Technical Capabilities and Limitations of Optical Spectroscopy and Calorimetry Using Water-Miscible Solvents: The Case of Dimethyl Sulfoxide, Acetonitrile, and 1,4-Dioxane
Technical Capabilities and Limitations of Optical Spectroscopy and Calorimetry Using Water-Miscible Solvents: The Case of Dimethyl Sulfoxide, Acetonitrile, and 1,4-Dioxane
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DOI：
10.1016/j.xphs.2019.10.056
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发表时间：
2020-01-01
影响因子：
3.8
通讯作者：
Arakawa, Tsutomu
中科院分区：
文献类型：
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作者：
Hirano, Atsushi;Nagatoishi, Satoru;Arakawa, Tsutomu
在药物开发中，水混溶性溶剂通常用于溶解药物物质。药物开发中的典型常规程序包括将储备药物溶液稀释到含有用于药物结合测定的靶大分子的水溶液中。然而，水混溶性溶剂由于其光吸收和热容量而对测定施加了一些技术限制。在这里，我们研究了稀释3水溶性溶剂，即二甲基亚砜，乙腈，和1，4-二氧六环，在圆二色谱，等温滴定量热法和差示扫描量热法的基线稳定性和信号/噪声比的影响。二甲基亚砜和1，4-二氧六环在常用浓度下会因其吸光度而影响圆二色光谱的信噪比。水溶性溶剂由于其混合热而在等温滴定量热法中产生干扰信号。它们在差示扫描量热法中显示负或正斜率。根据分析技术，通过适当稀释可降低溶剂的此类干扰效应。由于水混溶性溶剂对化学品的烷基链部分和芳族部分具有增溶能力，因此含有这些部分的药物物质可溶解于溶剂中，然后在适当稀释药物溶液后进行分析以检查其与靶蛋白的相互作用。(C)2020年美国药学协会。爱思唯尔公司出版All rights reserved.
In drug development, water-miscible solvents are commonly used to dissolve drug substances. Typical routine procedures in drug development include dilution of the stock drug solution into an aqueous solution containing target macromolecules for drug binding assays. However, water-miscible solvents impose some technical limitations on the assays on account of their light absorption and heat capacity. Here, we examined the effects of the dilution of 3 water-miscible solvents, that is, dimethyl sulfoxide, acetonitrile, and 1,4-dioxane, on the baseline stability and signal/noise ratio in circular dichroism spectroscopy, isothermal titration calorimetry, and differential scanning calorimetry. Dimethyl sulfoxide and 1,4-dioxane affect the signal/noise ratio of circular dichroism spectra at typically used concentrations due to their light absorbance. The water-miscible solvents generate interfering signals in the isothermal titration calorimetry due to their mixing heat. They show negative or positive slope in the differential scanning calorimetry. Such interfering effects of the solvents are reduced by appropriate dilution according to the analytical techniques. Because the water-miscible solvents have solubilization capacity for alkyl chain moieties and aromatic moieties of chemicals, drug substances containing these moieties can be dissolved into the solvents and then subjected to the analyses to examine their interactions with target proteins after appropriate dilution of the drug solutions. (C) 2020 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.