Carnamucio Federica, Foti Claudia, Saija Franz, Cassone Giuseppe, Giuffrè Ottavia
Department of Pharmaceutics and Center for Pharmaceutical Engineering and SciencesSchool of Pharmacy, Virginia Commonwealth University, 410 N 12th Street, Richmond, Virginia 23284, United States.
Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, Viale F. Stagno d'Alcontres 31, Messina 98166, Italy.
ACS Environ Au. 2025 May 12;5(4):404-414. doi: 10.1021/acsenvironau.5c00024. eCollection 2025 Jul 16.
Natural water sources are increasingly contaminated with a wide range of pollutants including heavy metals and pharmaceuticals. Arsenic, particularly in its more toxic trivalent form, i.e. As-(III), remains a significant environmental and public health concern due to its widespread presence and carcinogenic effects. In addition to that, pharmaceutical products like metronidazole (MNZ) and nalidixic acid (NAL), persistent in the environment due to their limited biodegradability, also pose significant threats to both ecosystems and human health. Recent research has highlighted the formation of antibiotic-metal complexes (AMCs) where antibiotics interact with heavy metals in aquatic environments, leading to altered physicochemical properties and increased toxicity.
The main objective of the present work is a speciation study on As-(III)-antibiotic complexes and particularly interaction between As-(III) and MNZ or NAL in aqueous solution.
Several temperatures and ionic strengths were probed by potentiometry to determine the formation constants and other thermodynamic parameters of As-(III)-MNZ and As-(III)-NAL complexes. UV spectrophotometric titrations were also employed to confirm formation constants of both systems. An estimation of the sequestering ability of both ligands toward As-(III) under relevant natural water conditions has also been performed. Further, density functional theory calculations have been executed with the purpose of investigating the molecular structure of these complexes and their relative stability.
It turns out that MNZ binds to As-(III) in either a neutral (AsMNZ) or protonated (As-(MNZ)-H) form via As-N and As-O interactions, with the hydroxyl oxygen being the preferred binding site in AsMNZ and both the nitro and hydroxyl groups being equally effective in As-(MNZ)-H, while NAL forms a stable chelated complex through bidentate coordination.
Findings reported in this study contribute to a deeper understanding of the complexes formed by As-(III) with pharmaceuticals and pave the way toward the development of improved technologies for the water treatment and remediation of AMCs.
天然水源正日益受到包括重金属和药物在内的多种污染物的污染。砷，尤其是毒性更强的三价形式，即As-(III)，由于其广泛存在和致癌作用，仍然是一个重大的环境和公共卫生问题。除此之外，甲硝唑（MNZ）和萘啶酸（NAL）等药品由于其有限的生物降解性而在环境中持久存在，也对生态系统和人类健康构成重大威胁。最近的研究强调了抗生素 - 金属络合物（AMCs）的形成，其中抗生素在水生环境中与重金属相互作用，导致物理化学性质改变和毒性增加。
本工作的主要目标是对As-(III)-抗生素络合物进行形态研究，特别是研究As-(III)与MNZ或NAL在水溶液中的相互作用。
通过电位滴定法探究了几种温度和离子强度，以确定As-(III)-MNZ和As-(III)-NAL络合物的形成常数和其他热力学参数。还采用紫外分光光度滴定法来确认两个体系的形成常数。此外，还对两种配体在相关天然水条件下对As-(III)的螯合能力进行了估算。此外，还进行了密度泛函理论计算，以研究这些络合物的分子结构及其相对稳定性。
结果表明，MNZ通过As-N和As-O相互作用以中性（AsMNZ）或质子化（As-(MNZ)-H）形式与As-(III)结合，在AsMNZ中羟基氧是首选结合位点，在As-(MNZ)-H中硝基和羟基同样有效，而NAL通过双齿配位形成稳定的螯合络合物。
本研究报告的结果有助于更深入地了解As-(III)与药物形成的络合物，并为开发改进的水处理和AMCs修复技术铺平道路。
