Rhenium Tricarbonyl Research Articles

Photochemistry of P,N-bidentate rhenium(i) tricarbonyl complexes: reactive species generation and potential application for antibacterial photodynamic therapy.

In this work, we describe the photoisomerization of facial rhenium(i) tricarbonyl complexes bearing P,N-bidentate pyridyl/phosphine ligands with different chelating rings and anions: RePNBr, RePNTfO, and RePNNBr, which are triggered under irradiation at 365 nm in solutions. The apparent photodegradation rate constants (kapp) depend on the coordinating ability of the solvent, being lowest in acetonitrile. The kapp value increases as the temperature rises, suggesting a reactive IL excited state thermally populated from the MLCT excited state involved. Using the Eyring equation, positive activation enthalpies (ΔH≠) accompanied by high negative values for the activation entropy (ΔS≠) were obtained. These results suggest whatever the P,N-ligand or anion, the reaction proceeds through a strongly solvated or a compact transition state, which is compatible with an associative mechanism for the photoisomerization. A 100-fold decrease in the log10 CFU value is observed for E. coli and S. aureus in irradiated solutions of the compounds, which follows the same tendency as their singlet oxygen generation quantum yield: RePNBr > RePNTfO > RePNNBr, while no antibacterial activity is observed in the darkness. This result indicates that the generation of singlet oxygen plays a key role in the antibacterial capacity of these complexes.

The role of zero-field splitting and π-stacking interaction of different nitrogen-donor ligands on the optical properties of luminescent rhenium tricarbonyl complexes

In this work, a systematic evaluation of the role of zero-field splitting (ZFS), and the geometric arrangement of different nitrogen-donor ligands, including π-stacking interactions, in five selected rhenium luminescent complexes was performed.

Substitution reactivity and structural variability induced by tryptamine on the biomimetic rhenium tricarbonyl complex.

A series of seven fac-[Re(CO)3(5Me-Sal-Trypt)(L)] complexes containing tryptamine on the N,O 5-methyl-salicylidene bidentate ligand backbone and where L is MeOH, Py, Imi, DMAP, PPh3 coordinated to the 6th position have been studied, including the formation of a dinuclear Re2 cluster. The crystallographic solid state structures show marked similarity in structural tendency, in particular the rigidity of the Re core and the hydrogen bond interactions similar to those found in protein structures. The rates of formation and stability of the complexes were evaluated by rapid time-resolved stopped-flow techniques and the methanol substitution reaction indicates the significant activation induced by the use of the N,O salicylidene bidentate ligand as manifested by the second-order rate constants for the entering nucleophiles. Both linear and limiting kinetics were observed and a systematic evaluation of the kinetics is reported clearly indicating an interchange type of intimate mechanism for the methanol substitution. The anticancer activity of compounds 1–7 was tested on HeLa cells and it was found that all compounds showed similar cytotoxicity where solubility allowed. IC50-values between ca. 11 and 22 μM indicate that some cytotoxicity resides most likely on the salicylidene–tryptamine ligand. The photoluminescence of the seven complexes is similar in maximum emission wavelength with little variation despite the broad range of ligands coordinated to the 6th position on the metal centre.

Proton-controlled non-exponential photoluminescence in a pyridylamidine-substituted Re(I) complex.

Chemical intuition and well-known design principles can typically be used to create ligand environments in transition metal complexes to deliberately tune reactivity for desired applications. However, intelligent ligand design does not always result in the expected outcomes. Herein we report the synthesis and characterization of a tricarbonyl rhenium (2,2'-bipyridine) 4-pyridylamidine, Re(4-Pam), complex with unexpected photophysical properties. Photoluminescence kinetics of Re(4-Pam) undergoes non-exponential decay, which can be deconvolved into two emission lifetimes. However, upon protonation of the amidine functionality of the 4-pyridylamidine to form Re(4-PamH), a single exponential decay is observed. To understand and rationalize these experimental observations, density functional theory (DFT) and time-dependent density functional theory (TDDFT) are employed. The symmetry or asymmetry of the protonated or deprotonated 4-pyridylamidine ligand, respectively, is the key factor in switching between one and two photoluminescence lifetimes. Specifically, rotation of the dihedral angle formed between the bipyridine and 4-Pam ligand leads to two rotamers of Re(4-Pam) with degenerate triplet- to ground-state transitions.

Aptamer-functionalized lipid-core micelles loaded with rhenium tricarbonyl complex

Due to its distinctive physicochemical properties, diimine rhenium(I) tricarbonyl complexes are one of the most common type of complexes used in cellular imaging. The reasonably simple synthesis and modification of rhenium complexes in addition to their stability and remarkable luminescent properties provide a robust method to perform this goal. In general, organometallic complexes must be biocompatible to development imaging agents. Consequently, modification and bio-functionalization of the transition complexes is crucial to enhance biocompatibility. Here, we synthesize and characterize the luminescent tricarbonyl rhenium complex, [(bpy)(H2O)Re(CO)3]+, and propose a reasonably simple preparation of an aptamer-functionalized lipid core micelle (LCM), loaded with this complex, to endow it with suitable properties to be used in cellular imaging. The [(bpy)(H2O)Re(CO)3]+ exhibit a broad emission band centered around 550 nm at room temperature after excitation at 360 nm. The luminescent intensity is higher in nonpolar solvents such as chloroform. The complex was loaded into LCMs and, at the same time, the carrier was functionalized in situ with the nucleolin aptamer, AS1411, to improve the complex delivery and uptake to target cells. After physicochemical and spectroscopic characterization of the aptamer-functionalized vehicle, cellular studies were performed to evaluate its toxicity and its efficiency as cellular imaging agent. The combined AS1411 aptamer-functionalized lipid core micelle system effectively encapsulated the [(bpy)(H2O)Re(CO)3]+ complex, maintained its luminescent properties, and showed potential features to be used in cellular imaging experiments.

Photocatalytic CO2 Reductions Catalyzed by meso-(1,10-Phenanthrolin-2-yl)-Porphyrins Having a Rhenium(I) Tricarbonyl Complex.

We have prepared Zn and free‐base porphyrins appended with a fac‐Re(phen)(CO)3Br (where phen is 1,10‐phenanthroline) at the meso position of the porphyrin, and performed photocatalytic CO2 reduction using porphyrin–Re dyads in the presence of either triethylamine (TEA) or 1,3‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐benzo[d]imidazole (BIH) as an electron donor. The Zn porphyrin dyad showed a high turnover number for CO production compared with the free‐base porphyrin dyad, suggesting that the central Zn ion of porphyrin plays an important role in suppressing electron accumulation on the porphyrin part and achieving high durability of the photocatalytic CO2 reduction using both TEA and BIH. The effect of acids on the CO2 reduction was investigated using the Zn porphyrin–Re dyad and BIH. Acetic acid, a relatively strong Brønsted acid, rapidly causes the porphyrin's color to fade upon irradiation and dramatically decreases CO production, whereas proper weak Brønsted acids such as 2,2,2‐trifluoroethanol and phenol enhance the CO2 reduction.

Manganese and Rhenium Tricarbonyl Complexes Equipped with Proton Relays in the Electrochemical CO2 Reduction Reaction

The minireview focuses on the electrochemical CO2 reduction catalysed by manganese and rhenium tricarbonyl complexes with α‐diimine ligands having pendant proton relays attached to the α‐diimine ligand. Since the pioneering work on [Re(CO)3(Lbpy)Cl], 1Cl, as molecular electrocatalyst in the CO2 reduction reaction in the 80's, some effort has been made to understand the mechanism of the catalytic cycle and to improve the efficiency of the conversion (Lbpy = 2,2'‐bipyrdine). Later it was shown that the corresponding Mn complex, [Mn(CO)3(Lbpy)Br], 2Br, is also active in the CO2‐to‐CO conversion. As the 2 electrons reduction of CO2 is coupled to the transfer of 2 protons, pendent proton relays have been introduced in the ligand framework with the aim to improve the proton management during catalysis, to stabilize intermediates, and to alter the redox and the pH‐dependent properties of the catalyst. We summarise in this review the outcome of these studies on the performance of the catalyst, in particular, with regard to the position of the proton relay and thus, its influence on the electronic structure, the reaction steps, and the kinetics.

Aptamer-Functionalized Lipid-Core Micelles Loaded with Rhenium Tricarbonyl Complex

Due to its distinctive physicochemical properties, diimine rhenium(I) tricarbonyl complexes are one of the most common type of complexes used in cellular imaging. The reasonably simple synthesis and modification of rhenium complexes in addition to their stability and remarkable luminescent properties provide a robust method to perform this goal. In general, organometallic complexes must be biocompatible to development imaging agents. Consequently, modification and bio-functionalization of the transition complexes is crucial to enhance biocompatibility. Here, we synthesize and characterize the luminescent tricarbonyl rhenium complex, [(bpy)(H 2 O)Re(CO) 3 ] + , and propose a reasonably simple preparation of an aptamer-functionalized lipid core micelle (LCM), loaded with this complex, to endow it with suitable properties to be used in cellular imaging. The [(bpy)(H 2 O)Re(CO) 3 ] + exhibit a broad emission band centered around 550 nm at room temperature after excitation at 360 nm. The luminescent intensity is higher in nonpolar solvents such as chloroform. The complex was loaded into LCMs and, at the same time, the carrier was functionalized in situ with the nucleolin aptamer, AS1411, to improve the complex delivery and uptake to target cells. After physicochemical and spectroscopic characterization of the aptamer-functionalized vehicle, cellular studies were performed to evaluate its toxicity and its efficiency as cellular imaging agent. The combined AS1411 aptamer-functionalized lipid core micelle system effectively encapsulated the [(bpy)(H 2 O)Re(CO) 3 ] + complex, maintained its luminescent properties, and showed potential features to be used in cellular imaging experiments.

Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy.

Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths.

A Bis-Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents.

The two independent and coordination sites of a newly synthesized bis[2-(hydroxyphenyl)-1,2,4-triazole] platform have been exploited to prepare four monometallic neutral ()PtII complexes carrying DMSO, pyridine, triphenylphosphine, or N-heterocyclic carbene as the fourth ligand. Then, the second coordination site was used to introduce an IR-active rhenium tricarbonyl entity, affording the four corresponding heterobimetallic neutral PtII /ReI complexes, as well as a cationic PtII /ReI derivative. X-ray crystallographic studies showed that distortion of the organic platform occurred to accommodate the coordination geometry of both metal centers. No ligand exchange or transchelation occurred upon incubation of the PtII complexes in aqueous environment or in the presence of FeIII , respectively. The antiproliferative activity of the ligand and complexes was first screened on the triple-negative breast cancer cell line MDA-MB-231. Then, the IC50 values of the most active candidates were determined on a wider panel of human cancer cells (MDA-MB-231, MCF-7, and A2780), as well as on a nontumorigenic cell line (MCF-10A). Low micromolar activities were reached for the complexes carrying a DMSO ligand, making them the first examples of highly active, but hydrolytically stable, PtII complexes. Finally, the characteristic mid-IR signature of the {Re(CO)3 } fragment in the Pt/Re heterobimetallic complexes was used to quantify their uptake in breast cancer cells.

Antibacterial activity of Mn(I) and Re(I) tricarbonyl complexes conjugated to a bile acid carrier molecule.

A bifunctional cholic acid-bis(2-pyridylmethyl)amine (bpa) ligand featuring an amide linker was coordinated to a manganese(i) or rhenium(i) tricarbonyl moiety to give [M(bpacholamide)(CO)3] with M = Mn, Re in good yield and very high purity. Strong antibacterial activity was observed against four strains of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, with minimum inhibitory concentrations (MICs) in the range of 2-3.5 μM. No difference in response was observed for the MSSA vs. MRSA strains. Activity was also independent of the nature of the metal center, as the Mn and Re complexes showed essentially identical MIC values. In contrast to some other metal carbonyl complexes, the activity seems to be unrelated to the release of carbon monoxide, as photoactivation of the Mn complex reduced the potency by a factor of 2-8. Both metal complexes were non-toxic in Galleria mellonella larvae at concentrations of up to 100× the MIC value. In vivo testing in Galleria larvae infected with MRSA/MSSA demonstrated a significant increase in overall survival rates from 46% in the control to 88% in the group treated with the metal complexes. ICP-MS analysis showed that the Mn and Re cholamide complexes are efficiently internalized by E. coli cells and do not interfere with membrane integrity, as evident from a lack of release of intracellular ATP. An increased sensitivity was observed in acrB, acrD, and mdt mutants that are defective in multidrug exporters, indicating that the compounds have an intracellular mechanism of action. Furthermore, E. coli mntP mutants defective in the gene encoding an Mn exporter were more sensitive than the wildtype, while inactivation of the regulator that controls expression of the Mn uptake proteins MntP and MntH slightly increased sensitivity to the compound. Single knockout mutants defective in genes linked to bile salt and oxidative stress response (dinF, yiaH, sodA, katE, and soxS) did not show increased sensitivity relative to the wild type. Overall, neither the cholic acid moiety nor the metal-carbonyl fragment alone appear to be responsible for the biological activity observed and thus the search for the primary intracellular target continues.

Luminescent Rhenium(I)tricarbonyl Complexes Containing Different Pyrazoles and Their Successive Deprotonation Products: CO2 Reduction Electrocatalysts.

Cationic fac-[Re(CO)3(pz*H)(pypzH)]OTf (pz*H = pyrazole, pzH; 3,5-dimethylpyrazole, dmpzH; indazole, indzH; 3-(2-pyridyl)pyrazole, pypzH) were obtained from fac-[ReBr(CO)3(pypzH)] by halide abstraction with AgOTf and subsequent addition of the corresponding pyrazole. Successive deprotonation with Na2CO3 and NaOH gave neutral fac-[Re(CO)3(pz*H)(pypz)] and anionic Na{fac-[Re(CO)3(pz*)(pypz)]} complexes, respectively. Cationic fac-[Re(CO)3(pz*H)(pypzH)]OTf, neutral complexes fac-[Re(CO)3(pz*H)(pypz)], and fac-[Re(CO)3(pypz)2Na] were subjected to photophysical and electrochemical studies. They exhibit phosphorescent decays from a prevalently 3MLCT excited state with quantum yields (Φ) in the range between 0.03 and 0.58 and long lifetimes (τ from 220 to 869 ns). The electrochemical behavior in Ar atmosphere of cationic and neutral complexes indicates that the oxidation processes assigned to ReI → ReII occurs at lower potentials for the neutral complex compared to cationic complex. The reduction processes occur at the ligands and do not depend on the charge of the complexes. The electrochemical behavior in CO2 saturated media is consistent with CO2 electrocatalyzed reduction, where the values of the catalytic activity [icat(CO2)/icat(Ar)] ranged from 2.7 to 11.5 (compared to 8.1 for fac-[Re(CO)3Cl(bipy)] studied as a reference). Controlled potential electrolysis for the pyrazole cationic (3a) and neutral (4a) complexes after 1 h affords CO in faraday yields of 61 and 89%, respectively. These values are higher for indazole complexes and may be related to the acidity of the coordinated pyrazole.

Design, synthesis and invivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).

We have prepared a series of ten 3-arylcoumarin molecules, their respective fac-[Re(CO)3(bpy)L]+ and fac-[Re(CO)3(L⁀L)Br] complexes and tested all compounds for their antimicrobial efficacy. Whereas the 3-arylcoumarin ligands are virtually inactive against the human-associated pathogens with minimum inhibitory concentrations (MICs)>150μM, when coordinated to the fac-[Re(CO)3]+ core, most of the resulting complexes showed remarkable antibacterial potency. Several rhenium complexes exhibit activity in nanomolar concentrations against Gram-positive pathogens such as Staphylococcus aureus strains, including methicillin-resistant S.aureus (MRSA) and Enterococcus faecium. The molecules do not affect bacterial cell membrane potential, but some of the most potent complexes strongly interact with DNA, indicating it as a possible target for their mode of action. Invivo studies in the zebrafish model showed that the complexes with anti-staphylococcal/MRSA activity were non-toxic to the organism even at much higher doses of the corresponding MICs. In the zebrafish-MRSA infection model, the complexes increased the survival rate of infected fish up to 100% and markedly reduced bacterial burden. Moreover, all rescued fish developed normally following the treatments with the metallic compounds.

Exploring the In Vivo and In Vitro Anticancer Activity of Rhenium Isonitrile Complexes.

The established platinum-based drugs form covalent DNA adducts to elicit their cytotoxic response. Although they are widely employed, these agents cause toxic side-effects and are susceptible to cancer-resistance mechanisms. To overcome these limitations, alternative metal complexes containing the rhenium(I) tricarbonyl core have been explored as anticancer agents. Based on a previous study ( Chem. Eur. J. 2019, 25, 9206), a series of highly active tricarbonyl rhenium isonitrile polypyridyl (TRIP) complexes of the general formula fac-[Re(CO)3(NN)(ICN)]+, where NN is a chelating diimine and ICN is an isonitrile ligand, that induce endoplasmic reticulum (ER) stress via activation of the unfolded protein response (UPR) pathway are investigated. A total of 11 of these TRIP complexes were synthesized, modifying both the equatorial polypyridyl and axial isonitrile ligands. Complexes with more electron-donating equatorial ligands were found to have greater anticancer activity, whereas the axial ICN ligands had a smaller effect on their overall potency. All 11 TRIP derivatives trigger a similar phenotype that is characterized by their abilities to induce ER stress and activate the UPR. Lastly, we explored the in vivo efficacy of one of the most potent complexes, fac-[Re(CO)3(dmphen)(ptolICN)]+ (TRIP-1a), where dmphen = 2,9-dimethyl-1,10-phenanthroline and ptolICN = para-tolyl isonitrile, in mice. The 99mTc congener of TRIP-1a was synthesized, and its biodistribution in BALB/c mice was investigated in comparison to the parent Re complex. The results illustrate that both complexes have similar biodistribution patterns, suggesting that 99mTc analogues of these TRIP complexes can be used as diagnostic partner agents. The in vivo antitumor activity of TRIP-1a was then investigated in NSG mice bearing A2780 ovarian cancer xenografts. When administered at a dose of 20 mg/kg twice weekly, this complex was able to inhibit tumor growth and prolong mouse survival by 150% compared to the vehicle control cohort.

Synthesis and characterization of rhenium(I) 4,4′-dicarboxy-2,2′-bipyridine tricarbonyl complexes for solar energy conversion

The synthesis of a series of rhenium(I) tricarbonyl complexes containing 4,4′-dicarboxy-2,2′-bipyridine (dcbpy) and various halide or pseudohalide ligands is reported. Deprotonation of the carboxylates occurs in basic medium resulting in upfield 1H NMR shifts for the protons of the carboxyl groups attached to 2,2′-bipyridine. Metal-to-ligand charge transfer (MLCT) due to dπ → π* transitions systematically shift in the halide series from 382 nm for Re(dcbpy)(CO)3F to 436 nm for Re(dcbpy)(CO)3I. The compounds emit in the 600–650 nm region and have emission lifetimes greater than 50 ns. The solar energy conversion efficiency is less than 1% when TiO2- Re(dcbpy)(CO)3X, (X = F, CN, SCN, Br, I), photoanodes are used in Grätzel cells.

Synthesis and characterization of novel naphthalene-derivatized tridentate ligands and their net neutral rhenium tricarbonyl complexes and cytotoxic effects on non-small cell lung cancer cells of interest

Rhenium complexes have possible fluorescence imaging, radioimaging and therapeutic applications and can also serve as a model system for 99mTc. The quest for new pharmaceutical agents is thus an expanding area of research. In this study, we report two net neutral complexes, [Re(CO)3(N(SO2)(1-nap)dien)] and [Re(CO)3(N(SO2)(2-nap)dien)], synthesized by treating fac-[Re(CO)3(H2O)3]+ with two novel tridentate ligands, (N(SO2)(1-nap)dienH and N(SO2)(2-nap)dienH), derived from diethylenetriamine (dien) attached to a sulfonamide group. The compounds were characterized by UV–Visible, FTIR, 1H NMR and fluorescence spectroscopies, together with X-ray crystallography. It is evident from the 1H NMR spectroscopic data recorded in DMSO‑d6 as well as X-ray crystallography supported by FTIR data, that upon coordination to the metal centre, the sulfonamide nitrogen atom is deprotonated and the ligand binds with the metal in a tridentate fashion. Both the complexes have a distorted octahedral structure where the Re(I) metal is coordinated by three nitrogen atoms of the dien backbone and three CO ligands. Emission spectra were recorded in methanol and an enhanced fluorescence emission was observed in the 330–345 nm range for the ligands while the corresponding Re complexes showed no or quenched fluorescence intensities. The in vitro cytotoxic activity of the synthesized compounds was examined using NCI-H292 (non-small cell lung cancer cells) and MRC-5 (the human normal lung fibroblast cell line). The highest cytotoxic activity was observed for the [Re(CO)3(N(SO2)(1-nap)dien)] complex on NCI-H292 cells with an IC50 value of 9.91 μM at 48 h. However all four compounds show acute cytotoxicity for MRC-5 cells at 24 h. The promising cytotoxic activity of the novel ligands and metal complexes indicate that these compounds may be good candidates to be utilized as anticancer drug leads against lung cancer.

Exploring ovarian cancer cell resistance to rhenium anticancer complexes.

Rhenium tricarbonyl complexes have been recently investigated as novel anticancer agents. However, little is understood about their mechanisms of action, as well as the means by which cancer cells respond to chronic exposure to these compounds. To gain a deeper mechanistic insight into these rhenium anticancer agents, we developed and characterized an ovarian cancer cell line that is resistant to a previously studied compound [Re(CO)3(dmphen)(ptolICN)]+, where dmphen = 2,9-dimethyl-1,10-phenanthroline and ptolICN = para-tolyl isonitrile, called TRIP. This TRIP-resistant ovarian cancer cell line, A2780TR, was found to be 9 times less sensitive to TRIP compared to the wild-type A2780 ovarian cancer cell line. Furthermore, the cytotoxicities of established drugs and other rhenium anticancer agents in the TRIP-resistant cell line were determined. Notably, the drug taxol was found to exhibit a 184-fold decrease in activity in the A2780TR cell line, suggesting that mechanisms of resistance towards TRIP and this drug are similar. Accordingly, expression levels of the ATP-binding cassette transporter P-glycoprotein, an efflux transporter known to detoxify taxol, were found to be elevated in the A2780TR cell line. Additionally, a gene expression analysis using the National Cancer Institute 60 cell line panel identified the MT1E gene to be overexpressed in cells that are less sensitive to TRIP. Because this gene encodes for metallothioneins, this result suggests that detoxification by this class of proteins is another mechanism for resistance to TRIP. The importance of this gene in the A2780TR cell line was assessed, confirming that its expression is elevated in this cell line as well. As the first study to investigate and identify the cancer cell resistance pathways in response to a rhenium complex, this report high-lights important similarities and differences in the resistance responses of ovarian cancer cells to TRIP and conventional drugs.

Exploring Ovarian Cancer Cell Resistance to Rhenium Anticancer Complexes.

Rhenium tricarbonyl complexes have been recently investigated as novel anticancer agents. However, little is understood about their mechanisms of action, as well as the means by which cancer cells respond to chronic exposure to these compounds. To gain a deeper mechanistic insight into these rhenium anticancer agents, we developed and characterized an ovarian cancer cell line that is resistant to a previously studied compound [Re(CO)3 (dmphen)(ptolICN)]+ , where dmphen=2,9-dimethyl-1,10-phenanthroline and ptolICN=para-tolyl isonitrile, called TRIP. This TRIP-resistant ovarian cancer cell line, A2780TR, was found to be 9 times less sensitive to TRIP compared to the wild-type A2780 ovarian cancer cell line. Furthermore, the cytotoxicities of established drugs and other rhenium anticancer agents in the TRIP-resistant cell line were determined. Notably, the drug taxol was found to exhibit a 184-fold decrease in activity in the A2780TR cell line, suggesting that mechanisms of resistance towards TRIP and this drug are similar. Accordingly, expression levels of the ATP-binding cassette transporter P-glycoprotein, an efflux transporter known to detoxify taxol, were found to be elevated in the A2780TR cell line. Additionally, a gene expression analysis using the National Cancer Institute 60 cell line panel identified the MT1E gene to be overexpressed in cells that are less sensitive to TRIP. Because this gene encodes for metallothioneins, this result suggests that detoxification by this class of proteins is another mechanism for resistance to TRIP. The importance of this gene in the A2780TR cell line was assessed, confirming that its expression is elevated in this cell line as well. As the first study to investigate and identify the cancer cell resistance pathways in response to a rhenium complex, this report highlights important similarities and differences in the resistance responses of ovarian cancer cells to TRIP and conventional drugs.

Photoactivatable Surface-Functionalized Diatom Microalgae for Colorectal Cancer Targeted Delivery and Enhanced Cytotoxicity of Anticancer Complexes.

Systemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and characterization of a bio-inspired hybrid multifunctional drug delivery system based on diatom microalgae. The microalgae’s surface was chemically functionalized with hybrid vitamin B12-photoactivatable molecules and the materials further loaded with highly active rhenium(I) tricarbonyl anticancer complexes. The constructs showed enhanced adherence to colorectal cancer (CRC) cells and slow release of the chemotherapeutic drugs. The overall toxicity of the hybrid multifunctional drug delivery system was further enhanced by photoactivation of the microalgae surface. Depending on the construct and anticancer drug, a 2-fold increase in the cytotoxic efficacy of the drug was observed upon light irradiation. The use of this targeted drug delivery strategy, together with selective spatial–temporal light activation, may lead to lower effective concentration of anticancer drugs, thereby reducing medication doses, possible side effects and overall burden for the patient.

Excited-State Switching Frustrates the Tuning of Properties in Triphenylamine-Donor-Ligand Rhenium(I) and Platinum(II) Complexes.

The photophysical properties of a series of rhenium(I) tricarbonyl and platinum(II) bis(acetylide) complexes containing a triphenylamine (TPA)-substituted 1,10-phenanthroline ligand have been examined. The complexes possess both metal-to-ligand charge-transfer (MLCT) and intraligand charge-transfer (ILCT) transitions that absorb in the visible region. The relative energies and ordering of the absorbing CT states have been successfully controlled by changing the metal center and modulating the donating ability of the TPA group through the addition of electron-donating methoxy and electron-withdrawing cyano groups. The ground-state properties behave in a predictable manner as a function of the TPA substituent and are characterized with a suite of techniques including electronic absorption spectroscopy, resonance Raman spectroscopy, electrochemistry, and time-dependent density functional theory calculations. However, systematic control over the ground-state properties of the complexes does not extend to their excited-state behavior. Unexpectedly, despite variation of both the MLCT and ILCT state energies, all of the luminescent complexes displayed near-isoenergetic emission at 298 K, yet the emissive lifetimes of the complexes vary from 290 ns to 3.9 μs. Excited-state techniques including transient absorption and transient resonance Raman, combined with a suite of quantum-chemical calculations, including scalar relativistic effects to elucidate competitive excited-state relaxation pathways, have been utilized to aid in assignment of the long-lived state in the complexes, which was shown to possess differing 3MLCT and 3ILCT contributions across the series.