Rapid method for screening of both calcium and magnesium chelation with comparison of 21 known metal chelators.

IF 2.7 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY JBIC Journal of Biological Inorganic Chemistry Pub Date : 2024-10-18 DOI:10.1007/s00775-024-02078-6

Lukáš Konečný, Zuzana Lomozová, Galina Karabanovich, Jaroslav Roh, Kateřina Vávrová, Přemysl Mladěnka

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Abstract

Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using o-cresolphthalein complexone (o-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by o-CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure-activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.

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通过比较 21 种已知金属螯合剂，快速筛选钙镁螯合剂的方法。

螯合是金属超载情况下的合理治疗方式，但螯合剂通常是非选择性的，因此可能导致包括钙和镁在内的生理金属平衡失调。本研究的目的是开发一种经济、快速但灵敏、精确的方法来确定钙镁离子的螯合程度，并将这种方法与已知的金属螯合剂进行比较。研究人员开发了使用邻甲酚酞络合酮（o-CC）的分光光度法，并通过阻抗聚集测定法确认了该方法在人体血小板中的生物相关性。o-CC 对钙离子和镁离子的最低检测浓度分别为 2.5 μM 和 2 μM。该指示剂至少在 110 天内保持稳定。21 种螯合剂中分别有 4 种和 7 种能强烈螯合钙离子和镁离子。重要的是，临床使用的螯合剂的螯合效果也不容忽视。八种喹啉-8-醇的结构-活性关系显示，螯合效果有所改善，尤其是在二卤素取代的情况下，并且观察到 pKa 与镁螯合之间存在负线性关系。钙螯合可抑制与复合物形成浓度相应的血小板聚集。开发并验证了一种用于筛选钙镁离子螯合有效性和安全性的新方法。

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来源期刊

JBIC Journal of Biological Inorganic Chemistry 化学-生化与分子生物学

CiteScore

5.90

自引率

3.30%

发文量

审稿时长

3 months

期刊介绍： Biological inorganic chemistry is a growing field of science that embraces the principles of biology and inorganic chemistry and impacts other fields ranging from medicine to the environment. JBIC (Journal of Biological Inorganic Chemistry) seeks to promote this field internationally. The Journal is primarily concerned with advances in understanding the role of metal ions within a biological matrix—be it a protein, DNA/RNA, or a cell, as well as appropriate model studies. Manuscripts describing high-quality original research on the above topics in English are invited for submission to this Journal. The Journal publishes original articles, minireviews, and commentaries on debated issues.