A method for promoting rapid co-crystallization of liquid sulfur-containing compounds by using a ternary mercury crystallization partner and application thereof

Abstract

The application provides a method for promoting rapid co-crystallization of liquid sulfur-containing compounds by using a trinuclear mercury complex and application thereof, and belongs to the technical field of crystal engineering.The trinuclear mercury complex is mixed with a liquid sulfur-containing compound to form a host-guest mixed liquid, then the mixed liquid is added dropwise in the form of liquid drops on the surface of a transparent substrate, and the liquid drops are naturally volatilized in an open environment at room temperature to obtain host-guest co-crystal crystals which can be used for single crystal X-ray diffraction test.The trinuclear mercury complex is used to realize directional interaction with the sulfur-containing guest, and the sulfur-containing liquid guest and the trinuclear mercury complex are formed into a micro-drop system on the transparent substrate, so that the system is rapidly volatilized, enriched, nucleated and grown in the open environment at room temperature, and thus the host-guest co-crystals which can be used for single crystal X-ray diffraction test are obtained within several minutes to tens of minutes.The method has the advantages of rapid operation and wide adaptability.

Description

Technical Field

[0001] This invention belongs to the field of crystal engineering technology, and in particular relates to a method and application of a trinuclear mercury crystallization chaperone to promote the rapid co-crystallization of liquid sulfur-containing compounds. Background Technology

[0002] Single-crystal X-ray diffraction is a reliable method for determining the three-dimensional structure of organic molecules, pharmaceutical intermediates, natural products, and functional molecules. However, this technique is highly dependent on obtaining high-quality single crystals. Many liquid sulfur-containing compounds, such as thioethers, thiols, dithiols, disulfides, sulfoxides, and highly sterically hindered aromatic sulfur-containing derivatives, have large differences in volatility, high molecular flexibility, high viscosity, weak intermolecular orientation, or are prone to dynamic transformation. Conventional slow volatilization, liquid-liquid diffusion, and cooling crystallization methods are difficult to use to obtain single crystals with good diffraction quality in a short time.

[0003] Existing crystallization-assisted strategies typically rely on methods such as salt formation, derivatization, seed induction, inclusion of the host, or adsorption into porous crystals. While these methods are effective in some systems, they also suffer from limitations such as limited applicability, complex sample pretreatment, the need for lengthy screening processes, incompatibility with small quantities or unstable liquid samples, and difficulty in capturing rapidly generated or dynamically transformed products. In particular, for low-volatility, high-viscosity liquid sulfur-containing guests, it is difficult to fully mix the sample with the crystallization aid; for volatile liquid sulfur-containing guests, the spreading, volatilization, and nucleation processes of the sample on the glass surface are difficult to control, easily resulting in oily residues, microcrystals, amorphous deposits, or untestable crystal agglomerations.

[0004] Therefore, there is an urgent need for a rapid crystallization method that is simple to operate, fast, consumes little sample, is highly adaptable to liquid sulfur-containing compounds, and can directly produce crystals that can be used for single-crystal X-ray diffraction testing. Summary of the Invention

[0005] To address the challenges of crystallizing liquid sulfur-containing compounds, the lengthy time required for conventional crystallization, the difficulty in homogenizing low-volatility or high-viscosity samples, the difficulty in stabilizing nucleation of volatile samples, and the difficulty in timely capturing the structure of dynamic sulfur-containing systems, this invention proposes a method and application for promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallization chaperone. This method utilizes a trinuclear mercury complex as a crystallization chaperone and promotes the rapid formation of host-guest co-crystallization of liquid sulfur-containing compounds in an open environment at room temperature, which can be used for single-crystal X-ray diffraction testing.

[0006] To achieve the above objectives, the present invention provides the following technical solution: This invention provides a method for promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallization chaperone, comprising the following steps: The trinuclear mercury crystallization chaperone is mixed with a liquid sulfur-containing compound (also known as a liquid sulfur-containing guest) to form a host-guest mixture; The host-guest mixture is dropped onto the surface of a transparent substrate in the form of droplets. The transparent substrate was placed in an open environment at room temperature to allow the droplets to evaporate naturally, resulting in a host-guest eutectic crystal. The trinuclear mercury crystallizer is a trinuclear mercury complex with a planar trinuclear mercury structure that can undergo directional mercury-sulfur interactions with sulfur-containing guests.

[0007] Furthermore, the trinuclear mercury crystallization chaperone is a trinuclear phenylmercury complex (Hg3Ph3, abbreviated as Hg3), with the following structural formula: This crystallization companion can dissolve in liquid sulfur-containing compounds (sulfur-containing liquid guests) or in organic cosolvents such as toluene, and induces the sulfur-containing guests to form ordered host-guest eutectics during droplet evaporation.

[0008] Furthermore, the liquid sulfur-containing compound is selected from volatile sulfur-containing liquids capable of directly dissolving the trinuclear mercury crystallizer, or low-volatility or high-viscosity sulfur-containing liquids requiring the addition of a volatile organic co-solvent: The volatile sulfur-containing liquid capable of directly dissolving the trinuclear mercury crystallizer is selected from at least one of the following: n-butyl sulfide, diethyl disulfide, isopropyl disulfide, dimethyl trisulfide, ethyl methyl sulfoxide, propyl methyl sulfoxide, 2-bromothiophene, anisole, 4-fluoroanisole, 2-methoxyanisole, 2-methylthiopyridine, 3-methyl-2-thiazolidinone, 2,3-butanediol, 1-methoxy-2-(methylthio)benzene, p-toluene methyl sulfide, and ethyl methyl sulfide. The low-volatility or high-viscosity sulfur-containing liquid that requires the addition of a volatile organic co-solvent is selected from at least one of 3-methylsulfinylpropanol, 2-chloroethylphenyl sulfide, phenyl butyl sulfide, 1,5-pentanedithiol, 1,8-octanedithiol, and diethyl sulfoxide.

[0009] Furthermore, the volatile organic co-solvent is at least one of toluene, dichloromethane, and chloroform; preferably, the volatile organic co-solvent is toluene.

[0010] Furthermore, the ratio of the volatile organic co-solvent to the trinuclear mercury crystallization chaperone is (0.1~1) mL: 5 mg.

[0011] Furthermore, the ratio of the trinuclear mercury crystallization chaperone to the liquid sulfur-containing compound is 5 mg: (20~500) μL.

[0012] Furthermore, the volume of the droplet is 10~100μL.

[0013] Furthermore, the transparent substrate is a glass plate, a glass slide, or a quartz plate.

[0014] This invention utilizes the directional interaction between a trinuclear mercury complex and a sulfur-containing guest to form a micro-droplet system of the sulfur-containing liquid guest and a trinuclear mercury crystallization chaperone on a transparent substrate. This system allows for rapid volatilization, enrichment, nucleation, and growth in an open environment at room temperature, resulting in a host-guest cocrystal suitable for single-crystal X-ray diffraction testing within minutes to tens of minutes. For liquid sulfur-containing compounds with different volatility and viscosity, this invention provides solvent-free rapid crystallization methods and organic solvent-assisted rapid crystallization methods, specifically: When the liquid sulfur-containing compound is a volatile sulfur-containing liquid (including at least one of short-chain sulfides, low molecular weight disulfides, low molecular weight sulfoxides, volatile aromatic sulfides, and short-chain thiols) capable of directly dissolving the trinuclear mercury crystallizer, the method for promoting rapid co-crystallization of the liquid sulfur-containing compound using the trinuclear mercury crystallizer employs a solvent-free rapid crystallization method. This method does not add any additional organic solvent, directly utilizing the liquid sulfur-containing guest itself to dissolve the trinuclear mercury crystallizer, and inducing rapid co-crystallization through drop plate evaporation. The method includes the following steps: (1) Add 5 mg of Hg3 solid powder and 500 μL of liquid sulfur-containing guest into a clean glass container (the amount of Hg3 and sulfur-containing guest can be adjusted according to the molecular structure, viscosity and volatility of the guest so that the Hg3 solid powder is completely dissolved in the liquid sulfur-containing guest or forms a homogeneous mixture) to obtain a mixture; (2) The mixture above is subjected to ultrasonic treatment or slight vortex oscillation for several seconds to several minutes to completely dissolve or fully disperse Hg3 and obtain a homogeneous host-guest mixture; (3) Use a pipette to draw up the host and guest mixture and quickly drop it onto a transparent substrate (glass plate, glass slide or quartz plate) to form a small droplet. The volume of a single droplet can be adjusted according to the sample amount and evaporation rate. Preferably, the volume is 10~100μL, and more preferably 50μL. (4) Place the transparent substrate in an open environment at room temperature (25±2℃) and let the droplets spread and evaporate naturally. After a few minutes, crystal precipitation can be observed at the edge or inside the droplets. (5) Select host-guest eutectic crystals with complete morphology and appropriate size under a polarizing microscope or stereomicroscope for single crystal X-ray diffraction testing.

[0015] When liquid sulfur-containing guests are simply added, the droplet volatilization and crystallization processes make it difficult to form testable crystals. However, after adding Hg3, the spread, volatilization behavior, and nucleation process of the droplets on the transparent substrate are significantly changed, and crystals suitable for single-crystal testing can be generated more quickly. This phenomenon indicates that Hg3 not only serves as the main structural unit in the crystal structure, but may also synergistically induce eutectic nucleation by changing the droplet interfacial behavior, promoting local enrichment, and providing directional Hg···S interactions (the directional interaction between the mercury center and sulfur atoms in the sulfur-containing guest is the important basis for promoting the eutectic formation of sulfur-containing guests in this invention).

[0016] When the liquid sulfur-containing compound is a low-volatility or high-viscosity sulfur-containing liquid (including at least one of long-chain sulfides, long-chain thiols, high molecular weight disulfides, low-volatility sulfoxides, highly sterically hindered aromatic sulfur-containing derivatives, and dithiols) that requires the addition of a volatile organic co-solvent, the method for promoting the rapid co-crystallization of the liquid sulfur-containing compound using a trinuclear mercury crystallization chaperone employs an organic solvent-assisted rapid crystallization method, including the following steps: (1) Add 5 mg of Hg3 solid powder and 200 μL of liquid sulfur-containing guest into a clean glass container (the amount of Hg3 and sulfur-containing guest can be adjusted according to the molecular structure, viscosity and volatility of the guest so that the Hg3 solid powder is completely dissolved in the liquid sulfur-containing guest or forms a homogeneous mixture) to obtain a mixture; (2) Add 0.1~1mL of volatile organic co-solvent (at least one of toluene, dichloromethane and chloroform) to the above mixture and sonicate or gently vortex for several seconds to several minutes to completely dissolve or fully disperse Hg3 and obtain a homogeneous host-guest mixture. (3) Use a pipette to draw up the host and guest mixture and quickly drop it onto a transparent substrate (glass plate, glass slide or quartz plate) to form a small droplet. The volume of a single droplet can be adjusted according to the sample amount and evaporation rate. Preferably, the volume is 10~100μL, and more preferably 50μL. (4) Place the transparent substrate in an open environment at room temperature (25±2℃) and let the toluene gradually evaporate. After a few minutes, crystal precipitation can be observed at the edge or inside the droplet. (5) Select host-guest eutectic crystals with complete morphology and appropriate size under a polarizing microscope or stereomicroscope for single crystal X-ray diffraction testing.

[0017] For certain low-volatility, high-viscosity liquid sulfur-containing guests, such as long-chain sulfides, dithiols, and sterically hindered aromatic sulfur derivatives, their low saturated vapor pressure and slow molecular diffusion rate make it difficult to achieve effective mixing and rapid crystallization of the host and guest components using solvent-free methods. Therefore, an organic solvent-assisted rapid crystallization method is employed, with toluene being the preferred choice. Toluene primarily functions to reduce system viscosity, improve the mixing uniformity of Hg3 and the sulfur-containing guest component, increase the droplet evaporation rate, and promote localized supersaturation. Toluene can also be replaced with organic solvents capable of simultaneously dissolving Hg3 and the target sulfur-containing guest component, and which exhibit high volatility under droplet conditions, such as dichloromethane, chloroform, or mixtures thereof; however, toluene is preferred to balance Hg3 solubility, sulfur-containing guest component compatibility, and mild volatility.

[0018] The present invention also provides an application of the host-guest eutectic crystal obtained by the above-mentioned method of promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallizer in single-crystal X-ray diffraction testing.

[0019] Compared with the prior art, the present invention has the following advantages and technical effects: (1) Fast operation: No complicated equipment or long diffusion process is required. Crystallization can be completed in an open environment at room temperature by dropping, evaporation and microscopic observation. Some samples can obtain testable crystals within minutes.

[0020] (2) Low sample consumption: Using micro-droplets as reaction and crystallization units, it is suitable for structural analysis of small, expensive or unstable sulfur-containing liquid samples.

[0021] (3) Wide range of applications: It covers both volatile liquid sulfur-containing substances and low-volatility, high-viscosity sulfur-containing substances; it complements the solvent-free method and the toluene-assisted method.

[0022] (4) High efficiency of structural analysis: The obtained crystal can be used for single-crystal X-ray diffraction testing to directly obtain the molecular structure of sulfur-containing guests or their dynamic transformation products.

[0023] (5) Capable of capturing dynamic conversion products: For systems such as thiols and dithiols that are prone to oxidation or coupling conversion, rapid drop plate crystallization is expected to selectively capture the eutectic structure of conversion products such as disulfides and sulfoxides.

[0024] (6) The mechanism is clear: the trinuclear mercury crystallization chaperone promotes the nucleation and growth of ordered eutectic through Hg···S directional interaction, planar host system structure and droplet evaporation-induced local enrichment. Attached Figure Description

[0025] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings: Figure 1 The single-crystal X-ray diffraction test results of the trinuclear phenylmercury complex (Hg3) prepared in this invention; Figure 2 Flowchart of the method for promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallization chaperone according to the present invention; Figure 3 This is a schematic diagram of the eutectic structure of Hg3 and n-butyl sulfide; Figure 4 This is a schematic diagram of the eutectic structure of Hg3 and 1,8-octanedithiol; Figure 5 This is a schematic diagram of the eutectic structure of Hg3 and oxidized ethyl methyl sulfoxide; Figure 6 Comparative photographs of droplets containing 4-fluoroanisole with (Example 4) Hg3 and without (Comparative Example 1); Figure 7This is a schematic diagram of the eutectic structure of Hg3 and dimethyl trisulfide; Figure 8 This is a schematic diagram of the eutectic structure of Hg3 and diethyldisulfide; Figure 9 SEM images of the early stage (40s~5min43s) of mixing sulfur-containing guest isopropyl disulfide with Hg3; Figure 10 The image shows the SEM image of the late stage of mixing the sulfur-containing guest isopropyl disulfide with Hg3 (time range: 13 min 18 s to 16 min 4 s). Detailed Implementation

[0026] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0027] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0028] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0029] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0030] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0031] This invention provides a method for promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallization chaperone, comprising the following steps: The trinuclear mercury crystallization chaperone is mixed with a liquid sulfur-containing compound (also known as a liquid sulfur-containing guest) to form a host-guest mixture; The host-guest mixture is dropped onto the surface of a transparent substrate in the form of droplets; A transparent substrate was placed in an open environment at room temperature to allow the droplets to evaporate naturally, resulting in a host-guest eutectic crystal. The aforementioned trinuclear mercury crystallization partners are trinuclear mercury complexes with a planar trinuclear mercury structure that can undergo directional mercury-sulfur interactions with sulfur-containing guests.

[0032] In a preferred embodiment of the present invention, the trinuclear mercury crystallization chaperone is a trinuclear phenylmercury complex (Hg3Ph3, abbreviated as Hg3). The synthesis method of Hg3 used in the embodiments of the present invention is as follows (wherein the reagents such as mercuric nitrate monohydrate and NaOH are commercially available): Glass tube oven synthesis method for Hg3: Mercuric nitrate monohydrate (3.4261 g, 9.47 mmol) was dissolved in 200 ml of water, and NaOH powder (4 g, 0.1 mol) was added. At this time, orange HgO(II) powder precipitated out. The solution was filtered and washed with ethanol to obtain mercuric oxide solid. The obtained mercuric oxide solid (3 g, 13.85 mmol) was dissolved in 5 mL of 50 wt% acetic acid solution (the solubility was increased in an 80 ℃ water bath). After complete dissolution, the solution was quickly placed in an ice-water bath. The white snowflake-like crystals that precipitated were mercuric acetate (II). The mercuric acetate was filtered and washed with ethanol, and dried to obtain mercuric acetate solid. Next, the prepared mercuric acetate solid (318.7 mg, 1.0 mmol) was completely dissolved in 24.3 mL AcOH / H2O (volume ratio 1:50). Tetrafluorophthalic acid solution (238 mg, 1.0 mmol; dissolved in 23.8 mL H2O) was added to the above solution. The precipitated white powder was washed with water and filtered to obtain mercuric tetrafluorophthalate. The obtained mercuric tetrafluorophthalate was dried in a vacuum oven at 50 °C for 24 h. The dried salt was then placed in a glass tube, sealed under vacuum, and heated at 300 °C for 24 h. The resulting dark brown powder was dissolved sequentially in dichloromethane and toluene. After filtering to remove insoluble impurities, the filtrates were combined and concentrated under reduced pressure to obtain brown Hg3 powder. Finally, the trinuclear phenylmercuric complex (Hg3) was obtained by recrystallization from dichloromethane or methanol. The single-crystal X-ray diffraction structure of the crystal obtained during the recrystallization process is shown in the figure. Figure 1 The structural formula of the trinuclear phenylmercury complex can be determined as follows: .

[0033] In a preferred embodiment of the present invention, the liquid sulfur-containing compound (liquid sulfur-containing guest) is selected from any one of those in Table 1: Table 1. Liquid sulfur-containing guests used in the examples In addition to the liquid sulfur-containing guests listed in Table 1, volatile sulfur-containing liquids that can directly dissolve the crystallizing companion of trinuclear mercury can also be selected from at least one of the following short-chain sulfides, low molecular weight disulfides, low molecular weight sulfoxides, volatile aromatic sulfides, and short-chain thiols; low-volatility or high-viscosity sulfur-containing liquids that require the addition of volatile organic co-solvents include at least one of long-chain sulfides, long-chain thiols, high molecular weight disulfides, low-volatility sulfoxides, highly sterically hindered aromatic sulfur-containing derivatives, and dithiols. Among them, short-chain sulfides are defined as sulfur-containing compounds with a carbon chain length of less than or equal to 4; low molecular weight disulfides are defined as compounds with disulfide bonds and a molecular weight of less than 500 M; low molecular weight sulfoxides are defined as compounds with a molecular weight of less than 500 M containing sulfoxide bonds; volatile aromatic sulfides are defined as volatile compounds with aromatic groups and sulfide-containing groups; short-chain thiols are defined as compounds containing a sulfur group (-SH) and a carbon chain length of less than or equal to 4; long-chain sulfides are defined as sulfur-containing compounds with a carbon chain length greater than 4; long-chain thiols are defined as compounds containing a sulfur group (-SH) and a carbon chain length greater than 4; high molecular weight disulfides are defined as compounds with disulfide bonds and a molecular weight greater than 500 M; low-volatility sulfoxides are defined as compounds containing sulfoxide bonds and difficult to volatilize at room temperature and pressure; and highly sterically hindered aromatic sulfur-containing derivatives are defined as sulfur-containing compounds with an aromatic ring and a large substituent group attached to it.

[0034] In a preferred embodiment of the present invention, the volatile organic co-solvent is at least one of toluene, dichloromethane and chloroform; preferably, the volatile organic co-solvent is toluene.

[0035] In a preferred embodiment of the present invention, the ratio of volatile organic co-solvent to trinuclear mercury crystallization chaperone is (0.1~1) mL: 5 mg.

[0036] In a preferred embodiment of the present invention, the ratio of the trinuclear mercury crystallization chaperone to the liquid sulfur-containing compound is 5 mg: (20~500) μL.

[0037] In a preferred embodiment of the present invention, the volume of the droplet is 10~100μL, preferably 50μL.

[0038] In a preferred embodiment of the present invention, the transparent substrate is a glass plate, a glass slide, or a quartz sheet.

[0039] The flowchart of the method for promoting rapid co-crystallization of liquid sulfur-containing compounds using the trinuclear mercury crystallization chaperone of this invention is shown below. Figure 2 .

[0040] This invention utilizes the directional interaction between a trinuclear mercury complex and a sulfur-containing guest to form a micro-droplet system of the sulfur-containing liquid guest and a trinuclear mercury crystallization chaperone on a glass substrate. This system allows for rapid volatilization, enrichment, nucleation, and growth in an open environment at room temperature, resulting in a host-guest eutectic suitable for single-crystal X-ray diffraction testing within minutes to tens of minutes. For liquid sulfur-containing compounds with different volatility and viscosity, this invention provides solvent-free rapid crystallization methods and organic solvent-assisted rapid crystallization methods, respectively. (1) When the liquid sulfur-containing compound is a volatile sulfur-containing liquid (including at least one of short-chain sulfides, low molecular weight disulfides, low molecular weight sulfoxides, volatile aromatic sulfides and short-chain thiols) that can directly dissolve the trinuclear mercury crystallizer, the method of promoting the rapid co-crystallization of the liquid sulfur-containing compound by the trinuclear mercury crystallizer adopts a solvent-free rapid crystallization method. This method does not add any organic solvent, directly uses the liquid sulfur-containing guest itself to dissolve the trinuclear mercury crystallizer, and induces rapid co-crystallization through drop plate evaporation. (2) When the liquid sulfur-containing compound is a low-volatility or high-viscosity sulfur-containing liquid (including at least one of long-chain sulfides, long-chain thiols, high molecular weight disulfides, low-volatility sulfoxides, high-steric-hind aromatic sulfur-containing derivatives and dithiols) that requires the addition of a volatile organic co-solvent, the method of promoting the rapid co-crystallization of the liquid sulfur-containing compound by the trinuclear mercury crystallization companion adopts the organic solvent-assisted rapid crystallization method.

[0041] This invention also provides an application of the host-guest eutectic crystal obtained by the above-mentioned method of promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallizer in single-crystal X-ray diffraction testing.

[0042] This invention is not limited to the specific object types and single operating parameters described above. Those skilled in the art can adjust the following conditions without departing from the concept of this invention: The mass ratio or molar ratio of Hg3 to sulfur-containing guest can be adjusted according to the number of sulfur atoms, volatility, viscosity and steric hindrance in the guest molecule; The droplet volume can be adjusted within a microliter range, preferably 10~100μL; The glass plate can be replaced with a transparent glass slide, a glass slide, a quartz slide, or other clean and inert substrates suitable for microscopic observation; The ambient temperature, humidity, and airflow can be adjusted according to the volatilization rate of the substance, preferably at room temperature, normal pressure, and in an air atmosphere; The co-solvent can be toluene or other volatile organic solvents that can dissolve Hg3 and are compatible with sulfur-containing guests; After crystal precipitation, single-crystal X-ray diffraction can be performed directly, or the crystal size can be further optimized by changing the droplet volume, concentration, substrate surface, or volatilization conditions.

[0043] The technical solution of the present invention will be further illustrated by the following embodiments. These embodiments are for illustrative purposes only and do not limit the scope of protection of the present invention. Any conventional substitutions or adjustments made based on the concept of the present invention to the type of object, amount of Hg3, type of solvent, droplet volume, type of substrate, or evaporation conditions should fall within the scope of protection of the present invention.

[0044] In the embodiments of this invention, the room temperature refers to 25±2℃.

[0045] Example 1 Solvent-free rapid crystallization method for volatile liquid sulfides: (1) Add 5 mg of Hg3 solid powder and 500 μL of n-butyl sulfide to a clean glass container to obtain a mixture; (2) The mixture above is subjected to ultrasonic treatment and oscillation for half a minute to completely dissolve or fully disperse Hg3 and obtain a homogeneous host-guest mixture; (3) Use a pipette to draw 50 μL of the host-guest mixture and quickly drop it onto a clean glass plate to form a 50 μL droplet; (4) Place the clean glass plate in air at room temperature (25±2℃) for 20 minutes. After that, observe the crystal formation under a microscope. Select the host-guest eutectic crystal with complete morphology and appropriate size for single crystal X-ray diffraction test.

[0046] A schematic diagram of the eutectic structure of Hg3 and n-butyl sulfide is shown below. Figure 3 It can be seen that the S atom and Hg atom of n-butyl sulfide are single-point bonded (S…Hg=3.27-3.50Å) and have a low residual factor (R1=0.0678).

[0047] Example 2 Toluene-assisted rapid co-crystallization method for low-volatility long-chain dithiols: (1) Add 5 mg of Hg3 solid powder and 20 μL of 1,8-octanedithiol to a clean glass container, and then add 0.5 mL of toluene as a co-solvent to obtain a mixture; (2) The mixture above is sonicated for half a minute to dissolve it, so that Hg3 is completely dissolved or fully dispersed. After mixing for 3 minutes, a homogeneous host-guest mixture is obtained. (3) Use a pipette to draw 50 μL of the host-guest mixture and quickly drop it onto a clean glass plate to form a small droplet; (4) Place the clean glass plate in room temperature air to allow the toluene to gradually evaporate. After 9 minutes, observe the crystal precipitation under a microscope. Select host-guest eutectic crystals with complete morphology and appropriate size for single crystal X-ray diffraction testing.

[0048] A schematic diagram of the eutectic structure of Hg3 and 1,8-octanedithiol is shown below. Figure 4 It can be seen that the S atom of 1,8-octanedithiol adopts a two-site coordination mode with Hg (S…Hg=3.39-3.46 Å), and the residual factor R1=0.1531.

[0049] Example 3 Same as Example 1, except that n-butyl sulfide was replaced with an equal volume of ethyl methyl sulfide, and the resulting oxidized ethyl methyl sulfoxide and Hg3 host-guest eutectic crystals were obtained by testing.

[0050] A schematic diagram of the eutectic structure of Hg3 and oxidized ethyl methyl sulfoxide is shown below. Figure 5 As can be seen, the addition of Hg3 to ethyl methyl sulfide yields a eutectic of oxidized ethyl methyl sulfoxide, in which the oxidized S atoms exhibit a single-point bonding pattern with Hg atoms (S…Hg = 2.76–2.83 Å), with R1 = 0.0613. This indicates that this method is not only applicable to stable liquid sulfur-containing compounds, but can also selectively capture the transformation products of sulfur-containing guests that are prone to dynamic transformations such as oxidation and coupling in air, precipitating them in eutectic form for single-crystal diffraction structure analysis.

[0051] Example 4 Same as Example 1, except that n-butyl sulfide is replaced with an equal volume of 4-fluoroanisole.

[0052] Settings for other embodiments: Based on Example 1, n-butyl sulfide was replaced with equal volumes of diethyl disulfide, isopropyl disulfide, dimethyl trisulfide, ethyl methyl sulfoxide, propyl methyl sulfoxide, 2-bromothiophene, anisole, 4-fluoroanisole, 2-methoxyanisole, 2-methylthiopyridine, 3-methyl-2-thiazolidinone, 2,3-butanediol, 1-methoxy-2-(methylthio)benzene, or p-toluene methyl sulfide to prepare host-guest eutectic crystals. Alternatively, based on Example 2, 1,8-octanedithiol can be replaced with equal volumes of 3-methylsulfinylpropanol, 2-chloroethylphenyl sulfide, phenylbutyl sulfide, 1,5-pentanedithiol, or diethyl sulfoxide to prepare a host-guest eutectic crystal.

[0053] Scale settings: Based on the respective examples, the addition of Hg3 was omitted, specifically as follows: Use a pipette to draw 50 μL of sulfur-containing substances in different states and quickly drop them onto a clean glass plate to form a small droplet. The clean glass plate was left to stand in air at room temperature (25±2℃) and observed under a microscope.

[0054] When the liquid sulfur-containing guest is 4-fluoroanisole, a comparison photo of droplets with and without Hg3 added (Example 4) is shown below. Figure 6 According to experimental records, in Example 4, the mixed droplets with added Hg3 were placed on a glass plate for 15 minutes to obtain crystals that were perfect for single crystal testing; while the droplets without added Hg3 took 280 minutes to completely evaporate.

[0055] The single crystal test temperature was 100 K. In the examples and comparative examples, the crystal appearance time during the preparation of guest eutectic crystals with different liquid sulfur-containing guests with or without the addition of Hg3 is shown in Table 2. The crystal size in the examples is shown in Table 3.

[0056] Table 2 Time of Crystal Appearance Table 3 Crystal Dimensions As can be seen from Tables 2 and 3, the rapid crystallization method can obtain high-quality single crystals that can be used for X-ray single crystal diffraction analysis in a short time (far shorter than the time for simple guest volatilization).

[0057] The schematic diagram of the eutectic structure of Hg3 and dimethyl trisulfide is shown below. Figure 7 A schematic diagram of the eutectic structure of Hg3 and diethyldisulfide is shown below. Figure 8 SEM images of the early stage (40 s ~ 5 min 43 s) of mixing the sulfur-containing guest isopropyl disulfide with Hg3 are shown below. Figure 9 SEM images of the late mixing phase (13 min 18 s ~ 16 min 4 s) are shown below. Figure 10 This figure illustrates the changes in droplet state and microscopic changes in crystal growth after the addition of Hg3 to the sulfur-containing guest. It shows that in the early stages, tidal motion occurs at the droplet edge due to the surface tension gradient; tiny crystals precipitate first at the edge due to supersaturation; subsequently, the edge crystals repeatedly precipitate and dissolve under tidal action, this reversible behavior stemming from the dynamic changes in the concentration gradient. Later, intense dissolution and recrystallization occur at the droplet center, generating numerous microbubbles at the liquid-solid and gas-solid interfaces. These bubbles introduce additional interfaces and voids, creating a porous environment conducive to vapor escape. After the solvent is largely removed, high-quality single crystals rapidly form at the droplet edge and center.

[0058] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallization chaperone, characterized in that, Includes the following steps: The trinuclear mercury crystallizer is mixed with a liquid sulfur-containing compound to form a host-guest mixture, wherein the ratio of the trinuclear mercury crystallizer to the liquid sulfur-containing compound is 5 mg: (20~500) μL; The host-guest mixture is dropped onto the surface of a transparent substrate in the form of droplets, the volume of which is 10~100μL; The transparent substrate after adding the host-guest mixture was placed in an open environment at room temperature to allow the droplets to evaporate naturally, thus obtaining a host-guest eutectic crystal. The trinuclear mercury crystallization chaperone is a trinuclear mercury complex with a planar trinuclear mercury structure capable of directional mercury-sulfur interactions with sulfur-containing guests; the trinuclear mercury crystallization chaperone is a trinuclear phenylmercury complex with the following structural formula: ； The liquid sulfur-containing compound is selected from volatile sulfur-containing liquids capable of directly dissolving the trinuclear mercury crystallizer, or low-volatility or high-viscosity sulfur-containing liquids requiring the addition of a volatile organic co-solvent. The volatile sulfur-containing liquid capable of directly dissolving the trinuclear mercury crystal chalcogenide is selected from one of the following: n-butyl sulfide, diethyl disulfide, isopropyl disulfide, dimethyl trisulfide, propyl methyl sulfoxide, 2-bromothiophene, anisole, 4-fluoroanisole, 2-methoxyanisole, 2-methylthiopyridine, 3-methyl-2-thiazolidinone, 2,3-butanediol, 1-methoxy-2-(methylthio)benzene, p-toluene methyl sulfide, and ethyl methyl sulfide. The low-volatility or high-viscosity sulfur-containing liquid that requires the addition of a volatile organic co-solvent is selected from one of 3-methylsulfinylpropanol, 2-chloroethylphenyl sulfide, phenyl butyl sulfide, 1,5-pentanedithiol, 1,8-octanedithiol, and diethyl sulfoxide. The volatile organic co-solvent is toluene.

2. The method for promoting rapid co-crystallization of liquid sulfur-containing compounds using a trinuclear mercury crystallization chaperone according to claim 1, characterized in that, The ratio of the volatile organic co-solvent to the trinuclear mercury crystallization chaperone is (0.1~1) mL: 5 mg.

3. The method for promoting rapid co-crystallization of liquid sulfur-containing compounds using the trinuclear mercury crystallization chaperone according to claim 1, characterized in that, The transparent substrate is a glass plate, a glass slide, or a quartz plate.

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