazolel-oxide2,5-dichloro-4- (nitromethyl) -1,3- thiazole2-chloro-4- (nitromethyl) -1, 3-thiazole2- (2, 5-dichloro-l, 3-thiazol-4-yl ) acetic acid2- ( 4-oxopyrrol-2-yl) oxyacetic acid5- ( 4 -chlorophenoxy ) -1,2, 4-triazol-3-one4-bromo-2- ( 4-chlorophenoxy ) -5-f luoropyrimidine2- ( 6-bromopyridin-2-yl ) sulfanylacetic acid2- [ (4-chloro-l, 3-thiazol-2-yl ) sulfanyl] acetic acid ethyl 2- [ ( 6-bromo-5-f luoropyridin-2-yl) sulfanyl] acetate ethyl2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetate2- (3, 6-dibromopyridin-2-yl ) sulfanylacetic acid2- [ (S) - (2, 5-dichloro-l, 3-thiazol-4-yl ) sulfinyl] acetic acid2- [ (2, 5-dichloro-l, 3-thiazol-4-yl ) sulfanyl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid4- (5, 6-dibromopyridin-2-yl ) sulfanylbutanoic acid62. An herbicidal composition, comprising at least one compound characterized by having a binding affinity to at least one area of the at least oneNO3- transporter , selected from the group consis ting of :63 . An herbicidal composition, comprising at least one compound characterized by having a b i n d i n g a f f i n i t y to at least one area of the at least one NO3- transporter selected from the group consisting of :2- (2-chloro-l, 3-thiazol-4-yl ) -2-fluoro-2- phenyl acet icacid2- (2-chloro-l, 3-thiazol-4-yl ) -2-phenylaceticacid2- (2-chloro-l, 3-thiazol-4-yl)hexanoicacid2- (2-chloro-l, 3-thiazol-4-yl) pent ano icacid2- (4-chloro-l, 3-thiazol-2-yl) -2, 2 -di fluoro acet icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2 -fluoro- 2- phenyl acet icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- fluorobut ano icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- fluoroheptanedio icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- fluorohept ano icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- fluorohexanedio icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- fluorohexano icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent anedio icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icacid2- ( 6-bromo-5-f luoropyridin-2-yl ) -2- f luor opent ano icacid2- ( 6-bromo-5-f luoropyridin-2-yl (octanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) heptanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) hexanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentane dioic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) pentanoic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) propanoic acid2.3 -dibromo- 6- ( 2 -ethoxy- 1 -fluoroethyl ) pyridine2.3-dibromo-6- [l-fluoro-2- (2- methoxyethoxy ) ethyl] pyridine2.3 -dibromo- 6- [l-fluoro-2- (hexyloxy) ethyl] pyridine2-chloro-4- [l-fluoro-2- (2-methoxyethoxy) ethyl] -1, 3- thiazole2-chloro-4- [l-fluoro-2- (pentyloxy) ethyl] -1, 3- thiazole4- ( 2-butoxy-l-f luoroethyl ) -2-chloro-l, 3-thiazole2- (2-chloro-l, 3-thiazol-4-yl ) -2-f luoroacetic acid2- [5- (carboxymethyl) -2-chloro-l, 3-thiazol-4-yl] -2- fluoroacetic acid2- [ 6-bromo-4- ( carboxymethyl ) -5-f luoropyridin-2- yl] acetic acid2- [2-bromo-6- (carboxymethoxy) -3-f luoropyridin-4- yl] acetic acid2-bromo-6- ( carboxymethylsulfanyl ) pyridine-3-carboxylic acid2-bromo-6- ( carboxymethylsulfanyl ) pyridine-4-carboxylic acid2- [ 2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-3- yl] acetic acid2- [ 2 -bromo- 6- ( carboxymethyl sulfanyl ) pyridin-4- yl] acetic acid2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridine-4- carboxylic acid2- [2-bromo-6- (carboxymethylsulfanyl) -3-f luoropyridin-4-yl] acetic acid2- [2- (carboxymethoxy) -6-chloropyridin-4-yl] acetic acid2- [2- (carboxymethylsulfanyl) -6-chloropyridin-4- yl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) oxypropanoic acid3- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylpropanoic acid2-bromo-6- (nitromethoxy) pyridine2-bromo-6- (nitromethylsulfanyl) pyridine2-bromo-3-f luoro-6- (nitromethyl) pyridine2- (5-chloro-4-oxopyrrol-2-yl) acetic acid4- (5-chloro-4-oxopyrrol-2-yl) butanoic acid4- ( 5-chloro-4-sulfanylidenepyrrol-2-yl ) butanoic acid4- ( 2-chloro-l-oxo-l , 3-thiazol-4-yl ) butanoic acid2-chloro-5- ( 3-nitropropyl ) pyrrol-3-one2-chloro-5- (3-nitropropyl) pyrrole-3-thione2-chloro-4- (3-nitropropyl) -1, 3-thiazolel-oxide2- ( 5-chloro-4-sulfanylidenepyrrol-2-yl ) acetic acid2- (2-chloro-l-oxo-l, 3-thiazol-4-yl ) acetic acid2-chloro-5- (nitromethyl) pyrrol-3-one2-chloro-5- (nitromethyl) pyrrole-3-thione2-chloro-4- (nitromethyl) -1, 3-thiazolel-oxide2,5-dichloro-4-( nitromethyl )-l, 3- thiazole2-chloro-4- (nitromethyl) -1, 3-thiazole2- (2, 5-dichloro-l, 3-thiazol-4-yl ) acetic acid2- ( 4-oxopyrrol-2-yl ) oxyacetic acid5- ( 4 -chlorophenoxy) -1,2, 4-triazol-3-one4-bromo-2- ( 4-chlorophenoxy) -5-f luoropyrimidine2- ( 6-bromopyridin-2-yl) sulfanylacetic acid2- [ (4-chloro-l, 3-thiazol-2-yl ) sulfanyl] acetic acid ethyl 2- [ ( 6-bromo-5-f luoropyridin-2- yl) sulfanyl] acetate ethyl2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetate2- (3, 6-dibromopyridin-2-yl ) sulfanylacetic acid2- [ (S) - (2, 5-dichloro-l, 3-thiazol-4-yl ) sulfinyl] acetic acid2- [ (2, 5-dichloro-l, 3-thiazol-4-yl ) sulfanyl] acetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) sulfanylacetic acid2- ( 6-bromo-5-f luoropyridin-2-yl ) oxyacetic acid4- (5, 6-dibromopyridin-2-yl ) sulfanylbutanoic acid64, The herbicidal composition of any one of claims 39additionally comprising at least one additional plant protection compound.

65. The herbicidal composition of claim 64, wherein the at least one additional plant protection agent is selected from the group consisting of herbicides, amino acid synthesis inhibitor herbicides, fungicides, insecticides and plant growth regulators.

66. The herbicidal composition of claim 65, wherein the amino acid synthesis inhibitor herbicide is selected from the group consisting of sulfonylurea herbicide, imidazolinone herbicide, sulfonamide herbicide and amino acid derivatives, imazamox, imazapic, imazethapyr, imazaquin, imazapyr and imazamethabenz , Chlorimuron, Primisulf uron, Thif ensulfuron,Triasulfuron, Nicosulf uron, Metsulfuron, Tribenuron, Rimsulfuron, glyphosate and Trif lusulf uron or a combination thereof.

67. The herbicidal composition of claim 65, wherein the plant growth regulator is selected from the group consisting of dicamba, 2,4-D, clopyralid, and fluroxypyr, or a combination thereof.

68. The herbicidal composition of any one of claims 39 to 67, further comprising applying a third herbicide or a plant growth regulator.

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