WO2016075685A1

WO2016075685A1 - Multi - ligand preparations containing one or more metal species

Info

Publication number: WO2016075685A1
Application number: PCT/IL2015/051083
Authority: WO
Inventors: Yoram Tsivion
Original assignee: Future Tense Technological Development & Entrepreneurship Ltd
Priority date: 2014-11-12
Filing date: 2015-11-10
Publication date: 2016-05-19
Also published as: EP3218328A1; EP3218328A4

Abstract

A mixture of more than one type of ligand and one or more species of di -or tri -valent metal ion. None of the ligands is an hexadentate ligand. At least two of the species of di or tri-valent metal ion species is capable of forming chelates. The use of the mixture is at least in introducing metals to biological systems.

Description

MULTI - LIGAND PREPARATIONS CONTAINING ONE OR MORE METAL

SPECIES

BACKGROUND OF THE INVENTION

Micronutrients are dispensed as fertilizers in the context of agriculture usually as ions of metals, being oftentimes chelated. A very common ligand used in the preparation of micronutrient fertilizers is EDTA. This ligand belongs to a family of complexing agents (or ligands) derived from ethylene diamine. Thus, HEDTA, DTPA, EDDHA, HEEDTA and some others derived from ethylene diamine which are typically capable of forming hexadentate coordination bonds with the metal ion, such as iron ion. The significance of this fact will be discussed to some extent below. Other examples of ligands commonly exploited in agriculture are free amino acids used for the formation of bi-dentate chelates with ions (e.g. Ni, Cu, Zn, Fe), such combinations are typically provided as micronutrients feed supplement in the field of animal husbandry.

Some other biological uses for chelated micronutrients are known in the art of waste water treatment, in which feed preparations for microbial colonies are supplied. Some micronutrients are used as agricultural pest control components. Copper ions are traditionally used in various combinations with other chemical components for preparing older and more recently developed fungicides and bactericides. Copper is used also in chelated form as a pesticide, a specific case is copper chelated by 8-hydroxyquinolate.

It is often assumed that the activity of copper on microflora in the agricultural pest control scenario, is that the microflora while taking up the micronutrient additives provided to them in their location on or within the host plant tissues, are more susceptible to the effect of the metals, whereas the host plants are considerably less susceptible to the effect of the micronutrient.

Mixed ligand chelates are known in the agricultural market, for example a company named catalytic innovations of 11601 Twitty Drive, Rolla, MO 65401 USA advertizes a product called Zinc-Citric-EDTA solution 10% Zinc. The advertisement However does not state how many moles of EDTA there are per mole of zinc and how many moles are there of citric acid per mole of zinc or EDTA. Moreover, since EDTA is hexadentate (has six coordination groups) and since EDTA has a much higher affinity for zinc than citric acid, if supplied in ample quantity, it may well be that the citric acid is indeed rendered inactive as a chelating ligand in such a mixture. Or, it may be that the citric acid is active as a chelant only in a negligible amount. Therefore the addition of EDTA as such may present an "exclusion factor", barring other ligands from expressing themselves as complexing agents. Similarly, Northwest Agricultural Products, Inc of POBox 3453 PASCO, WA 99302, USA advertize a 10% zinc chelate, in which the zinc is chelated with "EDTA and citric acid" which again raises the same questions as above and again it would seem that the producer may not be aware of a potential exclusion factor discussed above, at most some of the zinc ions in such cases are chelated by one ligand and the other ion are chelated by the other ligand. No explanation is given as to the actual mixture and no excuse as to its possible advantage over single ligand systems. It is to be stressed that if the relative amounts of the ligands provided in the mixture, are not specified, little can be said about the definition of the chelate formed.

"Iron complexation studies of gallic acid", published in J. Chem. Eng. Data 2009, 54, 35-42 discusses the difference between binary and ternary chelation systems. The binary system forms when the ferric ion is chelated by one gallic acid molecule. A ternary system forms when further the ferric iron gallic acid complex combines an additional type of ligand, an amino acid in this case. Ferric ion complexed by those two ligand types at once has four coordination occupied and therefore two are vacancies (as iron has a coordination number six ). If EDTA had been used in a multi-type ligand combination, the total binding of all six coordinates would have been favoured as the affinity of ferric iron with EDTA is extremely high.

In the above mentioned paper published on the Web on the 26th of November 2008, Fazary et al. demonstrated that Fe⁺³ has an increased stability as a ternary complex, as compared to the binary system (Fazary et al., J. Chem. Eng. Data 2009, 54, 35 - 42). More specifically Fe⁺³ complex with gallic acid is of lesser stability than the Fe⁺³ complexed with gallic acid and glycine together. This stands in some contrast to the results provided by Mapari and Mangaonkar in E-Journal of Chemistry 2011 , 8(2), 859 - 862, showing that ternary ligand system (metal ion complexed with two different types of ligands) is not more stable than the binary complex in which the metal ion is complexed with only one ligand.

DESCRIPTION OF THE PRESENT INVENTION

In accordance with the present invention, di and or tri-valent metal ions, typically but not exclusively heavy metals, such that are used in agriculture typically as fertilizers aimed at feeding crops and animals, and or as pesticides, are provided in a multi-ligand combination as will be described below in more detail. The invention provides a method in which the ions which are destined to be supplied typically, though not necessarily exclusively to the biological system, are combined with quantities of ligand molecules such that some ions may be chelated by different types of ligands or by a combination of ligands simultaneously. The use of EDTA or other such high affinity ligands also having six coordination sites is not favored, or, if used, only in a stoichiometric ratio smaller than 1 , relative to the other available one or more metal ions. A supply of an excess of high affinity, hexadentate ligand, may preclude binding by other ligands existing in the mix. A solution containing Zn⁺² ions, Cu⁺² ions and three types of ligands is a combination in which the present invention is exemplified. In this example, the ligands citric acid, glycolic acid and glycine (the simplest amino acid) co inhabit a container otherwise filled with water in which the above mentioned metals are introduced as soluble salts. Any alpha amino acid can be used as a ligand, and some compounds made of a number of amino acids can be used, such as the dipeptide carnosine. There are of course numerous other molecules, natural or synthetic that can be used as chelating agents for the purpose as described hereinabove. In a somewhat different scenario, metal salts, mixed with the prescribed ligands can be prepared dry. Once the mixture is combined with water, or another solvent, chelates may form and survive for various time periods, as promoted by the physical and chemical conditions existing in the immediate environment of the mixture components. Blockage of coordinates and the "exclusion factor"

The coexistence of several types of ligands in a solution with a potential for binding (via coordination bonding) one or more metal ions, does not necessarily facilitate the production of a wide variety of coordination complexes of mixed chelates. Thus, if a metal ion having six coordination number 6 such as Cu⁺², all occupied by a single ligand (e.g. EDTA) with which its affinity is high (in other words having a high stability constant) the probability of any of other ligands existing in the solution of binding with the metal ion, is low, or very low. In the present example (example 1) if citric acid which is a three dentate ligand occupies three coordinates of the Cu⁺² ion, there is still room for other ligand, tridentate or bi-dentate or mono-dentate, to wholly or partially occupy the set of six coordinate bonds available (or four coordination bonds in the case of zinc).

The formation of binary system chelate, ternary systems etc. The stoichiometric relations between the ligand types available for binding through coordination bonds, the coordination number of associated with the ion/s, and the affinity of the respective ligands to the respective ions, and possible interaction between the ligands, dictate the nature and variability of complexed ion in a given solution, in a scenario proposed as an embodiment of the present invention. It may also envisaged that on the one hand one ionic species may be complexed by several ligands while some ions of the other ionic species may be non complexed.

From the strict point of view of effect of the ligands in both binary (Metal ion - Ligandl) and ternary systems (Metal ion - Ligand 1- Ligand 2) on the stability constants of each of the ligands with the central metal is not easy to predict, and empirical studies have been performed, disclosed and discussed (e.g. "Stability Constants of Mixed Ligand Complexes of Transition Metal(ll) ions with N-(2-hydroxybenzylidene)-2,3-dimethylaniline as Primary Ligand and N-(2-hydroxy-1-naphthylidene)- 4-nitroaniline as Secondary Ligand" in E- Journal of Chemistry 2011 , 8(2). 859 - 862. It may be easiest to determine empirically which are the best combinations to account for the best effect, typically biologically oriented, of the metal ions with respect to the plurality of ligand types that should be available for binding. Further, in accordance with some embodiments of the present invention, the system presented is not only multi - ligand bearing but may also be such as multiplicity of metal species.

In accordance with the present invention, monodentate ligands may also be used. Ligands such as CO, cyanic acid, thiocyanic acid as well as other structures Example demonstrating ferric ion chelate formed with two ligands

The phenol derivative, 2-hydroxy - 5 - sulfophenyl acetic acid (formula 1 - hereinafter HSP) was useful as a ligand for iron, typically in equi- molar quantity with Fe⁺³,

Formula 1

HSP can be produced by subjecting 4- phenol sulfonic acid, (synonym p-hydroxybenzene sulfonic acid) to the presence of glyoxilic acid, which under the existing low pH, and preferably warming, binds to the phenol ring (electrophilic substitution on the ring). Another optional protocol, starts with phenol, which is sulfonated first when mixed with sulfuric acid, with heating or without heating. After sulfonation takes place, water is added and then glyoxilic acid introduced to bind to the phenol ring. The benzene derivative 1 ,2 dihydroxybenzene (pyrocatechol) was sulfonated by mixing in three times the weight of sulfuric acid, at about 80°C for 1 hour.

The resultant molecule, is depicted in formula 2. It is referred to hereinafter as SPC. The commercial product Tiron (CAS number 270573-71-2, is very similar to SPC of this invention, the difference being in the two sulfones attached to the ring, whereas in the procedure described hereinabove only one sulfone is probably attached to the ring, because the sulfonation is performed under comparatively mild conditions. However, one cannot rule out the possibility that some portion of the product molecules is doubly sulfonated.

The ternary chelate system

Mixing the two ligand species (HSP + SPC) described above with tri - valent iron in aqueous medium produces a very stable iron chelate, see formula 3. This Fe chelate was proven to be very useful for introducing iron to plants growing in calcareous soil.

Formula 3 The advantages of sulfonating the two ligands seems to be at least in the extra stability it gives to both molecules, and ease of handling.

Example demonstrating the chelation of zinc in a ternary system

A stable solution of chelated zinc in relatively high concentration is disclosed. To make a total of 100 grans product, 38.75 grams of water are poured to a receptacle, KOH (technical grade) 19.76 grams are added and mixed. Zinc oxide, 9.68 grams are added to the mixture while mixing, and then 26.18 grams of citric acid monohydrate, 5.63 grams of lactic acid (88% in water) are added. The entitre nixture is continuously mixed until it becomes clear - somewhat opaque. Such a solution is stable over a long period of time.

Claims

1. A mixture of at least two types of ligands and one or more species of di or tri valent metal ion, said mixture comprising:

• at least two types of ligands none of which is an hexadentate ligand;

• at least one species of di or tri-valent metal ion species each capable of forming chelates, and

• wherein said mixture is utilized for delivering of said metals in agriculture

2. A mixture as in claim 1 wherein at least one of said at least two types of ligands is lactic acid.

3. A mixture as in claim 1 wherein said mixture is utilized for delivering of said metals to biological systems.

4. A mixture as in claim 1 wherein said mixture is utilized for delivering said metals as nutrients in agriculture.

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5. A mixture as in claim 1 wherein said mixture is utilized for delivering said metals as pesticides in agriculture.