Organic / metal halide hybrid anticaries material based on triphenylphosphine derivatives and methods of making the same

Abstract

The application provides an organic / metal halide hybrid anti-caries material based on a triphenylphosphine derivative and a preparation method thereof. The organic / metal halide hybrid anti-caries material based on the triphenylphosphine derivative specifically comprises [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)], and the material has excellent antibacterial performance and good biological safety, and is expected to become a novel antibacterial material in the field of stomatology.

Description

Technical Field

[0001] This application relates to an invention of a low-dimensional organic / metal halide hybrid anti-caries material based on triphenylphosphine derivatives [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)]. This type of material consists of organic cations and inorganic metal halide anions, integrating the properties of organic and inorganic materials into a single crystalline molecular-level composite material. This invention has broad application prospects in the field of oral medicine, especially in the prevention and treatment of dental caries. Background Technology

[0002] In the field of dental caries prevention and treatment, known technologies mainly include fluoride preparations, antibacterial agents, natural medicines, and immunomodulators. However, these materials all have potential problems. For example, long-term excessive use of fluoride may lead to fluorosis, long-term use of antibacterial agents may cause taste abnormalities, the caries-preventing effect of natural medicines is questionable, and active immunization against dental caries lacks clinical research on safety and efficacy.

[0003] With the continuous development of antibiotics, drug resistance in human pathogens has become a major challenge in pharmaceutical and biomedical fields. Researchers have shifted their focus to nanomaterials to address the problem of multidrug-resistant pathogens. Organic-inorganic hybrid materials have attracted considerable attention due to their antibacterial potential. The crystal structure of these materials can be precisely controlled under different reaction conditions by selecting appropriate organic ligands and metal halides.

[0004] Existing organic-inorganic hybrid materials have limited research on antibacterial properties, and quaternary phosphine salts are rarely used as templates for metal halide systems. This application proposes the synthesis of two low-dimensional organic / metal halide hybrid materials [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] based on triphenylphosphine derivatives, and explores their antibacterial properties and biosafety, providing new candidate materials for the field of oral medicine.

[0005] Existing oral antibacterial materials suffer from insufficient safety with long-term use and drug resistance, necessitating the development of novel, efficient, and safe antibacterial materials. While organic-inorganic hybrid materials possess antibacterial potential, their research in the field of oral medicine is still inadequate.

[0006] Long-term excessive use of traditional oral antibacterial materials may lead to adverse reactions, and bacteria are prone to developing drug resistance. There is limited research on existing organic-inorganic hybrid materials in the field of oral medicine, and their antibacterial properties and biosafety require further investigation.

[0007] This application synthesizes two low-dimensional organic / metal halide hybrid materials based on triphenylphosphine derivatives, [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)], and confirms that they have excellent antibacterial properties and good biocompatibility, and are expected to become novel antibacterial materials in the field of oral medicine. Summary of the Invention

[0008] The purpose of this invention is to provide an organic / metal halide hybrid material [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] based on triphenylphosphine derivatives.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] A method for preparing an organo / metal halide hybrid material [(BTPPI)2(Ag2I4)] based on a triphenylphosphine derivative includes the following steps: weighing bis(triphenylphosphine)ammonium chloride ([BTPPI]·Cl), AgI, and KI into a glass bottle, adding a mixed solution of acetonitrile and acetone, stirring at room temperature for 15 min, filtering the solution, sealing the glass bottle mouth with a perforated membrane, and allowing it to slowly evaporate at room temperature. After 2-3 days, colorless and transparent rod-shaped crystals are obtained. The obtained crystals are washed three times with acetonitrile and ethanol, respectively, and then vacuum dried at 60 °C for 12 hours to obtain [(BTPPI)2(Ag2I4)] crystals.

[0011] Preferably, the molar ratio of [BTPPI]·Cl, AgI and KI is 1:1:6.

[0012] Preferably, the volume ratio of acetonitrile to acetone is 1:1.

[0013] Preferably, the [(BTPPI)2(Ag2I4)] material is used in the preparation of anti-caries and antibacterial materials.

[0014] A method for preparing an organo / metal halide hybrid material [(BTPPI)2(Cu2I4)] based on a triphenylphosphine derivative includes the following steps: weighing bis(triphenylphosphine)ammonium chloride ([BTPPI]·Cl), CuI, and KI into a glass bottle, adding acetonitrile, stirring at room temperature for 15 min, placing in a 90 ℃ oven for 1 day, then slowly cooling to room temperature over 12 hours, filtering the solution, sealing the glass bottle mouth with a perforated membrane, and allowing it to slowly evaporate at room temperature for 2-3 days to obtain pale white blocky crystals, washing the obtained crystals three times with acetonitrile and ethanol respectively, and then vacuum drying at 60 ℃ for 12 hours to obtain [(BTPPI)2(Cu2I4)] crystals.

[0015] Preferably, the molar ratio of [BTPPI]·Cl, CuI and KI is 1:1.5:6.

[0016] Preferably, the [(BTPPI)2(Cu2I4)] material is used in the preparation of anti-caries and antibacterial materials.

[0017] The advantages of this invention are:

[0018] 1. Anti-mutagenic Streptococcus properties

[0019] Advantages: The material in this application has antibacterial properties against Streptococcus mutans, a major cariogenic bacterium in the oral cavity.

[0020] 2. Anti-biofilm ability

[0021] Advantages: The material can effectively inhibit the formation of biofilms of oral cariogenic bacteria Streptococcus mutans, resulting in outstanding anti-caries effects.

[0022] 3. High biosafety

[0023] Advantages: Low hemolysis rate of the material.

[0024] 4. The synthesis method is simple.

[0025] Advantages: It adopts conventional solution reaction and slow volatilization crystallization, the preparation process is simple and the yield is high. Attached Figure Description

[0026] Figure 1 It has the structure [(BTPPI)2(Ag2I4)];

[0027] Figure 2 Powder diffraction pattern of compound [(BTPPI)2(Ag2I4)] (positive values ​​are experimental values);

[0028] Figure 3 The infrared spectrum of compound [(BTPPI)2(Ag2I4)] is shown below.

[0029] Figure 4 The structure of the compound [(BTPPI)2(Cu2I4)] is shown.

[0030] Figure 5 Powder diffraction pattern of compound [(BTPPI)2(Cu2I4)] (positive values ​​are experimental values);

[0031] Figure 6 The infrared spectrum of compound [(BTPPI)2(Cu2I4)] is shown below.

[0032] Figure 7The inhibition zones of [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] against Streptococcus mutans are: A. [(BTPPI)2(Ag2I4)], B. [(BTPPI)2(Cu2I4)];

[0033] Figure 8 For the minimum inhibitory concentration experiments of [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] against Streptococcus mutans, A. Streptococcus mutans [(BTPPI)2(Ag2I4)], B. Streptococcus mutans [(BTPPI)2(Cu2I4)];

[0034] Figure 9 To investigate the effect of [(BTPPI)2(Ag2I4)] on the formation of *Streptococcus mutans* biofilm, A. the macroscopic appearance of *Streptococcus mutans* biofilms formed under different concentrations of [(BTPPI)2(Ag2I4)], and B. the evaluation of the effect of different concentrations of [(BTPPI)2(Ag2I4)] on the formation of *Streptococcus mutans* biofilm by optical density measurement; (*: P <0.05; **: P <0.01:***: P <0.001;****: P <0.0001);

[0035] Figure 10 The effect of [(BTPPI)2(Cu2I4)] on the formation of *Streptococcus mutans* biofilm: A. Macroscopic observation of *Streptococcus mutans* biofilm formed under different concentrations of [(BTPPI)2(Cu2I4)]; B. Evaluation of the effect of different concentrations of [(BTPPI)2(Cu2I4)] on the formation of *Streptococcus mutans* biofilm by optical density measurement; (*: P <0.05; **: P <0.01:***: P <0.001;****: P <0.0001);

[0036] Figure 11 The hemolytic reaction of materials with different concentrations of [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] was recorded. Note that PN1 is [(BTPPI)2(Ag2I4)] and PN2 is [(BTPPI)2(Cu2I4)]. Detailed Implementation

[0037] To make the above-mentioned features and advantages of the present invention more apparent and understandable, specific embodiments are described below in detail. Unless otherwise specified, the methods of the present invention are conventional methods in the art.

[0038] Example 1

[0039] 1. Synthesis of materials [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)]

[0040] Synthesis of compound [(BTPPI)2(Ag2I4)]: Bis(triphenylphosphine)ammonium chloride ([BTPPI]·Cl) (0.0574 g, 0.1 mmol), AgI (0.0235 g, 0.1 mmol), and KI (0.0994 g, 0.6 mmol) were weighed into a 25 mL glass flask. A mixture of 5 mL acetonitrile and 5 mL acetone was added, and the mixture was stirred at room temperature for 15 min. The solution was filtered, and the mouth of the flask was sealed with a perforated membrane. The mixture was allowed to evaporate slowly at room temperature for approximately 2-3 days to obtain colorless, transparent rod-shaped crystals. The obtained crystals were washed three times with acetonitrile and ethanol, respectively, and then dried under vacuum at 60 °C for 12 hours to obtain 0.041 g of crystals, with a yield of 45.54% (based on Ag).

[0041] Synthesis of compound [(BTPPI)2(Cu2I4)]: Bis(triphenylphosphine)ammonium chloride ([BTPPI]·Cl) (0.0574 g, 0.1 mmol), CuI (0.0285 g, 0.15 mmol), and KI (0.0994 g, 0.6 mmol) were weighed into a 25 mL glass flask. 10 mL of acetonitrile solvent was added, and the mixture was stirred at room temperature for 15 min. The mixture was then placed in a 90 °C oven for 1 day, followed by slow cooling to room temperature over 12 hours. The solution was filtered, and the mouth of the beaker was sealed with a perforated membrane. The mixture was allowed to evaporate slowly at room temperature for approximately 2-3 days to obtain pale white blocky crystals. The obtained crystals were washed three times with acetonitrile and ethanol, respectively, and then dried under vacuum at 60 °C for 12 hours to obtain 0.0280 g of crystals, with a yield of 21.78% (based on Cu).

[0042] 2. Physical properties and characterization of materials

[0043] The synthesized [(BTPPI)₂(Ag₂I₄)] and [(BTPPI)₂(Cu₂I₄)] were characterized by infrared spectroscopy, ultraviolet spectroscopy, powder diffraction, and single-crystal structure determination. The results showed that both materials consist of two organic [BTPPI] cations and the corresponding dimer [Ag₂I₄]. 2- Or [Cu2I4] 2- It is composed of anion clusters, with organic and inorganic parts stacked together through electrostatic interactions.

[0044] 3. Verification of antibacterial effect

[0045] The excellent antibacterial activity of the two materials against *Streptococcus mutans* was confirmed by agar diffusion method and minimum inhibitory concentration (MIC) determination. Furthermore, both materials effectively inhibited the formation of single-species biofilms of *Streptococcus mutans*.

[0046] The Oxford cup inhibition zone experiment confirmed that [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] have antibacterial properties against Streptococcus mutans. Figure 7 The changes in optical density values ​​measured by the Bioscreen fully automated growth curve analyzer over 0-24 h were plotted, and the minimum inhibitory concentrations (MICs) of the two novel materials [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] against Streptococcus mutans were determined to be 4 μg / mL. Figure 8 (A) and 8 μg / mL ( Figure 8 (B)

[0047] The inhibitory effects of [(BTPPI)2(Ag2I4)] and [(BTPPI)2(Cu2I4)] on biofilm formation in *Streptococcus mutans* were evaluated using crystal violet staining. Figure 9 China A and Figure 10 As shown in Figure A, under visual observation, the *Streptococcus mutans* biofilms cultured at 4 μg / mL [(BTPPI)2(Ag2I4)] and 8 μg / mL [(BTPPI)2(Cu2I4)] showed almost no staining. This indicates that both high concentrations of [(BTPPI)2(Ag2I4)] (2 μg / mL and 4 μg / mL) and high concentrations of [(BTPPI)2(Cu2I4)] (4 μg / mL and 8 μg / mL) significantly inhibited *Streptococcus mutans* biofilm formation.

[0048] 4. Biosafety Testing

[0049] Hemolysis tests confirmed that [(BTPPI)2(Ag2I4)] had no significant hemolytic effect on erythrocytes below 40 μg / mL, while [(BTPPI)2(Cu2I4)] showed significant hemolysis at 20 μg / mL. Figure 11 It is much higher than the minimum inhibitory concentration of the material.

[0050] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made within the scope of the claims of the present invention should be included in the scope of the present invention.

Claims

1. A method for preparing an organic / metal halide hybrid anti-caries material [(BTPPI)2(Ag2I4)] based on a triphenylphosphine derivative, characterized in that, Includes the following steps: Weigh bis(triphenylphosphine)ammonium chloride ([BTPPI]·Cl), AgI and KI into a glass bottle, add a mixed solution of acetonitrile and acetone, stir at room temperature for 15 min, filter the solution, seal the glass bottle mouth with a perforated membrane, and allow it to slowly evaporate at room temperature. After 2-3 days, colorless transparent rod-shaped crystals are obtained. The obtained crystals are washed three times with acetonitrile and ethanol, respectively, and then dried under vacuum at 60 °C for 12 hours to obtain [(BTPPI)2(Ag2I4)] crystals.

2. The preparation method according to claim 1, characterized in that, The molar ratio of [BTPPI]·Cl, AgI, and KI is 1:1:

6.

3. The preparation method according to claim 1, characterized in that, The volume ratio of acetonitrile to acetone is 1:

1.

4. The [(BTPPI)2(Ag2I4)] material prepared by the preparation method according to claim 1.

5. The application of [(BTPPI)2(Ag2I4)] according to claim 4 in the preparation of anti-caries and antibacterial materials.

6. Application of an organic / metal halide hybrid anti-caries material based on triphenylphosphine derivative [(BTPPI)2(Cu2I4)] in the preparation of anti-caries and antibacterial materials.

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