CN-117903213-B - Butyl tin-cycloiridium salicylaldehyde Schiff base complex with AIE characteristics and preparation method and application thereof

CN117903213BCN 117903213 BCN117903213 BCN 117903213BCN-117903213-B

Abstract

The invention discloses a butyltin-cycloiridium salicylaldehyde Schiff base complex with aggregation-induced emission (AIE) characteristics, a preparation method and anticancer application thereof. The structural formula is shown in formula (I), and R is one of hydrogen, chlorine, bromine, methyl, methoxy and trifluoromethoxy. The target compound is tested to have growth inhibition rates on human alveolar basal epithelial cancer cells (A549) and cisplatin-resistant cancer cells (A549/DDP), cervical cancer cells (Hela) and human lung normal epithelial cells (BEAS-2B), and the target compound is found to show potential anti-proliferation activity better than cisplatin through comparison. In addition, the target compounds exhibit unique AIE luminescence properties. The target compound can target mitochondria of A549 cells, and lead to the reduction of mitochondrial membrane potential and show anticancer activity.

Inventors

LIU XICHENG
LIU ZHE
SUN YIWEI
LI GUANGXIAO
HUANG XIAOQING
ZHANG YUMENG

Assignees

曲阜师范大学

Dates

Publication Date: 20260512
Application Date: 20240124

Claims (7)

1. The cycloiridium salicylaldehyde Schiff base complex is characterized in that the structure is shown as a formula (II): ; In the formula (II), R is selected from one of chlorine, bromine, methyl, methoxy and trifluoromethoxy, wherein when R is chlorine, a specific structural formula is shown as a formula Ir2, when R is bromine, a specific structural formula is shown as a formula Ir3, when R is methyl, a specific structural formula is shown as a formula Ir4, when R is methoxy, a specific structural formula is shown as a formula Ir5, and when R is trifluoromethoxy, a specific structural formula is shown as a formula Ir 6; 。
2. A preparation method of a cycloiridium salicylaldehyde Schiff base complex according to claim 1 is characterized by comprising the following steps of reacting a basic iridium dimer Ir1 with a salicylaldehyde-benzoic acid Schiff base, wherein the salicylaldehyde-benzoic acid Schiff base is (E) -4- ((5-chloro-2-hydroxybenzaldehyde) amino) benzoic acid, (E) -4- ((5-bromo-2-hydroxybenzaldehyde) amino) benzoic acid, (E) -4- ((2-hydroxy-5-methylbenzaldehyde) amino) benzoic acid, (E) -4- ((2-hydroxy-5-methoxybenzaldehyde) amino) benzoic acid, and the reaction route is as follows: 。
3. The preparation method of the cycloiridium salicylaldehyde Schiff base complex according to claim 2, which is characterized by comprising the following steps: (1) When the complex is of the formula Ir2, the complex is prepared by the following method: Placing 0.100 g base iridium dimer Ir1, 0.062 g anhydrous sodium acetate and 0.051 g (E) -4- ((5-chloro-2-hydroxybenzaldehyde) amino) benzoic acid in a Schlenk bottle of 100mL, taking a mixed solution of dichloromethane and methanol with the volume ratio of 1:1 as a reaction solvent, stirring the mixed solution at normal temperature under a nitrogen atmosphere for reaction for 12 hours, monitoring the reaction progress by TCL, removing the solvent under reduced pressure after the reaction is finished, dissolving the mixture in dichloromethane, taking dichloromethane/methanol with the volume ratio of 20:1 as an eluent, purifying by a silica gel column chromatography, removing the solvent and drying to obtain an orange solid powder target product Ir2; (2) When the complex is of the formula Ir3, the complex is prepared by the following method: Placing 0.100 g base iridium dimer Ir1, 0.062 g anhydrous sodium acetate and 0.060 g (E) -4- ((5-bromo-2-hydroxybenzaldehyde) amino) benzoic acid in a Schlenk bottle of 100mL, taking a mixed solution of dichloromethane and methanol with the volume ratio of 1:1 as a reaction solvent, stirring the mixed solution at normal temperature under the nitrogen atmosphere for reaction for 12 hours, monitoring the reaction progress by TCL, removing the solvent under reduced pressure after the reaction is finished, dissolving the mixture in dichloromethane, taking dichloromethane/methanol with the volume ratio of 20:1 as an eluent, purifying by a silica gel column chromatography, removing the solvent and drying to obtain an orange solid powder target product Ir3; (3) When the complex is of the formula Ir4, the complex is prepared by the following method: placing 0.100 g base iridium dimer Ir1, 0.062 g anhydrous sodium acetate and 0.048 g (E) -4- ((2-hydroxy-5-methylbenzoyl) amino) benzoic acid in a Schlenk bottle of 100mL, taking a mixed solution of dichloromethane and methanol with the volume ratio of 1:1 as a reaction solvent, stirring at normal temperature under a nitrogen atmosphere for reacting for 12 hours, monitoring the reaction progress by TCL, removing the solvent under reduced pressure after the reaction is finished, dissolving the mixture in dichloromethane, taking dichloromethane/methanol with the volume ratio of 20:1 as an eluent, purifying by a silica gel column chromatography, removing the solvent and drying to obtain an orange solid powder target product Ir4; (4) When the complex is of the formula Ir5, the complex is prepared by the following method: Placing 0.100g base iridium dimer Ir1, 0.062g anhydrous sodium acetate and 0.051 g (E) -4- ((2-hydroxy-5-methoxybenzaldehyde) amino) benzoic acid in a Schlenk bottle of 100mL, taking a mixed solution of dichloromethane and methanol with the volume ratio of 1:1 as a reaction solvent, stirring at normal temperature under a nitrogen atmosphere for reacting for 12 hours, monitoring the reaction progress by TCL, removing the solvent under reduced pressure after the reaction is finished, dissolving the mixture in dichloromethane, taking dichloromethane/methanol with the volume ratio of 20:1 as an eluent, purifying by a silica gel column chromatography, removing the solvent and drying to obtain an orange red solid powder target product Ir5; (5) When the complex is of the formula Ir6, the complex is prepared by the following method: The preparation method comprises the steps of placing 0.100 g base iridium dimer Ir1, 0.062 g anhydrous sodium acetate and 0.061 g (E) -4- ((2-hydroxy-5- (trifluoromethoxy) benzaldehyde) amino) benzoic acid in a Schlenk bottle of 100 mL, taking a mixed solution of dichloromethane and methanol with the volume ratio of 1:1 as a reaction solvent, stirring the mixed solution at normal temperature under a nitrogen atmosphere for reaction for 12 hours, monitoring the reaction progress by TCL, decompressing and removing the solvent after the reaction is finished, dissolving the mixture in dichloromethane, taking dichloromethane/methanol with the volume ratio of 20:1 as an eluent, purifying by a silica gel column chromatography, removing the solvent and drying to obtain a red solid powder target product Ir6.
4. The butyl tin-cycloiridium salicylaldehyde Schiff base complex is characterized in that the structure is shown as a formula (I): ; In the formula (I), R is selected from one of hydrogen, chlorine, bromine, methyl, methoxy and trifluoromethoxy, wherein in the formula (I), when R is hydrogen, the specific structural formula is shown in the formula (1), when R is chlorine, the specific structural formula is shown in the formula (2), when R is bromine, the specific structural formula is shown in the formula (3), when R is methyl, the specific structural formula is shown in the formula (4), when R is methoxy, the specific structural formula is shown in the formula (5), and when R is trifluoromethoxy, the specific structural formula is shown in the formula (6); 。
5. A process for preparing a butyltin-cycloiridium salicylaldehyde Schiff base complex as claimed in claim 4, comprising the steps of Reacting with hexabutyltin oxide molecules to obtain a target complex shown in a formula (I), wherein the reaction route is as follows: 。
6. The preparation method of the butyltin-cycloiridium salicylaldehyde Schiff base complex according to claim 5, which is characterized by comprising the following steps of: (1) When the complex is represented by the formula (1), the complex is prepared by the following method: Placing 0.050 g, R=H cycloiridium salicylaldehyde Schiff base complex and 17.19 mu L of hexabutyltin oxide in a Dean-Stark device, taking 90 mL volume ratio of benzene and ethanol mixed solution as a solvent, heating and refluxing at 110 ℃ for 12H, decompressing after the reaction is finished, removing the solvent, and recrystallizing the obtained solid in volume ratio of 1:2 of dichloromethane and petroleum ether mixed solution to obtain an orange-yellow solid target product (1); (2) When the complex is represented by the formula (2), the complex is prepared by the following method: Placing 0.050 g, R=Cl cycloiridium salicylaldehyde Schiff base complex and 16.43 mu L of hexabutyltin oxide in a Dean-Stark device, taking 90 mL volume ratio of benzene and ethanol mixed solution as a solvent, heating and refluxing at 110 ℃ for 12 h, decompressing after the reaction is finished, removing the solvent, and recrystallizing the obtained solid in volume ratio of 1:2 of dichloromethane and petroleum ether mixed solution to obtain an orange-yellow solid target product (2); (3) When the complex is represented by the formula (3), the complex is prepared by the following method: placing 0.050 g, R=Br cycloiridium salicylaldehyde Schiff base complex and 15.54 mu L of hexabutyltin oxide in a Dean-Stark device, taking a mixed solution of benzene and ethanol with the volume ratio of 90 mL being 2:1 as a solvent, heating and refluxing for 12 h at 110 ℃, decompressing after the reaction is finished, removing the solvent, and recrystallizing the obtained solid in a mixed solution of dichloromethane and petroleum ether with the volume ratio of 1:2 to obtain an orange-yellow solid target product (3); (4) When the complex is represented by the formula (4), the complex is prepared by the following method: Placing 0.050 g, R=Me cycloiridium salicylaldehyde Schiff base complex and 16.87 mu L of hexabutyltin oxide in a Dean-Stark device, taking 90 mL volume ratio of benzene to ethanol mixed solution as a solvent, heating and refluxing at 110 ℃ for 12 h, decompressing after the reaction is finished, removing the solvent, and recrystallizing the obtained solid in volume ratio of 1:2 of dichloromethane to petroleum ether mixed solution to obtain an orange solid target product (4); (5) When the complex is represented by the formula (5), the complex is prepared by the following method: Placing 0.050 g, a cycloiridium salicylaldehyde Schiff base complex with R=OCH 3 and 16.52 mu L of hexabutyltin oxide in a Dean-Stark device, taking a mixed solution of benzene and ethanol with the volume ratio of 90 mL being 2:1 as a solvent, heating and refluxing at 110 ℃ for 12h, decompressing after the reaction is finished, removing the solvent, and recrystallizing the obtained solid in a mixed solution of dichloromethane and petroleum ether with the volume ratio of 1:2 to obtain an orange-red solid target product (5); (6) When the complex is represented by the formula (6), the complex is prepared by the following method: The preparation method comprises the steps of placing 0.050 g, R=OCF 3 of a cycloiridium salicylaldehyde Schiff base complex and 15.44 mu L of hexabutyltin oxide in a Dean-Stark device, taking 90 mL volume ratio of a mixed solution of benzene and ethanol as a solvent, heating and refluxing at 110 ℃ for 12 h, decompressing after the reaction is finished, removing the solvent, and recrystallizing the obtained solid in the mixed solution of dichloromethane and petroleum ether with the volume ratio of 1:2 to obtain a red solid target product (6).
7. An application of the butyltin-cycloiridium salicylaldehyde Schiff base complex prepared by the preparation method of claim 6 in the field of anticancer drugs.

Description

Butyl tin-cycloiridium salicylaldehyde Schiff base complex with AIE characteristics and preparation method and application thereof Technical field: The invention relates to a metal organic compound, in particular to a butyltin-cycloiridium salicylaldehyde Schiff base complex with AIE characteristics, and a preparation method and application thereof, and belongs to the field of chemical pharmacy. The background technology is as follows: Today in the twentieth century, cancer remains one of a highly-developed and highly-fatal group of human diseases. Chemotherapy is a common cancer treatment in the clinic. However, most platinum-based metal drugs used in clinic have the defects of high drug resistance, high toxic and side effects and the like, and the defects of the platinum-based metal drugs stimulate the exploration of other transition metal anti-cancer drugs, wherein the platinum-based metal drugs comprise Ru (II), rh (III), ir (III) and Sn (IV)) complexes (chem. Soc. Rev.2015,44, 8818-8835). The third transition metal iridium has been shown to have potent antiproliferative activity against cancer cells (acc. Chem. Res.2014,47, 1174-1185). According to structural characteristics, the iridium metal anticancer complex can be divided into a half sandwich structure and a ring iridium structure (Inorg. Chem.2023,62, 3395-3408). Among them, the iridium-based complex is widely used in fields of bioimaging, biosensing, anticancer, etc. due to its good photophysical properties (inorg. Chem.2013,52, 974-982). In addition, the butyltin compound also has obvious anti-tumor activity (appl. Organomet. Chem.2018,32,4475), but the serious toxic and side effects greatly limit the application range. In addition, the cyclic metal complex and the butyltin compound show weak fluorescence or luminescence quenching (ACQ) phenomenon caused by aggregation, which is very unfavorable for research on subcellular tissue targeting and the like, until the aggregation-induced emission (AIE) effect discovered by Tang Benzhong team effectively avoids fluorescence quenching caused by molecular aggregation, the metal compound with AIE characteristics is widely applied to fields such as photocatalysis, light-emitting diodes, biomedicine and the like (ACS cent. Sci.2020,6, 1689-1712), but the multi-active-center heteronuclear metal complex with AIE characteristics is not common in the research and development of anticancer drugs. The invention comprises the following steps: In view of this, the present invention introduces tributyltin molecules with good anticancer potential for increasing the anticancer activity of the complex as a whole. In addition, because of the existence of an imine bond in the Schiff base, a nitrogen atom on a hybridization orbit of the Schiff base has a lone pair electron, so that the Schiff base has good coordination capability, and the Schiff base can be coordinated with metallic iridium to obtain an iridium-tin multi-metal center complex with AIE characteristics, so that the target complex has good photophysical properties while playing good anticancer activity. The good AIE luminescence property can be used for detecting the target position (mitochondria) of a target complex in cancer cells, so that the target complex is hopeful to become a novel mitochondria targeting type metal anticancer drug. The structure of the cycloiridium salicylaldehyde Schiff base complex is shown as a formula (II): And R is selected from one of chlorine, bromine, methyl, methoxy and trifluoromethoxy. A butyltin-cycloiridium salicylaldehyde Schiff base complex has a structure shown in a formula (I): r is selected from one of hydrogen, chlorine, bromine, methyl, methoxy and trifluoromethoxy. Further, the chemical structural formula of the butyltin-cycloiridium salicylaldehyde Schiff base complex is as follows: The invention provides a preparation method of the complex, which comprises the steps of reacting a salicylaldehyde Schiff base benzoic acid compound with a base iridium dimer (Ir 1) to obtain a complex (Ir 2-Ir 6) shown in a formula (II), wherein the salicylaldehyde Schiff base benzoic acid is (E) -4- ((5-chloro-2-hydroxybenzaldehyde) amino) benzoic acid, (E) -4- ((5-bromo-2-hydroxybenzaldehyde) amino) benzoic acid, (E) -4- ((2-hydroxy-5-methylbenzoyl) amino) benzoic acid, (E) -4- ((2-hydroxy-5-methoxybenzaldehyde) amino) benzoic acid, and reacting the complex shown in the formula (II) with hexabutyl tin oxide (Bu 6Sn2 O) molecules to obtain a target complex shown in the formula (I), wherein the specific reaction route is as follows: further, when the compound is of formula (1), it is prepared by the following method: (1) 0.100g (Ir 1), 0.062g anhydrous sodium acetate, 0.045g (E) -4- ((2-hydroxybenzaldehyde) amino) benzoic acid were placed in a 100mL Schlenk flask, a 20mL mixed solution (1:1, v/v) of dichloromethane and methanol was used as a reaction solvent, the reaction was stirred at room temperature under nitrogen atmosphere fo