Near-infrared second-region molecular fluorescence probe luminescence performance evaluation method and system

Abstract

The present invention provides a method and system for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe, which relates to the technical field of fluorescence probes. The method includes: obtaining the initial configuration of the near-infrared second-region molecular fluorescence probe in an aqueous solution, performing molecular dynamics simulation on the initial configuration to obtain multiple representative conformations of the probe in the aqueous solution; performing quantum chemical calculations on each representative conformation to obtain the first system energy of each representative conformation in the stable state, the second system energy in the lowest singlet excited state, and the intensity parameter; generating a comprehensive evaluation factor based on the first system energy, the second system energy, and the intensity parameter; sorting the luminescence performance of the probe based on the comprehensive evaluation factor, and screening out the probe with the optimal performance. The method provided by the present invention realizes the quantitative evaluation of the luminescence performance of the near-infrared second-region molecular fluorescence probe, and provides technical support for the optimized design and clinical application of the probe.

Description

Technical Field

[0001] The present invention relates to the technical field of fluorescent probes, and specifically to a method and system for evaluating the luminescence performance of near-infrared region II molecular fluorescent probes. Background Art

[0002] The statements in this section merely provide background art related to the present disclosure and do not necessarily constitute prior art.

[0003] Due to the advantages of non-invasiveness, high sensitivity, and real-time dynamic monitoring, fluorescence imaging technology has been widely used in tumor detection, drug metabolism tracking, and surgical navigation in biomedical research. Traditional visible light region (400 - 700 nm) and near-infrared region I (NIR-I, 700 - 900 nm) fluorescent probes are limited in imaging depth and signal-to-noise ratio due to the high scattering and autofluorescence interference of biological tissues. In contrast, NIR-II fluorescent probes utilize photons with longer wavelengths (1000 - 1700 nm), significantly reducing scattering and background noise, and improving penetration depth and resolution, becoming a research hotspot in biological in vivo imaging.

[0004] Currently, the evaluation of NIR-II probes mainly relies on experimental tests, including spectroscopic analysis methods and in vitro cell experiments. Among them, spectroscopic analysis methods measure fluorescence intensity, lifetime, and quantum yield, but ignore the influence of molecular dynamic conformation; in vitro cell experiments verify the probe performance through cell imaging, but it is difficult to standardize the experimental conditions. How to scientifically and systematically evaluate the luminescence performance of NIR-II probes has become an urgent problem to be solved. Summary of the Invention

[0005] To solve the above problems, the present invention provides a method and system for evaluating the luminescence performance of near-infrared region II molecular fluorescent probes, which integrate molecular dynamics simulation and quantum chemical calculation to construct multi-dimensional evaluation factors, and solve the problems of single evaluation index, inconsistent standards, and high experimental costs in the prior art.

[0006] The first aspect of the present invention provides a method for evaluating the luminescence performance of near-infrared region II molecular fluorescent probes, including:

[0007] S1: Obtain the initial configuration of the near-infrared region II molecular fluorescent probe in aqueous solution, perform molecular dynamics simulation on the initial configuration to obtain multiple representative conformations of the probe in aqueous solution;

[0008] S2: Perform quantum chemical calculation on each representative conformation to obtain the first system energy of each representative conformation in the stable state, the second system energy and intensity parameters in the lowest singlet excited state;

[0009] S3: Generate a comprehensive evaluation factor based on the first system energy, the second system energy, and the intensity parameters;

[0010] S4: Rank the luminescence performance of the probes based on the comprehensive evaluation factor, and screen out the probe with the optimal performance.

[0011] Furthermore, in S1, performing molecular dynamics simulation on the initial configuration specifically includes:

[0012] S1.1: Construct a molecular structure model of the probe based on the initial configuration, convert the molecular structure model into a format compatible with the molecular dynamics simulation software, and generate a topology file suitable for molecular force field description;

[0013] S1.2: Define the three-dimensional space boundary of the simulation system, add water molecules to it, and form a simulation environment including the probe molecule and water molecules;

[0014] S1.3: Eliminate the high-energy configurations of the system through energy minimization, and then perform molecular dynamics simulation under the set time conditions, and use the clustering analysis method to screen out multiple representative conformations of the probe in water molecules.

[0015] Furthermore, the clustering analysis method screens the conformations by setting a cut-off value and retains the local environment information of the probe molecule and the water molecules around it.

[0016] Furthermore, S2 includes:

[0017] S2.1: Based on the density functional method and the ONIOM model, divide the probe molecule and its solvent environment into a high layer and a low layer, and describe them with a high-precision quantum chemical theory model and a simplified force field model respectively, and calculate the first system energy of each representative conformation in the stable state through structure optimization;

[0018] S2.2: Based on the time-dependent density functional method and the ONIOM model, divide the probe molecule and its solvent environment into a high layer and a low layer, and describe them with a high-precision quantum chemical theory model and a simplified force field model respectively, and calculate the second system energy of each representative conformation in the lowest singlet excited state through excited state structure optimization, and at the same time obtain the oscillator strength, that is, the intensity parameter, in the lowest singlet excited state.

[0019] Furthermore, S3 includes:

[0020] S3.1: Calculate the first system energy E a and the second system energy E b the energy difference between E ; [[ID= 42]]

[0021] S3.2: Perform correlation analysis on the energy difference E and the intensity parameter I to generate a comprehensive evaluation factor through mathematical modelingX .

[0022] Furthermore, the S3.2 includes:

[0023] S3.2.1: Statistics n The intensity parameters of the representative conformations I 1 , I 2 , I 3 ... I n and energy parameters E 1 , E 2 , E 3 ... E n ;

[0024] S3.2.2: Construct a strength matrix and energy matrix , whose matrix elements are and ,in ;

[0025] S3.2.3: Matrix I and E Add up to get the matrix , matrix element , ;

[0026] S3.2.4: Matrix C The sum of each row is used as the minuend, with 2 as the minuend. n As the subtrahend, the correction factor is obtained by subtraction. , ;

[0027] S3.2.5: Generate comprehensive evaluation factors based on the above data .

[0028] Furthermore, the S4 includes: judging the luminescence performance of the probe based on the numerical value of the comprehensive evaluation factor, wherein a larger numerical value indicates a better luminescence performance, and the molecular fluorescent probe with the largest numerical value is the probe with the best performance.

[0029] The second aspect of the present invention provides a near-infrared second region molecular fluorescent probe luminescence performance evaluation system, comprising:

[0030] A conformation acquisition unit is used to obtain the initial configuration of the near-infrared second region molecular fluorescent probe in aqueous solution, perform molecular dynamics simulation on the initial configuration, and obtain multiple representative conformations of the probe in aqueous solution;

[0031] An evaluation parameter acquisition unit for performing quantum chemical calculations on each representative conformation to obtain the first system energy of each representative conformation in the stable state, the second system energy in the lowest singlet excited state, and the intensity parameter;

[0032] An evaluation factor calculation unit for generating a comprehensive evaluation factor based on the first system energy, the second system energy, and the intensity parameter;

[0033] An evaluation and screening unit for ranking the luminescence performance of the probe based on the comprehensive evaluation factor and screening out the probe with the optimal performance.

[0034] The third aspect of the present invention provides a device for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe, the device including a memory and a processor; the memory is used for storing a computer program; the processor is used for implementing the above-mentioned method for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe when executing the computer program.

[0035] The fourth aspect of the present invention provides a computer-readable storage medium, on which a computer program is stored, and when the computer program is executed by a processor, the above-mentioned method for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe is implemented.

[0036] Compared with the prior art, the method and system for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe provided by the present invention have the following beneficial effects:

[0037] Based on the structural characteristics of the near-infrared second-region molecular fluorescence probe, the present invention constructs a comprehensive luminescence performance evaluation index by comprehensively considering influencing factors in multiple dimensions and introducing the time evolution effect weight. Using this index, the luminescence performance of the near-infrared second-region molecular fluorescence probe can be quantitatively considered under a unified standard. The method proposed by the present invention has the advantages of low cost, environmental friendliness, and high reliability, and can greatly save the input cost of time and resources. By applying the method of the present invention, the evaluation process of the luminescence performance of the near-infrared second-region molecular fluorescence probe can be effectively accelerated, providing technical support for the screening of high-performance near-infrared second-region molecular fluorescence probes, and laying a solid theoretical foundation for the design of new near-infrared second-region molecular fluorescence probes. The present invention not only provides a strong tool support for scientific research and medical applications, but also promotes the technological innovation and development in the field of biofluorescence imaging. Description of the Drawings

[0038] The specification drawings constituting a part of the present disclosure are used to provide a further understanding of the present disclosure. The schematic embodiments of the present disclosure and their descriptions are used to explain the present disclosure and do not constitute an improper limitation to the present disclosure.

[0039] Figure 1 It is a block diagram of the steps of the method for evaluating the luminescence performance of the probe provided by the present invention;

[0040] Figure 2 It is a flowchart of the steps of the method for evaluating the luminescence performance of the probe provided by the present invention;

[0041] Figure 3 It is a schematic structural diagram of Fluo1 provided by the present invention;

[0042] Figure 4 It is a schematic diagram of the representative conformation 1 of Fluo1 in an aqueous solution provided by the present invention;

[0043] Figure 5 It is a schematic diagram of the representative conformation 2 of Fluo1 in an aqueous solution provided by the present invention;

[0044] Figure 6 It is a schematic diagram of the representative conformation 3 of Fluo1 in an aqueous solution provided by the present invention;

[0045] Figure 7 It is a schematic diagram of the representative conformation 4 of Fluo1 in an aqueous solution provided by the present invention;

[0046] Figure 8 It is a schematic diagram of the representative conformation 5 of Fluo1 in an aqueous solution provided by the present invention;

[0047] Figure 9 It is a schematic diagram of the representative conformation 6 of Fluo1 in an aqueous solution provided by the present invention;

[0048] Figure 10 It is a schematic diagram of the representative conformation 7 of Fluo1 in an aqueous solution provided by the present invention;

[0049] Figure 11 It is a schematic structural diagram of Fluo2 provided by the present invention;

[0050] Figure 12 It is a schematic structural diagram of Fluo3 provided by the present invention;

[0051] Figure 13 It is a schematic diagram of the representative conformation 1 of Fluo2 in an aqueous solution provided by the present invention;

[0052] Figure 14 It is a schematic diagram of the representative conformation 2 of Fluo2 in an aqueous solution provided by the present invention;

[0053] Figure 15 It is a schematic diagram of the representative conformation 3 of Fluo2 in an aqueous solution provided by the present invention;

[0054] Figure 16It is a schematic diagram of the representative conformation 4 of Fluo2 in aqueous solution provided by the present invention;

[0055] Figure 17 It is a schematic diagram of the representative conformation 1 of Fluo3 in aqueous solution provided by the present invention;

[0056] Figure 18 It is a schematic diagram of the representative conformation 2 of Fluo3 in aqueous solution provided by the present invention;

[0057] Figure 19 It is a schematic diagram of the representative conformation 3 of Fluo3 in aqueous solution provided by the present invention;

[0058] Figure 20 It is a schematic diagram of the representative conformation 4 of Fluo3 in aqueous solution provided by the present invention;

[0059] Figure 21 It is a schematic diagram of the probe luminescence performance evaluation system provided by the present invention. Detailed implementation manners

[0060] It should be noted that the following detailed description is exemplary and is intended to provide further illustration of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0061] It should be noted that the terms used herein are only for describing specific implementation manners and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular forms are also intended to include the plural forms. In addition, it should be understood that the terms "comprises" and "has" and any variations thereof are intended to cover non-exclusive inclusion. For example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units not clearly listed or inherent to these processes, methods, products or devices.

[0062] Without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other.

[0063] All data acquisition in this embodiment is based on compliance with laws and regulations and user consent, and is a legal application of the data.

[0064] Example 1

[0065] Please refer to the accompanying drawings of the specification Figure 1 and Figure 2 , Figure 1 It is a block diagram of the steps of the probe luminescence performance evaluation method provided by the present invention, Figure 2It is the flowchart of the steps of the method for evaluating the luminescence performance of the probe provided by the present invention. From Figure 1 and Figure 2 it can be seen that the method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe includes:

[0066] S1: Obtain the initial configuration of the near-infrared second-region molecular fluorescence probe in aqueous solution, perform molecular dynamics simulation on the initial configuration, and obtain multiple representative conformations of the probe in aqueous solution;

[0067] S2: Perform quantum chemical calculations on each representative conformation to obtain the first system energy in the stable state, the second system energy and the intensity parameter in the lowest singlet excited state of each representative conformation;

[0068] S3: Generate a comprehensive evaluation factor based on the first system energy, the second system energy and the intensity parameter;

[0069] S4: Rank the luminescence performance of the probe based on the comprehensive evaluation factor, and screen out the probe with the optimal performance.

[0070] Specifically, the molecular dynamics simulation of the initial configuration in S1 specifically includes:

[0071] S1.1: Construct a molecular structure model of the probe based on the initial configuration, convert the molecular structure model into a format compatible with the molecular dynamics simulation software, and generate a topology file suitable for molecular force field description;

[0072] S1.2: Define the three-dimensional space boundary of the simulation system, add water molecules to it, and form a simulation environment including the probe molecule and water molecules;

[0073] S1.3: Eliminate the high-energy configurations of the system through energy minimization, and then perform molecular dynamics simulation under the set time conditions, and use the clustering analysis method to screen out multiple representative conformations of the probe in water molecules.

[0074] Specifically, the clustering analysis method screens conformations by setting a cut-off value and retains the local environment information of the probe molecule and the water molecules around it.

[0075] In a specific embodiment, the molecular dynamics simulation based on the initial configuration of the NIR-II molecular fluorescence probe in aqueous solution specifically includes:

[0076] (1) Construct the structure model of the NIR-II molecular fluorescence probe in ChemDraw software, and use AmberTools to convert it into the.gro format, and at the same time generate its topology file under the GAFF force field;

[0077] (2) Define the simulation box in the GROMACS software and add water solvent to the box. The preferred box size is 6 nm × 6 nm × 6 nm, which includes 1 NIR-II molecular fluorescence probe and thousands of water molecules;

[0078] (3) Run energy minimization calculations and 20 ns of molecular dynamics simulations through GROMACS. The preferred simulation time step is 2 fs, and the temperature is set at 298.15 K.

[0079] In S1, the method for obtaining n representative conformations of the NIR-II molecular fluorescence probe in aqueous solution is the clustering analysis method. The preferred cutoff value does not exceed 0.1 Å, and the intermediate structure in the n cluster with a larger capacity is selected, and the water molecules within 5 Å around the NIR-II molecular fluorescence probe are selected as representative conformations for subsequent calculations.

[0080] Specifically, S2 includes:

[0081] S2.1: Based on the density functional method and the ONIOM model, the probe molecule and its solvent environment are divided into a high layer and a low layer, which are described by a high-precision quantum chemical theory model and a simplified force field model respectively. The first system energy of each representative conformation in the stable state is calculated through structural optimization.

[0082] S2.2: Based on the time-dependent density functional method and the ONIOM model, the probe molecule and its solvent environment are divided into a high layer and a low layer, which are described by a high-precision quantum chemical theory model and a simplified force field model respectively. The second system energy of each representative conformation in the lowest singlet excited state is calculated through excited state structural optimization, and the oscillator strength, that is, the intensity parameter, in the lowest singlet excited state is obtained simultaneously.

[0083] In a specific embodiment, the first system energy ( E a ) of each representative conformation in the stable state, the second system energy ( E b ) in the lowest singlet excited state, and the intensity parameter ( I ) are obtained through quantum chemical calculations, specifically including:

[0084] (1) Based on the density functional method and the ONIOM model, the NIR-II molecular fluorescence probe and the water molecules around it are set as the high layer and the low layer respectively, and are described by cam-b3lyp / 6-31g(d) and UFF force fields respectively. The energy corresponding to the structure of each representative conformation in the stable state, that is, the first system energy, is obtained through structural optimization in the GAUSSIAN 16 software. Ea ;

[0085] (2) Based on the time-dependent density functional theory and the ONIOM model, the NIR-II molecular fluorescence probe and the surrounding water molecules are set as the high layer and the low layer respectively, and are described by the cam-b3lyp / 6-31g(d) and UFF force fields respectively. In the GAUSSIAN 16 software, the energy corresponding to the structure of each representative conformation in the lowest singlet excited state, that is, the second system energy, is obtained through the lowest singlet excited state structure optimization. E b Meanwhile, the oscillator strength of the lowest singlet excited state, that is, the intensity parameter, is obtained. I .

[0086] Specifically, S3 includes:

[0087] S3.1: Calculate the energy difference between the first system energy E a and the second system energy E b ; E， ;

[0088] S3.2: Conduct a correlation analysis on the energy difference E and the intensity parameter I to generate a comprehensive evaluation factor through mathematical modeling X .

[0089] Specifically, S3.2 includes:

[0090] S3.2.1: Statistically analyze the intensity parameters n of I 1 , I 2 , I 3 ... I n and the energy parameters E 1 , E 2 , E 3 ... E n ;

[0091] S3.2.2: Construct an intensity matrix and an energy matrix , whose matrix elements are and respectively, where ;

[0092] S3.2.3: Multiply the matrix Iand E are added together to obtain matrix , and the matrix element , ;

[0093] S3.2.4: Using the row sum of each row of matrix C as the minuend and 2 n as the subtrahend, the difference is calculated to obtain the correction factor , ;

[0094] S3.2.5: Generate the comprehensive evaluation factor based on the above data.

[0095] Specifically, S4 includes: judging the luminescence performance of the probe based on the numerical value of the comprehensive evaluation factor. The larger the value, the better the luminescence performance. The molecular fluorescence probe with the largest value is the probe with the best performance.

[0096] In a specific embodiment, the NIR-II molecular fluorescence probe is named Fluo1, and the structure of Fluo1 can be known from Figure 3 .

[0097] Step 1: Perform molecular dynamics simulations based on the initial conformation of Fluo1 in aqueous solution to obtain 7 representative conformations of Fluo1 in an aqueous solution environment, specifically including:

[0098] (1) Construct the structural model of Fluo1 in ChemDraw software (as shown in Figure 3 ), and convert it to the.gro format using AmberTools, and simultaneously generate its topology file under the GAFF force field;

[0099] (2) Define a simulation box with a size of 6 nm × 6 nm × 6 nm in GROMACS software, and add water solvent to the box. The box contains 1 Fluo1 and 6994 water molecules;

[0100] (3) Run energy minimization calculations and 20 ns of molecular dynamics simulations through GROMACS, with a simulation time step of 2 fs and the temperature set at 298.15 K.

[0101] (4) Based on the results of the molecular dynamics simulations, set the cutoff value to 0.1 Å for clustering analysis, screen out the intermediate structures in the 7 clusters with larger capacities, and select the water molecules within 5 Å around Fluo1 and itself as the representative conformations (as shown in Figures 4 to 10 ) for subsequent calculations.

[0102] Step 2: Obtain the first system energy of each representative conformation at steady state through quantum chemical calculations (E a ), the second system energy in the lowest singlet excited state ( E b ), and the intensity parameter ( I ), specifically including:

[0103] (1) Based on the density functional method and the ONIOM model, Fluo1 and the surrounding water molecules are respectively set as the high layer and the low layer, and described by the cam-b3lyp / 6-31g(d) and UFF force fields respectively. The energy corresponding to the structure of each representative conformation in the stable state is obtained through structural optimization in the GAUSSIAN 16 software, which is the first system energy E a (see Table 1);

[0104] (2) Based on the time-dependent density functional method and the ONIOM model, Fluo1 and the surrounding water molecules are respectively set as the high layer and the low layer, and described by the cam-b3lyp / 6-31g(d) and UFF force fields respectively. The energy corresponding to the structure of each representative conformation in the lowest singlet excited state is obtained through the lowest singlet excited state structural optimization in the GAUSSIAN 16 software, which is the second system energy E b (see Table 1), and at the same time, the oscillator strength of the lowest singlet excited state, that is, the intensity parameter I (see Table 1);

[0105] Table 1 The first system energy of the representative conformations of Fluo1 E a (unit: eV), the second system energy E b (unit: eV), the energy parameter E (unit: eV), and the intensity parameter I (unit: a.u.)

[0106]

[0107] Step 3: Calculate the evaluation factors based on the obtained first system energy ( E a ), the second system energy ( E b ), and the intensity parameter ( I ), specifically including:

[0108] (1) Calculate the energy parameter E a according to the first system energy E b and the second system energy of each representative conformation (see Table 1);

[0109] (2) Statistically analyze the intensity parameters of 7 representative conformations I 1 = 0.452, I 2 = 0.571, I 3 = 0.529, I 4 = 0.398, I 5 = 0.414 ，I 6 = 0.456 ，I 7 = 0.496 and the energy parameters E 1 = 1.978, E 2 = 2.152, E 3 = 2.701, E 4 = 2.887, E 5 = 2.309 ，E 6 = 2.165 ，E 7 = 2.435;

[0110] (3) Construct an intensity matrix with as the matrix elements, and construct an energy matrix with , and as the matrix elements ;

[0111] (4) Add the matrices I and E to get ;

[0112] (5) Use the row sum of each row of the matrix C as the minuend, and 2 × 7 as the subtrahend, and calculate the difference to obtain the correction factor

[0113]

[0114] (6) Calculate the evaluation factor of Fluo1 based on the above data

[0115] .

[0116] Step 4: Determine the luminescence performance of the NIR-II molecular fluorescence probe through the evaluation factor. Specifically, the luminescence performance evaluation factor of Fluo1 is 1.174.

[0117] In a specific embodiment, two NIR-II molecular fluorescence probes are respectively named Fluo2 and Fluo3, and from Figure 11 the structure of Fluo2 can be known, and from ​ the structure of Fluo3 can be known.

[0118] Step 1: Perform molecular dynamics simulations based on the initial configurations of Fluo2 and Fluo3 in aqueous solution to obtain 4 representative conformations of Fluo2 and Fluo3 in the aqueous solution environment, as shown in ​ and ​ respectively, specifically including:

[0119] (1) Construct the structural models of Fluo2 and Fluo3 in ChemDraw software (as shown in ​ and ​ respectively), and convert them into the.gro format using AmberTools, and simultaneously generate the topology files of Fluo2 and Fluo3 under the GAFF force field;

[0120] (2) Define a simulation box with a size of 6 nm × 6 nm × 6 nm in GROMACS software, and add water solvent to the box. The box contains 1 Fluo2 and 6994 water molecules, or 1 Fluo3 and 6990 water molecules;

[0121] (3) Run energy minimization calculations and 20 ns of kinetic simulations through GROMACS. The simulation time step is 2 fs, and the temperature is set at 298.15 K.

[0122] (4) Based on the kinetic simulation results of Fluo2 and Fluo3, set the cutoff value to 0.03 Å for clustering analysis, respectively screen out the intermediate structures in the 4 clusters with larger capacities, and select the water molecules within 5 Å around Fluo2 (or Fluo3) and itself as representative conformations for subsequent calculations.

[0123] Step 2: Obtain the first system energy of each representative conformation at the steady state through quantum chemical calculations ( E a), the second system energy in the lowest singlet excited state ( E b ), and the intensity parameter ( I ), specifically including:

[0124] (1) Based on the density functional method and the ONIOM model, Fluo2 (or Fluo3) and the surrounding water molecules are respectively set as the high layer and the low layer, and are described by the cam-b3lyp / 6-31g(d) and UFF force fields respectively. The energy corresponding to the structure of each representative conformation in the stable state is obtained through structural optimization in the GAUSSIAN 16 software, which is the first system energy E a (see Table 2);

[0125] (2) Based on the time-dependent density functional method and the ONIOM model, Fluo2 (or Fluo3) and the surrounding water molecules are respectively set as the high layer and the low layer, and are described by the cam-b3lyp / 6-31g(d) and UFF force fields respectively. The energy corresponding to the structure of each representative conformation in the lowest singlet excited state is obtained through the lowest singlet excited state structural optimization in the GAUSSIAN 16 software, which is the second system energy E b (see Table 2), and at the same time, the oscillator strength of the lowest singlet excited state, that is, the intensity parameter I (see Table 2);

[0126] Table 2 The first system energy of the representative conformations of Fluo2 and Fluo3 E a (unit: eV), the second system energy E b (unit: eV), the energy parameter E (unit: eV), and the intensity parameter I (unit: a.u.)

[0127]

[0128] Step 3: Calculate the evaluation factor based on the obtained first system energy ( E a ), the second system energy ( E b ), and the intensity parameter ( I ), specifically including:

[0129] (1) Calculate the energy parameter E a according to the first system energy E b and the second system energy of each representative conformation (see Table 2);

[0130] (2) Statistically analyze the intensity parameters of each representative conformation of Fluo2 I 1 = 0.540, I 2 = 0.613, I 3 = 0.698, I 4 = 0.566 and the energy parameter E 1 = 2.482, E 2 = 2.304, E 3 = 2.270, E 4 = 1.531. Meanwhile, statistically analyze the intensity parameters of each representative conformation of Fluo3 I' 1 = 0.750, I' 2 = 0.612, I' 3 = 0.644, I' 4 = 0.676 and the energy parameter E' 1 = 2.709, E' 2 = 1.676, E' 3 = 1.775, E' 4 = 2.675;

[0131] (3) Construct the intensity matrix and of Fluo2 with and as matrix elements. Meanwhile, construct the intensity matrix and of Fluo3 with and .

[0132] (4) Add the matrices I and E to obtain the matrix of Fluo2. Meanwhile, add the matrices and to obtain the matrix .

[0133] (5) Using the matrix Cand For each row, the row sum is used as the minuend, 2×4 is used as the subtrahend, and the difference is used as the correction factor P 1 = -0.06, P 2 = -0.33, P 3 = -0.76, P 4 = 1.88 and P 1' = -1.16, P 2' = 1.64, P 3' = 1.16, P 4' = -0.74;

[0134] (6) Calculate the evaluation factors of Fluo2 and Fluo3 based on the above data, which are and .

[0135] Step 4: Determine the luminescence performance of the NIR-II molecular fluorescence probe through the evaluation factor, and screen out the probe with the best performance. Specifically, the luminescence performance evaluation factors of Fluo2 and Fluo3 are 1.272 and 1.330 respectively, indicating that Fluo3 has better luminescence performance. Therefore, compared with Fluo2, Fluo3 is the probe with the best screened luminescence performance.

[0136] Example Two

[0137] As ​ shown, this example provides a system for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe, including:

[0138] A conformation acquisition unit for obtaining the initial conformation of the near-infrared second-region molecular fluorescence probe in aqueous solution, performing molecular dynamics simulation on the initial conformation, and obtaining multiple representative conformations of the probe in aqueous solution;

[0139] An evaluation parameter acquisition unit for performing quantum chemical calculations on each representative conformation to obtain the first system energy of each representative conformation in the stable state, the second system energy in the lowest singlet excited state, and the intensity parameter;

[0140] An evaluation factor calculation unit for generating a comprehensive evaluation factor based on the first system energy, the second system energy, and the intensity parameter;

[0141] An evaluation and screening unit for ranking the luminescence performance of the probe based on the comprehensive evaluation factor and screening out the probe with the best performance.

[0142] Example Three

[0143] This embodiment provides an evaluation device for the luminescence performance of a near-infrared second-region molecular fluorescence probe. The device includes a memory and a processor. The memory is used to store computer programs. The processor is used to implement the above-mentioned method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe when executing the computer programs.

[0144] Among them, the processor is connected to the memory. One or more of the above computer programs are stored in the memory. When the electronic device runs, the processor executes one or more computer programs stored in the memory, so that the electronic device executes the method described in the first embodiment above.

[0145] It should be understood that in this embodiment, the processor may be a central processing unit (CPU), and the processor may also be other general-purpose processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), off-the-shelf programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor may be a microprocessor, or the processor may also be any conventional processor, etc.

[0146] The memory may include a read-only memory and a random access memory, and provide instructions and data to the processor. A part of the memory may also include a non-volatile random access memory. For example, the memory may also store information about the device type.

[0147] In the implementation process, each step of the above method may be completed by the integrated logic circuit in the hardware of the processor or the instructions in the form of software.

[0148] The method in the first embodiment may be directly embodied as being executed by the hardware processor, or completed by a combination of the hardware and software modules in the processor. The software module may be located in a mature storage medium in the art such as a random access memory, a flash memory, a read-only memory, a programmable read-only memory, or an electrically erasable programmable memory, a register, etc. This storage medium is located in the memory, and the processor reads the information in the memory and combines its hardware to complete the steps of the above method. To avoid repetition, it will not be described in detail here.

[0149] Those of ordinary skill in the art can realize that, in combination with the units and algorithm steps of the examples described in this embodiment, they can be implemented by electronic hardware or a combination of computer software and electronic hardware. Whether these functions are executed in a hardware or software manner depends on the specific application and design constraints of the technical solution. Professional technicians can use different methods to implement the described functions for each specific application, but such implementation should not be considered to exceed the scope of the present invention.

[0150] Embodiment 4

[0151] A computer-readable storage medium provided by another embodiment of the present invention stores a computer program, which, when executed by a processor, implements the method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe as described above.

[0152] Those of ordinary skill in the art can understand that all or part of the processes in the methods of the above embodiments can be completed by instructing relevant hardware through a computer program. The program can be stored in a computer-readable storage medium. When the program is executed, it can include the processes of the embodiments of the above methods. Among them, the storage medium can be a magnetic disk, an optical disk, a read-only memory (ROM), or a random access memory (RAM), etc. In this application, the units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed to multiple network units. Some or all of the units can be selected according to actual needs to achieve the purpose of the solution of the embodiment of the present invention. In addition, the functional units in each embodiment of the present invention can be integrated into one processing unit, or each unit can exist physically alone, or two or more units can be integrated into one unit. The above integrated units can be implemented in the form of hardware or in the form of software functional units.

[0153] Although the present invention is disclosed as above, the protection scope of the present invention is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present invention, and these changes and modifications will all fall within the protection scope of the present invention.

Claims

1. A method for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe, characterized in that, including: S1: Obtain the initial configuration of the near-infrared second-region molecular fluorescence probe in aqueous solution, perform molecular dynamics simulation on the initial configuration, and obtain multiple representative conformations of the probe in aqueous solution; S2: Perform quantum chemical calculations on each representative conformation to obtain the first system energy of each representative conformation in the stable state, the second system energy and intensity parameters in the lowest singlet excited state; S3: Generate a comprehensive evaluation factor based on the first system energy, the second system energy and the intensity parameters; The S3 includes: S3.1: Calculate the first system energy E a and the second system energy E b the energy difference between them E ; S3.2: Correlate the energy difference E with the intensity parameter I to perform correlation analysis, and generate a comprehensive evaluation factor X； The S3.2 includes: S3.2.1: Statistic n intensity parameters of I 1 , I 2 , I 3 ... I n and energy parameters E 1 , E 2 , E 3 ... E n ; S3.2.2: Construct the strength matrix and the energy matrix , whose matrix elements are respectively and , where ; S3.2.3: Add the matrices I and E to obtain the matrix , with matrix elements , ; S3.2.4: Using the sum of each row of the matrix C as the minuend, and using 2 n as the subtrahend, calculate the difference to obtain the correction factor , ; S3.2.5: Generate a comprehensive evaluation factor based on the above data ; S4: Rank the luminescence performance of the probe based on the comprehensive evaluation factor, and screen out the probe with the best performance.

2. The evaluation method for the luminescence performance of the near-infrared second-region molecular fluorescence probe according to claim 1, wherein In the S1, performing the molecular dynamics simulation on the initial configuration specifically includes: S1.1: Construct a molecular structure model of the probe based on the initial configuration, convert the molecular structure model into a format compatible with the molecular dynamics simulation software, and generate a topology file suitable for molecular force field description; S1.2: Define the three-dimensional space boundary of the simulation system, add water molecules to it, and form a simulation environment including the probe molecule and water molecules; S1.3: Eliminate the high-energy configurations of the system through energy minimization, and then perform molecular dynamics simulation under the set time conditions, and use the clustering analysis method to screen out multiple representative conformations of the probe in water molecules.

3. The method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe according to claim 2, wherein The clustering analysis method screens conformations by setting a cut-off value and retains the local environment information of the probe molecule and the water molecules around it.

4. The method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe according to claim 1, wherein, The S2 includes: S2.1: Based on the density functional method and the ONIOM model, divide the probe molecule and its solvent environment into a high layer and a low layer, and describe them with a high-precision quantum chemical theory model and a simplified force field model respectively. Calculate the first system energy of each representative conformation in the stable state through structure optimization; S2.2: Based on the time-dependent density functional method and the ONIOM model, divide the probe molecule and its solvent environment into a high layer and a low layer, and describe them with a high-precision quantum chemical theory model and a simplified force field model respectively. Calculate the second system energy of each representative conformation in the lowest singlet excited state through excited state structure optimization, and at the same time obtain the oscillator strength in the lowest singlet excited state, that is, the intensity parameter.

5. The method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe according to claim 1, wherein, The S4 includes: Judging the luminescence performance of the probe based on the numerical value of the comprehensive evaluation factor. The larger the numerical value, the better the luminescence performance. The molecular fluorescence probe with the largest numerical value is the probe with the best performance.

6. A system for evaluating the luminescence performance of a near-infrared second-region molecular fluorescence probe, characterized in that, including: A conformation acquisition unit for obtaining the initial configuration of the near-infrared second-region molecular fluorescence probe in aqueous solution, performing molecular dynamics simulation on the initial configuration, and obtaining multiple representative conformations of the probe in aqueous solution; An evaluation parameter acquisition unit for performing quantum chemical calculations on each representative conformation to obtain the first system energy of each representative conformation in the stable state, the second system energy and intensity parameters in the lowest singlet excited state; An evaluation factor calculation unit for generating a comprehensive evaluation factor based on the first system energy, the second system energy and the intensity parameters; including: Calculate the energy of the first system E a and the energy of the second system E b to obtain the energy difference E ; Associate the energy difference E with the intensity parameter I to conduct a correlation analysis and generate a comprehensive evaluation factor through mathematical modeling X； including: Statistics n Strength parameters of I 1 , I 2 , I 3 ... I n and energy parameters E 1 , E 2 , E 3 ... E n ; Construct the intensity matrix and the energy matrix , whose matrix elements are respectively and , where ; Add the matrices I and E to obtain the matrix , with matrix elements , ; Using a matrix C Take the row sum of each row as the minuend, and use 2 n as the subtrahend to calculate the difference to obtain the correction factor , ; Generate a comprehensive evaluation factor based on the above data ; An evaluation and screening unit for ranking the luminescence performance of the probe based on the comprehensive evaluation factor and screening out the probe with the best performance.

7. An evaluation device for the luminescence performance of a near-infrared second-region molecular fluorescence probe, characterized in that, The device includes a memory and a processor; the memory is used for storing a computer program; the processor is used for implementing the method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe according to any one of claims 1 to 5 when executing the computer program.

8. A computer-readable storage medium, characterized in that, A computer program is stored on the storage medium, and when the computer program is executed by a processor, the method for evaluating the luminescence performance of the near-infrared second-region molecular fluorescence probe according to any one of claims 1 to 5 is implemented.

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