Lanthanum complex and synthesis method thereof

Abstract

4-methyl-1, 2, 3-thiadiazole-5-formic acid (HT) is used as a ligand and reacts with lanthanum nitrate hexahydrate to synthesize the thiadiazole lanthanum complex [LaT3. (H2O) 2] n, the structure of the complex is characterized through single crystal-X-ray diffraction, infrared spectroscopy, elemental analysis, ultraviolet spectroscopy and thermogravimetric analysis, the fluorescence performance of the complex is measured, and the thiadiazole lanthanum complex is obtained. The interaction of the lanthanum complex with calf thymus DNA (CT-DNA) and human serum albumin (HSA) is researched through ultraviolet and fluorescence spectra. The coordination compound belongs to a triclinic crystal and a Pi space group. Research on the biological activity of the lanthanum complex shows that the lanthanum complex shows good biological activity, and can be beneficial to development of novel antibacterial drugs, help to promote research and development of anti-cancer drugs and enrich the content of medicinal chemistry and pharmacology. Different types of compounds are combined or have a synergistic effect, so that a novel medicine with unique performance and advantages is developed.

Description

Technical Field

[0001] This invention relates to the field of chemistry, specifically to a lanthanum complex and its preparation method. Background Technology

[0002] Rare earth elements, due to their unique structures, readily coordinate with other compounds in diverse ways, leading to the significant applications of rare earth coordination complexes in fields such as bioactivity, magnetism, fluorescence, and catalysis. Lanthanum, as a rare earth element, has seen varying degrees of development in industry, optics, biomedicine, and agriculture, with lanthanum complexes showing immense potential in biomedicine and photocatalysis. Lanthanum complexes possess certain biological activities and can be used in areas such as anticancer, immune regulation, and bone repair. In anticancer applications, lanthanum complexes can inhibit tumor cell growth through interaction with DNA. For example, some lanthanum complexes can inhibit the proliferation of tumor cells such as prostate cancer, gastric cancer, and breast cancer by inducing apoptosis. Therefore, studying the interaction mechanisms between complexes and DNA provides new research directions for anticancer studies.

[0003] Thiadiazole derivatives, due to their unique chemical structures, exhibit good lipid solubility and readily cross cell membranes, thus demonstrating excellent biological activity. This activity is primarily manifested in antibacterial, anticancer, antiviral, antitumor, anti-inflammatory, and antioxidant properties. Regarding antibacterial activity, they exhibit varying degrees of inhibition against live bacteria. In antitumor activity, they demonstrate varying degrees of inhibitory effects; different thiadiazole derivatives have shown good inhibitory activity against pancreatic cancer cells, leukemia cells, and human liver cancer cells. The diverse biological activities of thiadiazoles make them of significant value in drug development and biomedical research. Summary of the Invention

[0004] This invention addresses the shortcomings of existing technologies by providing a lanthanum complex and its preparation method.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A lanthanum complex, wherein the chemical formula is [LaT3·(H2O)2]. n HT = 4-methyl-1,2,3-thiadiazole-5-carboxylic acid; The crystallographic data of the lanthanum complexes are shown in Table 1; Table 2 shows some of the bond lengths and bond angles in the single crystal structure of the lanthanum complex.

[0006] The smallest asymmetric unit of the lanthanum complex consists of a metal ion La(III) coordinated with three 4-methyl-1,2,3-thiadiazole-5-carboxylate ions and two water molecules.

[0007] The lanthanum complex is composed of La 3+It coordinates with six 4-methyl-1,2,3-thiadiazole-5-carboxylate ions and two water molecules to form a nine-coordinate aberration tri-capped trigonal prism configuration, which forms a one-dimensional chain through carboxyl oxygen bridging. The one-dimensional chain is stacked into a three-dimensional structure through NH and SH hydrogen bonds and π-π stacking of the thiadiazole ring.

[0008] A method for synthesizing the lanthanum complex as described in claim 1, comprising the following steps: (1) Weigh the reactant raw materials according to the molar ratio of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to La(NO3)3·6H2O of 2.8~3.2; (2) Measure ethanol according to the ratio of the amount of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to the volume of ethanol = 1 mmol : 6.66 mL. The alcohol and water were measured according to the ratio of the amount of La(NO3)3·6H2O to the volume of alcohol and water = 1 mmol : 20 mL, with an alcohol-to-water ratio of 4:1. (3) Place the 4-methyl-1,2,3-thiadiazole-5-carboxylic acid weighed in step (1) into a reaction vessel, add the ethanol measured in step (2) as a solvent into the reaction vessel, and stir at room temperature until completely dissolved. (4) Place the La(NO3)3·6H2O weighed in step (1) into a beaker, add the alcohol-water measured in step 2 into the beaker, and stir until the La(NO3)3·6H2O is completely dissolved. (5) Add the solution obtained in step (4) to the solution obtained in step (3) and stir until fully mixed; (6) Adjust the pH of the system to 7 and stir until well mixed; (7) Place the reactor in an oven and maintain the reaction temperature at 80 °C for 72 h; (8) Remove the product and allow it to cool naturally. Open the reactor and filter the product to obtain white blocky crystals, which are the lanthanum complex.

[0009] The method for synthesizing the lanthanum complex includes the following steps: (S1) Weigh 0.75 mmol of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid into the inner liner of the reaction vessel, add 5 mL of ethanol using a graduated cylinder, add a stir bar, and stir with a magnetic stirrer at room temperature until completely dissolved. (S2) Weigh 0.25 mmol La(NO3)3·6H2O into a beaker, add 5 mL of alcohol-water mixture with a ratio of 4:1 using a graduated cylinder, and stir with a glass to dissolve La(NO3)3·6H2O. (S3) Mix the solution obtained in step (1) with the solution obtained in step (2) and stir until fully mixed; (S4) Adjust the pH of the system to 7 and stir until well mixed; (S5) Place the reactor in an oven and maintain the reaction temperature at 80 °C for 72 h; (S6) Remove and allow to cool naturally, open the reactor and filter to obtain white blocky crystals, which are the lanthanum complex.

[0010] Compared with the prior art, the present invention has the following beneficial effects: The lanthanum 4-methyl-1,2,3-thiadiazole-5-carboxylic acid complex [LaT3·(H2O)2] was successfully constructed using a solvothermal method. n The lanthanum complex, HT = 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, was characterized in detail and its single-crystal structure was obtained. The interaction between the lanthanum complex and CT-DNA and HSA was also investigated, leading to the following conclusions: (1) Reaction of lanthanum complexes with CT-DNA: binding constant in ultraviolet light. K b =8.65×10 2 L∙mol -1 Electrostatic effects are the primary mechanism; fluorescence quenching is a static mechanism. K sv =4.75×10 4 L / mol, K q 4.75×10 12 L·mol -1 ·s -1 ), K a =2.45×10 5 L·mol -1 , n =1.18.

[0011] (2) Interaction between lanthanum complexes and HSA: UV-visible interaction, fluorescence static quenching K sv =9.83×10 4 L·mol -1 , K q =9.83×10¹² L·mol -1 ·s -1 . K a =67.61 L·mol -1 , n =0.39.

[0012] (3) Studies on the bioactivity of the lanthanum complex revealed that it exhibits good bioactivity, which can help develop novel antibacterial drugs, promote the research and development of anticancer drugs, and enrich the content of medicinal chemistry and pharmacology. By combining or synergistically utilizing different types of compounds, novel drugs with unique properties and advantages can be developed. Attached Figure Description

[0013] Figure 1 This is the synthetic route for lanthanum complexes.

[0014] Figure 2 This is a diagram of the smallest asymmetric unit cell of a lanthanum complex.

[0015] Figure 3 This is a coordination polyhedron diagram of the central ion in a lanthanum complex.

[0016] Figure 4 This is a one-dimensional chain diagram of a lanthanum complex.

[0017] Figure 5 This is a three-dimensional packing diagram of lanthanum complexes.

[0018] Figure 6 The image shows the infrared spectrum of the lanthanum complex.

[0019] Figure 7 Comparison of infrared spectra of lanthanum complex, ligand HT, and lanthanum nitrate.

[0020] Figure 8 Hirshfeld surface force diagram for lanthanum complexes.

[0021] Figure 9 Hirshfeld surface interaction fingerprint of lanthanum complexes.

[0022] Figure 10 The UV-Vis spectrum of the lanthanum complex and CT-DNA is shown.

[0023] Figure 11 The fluorescence spectrum of the lanthanum complex with EB-CT-DNA system is shown.

[0024] Figure 12 This represents the concentration ratio of the lanthanum complex to DNA.

[0025] Figure 13 This is a diagram showing the binding constant of lanthanum complexes to DNA.

[0026] Figure 14 The UV-Vis spectra are for lanthanum complexes and HSA.

[0027] Figure 15 The fluorescence spectrum is the result of the interaction between the lanthanum complex and HSA.

[0028] Figure 16 The concentration ratio of lanthanum complex to HSA is given.

[0029] Figure 17 The diagram shows the binding constants of lanthanum complexes with HSA. Detailed Implementation

[0030] The technical solution of the present invention will be further illustrated below through embodiments.

[0031] Example 1: Lanthanum Complex [LaT3·(H2O)2] n Synthesis method A method for synthesizing a lanthanum complex [LaT3·(H2O)2], the synthetic route is as follows: Figure 1 As shown, the specific steps are as follows: (1) Weigh 0.75 mmol (0.1074 g) of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid (HT) into the inner liner of the reaction vessel using an analytical balance, add 5 mL of ethanol to it using a graduated cylinder, add a stir bar, and stir at room temperature for about 20 min until completely dissolved using a magnetic stirrer.

[0032] (2) Weigh 0.25 mmol (0.1181 g) of La(NO3)3·6H2O into a beaker, add 5 mL of alcohol-water mixture (4:1) using a graduated cylinder, and stir with a glass to dissolve La(NO3)3·6H2O. (3) Mix the solution obtained in step (1) with the solution obtained in step (2) and stir for 20 min to mix thoroughly.

[0033] (4) Adjust the pH of the system to 7 with 1 mol / L NaOH solution and continue stirring for 30 min to ensure uniform mixing.

[0034] (5) Place the reactor in an oven and keep it at 80 °C for 72 h.

[0035] (6) Remove the reactor and allow it to cool naturally for 12 hours. Then, open the reactor and filter the mixture to obtain white blocky crystals. Since the crystals are insoluble in ethanol, rinse them with ethanol. After that, allow them to air dry naturally and store them in a sealed container.

[0036] Example 2: Crystal Structure Determination and Analysis 2.1 Elemental Analysis The elemental analysis results of the lanthanum complex are as follows: Theoretical values: C, 23.92%; H, 1.84%; N, 14.00%; Test values: C, 23.90%; H, 1.88%; N, 14.04%.

[0037] 2.2 Crystal Structure Determination A crystal measuring 0.15 mm × 0.13 mm × 0.10 mm was selected and placed on a Smart Apex II CCD X-ray surface probe diffractometer. The diffraction source was a graphite monochromatic MoKα (λ = 0.71073 Å). At a temperature of 100.0 (1) K, the data collection angle range was 4.056° < 2θ < 52.74°, and a total of 19931 diffraction points were collected, of which 4147 were independent diffraction points. The structural analysis was performed using Olex2 software, and some results are shown in Tables 1 and 2.

[0038] 2.3 Crystal Structure Analysis Depend on Figure 2 It is known that the lanthanum complex [LaT3·(H2O)2] n The smallest asymmetric unit consists of a La(III) ion coordinated with three 4-methyl-1,2,3-thiadiazole-5-carboxylate ions and two water molecules.

[0039] Depend on Figure 3 As shown, the lanthanum complex is formed by La³⁺ coordinating with six 4-methyl-1,2,3-thiadiazole-5-carboxylate ions and two water molecules to form a nine-coordination distorted tricapsular trigonal prism configuration. A one-dimensional chain is formed through carboxyl oxygen bridging. The one-dimensional chain is stacked in a three-dimensional shape through NH and SH hydrogen bonds and π-π stacking of the thiadiazole ring. Hirshfeld analysis shows that HH is the dominant factor.

[0040] Table 1 Crystallographic parameters of lanthanum thiadiazole complexes

[0041] Table 2 Bond lengths (Å) and bond angles (°) of lanthanum thiadiazole complexes

[0042] Symmetry codes: (i) - x , - y , - z (ii) - x +1, - y , - z .

[0043] Example 3 Infrared Spectroscopy Measurement and Analysis To minimize the impact of impurities on infrared measurements, potassium bromide was first baked in an oven at 80°C for 12 hours. An appropriate amount of lanthanum complex was then mixed with potassium bromide at a 1:100 ratio and ground until homogeneous, followed by tableting. The desired tablets were of uniform thickness, free of cracks, and completely transparent. Measurements were then taken at room temperature using wavelengths of 0-4000 cm⁻¹. -1 The infrared spectra of the lanthanum complex, ligand HT, and lanthanum nitrate were determined using a Fourier transform infrared spectrometer, and the results are as follows: Figure 6 and Figure 7 As shown.

[0044] The infrared spectrum of the lanthanum complex shows a value of 3400-3500 cm⁻¹. -1 The broad absorption band is attributed to the stretching vibration of the OH group within the water molecule, bound at 796 cm⁻¹. -1 The nearby absorption peaks indicate the presence of water molecules involved in coordination within the complex. The characteristic peak of the carboxyl group of the free ligand (1708 cm⁻¹) is also present. -1 The group disappears after forming a complex, and in turn, an asymmetric carboxyl group (V) appears. as (-COO - ), 1599cm -1 1633 cm -1 ) and symmetrical stretching vibration peak (V s (-COO - ), 1398 cm -1 1365 cm -1 This indicates that the carboxylate group coordinates with the metal in two ways: bidentate chelation and bidentate bridging. (608 cm⁻¹) -1 The stretching vibration peak at the point is attributed to the La-O bond vibration, further proving that the lanthanum complex and HT are different substances, which is consistent with the conclusion of the crystal structure analysis.

[0045] Example 4: Hirshfeld Surface Analysis The Hirshfeld surface analysis program was performed using CrystalExplorer 3.1 software, with the CIF file containing the crystal parameters of the lanthanum complex as the data source (results are shown below). Figure 8 As shown in the figure, dnorm (density function) values ​​in the range of -1.278 to 1.630 nm were obtained. This function indicates strong intermolecular interactions. The shape index ranges from -1.000 to 1.000 nm, representing the sensitive forces generated between molecules due to small distances. The curvature map ranges from -4.000 to 0.400 nm and can be used to describe the surface smoothness due to intermolecular forces.

[0046] Analysis of intermolecular forces within the crystal using 2D fingerprinting ( Figure 9 The results showed that there were significant differences in the proportion of different intermolecular forces. Among them, the HH interaction accounted for the largest proportion in the complex molecule, reaching 30.1%, reflecting the dominance of hydrogen atom interaction; CH interaction accounted for 24.1%, NH interaction accounted for 17.6%, OH interaction accounted for 16.1%, while SH interaction accounted for the lowest proportion, only 10.2%. The above data clearly reveal the compositional characteristics of intermolecular forces within the crystal and the differences in the contribution of each component.

[0047] Example 5: Interaction between lanthanum complexes and calf thymus DNA (CT-DNA) 5.1 Solution Preparation Tris-HCl / NaCl buffer solution: Weigh 5 × 10 -3 mol (0.6060 g) of Tris and 5 × 10 -2 Weigh out 2.9110 mol (2.9110 g) of NaCl and place it in a beaker. Use distilled water as a solvent and stir until Tris and NaCl are completely dissolved. Transfer the solution to a 1.0 L volumetric flask, add distilled water to the mark to make up to volume, and then adjust the pH value to 7.43 (7.2-7.5) with dilute HCl.

[0048] CT-DNA solution: Take a small piece of CT-DNA and place it in Tris-HCl / NaCl buffer solution. Sonicate for half an hour to dissolve the protein in the solution. Using the prepared buffer solution as the system background, measure the UV light of the sonicated solution and calculate A. 260 / A 280 The solution can be used in experiments if the ratio is greater than 1.8 but less than 1.9, according to the following formula: (1) Calculate the DNA concentration in the solution, where K This represents the dilution factor. After the calculation is complete, the solution must be stored in a refrigerator at 4°C for no more than 72 hours to ensure the stability of the solution.

[0049] 5.2 Determination and Analysis of Ultraviolet Absorption Spectra 5.2.1 Determination of Ultraviolet Absorption Spectroscopy Pour 2.5 mL of the prepared buffer solution into a quartz cuvette and place it in the UV instrument to establish the system background. Remove the buffer solution from the sample cell and add 2.50 mL of 50 μmol·L⁻¹ solution. -1A lanthanum complex solution was used, and the scanning wavelength was set to 200-300 nm. After each scan, 50.0 μL of 2.0 mmol·L⁻¹ solution was added to the sample cell. -1 CT-DNA solution. Each group was mixed by pipetting to allow the CT-DNA in the cuvette to fully react with the lanthanum complex for 5 min. The concentration of CT-DNA in the sample cell continuously increased, and a total of nine sets of data were measured.

[0050] 5.2.2 Analysis of Ultraviolet Absorption Spectra The measured data were made into Figure 10 Analysis revealed that as the concentration of CT-DNA increased, the maximum absorption peak of the lanthanum complex at 267 nm gradually weakened, indicating a weak hypochromic effect. However, after the complex bound to the CT-DNA solution, the maximum absorption peak wavelength remained at 267 nm. Based on this, it can be inferred that the interaction between the lanthanum complex and CT-DNA is not insertional, but more likely involves trenching or electrostatic interactions. This is because if DNA were to undergo insertional interaction with the complex, the complex would accumulate electrons with the DNA base pairs, leading to electron energy level transitions and a decrease in absorption capacity. This would typically manifest as a noticeable hypochromic effect and redshift at the maximum absorption peak. Further analysis of the binding characteristics can be performed by calculating the binding constant between the lanthanum complex and the CT-DNA solution using a formula. K b : (3) Calculations yielded K sv =4.75×10 4 L·mol -1 , K q =4.75×10 12 L·mol -1 ·s -1 , will calculate K q With the dynamic quenching rate constant of the mechanism (2×10) 10 L·mol -1 ·s -1 By comparison, it can be determined that the binding of the lanthanum complex to EB-CT-DNA is a static quenching. (Where C is in the formula...) DNA The concentration of CT-DNA, ε a ε is the molar absorptivity of the complex. b ε is the molar absorptivity of the complete complex after CT-DNA has fully bound to the complex. f (This represents the molar absorptivity of the complex for each interaction between CT-DNA and the complex.) 5.3 Determination and Analysis of Fluorescence Quenching Spectra 5.3.1 Determination of fluorescence quenching spectrum Measure 30.0 mL of 8.0 μmol / L ethidium bromide (EB) and 30.0 mL of 10.0 μmol / L CT-DNA solution into a beaker, mix thoroughly, and incubate at 4 °C for 12 h. Add 2.50 mL of EB solution to a four-sided transparent quartz cuvette. Set the emission wavelength scanning range to 480-520 nm at an excitation wavelength of 251 nm, a slit width of 10 nm, and a voltage of 700 V. Then remove the cuvette and add 2.5 mL of EB-CT-DNA solution, scanning the emission spectrum under the same conditions. Then, add 20.0 μL of 50 μmol / L CT-DNA solution to the cuvette each time. -1 The lanthanum complex solution was mixed by pipetting with a dropper to allow the EB-CT-DNA solution in the cuvette to react fully with the lanthanum complex for 5 min, and the emission spectrum was measured under the same conditions. The concentration of the lanthanum complex in the sample cell continuously increased, and a total of six sets of data were obtained.

[0051] 5.3.2 Analysis of fluorescence spectra When the excitation wavelength was 251 nm, the fluorescence emission peak of the EB-CT-DNA solution appeared at an emission wavelength of 500 nm. With each addition of the lanthanum complex, the fluorescence intensity of the lanthanum complex decreased, while the wavelength of the fluorescence absorption peak remained unchanged and consistently higher than that of free EB. Therefore, it is inferred that the interaction between the complex and EB-CT-DNA may be through electrostatic interaction with DNA, causing the DNA to contract and displacing the bound EB molecules, resulting in a decrease in the fluorescence intensity of the solution. This is consistent with the conclusions drawn from the UV data above, thus it can be inferred that DNA interacts with the lanthanum complex via electrostatic interaction. According to the classical Stern-Volmer equation: (4) in the formula F 0 represents the fluorescence intensity of the EB-CT-DNA solution itself. F This indicates the fluorescence intensity of the EB-CT-DNA solution after the addition of the complex. K q Let be the rate constant for the molecular quenching process. τ 0 represents the average lifetime of fluorescent molecules without quencher. K sv Let [ be the quenching constant], Q [This represents the concentration of the complex.] This was calculated. K sv =4.75×10 4 L·mol -1 From this, the quenching rate constant can be obtained. Kq =4.75×10 12 L·mol -1 ·s -1 This value is much larger than the rate constant of the dynamic quenching mechanism (2 × 10⁻⁶). 10 L·mol -1 ·s -1 Therefore, it was determined that the fluorescence quenching of CT-DNA by the lanthanum complex was static quenching. This was determined using the formula: (5) In the formula K a For the associative constant, n It is a binding site, with lg[( F 0- F ) / F As y-axis lg[ M Plot a scatter plot along the x-axis, and calculate the binding rate constant according to formula (5). K a =2.45×10 5 L·mol -1 binding site n =1.18. From Figure 13 It can be seen that, in different r At the value of [Complex] / [DNA], the initial fluorescence intensity decreased from 76.06% to 15.47%, a total decrease of 60.59%.

[0052] Example 6: Interaction between lanthanum complexes and human serum albumin (HSA) 6.1 Solution Preparation Tris-HCl / NaCl buffer solution: Weigh 5 × 10 -3 mol (0.6060 g) of Tris and 5 × 10 -2 Add 2.9110 g of NaCl to a beaker, using distilled water as the solvent. After the solution is completely dissolved by stirring with a glass rod, transfer the solution to a 1.0 L volumetric flask, add distilled water to the mark, and then adjust the pH of the solution to 7.43 (the allowable range is 7.2-7.5) using dilute hydrochloric acid solution.

[0053] Preparation of HSA solution: First, take an appropriate amount of HSA powder and add it to the buffer solution, stirring thoroughly until homogeneous. Use the prepared buffer solution as the background solution for UV spectroscopy, measure the UV spectrum of this solution, and calculate according to the formula: (2) Calculate the concentration of HSA, whereK This represents the dilution factor. The prepared HSA solution of a specified concentration should be stored in a refrigerator at 4 °C for no more than 72 hours.

[0054] 6.2 Determination and Analysis of Ultraviolet Absorption Spectra 6.2.1 Determination of Ultraviolet Absorption Spectroscopy Pour 2.5 mL of the prepared buffer solution into a quartz cuvette and place it in the UV instrument to establish the system background. Remove the buffer solution from the sample cell and add 2.50 mL of 50 μmol·L⁻¹ solution. -1 The lanthanum complex solution was scanned at a wavelength of 250-300 nm. After each scan, 50.0 μL of 5 μmol HSA solution was added to the sample cell. Each group was mixed by pipetting to ensure the HSA and lanthanum complex reacted fully in the cuvette for 5 min. The concentration of HSA in the sample cell continuously increased, and a total of fourteen sets of data were obtained.

[0055] 6.2.2 Analysis of Ultraviolet Absorption Spectra The α-helix and random coil conformation of HSA induces ultraviolet absorption. By comparing the ultraviolet spectra of the complex before and after interaction with HSA, and observing characteristics such as peak shifts and changes in absorption intensity, it can be determined whether an interaction occurs. Figure 14 As shown, a characteristic absorption peak exists at 267 nm in the ultraviolet region. With the gradual addition of HSA solution, the intensity of this characteristic peak gradually decreases, exhibiting a hypochromic effect. This phenomenon suggests that the complex and the EB-CT-DNA solution may interact through electrostatic interactions.

[0056] 6.3 Determination and Analysis of Fluorescence Quenching Spectra 6.3.1 Determination of fluorescence quenching spectrum First, take a four-sided transparent quartz cuvette and accurately add 2.50 mL of HSA solution. Next, turn on the fluorescence spectrophotometer and set the parameters: adjust the excitation wavelength to 295 nm, set both the excitation and emission slit widths to 5 nm, set the voltage to 700 V, and simultaneously determine the emission wavelength scanning range to 320-350 nm. After completing the parameter settings, perform a fluorescence spectrum scan on the HSA solution. After the scan, accurately pipette 20.0 μL of a 50 μmol·L⁻¹ solution each time. -1 The lanthanum complex solution was added to the sample cell of the cuvette. Then, the solution was gently agitated with a dropper for 5 minutes to ensure thorough mixing of the HSA solution and the lanthanum complex.

[0057] 6.3.2 Fluorescence quenching spectral analysis Human serum albumin (HSA) contains tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe) residues, and thus can emit strong endogenous fluorescence. Its fluorescence intensity and position vary due to different substituents and the spatial configuration of amino acids. From Figure 15 It can be seen that after the lanthanum complex reacts with HSA, there is a maximum fluorescence absorption peak at an emission wavelength of 327 nm. When no lanthanum complex is added, the fluorescence intensity of HSA is the strongest. As the lanthanum complex is continuously added and reacts with it, the fluorescence intensity decreases, showing a hypochromic effect. Calculated according to formula (4) K sv = 9.83×10 4 L·mol -1 , K q = 9.83×10 12 L·mol -1 ·s -1 , since K q is larger than the maximum diffusion collision quenching constant (2.0×10 10 L·mol -1 ·s -1 ) between drug small molecules and biological macromolecules, it is thus judged that the fluorescence quenching of the lanthanum complex on HSA is static quenching. According to formula (5), with lg[( F 0 - F ) / F as the y axis and lg M as the x axis, plot Figure 16 . And calculate the binding constant K a = 67.61 L·mol -1 , and the binding site n = 0.39. With [[ID= forty-nine]] F / F 0×100% as the y axis and r =[complex concentration] / [HSA concentration] as the x axis, make the binding constant graph of the lanthanum complex and the HSA solution, observe Figure 17 and calculate. It can be found that after adding the lanthanum complex, the fluorescence intensity decreases by 13.73%. This indicates that the endogenous fluorescence of HSA has been quenched, and the binding of the lanthanum complex to HSA has led to a decrease in the fluorescence intensity of the system.

[0058] Studying the binding affinity of the complex to HSA is crucial for predicting its transport, distribution, and ultimate reach and maintenance of effective concentrations at the tumor site in vivo. Good HSA binding properties are often a prerequisite for good in vivo drug activity. Furthermore, many effective antitumor drugs work by directly binding to DNA, interfering with DNA replication, transcription, or repair, ultimately leading to cancer cell death. Therefore, a compound that interacts with CT-DNA strongly suggests its potential to interfere with DNA function, an important mechanism of antitumor activity. The results of Examples 5 and 6 demonstrate that the lanthanum complex [LaT3·(H2O)2]... n It has certain application prospects in anti-tumor drugs.

[0059] Example 7 A method for synthesizing the lanthanum complex as described in claim 1, comprising the following steps: (1) Weigh the reactant raw materials according to the molar ratio of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to La(NO3)3·6H2O of 2.8; (2) Measure ethanol according to the ratio of the amount of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to the volume of ethanol = 1 mmol : 5 mL. The alcohol and water were measured according to the ratio of the amount of substance of La(NO3)3·6H2O to the volume of alcohol and water = 1 mmol : 18 mL, with an alcohol-to-water ratio of 4:1. (3) Place the 4-methyl-1,2,3-thiadiazole-5-carboxylic acid weighed in step (1) into a reaction vessel, add the ethanol measured in step (2) as a solvent into the reaction vessel, and stir at room temperature until completely dissolved. (4) Place the La(NO3)3·6H2O weighed in step (1) into a beaker, add the alcohol-water measured in step 2 into the beaker, and stir until the La(NO3)3·6H2O is completely dissolved. (5) Add the solution obtained in step (4) to the solution obtained in step (3) and stir until fully mixed; (6) Adjust the pH of the system to 6.8 and stir until well mixed; (7) Place the reactor in an oven and maintain the reaction temperature at 75 °C for 48 h; (8) Remove the product and allow it to cool naturally. Open the reactor and filter the product to obtain white blocky crystals, which are the lanthanum complex.

[0060] Example 8 A method for synthesizing the lanthanum complex as described in claim 1, comprising the following steps: (1) Weigh the reactant raw materials according to the molar ratio of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to La(NO3)3·6H2O of 3.2; (2) Measure ethanol according to the ratio of the amount of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to the volume of ethanol = 1 mmol : 8 mL. The alcohol and water were measured according to the ratio of the amount of La(NO3)3·6H2O to the volume of alcohol and water = 1 mmol : 22 mL, with an alcohol-to-water ratio of 4:1. (3) Place the 4-methyl-1,2,3-thiadiazole-5-carboxylic acid weighed in step (1) into a reaction vessel, add the ethanol measured in step (2) as a solvent into the reaction vessel, and stir at room temperature until completely dissolved. (4) Place the La(NO3)3·6H2O weighed in step (1) into a beaker, add the alcohol-water measured in step 2 into the beaker, and stir until the La(NO3)3·6H2O is completely dissolved. (5) Add the solution obtained in step (4) to the solution obtained in step (3) and stir until fully mixed; (6) Adjust the pH of the system to 7.2 and stir until well mixed; (7) Place the reactor in an oven and maintain the reaction temperature at 85 °C for 72 h; (8) Remove the product and allow it to cool naturally. Open the reactor and filter the product to obtain white blocky crystals, which are the lanthanum complex.

[0061] Example 9 A method for synthesizing the lanthanum complex as described in claim 1, comprising the following steps: (1) Weigh the reactant raw materials according to the molar ratio of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to La(NO3)3·6H2O of 2.8, 2.9, 3.0, 3.0 or 3.2; (2) Measure ethanol according to the ratio of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid: ethanol volume = 1 mmol : 5.5, 6.0, 6.5, 7.0, 7.5, or 8.0 mL. The alcohol and water should be measured according to the ratio of the amount of substance of La(NO3)3·6H2O to the volume of alcohol and water = 1 mmol : 18, 19, 20, 21 or 22 mL, with the alcohol-water ratio being 4:1. (3) Place the 4-methyl-1,2,3-thiadiazole-5-carboxylic acid weighed in step (1) into a reaction vessel, add the ethanol measured in step (2) as a solvent into the reaction vessel, and stir at room temperature until completely dissolved. (4) Place the La(NO3)3·6H2O weighed in step (1) into a beaker, add the alcohol-water measured in step 2 into the beaker, and stir until the La(NO3)3·6H2O is completely dissolved. (5) Add the solution obtained in step (4) to the solution obtained in step (3) and stir until fully mixed; (6) Adjust the pH of the system to 6.8, 6.9, 7.0, 7.1 or 7.2, and stir to mix evenly; (7) Place the reactor in an oven and maintain the reaction at 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 or 85 °C for 48, 60 or 72 h; (8) Remove the product and allow it to cool naturally. Open the reactor and filter the product to obtain white blocky crystals, which are the lanthanum complex.

Claims

1. A lanthanum complex, characterized in that, The chemical formula of the lanthanum complex is [LaT3·(H2O)2]. n HT = 4-methyl-1,2,3-thiadiazole-5-carboxylic acid; The crystallographic data of the lanthanum complexes are shown in Table 1. Table 2 shows some of the bond lengths and bond angles in the single crystal structure of the lanthanum complex. Table 1. Crystallographic parameters of lanthanum thiadiazole complexes Table 2 Bond lengths (Å) and bond angles (°) of lanthanum thiadiazole complexes Symmetry codes: (i) - x , - y , - z ; (ii) - x +1, - y , - z。 2. The lanthanum complex as described in claim 1, characterized in that, The smallest asymmetric unit of the lanthanum complex consists of a metal ion La(III) coordinated with three 4-methyl-1,2,3-thiadiazole-5-carboxylate ions and two water molecules.

3. The lanthanum complex as described in claim 1, characterized in that, The lanthanum complex is formed by La³⁺ coordinating with six 4-methyl-1,2,3-thiadiazole-5-carboxylate ions and two water molecules to form a nine-coordination distorted tri-capped trigonal prism configuration. A one-dimensional chain is formed by carboxyl oxygen bridging. The one-dimensional chain is stacked into a three-dimensional diagram through NH and SH hydrogen bonds and π-π stacking of thiadiazole rings.

4. A method for synthesizing the lanthanum complex as described in claim 1, characterized in that, Includes the following steps: (1) Weigh the reactant raw materials according to the molar ratio of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to La(NO3)3·6H2O of 2.8~3.2; (2) Measure ethanol according to the ratio of the amount of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid to the volume of ethanol = 1 mmol : 5~8 mL. The alcohol and water were measured according to the ratio of the amount of La(NO3)3·6H2O to the volume of alcohol and water = 1 mmol : 18~22 mL, with an alcohol-to-water ratio of 4:

1. (3) Place the 4-methyl-1,2,3-thiadiazole-5-carboxylic acid weighed in step (1) into a reaction vessel, add the ethanol measured in step (2) as a solvent into the reaction vessel, and stir at room temperature until completely dissolved. (4) Place the La(NO3)3·6H2O weighed in step (1) into a beaker, add the alcohol-water measured in step 2 into the beaker, and stir until the La(NO3)3·6H2O is completely dissolved. (5) Add the solution obtained in step (4) to the solution obtained in step (3) and stir until fully mixed; (6) Adjust the pH of the system to 6.8~7.2 and stir until well mixed; (7) Place the reactor in an oven and maintain the reaction temperature at 75-85 °C for 48-72 h; (8) Remove and allow to cool naturally, open the reactor and filter to obtain white blocky crystals, which are the lanthanum complex.

5. The method for synthesizing the lanthanum complex as described in claim 4, characterized in that, The steps are as follows: (S1) Weigh 0.75 mmol of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid into the inner liner of the reaction vessel, add 5 mL of ethanol using a graduated cylinder, add a stir bar, and stir with a magnetic stirrer at room temperature until completely dissolved. (S2) Weigh 0.25 mmol La(NO3)3·6H2O into a beaker, add 5 mL of alcohol-water mixture with a ratio of 4:1 using a graduated cylinder, and stir with a glass to dissolve La(NO3)3·6H2O. (S3) Mix the solution obtained in step (1) with the solution obtained in step (2) and stir until fully mixed; (S4) Adjust the pH of the system to 7 and stir until well mixed; (S5) Place the reactor in an oven and maintain the reaction temperature at 80 °C for 72 h; (S6) Remove and allow to cool naturally, open the reactor and filter to obtain white blocky crystals, which are the lanthanum complex.

6. The method for synthesizing the lanthanum complex as described in claim 4 or 5, characterized in that, Adjust the pH of the system to 7 using NaOH solution.

7. The lanthanum complex [LaT3·(H2O)2] n Application in anti-tumor drugs.

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