Antony Arsha, Thomas Tiju, Augustine Cyril
Department of Chemistry, St. Berchmans College, Mahatma Gandhi University, Kottayam, India.
Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai, India.
J Mol Model. 2023 May 1;29(5):167. doi: 10.1007/s00894-023-05565-w.
Iron is one of the essential metals required by almost all living organisms. However, nature has certain constraints in distributing this element among tissues. Since polymeric oxide-bridged Fe (III) is the prominent source of Fe (III) ions, the insolubility of Fe (III) ions in aqueous systems reduces the direct uptake by cells. Secondly, the free-Fe entities which generate OH radicals pave the way to the destruction of the cells. Hence, a protective coordination environment via sophisticated chemical systems is required for the acquisition of Fe, its successive transport, storage, and effective utilization in various tissues. Siderophores are polydentate ligands used by bacterial cells for Fe acquisition, with a relatively high affinity for Fe (III) ions. Secreted from the bacterial cells into the external aqueous medium, they sequester Fe to give a soluble complex which re-enters the organism at a specific receptor. Once it gets inside the cell, the Fe is released from the complex and utilized for essential biochemical reactions. The medicinal applications of these natural ligands, developing progressively in various research groups, necessitate the theoretical aspects of their coordination chemistry. This research paper deals with the coordination chemistry of one of the siderophores, cepabactin (Cep). The chemical computations confirm that the Fe(Cep) complex is octahedral and high spin. The oxygen atoms of Cep, which are hard and negatively charged, thus act as electron donors in the Fe(Cep) complex formation. This in turn makes the siderophores relatively less attractive towards Fe (II) ions.
铁是几乎所有生物所必需的金属元素之一。然而，自然界在将这种元素分配到各个组织方面存在一定限制。由于聚合的氧化物桥连Fe(III)是Fe(III)离子的主要来源，Fe(III)离子在水体系中的不溶性降低了细胞对其的直接摄取。其次，产生羟基自由基的游离铁实体为细胞的破坏铺平了道路。因此，需要通过复杂的化学体系提供一个保护性的配位环境，以实现铁的获取、后续运输、储存以及在各种组织中的有效利用。铁载体是细菌细胞用于获取铁的多齿配体，对Fe(III)离子具有相对较高的亲和力。它们从细菌细胞分泌到外部水介质中，螯合铁形成可溶性复合物，该复合物通过特定受体重新进入生物体。一旦进入细胞，铁从复合物中释放出来并用于基本的生化反应。这些天然配体在各个研究小组中逐渐发展的医学应用，需要其配位化学的理论支持。本研究论文探讨了其中一种铁载体——头孢菌素（Cep）的配位化学。化学计算证实Fe(Cep)配合物为八面体且高自旋。Cep的氧原子具有硬碱性且带负电荷，因此在Fe(Cep)配合物形成过程中充当电子供体。这反过来使得铁载体对Fe(II)离子的吸引力相对较小。
