人类疾病的早期诊断仍然是医学领域的挑战,其中一种有效的非侵入性技术是磁共振成像(MRI)。MRI能够检测各种疾病和状况,包括神经系统疾病和癌症,并使用NMR弛豫的原理来生成身体的详细内部图像。对于这样的调查,已经研究了不同的金属配合物作为潜在的MRI造影剂。考虑到这一点,本文旨在研究含钒配合物[VO(metf)2]·H2O(VC1)和[VO(bpy)2Cl](VC2)的两个体系,是各自配合物的二甲双胍和联吡啶配体,与生物靶标AMPK和ULK1。这些生物分子参与阿尔茨海默病和三阴性乳腺癌的进展,分别,并可能作为检测这些疾病的有前途的光谱探针。为了初步评估所研究的配体在上述蛋白质活性位点和水性环境中的行为,四个经典分子动力学(MD)模拟,包括VC1+H2O(1),VC2+H2O(2),VC1+AMPK+H2O(3),进行VC2+ULK1+H2O(4)。由此,得出的结论是,对于仅包含VC和水的两个系统,与DOTAREM相比,理论计算意味着更高的效率,一种著名的市售MRI造影剂。当评价含有VC1+AMPK+H2O的体系时,保持该结果。然而,对于系统VC2+ULK1+H2O,由于存在相关的空间位阻,观察到钒络合物效率降低。尽管如此,由于VC2和ULK1之间相互作用的性质及其配体的性质,这项研究提供了一个见解,对VC2结构的一些修改可能会提高其作为MRI探头的效率。
Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)2]·H2O (VC1) and [VO(bpy)2Cl]+ (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer\'s disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + H2O (1), VC2 + H2O (2), VC1 + AMPK + H2O (3), and VC2 + ULK1 + H2O (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with DOTAREM, a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + H2O. Nevertheless, for the system VC2 + ULK1 + H2O, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe.