Method for analyzing vibration mode and weak interaction of veratric acid and derivatives thereof based on terahertz spectrum and DFT theory

Abstract

Veratric acid is one of main benzoic acids separated from vegetables and fruits, and has certain anti-inflammatory activity. The vanillic acid is one of antioxidants from herbal medicines and fruits and has a heart protection effect as a phenolic compound, and the vanillic acid and the phenolic compound have similar molecular structures. The terahertz time-domain spectroscopy (THz-TDS) is used for measuring the absorption spectrum of the veratric acid and the vanillic acid in the range of 0.5-3.0 THz, the corresponding theoretical spectrum is calculated and predicted through the solid density functional theory (ss-DFT), and the absorption spectrum and the theoretical spectrum are highly matched. The vibration modes and weak interactions of veratric acid and vanillic acid are analyzed using a vibration mode automatic correlation determination method and an interaction area indicator (IRI), respectively. According to the method, THz-TDS and ss-DFT are combined, and the vibration mode and weak interaction of veratric acid and vanillic acid can be analyzed, so that reference is provided for future drug design.

Description

Technical Field

[0001] The present invention belongs to the technical field of terahertz spectroscopy detection, and particularly relates to a method for analyzing vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory. Background Art

[0002] Drug safety is a crucial foundation for safeguarding public health. Drugs play a vital role in treating diseases and improving quality of life, but improper use can cause serious side effects. Therefore, ensuring the proper use of drugs and identifying and studying these substances are crucial for drug quality assurance and patient safety. Veratric acid, a benzoic acid extracted from plants and fruits, has been reported to exhibit antimicrobial, anti-inflammatory, and other important therapeutic activities. Veratric acid is also used to treat skin conditions because it protects against UVB-induced skin damage. Furthermore, studies have shown that veratric acid possesses significant antihypertensive, anti-inflammatory, and antioxidant properties. Vanillic acid, a phenolic compound found in herbs, fruits, whole grains, juices, beer, and wine, exhibits various therapeutic properties, including cardioprotection. Furthermore, vanillic acid has potential hepatoprotective effects, inhibiting liver fibrosis in injured livers. The chemical structures of veratric acid and vanillic acid are highly similar. Vanillic acid differs from veratric acid in that a hydroxyl group replaces the methoxy group. Both vanillic acid and vanillic acid are white to pale yellow powders at room temperature. Currently, researchers' detection methods for veratric acid and vanillic acid mainly include LC-MS, NMR, and ESI-MS, but these methods do not conduct in-depth analysis at the molecular level.

[0003] Terahertz waves refer to electromagnetic waves with a frequency range of 0.1-10 THz (wavelength of 3000-30 μm). Terahertz time-domain spectroscopy (THz-TDS) is a vibrational spectroscopy technique and a powerful analytical tool for detecting non-covalent interactions (such as hydrogen bonds). Currently, THz-TDS technology has been widely used as a technology to assist in the study of solid drug crystallography and polymorphism. The widespread application of THz-TDS technology is due to the ability of terahertz radiation to detect intermolecular interactions and its ability to penetrate polymers. In recent years, terahertz wave detection technology has developed rapidly, and combining it with quantum chemical calculations has become an effective method for detecting and analyzing drug crystal structures and weak intermolecular interactions. Summary of the Invention

[0004] To address the above issues, the present invention provides a method for analyzing the vibrational modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory. To achieve the above objectives, the present invention adopts the following technical solutions:

[0005] A method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory comprises the following steps:

[0006] Step 1: Sample preparation: Grind the drug sample in a mortar and use a tablet press to make a 1 mm thick sample.

[0007] Step 2: Measure THz time-domain spectra. Use a THz-TDS system to measure the time-domain spectra of the two samples, and then convert the time-domain spectra into frequency-domain spectra through fast Fourier transform.

[0008] Step 3: Calculate the theoretical THz spectrum. After optimizing the structures of veratric acid and vanillic acid, perform frequency calculations to obtain the theoretical THz absorption spectrum.

[0009] Step 4: Comparison of theoretical and experimental spectra. Compare and analyze the experimental and theoretical spectra of veratric acid and vanillic acid.

[0010] Step 5: Analyze vibrational modes. Assign vibrational modes to the characteristic peaks of the absorption spectra of veratric acid and vanillic acid.

[0011] Step 6: Analyze weak interactions. Analyze the weak interactions between veratric acid and vanillic acid, and visualize their intramolecular and intermolecular interactions.

[0012] Preferably, the tablet press used in step 1 is a FW-4A powder tablet press.

[0013] Preferably, the THz-TDS system used in step 2 is a CCT-1800 terahertz time-domain spectrometer independently developed by China Huaxun Ark Technology Co., Ltd.

[0014] Preferably, the quantum chemical calculation software used in the experimental process in step 3 is CP2K.

[0015] Preferably, the theoretical spectrum is calculated in step 3 using a PBE-D3 density functional with dispersion correction and a 6-311G** basis set.

[0016] Preferably, the vibration mode assignment method in step five is vibration mode automatic correlation determination (VMARD).

[0017] Preferably, the weak interaction analysis method used in step six is the interaction region indicator function (IRI).

[0018] Through the above solution, compared with the prior art, the present invention has the following beneficial effects:

[0019] The present invention provides a method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory. The absorption spectra of veratric acid and vanillic acid in the range of 0.5-3.0 THz are measured using terahertz time-domain spectroscopy (THz-TDS), and the corresponding theoretical spectra are predicted by computational chemistry methods. The theoretical spectra of veratric acid and vanillic acid are highly consistent with the experimental spectra. The vibration modes of veratric acid and vanillic acid are then assigned, and the weak interactions between the two are analyzed using an interaction region indicator (IRI). The present invention combines THz-TDS technology with solid-state DFT and analyzes their vibration modes and weak interactions, which can provide reference value for future drug design. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below based on specific embodiments of the present invention in conjunction with the accompanying drawings, wherein:

[0021] Figure 1 This is a comparison diagram of the terahertz experimental and calculated spectra of veraric acid of the present invention. The experimental spectrum shows that the characteristic peaks of veraric acid are 1.56THz, 2.03THz and 2.49THz, and the calculated spectrum shows that the characteristic peaks of veraric acid are 1.65THz, 1.84THz and 2.53THz.

[0022] Figure 2 This is a comparison diagram of the terahertz experimental and calculated spectra of vanillic acid of the present invention. The experimental spectrum shows that the characteristic peaks of vanillic acid are 1.72THz, 2.23THz and 2.72THz, and the calculated spectrum shows that the characteristic peaks of veratric acid are 1.09THz, 1.72THz and 2.62THz.

[0023] Figure 3 This is the IRI weak interaction analysis result of the veratric acid of the present invention.

[0024] Figure 4 This is the IRI weak interaction analysis result of the vanillic acid of the present invention. DETAILED DESCRIPTION

[0025] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operating process. Obviously, the described embodiment is only a part of the embodiment of the present invention, not all embodiments. It should be understood that the specific embodiments described here are only used to illustrate the present invention.

[0026] The specific implementation steps of the present invention are as follows:

[0027] 1. Experimental Spectra

[0028] (1) Sample preparation. The veracid and vanillic acid powder crystals used in this experiment have a purity of more than 99% and can be used directly without additional purification. First, the sample was accurately weighed using a FA2004B electronic analytical balance; then, the pressure parameter of the FW-4A tablet press was set to 10 MPa. Under this pressure condition, the mixed material was pressed into a sheet sample with a diameter of 13 mm and a mass of 200 mg, while ensuring that the surface of the sample was smooth and free of cracks; finally, the prepared sample was placed in a vacuum oven set at 50°C and dried for 2 hours to remove the moisture contained in the sample.

[0029] (2) Spectral measurement. In the experimental phase, the terahertz time-domain spectra of veratric acid and vanillic acid in the 0.5-3.0THz frequency band were measured using a terahertz time-domain spectrometer CCT-1800. The spectrometer is equipped with a 780nm ultrashort pulse fiber laser and has a high signal-to-noise ratio of over 70dB. In the experiment, the laser beam is divided into pump light and probe light by a cubic beam splitter, and the two are responsible for the generation and detection of terahertz waves respectively. To ensure the reliability of the experimental data, the terahertz optical path is always kept in a closed state throughout the experimental process, and dry nitrogen is continuously filled to keep the relative humidity in the sample chamber below 2%, thereby effectively reducing the interference of moisture in the air on the absorption of terahertz waves.

[0030] (3) Obtaining frequency domain signals. The obtained time domain signals are converted into frequency domain signals through fast Fourier transform to obtain frequency domain absorption spectra containing more effective information.

[0031] 2. Calculation of Spectra

[0032] (1) Optimize the geometric structure.

[0033] Geometry optimization was performed using crystal structure data from the Cambridge Crystallographic Data Center. A dispersion-corrected PBE-D3 density functional and the 6-311G** basis set were used. The goal of the geometry optimization was to obtain the lowest-energy architecture with no imaginary frequencies. This structure is the most realistic, and the calculated spectrum closely matches the actual spectrum.

[0034] (2) Frequency calculation. Use the geometry obtained from the optimization to perform the frequency calculation. The basis set and functional used in the frequency calculation must be consistent with the geometry optimization. The frequency calculation result does not contain imaginary frequencies, and the spectrum is the desired calculated spectrum.

[0035] 3. Spectral Comparison

[0036] (1) Comparison of experimental and calculated spectra of veratric acid. Figure 1This is a comparison of the calculated and experimental spectra of veratric acid. It can be seen that the experimental spectrum has three characteristic peaks at 1.56THz, 2.03THz, and 2.49THz, while the calculated spectrum has three characteristic peaks at 1.65THz, 1.84THz, and 2.53THz. The 1.56THz absorption peak in the experimental spectrum corresponds to the 1.65THz absorption peak in the calculated spectrum, the 2.03THz absorption peak in the experimental spectrum corresponds to the 1.84THz absorption peak in the calculated spectrum, and the 2.49THz absorption peak in the experimental spectrum corresponds to the 2.53THz absorption peak in the calculated spectrum.

[0037] (2) Comparison of experimental and calculated spectra of vanillic acid. Figure 2 This is a comparison of the calculated and experimental spectra of vanillic acid. The experimental spectrum has three characteristic peaks at 1.72 THz, 2.23 THz, and 2.72 THz, which roughly match the calculated spectrum's three characteristic peaks at 1.09 THz, 1.72 THz, and 2.62 THz. The 1.72 THz absorption peak in the experimental spectrum corresponds to the 1.72 THz absorption peak in the calculated spectrum, and the 2.23 THz absorption peak in the experimental spectrum corresponds to the 2.72 THz absorption peak in the calculated spectrum. The discrepancy between the experimental and calculated spectra can be attributed to temperature errors.

[0038] 4. Results Analysis

[0039] (1) Assignment of vibration modes of veratric acid and vanillic acid.

[0040] The results of the vibrational mode assignments for veratric acid are shown in Table 1, and those for vanillic acid are shown in Table 2. VMARD assignments indicate that the absorption peak for veratric acid at 1.65 THz is primarily due to out-of-plane angle bending, while the absorption peaks at 1.84 THz and 2.53 THz are primarily due to dihedral angle torsion. The absorption peak for vanillic acid at 1.09 THz is primarily due to out-of-plane angle bending, the absorption peak at 1.72 THz is primarily due to dihedral angle torsion, and the absorption peak at 2.72 THz is primarily due to bond angle bending.

[0041] (2) Analysis of weak interaction between veratric acid and vanillic acid.

[0042] This study used the interaction region indicator (IRI) function. The function is defined as follows:

[0043]

[0044] Here, a is set to 1.1, an empirical parameter that can adapt to most systems and achieve optimal results. represents the electron density, and a function is also introduced, where represents the second largest eigenvalue of the electron density Hessian matrix.

[0045] The isosurface diagrams of veratric acid and vanillic acid were drawn using VMD software, as shown in the figure. Figure 3 and Figure 4 The green isosurfaces represent van der Waals interactions, and the blue isosurfaces between H and O atoms represent hydrogen bonding regions. It can be seen intuitively that the crystal structures of both veratric acid and vanillic acid contain not only chemical bonds but also van der Waals interactions and hydrogen bonds.

[0046] Table 1 Veratrylic acid vibration mode assignment results

[0047]

[0048] Table 2 Vanillic acid vibration mode assignment results

[0049]

[0050] a ν, δ, γ, and τ represent bond stretching, bond angle bending, out-of-plane angle bending, and dihedral angle torsion, respectively. The percentages in parentheses indicate the contribution of the vibrational modes.

Claims

1. A method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory, characterized in that: The following steps are involved: Step 1: Sample preparation: Grind the drug sample in a mortar and use a tablet press to make a 1 mm thick sample. Step 2: Measure THz time-domain spectra. Use a THz-TDS system to measure the time-domain spectra of the two samples, and then convert the time-domain spectra into frequency-domain spectra through fast Fourier transform. Step 3: Calculate the theoretical THz spectrum. After optimizing the structures of veratric acid and vanillic acid, perform frequency calculations to obtain the theoretical THz absorption spectrum. Step 4: Comparison of theoretical and experimental spectra. Compare and analyze the experimental and theoretical spectra of veratric acid and vanillic acid. Step 5: Analyze vibrational modes. Assign vibrational modes to the characteristic peaks of the absorption spectra of veratric acid and vanillic acid. Step 6: Analyze weak interactions. Analyze the weak interactions between veratric acid and vanillic acid, and visualize their intramolecular and intermolecular interactions.

2. The method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory according to claim 1, characterized in that: The tablet press used in step 1 is a FW-4A powder tablet press.

3. The method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory according to claim 1, characterized in that: The THz-TDS system used in step 2 is the CCT-1800 terahertz time-domain spectrometer independently developed by China Huaxun Ark Technology Co., Ltd.

4. The method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory according to claim 1, characterized in that: The quantum chemical calculation software used in the experimental process in step three is CP2K.

5. The method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory according to claim 1, characterized in that: In step 3, the theoretical spectrum was calculated using the PBE-D3 density functional with dispersion correction and the 6-311G** basis set.

6. The method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory according to claim 1, characterized in that: The vibration mode assignment method described in step five is vibration mode automatic correlation determination (VMARD).

7. The method for analyzing the vibration modes and weak interactions of veratric acid and its derivatives based on terahertz spectroscopy and DFT theory according to claim 1, characterized in that: The weak interaction analysis method used in step six is the interaction region indicator function (IRI).

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