[发明专利]配合物[Cu2(L13)(L14)]·(CH3OH)的原位合成方法及抗肿瘤应用

权利要求书

1.一种配合物[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)，其特征在于[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)的分子式为：C₇₂H₇₀Cu₂N₁₈O₂₁，分子量为：1650.53，HL¹³＝(4S)-4,6-二乙基3-甲基4-(5-(甲酯基)-2-(6-甲基吡啶)-3-氧-2,3-二氢-1氢-吡唑)-1,8-二(6-甲基吡啶)-9-氧-1,2,7,8-四氮杂螺[[4.4]壬-6-烯-3,4,6-三甲酸甲酯；HL¹⁴＝(4S)-4-乙基3,6-二甲基4-(5-(甲酯基)-2-(6-甲基吡啶)-3-氧-2,3-二氢-1氢-吡唑)-1,8-二(6-甲基吡啶)-9-氧-1,2,7,8-四氮杂螺[4.4]壬-6-烯-3,4,6-三甲酸甲酯，晶体结构参数表见表一，键长键角数据见表二；具有良好的抗肿瘤活性；

所述配合物[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)的原位合成方法具体步骤为：

(1)将0.07-0.14克分析纯1-(6-甲基吡啶)-5-羟基-1氢-吡唑-3-甲酸甲酯，0.05-0.15克分析纯三水硝酸铜溶于10-20毫升体积比为1：1的无水乙腈和无水乙醇的混合溶液中；

(2)将步骤(1)所制得的溶液转入聚四氟乙烯的反应釜中，在80-90℃下反应60-80小时，降温至室温，过滤，滤液置于室温下自然挥发结晶，16天后得到单晶级[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)配合物，其晶体学参数见表一，键长键角数据见表二；

表一：[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)的晶体学参数

表二：[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)的键长和键角(°)

Cu1-N162.001(3)C57-C561.384(7)Cu1-N31.978(3)C7-C81.483(6)Cu1-N182.034(3)C31-C301.384(6)Cu1-N12.039(4)C31-C321.374(7)Cu2-N72.023(3)C62-C611.482(5)Cu2-N102.043(3)C58-C591.508(6)Cu2-N92.068(3)N2-C61.408(5)Cu2-N121.998(3)C69-C701.371(6)O3-C101.256(5)C69-C681.377(7)O15-C501.318(5)O1-C81.210(5)O15-C511.467(6)C29-C251.553(6)O17-C481.331(5)C40-C411.499(6)O17-C491.434(5)C23-C221.356(7)C60-C531.583(5)C23-C241.508(7)C60-N141.468(5)C67-C681.371(6)C60-C651.553(5)C70-C711.499(7)C60-C611.505(5)C55-C561.372(7)O14-C501.194(5)O8-C271.190(6)C53-C461.503(5)C6-C51.390(6)C53-C501.557(5)C2-C31.365(7)C53-C471.532(5)C2-C11.491(7)N6-C191.328(6)C22-C211.377(8)N6-C231.353(6)C37-C381.365(7)O18-C651.207(5)C3-C41.358(7)C36-N101.340(5)C34-C331.395(7)C36-N111.403(5)C34-C351.498(7)C36-C371.383(6)C33-C321.356(7)N7-N81.392(4)C5-C41.368(7)N7-C261.276(5)C51-C521.261(11)N16-N171.395(4)C63-C641.366(19)N16-C611.291(5)C14-C151.121(12)O13-C451.250(4)C72-O211.550(10)N15-C541.326(5)O19-C621.177(5)N15-C581.331(5)N17-C661.414(5)N3-C71.328(5)N17-C651.391(5)N3-N21.382(4)C10-N21.408(5)N5-N41.369(5)N10-C401.346(5)N5-C191.394(5)N14-C541.398(5)N5-C251.464(5)O2-C81.317(5)C46-C451.419(5)O2-C91.468(5)C46-C421.411(5)C43-O111.213(5)O9-C271.323(6)C43-C421.479(5)O9-C281.470(7)N9-C301.339(5)C16-N41.281(5)N9-C341.351(6)C16-C121.532(5)O20-C621.318(5)C16-C171.470(6)O20-C631.457(7)C20-C191.386(6)O6-C131.200(5)C20-C211.386(6)C66-N181.333(5)O16-C481.197(5)C66-C671.380(6)O10-C291.197(5)N18-C701.347(5)O12-C431.305(5)C11-C121.503(5)O12-C441.439(5)C11-C71.396(5)O5-C171.313(5)N12-N111.384(4)O5-C181.459(5)N12-C421.333(5)O7-C131.326(5)C26-C251.526(6)O7-C141.451(7)C26-C271.474(6)

N13-N141.364(4)C45-N111.403(5)N13-C471.285(5)N1-C61.333(5)N8-C291.384(5)N1-C21.348(5)N8-C301.412(5)C12-C131.539(6)C10-C111.404(6)C12-C251.599(5)C47-C481.478(6)O4-C171.205(5)C39-C401.367(6)C54-C551.382(6)C39-C381.372(7)C57-C581.372(6)N16-Cu1-N1880.20(13)N9-C30-C31123.9(4)N16-Cu1-N1122.36(13)C31-C30-N8121.9(4)N3-Cu1-N16126.80(14)N6-C23-C22121.8(5)N3-Cu1-N18123.04(14)N6-C23-C24115.4(5)N3-Cu1-N181.65(13)C22-C23-C24122.7(5)N18-Cu1-N1129.42(14)C50-O15-C51115.6(4)N7-Cu2-N10122.50(14)C48-O17-C49116.4(3)N7-Cu2-N978.96(13)N14-C60-C53102.6(3)N10-Cu2-N9127.89(14)N14-C60-C65110.8(3)N12-Cu2-N7125.50(13)N14-C60-C61112.8(3)N12-Cu2-N1080.68(13)C65-C60-C53118.8(3)N12-Cu2-N9128.06(14)C61-C60-C53112.7(3)C61-C60-C6599.5(3)N18-C70-C69121.6(4)C46-C53-C60114.1(3)N18-C70-C71116.1(4)C46-C53-C50111.1(3)C69-C70-C71122.3(4)C68-C67-C66116.9(4)N5-C25-C12102.0(3)C56-C55-C54117.0(5)N5-C25-C26113.4(3)C46-C53-C47113.3(3)N5-C25-C29112.1(3)C50-C53-C60111.8(3)C26-C25-C12113.8(3)C47-C53-C6098.6(3)C26-C25-C2998.6(3)C47-C53-C50107.2(3)C29-C25-C12117.6(3)C19-N6-C23117.7(4)N1-C6-N2115.4(4)N10-C36-N11115.0(3)N1-C6-C5122.8(4)N10-C36-C37123.5(4)C5-C6-N2121.8(4)C37-C36-N11121.4(4)N1-C2-C3121.8(5)N8-N7-Cu2112.3(2)N1-C2-C1115.4(4)C26-N7-Cu2138.2(3)C3-C2-C1122.8(5)C26-N7-N8109.5(3)N2-N3-Cu1111.6(2)N17-N16-Cu1111.5(2)N4-N5-C19120.7(4)C61-N16-Cu1139.5(3)N4-N5-C25113.8(3)C61-N16-N17108.9(3)C19-N5-C25125.0(4)C54-N15-C58117.8(4)C45-C46-C53123.0(3)C7-N3-Cu1143.5(3)C42-C46-C53131.4(3)C7-N3-N2104.3(3)C38-C37-C36117.7(5)C23-C22-C21119.6(5)C42-C46-C45105.4(3)C27-O9-C28112.2(5)O9-C27-C26110.9(5)N4-C16-C12115.5(4)O8-C27-O9125.4(5)N4-C16-C17123.6(4)O8-C27-C26123.6(5)C17-C16-C12120.2(3)C4-C3-C2119.5(5)C16-N4-N5108.8(3)N9-C34-C33120.9(5)C19-C20-C21115.8(5)N9-C34-C35116.4(4)C43-O12-C44118.8(3)C13-O7-C14117.2(4)C17-O5-C18114.8(3)C47-N13-N14109.5(3)N7-N8-C30117.5(3)C36-N10-Cu2113.8(3)C29-N8-N7111.9(3)C36-N10-C40117.1(4)C29-N8-C30128.3(3)C40-N10-Cu2129.0(3)O3-C10-C11132.9(4)C33-C34-C35122.7(5)O3-C10-N2123.0(4)C22-C21-C20120.3(5)C11-C10-N2104.1(3)C55-C56-C57119.8(4)N16-N17-C66117.4(3)C65-N17-C66128.7(3)

C65-N17-N16111.9(3)O15-C50-C53111.2(3)O14-C50-O15124.4(4)C54-N14-C60122.3(3)O14-C50-C53124.4(4)C8-O2-C9117.2(4)N6-C19-N5114.3(4)O12-C43-C42113.2(3)N6-C19-C20124.7(4)O11-C43-O12124.6(4)C20-C19-N5120.9(4)C67-C68-C69120.3(4)N13-N14-C60112.0(3)C32-C33-C34120.1(5)N13-N14-C54120.2(3)C4-C5-C6117.5(5)O11-C43-C42122.1(4)C37-C38-C39120.1(5)C30-N9-Cu2114.8(3)C66-N18-C70118.0(3)C30-N9-C34117.6(4)C70-N18-Cu1126.8(3)C34-N9-Cu2127.2(3)C10-C11-C12122.9(4)C62-O20-C63115.4(5)C7-C11-C10106.3(3)N18-C66-N17114.0(3)C3-C4-C5120.3(5)N18-C66-C67124.0(4)C66-N18-Cu1115.1(3)C67-C66-N17122.0(4)O13-C45-C46131.8(4)C7-C11-C12130.6(4)O13-C45-N11123.4(4)N11-N12-Cu2111.9(2)N11-C45-C46104.8(3)C42-N12-Cu2142.8(3)C6-N1-Cu1113.0(3)C42-N12-N11104.7(3)C6-N1-C2118.1(4)N7-C26-C25113.6(3)C52-C51-O15112.7(8)N7-C26-C27117.1(4)C33-C32-C31119.8(5)C27-C26-C25129.2(4)O18-C65-C60126.9(4)C2-N1-Cu1128.9(3)O18-C65-N17127.2(4)C16-C12-C13106.3(3)N17-C65-C60105.9(3)C16-C12-C2598.9(3)N15-C54-N14113.2(3)C11-C12-C16112.1(3)N15-C54-C55124.2(4)C11-C12-C13112.1(3)C55-C54-N14122.6(4)C11-C12-C25114.2(3)O5-C17-C16114.4(3)C13-C12-C25112.4(3)O4-C17-C16120.5(4)N13-C47-C53114.7(3)O4-C17-O5125.1(4)N13-C47-C48119.0(4)N3-C7-C11113.1(4)C48-C47-C53126.1(4)N3-C7-C8115.9(4)C40-C39-C38119.0(4)C64-C63-O20106.7(9)C58-C57-C56118.6(4)C32-C31-C30117.6(4)C11-C7-C8130.9(4)O19-C62-O20126.3(4)O19-C62-C61121.9(4)C15-C14-O7120.9(11)O20-C62-C61111.8(4)C46-C42-C43130.7(4)N16-C61-C60113.8(3)N12-C42-C46113.0(3)N16-C61-C62121.0(4)N12-C42-C43116.2(3)C62-C61-C60124.6(3)N3-N2-C10112.2(3)N15-C58-C57122.6(4)N3-N2-C6117.8(3)N15-C58-C59115.7(4)C10-N2-C6130.0(4)C57-C58-C59121.7(4)C70-C69-C68119.2(4)N12-N11-C36117.7(3)C45-N11-C36130.1(3)N12-N11-C45112.2(3)O17-C48-C47110.4(3)O16-C48-O17125.2(4)N8-C29-C25106.4(3)O16-C48-C47124.4(4)O7-C13-C12110.9(4)O2-C8-C7112.3(4)O6-C13-O7124.1(4)O1-C8-O2124.8(4)O6-C13-C12125.0(4)O1-C8-C7122.9(4)N10-C40-C41116.0(4)O10-C29-N8126.1(4)C39-C40-C41121.4(4)O10-C29-C25127.5(4)N9-C30-N8114.1(3)N10-C40-C39122.6(4)  

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2.根据权利要求1所述的配合物[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)的应用，其特征在于配合物[Cu₂(L¹³)(L¹⁴)]·(CH₃OH)应用于抗肿瘤。