Stability Studies of New Caged bis ‐Deoxy‐Coelenterazine Derivatives and Their Potential Use as Cellular pH Probes,Photochemistry and Photobiology

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Stability Studies of New Caged bis ‐Deoxy‐Coelenterazine Derivatives and Their Potential Use as Cellular pH Probes
Photochemistry and Photobiology ( IF 2.6 ) Pub Date : 2020-11-11 , DOI: 10.1111/php.13347
Germano Giuliani ₁ , Assunta Merolla ₂ , Marco Paolino ₁ , Annalisa Reale ₁ , Mario Saletti ₁ , Lluís Blancafort ₃ , Andrea Cappelli ₁ , Fabio Benfenati _{2,

4} , Fabrizia Cesca _{2,

5}

Affiliation

The synthesis of new bis-deoxy-coelenterazine (1) derivatives bearing ester protective groups (acetate, propionate and butyrate esters) was accomplished. Moreover, their hydrolytic stability at room temperature was evaluated in dimethylsulfoxide (DMSO) as solvent, using the nuclear magnetic resonance (NMR) spectra of the key products at different time intervals. The results showed an increasing hydrolysis rate according to longest aliphatic chain, with a half-life of 24 days of the more stable acetate derivative (4a). Furthermore, the analysis of the experimental data revealed the greater stability of the enol tautomer in this aprotic polar solvent. This result was confirmed by theoretical calculations using the Density Functional Theory (DFT) approach, which gave us the opportunity to propose a detailed decomposition mechanism. Additionally, the derivatives obtained were tested by bioluminescence luciferase assays to evaluate their potential use as extra-cellular pH-sensitive reporter substrates of luciferase. The biological data support the idea that further structural modifications of these molecules may open promising perspectives in this field of research.

中文翻译：

新型笼式双脱氧腔肠素衍生物的稳定性研究及其作为细胞 pH 探针的潜在用途

完成了带有酯保护基团（乙酸酯、丙酸酯和丁酸酯）的新型双脱氧腔肠素 (1) 衍生物的合成。此外，使用关键产物在不同时间间隔的核磁共振 (NMR) 光谱，以二甲基亚砜 (DMSO) 为溶剂，评估了它们在室温下的水解稳定性。结果表明，根据最长的脂肪族链，水解速率增加，更稳定的乙酸酯衍生物 (4a) 的半衰期为 24 天。此外，对实验数据的分析表明，烯醇互变异构体在这种非质子极性溶剂中具有更高的稳定性。使用密度泛函理论 (DFT) 方法的理论计算证实了这一结果，这使我们有机会提出详细的分解机制。此外，获得的衍生物通过生物发光荧光素酶测定进行测试，以评估它们作为荧光素酶的细胞外 pH 敏感报告底物的潜在用途。生物学数据支持这样一种观点，即对这些分子进行进一步的结构修饰可能会在该研究领域开辟有前景的前景。

更新日期：2020-11-11

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