Rhenium Tricarbonyl Complexes Research Articles

Quinoline- rhenium(I) tricarbonyl complexes: synthesis, spectral characterization and antiproliferative activity on T-cell lymphoma

Novel 6-substituted 2-(trifluoromethyl)quinoline 5a-5e and coumarin 6a-6d ligands with aldoxime ether linked pyridine moiety were synthesized by O-alkylation of quinoline and coumarin with (E)-picolinaldehyde oxime and subsequently with [Re(CO)5Cl] gave rhenium(I) tricarbonyl complexes 5aRe–5eRe and 6aRe–6dRe that were fully characterized by NMR, single-crystal X-ray diffraction, IR and UV–Vis spectroscopy. The results of antiproliferative evaluation of quinoline and coumarin ligands and their rhenium(I) tricarbonyl complexes on various human tumor cell lines, including acute lymphoblastic leukemia (CCRF-CEM), acute monocytic leukemia (THP1), cervical adenocarcinoma (HeLa), colon adenocarcinoma (CaCo-2), T-cell lymphoma (HuT78), and non-tumor human fibroblasts (BJ) showed that the quinoline complexes 5aRe–5eRe had higher inhibitory activity than coumarin complexes 6aRe–6dRe, particularly against T-cell lymphoma (HuT78) cells. 6-Methoxy-2-(trifluoromethyl)quinoline 5e and 6-methylcoumarin 6d, and their rhenium(I) tricarbonyl complexes 5eRe and 6dRe were found to arrest the cell cycle of HuT78 cells by causing a significant accumulation of cells in the G0/G1 phase and a marked decrease in the number of cells in the G2/M phase. These rhenium(I) tricarbonyl complexes also slightly increased ROS production and significantly decreased the mitochondrial membrane potential by 50 % (5eRe) and 45 % (6dRe) compared to untreated cells and cells treated with 5e and 6d. These results suggest that the cytotoxic effects of these compounds are mediated by their effects on mitochondrial membrane potential and the subsequent increase in ROS production.

Synthesis and Biological Evaluation of Novel Cationic Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivative for Epidermal Growth Factor Receptor Targeting.

Background/Objectives: Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization. Methods: We synthesized a rhenium tricarbonyl complex (Complex 2) and its 99mTc analog (Complex 2') by incorporating triphenylphosphine instead of bromine as the monodentate ligand and PF6- as the counter-ion, resulting in a positively charged compound that forms cationic structures. Cytotoxicity and EGFR inhibition were evaluated in A431 cells overexpressing EGFR using MTT assays, Western blotting, and flow cytometry. Radiosensitization was tested through MTT and clonogenic assays. The 99mTc complex's radiochemical yield, stability, and lipophilicity were also assessed. Results: Complex 2 exhibited significant cytotoxicity with an IC50 of 2.6 μM and EGFR phosphorylation inhibition with an IC50 of 130.6 nM. Both complex 1 and 2 induced G0/G1 cell cycle arrest, with Complex 2 causing apoptosis. Radiosensitization was observed at doses above 2 Gy. Complex 2' demonstrated high stability and favorable lipophilicity (LogD7.4 3.2), showing 12% cellular uptake after 30 min. Conclusions: Complexes 2 and 2' show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models.

Revealing the Unusual behavior of rhenium (I) tricarbonyl complex functionalized with Aza-Macrocycles in response to metal ions

Three new rhenium phenanthroline tricarbonyl complexes were synthesized and fully characterized to examine changes in their photophysical properties and spectroscopic behavior in the presence of metal ions. To achieve this, the complexes were designed with modifications in both the phenanthroline and the axial ligand. The 4,7–dichloro–1,10–phenanthroline (Cl2phen) precursor was functionalized with two units of 1–aza–15–crown–5 (1A15C5) to obtain the complex [Re((A15C5)2phen)(CO)3Br] (1) with the aim to study the spectroscopic perturbations induced by the binding of the metal ions by this receptor. Interestingly, the rhenium complex 1 shows a particular behavior towards Hg(II) and Pb(II), as a result of the halide abstraction assisted by these metal ions. Additionally, in the presence of Cu(II) the interaction and coordination/binding with the macrocycle cavities is also presumed. The chemical reaction assisted by Hg(II) was confirmed by changes in the absorption, emission and FT–IR spectra of [Re(Cl2phen)(CO)3Br] (2) in presence of the heavy metal ion. These obtained profiles had similar patterns to the ones shown by the cationic complex [Re(Cl2phen)(CO)3(CH3CN)]PF6 (3). As final confirmation, this last complex was also studied in the presence of metal ions and its spectra remained unaltered.

Synthesis and structural elucidation of cytotoxic mono and dinuclear rhenium carbonyl complexes bearing bis-{1,3-(imino pyrrolyl)-m-chloro phenyl)} ligand

A mononuclear and dinuclear rhenium tricarbonyl compounds were synthesized by the one-pot condensation reaction of [Re(CO)5Br], pyrrole-2-carboxaldehyde and 4‑chloro-m-phenylene diamine. The mononuclear rhenium tricarbonyl complex containing {3-(imino pyrrolyl)-6‑chloro phenylamine)} ligand (IPP) with formula {[Re(CO)3Br(IPP)], (1), was obtained by refluxing stoichiometric quantities of amine, aldehyde and rhenium metal precursor in methanol solution. Similarly, dinuclear rhenium tricarbonyl compound {[Re(CO)3Br]2(BIPP)], BIPP = bis-{1,3-(imino pyrrolyl)-m-chlorophenyl)}, (2) has been synthesized by refluxing appropriate amounts of aldehyde, and rhenium metal precursor in the presence of one equivalent of amine ligand. Compounds 1 and 2 were characterized by FT-IR, 1H NMR, and UV–Vis spectroscopy, elemental analysis, and mass spectrometry. The luminescence properties of the formed complexes were studied in solution at room temperature, revealing an extended lifetime for the dinuclear complex 2 in comparison to 1. DFT calculations for the optimized structures helped to understand the geometry of the complexes, whereas TD-DFT revealed the vertical transitions responsible for the photophysical properties of the complexes. The cytotoxicity of such complexes against MCF-7 breast cancer has been also reported, revealing a dose-dependent growth inhibition attributed to a DNA-intercalating mode of binding for both complexes. The pronounced effect of the two metals on the cytotoxic studies and lifetime of the excited species were investigated. The greater intercalation ability of the complex 2 in comparison to complex1 obtained from circular dichroism studies also indicates the greater efficacy of Re complex 2.

Study of Mixed Re(I)/99mTc(I) Thiosemicarbazonate Complexes. Estrogen Receptor Affinity and Stability in Biological Media

Nine potentially bidentate thiosemicarbazone (HLn) ligands and their tricarbonylrhenium(I) complexes, [ReY(HLn)(CO)3] (Y = Cl, Br), were synthesized and their binding affinity towards estrogen beta receptors were determined using a competitive radiometric assay with [3H]‐estradiol. Even in the absence of a base, coordinated thiosemicarbazones can undergo deprotonation causing the release of the coordinated halide forming dimeric species, [Re2(Ln)2(CO)6]. The formation of the dinuclear complex with the thiosemicarbazone ligand zwitterionic form, [Re2(HL9)2(CO)6]Br2, motivated the theoretical study of the relative stability of these species. Despite the ease of formation of the dimer complexes, it was possible to optimize a synthetic route to obtain the complexes [2+1] [Re(Ln)(pym)(CO)3] where pym is a monodentate ligand 4‐dimethylamino‐pyridine or 4‐hydroxy ‐pyridine. The inclusion of this additional ligand substantially improves the affinity against the receptors. Complexes [99mTc(Ln)(pym)(CO)3] were also prepared using [99mTc(H2O)(CO)3]+, an excess of HLn ligand and in the presence of pym. The radiochromatograms show the formation of the first complex but also the presence of species resulting from the substitution of pym by chloride and water. However, the ratio of intensities between the three signals remains constant with the variation of the relative concentration suggesting an equilibrium between the three complexes.

The impact of biomolecule interactions on the cytotoxic effects of rhenium(I) tricarbonyl complexes

Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or dipyrido[3,2-a:2′3’-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 μM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 μM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).

Differential impact on oral cancer cell viability for three carboxylate-stabilized rhenium(I) tricarbonyl centers supported by 2,2′-bipyridine: One-pot synthesis, a structure, and proton-catalyzed carboxylate ligand substitution

A set of six carboxylate-stabilized rhenium(I) tricarbonyl complexes supported by a 2,2′-bipyridine (bpy) ligand, Re(O2CR)(CO)3(bpy) (R = H, CH3, CHF2, R- or S-CHBrCH(CH3)2, and C5H11), were prepared by acidolysis of the complex Re(OCO2C5H11)(CO)3(bpy) with the appropriate carboxylic acid and characterized by 1H and 13C-{1H} NMR and IR spectroscopy. The crystal structure of the complex, Re[R-O2CCHBrCH(CH3)2](CO)3(bpy), was determined by X-ray crystallography. An alternate one-pot route to the carboxylate-stabilized rhenium(I) complexes Re(O2CR’)(CO)3(bpy) (R’ = CH3 or C6H5) and Re(O2CCH3)(CO)3(1,10-pheanthroline), which starts with Re2(CO)10 and in which an ester solvent serves as the source of the carboxylate ligand, was also developed. Cell viability tests on three carboxylate-stabilized rhenium(I) complexes (R = H, CH3, or CHF2), using the HSC-2 oral cancer cell line, found different levels of cytotoxicity for each complex. NMR studies of the carboxylate ligand substitution reaction found that the reaction is catalyzed by protons. In a chloride-rich NMR solution, substitution of the carboxylate ligand leads to either a chloride-stabilized neutral complex (major product) or to a water-stabilized cation (minor product). Cytotoxicity results correlate positively with the Kb value of the carboxylate ligand. Apparently, the more substitutionally inert the carboxylate-stabilized complex is in a chloride-rich environment (similar to extracellular fluid) the greater the amount of cytotoxic [Re(CO)3(bpy)(H2O)]+ that forms in the cytosol.

Development of photoactivatable CO-releasing tricarbonylrhenium(I) complexes and their integration into cellulose nanocrystals in view of antibacterial activity

Infections caused by antibiotic-resistant bacteria represent a major public health problem, and efforts continue to be made to seek new ways of addressing this issue. Photoactivatable carbon monoxide (CO)-releasing molecules (photoCORMs) could be an alternative solution to conventional antibiotics, but their mechanism of action is complex and still badly known. In the present work, a tricarbonylrhenium(I) complex (Re-Phe(TPP)) was developed, as well as a more hydrophobic analogue substituted by an adamantyl moiety (Re-Ada(TPP)). When irradiated in the near UV, these molecules generate rapidly one molecule of CO, as well as small amounts of singlet oxygen (1O2). Their decarbonylated photoproducts D-Re-Phe(TPP) and D-Re-Ada(TPP) generate only 1O2, on a prolonged period of time. All these complexes were immobilized on a biocompatible cellulose nanocrystal (CNC) matrix, so that only the diffusive species (CO and 1O2) may be the active ones. Finally, the bactericidal activity of all these systems was evaluated on two bacteria strains, causative of the main wound infections. No compound was active against Pseudomonas aeruginosa. Free Re-Phe(TPP) appeared to be a very good antibacterial agent in the dark against Staphylococcus aureus, although the same molecule adsorbed on the CNC material was ineffective, so that its activity was mainly attributed to direct biological effect. The adamantyl derivative Re-Ada(TPP) was more active in the presence of light than in the dark, possibly due to the contribution of CO and 1O2. In contrast, the decarbonylated photoproduct D-Re-Phe(TPP) only showed moderate activity, suggesting that the production of 1O2 is not enough to induce a significant bactericidal effect. This work allows to identify the limits of Re(I) photoCORMs and corresponding nanomaterials, which are still little used in the fight against bacteria, and it provides good indications on how to improve their design.

Synthesis, characterization and photophysical properties of rhenium(I) tricarbonyl complexes with thiacrown ethers

Crown ethers and their derivatives are known to coordinate metal cations and organic molecules. They have an adaptable ring-opening diameter, which makes their complexations very selective. In this work, a series of rhenium (I) tricarbonyl complexes (C1–C3) based on oxathiacrown ethers conjugated with 1,10-phenanthroline (L1–L3) were designed and prepared. They were characterized by elemental analysis, spectral and electrochemical methods. They displayed microanalytical, NMR and mass spectral data consistent with their formulations. Electronic absorptions associated with 1MLCT transitions were observed at ca. 400 nm in the complexes. Their emission spectra displayed a low intensity peak at ca. 451–467 nm and a high intensity peak at ca. 605–608 nm. The low intensity peak appearing at high energy may be assigned to 3LC while the high intensity peak appearing at low energy may be assigned to 3MLCT transition. The complexes exhibited quantum yields between 0.0072 and 0.0088, lifetime measurements of 41–48 ns and large Stokes shifts at ca. 8500 cm−1. The CV of the complexes displayed one reversible ligand-centered reduction wave at ca. −1.6 V and an irreversible metal-centered oxidation wave at ca. 1.1 V (vs Ag/AgNO3). No remarkable changes were observed in the photophysical and electrochemical properties of the complexes upon increasing the macrocyclic cavity. The promising photophysical properties make them suitable candidates for application in chemosensing.

Neutral rhenium(I) tricarbonyl complexes with sulfur-donor ligands: anti-proliferative activity and cellular localization.

Rhenium(I) tricarbonyl complexes are widely studied for their cell imaging properties and anti-cancer and anti-microbial activities, but the complexes with S-donor ligands remain relatively unexplored. A series of six fac-[Re(NN)(CO)3(SR)] complexes, where (NN) is 2,2'-bipyridyl (bipy) or 1,10-phenanthroline (phen), and RSH is a series of thiocarboxylic acid methyl esters, have been synthesized and characterized. Cellular uptake and anti-proliferative activities of these complexes in human breast cancer cell lines (MDA-MB-231 and MCF-7) were generally lower than those of the previously described fac-[Re(NN)(CO)3(OH2)]+ complexes; however, one of the complexes, fac-[Re(CO)3(phen)(SC(Ph)CH2C(O)OMe)] (3b), was active (IC50 ∼ 10 μM at 72 h treatment) in thiol-depleted MDA-MB-231 cells. Moreover, unlike fac-[Re(CO)3(phen)(OH2)]+, this complex did not lose activity in the presence of extracellular glutathione. Taken together these properties show promise for further development of 3b and its analogues as potential anti-cancer drugs for co-treatment with thiol-depleting agents. Conversely, the stable and non-toxic complex, fac-[Re(bipy)(CO)3(SC(Me)C(O)OMe)] (1a), predominantly localized in the lysosomes of MDA-MB-231 cells, as shown by live cell confocal microscopy (λex = 405 nm, λem = 470-570 nm). It is strongly localized in a subset of lysosomes (25 μM Re, 4 h treatment), as shown by co-localization with a Lysotracker dye. Longer treatment times with 1a (25 μM Re for 48 h) resulted in partial migration of the probe into the mitochondria, as shown by co-localization with a Mitotracker dye. These properties make complex 1a an attractive target for further development as an organelle probe for multimodal imaging, including phosphorescence, carbonyl tag for vibrational spectroscopy, and Re tag for X-ray fluorescence microscopy.

Tricarbonyl rhenium(i) complexes with 8-hydroxyquinolines: structural, chemical, antibacterial, and anticancer characteristics.

Twelve tricarbonyl rhenium(i) complexes in the '2 + 1' system with the anionic bidentate N,O-donor ligand (deprotonated 8-hydroxyquinoline (HQ) or its 2-methyl (MeHQ) or 5-chloro (ClHQ) derivative) and neutral N-donor diazoles (imidazole (Him), 2-methylimidazole (MeHim), 3,5-dimethylpyrazole (Hdmpz), and 3-phenylpyrazole (HPhpz)) were synthesized: [Re(CO)3(LN,O)LN] (LN,O = Q-, MeQ-, ClQ-; LN = Him, MeHim, Hdmpz, HPhpz). Their crystal structures were determined by the scXRD method, compared with the DFT-calculated ones, and characterized by analytical (EA) and spectroscopic techniques (FT-IR, NMR, and UV-Vis) interpreted with DFT and TD-DFT calculations. Most of the Re(i) complexes did not show relevant antibacterial activity against Gram-negative and Gram-positive bacterial strains. Only [Re(CO)3(MeQ)Him] demonstrated significant action 4-fold better against Gram-negative Pseudomonas aeruginosa than the free MeHQ ligand. The cytotoxicity of the compounds was estimated using human acute promyelocytic leukemia (HL-60), ovarian (SKOV-3), prostate (PC-3), and breast (MCF-7) cancer, and breast non-cancerous (MCF-10A) cell lines. Only HQ and ClHQ ligands and [Re(CO)3(Q)Hdmpz] complex had good selectivity toward MCF-7 cell line. HL-60 cells were sensitive to all complexes (IC50 = 1.5-14 μM). Still, pure HQ and ClHQ ligands were slightly more active than the complexes.

1,2,3-Triazol-5-ylidene- vs. 1,2,3-triazole-based tricarbonylrhenium(I) complexes: influence of a mesoionic carbene ligand on the electronic and biological properties.

The tricarbonylrhenium complexes that incorporate a mesoionic carbene ligand represent an emerging and promising class of molecules, the solid-state optical properties of which have rarely been investigated. The aim of this comprehensive study is to compare three of these complexes with their 1,2,3-triazole-based analogues. The Hirshfeld surface analysis of the crystallographic data revealed that the triazolylidene derivatives are more prone to π-π interactions than their 1,2,3-triazole-based counterparts. The FT-IR and electrochemical data indicated a stronger electron donor effect from the organic ligand to the rhenium atom for triazolylidene derivatives, which was confirmed by DFT calculations. All compounds were phosphorescent in solution, where the 1,2,3-triazole-based complexes showed unusually strong dependence on dissolved oxygen. All compounds also emitted in the solid state, some of them exhibited marked solid-state luminescence enhancement (SLE) effect. The 1,2,3-triazole based complex Re-Phe even displayed astounding photoluminescence efficiency with quantum yield up to 0.69, and proved to be an excellent candidate for applications linked to aggregation-induced emission (AIE). Interestingly, one triazolylidene-based complex (Re-T-BOP) showed attractive antibacterial activity. This study highlights the potential of these new molecules for applications in the fields of photoluminescent and therapeutic materials, and provides the first bases for the design of efficient molecules in these research areas.

Chiroptical activity of benzannulated N-heterocyclic carbene rhenium(I) tricarbonyl halide complexes: towards efficient circularly polarized luminescence emitters.

The design of enantiomerically pure circularly polarized luminescent (CPL) emitters would enormously benefit from the accurate and in-depth interpretation of the chiroptical properties by means of jointly (chiroptical) photophysical measurements and state-of-the-art theoretical investigation. Herein, computed and experimental (chiro-)optical properties of a series of eight enantiopure phosphorescent rhenium(I) tricarbonyl complexes are systematically compared in terms of electronic circular dichroism (ECD) and CPL. The compounds have general formula fac-[ReX(CO)3(N^CNHC)], where N^CNHC is a pyridyl benzannulated N-heterocyclic carbene deriving from a (substituted) 2-(pyridin-2-yl)imidazo[1,5-a]pyridin-2-ium proligand and X = Cl, Br and I, and display structured red phosphorescence with long-lived (τ = 7.0-19.1 μs) excited-state lifetime and dissymmetry factors |gLum| up to 4 × 10-3. The mixing of the character of the lowest-lying emitting triplet excited state is finely modulated between ligand centred (3LC), metal-to-ligand charge transfer (3MLCT) and halogen-to-ligand charge transfer (3XLCT) by the nature of the ancillary halogen and the chromophoric N^CNHC ligand. The study unravels the effect exerted by the nature of the excited state onto the ECD and CPL activity and will help to pave the way to construct efficient CPL emitters by chemical design.

Photocatalytic CO2 reduction of Rhenium tricarbonyl complexes with high CO selectivity under visible light

Visible-light-driven photocatalytic CO2 reduction can address climate change and energy short-age. Homogenous photocatalysis converted CO2 to value chemicals have a straightforward procedure synthesis and CO2 conversion mechanism. Rhenium complexes based on pyridyl-triazole work as efficient catalysts for CO2 reduction at room conditions and under visible light. Photo-catalytic measurements show Re(bpy-COOH) possesses the highest catalytic CO2 conversion activity, whereas Re(Hpytr) is the lowest catalytic activity. These complexes posses the high product selectively, which produce two gases CO and H2 with high CO selectively. CO selectivity of Re(bpy-COOH), Re(Hphtr), and Re(Hpytr) are determined by 99.0, 97.9 and 92.8, respectively. TONCO reaches the highest value at 100 min are 5.46, 1.56, and 0.51 for Re(bpy-COOH), Re(Hphtr), and Re(Hpytr), respectively. This study explore the new property as photocatalysts active for CO2 reduction of these complexes with high CO selectively.

Further Insights into the Impact of Ligand-Localized Excited States on the Photophysics of Phenanthroline-Based Rhenium(I) Tricarbonyl Complexes.

The present work shows the pivotal role of N-donor substituents attached to 1,10-phenanthroline at the 4,7-positions in perturbation of ground- and excited-state properties of fac-[ReCl(CO)3(R2phen)]. Excited-state processes occurring upon photoexcitation in the designed systems were thoroughly explored with a wide range of steady-state and time-resolved spectroscopic techniques, including transient absorption, as well as experimental results were complemented by theoretical studies based on the density functional theory (DFT). It was demonstrated that the attachment of six-membered heterocyclic amines (piperidine─ppr, morpholine─mor, and thiomorpholine─tmor) is a very effective tool for extending absorptivity and excited-state lifetimes of resulting fac-[ReCl(CO)3(R2phen)] due to the contribution of the excited state localized on the phenanthroline-based ligand. Both absorption and emission properties of these systems were attributed to configurationally mixed MLCT/IL excited states. Re(I) complexes with phenoxazine (pxz) and phenothiazine (ptz) substituents were shown to possess charge-separated excited states, clearly evidenced by the simultaneous presence of signals typical of phen-* and pxz+* or ptz+* in transient absorption spectra. Both complexes are rare examples of NIR light-emitting coordination compounds. The decoration of the phen framework with less polar 9,9-dimethyl-9,10-dihydroacridine (dmac) groups resulted in the formation of [ReCl(CO)3(R2phen)] with mixed 3MLCT/3ILCT triplet excited state.

Aminoquinoline-based Re(I) tricarbonyl complexes: Insights into their antiproliferative activity and mechanisms of action

In an effort to develop new potent anticancer agents, two Schiff base rhenium(I) tricarbonyl complexes, containing the ubiquitous aminoquinoline scaffold, were synthesized. Both aminoquinoline ligands and Re(I) complexes showed adequate stability over a 48-h incubation period. Furthermore, the cytotoxic activity of the precursor ligands and rhenium(I) complexes were evaluated against the hormone-dependent MCF-7 and hormone-independent triple negative MDA-MB-231 breast cancer cell lines. Inclusion of the [Re(CO)3Cl]+ entity significantly enhanced the cytotoxicity of the aminoquinoline Schiff base ligands against the tested cancer cell lines. Remarkably, the incorporation of the Schiff-base iminoquinolyl entity notably enhanced the cytotoxic activity of the Re(I) complexes, in comparison with the iminopyridyl entity. Notably, the quinolyl-substituted complex showed up to three-fold higher activity than cisplatin against breast cancer cell lines, underpinning the significance of the quinoline pharmacophore in rational drug design. In addition, the most active Re(I) complex showed better selectivity towards the breast cancer cells over non-tumorigenic FG-0 cells. Western blotting revealed that the complexes increased levels of γH2AX, a key DNA damage response protein. Moreover, apoptosis was confirmed in both cell lines due to the detection of cleaved PARP. The complexes show favourable binding affinities towards both calf thymus DNA (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions align with their cytotoxic effects. The in silico molecular simulations of the complexes were also performed with CT-DNA and BSA targets.

DNA structural changes (photo)induced by tricarbonyl (pterin)rhenium(I) complex

We report on interactions of different types of DNA molecules including double-stranded and plasmid DNA as well as polynucleotides (poly[dGdC]2 and poly[dAdT]2) with fac-[ReI(CO)3(pterin)(H2O)] (or Reptr) complex. The interaction was characterized spectroscopically and changes in the plasmid structure were verified by both electrophoresis and AFM microscopy. For comparative reasons, two others related tricarbonyl rhenium(I) complexes, fac-[(4,4′-bpy)ReI(CO)3(dppz)]+ (or Redppz) and fac-[(CF3SO3)ReI(CO)3(2,2′-bpy)] (or Rebpy) were also studied to further explore the influence of the different co-ligands on the interaction and DNA (photo)damage. Data reported herein suggests that DNA molecules can be structurally modified either by direct interaction with Re(I) complexes in their ground states inducing DNA relaxation, and/or through photoinduced cross-linking processes. The chemical nature of the co-ligands modulates the extent of the damage observed.

Synthesis and biological evaluation of 99mTc-tricarbonyl complexes of C-3 carboxy derivatives of fluoroquinolones in infection and tumor animal models

Fluoroquinolones (FQ) are clinically used antibacterial agents. Antibacterial fluoroquinolone derivatives have been shown to exhibit cytotoxic properties in tumor cells. In this work, C3-carboxy fluoroquinolones derivatives were radiolabeled with the diagnostic radionuclide technetium-99 m and were evaluated as infection- and tumor-targeted agents. First, ciprofloxacin and enrofloxacin were converted to 3-hydrazides and then to the respective pyridine hydrazones (L1 and L2). Secondly, 3-carboxamide of enrofloxacin was converted to dipicolylamine (L3), and picolylaminoacetate (L4) tridentate chelators. The respective rhenium-tricarbonyl complexes of L1-L4 were synthesized and characterized by spectroscopic methods and were used as non-radioactive standards to characterize the analogous 99mTc-radiotracers. The 99mTc-tricarbonyl complexes were synthesized and their lipophilicity and stability were evaluated in vitro. The most stable tracers 99mTcL3, 99mTcL4, were incubated with E. coli cells and CT-26 murine colon adenocarcinoma cells to assess their cellular uptake. Also, the 99mTc-tracers were injected in mice, infected with E. coli, as well as in mice, bearing CT-26 tumors.

Rhenium (I) tricarbonyl complex with thiosemicarbazone ligand derived from Indole-2-carboxaldehyde: Synthesis, crystal structure, computational investigations, antimicrobial activity, and molecular docking studies

Antibiotic resistance is becoming a cause of serious concern to human health causing a significant impact on the global economy. The demand for novel antimicrobial agents is pressing since drug resistance is spreading and making antibiotics less and less effective. There is unrealized antibacterial potential in metal complexes. Among other compounds, rhenium complexes are particularly appealing because of their strong antibacterial activity and minimal in vivo toxicity. In this study, three Re carbonyl thiosemicarbazone (TSC) complexes were synthesized and characterized and their antibacterial potential was evaluated against various types of gram-positive and gram-negative bacteria. The structure of the ligands and their corresponding Re complexes were optimized at the DFT/B3LYP level of theory employing 6–311++G(d,p) and LANL2DZ basis sets for C, H, N, O, S, and Re atoms respectively. The MS studies performed with time show that [fac-[Re(CO)3Br(HL)] was converted into dimer [Re2(CO)6(L)2] in solution and the crystal structure of the dimer [Re2(CO)6(L)2] obtained as the result of dimerization of the complex was solved. Among the three Re TSC complexes, [fac-[Re(CO)3Br(HL1)] exhibits the greatest antibacterial activity against S.aureus with MIC value 0.5 µg/mL. The data obtained showed that the synthesized complexes were ineffective against gram-negative bacteria but showed excellent antibacterial activity against gram-positive S.aureus. The [fac-[Re(CO)3Br(HL2)] complex derived from isatin-β-thiosemicarbazone showed lesser activity than the other two rhenium TSC complexes which were obtained by condensation of indole-2-carboxaldehyde and thiosemicarbazide. Furthermore, the in-silico molecular docking studies revealed that the binding energy of the docked compound [Re(CO)3Br(HL)] with E. Coli and MRSA targets were extremely favorable (-7.18 and -5.67 kcal/mol, respectively which further demonstrates the potential of the synthesized complexes in the development of new antibacterial drugs. The molecular docking studies as well as experimental investigations demonstrate the effect of substituents on the ligand backbone on the antimicrobial activity of the synthesized rhenium carbonyl complexes. The enhanced antibacterial properties of rhenium carbonyl complexes with the TSC ligands in comparison to the ligand alone also suggest a possible synergistic effect of the metal center and the organic ligand.

Photoinduced behaviour of N,N-bidentate manganese(I) and rhenium(I) tricarbonyl complexes for singlet oxygen generation and CO release.

The combined action of singlet oxygen (1O2) and photoinduced carbon monoxide (CO) released by tricarbonyl metal complexes is a promising synergic treatment against multi-resistant bacterial infections. In this work, we explore the use of a polydentate ligand (bpm = 2,2-bipyrimidine) that offers the opportunity to accommodate two metal centers exhibiting both singlet oxygen generation and carbon monoxide releasing properties in a single molecule. A series of monometallic ([(bpm)M(CO)3Br]; M = Mn, Re) and homo or hetero bimetallic ([Br(CO)3M(bpm)M'(CO)3Br]; M = Mn, Re) compounds were synthesized in moderate to good yields by modulating the metal precursor or the stoichiometry, also the syn:anti isomers ratio for the bimetallic complexes was dependent on the experimental conditions used. DFT modelling shows the anti-isomer is more stable than the syn-isomer by less than 8 kJ mol-1, which is consistent with those experimentally observed in terms of majority product and the effect of experimental conditions over the anti-syn ratio. The HOMO-LUMO gap is lower for the mono and bimetallic rhenium(I) compounds compared to the values for the manganese(I) analogues, while the heterometallic complex shows intermediate values for the anti-isomer. The photophysical characterization shows typical absorption and emission bands with MLCT character. In addition, CO-release and 1O2 generation quantum yields were evaluated for the monometallic Mnbpm and Rebpm homologues and compared with values obtained for the homo- and hetero-bimetallic complexes. Interestingly the replacement of a Mn(CO)3Br moiety in MnbpmMn by a Re(CO)3Br one makes the heterometallic MnbpmRe molecule a molecular oxygen sensitizer and partially retaining its carbon monoxide releasing ability.