Organometallic compounds are increasingly recognized as promising anticancer and antibiotic drug candidates. Among the transition metal ions investigated for these purposes, rhenium occupies a special role. Its tri- and dicarbonyl complexes, in particular, attract continuous attention due to their relative ease of preparation, stability and unique photophysical and luminescent properties that allow the combination of diagnostic and therapeutic purposes, thereby permitting, e.g., molecules to be tracked within cells. In this review, we discuss the anticancer and antibiotic properties of rhenium tri- and dicarbonyl complexes described in the last seven years, mainly in terms of their structural variations and in vitro efficacy. Given the abundant literature available, the focus is initially directed on tricarbonyl complexes of rhenium. Dicarbonyl species of the metal ion, which are slowly gaining momentum, are discussed in the second part in terms of future perspective for the possible developments in the field.

Antimicrobial resistance is one of the major human health threats, with significant impacts on the global economy. Antibiotics are becoming increasingly ineffective as drug-resistance spreads, imposing an urgent need for new and innovative antimicrobial agents. Metal complexes are an untapped source of antimicrobial potential. Rhenium complexes, amongst others, are particularly attractive due to their low in vivo toxicity and high antimicrobial activity, but little is known about their targets and mechanism of action. In this study, a series of rhenium di- and tricarbonyl diimine complexes were prepared and evaluated for their antimicrobial potential against eight different microorganisms comprising Gram-negative and -positive bacteria. Our data showed that none of the Re dicarbonyl or neutral tricarbonyl species have either bactericidal or bacteriostatic potential. In order to identify possible targets of the molecules, and thus possibly understand the observed differences in the antimicrobial efficacy of the molecules, we computationally evaluated the binding affinity of active and inactive complexes against structurally characterized membrane-bound S. aureus proteins. The computational analysis indicates two possible major targets for this class of compounds, namely lipoteichoic acids flippase (LtaA) and lipoprotein signal peptidase II (LspA). Our results, consistent with the published in vitro studies, will be useful for the future design of rhenium tricarbonyl diimine-based antibiotics.

In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug design (CADD) based on a ‘scaffold-hopping’ approach for the synthesis and antibacterial evaluation of fac-Re(I) tricarbonyl complexes bearing clotrimazole (ctz) as a monodentate ligand. The prepared molecules were selected following a pre-screening in silico analysis according to modification of the 2,2′-bipyridine (bpy) ligand in the coordination sphere of the complexes. CADD pointed to chiral 4,5-pinene and 5,6-pinene bipyridine derivatives as the most promising candidates. The corresponding complexes were synthesized, tested toward methicillin-sensitive and -resistant S. aureus strains, and the obtained results evaluated with regard to their binding affinity with a homology model of the S. aureus MurG enzyme. Overall, the title species revealed very similar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as those of the reference compound used as the scaffold in our approach. The obtained docking scores advocate the viability of ‘scaffold-hopping’ for de novo design, a potential strategy for more cost- and time-efficient discovery of new antibiotics.

The presence and position of a reactive halomethyl substituent on the diimine ligand system offac-[Re(CO)₃]⁺complexes influences the anticancer activity of the compounds in zebrafish xenografts.

New synthetic routes to aerobically stable and substitutionally labile α-diimine rhenium( i ) dicarbonyl complexes offer a convenient entry in the chemistry of the cis -[Re(CO) ₂ ] ⁺ core.

Cancer remains one of the leading causes of death worldwide. The interest in organometallic complexes as anticancer drug candidates continues to be pivotal for many researchers. Initially underestimated for their therapeutic potentials, rhenium complexes are now slowly gaining momentum. While tricarbonyl complexes of rhenium are widely investigated, dicarbonyl derivatives of the cis-[Re(CO)₂]⁺ core remain largely unexplored. In this study, we tested in vitro a variety of rhenium dicarbonyl complexes for their activity towards three cancer cell lines (A549, MCF-7 and HCT116) and one healthy cell line (HEK293). The most lipophilic compounds showed, like the tricarbonyl species, good activity against specific cancer lines (IC₅₀ = 1.5–2.5 µM); however, the same were also toxic towards healthy cells. In order to understand these differences, we performed a reactivity study of cis-[Re(CO)₂(NN)]⁺ species (where NN = diimine) with biologically relevant functional groups (-COOH, -NH₂, -SH and aromatic nitrogen-based ligands) and compared the chemistry to what is known for the fac-[Re(CO)₃]⁺ core. Overall, we found that the rhenium dicarbonyl complexes only show good reactivity with aromatic nitrogen-based ligands. The reaction of cis-[Re(CO)₂(NN)]⁺ species with common bio-functional groups leads, rather, to the formation of bis-diimine dicarbonyl complexes (cis-[Re(CO)₂(NN)₂]⁺) as the major by-product.