Singlet Oxygen Sensitizers Research Articles

Electron Transfer Drives the Photosensitized Polymerization of Contrast Agents by Flavoprotein Tags for Correlative Microscopy.

Singlet oxygen generation has long been considered the key feature that allows genetically encoded fluorescent tags to produce polymeric contrast agents for electron microscopy. Optimization of the singlet oxygen sensitization quantum yield has not included the effects of electron-rich monomers on the sensitizer's photocycle. We report that at monomer concentrations employed for staining, quenching by electron transfer is the primary deactivation pathway for photoexcitations. A simple photochemical model including contributions from both processes reproduces the observed reaction rates and indicates that most of the product is driven by pathways that involve electron transfer with monomers─not by the sensitization of singlet oxygen. Realizing the importance of these competing reaction pathways offers a new paradigm to guide the development of genetically encodable tags and suggests opportunities to expand the materials scope and growth conditions for polymeric contrast agents (e.g., biocompatible monomers, O2 poor environments).

Photocatalytic oxidation of benzylamines and sulfides using selected organoboron complexes as molecular oxygen activators

In this work a synthetic protocol was developed to obtain a series of diarylborinic complexes bearing a diarylboron moiety chelated with various bidentate N,O-ligands derived from 5-chloro-8-hydroxy-7-iodoquinoline, quinoline-2,4-dicarboxylic acid or 2-(2-hydroxy-5-methylphenyl)benzotriazole. The obtained complexes were characterized by NMR, IR, CV, UV–vis and single-crystal X–ray diffraction analyses. The experimental data were supported by theoretical calculations. The obtained complexes were tested as singlet oxygen sensitizers for the oxidation of 2-furancarboxylic acid, oxidative coupling of benzylamines and oxidation of sulfides. Among the studied compounds, the diarylborinic derivative bearing a 5-chloro-8-oxy-7-iodoquinolinate ligand was selected as the most economic singlet oxygen sensitizer. However, the diphenylborinic complex bearing an 8-oxyquinolinate ligand was the most efficient for the selective oxidation of various benzylamines to their respective N-benzylidene benzylamines.

Transition metal azahemiporphycenes as singlet oxygen sensitizers

Using free-base tris([Formula: see text]-X-phenyl)corrole (X = H, Me, OMe) as starting materials and 4-aminotriazole as the nitrogen source, we used a DDQ-mediated, room-temperature strategy for generating isocorroles to obtain the corresponding 6-azahemiporphycenes, H2[X-AHP], one of which was structurally characterized with single-crystal X-ray diffraction analysis. The free-base ligands were readily derivatized to their Pd(II), Pt(II), and Mn(II) complexes; of these, one Pd(II) complex was structurally characterized. Three of the complexes, M[Me-AHP] (M = Pd, Pt, Mn), were singled out for photophysical and singlet oxygen sensitization studies. Although none of the new complexes proved luminescent, Pd[Me-AHP] was found to be an excellent singlet oxygen sensitizer, with a singlet oxygen quantum yield of 84% in 9:1 v/v ethanol:tetrahydrofuran at room temperature. The corresponding value for Pt[Me-AHP] was found to be only 11% and that for Mn[Me-AHP] was essentially 0%. These singlet oxygen quantum yields were consonant with triplet lifetimes accessed via transition absorption spectroscopy. Combined with their strong absorption in the red, these findings suggest that palladium 6-azahemiporphycenes are worthy of exploration as a new class of triplet photosensitizers for photodynamic therapy of cancer and other diseases.

Role of Direct and Sensitized Photolysis in the Photomineralization of Dissolved Organic Matter and Model Chromophores to Carbon Dioxide.

This study addresses the fundamental processes that drive the photomineralization of dissolved organic matter (DOM) to carbon dioxide (CO2), deconvoluting the role of direct and sensitized photolysis. Here, a suite of DOM isolates and model compounds were exposed to simulated sunlight in the presence of various physical and chemical quenchers to assess the magnitude, rate, and extent of direct and sensitized photomineralization to CO2. Results suggest that CO2 formation occurs in a biphasic kinetic system, with fast production occurring within the first 3 h, followed by slower production thereafter. Notably, phenol model chromophores were the highest CO2 formers and, when conjugated with carboxylic functional groups, exhibited a high efficiency for CO2 formation relative to absorbed light. Simple polycarboxylated aromatic compounds included in this study were shown to be resistant to photomineralization. Quencher results suggest that direct photolysis and excited triplet state sensitization may be largely responsible for CO2 photoproduction in DOM, while singlet oxygen and hydroxyl radical sensitization may play a limited role. After 3 h of irradiation, the CO2 formation rate significantly decreased, and the role of sensitized reactions in CO2 formation increased. Together, the results from this study advance the understanding of the fundamental reactions driving DOM photomineralization to CO2, which is an important part of the global carbon cycle.

Plasmon-enhanced sensitization of singlet oxygen on silver island films

The influence of the plasmonic effect of silver island films on the absorption, fluorescence and long-term luminescence of rose bengal in polyvinyl butyral films has been studied. Under the plasmon effect, the optical density of the dye increased by 3.3 times, the fluorescence intensity by 8.5 times, and the long-lived fluorescence and phosphorescence by 7.08 times and 10.21, respectively. It is shown that in the plasmon field of metal nanoparticles, both an increase in the excitation rate and an increase in the rates of radiative decay of excited singlet and triplet states occur. Phosphorescence of singlet oxygen with a lifetime of 86.46 μs was observed when excited in the absorption band of rose bengal. Based on the calculation of the quenching constants of rose bengal phosphorescence by molecular oxygen molecules, it is shown that the plasmonic effect enhances the energy transfer from dye triplets to oxygen molecules in collision complexes [ТPS…3  g –] as a result of heteroannihilation. Subsequently, the triplet pair decomposes to form a singlet oxygen molecule and a photosensitizer molecule in the ground state. The plasmonic effect of silver nanoparticles leads to an increase in the generation of singlet oxygen by 4.8 times.

Phenazine Cations as Anticancer Theranostics†.

The biological properties of two water-soluble organic cations based on polypyridyl structures commonly used as ligands for photoactive transition metal complexes designed to interact with biomolecules are investigated. A cytotoxicity screen employing a small panel of cell lines reveals that both cations show cytotoxicity toward cancer cells but show reduced cytotoxicity to noncancerous HEK293 cells with the more extended system being notably more active. Although it is not a singlet oxygen sensitizer, the more active cation also displayed enhanced potency on irradiation with visible light, making it active at nanomolar concentrations. Using the intrinsic luminescence of the cations, their cellular uptake was investigated in more detail, revealing that the active compound is more readily internalized than its less lipophilic analogue. Colocalization studies with established cell probes reveal that the active cation predominantly localizes within lysosomes and that irradiation leads to the disruption of mitochondrial structure and function. Stimulated emission depletion (STED) nanoscopy and transmission electron microscopy (TEM) imaging reveal that treatment results in distinct lysosomal swelling and extensive cellular vacuolization. Further imaging-based studies confirm that treatment with the active cation induces lysosomal membrane permeabilization, which triggers lysosome-dependent cell-death due to both necrosis and caspase-dependent apoptosis. A preliminary toxicity screen in the Galleria melonella animal model was carried out on both cations and revealed no detectable toxicity up to concentrations of 80 mg/kg. Taken together, these studies indicate that this class of synthetically easy-to-access photoactive compounds offers potential as novel therapeutic leads.

FDevelopment of Self-Activated Photosensitizers based on the Chemiluminescent System of Marine Coelenterazine

IntroductionPhotodynamic therapy (PDT) of cancer possesses advantageous features, such as a minimally invasive nature and few side-effect [1]. However, its use can be restricted to more surface tumors, due to its dependance on light-irradiation. To overcome this problem, we propose the development of single-molecule photosensitizers (PSs), based on chemiluminescent (CL) marine Coelenterazine (Clz) [2-6], which can be self-activated in the absence of light. ApproachClz analogs were synthesized via routes optimized by our team [2-6], and their structure was characterized by HR-MS, NMR and FTIR spectroscopy. They were subjected to a through luminometric and photophysical characterization, to determine their CL features and singlet oxygen sensitization [2-6]. Their toxicity was investigated in vitro toward different cancer (breast, prostate, neuroblastoma, lung and gastric) and noncancer (breast and keratinocytes) cell lines, via the MTT assay in the absence of light [2-6]. ResultsThe obtained Clz analogs were designed so their CL reaction generate mainly triplet states, instead of singlet excited ones [2-6]. They were shown to indeed be able to sensitize the highly cytotoxic singlet oxygen, without light-irradiation, due to a CL reaction triggered solely by molecule overexpressed in cancer cells (superoxide anion) [2-6]. In vitro assays showed that these analogs present cytotoxicity toward all the different studied cancer cell lines [2-6]. Moreover, some of them even showed comparable or even better activity than a reference chemotherapeutic drug [3,4]. Finally, a promising profile of safety was observed in testing with noncancer cells [3]. ConclusionsDifferent single-molecule PSs were developed, which are capable of intracellular self-activation without light-irradiation [2-6]. Namely, they are directly chemiexcited to triplet excited states via a CL reaction triggered by a molecule overexpressed in cancer cells, which generates singlet oxygen without light-irradiation. This new approach was found to induce toxicity toward different cancer cell lines, while possessing a promising profile of safety for noncancer cells. Thus, these PSs can provide a pathway for eliminating the light-related restrictions of PDT, while maintaining its advantages.

Modulation of the Excited States of Ruthenium(II)-perylene Dyad to Access Near-IR Luminescence, Long-Lived Perylene Triplet State and Singlet Oxygen Photosensitization.

Herein, we present a novel ruthenium(II)-perylene dyad (RuPDI-Py) that combines the photophysical properties of pyrrolidine-substituted perylene diimide (PDI-Py) and the ruthenium(II) polypyridine complex [Ru(phen)3]2+. A comprehensive study of excited-state dynamics was carried out using time-resolved and steady-state methods in a dimethyl sulfoxide solution. The RuPDI-Py dyad demonstrated excitation wavelength-dependent photophysical behavior. Upon photoexcitation above 600 nm, the dyad exclusively exhibits the near-infrared (NIR) fluorescence of the 1PDI-Py state at 785 nm (τfl = 1.50 ns). In contrast, upon photoexcitation between 350 and 450 nm, the dyad also exhibits a photoinduced electron transfer from the {[Ru(phen)3]2+} moiety to PDI-Py, generating the charge-separated intermediate state {Ru(III)-(PDI-Py)•-} (4 μs). This state subsequently decays to the long-lived triplet excited state 3PDI-Py (36 μs), which is able to sensitize singlet oxygen (1O2). Overall, tuning 1O2 photoactivation or NIR fluorescence makes RuPDI-Py a promising candidate for using absorbed light energy to perform the desired functions in theranostic applications.

Structure and Photophysics of N-Tolanyl-phenochalcogenazines and their Radical Cations.

The study focuses on the structural and photophysical characteristics of neutral and oxidized forms of N-tolanyl-phenochalcogenazines PZX-tolan with X=O, S, Se, and Te. X-ray crystal structure analyses show a pseudo-equatorial (pe) structure of the tolan substituent in the O, S, and Se dyads, while the Te dyad possesses a pseudo-axial (pa) structure. DFT calculations suggest the pe structure for O and S, and the pa structure for Se and Te as stable forms. Steady-state and femtosecond-time resolved optical spectroscopy in toluene solution indicate that the O and S dyads emit from a CT state, whereas the Se and Te dyads emit from a tolan-localized state. The T1 state is tolan-localized in all cases, showing phosphorescence at 77 K. The heavy atom effect of chalcogens induces intersystem crossing from S1 to Tx, resulting in a decreasing S1 lifetime from 2.1 ns to 0.42 ps. The T1 states possess potential for singlet oxygen sensitization with a high quantum yield (ca. 40 %) for the O, S, and Se dyads. Radical cations exhibit spin density primarily localized at the heterocycle. EPR measurements and quasirelativistic DFT calculations reveal a very strong g-tensor anisotropy, supporting the pe structure for the S and Se derivatives.

Measuring the total photon economy of molecular species through fluorescent optical cycling.

The total photon economy of a chromophore molecular species represents a study of how absorbed photons partition among various electronic states and ultimately dissipate their excited energy into the environment. A complete accounting of these rates and pathways would allow one to optimize chromophores and their environments for applications. We describe a technique, fluorescent optical cycling (FOC), which allows for simultaneous observation of prompt and delayed emission during and after multiple pulsed excitation, ultimately granting access to multi-state photophysical rates. We exercise control over the excitation pulse train, which allows us to "optically shelve" long-lived intermediate states without the use of diode or flashlamp excitation. By recording all photon arrival times in the visible and shortwave infrared, we can simultaneously resolve fluorescence, phosphorescence, and singlet oxygen sensitization in a single experiment. We use FOC to examine the photophysics of dual emitting bis(di-R-phosphino)alkanethiophene-pyridine-platinum ([Pt(thpy)(dppm)]+) under different solvation conditions, revealing changes in intersystem crossing and phosphorescent rates induced by the external heavy atom effect. Coupling FOC with decay associated Fourier spectroscopy (DAFS), we demonstrate simultaneous correlated spectral and lifetime data in this dual emitting complex. Finally, FOC combined with superconducting nanowire single photon detectors (SNSPDs) allows us to observe the shortwave infrared region (SWIR) phosphorescence of singlet oxygen sensitized by Rose Bengal. Overall, FOC provides a powerful tool to simultaneously study multiple photophysics across timescales, even in weakly populated electronic states.

Ultrafast photophysics of para-substituted 2,5-bis(arylethynyl) rhodacyclopentadienes: thermally activated intersystem crossing.

2,5-Bis(phenylethynyl) rhodacyclopentadienes (RCPDs), as a type of Rh(iii) complex, exhibit unusually intense fluorescence and slow intersystem crossing (ISC) due to weak metal-ligand interactions. However, details on their ultrafast photophysics and ISC dynamics are limited. In this work, electronic relaxation upon photoexcitation of two substituted RCPDs with two -CO2Me (A-RC-A) or -NMe2/-CO2Me (D-RC-A) end groups are comprehensively investigated using femtosecond transient absorption spectroscopy and theoretical analysis. Upon ultraviolet and visible excitation, dephasing of vibrational coherence, charge transfer, conformation relaxation, and ISC are observed experimentally. By calculating the spin-orbit coupling, reorganization energy, and adiabatic energy gap of plausible ISC channels, semi-classical Marcus theory revealed the dominance of thermally activated ISC (S1 → T2) for both D-RC-A and A-RC-A, while S1 → T1 channels are largely blocked due to high ISC barriers. With weak spin-orbit coupling, such differences in plausible ISC channels are predominately tuned by energetic parameters. Singlet oxygen sensitization studies of A-RC-A provide additional insight into the excited-state behavior of this complex.

Porphyrin(2.1.2.1) organopalladium complexes as efficient singlet oxygen sensitizers.

Four new non-planar and non-aromatic porphyrin organopalladium complexes were synthesized. Conformational structures and optical and electronic properties of the obtained organopalladium complexes containing meso-substituted phenyl, p-tert-butylphenyl, or pentafluorophenyl groups were fully investigated. These complexes showed potent capacity for singlet oxygen (1O2) generation under blue-light irradiation, and the 1O2 quantum yields were in the range of 41%-56%, which were comparable to that of Ru(bpy)3Cl2 (57%), and such potency made these organopalladium complexes potential 1O2 photo sensitizers for photodynamic therapy.

Two-Pronged Dormant Photosensitizer-Antibiotic Bacterial Inactivation: Mechanism, Dosage, and Cellular Evolution Visualized at the Single-Cell Level.

Innovative therapeutic approaches are required to battle the rise of antibiotic-resistant bacterial strains. Tapping on reactive oxygen species (ROS) generation in bacteria induced by bactericidal antibiotics, here we report a two-pronged strategy for bacterial inactivation relying on the synergistic combination of a bactericidal antibiotic and newly designed dormant photosensitizers (DoPSs) that activate in the presence of ROS. Intramolecular quenching renders DoPS inert in the presence of light. ROS trapping by DoPS aborts the quenching mechanism unmasking, in equal proportions, singlet oxygen (1O2) sensitization and fluorescence emission. Juxtaposed antioxidant-prooxidant activity built within our DoPS enables (i) initial activation of a few molecules by ROS and (ii) subsequent rapid activation of all DoPS in a bacterium via a domino effect mediated by photogenerated 1O2. Bulk colony forming unit studies employing the minimum inhibitory concentration of the antibiotic illustrate rapid and selective inactivation of Escherichia coli and Pseudomonas aeruginosa only in the presence of light, antibiotic, and DoPS. Single-cell, real-time imaging studies on E. coli reveal an autocatalytic progression of DoPS activation from focal points, providing a unique amplification system for sensing. Single-cell analysis further illustrates the impact of DoPS cellular loading on the rate of DoPS activation and cell death times and on the 1O2 dosing necessary for cell death to occur. Our two-pronged therapy discriminates based on cell metabolites and has the potential to result in lower toxicity, pave the way to reduced drug resistance, and provide insightful mechanistic information about bacterial membrane response to 1O2.

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents.

Ru(II) polypyridyl complexes have gained widespread attention as photosensitizers for photodynamic therapy (PDT). Herein, we systematically investigate a series of the type [Ru(phen)2(IP-nT)]2+, featuring 1,10-phenanthroline (phen) coligands and imidazo[4,5-f][1,10]phenanthroline ligands tethered to n = 0-4 thiophene rings (IP-nT). The complexes were characterized and investigated for their electrochemical, spectroscopic, and (photo)biological properties. The electrochemical oxidation of the nT unit shifted by -350 mV as n = 1 → 4 (+920 mV for Ru-1T, +570 mV for Ru-4T); nT reductions were observed in complexes Ru-3T (-2530 mV) and Ru-4T (-2300 mV). Singlet oxygen quantum yields ranged from 0.53 to 0.88, with Ru-3T and Ru-4T being equally efficient (∼0.88). Time-resolved absorption spectra of Ru-0T-1T were dominated by metal-to-ligand charge-transfer (3MLCT) states (τTA = 0.40-0.85 μs), but long-lived intraligand charge-transfer (3ILCT) states were observed in Ru-2T-4T (τTA = 25-148 μs). The 3ILCT energies of Ru-3T and Ru-4T were computed to be 1.6 and 1.4 eV, respectively. The phototherapeutic efficacy against melanoma cells (SK-MEL-28) under broad-band visible light (400-700 nm) increases as n = 0 → 4: Ru-0T was inactive up to 300 μM, Ru-1T-2T were moderately active (EC50 ∼ 600 nM, PI = 200), and Ru-3T (EC50 = 57 nM, PI > 1100) and Ru-4T (EC50 = 740 pM, PI = 114,000) were the most phototoxic. The activity diminishes with longer wavelengths of light and is completely suppressed for all complexes except Ru-3T and Ru-4T in hypoxia. Ru-4T is the more potent and robust PS in 1% O2 over seven biological replicates (avg EC50 = 1.3 μM, avg PI = 985). Ru-3T exhibited hypoxic activity in five of seven replicates, underscoring the need for biological replicates in compound evaluation. Singlet oxygen sensitization is likely responsible for phototoxic effects of the compounds in normoxia, but the presence of redox-active excited states may facilitate additional photoactive pathways for complexes with three or more thienyl groups. The 3ILCT state with its extended lifetime (30-40× longer than the 3MLCT state for Ru-3T and Ru-4T) implicates its predominant role in photocytotoxicity.

Cover Feature: Synthesis, Characterization, and Singlet Oxygen Sensitization by Antimony (III/V) Corrole Complexes (Eur. J. Inorg. Chem. 24/2023)

Cover Feature: Synthesis, Characterization, and Singlet Oxygen Sensitization by Antimony (III/V) Corrole Complexes (Eur. J. Inorg. Chem. 24/2023)

On the photobehaviour of curcumin in biocompatible hosts: The role of H-abstraction in the photodegradation and photosensitization.

Curcumin (CUR) is a naturally occurring pigment extensively studied due to its therapeutic activity and delivered by suitable nanocarriers to overcome poor solubility in aqueous media. The significant absorption of CUR in the visible blue region has prompted its use as a potential phototherapeutic agent in treating infectious and cancer diseases, although the mechanism underlying the phototoxic effects is still not fully understood. This contribution investigates the photobehaviour of CUR within polymeric micelles, microemulsions, and zein nanoparticles, chosen as biocompatible nanocarriers, and human serum albumin as a representative biomolecule. Spectroscopic studies indicate that in all host systems, the enolic tautomeric form of CUR is converted in a significant amount of the diketo form because of the perturbation of the intramolecular hydrogen bond. This leads to intermolecular H-abstraction from the host components by the lowest excited triplet state of CUR with the formation of the corresponding ketyl radical, detected by nanosecond laser flash photolysis. This radical is oxidized by molecular oxygen, likely generating peroxyl and hydroperoxyl radical species, unless in Zein, reasonably due to the poor availability of oxygen in the closely packed structure of this nanocarrier. In contrast, no detectable formation of singlet oxygen was revealed in all the systems. Overall these results highlight the key role of the H-abstraction process over singlet oxygen sensitization as a primary photochemical pathway strictly dictated by the specific features of the microenvironment, providing new insights into the photoreactivity of CUR in biocompatible hosts that can also be useful for a better understanding of its phototoxicity mechanism.

Synthesis, Characterization, and Singlet Oxygen Sensitization by Antimony (III/V) Corrole Complexes

AbstractThe synthesis, structural, spectroscopic characterization, and DFT/TD‐DFT calculations of antimony corroles are reported herein. The studied complexes can be described as [(Corr)SbIII] and [(Corr)(oxo)SbV]2, where Corr is the trianion of corrole. All these complexes are diamagnetic in nature as is evident from sharp peaks with normal chemical shifts in the 1H NMR spectra. Single crystal XRD analysis reveals that the antimony(V) corrole complex is the bis‐μ‐oxo‐bridged dinuclear antimony(V). Both the tetra and hexa‐coordinated [(Corr)SbIII] and [(Corr)(oxo)SbV]2 antimony complexes adopt domed‐structure with weak d‐π electron coupling. The Sb−O bond distances in the co‐facial dimer of [(Corr)(oxo)SbV]2 are 1.9802(16) Å (DFT: 2.0141 Å) (for Sb1−O1), and 1.9639(17) Å (DFT: 1.9957 Å) (for Sb2−O2) respectively. We observed that even though iodosobenzene is frequently used to oxidize [(Corr)SbIII] species, the oxidation of [(Corr)SbIII] is indeed very facile in nature and it even occurred in the air‐equilibrated CHCl3 solution while storing for few days. Excitation of these antimony (III/V) corrole complexes in DCM/MeOH (1 : 1) at 77 K results in red emission with maxima at 640–720 nm. The singlet oxygen production of [(Corr)(oxo)SbV]2 has a quantum yield of 69 % and is two times higher than the analogous [(Corr)SbIII] derivatives.

Transition-Metal Isocorroles as Singlet Oxygen Sensitizers.

Building on a highly efficient synthesis of pyrrole-appended isocorroles, we have worked out conditions for manganese, palladium, and platinum insertion into free-base 5/10-(2-pyrrolyl)-5,10,15-tris(4-methylphenyl)isocorrole, H2[5/10-(2-py)TpMePiC]. Platinum insertion proved exceedingly challenging but was finally accomplished with cis-Pt(PhCN)2Cl2. All the complexes proved weakly phosphorescent in the near-infrared under ambient conditions, with a maximum phosphorescence quantum yield of 0.1% observed for Pd[5-(2-py)TpMePiC]. The emission maximum was found to exhibit a strong metal ion dependence for the 5-regioisomeric complexes but not for the 10-regioisomers. Despite the low phosphorescence quantum yields, all the complexes were found to sensitize singlet oxygen formation with moderate to good efficiency, with singlet oxygen quantum yields ranging over 21-52%. With significant absorption in the near-infrared and good singlet oxygen-sensitizing ability, metalloisocorroles deserve examination as photosensitizers in the photodynamic therapy of cancer and other diseases.

From Chemotherapy to Phototherapy - Changing the Therapeutic Action of a Metallo-Intercalating RuII -ReI Luminescent System by Switching its Sub-Cellular Location.

The synthesis of a new heterodinuclear ReI RuII metallointercalator containing RuII (dppz) and ReI (dppn) moieties is reported. Cell-free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in-cell properties to its parent. In complete contrast to the homoleptic system, the RuII (dppz)/ReI (dppn) complex is not intrinsically cytotoxic but displays appreciable phototoxic, despite both complexes displaying very similar quantum yields for singlet oxygen sensitization. Optical microscopy suggests that the reason for these contrasting biological effects is that whereas the homoleptic complex localises in the nuclei of cells, the RuII (dppz)/ReI (dppn) complex preferentially accumulates in mitochondria. These observations illustrate how even small structural changes in metal based therapeutic leads can modulate their mechanism of action.

Rhenium(I) bromo tricarbonyl complexes from anthracenyl derivatized ligands

The ligand 2-(1H-pyrazol-1-yl)pyrazine (pypyr) was prepared by reaction of 2-bromopyrazine with N-lithium pyrazolate with 92.5% yield, while the anthracenyl derivatives 2-(anthracen-9-yl)-5-(1H-pyrazol-1-yl)pyrazine (pypyr-anthra) and 9,10-bis(5-(1H-pyrazol-1-yl)pyrazin-2-yl)anthracene (pypyr-anthra-pypyr) were prepared by reaction of the 9-anthraceneboronic or bis-boronic acid pinacol ester with 2-bromo-5-(1H-pyrazol-1-yl)pyrazine with medium yields (49.6 and 31.5 % respectively). The respective ReI(CO)3Br complexes: [(pypyr)Re(CO)3Br], [(pypyr-anthra)Re(CO)3Br] and [Br(CO)3Re(pypyr-anthra-pypyr)Re(CO)3Br] were prepared in high yields (94, 84 and 78 % respectively) by reaction with bromotricarbonyl(tetrahydrofuran)rhenium(I) dimer. DFT modelling suggests the anthracenyl moiety is not coplanar with the pyrazolyl-pyrazine fragment, defining a dihedral angle of 65° and 67° for [(pypyr-anthra)Re(CO)3Br] and [Br(CO)3Re(pypyr-anthra-pypyr)Re(CO)3Br] respectively. Each one of the three rhenium(I) molecules shows a quasi-reversible reduction wave around − 1.10 V, assigned by comparison with the uncoordinated ligand, the pypyr fragment, while additional reductions waves related to this core or the anthryl arms are present. UV–Vis spectra show absorption bands and/or shoulders around 400–450 nm for the series of compounds in solution. The respective extinction coefficients (∼4 × 103 M−1cm−1), the sensitivity to solvent polarity and DFT modelling suggest they corresponds to MLCT Redπ → π(pyr)* transitions. Despite their high emissivity, the uncoordinated ligands completely lose their emission upon coordinated to ReI(CO)3Br. The rhenium(I) complexes emit around 650 nm upon excitation, although [(pypyr)Re(CO)3Br] is a moderate emissive molecule, while [(pypyr-anthra)Re(CO)3Br] and [Br(CO)3Re(pypyr-anthra-pypyr)Re(CO)3Br] are very weak ones. In contrast these two last molecules showed a remarkably high yield as singlet oxygen sensitizers.