CN101781325A - Gallium salicylaldehyde amino acid Schiff base quaternary coordination compound, preparation method and application thereof - Google Patents
Gallium salicylaldehyde amino acid Schiff base quaternary coordination compound, preparation method and application thereofDownload PDFInfo
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Abstract
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Translated fromChinese所属技术领域Technical field
本发明涉及金属抗肿瘤药物化学领域，具体说是涉及到一种镓水杨醛氨基酸希夫碱四元配合物及其制备方法和应用。The invention relates to the field of metal anti-tumor medicinal chemistry, in particular to a gallium salicylaldehyde amino acid Schiff base quaternary complex and its preparation method and application.
背景技术Background technique
恶性肿瘤是当今社会危害人类健康的主要杀手。迄今为止，化疗药物是治疗肿瘤的主要药物。在目前广泛使用的抗癌药物中，第一个金属抗癌药物顺铂的发明使人类首次获得一种抗实体瘤的武器，但是与很多化疗药物一样，它仍然存在抗药性、毒副性、使用范围窄问题。此外，有些癌症至今还没有特效治疗药物，因此需要不懈地开发高效、低毒的新型抗癌药物。GaIII化合物是目前的一个新兴研究方向，具有重要的现实意义。研究表明，GaIII的配位化学与FeIII相似，在生命体中它可以通过模仿FeIII的行为而对生命必需元素铁的代谢产生干扰(例如通过铁传递蛋白)，这可能是其产生药物活性的一种重要途径。此外，已有证据揭示镓配合物还具有其他作用机理，这意味着它产生生物学活性的途径是多样化的，这对于开发其新型药物极有意义。镓的简单盐硝酸镓(GaN)已经作为抗癌药物在临床使用(例如治疗继发性癌症高钙血症、非何杰金氏淋巴瘤)，但是其生物利用率不够高。另一个简单盐氯化镓在临床上与其他药物配合使用时，可增强疗效。至今不断有动物实验、药代动力学研究及临床研究结果证明某些镓配合物具有明显的抑瘤效应，且毒副作用小。GaIII配合物中引入了有机配体，尤其是螯合配体，分子获得较好的稳定性，抗癌活性得到改善。例如，八羟基喹啉镓(tris(8-quinolinato)galliumIII，KP46)具有很强的抗癌活性，口服比氯化镓的生物特效性好，但由于毒副作用较高而终止于一期临床试验。而麦芽酚Ga(galliumIIImaltolate，GaM)在I/II临床试验中表现出治疗癌症、传染病、炎症的潜在口服药物特质。鉴于GaIII的优异抗增生品质，如何通过引入相适应的配体，将镓的亲肿瘤特性与希夫碱的抑菌抗增生活性相结合，增强配合物的DNA靶向性，从而研制出制备简便、价格低廉、热力学稳定性及动力学稳定性适宜、具有抗肿瘤活性的新型镓配合物，是本技术领域目前需要解决的一个重要课题。Malignant tumors are the main killers that endanger human health in today's society. So far, chemotherapy drugs are the main drugs for the treatment of tumors. Among the currently widely used anticancer drugs, the invention of the first metal anticancer drug cisplatin enables humans to obtain a weapon against solid tumors for the first time, but like many chemotherapy drugs, it still has drug resistance, side effects, Narrow range of use. In addition, some cancers have no specific therapeutic drugs so far, so it is necessary to unremittingly develop new anticancer drugs with high efficiency and low toxicity. GaIII compound is an emerging research direction at present, which has important practical significance. Studies have shown that the coordination chemistry of GaIII is similar to that of FeIII . In living organisms, it can interfere with the metabolism of iron, an essential element of life, by imitating the behavior of FeIII (such as through transferrin), which may be the reason for its production of drugs. An important way of activity. In addition, evidence has revealed that gallium complexes have other mechanisms of action, which means that the pathways for their biological activity are diverse, which is of great significance for the development of new drugs. The simple salt of gallium, gallium nitrate (GaN), has been used clinically as an anticancer drug (eg, in the treatment of secondary cancer hypercalcemia, non-Hodgkin's lymphoma), but its bioavailability is not high enough. Another simple salt, gallium chloride, can enhance the efficacy when used in combination with other drugs in clinical practice. So far, animal experiments, pharmacokinetic studies and clinical research results have proved that certain gallium complexes have obvious tumor-inhibiting effects, and have little toxic and side effects. Organic ligands, especially chelating ligands, are introduced into the GaIII complex, the molecules get better stability and the anticancer activity is improved. For example, gallium octahydroxyquinolate (tris(8-quinolinato) galliumIII , KP46) has strong anticancer activity, and its biospecific effect is better than that of gallium chloride when taken orally, but it was terminated in phase I clinical trials due to its high toxicity and side effects test. And maltol Ga (galliumIII maltolate, GaM) in I/II clinical trials showed potential oral drug properties for the treatment of cancer, infectious diseases, and inflammation. In view of the excellent anti-proliferative properties of GaIII , how to combine the pro-tumor properties of gallium with the antibacterial and anti-proliferative activities of Schiff base by introducing suitable ligands to enhance the DNA targeting of the complexes, so as to develop a preparation A novel gallium complex that is simple, cheap, suitable for thermodynamic stability and kinetic stability, and has antitumor activity is an important subject to be solved in this technical field.
发明内容Contents of the invention
本发明的目的是提供一种稳定性适宜，制备简便且价格低廉，应用在抗肿瘤药物领域的镓水杨醛氨基酸希夫碱四元配合物，同时还提供镓水杨醛氨基酸希夫碱四元配合物的制备方法。The purpose of the present invention is to provide a gallium salicylaldehyde amino acid Schiff base quaternary complex with suitable stability, easy preparation and low price, which is applied in the field of antitumor drugs, and also provides gallium salicylaldehyde amino acid Schiff base tetra Methods for the preparation of metacomplexes.
为了达到上述目的，本发明采用以下技术方案：一种镓水杨醛氨基酸希夫碱四元配合物，其通式为GaLiLi′X，一氯(水杨醛氨基酸希夫碱)(杂环碱)合镓(III)，其结构式为：In order to achieve the above object, the present invention adopts the following technical scheme: a kind of gallium salicylaldehyde amino acid Schiff base quaternary complex, its general formula is GaLi Li 'X, a chlorine (salicylaldehyde amino acid Schiff base) ( Heterocyclic base) gallium (III), its structural formula is:
配合物中，中心GaIII离子为六配位，具有不规则八面体几何构型；希夫碱配体呈负二价，以一个羧基氧、亚胺氮原子、酚氧ONO三齿配位，形成两个螯合环；NN杂环碱配体双齿螯合配位；分子中含有一个配位X-1离子；In the complex, the central GaIII ion is six-coordinated and has an irregular octahedral geometry; the Schiff base ligand is negatively divalent, and is coordinated with a carboxyl oxygen, imine nitrogen atom, and phenolic oxygen ONO tridentate. Form two chelate rings; NN heterocyclic base ligand bidentate chelation coordination; the molecule contains a coordination X-1 ion;
其中：配体Li＝天然氨基酸的水杨醛氨基酸希夫碱，包含L1：R＝CH2COOH，Aspartic acid，水杨醛天冬氨酸希夫碱；L2：R＝CH2CH2COOH，Glutamic acid，水杨醛谷氨酸希夫碱。Wherein: Ligand Li =Salicylaldehyde Schiff base of natural amino acid, including L1 : R=CH2 COOH, Aspartic acid, salicylaldehyde aspartic acid Schiff base; L2 : R=CH2 CH2 COOH , Glutamic acid, salicylaldehyde glutamic acid Schiff base.
配体Li′＝bipy、phen等NN杂环碱螯合配体，包含L1′＝bipy，L2′＝phen。Ligand Li ′=bipy, phen and other NN heterocyclic base chelating ligands, including L1 ′=bipy, L2 ′=phen.
配体X＝负一价阴离子，包含卤离子Cl-、Br-、I-。Ligand X = negative monovalent anion, including halide ions Cl- , Br- , I- .
上述配体Li还包括：甘氨酸Glycine、丙氨酸Alanine、苯丙氨酸Phenylalanine、酪氨酸Tyrosine、缬氨酸Valine、丝氨酸Serine、半胱氨酸Cysteine、组氨酸Histidine、亮氨酸Leucine、异亮氨酸Isoleucine、苏氨酸Threonine、天冬酰胺Asparagine、色氨酸Tryptophan、谷氨酰胺Glutamine、蛋氨酸Methionine、赖氨酸Lysine、精氨酸Arginine、脯氨酸Proline的水杨醛氨基酸希夫碱。The above-mentioned ligand Lalso includes: Glycine, Alanine, Phenylalanine, Tyrosine, Valine, Serine, Cysteine, Histidine, Leucine , Isoleucine Isoleucine, Threonine Threonine, Asparagine Asparagine, Tryptophan Tryptophan, Glutamine Glutamine, Methionine Methionine, Lysine Lysine, Arginine Arginine, Proline Proline Salicylaldehyde Amino Acid husband base.
镓水杨醛氨基酸希夫碱四元配合物的制备方法如下：The preparation method of gallium salicylaldehyde amino acid Schiff base quaternary complex is as follows:
于氮气氛、搅拌回流下，45-50℃水浴中，在三颈烧瓶中，将等摩尔的氨基酸和KOH(氢氧化钾)混合溶于适量无水甲醇/无水乙醇中，氨基酸中R基团含有羧基时，KOH过量1倍，氨基酸中R基团含有酚基时，KOH过量1.5倍；逐滴加入比氨基酸过量0.25倍的水杨醛无水甲醇/无水乙醇溶液，反应1h；向反应溶液中滴加与氨基酸等摩尔的GaCl3·6H2O无水甲醇/无水乙醇溶液，反应1～4h后，再滴加等摩尔的Li′无水甲醇/无水乙醇溶液，反应8h；旋转蒸发浓缩后，抽滤，红外灯烘干得到浅黄色粉末状配合物；对于浓缩后不产生沉淀的配合物，加入异丙醇使产物析出；合成路线为：In a nitrogen atmosphere, under stirring and reflux, in a water bath at 45-50°C, in a three-necked flask, mix equimolar amino acids and KOH (potassium hydroxide) and dissolve them in an appropriate amount of anhydrous methanol/anhydrous ethanol. The R group in the amino acid When the group contains a carboxyl group, the excess of KOH is 1 times, and when the R group in the amino acid contains a phenolic group, the excess of KOH is 1.5 times; add salicylaldehyde anhydrous methanol/absolute ethanol solution with an excess of 0.25 times that of the amino acid, and react for 1 h; Add dropwise GaCl3 6H2 O absolute methanol/dehydrated ethanol solution equal to amino acid in the reaction solution, react for 1 to 4 hours, then add dropwise equimolar Li ′ anhydrous methanol/dehydrated ethanol solution, and react 8h; after concentration by rotary evaporation, suction filtration, and drying by infrared light to obtain a light yellow powdery complex; for complexes that do not produce precipitation after concentration, add isopropanol to precipitate the product; the synthetic route is:
合成产物固体中含有不定量的溶剂分子和KOH，决定于每次实验条件的微小差别(例如干燥程度)，这并不影响分子的结构和性质。The solids of the synthesized products contain variable amounts of solvent molecules and KOH, which are determined by the small differences in each experimental condition (such as the degree of dryness), which does not affect the structure and properties of the molecules.
上述所有化学合成试剂，包括配体Li′，均是市售商品，来源广泛，容易获得。All the chemical synthesis reagents mentioned above, including the ligand Li ′, are commercially available, widely sourced and easy to obtain.
本发明将镓的亲肿瘤特性与第一配体希夫碱的抑菌抗增生活性相结合，并引入第二配体phen、bipy以及其他中性NN螯合配体，借助于其较大共轭平面，增强配合物的DNA靶向性，研制出的镓水杨醛氨基酸希夫碱四元配合物，制备方法简便、价格低廉、热力学稳定性及动力学稳定性适宜、是一种具有抗肿瘤活性的新型镓配合物。以镓水杨醛氨基酸希夫碱四元配合物的4个实例分子，在体外对癌细胞(A549人肺癌、MCF-7人乳腺癌)和正常细胞(H-MSC人间充质干细胞)进行细胞毒性实验，并以抗癌药物顺铂作为对照，对照数据如表1：The present invention combines the pro-tumor properties of gallium with the antibacterial and anti-proliferative activity of the first ligand Schiff base, and introduces the second ligand phen, bipy and other neutral NN chelating ligands. The yoke plane enhances the DNA targeting of the complex, and the developed gallium salicylaldehyde amino acid Schiff base quaternary complex has a simple preparation method, low price, suitable thermodynamic stability and kinetic stability, and is an anti- Novel gallium complexes with tumor activity. Cancer cells (A549 human lung cancer, MCF-7 human breast cancer) and normal cells (H-MSC human mesenchymal stem cells) were treated in vitro with four example molecules of gallium salicylaldehyde amino acid Schiff base quaternary complexes Toxicity test, and the anticancer drug cisplatin was used as a control, and the control data are shown in Table 1:
表1Table 1
结果表明：配合物实例1对肺癌细胞A549的抑制活性虽然略小于顺铂，但它对正常细胞H-MSC的毒性远小于顺铂。配合物实例2虽然对乳腺癌细胞MCF-7的抑制活性小于顺铂，但它对正常细胞H-MSC的毒性也是远远小于顺铂。含有phen的配合物实例3、4对癌细胞的抑制活性最强，其对MCF-7细胞的抑制活性等同于顺铂，而对A549细胞的抑制活性强于顺铂。对于正常细胞H-MSC，配合物实例的毒性都低于顺铂。检测结果表明，本发明配合物具有作为抗癌剂的价值，尤其是配合物实例3、4表现出高效、低毒抗癌剂特性，值得推广。The results showed that although the inhibitory activity of complex example 1 on lung cancer cell A549 was slightly lower than that of cisplatin, its toxicity to normal cell H-MSC was much lower than that of cisplatin. Although complex example 2 has less inhibitory activity on breast cancer cell MCF-7 than cisplatin, its toxicity to normal cell H-MSC is far less than cisplatin. Compound examples 3 and 4 containing phen have the strongest inhibitory activity on cancer cells, and their inhibitory activity on MCF-7 cells is equal to that of cisplatin, while their inhibitory activity on A549 cells is stronger than that of cisplatin. For normal cell H-MSC, the toxicity of the complexes is lower than that of cisplatin. The test results show that the complexes of the present invention are valuable as anticancer agents, especially complexes 3 and 4 exhibit high-efficiency, low-toxicity anticancer properties, and are worthy of popularization.
实验表明，镓水杨醛氨基酸希夫碱四元配合物的基本性能如下：Experiments have shown that the basic properties of the gallium salicylaldehyde amino acid Schiff base quaternary complex are as follows:
1.配合物实例在溶液中的衰变动力学1. The decay kinetics of complex examples in solution
通过配合物实例的电子光谱测定，获得配合物实例在溶液中的衰变速率常数及半衰期数据，见表2。在正常光照条件下，在中性酸度下，配合物实例的半衰期t1/2大于34h(配合物实例4的t1/2值高达67.76h)，表明具有较好的水溶液稳定性，因而具有水剂注射药物的潜能。而顺铂在正常光照下发生显著光解，本发明配合物实例这一性质优于顺铂。The decay rate constant and half-life data of the complex examples in solution were obtained through the electron spectrum measurement of the complex examples, as shown in Table 2. Under normal light conditions, at neutral acidity, the half-life t1/2 of the complex example is greater than 34h (the t1/2 value of the complex example 4 is as high as 67.76h), indicating that it has better aqueous solution stability, and thus has Potential of aqueous injectable drugs. However, cisplatin undergoes significant photolysis under normal light, and this property of the complex example of the present invention is superior to cisplatin.
表2 配合物实例在溶液中的衰变数据Table 2 The decay data of complex examples in solution
2.配合物实例的循环-伏安曲线特性2. Cyclic-voltammetry characteristics of complex examples
在除氧条件下，由循环伏安曲线观察得知，表明配合物实例溶液的氧化还原稳定性比抗癌药物GaCl3溶液强，更加便于使用。Under the condition of deoxygenation, the observation of the cyclic voltammetry curve shows that the redox stability of the complex example solution is stronger than that of the anticancer drug GaCl3 solution, and it is more convenient to use.
3.溶液酸碱性对配合物实例稳定性的影响3. The influence of the acidity and alkalinity of the solution on the stability of the complex example
通过电子光谱和循环-伏安曲线测定揭示，溶液的酸碱性对配合物实例的稳定性产生影响，配合物实例存在一个稳定pH范围，一般在pH＝4左右。在胃酸酸度下，电子光谱数据(表2)表明配合物实例具有较好的口服药物潜力，配合物实例3、4的衰变半衰期t1/2分别达到102min、112min。而顺铂只能注射使用，本发明配合物实例在这一性质上优于顺铂。Electron spectroscopy and cyclic-voltammetry curve measurements reveal that the acidity and alkalinity of the solution affects the stability of the complex example, and the complex example has a stable pH range, generally around pH=4. Under the acidity of gastric acidity, the electronic spectrum data (Table 2) shows that the complex examples have good oral drug potential, and the decay half-lives t1/2 of the complex examples 3 and 4 respectively reach 102min and 112min. While cisplatin can only be used by injection, the complex example of the present invention is superior to cisplatin in this property.
4.配合物实例的脂水分配系数测定4. Determination of the lipid-water partition coefficient of complex examples
摇瓶法测定配合物实例的表观脂水分配系数数据表明，配合物实例均具有良好的水溶性。而顺铂因水溶性不够而只能注射使用，本发明配合物实例在这一性质上优于顺铂。The apparent lipid-water partition coefficient data of the complex examples determined by the shake flask method showed that the complex examples all had good water solubility. However, cisplatin can only be used by injection because of insufficient water solubility, and the complex example of the present invention is superior to cisplatin in this property.
5.配合物实例与DNA的作用5. Examples of complexes and the role of DNA
DNA是许多抗癌药物的靶分子，顺铂就是通过以DNA为主要靶分子而产生抗癌活性。本发明研究了配合物实例对DNA的作用情况，包括与DNA的键合(可见-紫外光谱、循环伏安曲线、粘度法)，以及对DNA的剪切作用(凝胶电泳法)。结果表明配合物实例分子既可与DNA发生键合作用(键合常数Kb为103数量级)，又可剪切DNA(通过几乎仅涉及羟基自由基的氧化还原机理)，表明DNA是本发明配合物实例的一种重要靶分子，有助于确定其抗癌机理。DNA is the target molecule of many anticancer drugs, and cisplatin produces anticancer activity by using DNA as the main target molecule. The present invention studies the effect of complex examples on DNA, including the bonding with DNA (visible-ultraviolet spectrum, cyclic voltammetry curve, viscosity method), and the shearing effect on DNA (gel electrophoresis method). The results show that the molecule of the complex example can not only bond with DNA (the bonding constant Kb is on the order of 103 ), but also shear DNA (through a redox mechanism that almost only involves hydroxyl radicals), indicating that DNA is an important component of the present invention. An important target molecule for complex examples, which helps to determine its anticancer mechanism.
具体实施方式Detailed ways
下面通过实施例详述本发明：Describe the present invention in detail below by embodiment:
实施例1Example 1
一种镓水杨醛氨基酸希夫碱四元配合物，其通式为GaLiLi′X，一氯(水杨醛氨基酸希夫碱)(杂环碱)合镓(III)，结构式为：A gallium salicylaldehyde amino acid Schiff base quaternary complex, its general formula is GaLi Li' X, a chlorine (salicylaldehyde amino acid Schiff base) (heterocyclic base) gallium (III), and the structural formula is :
配合物中，中心GaIII离子为六配位，具有不规则八面体几何构型；希夫碱呈负二价，以一个羧基氧、亚胺氮原子、酚氧ONO三齿配位，形成两个螯合环；NN杂环碱双齿螯合配位；分子中含有一个配位X-1离子；In the complex, the central GaIII ion is six-coordinated and has an irregular octahedral geometry; the Schiff base is negatively divalent and coordinates with a carboxyl oxygen, imine nitrogen atom, and phenolic oxygen ONO tridentate to form two a chelate ring; NN heterocyclic base bidentate chelation coordination; the molecule contains a coordination X-1 ion;
配体Li＝天然氨基酸的水杨醛氨基酸希夫碱，在此为L1：R＝CH2COOH，Aspartic acid，水杨醛天冬氨酸希夫碱；L2：R＝CH2CH2COOH，Glutamic acid，水杨醛谷氨酸希夫碱。Ligand Li =salicylaldehyde amino acid Schiff base of natural amino acids, here L1 : R=CH2 COOH, Aspartic acid, salicylaldehyde aspartic acid Schiff base; L2 : R=CH2 CH2 COOH , Glutamic acid, salicylaldehyde glutamic acid Schiff base.
配体Li′＝bipy、phen等NN杂环碱螯合配体，在此为L1′＝bipy，L2′＝phen。Ligand Li ′=bipy, phen and other NN heterocyclic base chelating ligands, here L1 ′=bipy, L2 ′=phen.
配体X＝负一价阴离子，在此为Cl-离子。Ligand X=negative monovalent anion, here Cl− ion.
镓水杨醛氨基酸希夫碱四元配合物的制备方法如下：The preparation method of gallium salicylaldehyde amino acid Schiff base quaternary complex is as follows:
将天冬氨酸(2mmol，0.2662g)和KOH(4mmol，0.2244g)加入30mmL无水甲醇，在氮气保护下，于50℃下搅拌回流使之全部溶解。在同样反应条件下，滴加溶于少量无水甲醇的水杨醛(2.5mmol，0.3053g)，反应1h后滴加溶于少量无水甲醇的GaCl3·6H2O(2mmol，0.5684g)。反应1h，滴加溶于少量无水甲醇的bipy(2mmol，0.3124g)，反应8h后旋转蒸发浓缩，抽滤，红外灯烘干得到浅黄色粉末配合物。其合成路线为：Aspartic acid (2mmol, 0.2662g) and KOH (4mmol, 0.2244g) were added into 30mmL of anhydrous methanol, under nitrogen protection, stirred and refluxed at 50°C to dissolve them all. Under the same reaction conditions, add salicylaldehyde (2.5mmol, 0.3053g) dissolved in a small amount of anhydrous methanol dropwise, and add GaCl3 ·6H2 O (2mmol, 0.5684g) dissolved in a small amount of anhydrous methanol dropwise after 1h of reaction . After reacting for 1 h, bipy (2 mmol, 0.3124 g) dissolved in a small amount of anhydrous methanol was added dropwise. After reacting for 8 h, the mixture was concentrated by rotary evaporation, filtered by suction, and dried by infrared light to obtain a light yellow powder complex. Its synthetic route is:
本实施例中，1·2KOH·CH3OH·3.5H2O(一氯(水杨醛天冬氨酸希夫碱)(联吡啶)合镓(III))各元素理论含量/％：C：35.61；H：3.940；N：5.663；Ga：9.379；K：5.270；Cl：4.778。测定含量/％：C：35.99；H：3.602；N：5.175；Ga：11.974；K：4.806；Cl：5.115。IR(KBr)：3412ν(OH)；1633νas、1400νs(配位COO-)；1547νas、1448νs(未配位COO-)；768ν(C-H of bipy)；562、545ν(Ga-N)；445ν(Ga-O)。UV-Visible(nm/L·mol-1·cm-1×104)：(π-π*)1：232.4/2.991、311.4/0.970；(π-π*)2：277.6/2.393、299sh；(n-π*)：353.1/0.6965。51℃失去溶剂分子，255℃开始分解。In this example, 1.2KOH·CH3 OH·3.5H2 O (monochloro(salicylaldehyde aspartic acid Schiff base) (bipyridine) gallium(III)) theoretical content/% of each element: C: 35.61 ; H: 3.940; N: 5.663; Ga: 9.379; K: 5.270; Cl: 4.778. Measured content/%: C: 35.99; H: 3.602; N: 5.175; Ga: 11.974; K: 4.806; Cl: 5.115. IR(KBr): 3412ν(OH); 1633νas , 1400νs (coordinated COO- ); 1547νas , 1448νs (uncoordinated COO- ); 768ν(CH of bipy); 562, 545ν(Ga-N) ; 445ν(Ga-O). UV-Visible (nm/L·mol-1 cm-1 ×104 ): (π-π* )1 : 232.4/2.991, 311.4/0.970; (π-π* )2 : 277.6/2.393, 299sh; (n-π* ): 353.1/0.6965. It loses solvent molecules at 51°C and begins to decompose at 255°C.
实施例2Example 2
一种镓水杨醛氨基酸希夫碱四元配合物，其通式为GaLiLi′X和制备方法如实施例1，只是将天冬氨酸换成谷氨酸(2mmol，0.2943g)，得到浅黄色粉末配合物。其合成路线为：A kind of gallium salicylaldehyde amino acid Schiff base quaternary complex, its general formula is GaLi Li 'X and preparation method as embodiment 1, just change aspartic acid into glutamic acid (2mmol, 0.2943g) , to obtain light yellow powder complex. Its synthetic route is:
本实施例中，2·2KOH·CH3OH·3H2O(一氯(水杨醛谷氨酸希夫碱)(联吡啶)合镓(III))各元素理论含量/％：C：36.98；H：4.048；N：5.625；Ga：9.334；K：5.234；Cl：4.746。测定含量/％：C：37.36；H：3.831；N：5.145；Ga：11.905；K：3.879；Cl：4.871。IR(KBr)：3396ν(OH)；1630νas、1404νs(配位COO-)；1543νas、1448νs(未配位COO-)；769ν(C-H of bipy)；562ν(Ga-N)；452、416ν(Ga-O)。UV-Visible(nm/L·mol-1·cm-1×104)：(π-π*)1：233.3/2.335、310.6/0.720；(π-π*)2：276.7/1.994；(n-π*)：354.9/0.5292。47℃失去溶剂分子，294℃开始分解。In this example, 2·2KOH·CH3 OH·3H2 O (monochloro(salicylaldehyde glutamic acid Schiff base) (bipyridine) gallium(III)) theoretical content/% of each element: C: 36.98; H : 4.048; N: 5.625; Ga: 9.334; K: 5.234; Cl: 4.746. Measured content/%: C: 37.36; H: 3.831; N: 5.145; Ga: 11.905; K: 3.879; Cl: 4.871. IR(KBr): 3396ν(OH); 1630νas , 1404νs (coordinated COO- ); 1543νas , 1448νs (uncoordinated COO- ); 769ν(CH of bipy); 562ν(Ga-N); 452 , 416ν(Ga-O). UV-Visible (nm/L·mol-1 cm-1 ×104 ): (π-π* )1 : 233.3/2.335, 310.6/0.720; (π-π* )2 : 276.7/1.994; (n -π* ): 354.9/0.5292. Solvent molecules are lost at 47°C and decompose at 294°C.
实施例3Example 3
一种镓水杨醛氨基酸希夫碱四元配合物，其通式和结构式及制备方法均同实施例1，只是将滴加的配体bipy换为配体phen(2mmol，0.3604g)，反应8h后旋转蒸发浓缩，抽滤，红外灯烘干得到浅黄色粉末配合物。A kind of gallium salicylaldehyde amino acid Schiff base quaternary complex, its general formula and structural formula and preparation method are all the same as embodiment 1, just change the ligand bipy dropwise to ligand phen (2mmol, 0.3604g), react After 8 hours, it was concentrated by rotary evaporation, filtered by suction, and dried by an infrared lamp to obtain a light yellow powder complex.
合成路线为：The synthetic route is:
本实施例中3·1.6KOH·CH3OH·3H2O(一氯(水杨醛天冬氨酸希夫碱)(邻菲罗啉)合镓(III))各元素理论含量/％：C：39.24；H：3.787；N：5.721；Ga：9.322；K：5.227；Cl：4.740。测定含量/％：C：38.98；H：3.507；N：5.214；Ga：12.382；K：4.971；Cl：4.811。IR(KBr)：3421ν(OH)；1632νas、1398νs(配位COO-)；1543νas、1448νs(未配位COO-)；850、723ν(C-H of phen)；564、547ν(Ga-N)；451、433ν(Ga-O)。UV-Visible(nm/L·mol-1·cm-1×104)：(π-π*)1：225.5/3.815；(π-π*)2：272.9/3.502；(n-π*)：350.7/0.4839。51℃失去溶剂分子，261℃开始分解。In this example, 3.1.6KOH.CH3 OH.3H2 O (monochloro(salicylaldehyde aspartic acid Schiff base) (o-phenanthroline) gallium(III)) theoretical content of each element/%: C: 39.24; H: 3.787; N: 5.721; Ga: 9.322; K: 5.227; Cl: 4.740. Measured content/%: C: 38.98; H: 3.507; N: 5.214; Ga: 12.382; K: 4.971; Cl: 4.811. IR(KBr): 3421ν(OH); 1632νas , 1398νs (coordinated COO- ); 1543νas , 1448νs (uncoordinated COO- ); 850, 723ν(CH of phen); 564, 547ν(Ga- N); 451, 433ν(Ga-O). UV-Visible (nm/L·mol-1 cm-1 ×104 ): (π-π* )1 : 225.5/3.815; (π-π* )2 : 272.9/3.502; (n-π* ) : 350.7/0.4839. It loses solvent molecules at 51°C and begins to decompose at 261°C.
实施例4Example 4
一种镓水杨醛氨基酸希夫碱四元配合物，其通式和结构式及制备方法均同实施例2，将滴加的配体bipy换为配体phen(2mmol，0.3604g)，反应8h后旋转蒸发浓缩，抽滤，红外灯烘干得到浅黄色粉末配合物。其合成路线为：A gallium salicylaldehyde amino acid Schiff base quaternary complex, its general formula, structural formula and preparation method are the same as in Example 2, the ligand bipy added dropwise is replaced by ligand phen (2mmol, 0.3604g), and the reaction is 8h After that, it was concentrated by rotary evaporation, filtered by suction, and dried by an infrared lamp to obtain a pale yellow powder complex. Its synthetic route is:
本实施例中4·1.1KOH·5.5H2O(一氯(水杨醛谷氨酸希夫碱)(邻菲罗啉)合镓(III))各元素理论含量/％：C：39.30；H：4.136；N：5.729；Ga：9.506；K：5.330；Cl：4.833。测定含量/％：C：39.59；H：4.014；N：5.164；Ga：12.557；K：4.567；Cl：4.561。IR(KBr)：3419ν(OH)；1630νas、1385νs(配位COO-)；1545νas、1450νs(未配位COO-)；850、723ν(C-H of phen)；567ν(Ga-N)；455、431ν(Ga-O)。UV-Visible(nm/L·mol-1·cm-1×104)：(π-π*)1：222.2/3.913；(π-π*)2：273.4/3.729；(n-π*)：355.8/0.5172。61℃失去溶剂分子，265℃开始分解。In this example, the theoretical content of each element in 4·1.1KOH·5.5H2 O (monochloro(salicylaldehyde glutamic acid Schiff base) (o-phenanthroline) gallium(III))/%: C: 39.30; H: 4.136; N: 5.729; Ga: 9.506; K: 5.330; Cl: 4.833. Measured content/%: C: 39.59; H: 4.014; N: 5.164; Ga: 12.557; K: 4.567; Cl: 4.561. IR(KBr): 3419ν(OH); 1630νas , 1385νs (coordinated COO- ); 1545νas , 1450νs (uncoordinated COO- ); 850, 723ν(CH of phen); 567ν(Ga-N) ; 455, 431ν(Ga-O). UV-Visible (nm/L·mol-1 cm-1 ×104 ): (π-π* )1 : 222.2/3.913; (π-π* )2 : 273.4/3.729; (n-π* ) : 355.8/0.5172. It loses solvent molecules at 61°C and begins to decompose at 265°C.
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| CN102584871A (en)* | 2012-01-09 | 2012-07-18 | 内蒙古大学 | Rare earth coordination compound containing Schiff base and bipyridyl and preparation method and bacteriostasis application thereof |
| CN102786538A (en)* | 2012-08-31 | 2012-11-21 | 聊城大学 | Salicylaldehyde glycine Schiff base and o-phenanthroline copper (II) coordination compound and preparation process and application thereof |
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| CN102584871A (en)* | 2012-01-09 | 2012-07-18 | 内蒙古大学 | Rare earth coordination compound containing Schiff base and bipyridyl and preparation method and bacteriostasis application thereof |
| CN102786538A (en)* | 2012-08-31 | 2012-11-21 | 聊城大学 | Salicylaldehyde glycine Schiff base and o-phenanthroline copper (II) coordination compound and preparation process and application thereof |
| CN102786538B (en)* | 2012-08-31 | 2015-03-18 | 聊城大学 | Salicylaldehyde glycine Schiff base and o-phenanthroline copper (II) coordination compound and preparation process and application thereof |
| CN107698460A (en)* | 2017-10-01 | 2018-02-16 | 桂林理工大学 | A kind of schiff bases sylvite and preparation method thereof |
| CN110625125A (en)* | 2019-09-25 | 2019-12-31 | 苏州大学 | A method for preparing liquid metal nanoparticles using amino acids as ligands |
| CN114410296A (en)* | 2022-03-15 | 2022-04-29 | 贵州医科大学 | Preparation method and application of MOF composites based on isoleucine derivative ligands |
| CN114410296B (en)* | 2022-03-15 | 2023-08-22 | 贵州医科大学 | Preparation method and application of MOF composite material based on isoleucine derivative ligand |
| CN117865802A (en)* | 2024-03-11 | 2024-04-12 | 山东顺成化学有限公司 | Preparation method of ethyl 4-bromobutyrate |
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