基于L-谷氨酸的手性硅胶球的制备及其应用

无机介孔硅球因其具有足够的机械强度、热稳定性,以及适应多种流动相的优点,成为高效液相色谱(HPLC)柱填料中使用最广泛和最重要的材料。但在此研究领域中,并未见球形的全无机手性硅胶用作HPLC手性固定相。该文以无机球形介孔硅胶作为研究对象,通过堆砌硅珠法,以硅溶胶为原料,L-谷氨酸(L-Glu)为手性源,在手性环境中制造出脲醛树脂与胶体二氧化硅混合的小球,在550 ℃高温下煅烧除去树脂部分,制备基于L-Glu的无机介孔硅胶球。通过元素分析、红外光谱、扫描电镜、透射电镜和氮气吸附等表征证明这是一种具有规则球形的手性硅胶球,其手性来源于硅胶球自身的骨架和孔结构。将L-Glu手性硅胶球作为固定相制备了HPLC色谱柱,以正己烷-异丙醇(9∶1, v/v)作为流动相,流速为0.1 mL/min,考察了该手性柱对一系列外消旋化合物的拆分性能。实验表明,该手性柱拆分了15种外消旋化合物,其中特罗格尔碱、吡喹酮、3-苄氧基-1,2-丙二醇、1,2-环氧己烷、3-羟基-2-丁酮、2-甲基四氢呋喃-3-酮、异丙基缩水甘油醚达到基线分离;还分离了10种苯系位置异构体,o,m,p-氨基苯酚、o,p-氯苯酚、o,m,p-碘苯胺、o,m,p-甲苯胺、o,m,p-二硝基苯、o,m,p-氯苯胺、o,m,p-硝基苯酚、o,m,p-溴苯胺达到基线分离。实验表明,L-Glu手性硅胶球在手性分离方面具有良好的可行性,与普通硅胶相比不需要进一步修饰就可以有较好的手性分离效果,是一种低成本、制备便捷的手性无机硅胶固定相。     

基于共价有机框架材料TpPa-NH2-Glu的高效液相色谱固定相用于分离手性化合物

共价有机框架材料（COFs）是一类由多齿有机单元通过共价键连接而成的新兴孔晶体材料。通过合成后修饰所得到的COFs通常具有较高的结晶度与孔隙率,并且在手性拆分、不对称催化与色谱分析等领域具有良好的应用价值。该文用1,3,5-三甲醛间苯三酚与2-硝基-1,4-苯二胺合成TpPa-NO₂,对其还原得到TpPa-NH₂,然后通过合成后修饰策略将D-葡萄糖修饰到该材料上,得到手性材料TpPa-NH₂的D-葡萄糖衍生物（TpPa-NH₂-Glu）。利用“网包法”将其固载在球形硅胶表面用作高效液相色谱固定相并制备了液相色谱柱,分别以正己烷-异丙醇（9∶1, v/v）或甲醇-水（9∶1, v/v）为流动相,流速0.5 mL/min,成功拆分了16种包括多个手性药物的外消旋体和2种苯系位置异构体o,m,p-硝基苯胺和o,m,p-碘苯胺。在甲醇-水（9∶1, v/v）流动相条件下,拆分了5种外消旋体,其中盐酸普萘洛尔、华法林、美托洛尔达到了基线分离;在正己烷-异丙醇（9∶1, v/v）流动相条件下,拆分了11种外消旋体,其中2-溴丙酸乙酯、3-丁炔-2-醇达到了基线分离。此外还探究了温度对TpPa-NH₂-Glu液相色谱柱的影响以及TpPa-NH₂-Glu液相色谱柱的重复性,结果表明,温度对TpPa-NH₂-Glu所制备的高效液相色谱柱影响不大,且TpPa-NH₂-Glu所制备的高效液相色谱柱具有良好的重复性,其相对标准偏差（RSD）分别为1.55%和1.46%。实验结果表明,TpPa-NH₂-Glu对手性化合物有良好的拆分能力。     

芳香取代基结构对螺旋聚乙炔高效液相色谱手性固定相手性识别性能的影响

设计合成了3种源于脯氨酸的手性乙炔基单体——(S)-2-乙炔基-N-芳香胺基甲酰基吡咯烷. 在氯化降冰片二烯铑二聚体{[Rh(nbd)Cl]₂}-三乙胺催化下, 3种单体被转化为相应的光学活性螺旋聚合物. 用高效液相色谱评估了3种聚合物作为手性固定相(CSPs)对9种底物的手性识别性能. 以正己烷/异丙醇(体积比9∶1)为流动相时, 3种聚合物对3对种氢键给体分子苯偶姻(α=1.35~1.44)、 三氟-1-(9-蒽基)乙醇(α=1.11~1.53)、 2,2′-二羟基-1,1′-联萘(α=1.09~1.11)及乙酰丙酮钴(α=1.84~2.38)表现出很好的手性识别能力; 当以正己烷为流动相时, 3种聚合物都能立体选择性地识别氢键给体分子2,2-二甲基-1-苯基-1-丙醇(α=1.12~1.22), 聚[(S)-2-乙炔基-N-(2′-萘基胺基甲酰基)吡咯烷]能识别氢键受体分子2-苯基环己酮(α=1.11). 结合核磁共振波谱、 拉曼光谱、 旋光测试、 紫外吸收光谱和圆二色光谱及液相色谱等方法, 系统研究了芳香侧基结构与连接位置对聚合物螺旋构象和对映体选择性拆分能力的影响. 分子对接模拟结果表明, 1-萘基的空间位阻大于2-萘基且可促进形成更强的分子内氢键, 不利于大尺寸底物(如联萘酚)的手性拆分. 与苯基相比, 引入萘基有利于增强聚合物与底物间的π-π相互作用, 提高聚合物的立体选择性和手性识别能力.     

多孔有机笼的制备及其用作毛细管电色谱手性固定相

多孔有机笼(POCs)是具有一类内在的、客体可及的空腔的离散分子，是一类独特的微孔材料。本文根据席夫碱反应原理，用(1R,2R)-二氨基环己烷和3,3′,5,5′-四醛基-4,4′-联苯二酚缩合成一种孔径均匀、高比表面积、热化学稳定性良好的棱柱形手性多孔有机笼(POCs)。采用核磁共振氢谱仪、红外光谱、热重分析和扫描电子显微镜对该材料进行表征。将该材料溶解在二氯甲烷中，用动态涂覆法将溶液均匀地涂覆在石英毛细管内壁上，制成毛细管电色谱柱。结果表明，该手性电色谱柱不仅能拆分氧氟沙星、特罗格尔碱、2-氨基-1-丁醇和1-苯基-1-戊醇4种手性药物，还能拆分o,m,p-甲苯胺和o,m,p-氯苯胺2种位置异构体，说明该手性柱具有良好的手性分离能力。通过研究氧氟沙星、特罗格尔碱、2-氨基-1-丁醇和1-苯基-1-戊醇的最佳拆分条件，得出电压、缓冲溶液浓度和pH值对组分分离度有显著影响，其中，氧氟沙星、特罗格尔碱、2-氨基-1-丁醇的最优分离电压均为15 kV, 1-苯基-1-戊醇的最佳分离电压为17 kV;氧氟沙星、特罗格尔碱、2-氨基-1-丁醇、1-苯基-1-戊醇的最佳缓冲液浓度均为0.100 ...     

高效毛细管电泳用于二肽衍生物的手性拆分

以新型荧光试剂1,2-苯并-3,4-二氢咔唑-9-乙基氯甲酸酯(BCEOC)作为柱前衍生试剂,基于二元手性选择剂协同作用,在胶束电动色谱模式下考察并优化了二肽类衍生物手性分离的实验条件,实现了15种二肽衍生物的手性拆分,分离度均在2.85以上,其中11种在10.38以上,最高分离度达35.29。     

锆基纤维素手性固定相直接拆分萘普生衍生物

萘普生是一种消炎镇痛药 ,其 S对映体的抗炎作用是 R构型的 2 8倍 ,萘普生及其衍生物的拆分具有重要意义 .手性固定相 HPLC直接拆分 [1～ 4 ] 是最简便的分析方法 .氧化锆是近年来备受关注的色谱载体 [5,6 ] .Carr等 [7] 对碱性药物快速拆分表明氧化锆在手性分离Scheme1　 Structuresof chiral naproxen and its derivatives中的独特选择性 .萘普生及其衍生物在锆基手性固定相上的分离未见文献报道 .本组利用自制的球形氧化锆制备了涂敷型纤维素 -三 ( 3,5 -二甲基苯基氨基甲酸酯 ) -Zr O2 手性固定相 ( CDMPC- Zr O2 - CSP) ,在正…     

D-苯甘氨酸手性固定相的制备及对多种手性化合物的拆分

以D-3,5-二硝基苯甲酰苯甘氨酸和3-氨丙基硅烷化硅胶合成了D-苯甘氨酸衍生手性固定相,并自制了手性高效液相色谱分离柱,用正己烷-异丙醇作流动相,对非衍生化的氨基酸、胺、醇和羧酸类等10种手性化合物进行了高效液相色谱拆分。结果表明:所拆分的10种手性化合物,有7种手性化合物能得到基线分离,最好的分离度Rs=5.56。该文还用苯对柱性能进行了评价,理论塔板数达每米8万块。     

高效液相色谱法对二氢吡喃酮衍生物的手性拆分

介绍了利用手性chiralcel OD和chiralpak AD柱在高效液相色谱上对一系列二氢吡喃酮衍生物进行手性拆分，获得了良好的分离结果，考察了部分对映体在这两种柱上的色谱行为。实验表明手性化合物与手性柱之间存在着化学作用与空间作用，两者的共同作用决定了分离结果。     

直链淀粉-三[(S)-1-苯乙基氨基甲酸酯]手性固定相拆分布地奈德对映体及其制剂含量的测定

22R-布地奈德的药物活性比22S-布地奈德的强2~3倍,开发布地奈德对映体拆分和定量分析方法,可为其药物研发及质量控制提供重要依据。目前,主要以反相C₁₈固定相对布地奈德对映体进行拆分,而采用手性固定相对其进行拆分少有报道。通过考察固定相、流动相和柱温对布地奈德对映体拆分的影响,建立了基于直链淀粉-三[(S)-1-苯乙基氨基甲酸酯]手性固定相快速拆分和检测布地奈德对映体的高效液相色谱方法,其色谱条件如下:色谱柱为Chiralpak AS-RH色谱柱(150 mm×4.6 mm, 5.0 μm),流动相为乙腈-水(45∶55, v/v),柱温40 ℃,流速1.0 mL/min,二极管阵列检测器(DAD),检测波长246 nm,进样量10 μL。在该色谱条件下,布地奈德的两个对映体得到较好拆分,22R-布地奈德和22S-布地奈德的保留时间分别6.40 min和7.77 min,分离度为4.64; 22R-布地奈德和22S-布地奈德分别在各自范围内线性关系良好,相关系数(R²)均为0.9999,检出限分别为0.05 μg/mL和0.07 μg/mL,定量限分别为0.16 μg/mL和0.20 μg/mL; 4个添加水平的样品加标回收率为102.63%~104.17%,相对标准偏差(RSD)为0.08%~0.57%(n=6)。将该方法应用于1批次4个吸入用布地奈德混悬液实际样品进行检测,22R-布地奈德和22S-布地奈德的含量分别为283.15~284.63 μg/mL和259.86~261.51 μg/mL。该方法操作简便,分析时间短,重复性好,准确度高,可用于布地奈德对映体的拆分及其制剂的质量控制。     

二脲基桥联β-环糊精手性液相色谱键合相的制备与性能评价

采用六亚甲基二异氰酸酯与6-脱氧-6-羟乙基胺基-β-环糊精反应,合成二脲基桥联β-环糊精,并将其键合到硅胶表面,制备一种新型的二脲基桥联β-环糊精固定相(UBCDP)。通过红外光谱、质谱、元素分析等进行结构表征,以黄烷酮类、氨基酸类、三唑类手性药物和农药为探针,评价其手性色谱性能,探讨相关分离机理。进行色谱条件优化,并与单β-环糊精固定相(CDCSP)比较。试验了多种手性化合物,其中25个被拆分,2'-羟基黄烷酮、己唑醇、丹磺酰亮氨酸等分离度(R_s)达到1.52~4.35,且能拆分体积较大的橙皮甙。这与桥联β-环糊精的协同包结作用有关。而CDCSP仅能拆分少量的对映体,且分离度较低。UBCDP手性拆分能力更强,在手性药物和农药监测中有应用价值。     

Photografted methacrylate‐based monolithic columns coated with cellulose tris(3,5‐dimethylphenylcarbamate) for chiral separation in CEC

A chiral capillary monolithic column for enantiomer separation in capillary electrochromatography was prepared by coating cellulose tris(3,5‐dimethylphenylcarbamate) on porous glycidyl methacrylate‐co‐ethylene dimethacrylate monolith in capillary format grafted with chains of [2(methacryloyloxy)ethyl] trimethylammonium chloride. The surface modification of the monolith by the photografting of [2(methacryloyloxy)ethyl] trimethylammonium chloride monomer as well as the coating conditions of cellulose tris(3,5‐dimethylphenylcarbamate) onto the grafted monolithic scaffold were optimized to obtain a stable and reproducible chiral stationary phase for capillary electrochromatography. The effect of organic modifier (acetonitrile) in aqueous mobile phase for the enantiomer separation by capillary electrochromatography was also investigated. Several pairs of enantiomers including acidic, neutral, and basic analytes were tested and most of them were partially or completely resolved under aqueous mobile phases. The prepared monolithic chiral stationary phases exhibited a good stability, repeatability, and column‐to‐column reproducibility, with relative standard deviations below 11% in the studied electrochromatographic parameters.     

Syntheses, crystal structures and electronic properties of a series of copper(II) complexes with 3,5-halogen-substituted Schiff base ligands and their solutions

We have systematically investigated the structural features, electronic properties, thermally-induced structural phase transitions and absorption spectra depending on the solvent for ten Cu(II) complexes with 3,5-halogen-substituted Schiff base ligands. Structural characterization of two new complexes, bis(N-R-1-phenylethyl- and N-R,S-2-butyl-5-bromosalicydenaminato-κ²N,O)copper(II), reveals that they afford a compressed tetrahedral trans-[CuN₂O₂] coordination geometry with trans-N–Cu–N = 159.4(2)° and trans-O–Cu–O = 151.7(3)° for the 1-phenylethyl complex and trans-N–Cu–N = 157.9(3)° and trans-O–Cu–O = 151.0(3)° for the 2-butyl one. All the complexes exhibit a structural phase transition by heating in the solid state regardless of their structures at room temperature. The absorption spectra of a series of ten complexes exhibit a slight shift of the d–d band at 16 000–20 000 cm⁻¹ and remarkable shift of the π–π* band at 24 000–28 000 cm⁻¹, which suggests that the dipole moment of the solvents presumably affects the conformation of the π-conjugated moieties of the ligands rather than the coordination environment. We have also attempted ‘photochromic solute-induced solvatochromism’ by a system of bis(N-R-1-phenylethyl-3,5-dichlorosalicydenaminato-κ²N,O)copper(II) and photochromic 4-hydroxyazobenzene in chloroform solution. We successfully observed a change of the d–d and π–π* bands of the complex in the absorption spectra caused by cis–trans photoisomerization of 4-hydroxyazobenzene.     

3种金属有机骨架材料用于开管毛细管电色谱手性固定相分离外消旋体

金属有机骨架（MOFs）材料因具有丰富的拓扑结构、高比表面积、良好的稳定性、持久的孔结构以及可修饰的孔道表面等特点,在对映选择性催化和手性分离方面备受关注。该文通过水热法合成了3种具有手性的MOFs晶体,分别为Co₂（D-cam）₂（TMDPy）（简称为MOF 1）、[Cd（D-cam）（tmdpy）]·2H₂O（简称为MOF 2）和[Co_0.5Zn_0.5（L-Tyr）]_n（L-tyrCo/Zn）（简称为MOF 3）,并把它们用作固定相分别制成MOFs手性柱进行开管毛细管电色谱（OT-CEC）研究。在磷酸二氢钠-乙腈的流动相体系下,考察了3根MOFs手性柱对手性化合物的拆分性能。实验结果表明,这3种MOFs手性毛细管柱对部分外消旋体具有较好的拆分效果。目前将手性MOFs作为毛细管电色谱手性分离的研究正处在起步阶段并且具有良好的应用前景。     

基于手性固定相的超高效液相色谱-串联质谱法检测小麦及其加工制品中的腈菌唑对映体

建立了手性超高效液相色谱-串联质谱检测小麦及其加工制品中腈菌唑对映体残留的分析方法。样品经乙腈提取,N-丙基乙二胺(PSA)和C18净化,手性色谱柱Lux Cellulose-1(150 mm×2.0 mm, 3 μm)分离,质谱电喷雾正离子扫描(ESI⁺),多反应监测(MRM)模式进行检测。为准确定量,考察了小麦籽粒及其加工制品的基质效应,最终采用基质匹配校准法来补偿基质效应,并进行样品中腈菌唑对映体残留的校准定量。结果表明,腈菌唑的两个对映体得到良好的拆分。S-(+)-腈菌唑先出峰,R-(-)-腈菌唑后出峰,保留时间分别为4.34 min和5.13 min。S-(+)-腈菌唑和R-(-)-腈菌唑在小麦及其加工制品中的检出限均为0.2 μg/kg,定量限均为0.5 μg/kg。在0.5~25 μg/L范围内,腈菌唑对映体的峰面积与其质量浓度呈现良好的线性关系,相关系数(R²)均大于0.99。在对映体添加水平为5、50、100 μg/kg时,在小麦籽粒、麸皮、面粉、面团、馒头、面条、煮面水中,S-(+)-腈菌唑的平均回收率在82%~110%之间,RSD在0.9%~6.8%之间;R-(-)-腈菌唑的平均回收率在80%~109%之间,RSD在0.9%~6.8%之间。将该方法应用于实际样品的检测,在5份面粉、2份面条及2份馒头样品中均未检出腈菌唑对映体。该方法为手性农药腈菌唑对映体在初级农产品及其加工制品中的残留分析提供了有效的方法。     

Fast separations of chiral β-blockers on a cellulose tris(3,5-dimethylphenylcarbamate)-coated zirconia monolithic column by capillary electrochromatography

Cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) is an excellent chiral selector for enantioseparation of a wide variety of chiral compounds. The monolithic chiral columns are becoming popular in liquid chromatography and capillary electrochromatography. In this work, we present the fast separation of chiral β-blockers on a CDMPC-modified zirconia monolithic column by capillary electrochromatography (CEC). The porous zirconia monolithic capillary column was prepared by using the sol-gel technology and then zirconia surface modified with CDMPC. The enantioseparations were performed in reversed-phase (RP) eluents of a phosphate solution (pH 4.4) modified with acetonitrile or alcohol. The enantioseparations of a set of eight chiral β-blockers were achieved in less than one minute. Influences of the applied voltage, column temperature, concentration of acetonitrile and the type of alcohol as the organic modifier in the mobile phase, and sample injection time on enantioseparation were investigated. CEC separations at the applied voltage of 10 kV and 15 °C in the ACN-modified mobile phase provided the best resolutions for the analytes studied. Run-to-run and day-to-day repeatabilities of the column in the RP-CEC separation were less than 1 and 2%, respectively.     

亚微米C18键合硅胶固定相加压毛细管电色谱法同时拆分3种手性三唑类农药

采用改良Stöber法制备420 nm亚微米单分散二氧化硅微球,采用C18硅烷化修饰后装填成毛细管色谱柱。采用该色谱柱,在加压毛细管电色谱平台上成功地实现了3对手性三唑类农药烯效唑、烯唑醇和丙环唑的同时拆分和分离。考察了各因素对手性分离效果的影响,优化后的色谱条件为：流动相为乙腈-20 mmol/L磷酸盐缓冲液（pH=6.8）（45：55,v/v）,其中缓冲液中含20 mmol/L羟丙基-γ-环糊精（HP-γ-CD）;泵流速为0.04 mL/min;施加电压-9.4 kV;检测波长220 nm。在上述条件下,烯效唑、烯唑醇和丙环唑3种对映体同时得到拆分和分离,相邻两峰之间的分离度依次为4.20、12.9、4.41、4.09、1.70,分离时间仅为12 min,柱效最高达到310000 plates/m。该研究为手性三唑类农药的同时分离提供了新的分离分析思路。     

Synthesis of a novel copper(II) complex and its crystal structure

One novel chiral copper(II) complex was successfully synthesized from the reaction of chiral 1,3-thiazolidine-2-thione ligand with CuCl₂ in dichloromethane in the presence of Et₃N and DMAP at room temperature. Its unique crystal structure was unambiguously disclosed by X-ray analysis. The crystal is tetragonal, space group I4(1), space group a=15.0875(11), b=15.0875(11), c=19.362(3) Å, =90, β=90, γ=90°, V=4407.4(8) ų, Z=8, ρ_calc=1.639 mg cm⁻³.     

Ferroelectric liquid crystals with fluoro- and aza-fluorenone cores: the effect of stereo-polar coupling

The chiral fluorenone mesogens (R)-1-fluoro-2-(2-octyloxy)-7-(4-undecyloxybenzoyloxy)fluoren-9-one (2) and (R)-2-(2-octyloxy)-7-(4-undecyloxybenzoyloxy)-3-azafluoren-9-one (3) were synthesized using a combined ortho-directed and remote metalation strategy, which also incorporates a Suzuki-Miyaura crosscoupling step. These compounds form chiral SmC* liquid crystal phases with reduced polarizations (P _o) of +475 and +332 nC cm^-2 at 10 K below the Curie point, respectively. These values are considerably larger than that previously reported for the unsubstituted fluorenone (R)-2-(2-octyloxy)-7-(4-undecyloxybenzoyloxy)fluoren-9-one (1), which is +111 nC cm^-2 at 10 K below the Curie point. Molecular modelling based on the Boulder model suggests that the larger polarizations result from a conformational bias of the fluorenone core dipole moment along the polar axis of the SmC* phase caused by stereo-polar coupling with the chiral 2-octyloxy side chain.     

Synthesis and characterization of planarly chiral nonbridged bis(1-R-indenyl) zirconium dichloride complexes and X-ray structure of rac-[(η-C9H6-1-C(CH3)2---o-C6H4---OCH3)2ZrCl2]·THF

Reactions of the lithium salts of 3-substituted indenes 1, 2 with ZrCl₄(THF)₂ gave two series of nonbridged bis(1-substituted)indenyl zirconocene dichloride complexes. Fractional recrystallization from THF–petroleum ether furnished the pure racemic and mesomeric isomers of [(η⁵-C₉H₆-1-C(R¹)(R²)---o-C₆H₄---OCH₃)₂ZrCl₂]·nTHF (R¹=R²=CH₃, n=1, rac-1a and meso-1b; R¹=CH₃, R²=C₂H₅; n=0.5 or 0, rac-2a and meso-2b), respectively. Complex 1a was further characterized by X-ray diffraction to have a C₂ symmetrically racemic structure, where the six-member rings of the indenyl parts are oriented laterally and two o-CH₃O---C₆H₄---C(CH₃)₂--- substituents are oriented to the open side of the metallocene (Ind: bis-lateral, anti; Substituent: bis-central, syn). The four zirconocene complexes are highly symmetrical in solution as characterized by room temperature ¹H-NMR, however ¹H–¹H NOESY of meso-1b shows that some of the NOE interactions arise from the two separated indenyl parts of the same molecule, which can only be well explained by taking into account the torsion isomers in solution.