黄连素-染料木素有机盐水合物的制备、晶体结构及溶解性
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摘要
合成了黄连素和染料木素的有机盐水合物[C_(20)H_(18_NO_4]~+·[C_(15)H_9O_5]~-·2. 5H_2O·0. 5(C_2H_5OH),并测定了其晶体结构。解析结果表明,该有机盐水合物属于单斜晶系,P2_1/c空间群。染料木素7取代位的羟基失去了质子变成了染料木素阴离子。羟基阴离子与4'取代位上的羟基形成了O—H…O-氢键,产生了一维的氢键链状结构。两个水分子通过氢键作用形成了链状结构,并与染料木素阴离子形成二维的氢键结构。加热失去水分子后,有机盐水合物变成无定型状态。在乙醇水溶液中悬浮后,无定型可以转变成结晶的水合物结构。形成黄连素-染料木素有机盐水合物后,染料木素在水中的溶解度略有增加。
The organic salt hydrate of berberine with genistein, [C20 H18 NO4]+·[C15 H9 O5]-·2. 5 H2 O·0. 5( C2 H5 OH),was prepared and its crystal structure was determined. The result showed that the organic salt hydrate crystallized in monoclinic crystal system and P21/c space group. The 7-substituted hydroxyl of genistein lost its proton and turned to be anion. The resulting hydroxyl anion was involved in O—H…O-hydrogen bonding with 4'-substituted hydroxyl,which gave rise to an one-dimensional hydrogenbonded chain-like structure. Two water molecules formed a chain-like structure through hydrogen-bonding interactions and further connected the 1 D chain of genistein into a 2 D hydrogen-bonded network. The hydrate turned to be amorphous form after losing water molecules by heating. The amorphous form could transform into crystalline organic salt hydrate after suspending in ethanol-water for 24 h. After forming berberine-genistein salt hydrate,the solubility of genistein in water increased slightly.
The organic salt hydrate of berberine with genistein, [C20 H18 NO4]+·[C15 H9 O5]-·2. 5 H2 O·0. 5( C2 H5 OH),was prepared and its crystal structure was determined. The result showed that the organic salt hydrate crystallized in monoclinic crystal system and P21/c space group. The 7-substituted hydroxyl of genistein lost its proton and turned to be anion. The resulting hydroxyl anion was involved in O—H…O-hydrogen bonding with 4'-substituted hydroxyl,which gave rise to an one-dimensional hydrogenbonded chain-like structure. Two water molecules formed a chain-like structure through hydrogen-bonding interactions and further connected the 1 D chain of genistein into a 2 D hydrogen-bonded network. The hydrate turned to be amorphous form after losing water molecules by heating. The amorphous form could transform into crystalline organic salt hydrate after suspending in ethanol-water for 24 h. After forming berberine-genistein salt hydrate,the solubility of genistein in water increased slightly.
引文
[1]Stahl P H,Wermuth C G.Handbook of Pharmaceutical Salts:Properties,Selection and Use[M].Wiley-VCH,Chichester,2002.
[2]Sanphui P,Tothadi S,Ganguly S,et al.Salt and Cocrystals of Sildenafil with Dicarboxylic Acids:Solubility and Pharmacokinetic Advantage of the Glutarate Salt[J].Mol Pharm,2013,10(12):4687-4697.
[3]Black S N,Collier E,Davey R J,et al.Structure,Solubility,Screening and Synthesis of Molecular Salts[J].J Pharm Sci,2007,96(5):1053-1068.
[4]Thorat S H,Sahu S K,Patwadkar M V,et al.Drug-Drug Molecular Salt Hydrate of an Anticancer Drug Gefitinib and a Loop Diuretic Drug Furosemide:An Alternative for Multidrug Treatment[J].J Pharm Sci,2015,104(12):4207-4216.
[5]Bag P P,Ghosh S,Khan H,et al.Drug-Drug Salt Forms of Ciprofloxacin with Diflunisal and Indoprofen[J].Cryst Eng Comm,2014,16(32):7393-7396.
[6]Gopi S P,Ganguly S,Desiraju G R.A Drug-Drug Salt Hydrate of Norfloxacin and Sulfathiazole:Enhancement of in Vitro Biological Properties via Improved Physicochemical Properties[J].Mol Pharm,2016,13(10):3590-3594.
[7]Crozier A,Jaganath I B,Clifford M N.Dietary Phenolics:Chemistry,Bioavailability and Effects on Health[J].Nat Prod Rep,2009,26(8):1001-1043.
[8]LIN Fangxia,QIU Bingqing,LOU Benyong.Preparation,Crystal Structure and Solubility of Triethylamine Salt Monohydrate of Naringenin[J].Chinese J Appl Chem,2017,34(4):481-485(in Chinese).林芳霞,邱冰清,娄本勇.柚皮素三乙胺盐一水合物的制备、晶体结构及溶解度[J].应用化学,2017,34(4):481-485.
[9]Baird A W,Taylor C T,Brayden D J.Non-Antibiotic Anti-Diarrhoeal Drugs:Factors Affecting Oral Bioavailability of Berberine and Loperamide in Intestinal Tissue[J].Adv Drug Delivery Rev,1997,23(1/2/3):111-120.
[10]Habtemariam S.Berberine and Inflammatory Bowel Disease:A Concise Review[J].Pharmacol Res,2016,113(part A):592-599.
[11]Jin Y,Khadka D B,Cho W J.Pharmacological Effects of Berberine and Its Derivatives:A Patent Update[J].Expert Opin Ther Pat,2016,26(2):229-243.
[12]Sun Y Y,Xu K L,Wang Y T,et al.A Systematic Review of the Anticancer Properties of Berberine,A Natural Product from Chinese Herbs[J].Anti-Cancer Drug,2009,20(9):757-769.
[13]Wang C,Perumalla SR,Lu R,et al.Sweet Berberine[J].Cryst Growth Des,2016,16(2):933-939.
[14]Zhang Y J,Lou B Y,Huang Y L,et al.Crystal Structure,Stability and Dissolution of a Drug-Drug Molecular Salt Hydrate of Berberine with Protocatechuic Acid[J].Chinese J Struct Chem,2018,37(3):400-406.
[15]Zhou R J,Yang X Q,Wang D,et al.Anti-Tumor Effects of All-Trans Retinoic Acid Are Enhenced by Genistein[J].Cell Biochem Biophys,2012,62(1):177-184.
[16]Rigaku.Crystal Clear Programs for Data Collection,Cell Refinement and Structure Solution[CP].Japan:Rigaku Corp,2000.
[17]Sheldrick G M.A Short History of SHELX[J].Acta Cryst Sect A,2008,64(1):112-122.
[18]Sheldrick G M.Crystal Structure Refinement with SHELXL[J].Acta Cryst Sect C,2015,71(1):3-8.
[2]Sanphui P,Tothadi S,Ganguly S,et al.Salt and Cocrystals of Sildenafil with Dicarboxylic Acids:Solubility and Pharmacokinetic Advantage of the Glutarate Salt[J].Mol Pharm,2013,10(12):4687-4697.
[3]Black S N,Collier E,Davey R J,et al.Structure,Solubility,Screening and Synthesis of Molecular Salts[J].J Pharm Sci,2007,96(5):1053-1068.
[4]Thorat S H,Sahu S K,Patwadkar M V,et al.Drug-Drug Molecular Salt Hydrate of an Anticancer Drug Gefitinib and a Loop Diuretic Drug Furosemide:An Alternative for Multidrug Treatment[J].J Pharm Sci,2015,104(12):4207-4216.
[5]Bag P P,Ghosh S,Khan H,et al.Drug-Drug Salt Forms of Ciprofloxacin with Diflunisal and Indoprofen[J].Cryst Eng Comm,2014,16(32):7393-7396.
[6]Gopi S P,Ganguly S,Desiraju G R.A Drug-Drug Salt Hydrate of Norfloxacin and Sulfathiazole:Enhancement of in Vitro Biological Properties via Improved Physicochemical Properties[J].Mol Pharm,2016,13(10):3590-3594.
[7]Crozier A,Jaganath I B,Clifford M N.Dietary Phenolics:Chemistry,Bioavailability and Effects on Health[J].Nat Prod Rep,2009,26(8):1001-1043.
[8]LIN Fangxia,QIU Bingqing,LOU Benyong.Preparation,Crystal Structure and Solubility of Triethylamine Salt Monohydrate of Naringenin[J].Chinese J Appl Chem,2017,34(4):481-485(in Chinese).林芳霞,邱冰清,娄本勇.柚皮素三乙胺盐一水合物的制备、晶体结构及溶解度[J].应用化学,2017,34(4):481-485.
[9]Baird A W,Taylor C T,Brayden D J.Non-Antibiotic Anti-Diarrhoeal Drugs:Factors Affecting Oral Bioavailability of Berberine and Loperamide in Intestinal Tissue[J].Adv Drug Delivery Rev,1997,23(1/2/3):111-120.
[10]Habtemariam S.Berberine and Inflammatory Bowel Disease:A Concise Review[J].Pharmacol Res,2016,113(part A):592-599.
[11]Jin Y,Khadka D B,Cho W J.Pharmacological Effects of Berberine and Its Derivatives:A Patent Update[J].Expert Opin Ther Pat,2016,26(2):229-243.
[12]Sun Y Y,Xu K L,Wang Y T,et al.A Systematic Review of the Anticancer Properties of Berberine,A Natural Product from Chinese Herbs[J].Anti-Cancer Drug,2009,20(9):757-769.
[13]Wang C,Perumalla SR,Lu R,et al.Sweet Berberine[J].Cryst Growth Des,2016,16(2):933-939.
[14]Zhang Y J,Lou B Y,Huang Y L,et al.Crystal Structure,Stability and Dissolution of a Drug-Drug Molecular Salt Hydrate of Berberine with Protocatechuic Acid[J].Chinese J Struct Chem,2018,37(3):400-406.
[15]Zhou R J,Yang X Q,Wang D,et al.Anti-Tumor Effects of All-Trans Retinoic Acid Are Enhenced by Genistein[J].Cell Biochem Biophys,2012,62(1):177-184.
[16]Rigaku.Crystal Clear Programs for Data Collection,Cell Refinement and Structure Solution[CP].Japan:Rigaku Corp,2000.
[17]Sheldrick G M.A Short History of SHELX[J].Acta Cryst Sect A,2008,64(1):112-122.
[18]Sheldrick G M.Crystal Structure Refinement with SHELXL[J].Acta Cryst Sect C,2015,71(1):3-8.