A fertilizer Cu II Process for the preparation of a complex polymer urease inhibitor
By synthesizing the nitrogen-containing tetradentate ligand 5-hydroxy-N1,N3-bis(pyridin-3-yl)isophthalamide and constructing a CuII coordination polymer, the problems of nitrogen fertilizer decomposition and ammonia volatilization were solved, achieving efficient nitrogen fertilizer utilization and low toxicity inhibition.
Patent Information
- Application Number
- CN202310648277.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-02
- Publication Date
- 2026-02-13
- Estimated Expiration
- 2043-06-02
AI Technical Summary
The decomposition of nitrogen fertilizer and ammonia volatilization in existing fertilizers result in low nitrogen fertilizer utilization, and traditional urease inhibitors have problems such as high toxicity and significant environmental impact.
Nitrogen-containing tetradentate ligand 5-hydroxy-N1,N3-bis(pyridin-3-yl)isophthalamide was synthesized using raw materials such as 5-hydroxyisophthalic acid and 3-aminopyridine. CuII coordination polymers were constructed by hydrothermal method to enhance their coordination ability with transition metal ions, forming CuII coordination polymers with a tetragonal pyramidal geometry, which were then applied in fertilizers to inhibit urease activity.
It effectively inhibits the activity of urease in the soil, delays nitrogen fertilizer decomposition and ammonia volatilization, improves nitrogen fertilizer utilization, reduces nitrogen fertilizer loss, and lowers toxicity and environmental impact.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to a preparation method of a fertilizer inhibitor, in particular to a preparation method of a Cu II coordination polymer urease inhibitor suitable for fertilizer. BACKGROUND
[0002] Coordination polymers are inorganic or metal cation-containing metal-organic polymers connected by organic ligands, and are crystalline materials with certain rules. Metal-organic coordination polymers, also known as metal-organic framework structures, have become the focus of scientists in various countries in recent years due to their various special properties. MOFs contain organic ligands and metal ions, so such structures of substances may contain the properties of both metals and organic compounds, and may also contain properties that neither metals nor organic compounds have.
[0003] Compared with metal salts, organic compounds and plant extracts, the composite urease inhibitor has the characteristics of low toxicity, strong inhibition and stability, etc. Among them, the transition metal coordination polymer as a urease inhibitor has attracted widespread attention, and the copper coordination polymer has the best effect. It not only can inhibit the activation process of urease apoprotein, but also can fill in the active pocket of urease well, establish interaction between the active site of urease and the active site of urease, occupy the binding site that should belong to nickel, thereby causing irreversible inhibition of urease activity, and then blocking the path of urea into the active site, so as to achieve the effect of inhibiting urease activity. By adding Cu Ⅱ The coordination polymer produced can alleviate the hydrolysis of nitrogen fertilizer, reduce ammonia volatilization, and improve the utilization rate of nitrogen fertilizer.
[0004] Urease is a nickel-dependent metal enzyme that widely exists in the biological world and can catalyze the hydrolysis of urea into ammonia and carbon dioxide to provide nitrogen source for organisms. Urease has important uses in agriculture and medicine because it can catalyze the production of ammonia. The research content includes urease inhibition, structure-activity relationship, molecular docking, etc. Importantly, among the effective urease inhibitors, most copper metal complexes show stronger urease inhibition, with IC 50 values ranging from 0.46 μM to 41.11 μM.
[0005] Further development and research on its properties can make the copper coordination polymer play an important role in the field of fertilizers. SUMMARY
[0006] The purpose of the present application is to provide a Cu II coordination polymer urease inhibitor suitable for fertilizer. The present application selects 5-hydroxyisophthalic acid, 3-aminopyridine, triphenyl phosphite and pyridine as raw materials, and obtains nitrogen-containing tetradentate ligand 5-hydroxy-N 1 , N 3Bis (pyridine-3-yl) isophthalamide, which has more coordination sites and is easier to coordinate with transition metal ions. A Cu II Coordination polymer is constructed by a hydrothermal method, the polymer has good activity of inhibiting urease bacteria in soil, delaying decomposition of nitrogen fertilizer, ammonia volatilization is blocked by soil layer, soil colloid adsorption of ammonium ion (NH4 + ) produced by urea decomposition is enhanced, so that nitrogen loss can be reduced, nitrogen is retained in soil in the form of ammonium nitrogen which is more easily adsorbed by soil for a long time, and the utilization rate of fertilizer is improved.
[0007] The purpose of the present application is achieved by the following technical solutions:
[0008] A preparation method of a Cu II coordination polymer urease inhibitor suitable for fertilizer, the method comprises the following preparation process:
[0009] The Cu II coordination polymer, the crystal form belongs to a monoclinic system, the space group is P21 / n, the Cu II ion adopts a four-coordinated coordination mode, and is coordinated with two nitrogen atoms in the 5-hydroxy-N 1 , N 3 -bis (pyridine-3-yl) isophthalamide ligand and two carboxyl oxygen atoms in two separate 1,3,5-benzenetricarboxylic acid anions, and exhibits a square pyramid geometry; the Cu II coordination environment of the coordination polymer is shown as (I): The Cu II coordination polymer is prepared by the following steps: taking the ligand 5-hydroxy-N 1 , N 3 -bis (pyridine-3-yl) isophthalamide, 1,3,5-benzenetricarboxylic acid and CuCl2·2H2O, placing them in a tetrafluoroethylene liner, adding deionized water and sodium hydroxide, sealing the reaction kettle, and carrying out a hydrothermal reaction, after the reaction is completed, washing, filtering and drying the product to obtain the target product Cu II coordination polymer.
[0010] The preparation method of the Cu II coordination polymer urease inhibitor suitable for fertilizer, the preparation of the ligand 5-hydroxy-N 1 , N 3 -bis (pyridine-3-yl) isophthalamide comprises the following steps:
[0011] 5-hydroxyisophthalic acid was dissolved in a pyridine solution, and 3-aminopyridine was dissolved in a pyridine solution. The solution was then slowly transferred to a 5-hydroxyisophthalic acid solution. After stirring at room temperature for 30 min, triphenyl phosphite was added dropwise over 15 min, and the mixture was heated under reflux for 10 h. After standing overnight at room temperature, water was added to precipitate the solid. The solid was then filtered, washed with water, and dried in air to obtain a white powdery solid.
[0012] The aforementioned method is suitable for fertilizer Cu II A method for preparing a coordination polymer urease inhibitor, wherein the ligand is 5-hydroxy-N 1 N 3 The synthesis of bis(pyridin-3-yl)isophthalamide is carried out by using 5-hydroxyisophthalic acid and 3-aminopyridine in a molar ratio of 1:1-2.
[0013] The aforementioned method is suitable for fertilizer Cu II A method for preparing coordination polymer urease inhibitors, wherein the hydrothermal reaction is carried out at 120°C for 4 days.
[0014] The aforementioned method is suitable for fertilizer Cu II A method for preparing a coordination polymer urease inhibitor, wherein the ligand is 5-hydroxy-N 1 N 3 The molar ratio of bis(pyridin-3-yl)isophthalamide:copper chloride dihydrate:1,3,5-benzenetricarboxylic acid is 1:1-2:1-2.
[0015] The aforementioned method is suitable for fertilizer Cu II A method for preparing a coordination polymer urease inhibitor, wherein the Cu II Coordination polymers are used as urease inhibitors in fertilizers, specifically nitrogen fertilizers.
[0016] The aforementioned method is suitable for fertilizer Cu II A method for preparing a coordination polymer urease inhibitor, wherein the nitrogen fertilizer is urea.
[0017] The beneficial effects of this invention are:
[0018] 1. This invention uses 5-hydroxyisophthalic acid and 3-aminopyridine as raw materials to obtain the nitrogen-containing ligand 5-hydroxy-N through a one-pot process. 1 N 3 -Bis(pyridin-3-yl)isophthalamide makes it easier for it to coordinate with metal chlorides, increasing the number of coordination sites.
[0019] 2. This invention constructs Cu using a hydrothermal method. II Coordination polymers, Cu IIThe ion occupies the binding site near the active center nickel atom of the urease apoprotein activation process, delays the decomposition of nitrogen fertilizer, ammonia volatilization is blocked by the soil layer, and the adsorption of soil colloid to ammonium ion (NH4 + ) produced by urea decomposition is enhanced, so that the loss of nitrogen fertilizer can be reduced, and nitrogen is retained in the soil in the form of ammonium nitrogen which is more easily adsorbed by the soil for a long time.
[0020] 3. The Cu II coordination polymer provided by the present application has good activity of inhibiting urease bacteria in soil, delays the decomposition of nitrogen fertilizer, ammonia volatilization is blocked by the soil layer, and the adsorption of soil colloid to ammonium ion (NH4 + ) produced by urea decomposition is enhanced, so that the loss of nitrogen fertilizer can be reduced, and nitrogen is retained in the soil in the form of ammonium nitrogen which is more easily adsorbed by the soil for a long time, thereby improving the utilization rate of fertilizer.
[0021] 4. The Cu II coordination polymer provided by the present application has low dosage, high inhibition rate, long half-life, small toxicity, and small environmental impact. BRIEF DESCRIPTION OF DRAWINGS
[0022] Figure 1 is a Cu II coordination polymer coordination environment diagram;
[0023] Figure 2 is a Cu II coordination polymer X-ray diffraction pattern and simulation data diagram;
[0024] Figure 3 is a Cu II coordination polymer half-inhibitory concentration. EMBODIMENT
[0025] 1. The preparation method of the ligand 5-hydroxy-N 1 , N 3 -bis (pyridine-3-yl) isophthalic acid diamide is as follows:
[0026]
[0027] 5-hydroxy isophthalic acid (0.05 mol) is dissolved in 20 mL of pyridine solution, 3-aminopyridine (0.1 mol) is dissolved in 35 mL of pyridine solution, and then slowly transferred to the 5-hydroxy isophthalic acid solution. After stirring at room temperature for 30 min, triphenyl phosphite (15.5 g, 0.05 mol) is added dropwise within 15 min, and heated to reflux at 120℃ for 10 h. After standing at room temperature overnight, add water to precipitate the solid, suction filter, wash with water, and dry in air to obtain a white powder solid.
[0028] 2. The Cu ⅡCoordination polymer preparation method
[0029] Weigh out the ligand 5-hydroxy-N 1 N 3 0.033 g (0.1 mmol) of bis(pyridin-3-yl)-isophthalamide, 0.032 g (0.15 mmol) of 1,3,5-benzenetricarboxylic acid, and 0.034 g (0.2 mmol) of CuCl2·2H2O were placed in a tetrafluoroethylene liner, 8 ml of deionized water was added, followed by 0.016 g of NaOH solution. The reaction vessel was then sealed and placed at 120 °C. o The crystals were calcined in a drying oven for 4 days, and then the blocky crystals were washed, filtered and dried to obtain blue crystals.
[0030] (ii) Characterization
[0031] Diffraction intensity data of the single crystal were collected using graphite monochromatic Mo Kα (λ = 0.71073 Å) radiation as the diffraction source on a Bruker D8-ray diffractometer. Combined with Cu... II SC-XRD data of coordination polymers were obtained, further yielding Cu II The structural diagram of the coordination polymer is shown below. Figure 1 As shown. Figure 1 The exhibit is metallic Cu II Coordination environment of ions. Cu II The ions adopt a four-coordinate mode, each coordinating with one of the two 5-hydroxy-N groups. 1 N 3 The two nitrogen atoms in the bis(pyridin-3-yl)isophthalamide ligand are coordinated from the two carboxyl oxygen atoms of two separate 1,3,5-phenyltricarboxylic acid anions (Cu–N=2.055(4)–2.068(4)Å, Cu–O=1.938(3)–1.953(3)Å) (see Table 1 for the main bond lengths and bond angles).
[0032] Table 1. Crystallographic data of coordination polymers
[0033] Empirical formula C 30 H 30 CuN4O7]]> Formula weight 622.13 Temperature / K 296.0 Crystal system Monoclinic Space group C2 / c a / Å 21.2585(17) b / Å 5.5487(4) c / Å 25.050(2) α / ° 90 β / ° 101.173(3) γ / ° 90 Volume / Å 3 ]]> 2898.8(19) Z 4 ρcalc g / cm3 3 ]] 1.426 μ / mm1 0.807 F(000) 1292.0 [R int ]] 0.0492(2520) s 1.024 Rf / wRf 0.0492 / 0.1086 All data Rf / wRf 0.0928 / 0.1245
[0034] Powder diffraction experiments were performed on the crystal using a Bruker D8 Advance X-ray powder diffractometer. Graphite monochromatized Cu Kα radiation was used at a wavelength λ = 1.54056 Å, with a solid-state detector, a step size of 0.01°, a step time of 0.3 sec, and a scan range of 5° ≤ 2θ ≤ 45°. The prepared Cu... II X-ray diffraction patterns and simulation data of coordination polymers are shown below. Figure 2As shown, the sharp diffraction peaks in both crystals indicate that they have good crystal quality. In addition, the powder X-ray diffraction pattern is the same as the characteristic peak position and intensity of the corresponding single crystal structure simulation, confirming that the powder sample and the crystal are the same crystal phase.
[0035] Example 1 A Cu Ⅱ Coordination polymer and preparation thereof
[0036] 5-hydroxy-N 1 , N 3 -bis (pyridine-3-yl) isophthalamide 0.033 g (0.1 mmol), 1.3.5-benzenetricarboxylic acid 0.032 g (0.15 mmol), CuCl2·2H2O 0.034 g (0.2 mmol) were placed in a tetrafluoroethylene liner, the reaction kettle was sealed, and calcination was carried out in a 120°C oven for 4 days to obtain blue block crystals, which were then washed, filtered, and dried to obtain a copper coordination polymer, with a yield of about 45%.
[0037] Example 2 A Cu Ⅱ Coordination polymer and preparation thereof
[0038] 5-hydroxy-N 1 , N 3 -bis (pyridine-3-yl) isophthalamide 0.033 g (0.1 mmol), 1.3.5-benzenetricarboxylic acid 0.064 g (0.3 mmol), CuCl2·2H2O 0.068 g (0.4 mmol) were placed in a tetrafluoroethylene liner, the reaction kettle was sealed, and calcination was carried out in a 120°C oven for 4 days to obtain blue block crystals, which were then washed, filtered, and dried to obtain a copper coordination polymer, with a yield of about 40%.
[0039] Example 3 A Cu Ⅱ Coordination polymer and preparation thereof
[0040] 5-hydroxy-N 1 , N 3 -bis (pyridine-3-yl) isophthalamide 0.033 g (0.1 mmol), 1.3.5-benzenetricarboxylic acid 0.064 g (0.3 mmol), CuCl2·2H2O 0.034 g (0.2 mmol) were placed in a tetrafluoroethylene liner, the reaction kettle was sealed, and calcination was carried out in a 120°C oven for 4 days to obtain blue block crystals, which were then washed, filtered, and dried to obtain a Cu Ⅱ Coordination polymer, with a yield of about 38%.
[0041] Example 4 A Cu Ⅱ Coordination polymer and preparation thereof
[0042] 5-hydroxy-N 1 N 3 0.033 g (0.1 mmol) of bis(pyridin-3-yl)-isophthalamide, 0.032 g (0.15 mmol) of 1,3,5-benzenetricarboxylic acid, and 0.068 g (0.4 mmol) of CuCl2·2H2O were placed in a tetrafluoroethylene liner, the reaction vessel was sealed, and calcined at 120 °C for 4 days to obtain blue blocky crystals. The blocky crystals were then washed, filtered, and dried to obtain CuCl2·2H2O. Ⅱ Coordination polymer, yield approximately 32%.
[0043] Determination of urease inhibitory activity: Urease was purchased from Shanghai Maclean Biochemical Technology Co., Ltd. 1 mL (10 KU / L) of urease and 1 mL of Cu with different concentrations were used. II After the coordination polymer sample (dissolved in DMSO:H2O = 1:1) was thoroughly mixed, it was pre-incubated in a 37°C constant temperature shaking incubator for 1 hour. Then, 8 mL of phosphate buffer (pH 6.8, containing 500 mM urea and 0.002% phenol red indicator) was added. The absorbance was measured at 570 nm using a UV spectrometer at 1-hour intervals. The endpoint of the test was determined by the phenol red indicator; the test was stopped when the solution changed from light yellow to red.
[0044] IC 50 Calculation: The absorbance was determined by the phenol red method and the IC was calculated. 50 To obtain Cu II Coordination polymers were used as a measure of urease inhibition using a modified Kohl's method.
[0045] lgIC 50 =Xm-I(P-(3-Pm-Pn) / 4),
[0046] Where, Xm: lg maximum dose;
[0047] I: lg(maximum dose / adjacent dose);
[0048] P: The sum of positive reaction rates;
[0049] Pm: Maximum positive reaction rate;
[0050] Pn: Minimum positive reaction rate;
[0051] The results are as follows Figure 3 IC was calculated 50 =1.60±0.01μM, while the IC50 of organic compounds is... 50 At 0.62 μM < IC 50 The IC50 values for some organic compounds are between 42.74 μM and 42.74 μM. 50 The values are shown in Table 2.
[0052] Table 2 Comparison of half-inhibitory concentration of different kinds of inhibitors
[0053] Inhibitor type Half maximal inhibitory concentration IC 50 Values (μM) Benzimidazole derivative 22±6.2-99±0.4 Thiourea derivative 11.73±0.28-212.24±0.42 Thiadiazole derivative 3.4±0.01-33.20±1.20 Bisphosphonate derivative 1.91±0.03-3.4±0.03 Cu II coordination polymer 1.6±0.01
[0054] From the comparison of Table 2, when Cu II The coordination polymer has a lower half-inhibitory concentration as a urease inhibitor, and the amount of the additive is small. Therefore, it can be concluded that the Cu II The coordination polymer can be used as a urease inhibitor in the fertilizer urea.
Claims
1. A fertilizer Cu II A process for the preparation of a complex polymer urease inhibitor characterized in that, The method is: (1) The preparation method of ligand 5-hydroxy-N1, N3-bis (pyridine-3-yl) phthalic acid diamide is as follows: ； Dissolve 0.05 mol of 5-hydroxy phthalic acid in 20 mL of pyridine solution, dissolve 0.1 mol of 3-aminopyridine in 35 mL of pyridine solution, then slowly transfer to the 5-hydroxy phthalic acid solution, stir at room temperature for 30 min, then add 15.5 g, 0.05 mol of triphenyl phosphite dropwise within 15 min, heat to reflux at 120°C for 10 h; After standing at room temperature overnight, add water to precipitate the solid, filter, wash with water, and dry in air to obtain white powder solid; (2) Cu II Process for the preparation of coordination polymers Take 0.1 mmol of ligand 5-hydroxy-N1, N3-bis (pyridine-3-yl) phthalic acid diamide 0.033 g, 0.15 mmol of 1, 3, 5-benzene tricarboxylic acid 0.032 g, 0.2 mmol of CuCl2·2H2O 0.034 g, place in a tetrafluoroethylene liner, add 8 ml of deionized water, then add 0.016 g of NaOH solution, seal the reaction kettle, and place it in a 120°C drying oven for calcination for 4 d, then wash, filter and dry the blocky crystal to obtain blue crystal.