Method for accelerating oxidation etching of gold nanorods by trivalent iron ions with a carboxyl-containing mercapto small molecule and application thereof

Abstract

The present invention provides a method for accelerating the oxidative etching of gold nanorods by ferric ions using a carboxyl-containing thiol small molecule and its application. The method comprises the following steps: (1) adding a carboxyl-containing thiol small molecule to a mixed solution of incubated gold nanoparticles and a surfactant for incubation; (2) centrifuging the solution incubated in step (1), discarding the supernatant, dispersing the precipitate into an acidified surfactant solution, and then adding an etching solution containing ferric ions to initiate the etching reaction. The present invention utilizes a carboxyl-containing thiol small molecule to significantly accelerate the oxidative etching of gold nanoparticles by ferric ions and can be used to detect the spatial distribution of thiol molecules. The method is simple, rapid and highly reproducible.

Description

Technical Field

[0001] The present invention belongs to the technical field of nanomaterials, and relates to a method for regulating the oxidative etching of gold nanorods by ferric ions mediated by thiol molecules and its applications. Background Art

[0002] Plasmonic nanomaterials have potential applications in many fields such as optical metamaterials, sensing, catalysis, and biomedicine due to their unique local surface plasmon resonance characteristics. Among them, rod-shaped plasmonic nanoparticles, especially gold nanorods, have received extensive attention due to their tunable aspect ratio of local surface plasmon resonance and mature synthesis methods. Thiol ligands can adsorb on the surface of gold nanorods by forming strong Au-S covalent bonds and replacing weakly interacting surface ligands, which has a certain blocking effect on the surface sites of the rods. Usually, due to the larger curvature of the rod head, the ligand layer formed by weakly interacting ligands has a lower order, and thiol ligands preferentially adsorb on the head, providing a basis for the spatial selective adsorption of functional molecules. On this basis, the adsorption amount, adsorption configuration, and spatial distribution of thiol ligands on the particle surface can be regulated by changing the types of weakly interacting ligands, the order of the surface ligand layer, as well as parameters such as thiol molecule concentration, adsorption temperature, and adsorption time.

[0003] Also because of the larger curvature of the head, the oxidative etching of gold nanorods modified with weakly interacting ligands usually mainly occurs at the head, resulting in a decrease in the aspect ratio of the rods and a blue shift of the long-wavelength surface plasmon resonance peak (LSPR). Utilizing this feature, detection applications based on the change of the LSPR peak position can be realized. For example, by using the change in the rod size caused by the oxidative etching of gold nanorods by hydrogen peroxide generated by enzyme catalysis, colorimetric enzyme activity tests and enzyme inhibitor screening can be achieved (SaaL, Grinyte R, A Sánchez-Iglesias, et al. Blocked Enzymatic Etching of Gold Nanorods: Application to Colorimetric Detection of Acetylcholinesterase Activity and Its Inhibitors [J]. ACS Appl Mater Interfaces, 2016: 11139-11146.).

[0004] Biothiols such as cysteine and reduced glutathione play a fundamental role in various physiological and pathological processes of biological organisms, involving processes such as protein synthesis, detoxification, and metabolism. Cysteine has a thiol functional group, which can be used as a surface modification molecule to improve the optical properties or biocompatibility of nanomaterials. On the other hand, as a chiral biomolecule, the spatial distribution of cysteine adsorption plays a key role in the synthesis of chiral nanoparticles and the regulation of chiral signals in assemblies. Summary of the Invention

[0005] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide a method for accelerating the oxidative etching of gold nanorods by ferric ions with a carboxyl-containing thiol small molecule and its application.

[0006] To achieve the purpose of this invention, the following technical solutions are adopted:

[0007] In the first aspect, the present invention provides a method for accelerating the oxidative etching of gold nanoparticles by ferric ions with a carboxyl-containing thiol small molecule, and the method includes the following steps:

[0008] (1) Add a carboxyl-containing thiol small molecule to the mixed solution of incubated gold nanoparticles and surfactant for incubation;

[0009] (2) Centrifuge the solution incubated in step (1), discard the supernatant, disperse the precipitate in an acidified surfactant solution, and then add an etching solution containing ferric ions to initiate the etching reaction.

[0010] In the present invention, the method reveals the influence of thiol molecule adsorption on the oxidative etching of gold nanoparticles (especially gold nanorods) by ferric ions. In particular, the oxidative etching of gold nanoparticles by ferric ions can be accelerated with the assistance of a carboxyl-containing thiol small molecule, and the use of a carboxyl-containing thiol small molecule can significantly accelerate the etching. The spatial distribution of gold nanorods can be detected by utilizing the influence of its adsorption amount and spatial distribution on the etching rate and the regulation of the etching mode. The method has simple operation steps, mild reaction conditions, and the reagents used are cheap and non-toxic.

[0011] Preferably, the gold nanoparticles in step (1) are gold nanorods with an aspect ratio greater than 1, such as aspect ratios of 1.1, 1.5, 1.8, 2, 2.5, 3, 3.5, 4, etc.

[0012] In the present invention, there is no special requirement for the concentration of the gold nanoparticles in step (1), and it can be selected according to specific circumstances. Preferably, the gold nanoparticles are gold nanorods.

[0013] Preferably, the concentration of gold nanoparticles in the mixed solution in step (1) is 0.05 - 0.2 nM, such as 0.05 nM, 0.08 nM, 0.1 nM, 0.12 nM, 0.15 nM, 0.18 nM or 0.2 nM, and its preferred concentration is 0.1 nM.

[0014] Preferably, the surfactant in step (1) is cetyltrimethylammonium bromide (CTAB) or a surfactant composed of cetyltrimethylammonium chloride and sodium bromide, and cetyltrimethylammonium bromide is preferred.

[0015] In the present invention, by incubating nanoparticles and a surfactant, ligands with weak interactions (such as CTAB) are present on the surface of the nanoparticles. These ligands with weak interactions can be replaced by ligands with strong interactions, such as mercapto ligands.

[0016] In the present invention, the solvent in the mixed solution in step (1) is water.

[0017] In the present invention, the concentration of the surfactant in the mixed solution in step (1) is 0.05 - 100 mM, such as 0.05 mM, 0.1 mM, 0.2 mM, 0.5 mM, 1 mM, 5 mM, 10 mM or 100 mM, etc.

[0018] Preferably, the mercapto small molecule containing a carboxyl group in step (1) is selected from but not limited to any one or a combination of at least two of cysteine (Cysteine, Cys), acetylcysteine, p-mercaptobenzoic acid or reduced glutathione, and preferably any one or a combination of at least two of cysteine, glutathione or p-mercaptobenzoic acid.

[0019] Preferably, the concentration of the mercapto small molecule containing a carboxyl group added to the mixed solution in step (1) is 1 - 40 μM, such as 1 μM, 5 μM, 10 μM, 15 μM, 20 μM, 25 μM, 30 μM, 35 μM or 40 μM, etc., preferably 1 - 30 μM, and more preferably 1 - 10 μM.

[0020] In the present invention, the higher the concentration of the mercapto small molecule containing a carboxyl group, the faster the oxidation etching rate of the gold nanorods after incubation; for 0.1 nM Au720 nanorods dispersed in 1 mM CTAB, when the cysteine incubation concentration is less than 1 μM, the etching rate increases significantly; when the cysteine incubation concentration is greater than 1 and less than or equal to 30 μM, the change in the etching rate tends to be stable; however, the higher the concentration, the more cysteine adsorbs on the head, the better the head capping effect, and the etching mode gradually changes from an etching mode where both the head and the side are etched to an etching mode dominated by side etching, and the dumbbell-shaped morphology becomes more obvious.

[0021] Preferably, the temperature for incubating with a thiol small molecule containing a carboxyl group in step (1) is 30 - 90°C, such as 30°C, 35°C, 38°C, 40°C, 45°C, 50°C, 60°C, 70°C, 80°C or 90°C, preferably 30°C, and the incubation time is 0.5 - 3 h, such as 0.5 h, 1 h, 2 h or 3 h, etc., preferably, the incubation time is 0.5 h.

[0022] Preferably, the centrifugation treatment in step (2) is carried out at a rotational speed of 8000 - 12000 rpm (such as 8000 rpm, 8500 rpm, 9000 rpm, 9500 rpm, 10000 rpm, 11000 rpm or 12000 rpm) for 5 - 10 min (such as 5 min, 6 min, 7 min, 8 min, 9 min or 10 min).

[0023] Preferably, the acidified surfactant solution in step (2) is a mixed solution of 10 mM - 100 mM (such as 10 mM, 30 mM, 50 mM, 80 mM or 100 mM) CTAB and 10 mM hydrochloric acid.

[0024] Preferably, the concentration of the surfactant in the etching system in step (2) is 1 - 100 mM, such as 1 mM, 5 mM, 10 mM, 20 mM, 40 mM, 60 mM, 80 mM or 100 mM, etc. The higher the surfactant concentration, the faster the etching rate. It can be selected according to specific circumstances. For the case where rapid etching is required, 100 mM is preferred.

[0025] In the present invention, if the surfactant concentration in the etching system is too low, the rate of oxidation etching of gold nanorods by ferric ions is very slow.

[0026] In the present invention, the etchant is ferric chloride. Since ferric ions are etching ions, to inhibit their hydrolysis, the pH value of the etching system should be controlled at 2 - 4, such as 2, 2.4, 2.8, 3, 3.3, 3.5, 3.8 or 4.

[0027] Preferably, the concentration of ferric ions in the etching system in step (2) is 1 - 10 mM, such as 1 mM, 3 mM, 5 mM, 8 mM or 10 mM, preferably 3 mM.

[0028] Preferably, the temperature of the etching reaction in step (2) is 30°C, and the etching time is 10 - 40 min, such as 10 min, 15 min, 20 min, 25 min, 30 min, 35 min or 40 min, preferably 30 min.

[0029] In the present invention, a high concentration of surfactant and a high concentration of cysteine in the incubation system are beneficial for the highly selective head closure of thiol molecules.

[0030] Preferably, in the etching system of step (2), the concentration of the surfactant is greater than 10 mM and less than or equal to 100 mM. When it is preferably 100 mM, the trivalent iron ion oxidation etching is in the fast etching mode.

[0031] As one of the preferred technical solutions, the fast etching mode of the well - capped gold nanorods corresponding to the present invention includes the following steps:

[0032] (1) Disperse gold nanorods with a final particle concentration of 0.1 nM in a 0.1 M surfactant solution and leave it overnight at 30 °C. Add cysteine with a final concentration of 10 μM, and place the mixed solution in a 30 °C water bath for incubation for 2 h for later use;

[0033] (2) Centrifuge 1 mL of the gold nanorod solution with cysteine adsorbed on its surface obtained in step (1). After centrifuging at a speed of 12,000 revolutions per minute for 5 min, disperse the precipitate in the etching solution. The etching solution includes an acidic mixed solution of cetyltrimethylammonium bromide with a concentration of 100 mM and 10 mM hydrochloric acid; finally, add a 3 mM iron chloride solution to initiate the etching reaction. During this process, use an ultraviolet - visible - infrared absorption spectrometer to record the change in its extinction spectrum every 1 min.

[0034] In the present invention, the etching conditions affect whether the thiol ligand migrates, and it can be judged according to the etching mode of the well - capped gold nanorods corresponding to different etching solution concentrations.

[0035] In the present invention, by changing the concentration of the surfactant in the etching system of step (2), it can be converted to the slow etching mode. When the concentration of the surfactant in the etching system of step (2) is 1 - 10 mM, the trivalent iron ion oxidation etching is in the slow etching mode.

[0036] As one of the preferred technical solutions, the slow etching mode of the well - capped gold nanorods corresponding to the present invention includes the following steps:

[0037] (1) Disperse gold nanorods with a final particle concentration of 0.1 nM in a 0.1 M surfactant solution and leave it overnight at 30 °C. Add cysteine with a final concentration of 10 μM, and place the mixed solution in a 30 °C water bath for incubation for 2 h for later use;

[0038] (2) Centrifuge 1 mL of the gold nanorod solution with cysteine adsorbed on its surface obtained in step (1) at a speed of 12,000 revolutions per minute for 5 minutes. Then disperse the precipitate in the etching solution, which is an acidic mixed solution containing 10 mM cetyltrimethylammonium bromide and 10 mM hydrochloric acid. Finally, add 3 mM ferric chloride solution to initiate the etching reaction. During this process, use a UV-Vis-NIR absorption spectrometer to record the change in its extinction spectrum every 1 minute.

[0039] In the present invention, based on the fast and slow etching modes of gold nanorods with intact heads, and corresponding to the etching kinetic spectra and etching morphologies, in the fast etching system, due to the intact head, the etching rate of the head is significantly slower than that of the side of the rod. The LSPR peak position of the gold nanorods monitored kinetically has been redshifted, so there is an obvious dumbbell-shaped morphology. In the slow etching system, no side depression morphologies such as dumbbell shapes are seen. The LSPR peak position of the gold nanorods monitored kinetically first redshifts and then blueshifts after reaching an extreme value. Considering the migration of thiol ligands during the etching process, when the etching rate of the head is lower than the migration rate of the thiol ligands, the thiol small molecules gradually migrate from the original adsorption sites to the side, resulting in the exposure of fresh active sites at the head, promoting the carboxyl group to attract ferric ions to the head for faster etching, and finally presenting an etching mode in which the aspect ratio first increases and then decreases.

[0040] In the present invention, unless otherwise specified, the concentration unit M means mol / L, mM means mmol / L, and μM means μmol / L.

[0041] In a second aspect, the present invention provides an application of using the method for accelerating the oxidative etching of gold nanoparticles by ferric ions with the thiol small molecule containing a carboxyl group as described above to detect the spatial distribution of thiol molecules.

[0042] In specific application scenarios of this application, it is necessary to regulate the etching conditions to ensure that the etching rate is much greater than the migration rate of surface atoms in order to detect the original adsorption spatial position distribution of thiol molecules.

[0043] In the present invention, in order to detect the spatial distribution of the original adsorption position of cysteine and avoid the influence of the change in morphology caused by the migration of metal atoms during the etching process, a fast etching mode is adopted.

[0044] Preferably, the detection of the spatial distribution of thiol molecules is to monitor the etching kinetics by UV-Vis absorption spectroscopy during the process of oxidative etching of gold nanoparticles regulated by the thiol molecules.

[0045] As a preferred technical solution, the method for detecting the spatial distribution of thiol molecules includes the following steps:

[0046] (1) Disperse the gold nanorod solution into surfactant solutions with different concentrations (such as 0.1 mM, 0.2 mM, 0.5 mM, 1 mM, etc.) respectively, let it stand overnight at 30 °C, then add 1 μM cysteine and mix well, and then place it in a water bath at 30 °C and 60 °C for incubation for 30 min respectively;

[0047] (2) Centrifuge the mixed solutions after incubation in step (1). Disperse the precipitate after centrifugation into a solution containing 100 mM cetyltrimethylammonium bromide and 10 mM HCl, and finally add 3 mM ferric chloride solution. React at room temperature, and monitor the etching kinetics by UV-vis absorption spectroscopy.

[0048] In the present invention, the surface distribution of the thiol ligand is mainly achieved by regulating the coverage of the surfactant ligand layer and the incubation temperature of the thiol molecules. The distribution of cysteine molecules on the head and side of the rod is judged by comparing the change in the red shift amount of the LSPR peak position during the etching process of the gold nanorods combined with the TEM morphology map. When the surfactant concentration is low, due to the poor order of the ligand layers on the head and side, thiol ligands (such as Cys) will be adsorbed on both the head and side, resulting in simultaneous etching of the side and head. At the same etching rate (nm / min), the volume reduction caused by side etching is more.

[0049] In summary, for rod-shaped nanoparticles, usually due to the large curvature of the head, the long-chain weak interaction ligands used to stabilize the dispersion of nanorods, such as surfactant molecules adsorbed on the rod surface, have poor ligand layer order on the rod head. After adding strong interaction ligand mercapto molecules, these mercapto molecules will preferentially adsorb on the rod head. This differential adsorption of mercapto molecules is of great significance for the further regulation of the properties of nanorods, such as driving head-to-head assembly of rods and regulating plasmonic chiral optical activity. The present invention proposes a method for accelerating the oxidative etching of gold nanorods based on carboxyl-containing mercapto molecules and applying this method to detect the spatial distribution of adsorbed mercapto molecules on the surface of nanorods. The adsorbed mercapto molecules can regulate the oxidative etching of gold nanorods by ferric ions, which is closely related to the functional groups contained in the used mercapto molecules, the coverage of mercapto molecules, the adsorption configuration, and the spatial position of adsorption. Generally speaking, the formation of Au-S bonds can stabilize surface gold atoms and inhibit their oxidative etching. However, if the mercapto ligand adsorption destroys the original weak ligand adsorption layer, it is more conducive for the etchant to approach the particle surface, which will in turn accelerate the etching. The present invention finds that carboxyl-containing mercapto molecules can bring ferric ions to the surface of gold rods through the complexation of carboxyl with iron ions, thereby accelerating the oxidative etching of gold rods. Mercapto molecules without carboxyl groups, especially benzenethiol-based mercapto molecules, are dominated by the stabilizing effect after the formation of Au-S bonds; furthermore, the interaction between the benzene ring and the ligand layer may improve the order of the ligand layer, and as a result, the etching of gold rods is generally inhibited. During the etching process, there are unstable intermediate morphologies, and surface atom migration will occur, causing changes in the particle morphology and thus changing the original spatial distribution of mercapto ligands. To avoid this phenomenon, it is necessary to make the etching rate much greater than the surface atom migration rate. When this condition is met, the spatial distribution of mercapto molecules adsorbed on the surface of gold nanorods can be detected by using the etching rate change law of the corresponding system and the relative displacement change of the longitudinal surface plasmon resonance peak (LSPR) of gold nanorods.

[0050] Compared with the prior art, the present invention has the following beneficial effects:

[0051] (1) The present invention finds that carboxyl-containing small mercapto molecules can significantly accelerate the oxidative etching of gold nanoparticles by ferric ions, while mercapto molecules containing other functional groups have no obvious accelerating effect.

[0052] (2) The method for regulating the oxidative etching of gold nanoparticles by ferric ions using the mercapto molecules of the present invention can detect the spatial distribution of mercapto molecules, providing a "nano-surface reactor" for detecting the distribution of adsorbed thiols on the rod surface. By measuring the extinction spectrum change during the etching process through UV-vis extinction spectroscopy and analyzing the etching process combined with TEM imaging, the spatial distribution of mercapto molecules can be judged. This method is simple, fast, and has good repeatability. Description of the Drawings

[0053] Figure 1-a The extinction spectra of gold nanorods incubated with 10 μM p-mercaptobenzoic acid in Example 1 before and after 30 min of oxidative etching with 0.1 M CTAB.

[0054] Figure 1-b The extinction spectra of the blank sample of gold nanorods without p-mercaptobenzoic acid incubation in Example 1 before and after 30 min of oxidative etching with 0.1 M CTAB.

[0055] Figure 2-a The extinction spectra of gold nanorods incubated with 10 μM benzenethiol in Comparative Example 1 before and after 30 min of oxidative etching with 0.1 M CTAB.

[0056] Figure 2-b The extinction spectra of gold nanorods incubated with 10 μM p-aminothiophenol in Comparative Example 1 before and after 30 min of oxidative etching with 0.1 M CTAB.

[0057] Figure 2-c The extinction spectra of gold nanorods incubated with 10 μM p-mercaptobenzeneboronic acid in Comparative Example 1 before and after 30 min of oxidative etching with 0.1 M CTAB.

[0058] Figure 2-d The variation law of the extinction change at 476 nm with time for gold nanorods assisted by small molecule compounds containing thiol and benzene ring in Comparative Example 1 under the system with an etching solution concentration of 0.1 M CTAB.

[0059] Figure 3-a The kinetic process of the oxidative etching of gold nanorods with the assistance of cysteine in Example 2.

[0060] Figure 3-b The kinetic process of the oxidative etching of gold nanorods without the assistance of cysteine in Example 2.

[0061] Figure 3-c The relationship between the initial etching rate and the cysteine incubation concentration in Example 3.

[0062] Figure 4-a The variation law of the extinction change value at 476 nm with time for the oxidative etching system of gold nanorods assisted by different thiol-containing small molecules with carboxyl groups in Example 4.

[0063] Figure 4-b The variation law of the extinction change value at 476 nm with time for the oxidative etching system of gold nanorods assisted by different thiol-containing small molecules in Comparative Example 2.

[0064] Figure 4-c The initial etching rate of the oxidative etching of gold nanorods assisted by different thiol-containing small molecules in Comparative Example 2.

[0065] Figure 5-a It is the kinetic spectrogram of the rapid etching of well - capped gold nanorods in 0.1 M CTAB in Example 5.

[0066] Figure 5-b It is the TEM morphology diagram corresponding to when the LSPR peak of the gold nanorods reaches 1000 nm in this etching system, and its scale bar is 50 nm.

[0067] Figure 6-a It is the kinetic spectrogram of the slow etching of well - capped gold nanorods in 10 mM CTAB in Comparative Example 3.

[0068] Figure 6-b It is the TEM morphology diagram corresponding to when the LSPR peak of the gold nanorods reaches 900 nm in this etching system, and its scale bar is 50 nm.

[0069] Figure 7-a It is the extinction kinetic spectrum corresponding to the etching when the CTAB concentration of the etching solution is 10 mM in Example 6.

[0070] Figure 7-b It is the extinction kinetic spectrum corresponding to the etching when the CTAB concentration of the etching solution is 20 mM in Example 6.

[0071] Figure 7-c It is the extinction kinetic spectrum corresponding to the etching when the CTAB concentration of the etching solution is 40 mM in Example 6.

[0072] Figure 7-d It is the extinction kinetic spectrum corresponding to the etching when the CTAB concentration of the etching solution is 60 mM in Example 6.

[0073] Figure 7-e It is the extinction kinetic spectrum corresponding to the etching when the CTAB concentration of the etching solution is 80 mM in Example 6.

[0074] Figure 7-f It is the extinction kinetic spectrum corresponding to the etching when the CTAB concentration of the etching solution is 100 mM in Example 6.

[0075] Figure 8-a It is the curve graph of the etching time used when the LSPR peak of the gold nanorods reaches 1000 nm with the regulation of different CTAB concentrations of the etching solution.

[0076] Figure 8-b It is the curve graph of the etching amount when the LSPR peak of the gold nanorods reaches 1000 nm with the regulation of different CTAB concentrations of the etching solution.

[0077] Figure 9-a It is the etching kinetics of gold nanorods assisted by 1 μM of the final concentration of cysteine in Example 7.

[0078] Figure 9-b The etching time and etching amount used when the LSPR peak of gold nanorods reaches 1000 nm under the assistance of cysteine at different concentrations.

[0079] Figure 10 TEM images of the etched morphologies of gold nanorods assisted by different cysteine concentrations in Example 8. Among them, a is the morphology image of gold nanorods etched with the assistance of 1 μM cysteine when the LSPR peak position reaches 923 nm, b is the morphology image of gold nanorods etched with the assistance of 2.5 μM cysteine when the LSPR peak position reaches 923 nm, c is the morphology image of gold nanorods etched with the assistance of 5 μM cysteine when the LSPR peak position reaches 1100 nm, d is the morphology image of gold nanorods etched with the assistance of 10 μM cysteine when the LSPR peak position reaches 970 nm, and the scale bar of each is 50 nm.

[0080] Figure 11-a During the early incubation process, cysteine regulates the CTAB concentration and incubation temperature, corresponding to the variation law of the LSPR peak value of gold nanorods with etching time during the etching process.

[0081] Figure 11-b The change in the etching amount of gold nanorods when the LSPR peak reaches 1000 nm.

[0082] Figure 11-c Respectively corresponding to the time used for etching gold nanorods when the LSPR peak reaches 1000 nm.

[0083] Figure 12 Morphology image of gold nanorods etched with the assistance of 1 μM cysteine in a gold nanorod solution with a CTAB concentration of 0.2 mM at 30 °C incubation system, when the LSPR peak position reaches 955 nm, and the scale bar is 50 nm.

[0084] Figure 13 Morphology image of gold nanorods etched with the assistance of 1 μM cysteine in a gold nanorod solution with a CTAB concentration of 1 mM at 60 °C incubation system, when the LSPR peak position reaches 980 nm, and the scale bar is 50 nm.

[0085] Figure 14 For the extinction change with time of 1 μM cysteine-assisted accelerated etching of gold nanorods with a large aspect ratio (LSPR 1000 nm ) and gold nanospheres (diameter 40 nm), where a is the case of gold nanorods with a large aspect ratio and b is the case of gold nanospheres (diameter 40 nm).

[0086] Figure 15 The variation law of the etching amount of cysteine-assisted gold nanorods in hydrogen peroxide with time. Detailed implementation manners

[0087] The technical solutions of the present invention will be further described below through specific implementation manners. Those skilled in the art should understand that the embodiments are only for helping to understand the present invention and should not be regarded as specific limitations on the present invention.

[0088] In the following embodiments, the experimental methods are all conventional methods unless otherwise specified; the experimental materials used are all purchased from conventional biochemical reagent manufacturers unless otherwise specified.

[0089] In the following embodiments, the sources of the reagents used are as follows: cetyltrimethylammonium bromide CTAB (Amresco), cysteine Cys (Sigma). Among them, the smooth absorption in the spectral range of 470 - 490 nm can reflect the total amount of gold atoms in the gold nanorods.

[0090] In the following embodiments, the etching amount is calculated by the change in the extinction value at 476 nm, and is represented by ΔExt 476 nm / Ext 0 476 nm to represent. LSPR max represents the maximum value corresponding to each minute during the oxidative etching process of the LSPR peak position of the gold nanorods. The wavelength of the ultraviolet - visible - infrared absorption spectrometer is up to 1100 nm at most.

[0091] Example 1 4 - Mercaptobenzoic acid accelerates the etching of gold nanorods

[0092] 4 - Mercaptobenzoic acid (4 - MBA) with a concentration of 10 μM was added to the gold rod (0.1 nM) sol dispersed in 0.1 M CTAB, and incubated in a 30 °C water bath for 2 h. Then, it was centrifuged at 12000 revolutions per minute for 5 min, and the precipitate was dispersed in an acidified solution of 0.1 M CTAB, and ferric ions were added for etching. The etching results are as Figure 1-a shown. Compared with the blank, the mercapto molecules with benzene rings can be divided into two groups. The etching rate of the gold rods modified with 4 - mercaptobenzoic acid is significantly accelerated; while benzenethiol and p - aminobenzenethiol without carboxyl functional groups slow down the etching of the gold nanorods, showing a stabilizing effect. In particular, the etching accelerated by 4 - mercaptobenzoic acid shows that the LSPR peak position of the rod shows continuous blue - shift, as Figure 1-b shown, indicating that the etching rate of the head is faster than that of the side. After etching for 30 min, the etching amount reaches about 50%.

[0093] Comparative Example 1

[0094] Gold nanorods (0.1 nM) dispersed in 0.1 M CTAB were incubated with thiol benzene ring molecules without carboxyl functional groups such as benzenethiol, 4-mercaptobenzeneboronic acid, and 4-aminobenzenethiol. The remaining raw materials, their dosages, and the treatment methods and conditions were the same as those in Example 1. The changes in the extinction spectra of benzenethiol, 4-aminobenzenethiol, and 4-mercaptobenzeneboronic acid during the etching process are shown in Figure 2-a , 2-b, and 2-c respectively, and the initial etching rate is shown in Figure 2-d . The results preliminarily show that methyl cysteine, 4-aminobenzenethiol, and 4-mercaptobenzeneboronic acid without carboxyl functional groups do not show an obvious effect of promoting the etching of gold nanorods (only increasing from 2% to 8%).

[0095] Example 2 Cysteine Accelerates the Etching of Gold Nanorods

[0096] 0.1 nM gold nanorods (aspect ratio 2.85) were dispersed in 1 mM CTAB aqueous solution and left overnight at 30 °C. Then, 1 μM cysteine (Cys) was added, mixed well, and incubated in a 30 °C water bath for 30 min. The incubation system was centrifuged, and the precipitate was dispersed in an acidified CTAB solution (10 mM CTAB solution containing 10 mM HCl). Then, 3 mM ferric chloride solution with pH = 2 was added to initiate the etching. The etching kinetics of gold nanorods at 1-min intervals is shown by the extinction spectrum in Figure 3-a . The phenomenon that the LSPR peak position first shows a small red shift (from 700 nm to 750 nm) and then a blue shift (from 750 nm to 640 nm) appears. When the etching reaches 30 min, the extinction value at 480 nm decreases by 0.12, and the etching amount reaches 55%, which is much higher than the etching without adsorbed cysteine ( Figure 3-b ), indicating that the adsorbed cysteine can accelerate the etching of gold nanorods. Compared with the thiol small molecules with benzene rings, cysteine significantly accelerates the etching.

[0097] Example 3 Effect of Cysteine Concentration on the Etching Rate

[0098] The above Example 2 experiments were conducted by adjusting the cysteine incubation concentrations to 1 μM, 5 μM, 10 μM, 20 μM, and 30 μM respectively, with other experimental conditions unchanged. Figure 3-c The etching rate change rate with time obtained from the extinction value at 476 nm of the spectrum can be used to obtain the initial etching rate of gold nanorods assisted by different concentrations of cysteine. It can be concluded from the figure that the initial etching rate increases with the increase in the cysteine incubation concentration.

[0099] Example 4 The Complexation of Carboxyl Functional Groups with Iron Ions Promotes the Oxidative Etching of Gold Rods

[0100] The steps are basically the same as those in Example 2, except that in this example, glutathione (1 μM), N-acetylcysteine or p-mercaptobenzoic acid was added to gold nanorods (0.1 nM) dispersed in 1 mM CTAB. The UV-Vis-NIR absorption spectrometer was used to record the change of the extinction spectrum during the etching process of gold nanorods every 1 min. The results are as Figure 4-a shown. For acetylcysteine, glutathione and p-mercaptobenzoic acid, the test results show that the carboxyl functional group has the effect of accelerating the etching of gold nanorods in the oxidation etching of ferric ions. The acceleration order is cysteine > glutathione ≈ acetylcysteine > p-mercaptobenzoic acid. After etching for 40 min, the etching amounts are about 45% for the cysteine-modified sample, about 32% for the glutathione ≈ acetylcysteine-modified sample, and about 8.4% for the p-mercaptobenzoic acid-modified sample, indicating that in addition to the carboxyl functional group, the size and adsorption conformation of the mercapto molecule also play a role.

[0101] Comparative Example 2

[0102] To gold nanorods (0.1 nM) dispersed in 1 mM CTAB, mercapto small molecules without carboxyl groups such as cysteine methyl ester, p-mercaptobenzeneboronic acid, and p-aminothiophenol were added for incubation. The remaining raw materials, their dosages, and the treatment methods and conditions were the same as those in Example 1. The change of the extinction spectrum during the etching process is as Figure 4-b , and the initial etching rate is as Figure 4-c shown. The results show that cysteine methyl ester, p-aminothiophenol and p-mercaptobenzeneboronic acid without carboxyl functional groups did not show an obvious effect of promoting the etching of gold nanorods (only increased from 2% to 8%).

[0103] Example 5 Cysteine-capped gold nanorods initiate side etching mode

[0104] 0.1 nM gold nanorods were dispersed in 0.1 M CTAB solution and left overnight at 30 °C. Then 10 μM cysteine was added and incubated in a 30 °C water bath for 2 h. Then, it was centrifuged at 12,000 rpm for 5 min, and the obtained precipitate was dispersed in 0.1 M CTAB solution acidified with 10 mM HCl. 3 mM FeCl3 was added to initiate etching, and the change of the extinction spectrum of the nanorods was recorded every 0.5 min with a UV-Vis-NIR absorption spectrometer, as Figure 5-a shown. Under this condition, the gold nanorods were etched quickly. When etched for 2 min, the LSPR peak position of the corresponding etched gold nanorods had redshifted to 1100 nm. From the TEM morphology Figure 5-bIt can be seen that the nanorods exhibit an obvious dumbbell-like morphology, indicating that the rod heads are well closed and the etching mainly occurs on the side. Compared with the LSPR blue shift of the 4-MBA modified sample under similar incubation and etching conditions (Example 1), it shows that Cys forms a grid on the rod head, inhibiting the head etching; the initial etching rate is 3 times faster than that of the 4-MBA modified sample (15.3% / min vs 4.9% / min), indicating that the side etching accelerated by Cys is more effective.

[0105] Comparative Example 3

[0106] The difference from Example 5 is only that the CTAB concentration in the etching system is adjusted to 10 mM, and the etching is monitored by extinction spectrum for 10 min. The change of the extinction spectrum is as Figure 6-a shown. Since the bromide ions in CTAB promote the oxidation of Fe 3+ to Au[[AuBr2]] - , increasing the CTAB concentration accelerates the etching. From the TEM morphology diagram Figure 6-b it can be seen that there is a blue shift process in the speed change. The position originally adsorbed on the head migrates to the side, and finally the rod-shaped head continues to be etched, no longer the dumbbell-like structure. Compared with the 0.1 M CTAB etching system in Example 3, it leads to morphological changes caused by the migration of surface gold atoms during the etching process of gold nanorods and the resulting change in the spatial distribution of thiol molecules. Therefore, in order to detect the original adsorption distribution of thiol molecules, the etching rate should be increased as much as possible.

[0107] Example 6 Regulation of Etching Rate by CTAB Concentration

[0108] This example is the same as the steps described in Example 2. The cysteine incubation concentration is 1 μM. The CTAB concentration in the etching system is adjusted to 10 mM, 20 mM, 40 mM, 60 mM, 80 mM, and 100 mM respectively. The change of the extinction spectrum of gold nanorods during the etching process is recorded at 0.5 min intervals. The results are as Figures 7-a to 7-f shown. From the spectral changes, when the CTAB concentration in the etching solution ≤ 60 mM, the LSPR peak of the gold nanorods redshifts to the maximum value and then blueshifts, indicating a change in the etching mode. At low CTAB concentrations, due to the slow etching rate, the migration of gold atoms on the surface causes a change in the Cys adsorption distribution, and the Cys coverage rate on the head decreases. Cys changes from the closed effect at high coverage to the accelerated etching effect at low coverage, initiating the head-preferred etching, resulting in the LSPR shifting from red to blue in the early stage of etching. The lower the CTAB concentration, the faster this transformation, resulting in a decrease in both the maximum red shift amount and the etching amount in the early stage of etching, as Figure 8-a and 8-bAs shown. Therefore, increasing the CTAB concentration and accelerating the etching can better reflect the initial spatial distribution of Cys. With the increase of CTAB concentration in the etching system, the more the LSPR peak position of the gold nanorods redshifts due to the early etching, and the etching amount at the maximum redshift peak position is also the largest. Combining Example 5 and Comparative Example 3, preferably, in the etching system for detecting the adsorption spatial distribution position of cysteine in the present invention, the CTAB concentration is 0.1 M.

[0109] Example 7 Influence of Cysteine Concentration under Fast Etching Conditions

[0110] For gold nanorods (0.1 nM) dispersed in 1 mM CTAB, the cysteine incubation concentrations were adjusted to 1 μM, 2.5 μM, 5 μM, 7.5 μM, and 10 μM respectively, and other experimental conditions and methods were the same as those in Example 2. During the etching process of the gold nanorods, the change of their extinction spectra was recorded every 0.5 min, and the results are as Figure 9-a and Figure 9-b shown. Referring to the optimized concentration of CTAB concentration in the etching system in Example 6, preferably, under the fast etching condition of increasing the CTAB concentration in the etching system to 0.1 M, the morphology of the gold nanorods assisted by cysteine etching changes from the TEM morphology Figure 10 It can be seen that with the increase of Cys concentration, the etching amount corresponding to the LSPR peak position of the gold nanorods redshifted to 1000 nm gradually decreases. It indicates that when high-concentration Cys adsorbs, the head closure of the gold nanorods is gradually intact, and the etching preferentially occurs on the side. A small amount of cysteine adsorbed on the side can also accelerate the etching on the side, showing the effect of accelerating the etching on the side. From the TEM morphology Figure 10 It can be seen that no irregular morphology appears when the Cys concentration is 1 μM, the concave feature of side etching gradually appears at 2.5 μM, and the dumbbell-like morphology becomes more and more obvious when it is higher than 5 μM.

[0111] Example 8 Application Example

[0112] Application Example 8-1 - Judging the Influence of CTAB Concentration in Gold Nanorod Sol on Cysteine Adsorption

[0113] The present invention's research found that the CTAB concentration in the gold rod dispersion affects the adsorption amount and adsorption position of Cys on the gold nanorods, and further affects the chiral optical response of the subsequently formed chiral assemblies. The above-mentioned etching method of the invention can be used to judge the Cys adsorption amount and adsorption position.

[0114] The specific steps are as follows:

[0115] Step (1): Gold nanorods with a final particle concentration of 0.1 nM were respectively dispersed in four CTAB solutions with different concentrations of 0.1 mM, 0.2 mM, 0.5 mM, and 1 mM, and left overnight at 30 °C. Cysteine with a final concentration of 1 μM was added, and the mixed solution was placed in a 30 °C water bath and incubated for 30 min for later use.

[0116] Step (2): 1 mL of the gold nanorod solution with L-Cys adsorbed on the surface obtained in step (1) was centrifuged. After centrifugation at a speed of 12,000 revolutions per minute for 5 min, the precipitate was dispersed in an etching solution, which included an acidic mixed solution of CTAB with a concentration of 0.1 M and 10 mM HCl. Finally, 3 mM FeCl3 was added to initiate the etching reaction. During this process, an ultraviolet-visible-infrared absorption spectrometer was used to record the change in its extinction spectrum at intervals of 0.5 min. The results are as Figures 11-a to 11-c shown.

[0117] For different incubation concentration systems of CTAB, the etching amount and the required etching time corresponding to when the LSPR peak value reaches 1000 nm during the gold nanorod etching process can be seen Figure 11-b . Among them, for the etching of gold nanorods incubated with 1 μM Cys in a 0.2 mM CTAB solution, the TEM morphology corresponding to the LSPR red shift of the gold nanorods in this etching system to 955 nm is as Figure 12 shown. The length of the gold nanorods before etching was 71.7 ± 3.8 nm, while after etching in Figure 12 , the length was 66.7 ± 3.5 nm, indicating that the head was not completely closed and there was a certain degree of etching. The irregularity of the rod morphology after etching increased, with dumbbell shapes, rods with more etching at one end, flat-headed rods, and broken rods, etc., indicating that at a low CTAB coverage, the overall adsorption amount of Cys was large, but the selectivity of the head and side was poor.

[0118] Application Example 8-2 - Judging the influence of adsorption temperature on the adsorption amount and adsorption position of cysteine

[0119] Keeping other conditions unchanged for the several systems described in Example 8-1, only changing the temperature of the gold nanorods and the incubated Cys in step (1). For example, after adding 1 μM Cys to the mixed solution of 1 mM CTAB and gold nanorods, it was placed in a 60 °C water bath and incubated for 30 min. The TEM morphology corresponding to the LSPR red shift of the gold nanorods in this etching system to 980 nm is as Figure 13 shown. Comparing Figure 10In Figure a, the etching of gold nanorods corresponds to a 30 °C incubation system. The length becomes 58.0 ± 5.7 nm, the width becomes 15.0 ± 1.9 nm, and the aspect ratio increases from the original 2.85 ± 0.22 nm to 4.13 ± 0.12 nm. This shows that in 1 mM CTAB, 1 μM Cys adsorbs less on the surface of gold nanorods, and the head adsorption is less and difficult to block. The small amount of Cys adsorbed on the side accelerates together, and the overall performance is uniform etching of the head and side, and finally proceeds in an etching mode with a gradually increasing aspect ratio. In the 60 °C incubation system, the high temperature increases the perturbation of the CTAB layer on the surface of gold nanorods, and more Cys will adsorb on the surface. At the same time, since the better double layer on the side of 1 mM CTAB is destroyed at high temperature, the probability of Cys adsorbing on the side is higher than that under low temperature incubation conditions. As described above, more Cys adsorbed on the side has the same effect as more simple head adsorption in closing the head, both of which promote the etching of the rod side and are more likely to form a dumbbell-shaped morphology.

[0120] In addition, Figure 14 For the variation law of the extinction of 1 μM cysteine-assisted accelerated etching of gold nanorods with large aspect ratio (LSPR 1000 nm ) and gold nanospheres (diameter 40 nm) with time, where a is the case of gold nanorods with large aspect ratio and b is the case of gold nanospheres (diameter 40 nm), indicating the universality of the acceleration of etching by thiol small molecules containing carboxyl functional groups in the field of plasmonic nanoparticles. Figure 15 For the variation law of the etching amount with time of 1 μM cysteine-assisted gold nanorods in the oxidation etching kinetics of 100 mM hydrogen peroxide, compared with the etching of gold nanorods without adding Cys, Cys has no obvious effect on hydrogen peroxide, indicating that the etching mechanism is that Cys complexes with Fe 3+ and brings it to the particle surface to accelerate etching. In addition, it also shows that the acceleration of etching is not caused by the destruction of the surfactant ligand layer by Cys.

[0121] It can be seen from Example 1 and Comparative Example 1 that compared with other types of thiol small molecules containing benzene rings, p-mercaptobenzoic acid significantly assists ferric iron in accelerating the oxidation etching of gold nanorods.

[0122] It can be seen from Examples 2 and 3 that cysteine assists in accelerating the oxidation etching of gold nanorods, and as the concentration increases, the rate increases.

[0123] It can be seen from Examples 1-4 and Comparative Examples 1 and 2 that the carboxyl functional group has the effect of accelerating the etching of gold nanorods in the oxidation etching of ferric iron, that is, the complexation of the carboxyl with ferric iron ions promotes etching. Among them, the distance between the thiol group and the carboxyl group affects the degree of etching acceleration to a certain extent, and the thiol molecule with a benzene ring makes the ligand layer denser due to the hydrophobic effect with the CTAB layer, which inhibits etching to a certain extent.

[0124] From Examples 5 and 6 and Comparative Example 3, it can be seen that the concentration of CTAB in the etching solution affects the speed of the overall etching. When the concentration is low, it will cause the migration of mercapto ligands during the etching process, manifested as LSPR max After a red shift, a blue shift process is shown again, resulting in that after the initial aspect ratio of the cysteine-modified gold nanorods increases during etching, the etching of the head is still the main process in the end.

[0125] From Example 7, it can be seen that the final concentration of cysteine will affect the red shift speed of the LSPR peak of the gold nanorods. As the concentration of cysteine increases, the etching amount per unit time decreases while the red shift amount is more. Further explanation shows that the head is more perfectly closed and the dumbbell-shaped morphology is more obvious.

[0126] From Application Example 8, it can be seen that when the CTAB incubation concentration is low, because the ligand coverage on the side surface of the rod is low, Cys is more likely to adsorb on the side of the rod, thus promoting the etching of the side. When the temperature rises, the total adsorption amount of surface Cys increases. While the adsorption on the head increases, the adsorption amount of Cys on the side also becomes more as the coverage decreases.

[0127] The applicant declares that the present invention uses the above examples to illustrate the process method of the present invention, but the present invention is not limited to the above process steps, that is, it does not mean that the present invention must rely on the above process steps to be implemented. Those skilled in the art should understand that any improvement to the present invention, the equivalent replacement of the raw materials selected for the present invention, the addition of auxiliary components, the selection of specific methods, etc. all fall within the protection scope and the disclosure scope of the present invention.

Claims

1. A method for accelerating the oxidative etching of gold nanoparticles by ferric ions using a carboxyl-containing thiol small molecule, characterized in that, The method includes the following steps: (1) Add a thiol small molecule containing a carboxyl group to the mixed solution of the incubated gold nanoparticles and the surfactant for incubation; the gold nanoparticles are gold nanorods; the thiol small molecule containing a carboxyl group will preferentially adsorb on the head of the gold nanorods; (2) Centrifuge the solution after incubation in step (1), discard the supernatant, disperse the precipitate into the acidified surfactant solution, and then add an etching solution containing ferric ions to initiate the etching reaction; the concentration of ferric ions in the etching system is 1 - 8 mM.

2. The method according to claim 1, characterized in that, In step (1), the gold nanoparticles are gold nanorods with an aspect ratio greater than 1.

3. The method according to claim 1, characterized in that, In step (1), the concentration of the gold nanoparticles in the mixed solution is 0.05 - 0.2 nM.

4. The method according to claim 1, wherein In step (1), the surfactant is cetyltrimethylammonium bromide or a surfactant composed of cetyltrimethylammonium chloride and sodium bromide.

5. The method according to claim 4, wherein In step (1), the surfactant is cetyltrimethylammonium bromide.

6. The method according to claim 1, characterized in that, In step (1), the solvent in the mixed solution is water.

7. The method according to claim 1, wherein In step (1), the concentration of the surfactant in the mixed solution is 0.05 - 100 mM.

8. The method according to claim 1, characterized in that, In step (1), the thiol small molecule containing a carboxyl group is selected from any one or a combination of at least two of cysteine, acetylcysteine, p-mercaptobenzoic acid, or reduced glutathione.

9. The method according to claim 8, characterized in that, In step (1), the thiol small molecule containing a carboxyl group is any one or a combination of at least two of cysteine, reduced glutathione, or p-mercaptobenzoic acid.

10. The method according to claim 1, wherein In step (1), the concentration of the thiol small molecule containing a carboxyl group added to the mixed solution is 1 - 40 μM.

11. The method according to claim 10, wherein In step (1), the concentration of the thiol small molecule containing a carboxyl group added to the mixed solution is 1 - 30 μM.

12. The method according to claim 11, wherein In step (1), the concentration of the thiol small molecule containing a carboxyl group added to the mixed solution is 1 - 10 μM.

13. The method according to claim 1, characterized in that In step (1), the temperature for adding the thiol small molecule containing a carboxyl group for incubation is 30 - 90 °C, and the incubation time is 0.5 - 3 h.

14. The method according to claim 13, wherein In step (1), the temperature for adding the thiol small molecule containing a carboxyl group for incubation is 30 °C, and the incubation time is 0.5 h.

15. The method according to claim 1, wherein In step (2), the centrifugation is carried out at a rotational speed of 8000 - 12000 rpm for 5 - 10 min.

16. The method according to claim 1, characterized in that, In step (2), the acidified surfactant solution is a mixed solution of 10 mM - 100 mM CTAB and 10 mM hydrochloric acid.

17. The method according to claim 1, wherein In step (2), the concentration of the surfactant in the etching system is 1 - 100 mM.

18. The method according to claim 17, wherein In step (2), the concentration of the surfactant in the etching system is 100 mM.

19. The method according to claim 1, wherein The pH value of the etching system should be controlled at 2 - 4.

20. The method according to claim 1, characterized in that, The concentration of ferric ions in the etching system is 3 mM.

21. The method according to claim 1, characterized in that, In step (2), the temperature of the etching reaction is 30 °C, and the etching time is 10 - 40 min.

22. The method according to claim 17, wherein In step (2), when the concentration of the surfactant in the etching system is greater than 10 mM and less than or equal to 100 mM, the oxidation etching of ferric ions is in the fast etching mode.

23. The method according to claim 17, wherein In step (2), when the concentration of the surfactant in the etching system is 1 - 10 mM, the oxidation etching of ferric ions is in the slow etching mode.

24. Application of detecting the spatial distribution of thiol molecules by using a carboxyl-containing thiol small molecule as described in any one of claims 1-23 to accelerate the oxidative etching of gold nanoparticles by ferric ions.

25. The application according to claim 24, characterized in that, The detection of the spatial distribution of thiol molecules is to monitor the etching kinetics by ultraviolet-visible absorption spectroscopy during the process of accelerating the oxidative etching of gold nanoparticles by ferric ions with the carboxyl-containing thiol small molecule.

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