A water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex and its preparation method and application

Abstract

The invention discloses a water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex and its application as a catalyst in photolysis of water to produce hydrogen, and in preparing photosensitizers and photothermal agents for photodynamic therapy of tumors. The synthesis route of the ruthenium platinum complex of the invention is: cis-[Ru(bpy)2Cl2] and 1,10-phenanthroline-5,6-dione are reacted in an ethanol aqueous solution, and then refluxed with pyrazino[2,3-f][1,10]phenanthroline-2,3-diamine in glacial acetic acid, acetonitrile, and ethanol solution to generate a mononuclear complex Ru-pppp, and then react with cis-[Pt(DMSO)2Cl2] to obtain a target compound RuPt1. Ru-pppp reacts with [Pt2(ppy)2Cl2] to obtain a target compound RuPt2. The ruthenium-platinum binuclear heterometallic complex prepared by the present invention combines the excellent photosensitivity of polypyridine ruthenium complexes with the high catalytic activity of platinum complexes, can be used as a photosensitizer and catalyst at the same time, catalyze the photolysis of water to produce hydrogen, and the singlet oxygen generation reaction, and has a high photothermal conversion efficiency. It is a potential new type of photodynamic photosensitizer and photothermal agent, and has broad application prospects in the preparation of photodynamic-photothermal dual treatment of tumors.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogen production by photolysis of water, and in particular to a water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex and its application in hydrogen production by photolysis of water, and preparation of photosensitizer and photothermal agent for tumor photodynamic therapy. Background Art

[0002] The waste gas pollution generated by the use of fossil energy such as coal, oil and natural gas seriously threatens the global ecology. The heavy dependence on fossil fuels has caused people to worry about the sustainability and environmental impact of modern energy production. Hydrogen is an efficient and ideal clean energy. Due to its many advantages such as pollution-free combustion, abundant and renewable, it is considered to be one of the more ideal energy sources to replace traditional fossil energy. Hydrogen is mainly stored in water in the form of compounds, and water is the most widely distributed substance in the world. In addition, its combustion products can be decomposed into hydrogen and oxygen again and reused. Compared with photolysis of water, traditional electrolysis of water requires a large amount of fossil energy to provide electricity, while solar energy is inexhaustible and can be directly developed and utilized without mining and transportation. It is one of the cleanest energy sources. Therefore, the use of photocatalytic decomposition of water to produce hydrogen is a solution with broad development prospects and helps to achieve sustainable social development.

[0003] Studies have shown that photocatalytic performance can be adjusted through the design of bridging ligands. The type of catalytic center determines not only the stability and activity, but also the mechanism of light-driven water splitting to produce hydrogen. Recently, researchers have developed a photocatalyst for hydrogen production from water by photolysis, Ru(tpphz)PtI2, which not only shows relatively high catalytic activity, but also has high long-term stability. Studies have also shown that conjugated bridging ligands with sizes larger than 2,2′-bipyridine enhance the stability of the Ru-Cl bond of the catalytic center designed for water oxidation. Therefore, designing a bridging ligand to conjugate the two metal centers can achieve efficient electron and energy transfer between the catalytic center and the photosensitive center, which is of great significance to the key issue of improving the performance of photocatalytic hydrogen production from water splitting. Summary of the invention

[0004] The first inventive object of the present invention is to provide a water-soluble fully conjugated bridged hetero-dinuclear ruthenium-platinum complex in view of the current research progress in photocatalytic water decomposition to produce hydrogen, which can serve as both a photosensitizer and a catalyst and exhibits good photocatalytic water decomposition to produce hydrogen performance.

[0005] The technical solution adopted by the present invention is as follows: a fully conjugated bridged heterobinuclear ruthenium platinum complex, composed of a cation and an anion, characterized in that the cation has a structural formula as shown in Formula I:

[0006]

[0007] Furthermore, the fully conjugated bridged heterobinuclear ruthenium platinum complex does not limit the type of anion, and conventional anions in the technical field can achieve the purpose of the present invention. Preferably, the anion is an inorganic salt anion, more preferably PF6 － 、ClO4 － , Cl － 、NO3 － 、BF4 － or BPh4 － As a most preferred embodiment, the anion of the fully conjugated bridged heterobinuclear ruthenium platinum complex of the present invention is PF6 － .

[0008] The second object of the present invention is to provide a method for preparing the above-mentioned fully conjugated bridged heterobinuclear ruthenium platinum complex.

[0009] The technical solution adopted by the present invention is as follows: A method for preparing a fully conjugated bridged heterobinuclear ruthenium-platinum complex, characterized in that it comprises the following steps:

[0010] Step 1: Mix the ligand 1,10-phenanthroline-5,6-dione (dione) and the precursor cis-[Ru(bpy)2Cl2] in a solution of ethanol and water, and heat under reflux to generate [Ru(bpy)2(dione)] 2+ ;

[0011] Step 2: Add the above [Ru(bpy)2(dione)] 2+ After reflux reaction with pyrazino[2,3-f][1,10]phenanthroline-2,3-diamine in acetic acid, acetonitrile and ethanol solution under argon, the mononuclear key intermediate [Ru(bpy)2(pppp)] 2+ (Ru-pppp);

[0012] Step 3, reflux the Ru-pppp and cis-[Pt(DMSO)2Cl2] in methanol to obtain the target compound RuPt1;

[0013] Step 4: reflux the Ru-pppp and [Pt2(ppy)2Cl2] in methanol to obtain the target compound RuPt2.

[0014] Further, in order to obtain a high yield of mononuclear ruthenium ligand, the step 2 is specifically: [Ru(bpy)2(dione)] 2+ , acetonitrile, pyrazino[2,3-f][1,10]phenanthroline-2,3-diamine, glacial acetic acid, and ethanol were added to the reaction vessel and refluxed under argon to obtain the mononuclear complex [Ru(bpy)2(pppp)] 2+ (Ru-pppp);

[0015] Furthermore, in order to improve the purity of the mononuclear ruthenium ligand, the reaction was dried by rotation, acetonitrile was added for ultrasonic dissolution, and then the mixture was passed through a column and allowed to stand and dry to obtain a high-purity mononuclear complex Ru-pppp.

[0016] Furthermore, the step 3 is specifically as follows: dissolving the mononuclear ruthenium complex Ru-pppp in anhydrous methanol, adding cis-[Pt(DMSO)2Cl2] to reflux reaction, and standing to dry to obtain the target product, a fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt1.

[0017] Furthermore, the step 4 is specifically as follows: dissolving the mononuclear ruthenium complex Ru-pppp in anhydrous methanol, adding [Pt2(ppy)2Cl2] to reflux reaction, and standing to dry to obtain the target product, a fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt2.

[0018] The third object of the present invention is to provide a fully conjugated bridged heterobinuclear ruthenium platinum complex for use in photocatalytic water splitting to produce hydrogen.

[0019] Furthermore, when the ruthenium-platinum binuclear heterometallic complex is used for photolysis of water to produce hydrogen, the ruthenium-platinum binuclear heterometallic complex is used as a photosensitizer and catalyst for photolysis of water.

[0020] The fourth object of the present invention is to provide a fully conjugated bridged heterobinuclear ruthenium platinum complex for use in the preparation of photosensitizers and photothermal agents for tumor photodynamic therapy.

[0021] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0022] 1. The fully conjugated bridged heterobinuclear ruthenium platinum complex provided by the present invention can be used as a photocatalyst for visible light water splitting to produce hydrogen. It has a stable structure and good, wide-range spectral absorption properties. It is a new type of single-molecule photosensitive-catalytic system for water splitting to produce hydrogen, and has obtained good catalytic performance;

[0023] 2. The fully conjugated bridged heterobinuclear ruthenium platinum complex designed by the present invention combines the excellent photosensitivity of polypyridine ruthenium complexes with the high catalytic activity of platinum complexes, and can be used as a single-molecule photosensitizer and photocatalyst at the same time, making the energy / electron transfer process between the photosensitizer and the catalytic center extremely convenient, greatly enhancing the catalytic activity of photocatalytic water splitting to produce hydrogen;

[0024] 3. When the water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex of the present invention is used in photolysis of water to produce hydrogen, it has the following advantages: (1) it has good water solubility; (2) it has good spectral properties, especially excellent light absorption properties in the visible region. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1A synthetic route for the fully conjugated bridged heterobinuclear ruthenium-platinum complex prepared by the present invention;

[0026] Figure 2 This is an absorption spectrum of the fully conjugated bridged heterobinuclear ruthenium-platinum complex prepared in the present invention in aqueous solution;

[0027] Figure 3 This is a graph showing the experimental data of the fully conjugated bridged heterobinuclear ruthenium-platinum complex prepared in the present invention for photolysis of water to produce hydrogen in the visible region;

[0028] Figure 4 This is an experimental data diagram of light-induced singlet oxygen production of the fully conjugated bridged heterobinuclear ruthenium-platinum complex prepared by the present invention;

[0029] Figure 5 This is a graph of experimental data on photothermal conversion of the fully conjugated bridged heterobinuclear ruthenium-platinum complex prepared in the present invention. DETAILED DESCRIPTION

[0030] The present invention will be described in detail below in conjunction with the accompanying drawings.

[0031] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the accompanying drawings and Examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art, and the reagents and materials used are all commercially available.

[0032] Example 1

[0033] Preparation of fully conjugated bridged heterobinuclear ruthenium platinum complexes:

[0034] Step 1: In a 150 ml conical flask, add 0.210 g of ligand 1,10-phenanthroline-5,6-dione to a suspension of 0.520 g of precursor cis-[Ru(bpy)2Cl2] in 30 ml of ethanol and water (1:1), stir well, heat under reflux at 85 ° C for 3 hours, add 0.200 g of NH4PF6 after cooling, stir to precipitate a large amount of brown crystals, let stand and filter, wash with water and dry to obtain 0.340 g of solid powder product [Ru(bpy)2(dione)] 2+ , the calculated yield is 55%;

[0035] Step 2: 0.624 g of the above [Ru(bpy)2(dione)] 2+Dissolve 0.210g of pyrazino[2,3-f][1,10]phenanthroline-2,3-diamine in 20ml of acetonitrile, and dissolve it in a mixed solution of glacial acetic acid and ethanol (1:1). After reflux at 120℃ for 12 hours under argon, evaporate the solvent and chromatograph it on an acetonitrile column to obtain a solid powder, which is the mononuclear complex [Ru(bpy)2(pppp)] 2+ (Ru-pppp);

[0036] Step 3: Dissolve 0.202 g of the above mononuclear ruthenium complex Ru-pppp and 0.111 g of cis-[Pt(DMSO)2Cl2] in 30 ml of anhydrous methanol, reflux at 65°C for 15 hours, and allow to stand to precipitate a solid, which is the target product, a fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt1, with a yield of 87%. 1 HNMR(400MHz,DMSO-d6)δ(ppm):9.67(s,4H),9.21(s,2H),8.92(t,J=9.6Hz,4H),8.35(s,2H),8.26(td,J=7.9,1.5Hz,2H),8.17(td,J=7.9,1.5 Hz,2H),8.10(s,2H),8.04(s,2H),7.90(d,J=5.7Hz,2H),7.85(d,J=5.2Hz,2H),7.63(t,J=6.3Hz,2H),7.45(t,J=6.3Hz,2H).ESI-MS(MeOH)m / z calc.for C 46 H 28 Cl2N 12 PtRu[M–2PF6] 2+ :558.0348;Found:558.0288.

[0037] Step 4: Dissolve the above-mentioned 0.202 g of mononuclear ruthenium complex Ru-pppp and 0.060 g of [Pt2(ppy)2Cl2] in 50 ml of anhydrous methanol, reflux at 65°C under argon for 20 hours, add 0.200 g of NH4PF6 after cooling, precipitate, filter, wash and dry to obtain a crude product, and then chromatograph it with toluene and acetonitrile (1:2, v:v) as eluent to collect the brown component, which is the target product, the fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt2, with a yield of 47%. 1H NMR (400MHz, DMSO-d6) δ (ppm): 10.15 (s, 2H), 9.74 (dd, J = 28Hz, 2H), 9.20 (s, 1H), 8.98– 8.82(m,5H),8.56(s,2H),8.28(dd,J=20Hz,5H),8.18(t,J=7.8Hz,5H),7.92(d,J=7.6H z,1H),7.85(d,J=5.7Hz,5H),7.68(s,1H),7.64(t,J=6.7Hz,2H),7.57(d,J=7.5Hz,1H) ,7.45(t,J=6.8Hz,2H),7.40(d,J=7.5Hz,1H),7.32(t,J=7.4Hz,1H).ESI-MS(MeOH)m / z calc.for C 57 H 36 N 13 PtRu[M–3PF6] 3+ :399.7297;Found:399.7302.

[0038] Example 2

[0039] Absorption spectrum test of fully conjugated bridged heterobinuclear ruthenium platinum complex:

[0040] At 25°C, the fully conjugated bridged heterobinuclear ruthenium platinum complex was prepared into a 10 μM aqueous solution, and the UV-visible absorption spectrum was measured in the range of 300-800 nm. Figure 2 It can be seen that the fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt1 has a strong absorption peak at 450nm in the visible region, and RuPt2 has a strong absorption peak at 430nm in the visible region.

[0041] Example 3

[0042] Photocatalytic water splitting test of fully conjugated bridged heterobinuclear ruthenium platinum complex:

[0043] The ruthenium-platinum binuclear heterometallic complex was prepared into a pure aqueous solution with a concentration of 28.44 μM. 50 ml of the solution was taken and the pH was adjusted to 4.3. The photolysis of water was carried out in a Labsolar-6A all-glass automatic online trace gas analysis system. The samples were automatically taken at intervals of 20 minutes, and the hydrogen production was analyzed by gas chromatography. Figure 3 It can be seen that the fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt1 has a high efficiency in photolysis of water to produce hydrogen, with a TON of 64.5 at 260 minutes. It is followed by the complex RuPt2, whose TON is 20.0. The TON of the mononuclear ruthenium complex Ru-pppp without a platinum catalytic center is only 1.21, proving the necessity of the heteronuclear combination structure of ruthenium platinum for the photolysis of water to produce hydrogen.

[0044] Therefore, the fully conjugated bridged heterobinuclear ruthenium platinum complex prepared by the present invention has strong visible light absorption properties, can be used as a photosensitizer and catalyst at the same time, can be used as a homogeneous photosensitizer and catalyst for single-molecule photolysis of water to produce hydrogen in aqueous solution, has good catalytic performance, and can effectively catalyze the photolysis of water to produce hydrogen.

[0045] Example 4

[0046] Photoexcited singlet oxygen generation performance of fully conjugated bridged heterobinuclear ruthenium-platinum complexes:

[0047] ABDA (9,10-anthracenediyl-bis(methylene)dimalonic acid) was used as singlet oxygen ( 1 O2) capture agent, prepare an ABDA solution containing the complex RuPt1, RuPt2 or Ru-pppp, the solution is prepared using pure water as solvent, wherein the concentration of the complex is 10 μM, and the concentration of ABDA is 100 μM.

[0048] The singlet oxygen generation efficiency of the complex was studied by measuring the absorption spectrum changes of ABDA solution containing complex RuPt1, RuPt2 or Ru-pppp using UV / Vis spectrophotometer. The UV absorption spectrum of singlet oxygen scavenger ABDA in the solution after irradiation with 450nm or 808nm light in the presence of complex RuPt1, RuPt2 or Ru-pppp is shown in the figure below. Figure 4 Experiments show that the fully conjugated bridged heterobinuclear ruthenium platinum complex provided by the present invention has a very strong ability to induce the production of singlet oxygen under visible light and infrared light excitation.

[0049] Example 5

[0050] Infrared photothermal conversion capability of fully conjugated bridged heterobinuclear ruthenium-platinum complexes:

[0051] Using PBS buffer containing 10% DMSO as a control, 808nm infrared light was used to illuminate the solution of 100μM complex RuPt1, RuPt2 or Ru-pppp (the solvent was PBS buffer containing 10% DMSO), and thermal imaging of the solution was performed at 0 minutes, 1 minute, 2 minutes, 5 minutes and 10 minutes. The results are shown in Figure 2. Figure 5 shown.

[0052] according to Figure 5It can be seen that compared with the control group PBS, the complex RuPt1 of the present invention generates significant heat under 808nm light conditions; while the complexes RuPt2 and Ru-pppp generate less heat under the same conditions. The above results show that the fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt1 provided by the present invention has excellent infrared light-to-heat conversion ability, while the complexes RuPt2 and Ru-pppp have relatively weak light-to-heat conversion ability.

[0053] Example 6

[0054] Inhibitory activity of fully conjugated bridged heterobinuclear ruthenium-platinum complexes against melanoma growth:

[0055] The binuclear ruthenium complex of the present invention is dissolved in a 0.9% DMSO-PBS buffer solution. The tested complex is prepared into a desired concentration using a culture medium containing 10% serum, and the CCK-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid benzene)-2H-tetrazole monosodium salt) method is used to detect the inhibitory effect of the target complex on the proliferation and growth of human malignant melanoma cell line (A375), and cisplatin is used as a positive control.

[0056] CCK-8 method: Inoculate cells in the logarithmic growth phase into a 96-well culture plate, incubate at 37°C and 5% CO2 for 24 hours, then add different concentrations of drugs. Set up 3 groups of repeated experiments for each concentration, and set up solvent controls of corresponding concentrations. After incubating the cells and drugs together for 15 hours, replace with new culture medium and irradiate with 450nm visible light or 808nm infrared light for 5 minutes. Continue incubation for 48 hours, stain the cells with CCK-8, measure the OD value with an enzyme reader, and calculate the cell growth inhibition rate with the following formula. According to the inhibition rate of each concentration, calculate the half inhibitory concentration IC according to the nonlinear regression method. 50 , and according to the IC under dark conditions and light conditions 50 The phototoxicity index PI under light is calculated by the value, and the specific calculation formula is as follows:

[0057] Inhibition rate = (OD value 对照孔 -OD value 给药孔 ) / OD value 对照孔 ×100%

[0058] Phototoxicity index PI = IC 50 Dark / IC 50 Light

[0059] The fully conjugated bridged heterodinuclear ruthenium-platinum complexes RuPt1 and RuPt2 inhibit melanoma growth with phototoxicity indexes PI of 119 and 846 respectively under 450nm visible light excitation and phototoxicity indexes PI of 243 and 1512 respectively under 808nm infrared light excitation, making them potential drug molecules for effective phototherapy of melanoma.

[0060] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex, consisting of a cation and an anion, characterized in that: The structural formula of the cation is shown in Formula I:

2. The water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex according to claim 1, characterized in that: The anion is an inorganic salt anion.

3. The water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex according to claim 1, characterized in that: The anion is PF6 － 、ClO4 － , Cl － 、NO3 － 、BF4 － or BPh4 － .

4. The method for preparing the water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex according to claim 1, characterized in that: The following steps are involved: (i) mixing the compounds having the structures represented by formula a and formula b in an organic solvent for coordination reaction to obtain a compound having the structure represented by formula c; (ii) mixing the compound having the structure shown in formula c and the compound having the structure shown in formula d in an organic solvent for condensation reaction to obtain an intermediate ruthenium complex having the structure shown in formula e; (iii) mixing the compound having the structure shown in formula e and the compound having the structure shown in formula f in an organic solvent for a second coordination reaction to obtain an anion of Cl － A water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt1 having a structure shown in Formula I; (iv) mixing the compound having the structure shown in formula e and the compound having the structure shown in formula g in an organic solvent for a second coordination reaction to obtain an anion of Cl － A water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex RuPt2 having a structure shown in Formula I; 5. The preparation method according to claim 4, characterized in that: The reaction temperature in step (i) is 40 to 80° C. and the reaction time is 1 to 24 hours; The condensation reaction temperature in step (ii) is 80 to 130° C. and the reaction time is 1 to 24 hours; The condensation reaction in step (iii) is carried out at a temperature of 40 to 60° C. and for a time of 1 to 24 hours; The condensation reaction temperature in step (iv) is 40-60° C. and the reaction time is 1-24 hours.

6. The preparation method according to claim 4, characterized in that: In the step (iv), after the second coordination reaction is completed, the aqueous solution containing an anion compound is added to the obtained reaction solution to convert the Cl in the water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex into － Make a replacement.

7. Use of the water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex according to claim 1 in a catalyst for photocatalytic hydrogen production from water.

8. Use of the water-soluble fully conjugated bridged heterobinuclear ruthenium platinum complex according to claim 1 in the preparation of photosensitizers and photothermal agents for tumor photodynamic therapy.

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