Godini Zahra, Nematollahi Davood, Mohamadighader Niloofar, Mashhadi Pegah
Faculty of Chemistry and Petroleum Sciences, Bu-Ali Sina University, Hamedan, 65178-38683, Iran.
Planet Chemistry Research Center, Bu-Ali Sina University, Hamedan, Iran.
Sci Rep. 2025 Jul 22;15(1):26568. doi: 10.1038/s41598-025-12528-z.
The electrochemical synthesis of new benzodiazepine derivatives, via late-stage modification of clonazepam (CZP), a benzodiazepine anticonvulsant drug, is one of the two main objectives of this research. To achieve this goal, electrochemical oxidation of this drug was carried out in the presence of arylsulfinic acid derivatives (ASA) in an undivided cell equipped with a graphite anode and cathode, in a water/ethanol mixture, under controlled potential conditions. In this method, new benzodiazepines were synthesized under easy workup and environmentally friendly conditions without the need for catalysts, reagents, or toxic solvents, at room temperature and pressure. In another part of this research, the electrochemical behavior of CZP was thoroughly investigated and new information was reported on the electrochemical reaction mechanism, the major metabolite of CZP, and the relationship between potential and pH. The proposed mechanism for the late-stage modification of CZP involves the sequential reduction and oxidation of CZP at the cathode and anode, respectively, followed by reaction with the nucleophile (ASA). In addition, docking studies were performed on the synthesized compounds and it was found that the synthesized derivatives can interact well with the gamma-aminobutyric acid agonist (GABA).
通过苯二氮䓬类抗惊厥药物氯硝西泮（CZP）的后期修饰进行新型苯二氮䓬衍生物的电化学合成，是本研究的两个主要目标之一。为实现这一目标，在配备石墨阳极和阴极的无隔膜电解池中，于水/乙醇混合物中，在可控电位条件下，在芳基亚磺酸衍生物（ASA）存在的情况下对该药物进行电化学氧化。在此方法中，新型苯二氮䓬在易于后处理且环境友好的条件下合成，无需催化剂、试剂或有毒溶剂，在室温和常压下即可进行。在本研究的另一部分，对 CZP 的电化学行为进行了深入研究，并报道了有关电化学反应机理、CZP 的主要代谢产物以及电位与 pH 之间关系的新信息。所提出的 CZP 后期修饰机制涉及 CZP 分别在阴极和阳极依次进行还原和氧化，随后与亲核试剂（ASA）反应。此外，对合成的化合物进行了对接研究，发现合成的衍生物能够与γ-氨基丁酸激动剂（GABA）良好相互作用。
