Imaging the Cellular Distribution of Amino Acid Derivatives of Tricarbonylrhenium(I) 1, 10-orthophenanthroline Compounds
Year: 2023
Type: article
Abstract: Transition metals, such as zinc, iron magnesium, molybdenum, and copper, are essential in cellular biochemistry as they function as components of enzyme active sites, assist in protein folding, and function as electron carriers. In these functions, the metal ions are complexed with proteins. Transition metal complexes have also found applications as diagnostic, therapeutic, and imaging agents. A diversity of organic ligands has been complexed with d-block transition elements such as rhenium (I) and ruthenium (II) to develop luminescent compounds for use in microscopy [1–3]. The compounds display favorable optical properties for imaging including a large Stoke’s shift and long excited-state lifetimes [3]. The luminescence has been attributed to metal-to-ligand charge transfers (MLCT) that are forbidden and that, consequently, exhibit long half-lives [4]. The emissions are influenced by the environment of complexes. These characteristics are particularly important in biological systems that can exhibit high levels of autofluorescence [1]. To image different cellular locales, the complexes have been modified with different ligands. Further, by conjugating the complexes with ligands for specific proteins, the rhenium compounds have shown effectiveness in imaging hormone receptors in cells [2]. It has also been possible to target specific organelles such as Golgi, nucleolus, the endoplasmic reticulum and cellular nitric oxide [4]. In this study, several new Re(I) tricarbonyl, 1, 10-orthophenanthroline compounds have been synthesized via the functionalization with N-acetyl alanine, N-acetyl glycine, N-acetyl proline, and N-acetyl tyrosine. The generic methods for the synthesis have been reported elsewhere [5–6]. The compounds accommodate three carbonyl ligands forming an octahedral face, a di-nitrogen ligand 1, 10 ortho phenanthroline and a labile carboxylate functional group coming from the amino acid that is axial to the equator of the rhenium complex (Figure 1). Spectrofluorimetric analysis revealed absorption maxima at 295nm and 389nm and emission maximum at 594.94–598.13nm. The interaction of the compounds with mammalian cells was studied with confocal microscopy (Figure 2). U937 cells were cultured using standard techniques and treated for 24 hours with the compounds prior to imaging. The results show the concentration of the compounds in the nucleus with distributions that are reminiscent of chromatin. Similarly, pyridyl triazine core Re(I) complexes were synthesized and shown to accumulate in nuclei of animal and plant cells [7]. Of interest would be to understand how the ligands contribute to the targeting to specific subcellular locales in the absence of affinity ligands. Still, it has been reported that the use di-nitrogenated ligands as well as a positive net charge are important conditions for uptake by organisms with a cell wall [2, 8].
Source: Microscopy and Microanalysis
Authors: Birsen Varisli, James Wachira, Santosh Mandal
Institution: Morgan State University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4385072371