Aluminum-based metal organic framework-titanium dioxide composite material with surface modified by gold nanoparticles as well as preparation method and application of aluminum-based metal organic framework-titanium dioxide composite material

Abstract

The invention relates to the field of nano materials, in particular to an aluminum-based metal organic framework-titanium dioxide composite material with the surface modified by nano-gold particles and a preparation method and application of the aluminum-based metal organic framework-titanium dioxide composite material. According to the preparation method, aluminum chloride hexahydrate and 3, 5-pyrazole dicarboxylic acid are taken as monomers, titanium dioxide is taken as a compound, and deionized water is taken as a solvent, so that a novel aluminum-based metal organic framework-titanium dioxide cubic nano material precursor (Al-MOF / TiO2) is prepared; then the surface of the Al-MOF / TiO2 is modified with gold nanoparticles, the Al-MOF / TiO2 (at) Au cubic composite nanomaterial is obtained, and the synthesis process is simple, convenient and environmentally friendly; the Al-MOF / TiO2 (at) Au has a large specific surface area and excellent optical performance, which indicates that the Al-MOF / TiO2 (at) Au has huge potential in the research of drug-resistant bacterium metabolism fingerprint extraction.

Description

Technical Field

[0001] The invention relates to the field of nanomaterials, and in particular to an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles, and a preparation method and application thereof. Background Art

[0002] With the widespread clinical use of carbapenems, bacterial resistance to them has gradually increased. In the past two decades, carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged and spread rapidly around the world. The main resistance mechanism of CRKP is that bacteria produce carbapenemases that can hydrolyze carbapenem antibiotics, thereby producing resistance. Different genotypes of carbapenemases CRKP have different activities against antibiotics, and the mortality rate of resistant bacteria infection is also different. Therefore, there is an urgent need to develop an efficient, simple, and specific detection method to achieve rapid identification of CRKP and identification of drug-resistant genotypes.

[0003] Matrix-assisted laser desorption / ionization-mass spectrometry (MALDI-MS) has important application value in the field of microbial species identification due to its advantages such as high throughput, high precision and fast analysis speed. In the process of microbial cell metabolite analysis, the desorption / ionization process of metabolic small molecules by nanomatrix is ​​a key step, which directly affects the sensitivity, specificity and stability of detection. Some nanomaterial matrices such as amorphous silicon and metal nanoparticles have been successfully used to extract metabolic fingerprints of clinically infected bacterial cells. However, the sensitivity of a single nanomaterial is limited, and there are problems such as difficulty in distinguishing similar bacterial species or strains and drug-resistant strains. Summary of the invention

[0004] The purpose of the present invention is to provide an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles and a preparation method and application thereof in view of the deficiencies in the prior art.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] The first aspect of the present invention is to provide a method for preparing an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles, the steps comprising:

[0007] S1, weighing titanium dioxide, dispersing it into deionized water and shaking it to obtain a first solution;

[0008] S2, weighing chlorine trioxide hexahydrate, 3,5-pyrazoledicarboxylic acid monohydrate and sodium hydroxide, and dissolving them in deionized water to prepare a second solution;

[0009] S3, mixing the first solution and the second solution to react, and after the reaction is completed, washing and drying the reaction product to obtain an aluminum-based metal organic framework-titanium dioxide composite material;

[0010] S4, dispersing the aluminum-based metal organic framework-titanium dioxide composite material into a nano-gold colloid solution and performing a shaking treatment, washing and drying the product after the shaking treatment, so as to obtain the aluminum-based metal organic framework-titanium dioxide composite material with surface modified nano-gold particles.

[0011] Preferably, in step S2, in the second solution, the concentration ratio of the chlorine trioxide hexahydrate, the 3,5-pyrazoledicarboxylic acid monohydrate and the sodium hydroxide is 1:(0.9-1.2):(1.0-2.0).

[0012] Preferably, in step S3, the reaction temperature of the first solution and the second solution is 80° C.-100° C., and the reaction time is 8 h-12 h.

[0013] Preferably, in step S3 and step S4, the washing treatment includes: washing sufficiently with deionized water and ethanol.

[0014] The second aspect of the present invention is to provide an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles prepared by the above preparation method.

[0015] The third aspect of the present invention is to provide an application of an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles prepared by the above preparation method in the extraction of bacterial mass spectrometry metabolic fingerprints.

[0016] Preferably, the bacteria are drug-resistant bacteria.

[0017] More preferably, the drug-resistant bacteria is carbapenem-resistant Klebsiella pneumoniae.

[0018] The present invention adopts the above technical solution, and has the following technical effects compared with the prior art:

[0019] The present invention prepares a novel aluminum-based metal organic framework-titanium dioxide cubic nanomaterial precursor (Al-MOF / TiO2) by using aluminum trichloride hexahydrate and 3,5-pyrazoledicarboxylic acid as monomers, titanium dioxide as a composite, and deionized water as a solvent; then, nano-gold particles are modified on the surface of Al-MOF / TiO2 to obtain Al-MOF / TiO2@Au cubic composite nanomaterial, and the synthesis process is simple and environmentally friendly; Al-MOF / TiO2@Au has a large specific surface area and excellent optical properties, indicating its great potential in the research of metabolic fingerprint extraction of drug-resistant bacteria. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a scanning electron micrograph of the aluminum-based metal organic framework-titanium dioxide composite matrix modified with surface nano-gold particles;

[0021] Figure 2 The nitrogen isothermal adsorption-desorption curve of the aluminum-based metal organic framework-titanium dioxide composite matrix modified with surface nano-gold particles;

[0022] Figure 3 This is the UV absorption spectrum of the aluminum-based metal organic framework-titanium dioxide composite material matrix modified with surface nano-gold particles;

[0023] Figure 4 Comparison of mass spectrometry metabolic fingerprints of different clinical infectious bacteria based on aluminum-based metal organic framework-titanium dioxide composite matrix modified with surface nano-gold particles;

[0024] Figure 5 Comparison of mass spectrometry metabolic fingerprints of clinical Klebsiella pneumoniae resistant and sensitive strains based on aluminum-based metal organic framework-titanium dioxide composite matrix modified with surface nano-gold particles;

[0025] Figure 6 Comparison of mass spectrometry metabolic fingerprints of Klebsiella pneumoniae with different carbapenemase-resistant genotypes based on aluminum-based metal-organic framework-titanium dioxide composite matrix modified with surface nano-gold particles;

[0026] Figure 7 The OPLS-DA model score diagram for three clinical infectious bacteria;

[0027] Figure 8 This is the OPLS-DA model score diagram of clinical Klebsiella pneumoniae resistant and sensitive strains;

[0028] Fig. 9 OPLS-DA model score diagram of Klebsiella pneumoniae with different carbapenemase-resistant genotypes. DETAILED DESCRIPTION

[0029] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0031] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, but they are not intended to limit the present invention.

[0032] Example 1

[0033] This embodiment provides a method for preparing an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles, the steps comprising:

[0034] S1. Weigh 100 mg of titanium dioxide and disperse it into 75 mL of deionized water and shake it at a constant temperature for 30 minutes to prepare a first solution;

[0035] S2, weigh 1.06 g of chlorine trioxide hexahydrate (4.39 mmol), 76 mg of 3,5-pyrazoledicarboxylic acid monohydrate (4.39 mmol) and 270 mg of sodium hydroxide (6.75 mmol), and dissolve them in 75 mL of deionized water to prepare a second solution;

[0036] S3, mixing the first solution and the second solution and placing them in a constant temperature magnetic stirring oil bath pot, reacting at 90° C. for 10 hours, after the reaction is completed, washing the reaction product with deionized water and ethanol to remove impurities and raw material monomers on the surface of the product, and drying them in a vacuum drying oven at 50° C. overnight to obtain an aluminum-based metal organic framework-titanium dioxide composite material;

[0037] S4. Disperse 30 mg of the aluminum-based metal organic framework-titanium dioxide composite material into 20 mL of nano-gold colloid solution, shake at a constant temperature for 2 hours, wash the shaken product with deionized water and ethanol, and then dry the product in a vacuum dryer to obtain the aluminum-based metal organic framework-titanium dioxide composite material with surface modified nano-gold particles.

[0038] The scanning electron micrograph (20KV, Philips XL30 electron microscope, Netherlands) of the aluminum-based metal organic framework-titanium dioxide composite matrix modified with surface nano-gold particles is shown in FIG. Figure 1 As shown, the product exhibits a uniform cubic morphology with an average size of about 1 μm.

[0039] The nitrogen isothermal adsorption-desorption curve (Micromeritics ASAP-2010, USA) showed that the product had a large specific surface area ( Figure 2 ). The ultraviolet absorption spectrum (Shimadzu UV-1900, Japan) showed that compared with the aluminum-based metal organic framework-titanium dioxide precursor (product 1), the obtained aluminum-based metal organic framework-titanium dioxide composite matrix modified with surface nano-gold particles (product 2) had a stronger ultraviolet-visible (UV-vis) absorbance at a wavelength of 355 nm (e.g. Figure 3 ).

[0040] Example 2

[0041] This embodiment provides an application of an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles prepared by the preparation method described in Example 1 in the mass spectrometry metabolic fingerprint extraction of different bacteria.

[0042] (1) Sample preparation

[0043] 1 mg of Al-MOF / TiO2@Au nanomaterials were dispersed in 1 mL of deionized water. Clinical Escherichia coli (ECO, 71 strains), Staphylococcus aureus (SA, 76 strains), and Klebsiella pneumoniae (KP, 64 strains) were collected and resuspended in deionized water after liquid culture at a concentration of about 1×10 10 CFU / mL.

[0044] (2) Mass spectrometry

[0045] 1 μL Al-MOF / TiO2@Au nanomaterial was deposited on the MALDI target plate, 1 μL of different bacterial suspensions were spotted on the Al-MOF / TiO2@Au nanomaterial, and then cell wall lysate including formic acid (0.5 μL, 70% aqueous solution), 1-butanol (0.5 μL) and salicylic acid (1 μL, 1 mg / mL aqueous solution) was deposited on the above target. After it was naturally dried, laser desorption ionization mass spectrometry analysis was performed using a Bruker MicroFlex LRF mass spectrometer with a 355nm Nd:YAG laser light source, a laser frequency of 2000 Hz, and an acceleration voltage of 20 kV; the acquisition mode was a cation reflector mode, and the collection mass-to-charge ratio range was 100-1000 Da; mass spectrometry data was obtained from FlexControl 3.4, and the data was exported in flexAnalysis 3.4 to obtain rich metabolite mass spectrometry spectra of different bacteria.

[0046] Figure 4 Comparison of mass spectrometry metabolic fingerprints of clinical Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae extracted from Al-MOF / TiO2@Au nanomaterial matrix.

[0047] Example 3

[0048] This embodiment provides an application of an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles prepared by the preparation method described in Example 1 in mass spectrometry metabolic fingerprint extraction of resistant and sensitive strains of Klebsiella pneumoniae.

[0049] (1) Sample preparation

[0050] 1 mg of Al-MOF / TiO2@Au nanomaterials were dispersed in 1 mL of deionized water, and carbapenem-resistant Klebsiella pneumoniae (CRKP, 80 strains) and carbapenem-sensitive Klebsiella pneumoniae (CSKP, 89 strains) were collected and cultured in liquid and then resuspended in deionized water at a concentration of about 1×10 10 CFU / mL.

[0051] (2) Mass spectrometry

[0052] 1 μL Al-MOF / TiO2@Au nanomaterial was deposited on the MALDI target plate, 1 μL Klebsiella pneumoniae suspension with different drug resistance was spotted on the Al-MOF / TiO2@Au nanomaterial, and then cell wall lysate including formic acid (0.5 μL, 70% aqueous solution), 1-butanol (0.5 μL) and salicylic acid (1 μL, 1 mg / mL aqueous solution) was deposited on the above target. After it was naturally dried, laser desorption ionization mass spectrometry analysis was performed using a Bruker Bruker MicroFlex LRF mass spectrometer with a 355nm Nd:YAG laser light source, a laser frequency of 2000 Hz, and an acceleration voltage of 20 kV; the acquisition mode was a cation reflector mode, and the collection mass-to-charge ratio range was 100-1000 Da; mass spectrometry data was obtained from FlexControl 3.4, and the data was exported in flexAnalysis 3.4 to obtain the bacterial metabolite mass spectrometry spectrum.

[0053] Figure 5 Comparison of mass spectrometry metabolic fingerprints of clinical Klebsiella pneumoniae resistant and sensitive strains extracted from Al-MOF / TiO2@Au nanomaterial matrix.

[0054] Example 4

[0055] This embodiment provides an application of an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nanogold particles prepared by the preparation method described in Example 1 in mass spectrometry metabolic fingerprint extraction of Klebsiella pneumoniae of different carbapenemase-resistant genotypes.

[0056] (1) Sample preparation

[0057] 1 mg Al-MOF / TiO2@Au nanomaterials were dispersed in 1 mL deionized water. Different genotypes of clinical carbapenemase-resistant Klebsiella pneumoniae strains (IMP, 12 strains; KPC, 12 strains; NDM, 12 strains) were collected and resuspended in deionized water after liquid culture at a concentration of about 1×10 10 CFU / mL.

[0058] (2) Mass spectrometry

[0059] 1 μL Al-MOF / TiO2@Au nanomaterial was deposited on the MALDI target plate, 1 μL cell suspension was spotted on the Al-MOF / TiO2@Au nanomaterial, and then cell wall lysate including formic acid (0.5 μL, 70% aqueous solution), 1-butanol (0.5 μL) and salicylic acid (1 μL, 1 mg / mL aqueous solution) was deposited on the above target. After it was naturally dried, laser desorption ionization mass spectrometry analysis was performed using a Bruker Bruker MicroFlex LRF mass spectrometer with a 355nm Nd:YAG laser light source, a laser frequency of 2000 Hz, and an acceleration voltage of 20 kV; the acquisition mode was a cation reflector mode, and the collection mass-to-charge ratio range was 100-1000 Da; mass spectrometry data was obtained from FlexControl 3.4, and the data was exported in flexAnalysis 3.4 to obtain the bacterial metabolite mass spectrometry spectrum.

[0060] Figure 6 Comparison of mass spectrometry metabolic fingerprints of Klebsiella pneumoniae with different carbapenemase-resistant genotypes extracted from Al-MOF / TiO2@Au nanomaterial matrix.

[0061] Application Examples

[0062] An orthogonal partial least squares discriminant analysis (OPLS-DA) model was established based on the bacterial metabolite mass spectra obtained in Example 2-4, and the steps included:

[0063] (1) The urine mass spectra were preprocessed using R language based on MALDIquant and MALDIquantForeign packages, including peak intensity conversion and normalization, peak smoothing, baseline subtraction, peak alignment, peak identification, and peak grouping;

[0064] (2) Based on the bacterial metabolic mass spectrometry, SIMCA software (version 14.1, Umetrics, Sweden) to build an OPLS-DA model to distinguish different bacterial species ( Figure 7 ), Differentiation between carbapenem-resistant and susceptible strains of Klebsiella pneumoniae ( Figure 8 ), differentiation of Klebsiella pneumoniae with different carbapenemase genotypes ( Fig. 9 ).

[0065] In summary, the aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles of the present invention has great potential in the research on metabolic fingerprint extraction of drug-resistant bacteria.

[0066] The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the description and illustrations of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles, characterized in that the steps include: S1, weighing titanium dioxide, dispersing it into deionized water and shaking it to obtain a first solution; S2, weighing chlorine trioxide hexahydrate, 3,5-pyrazoledicarboxylic acid monohydrate and sodium hydroxide, and dissolving them in deionized water to prepare a second solution; S3, mixing the first solution and the second solution to react, and after the reaction is completed, washing and drying the reaction product to obtain an aluminum-based metal organic framework-titanium dioxide composite material; S4, dispersing the aluminum-based metal organic framework-titanium dioxide composite material into a nano-gold colloid solution and performing a shaking treatment, washing and drying the product after the shaking treatment, so as to obtain the aluminum-based metal organic framework-titanium dioxide composite material with surface modified nano-gold particles.

2. The preparation method according to claim 1, characterized in that: In step S2, in the second solution, the concentration ratio of the chlorine trioxide hexahydrate, the 3,5-pyrazoledicarboxylic acid monohydrate and the sodium hydroxide is 1:(0.9-1.2):(1.0-2.0).

3. The preparation method according to claim 1, characterized in that: In step S3, the reaction temperature of the first solution and the second solution is 80° C.-100° C., and the reaction time is 8 h-12 h.

4. The preparation method according to claim 1, characterized in that: In step S3 and step S4, the washing process includes: washing sufficiently with deionized water and ethanol.

5. An aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles prepared by the preparation method according to any one of claims 1 to 4.

6. Use of an aluminum-based metal organic framework-titanium dioxide composite material modified with surface nano-gold particles prepared by the preparation method according to any one of claims 1 to 4 in bacterial mass spectrometry metabolic fingerprint extraction.

7. The use according to claim 6, characterized in that: The bacteria are drug-resistant bacteria.

8. The use according to claim 7, characterized in that: The drug-resistant bacteria is carbapenem-resistant Klebsiella pneumoniae.

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