使用96孔微量滴定板通过紫外光谱法快速测定电离常数（pKa）
Rapid Determination of Ionization Constants (pK a) by UV Spectroscopy Using 96-Well Microtiter Plates.
作者信息
Martínez Carlos H Ríos, Dardonville Christophe
机构信息
Instituto de Química Médica, IQM-CSIC , Juan de la Cierva 3, E-28006 Madrid, Spain.
出版信息
ACS Med Chem Lett. 2012 Nov 20;4(1):142-5. doi: 10.1021/ml300326v. eCollection 2013 Jan 10.
Abstract
We have developed a methodology that enables for the rapid measurement of ionization constants (pK a) of series of compounds by UV spectrophotometry. This protocol, which is straightforward to set up, takes advantage of the sensitivity of UV spectroscopy and the throughput enabled by the 96-well microplate (as opposed to the use of 1 cm quartz cuvette). The compounds, in stock solutions in DMSO, are dissolved in several aqueous buffer solutions directly in the microtiter plate, allowing the simultaneous determination of the UV spectra as a function of pH. Further treatment of the data provides the pK a values in a medium-throughput manner. The pK a values of 11 new antitrypanosomal dibasic compounds were determined using this methodology.
摘要
我们开发了一种方法，能够通过紫外分光光度法快速测量一系列化合物的电离常数（pKa）。该方案易于设置，利用了紫外光谱的灵敏度以及96孔微孔板实现的通量（与使用1厘米石英比色皿相反）。将二甲基亚砜储备溶液中的化合物直接溶解在微孔板中的几种水性缓冲溶液中，从而能够同时测定作为pH函数的紫外光谱。对数据的进一步处理以中等通量的方式提供pKa值。使用该方法测定了11种新型抗锥虫二元化合物的pKa值。
相似文献
1
Rapid Determination of Ionization Constants (pK a) by UV Spectroscopy Using 96-Well Microtiter Plates.使用96孔微量滴定板通过紫外光谱法快速测定电离常数（pKa）
ACS Med Chem Lett. 2012 Nov 20;4(1):142-5. doi: 10.1021/ml300326v. eCollection 2013 Jan 10.
2
Determining Partition Coefficient (Log P), Distribution Coefficient (Log D) and Ionization Constant (pKa) in Early Drug Discovery.在早期药物发现中测定分配系数（Log P）、分布系数（Log D）和电离常数（pKa）。
Comb Chem High Throughput Screen. 2016;19(6):461-9. doi: 10.2174/1386207319666160502123917.
3
High-throughput measurement of pKa values in a mixed-buffer linear pH gradient system.混合缓冲液线性pH梯度系统中pKa值的高通量测量
Anal Chem. 2003 Feb 15;75(4):883-92. doi: 10.1021/ac020329y.
4
Thermodynamic equilibrium solubility measurements in simulated fluids by 96-well plate method in early drug discovery.早期药物研发中采用96孔板法在模拟流体中进行热力学平衡溶解度测定。
Bioorg Med Chem Lett. 2015 Apr 1;25(7):1561-7. doi: 10.1016/j.bmcl.2015.02.013. Epub 2015 Feb 16.
5
Development and validation of a FIA/UV-vis method for pK(a) determination of oxime based acetylcholinesterase reactivators.一种基于流动注射分析/紫外可见分光光度法测定肟类乙酰胆碱酯酶复活剂pK(a)的方法的开发与验证
J Pharm Biomed Anal. 2016 Jan 5;117:240-6. doi: 10.1016/j.jpba.2015.09.010. Epub 2015 Sep 11.
6
Spectrophotometric pKa determination of ionizable pharmaceuticals: Resolution of molecules with weak pH-dependent spectral shift.分光光度法测定可电离药物的pKa：解决具有弱pH依赖性光谱位移的分子问题。
J Pharm Biomed Anal. 2015 Oct 10;114:88-96. doi: 10.1016/j.jpba.2015.05.009. Epub 2015 May 21.
7
pH indicator titration: a novel fast pKa determination method.pH指示剂滴定法：一种新型快速pKa测定方法。
J Pharm Sci. 2007 Oct;96(10):2777-83. doi: 10.1002/jps.20959.
8
Novel Instrument for Automated pK(a) Determination by Internal Standard Capillary Electrophoresis.新型内标毛细管电泳自动 pK(a)测定仪。
Anal Chem. 2015 Jun 16;87(12):6165-72. doi: 10.1021/acs.analchem.5b00845. Epub 2015 May 29.
9
Determination of pK(a) of felodipine using UV-Visible spectroscopy.使用紫外可见光谱法测定非洛地平的 pK(a)。
Spectrochim Acta A Mol Biomol Spectrosc. 2013 Nov;115:887-90. doi: 10.1016/j.saa.2013.07.001. Epub 2013 Jul 10.
10
Determination of dissociation constants of labile drug compounds by capillary electrophoresis.通过毛细管电泳法测定不稳定药物化合物的解离常数
J Pharm Biomed Anal. 2003 Oct 15;33(3):379-91. doi: 10.1016/s0731-7085(03)00238-3.
引用本文的文献
1
Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids.仿生合成与化学蛋白质组学揭示间苯三酚倍半萜类化合物的作用机制和功能靶点。
J Am Chem Soc. 2024 Jan 31;146(4):2524-2548. doi: 10.1021/jacs.3c10741. Epub 2024 Jan 17.
2
Synthesis and Biophysical and Biological Studies of -Phenylbenzamide Derivatives Targeting Kinetoplastid Parasites.合成及含苯甲酰胺衍生物的生物物理和生物学研究，针对原生动物寄生虫。
J Med Chem. 2023 Oct 12;66(19):13452-13480. doi: 10.1021/acs.jmedchem.3c00697. Epub 2023 Sep 20.
3
Ultrafast Spectroscopies of Nitrophenols and Nitrophenolates in Solution: From Electronic Dynamics and Vibrational Structures to Photochemical and Environmental Implications.溶液中硝基酚和硝基酚盐的超快光谱学：从电子动力学和振动结构到光化学和环境意义。
Molecules. 2023 Jan 6;28(2):601. doi: 10.3390/molecules28020601.
4
Integration of In Silico, In Vitro and In Situ Tools for the Preformulation and Characterization of a Novel Cardio-Neuroprotective Compound during the Early Stages of Drug Development.在药物研发早期阶段，整合计算机模拟、体外和原位工具用于一种新型心脏神经保护化合物的处方前研究和表征
Pharmaceutics. 2022 Jan 13;14(1):182. doi: 10.3390/pharmaceutics14010182.
5
Measurement of the Free-Base Nicotine Fraction (α) in Electronic Cigarette Liquids by Headspace Solid-Phase Microextraction.通过顶空固相微萃取测量电子烟液中的游离碱尼古丁分数 (α)。
Chem Res Toxicol. 2021 Oct 18;34(10):2227-2233. doi: 10.1021/acs.chemrestox.1c00285. Epub 2021 Oct 5.
6
Metabolic Profiles of New Unsymmetrical Bisacridine Antitumor Agents in Electrochemical and Enzymatic Noncellular Systems and in Tumor Cells.新型不对称双吖啶抗肿瘤药物在电化学和酶促非细胞体系以及肿瘤细胞中的代谢谱
Pharmaceuticals (Basel). 2021 Apr 1;14(4):317. doi: 10.3390/ph14040317.
7
Spectrophotometric determination of α-hydroxytropolone p values: A structure-acidity relationship study.分光光度法测定α-羟基托酚酮的pKa值：结构-酸度关系研究。
Tetrahedron Lett. 2019 Jun 20;60(25):1643-1645. doi: 10.1016/j.tetlet.2019.05.034. Epub 2019 May 20.
8
NIR Absorbing AzaBODIPY Dyes for pH Sensing.用于 pH 传感的近红外吸收 AzaBODIPY 染料。
Molecules. 2020 Aug 13;25(16):3689. doi: 10.3390/molecules25163689.
9
The Effects of pH on the Structure and Bioavailability of Imidazobenzodiazepine-3-Carboxylate MIDD0301.pH 值对咪唑并苯并二氮杂卓-3-羧酸甲酯（MIDD0301）结构和生物利用度的影响。
Mol Pharm. 2020 Apr 6;17(4):1182-1192. doi: 10.1021/acs.molpharmaceut.9b01210. Epub 2020 Feb 26.
10
In Vivo Anticancer Activity of a Rhenium(I) Tricarbonyl Complex.铼（I）三羰基配合物的体内抗癌活性
ACS Med Chem Lett. 2019 Apr 23;10(5):822-827. doi: 10.1021/acsmedchemlett.9b00128. eCollection 2019 May 9.
本文引用的文献
1
Ring Structure and Aromatic Substituent Effects on the pK a of the Benzoxaborole Pharmacophore.苯并硼氧六环药效团的环结构和芳香取代基对其pKa的影响。
ACS Med Chem Lett. 2011 Oct 19;3(1):48-52. doi: 10.1021/ml200215j. eCollection 2012 Jan 12.
2
A fast high throughput method for the determination of acidity constants by capillary electrophoresis. 3. Basic internal standards.一种快速高通量的毛细管电泳法测定酸度常数。3. 碱性内标。
J Chromatogr A. 2011 Jun 24;1218(25):3928-34. doi: 10.1016/j.chroma.2011.04.054. Epub 2011 Apr 27.
3
Synthesis and antiprotozoal activity of N-alkoxy analogues of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine with improved human blood-brain barrier permeability.合成和抗原生动物活性的 N-烷氧基类似物的抗锥虫先导化合物 4,4'-双(咪唑啉基氨基)二苯胺与人血脑屏障通透性提高。
J Med Chem. 2011 Jan 27;54(2):485-94. doi: 10.1021/jm101335q. Epub 2010 Dec 22.
4
Fast high-throughput method for the determination of acidity constants by capillary electrophoresis. II. Acidic internal standards.快速高通量毛细管电泳法测定酸度常数。二、酸性内标。
J Chromatogr A. 2010 Dec 24;1217(52):8340-5. doi: 10.1016/j.chroma.2010.10.060. Epub 2010 Oct 23.
5
The pK(a) Distribution of Drugs: Application to Drug Discovery.药物的pK(a)分布：在药物发现中的应用。
Perspect Medicin Chem. 2007 Sep 17;1:25-38.
6
Fast high-throughput method for the determination of acidity constants by capillary electrophoresis: I. Monoprotic weak acids and bases.毛细管电泳法快速高通量测定酸度常数：I. 一元弱酸和弱碱
J Chromatogr A. 2009 Apr 24;1216(17):3646-51. doi: 10.1016/j.chroma.2008.12.090. Epub 2009 Jan 8.
7
New bis(2-aminoimidazoline) and bisguanidine DNA minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity.新型双（2-氨基咪唑啉）和双胍DNA小沟结合剂，具有强大的体内抗锥虫和抗疟原虫活性。
J Med Chem. 2008 Feb 28;51(4):909-23. doi: 10.1021/jm7013088. Epub 2008 Feb 5.
8
Computational approach to the basicity of a series of alpha1-adrenoceptor ligands in aqueous solution.水溶液中一系列α1-肾上腺素能受体配体碱性的计算方法。
Bioorg Med Chem. 2007 Apr 15;15(8):2850-5. doi: 10.1016/j.bmc.2007.02.026. Epub 2007 Feb 15.
9
DNA binding affinity of bisguanidine and bis(2-aminoimidazoline) derivatives with in vivo antitrypanosomal activity.具有体内抗锥虫活性的双胍和双（2-氨基咪唑啉）衍生物的DNA结合亲和力。
J Med Chem. 2006 Jun 15;49(12):3748-52. doi: 10.1021/jm060295c.
10
Rapid pKa estimation using vacuum-assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection.使用带有紫外检测的真空辅助多重毛细管电泳（VAMCE）进行快速pKa估计。
J Pharm Sci. 2005 Mar;94(3):576-89. doi: 10.1002/jps.20275.
Zotero 插件