Polypyridyl Complexes Research Articles

Enabling Visible Light Sensitization of YbIII, NdIII and ErIII in Dimeric LnIII/GaIII Metallacrowns through Functionalization with RuII Complexes for NIR‐II Multiplex Imaging

AbstractMultiplex imaging in the second near‐infrared window (NIR‐II, 1000–1700 nm) provides exciting opportunities for more precise understanding of biological processes and more accurate diagnosis of diseases by enabling real‐time acquisition of images with improved contrast and spatial resolution in deeper tissues. Today, the number of imaging agents suitable for this modality remains very scarce. In this work, we have synthesized and fully characterized, including theoretical calculations, a series of dimeric LnIII/GaIII metallacrowns bearing RuII polypyridyl complexes, LnRu‐3 (Ln=YIII, YbIII, NdIII, ErIII). Relaxed structures of YRu‐3 in the ground and the excited electronic states have been calculated using dispersion‐corrected density functional theory methods. Detailed photophysical studies of LnRu‐3 have demonstrated that characteristic emission signals of YbIII, NdIII and ErIII in the NIR‐II range can be sensitized upon excitation in the visible range through RuII‐centered metal‐to‐ligand charge transfer (MLCT) states. We have also showed that these NIR‐II signals are unambiguously detected in an imaging experiment using capillaries and biological tissue‐mimicking phantoms. This work opens unprecedented perspectives for NIR‐II multiplex imaging using LnIII‐based molecular compounds.

An Increase in the Rigidity of the Environment Favors MLCT over the MC State in [Ru(bpy)2(Nicotine)2](Cl)2: A Case Study of Photolabile Ligands.

Ru(II)-complexes with photolabile ligands find a wide range of applications, e.g., in drug release and in the design of light-responsive interfaces. While light-driven ligand loss has been studied mechanistically in detail for complexes in solution, comparably few studies are present that investigate the process in a material context, i.e., in a rigid environment and in the absence of solvent. This paper adds to this underrepresented perspective by studying the excited-state dynamics of [Ru(bpy)2(nicotine)2] (Cl)2 (Ru-nico) as a model system in poly(methyl methacrylate) (PMMA) and polyacrylonitrile (PAN) matrices. Femtosecond transient absorption spectroscopy and time-resolved emission spectroscopy are employed to monitor the photodissociation of labile nicotine ligands in polymer environments. Photoexcitation within the metal-to-ligand charge transfer (MLCT) band leads to transient dissociation of the nicotine ligand when the complex is dissolved in water. However, optical excitation of the 1MLCT transition of the complexes embedded in polymer matrices does not result in photodissociation, likely due to the rigidity of the environment, which cannot solvate the undercoordinated complex after ligand dissociation and the dissociated ligand. These insights shed light on the role of the local environment when considering the photophysics of ligand loss from Ru(II)-polypyridyl complexes and, hence, their use in the light-activation of reactive molecular components in materials.

100 μs Luminescence Lifetime Boosts the Excited State Reactivity of a Ruthenium(II)-Anthracene Complex in Photon Upconversion and Photocatalytic Polymerizations with Red Light.

The triplet excited state lifetime of a photosensitizer is an essential parameter for diffusion-controlled energy- and electron-transfer, which occurs usually in a competitive manner to the intrinsic decay of a triplet excited state. Here we show the decisive role of luminescence lifetime in the triplet excited state reactivity toward energy- and electron transfer. Anchoring two phenyl anthracene chromophores to a ruthenium(II) polypyridyl complex (RuII ref) leads to a RuII triad with a luminescence lifetime above 100 μs, which is more than 40 times longer than that of the prototypical complex. The obtained RuII triad sensitizes energy transfer to anthracene-based annihilators more efficiently than RuII ref and enables red-to-blue photon upconversion with a pseudo anti-Stokes shift of 0.94 eV and a moderate upconversion efficiency near 1 % in aerated solution. Particularly, RuII triad allows rapid photoredox catalytic polymerizations of acrylate and acrylamide monomers under aerobic condition with red light, which are kinetically hindered for RuII ref. Our work shows that excited state lifetime of a photosensitizer governs the dynamics of the excited state reactions, which seems an overlooked but important aspect for photochemistry.

Targeted Modulation of Photocatalytic Hydrogen Evolution Activity by Nickel-Substituted Rubredoxin through Functionalized Ruthenium Phototriggers.

Light-driven hydrogen evolution is a promising means of sustainable energy production to meet global energy demand. This study investigates the photocatalytic hydrogen evolution activity of nickel-substituted rubredoxin (NiRd), an artificial hydrogenase mimic, covalently attached to a ruthenium phototrigger (RuNiRd). By systematically modifying the para-substituents on Ru(II) polypyridyl complexes, we sought to optimize the intramolecular electron transfer processes within the RuNiRd system. A series of electron-donating and electron-withdrawing groups were introduced to tune the photophysical, photochemical, and electrochemical properties of the ruthenium complexes. Our findings reveal that electron-donating substituents can increase the hydrogen evolution capabilities of the artificial enzyme to a point; however, the complexes with the most electron-donating substituents suffer from short lifetimes and inefficient reductive quenching, rendering them inactive. The present work highlights the intricate balance required between driving force, lifetime, and quenching efficiency for effective light-driven catalysis, providing valuable insights into the design of artificial enzyme-photosensitizer constructs.

Tailoring Ruthenium(II) and Rhenium(I) Complexes for Turn-On Luminescent Sensing of Antimony(III)

Antimony (Sb) is currently a widespread element with key roles in telecommunication, sustainable energy, and military industries, among others. Its significant toxicity determines the need to realize sensors for water, air, and soil and the industrial process monitoring of Sb species. Unfortunately, no antimony sensors exist so far, and just laboratory analysis methods are in use. We aimed to contribute to the development of optical sensors for the metalloid by tailoring, for the first time, luminescent Ru(II) and Re(I) polypyridyl complexes to probe and quantify the presence of Sb(III). The molecular design of the complexes includes the multifunctional Sb-binding 2-(2,2′-bithien-5-yl)-1H-imidazo[4,5-f]-1,10-phenanthroline (btip) ligand that ensures the molecular binding of Sb(III) in organic media. The Ru(II)-btip complex is additionally endowed with one 2,2′-bipyrazine (bpz) or two 1,4,5,8-tetraazaphenanthrene (tap) ligands, namely [Ru(bpz)(btip)2]2+ and [Ru(tap)2(btip)]2+, that boost the excited state oxidation potential of the probe, leading to an intramolecular photoinduced electron transfer from btip to the Ru(II) core. The latter is suppressed upon interaction with Sb(III), leading to an 11-fold increase in both the luminescence intensity and lifetime of [Ru(bpz)(btip)2]2+ in the presence of ca. 50 μmol L−1 of SbCl3 in organic medium. The fluorescence intensity of [Re(CO)3(H2O)(btip)]+ also increases upon interaction with Sb(III) but to a much lesser extent due to the intraligand π*→π nature of its emission compared to the Ru(II) ligand-to-metal excited state deactivation. However, the weak π*→d emission band in the red spectral region of the former is quenched by the semimetallic element. The sensing mechanisms of the Ru(II)- and Re(I)-btip probes that allow luminescence intensity (Ru, Re), ratiometric (Ru), and lifetime measurements (Ru) are compared and discussed in this initial solution sensing study.

DFT Computational Analysis of the Mechanism of Action of Ru(II) Polypyridyl Complexes as Photoactivated Chemotherapy Agents: From Photoinduced Ligand Solvolysis to DNA Binding.

Photoactivated chemotherapy (PACT) is a form of target-oriented cancer therapy that exploits light of the proper wavelength to selectively activate the drug. Among the prodrugs used for this purpose, ruthenium-based complexes are particularly interesting, as when irradiated by light, they can release ligands by forming aquo-complexes able to bind DNA in both single and double strand fashions, causing its distortion. Using as model system a Ru(II) polypyridyl complex that has been demonstrated to be a promising photochemotherapeutic agent, all of the key aspects of the photoinduced solvolysis process and subsequent DNA interaction have been scrutinized using density functional theory (DFT) and time-dependent-DFT (TDDFT). Photoexcitation, intersystem crossing, internal conversion, mechanism by which photoinduced ligand release, and subsequent aquation steps occur have been examined. Pathways leading to the formation of both cis and trans biaquated photoproducts have been described, and the formation of the cis form of the biaquated photoproduct being the most favorable one, its reaction with a guanine base has also been reported in order to account for DNA binding.

Theoretical Investigation of Novel Nitrogen-Heterocyclic Iridium(III) Polypyridyl Complexes as Photosensitizers for Two-Photon Photodynamic Therapy.

Two-photon photodynamic therapy (TP-PDT) has become a major cancer treatment due to its larger tissue penetration depth, good spatial selectivity, and less damage to normal cells. In this contribution, a series of novel photosensitizer molecules (Ir-2, Ir-2-1∼Ir-2-4) have been designed based on the experimentally demonstrated photosensitizer [Ir(ppy)2(osip)] (PF6) by fine tuning the π-conjugated structure and introducing different nitrogen-heterocyclic substituents. The electronic structures, one- and two-photon absorption spectra, triplet excited state lifetime, solvation-free energy, and photosensitizing performance were evaluated by means of density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results suggested that the molecule Ir-2, incorporating thiophene as the π-connecting group, exhibits a higher probability of triplet state formation, enhanced two-photon absorption cross-section, and prolonged triplet state lifetime. Furthermore, the four designed nitrogen-heterocyclic complexes Ir-2-1∼Ir-2-4 demonstrate favorable photosensitizing properties, with two-photon absorption cross-sections reaching up to 110 GM and triplet excited state lifetimes exceeding 1000 μs for Ir-2-4.

Enantioselectively generating imidazolone dIz by the chiral DNA intercalating and “light-switching” Ru(II) polypyridyl complex via a novel flash-quench method

The 2-aminoimidazolone is a major and ubiquitous in vitro product of guanine oxidation. The flash-quench method, combining spectroscopy and product analysis, offers a novel and tunable approach to study guanine oxidation on double helical DNA. Herein we found that imidazolone dIz (2-amino-5-[(2-deoxy-β-D-erythro-pentofuranosyl)amino]-4H-imidazole-4-one) and dZ (2,2-diamino-5-[2-deoxy-β-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone) were the major oxidation products of double-strand DNA from the visible-light irradiation of the well-known DNA intercalating and light-switching Ru(OP)2dppz2+ (OP = 1,10-phenanthroline, dppz = dipyrido [3,2-a:2′,3′-c]phenazine) in the presence of a typical quencher methyl viologen (MV2+). Using ESR spin-trapping method, the radical intermediate MV•+ with typical hyperfine pattern was detected which indicated the successful formation of the corresponding Ru3+ intercalated oxidant. The formation of dIz and dZ decreased markedly with the addition of nitrotetrazolium blue chloride (NBT), a typical O2•- reactant. With a more specific and highly sensitive O2•- probe CT02-H, its ESR signal decayed rapidly in the presence of Ru(OP)2dppz2+ and MV2+, suggesting that O2•- was indeed produced. More interestingly, enantio-selective generation of oxidation products from dsDNA was observed with the two chiral forms of Ru(OP)2dppz2+. This represents the first report that the flash-quench technique with MV2+ as the quencher can oxidize dsDNA effectively to form dIz and dZ via the Ru3+/O2•- mediated mechanism. Our new findings provide a novel method to generate two radicals simultaneously, G (-H)• and O2•-, in close proximity to one another in dsDNA.

Enabling Visible Light Sensitization of YbIII, NdIII and ErIII in Dimeric LnIII/GaIII Metallacrowns through Functionalization with RuII Complexes for NIR-II Multiplex Imaging.

Multiplex imaging in the second near-infrared window (NIR-II, 1000-1700 nm) provides exciting opportunities for more precise understanding of biological processes and more accurate diagnosis of diseases by enabling real-time acquisition of images with improved contrast and spatial resolution in deeper tissues. Today, the number of imaging agents suitable for this modality remains very scarce. In this work, we have synthesized and fully characterized, including theoretical calculations, a series of dimeric LnIII/GaIII metallacrowns bearing RuII polypyridyl complexes, LnRu-3 (Ln = YIII, YbIII, NdIII, ErIII). Relaxed structures of YRu-3 in the ground and the excited electronic states have been calculated using dispersion-corrected density functional theory methods. Detailed photophysical studies of LnRu-3 have demonstrated that characteristic emission signals of YbIII, NdIII and ErIII in the NIR-II range can be sensitized upon excitation in the visible range through RuII-centered metal-to-ligand charge transfer (MLCT) states. We have also showed that these NIR-II signals are unambiguously detected in an imaging experiment using capillaries and biological tissue-mimicking phantoms. This work opens unprecedented perspectives for NIR-II multiplex imaging using LnIII-based molecular compounds.

The photophysical, photobiological, and light-up calf-thymus-DNA sensor activity of Pd(II) and Pt(II) polypyridyl derivatives coordinated to vinyl-pyridyl corroles

A series of mono-cationic corroles containing bipyridyl derivatives coordinated with Pd(II) and Pt(II) polypyridyl complexes is reported here. These corroles were characterized by microanalysis, UV–Vis absorption, steady-state and time-resolved fluorescence emission, theoretical DFT calculations, and electrochemical techniques. Photobiological parameters, such as photostability and ROS production, were also assessed. Spectroscopic and viscometry studies, along with molecular docking calculations, revealed each corrole derivative's ability to interact with the minor grooves of calf-thymus DNA. Additionally, the potential of these derivatives to act as emissive optical sensors for CT-DNA was evaluated.

A Ru(II) Polypyridyl Complex Bearing Bathocuproine Ligand is a Potent Chemotherapeutic Agent Against Chemically Induced Skin Cancer Model

A Ru(II) Polypyridyl Complex Bearing Bathocuproine Ligand is a Potent Chemotherapeutic Agent Against Chemically Induced Skin Cancer Model

Computational Exploration of the Mechanism of Action of a Sorafenib-Containing Ruthenium Complex as an Anticancer Agent for Photoactivated Chemotherapy.

Ruthenium(II) polypyridyl complexes are being tested as potential anticancer agents in different therapies, which include conventional chemotherapy and light-activated approaches. A mechanistic study on a recently synthesized dual-action Ru(II) complex [Ru(bpy)2(sora)Cl]+ is described here. It is characterized by two mono-dentate leaving ligands, namely, chloride and sorafenib ligands, which make it possible to form a di-aquo complex able to bind DNA. At the same time, while the released sorafenib can induce ferroptosis, the complex is also able to act as a photosensitizer according to type II photodynamic therapy processes, thus generating one of the most harmful cytotoxic species, 1O2. In order to clarify the mechanism of action of the drug, computational strategies based on density functional theory are exploited. The photophysical properties of the complex, which include the absorption spectrum, the kinetics of ISC, and the character of all the excited states potentially involved in 1O2 generation, as well as the pathway providing the di-aquo complex, are fully explored. Interestingly, the outcomes show that light is needed to form the mono-aquo complex, after releasing both chloride and sorafenib ligands, while the second solvent molecule enters the coordination sphere of the metal once the system has come back to the ground-state potential energy surface. In order to simulate the interaction with canonical DNA, the di-aquo complex interaction with a guanine nucleobase as a model has also been studied. The whole study aims to elucidate the intricate details of the photodissociation process, which could help with designing tailored metal complexes as potential anticancer agents.

Exploring the DNA-binding and anticancer potential of polypyridyl ruthenium(II) complexes

Organometallic medicines based on ruthenium (Ru) have attracted interest as chemotherapeutic and bioimaging agents due to their low toxicity and superior physical optical characteristics. However, there are still no ideal candidates in clinical trials due to the lack of understanding of the structure-activity relationships (SARs) of polypyrodyl Ru(II) complexes. Though increasing the electron-donating ability of the ligands has been proven to benefit bioactivity due to the fast hydroxylation rate between chlorine and DNA, the total electronic effects are much more important, especially for the binding modes between Ru(II)-polypyridyl complexes and DNA. By evaluating the electron-donating ability of the ligand complexes 1 - 4 through density functional theory (DFT) calculations, bioactivities tests, and docking studies, we investigated the relationship between the structures of Ru(II) complexes and cytotoxicity. Our findings showed that it was insufficient to merely consider the impact of electron-donating effects on biological activities in place of interaction modes. Furthermore, the cellular imaging study investigated the complex with phenyl substituents (1) and confirmed that the main target was DNA. Besides, the “off-on” emission phenomena of complex 1 indicated that there is also covalent interaction with DNA. These findings offer valuable insight into the development of SARs of polypyrodyl Ru(II) complexes.

Near-Infrared Laser-Switching DNA Phase Separation Nanoinducer for Glioma Therapy.

DNA phase separation participates in chromatin packing for the modulation of gene transcription, but the induction of DNA phase separation in living cells for disease treatment faces huge challenges. Herein, we construct a Ru(II)-polypyridyl-loaded upconversion nanoplatform (denoted as UCSNs-R) to achieve the manipulation of DNA phase separation and production of abundant singlet oxygen (1O2) for efficient treatment of gliomas. The utilization of the UCSN not only facilitates high loading of Ru(II)-polypyridyl complexes (RuC) but also promotes the conversion of near-infrared (NIR) laser to ultraviolet light for efficient 1O2 generation. The released RuC exhibit DNA "light-switch" behavior and high DNA binding affinity that induce phase separation of DNA in living cells, thus resulting in DNA damage and suppressing tumor-cell growth. In vivo investigation demonstrates the high capability of UCSNs-R in inhibiting tumor proliferation under NIR laser illumination. This work represents a paradigm for designing a DNA phase separation nanoinducer through integration of the UCSN with Ru(II)-polypyridyl-based complexes for efficient therapy of gliomas.

Role of non-redox innocent ligand units in the oxidation of alcohols with H2O2 catalyzed by μ-oxido-diiron(III) bis-phenolato polypyridyl complexes

Redox non-innocent ligands hold the potential to expand the redox chemistry and activity of transition metal catalysts. The impact of the additional redox chemistry of phenol ligands in oxidation catalysis is explored here in the complex μ-oxido-diiron(III) polypyridyl (1) [(L)Fe(III)(μ–O)Fe(III)(L)](ClO4)2 (where HL is 2-(((di(pyridin-2-yl)methyl) (pyridin-2-ylmethyl) amino)methyl)phenol) and its tert-butyl substituted analog 2, in which each of the Fe(III) centers is coordinated to a phenolato moiety of the ligand. Complex 1 was shown earlier to catalyse the oxidation of benzyl alcohols to aldehydes with H2O2. In particular acid was found to accelerate the reactions by removal of a lag period before catalysis initiated. Here, we use reaction monitoring with resonance Raman, UV/vis absorption and EPR spectroscopy to show that under catalytic conditions, i.e. with excess H2O2, rapid (< 5 s) loss of the phenolato moiety occurs, resulting in the formation of an N4 ligated Fe(III) complex. This N4 coordinated complex forms a Fe(III)-OOH species, which is responsible for alcohol oxidation and over time a relatively stable oxido-bridged dinuclear Fe(III) complex forms as a resting state in the catalytic system. The main role of acid in the catalysis is shown to be to facilitate the initial coordination of H2O2 by driving the formation of mononuclear complexes from 1 and 2. The data show that although the phenolato moiety imparts interesting redox properties on complex 1, it does not contribute directly to the oxidation catalysis observed with H2O2.

Contrasting Photosensitized Processes of Ru(II) Polypyridyl Structural Isomers Containing Linear and Hooked Intercalating Ligands Bound to Guanine-Rich DNA.

The DNA binding and cellular uptake of the lambda enantiomer of two bis-tetraazaphenanthrene (TAP) Ru(II) polypyridyl complexes containing either a linear dppn (1) or a hooked bdppz (2) benzodipyridophenazine ligand are reported, and the role of different charge-transfer states of the structural isomers in the photo-oxidation of guanine is explored. Both complexes possess characteristic metal-to-ligand charge-transfer (MLCT) bands between 400 and 500 nm and emission at ca. 630 nm in an aerated aqueous solution. Transient visible absorption (TrA) spectroscopy reveals that 400 nm excitation of 1 yields a dppn-based metal-to-ligand charge-transfer (MLCT) state, which in turn populates a dppn intraligand (3IL) state. In contrast, photoexcitation of 2 results in an MLCT state on the TAP ligand and not the intercalating bdppz ligand. Both 1 and 2 bind strongly to double-stranded guanine-rich DNA with a loss of emission. Combined TrA and time-resolved infrared (TRIR) spectroscopy confirms formation of the guanine radical cation when 2 is bound to the d(G5C5)2 duplex, which is not the case when 1 is bound to the same duplex and indicates a different mechanism of action in DNA. Utilizing the long-lived triplet excited lifetime, we show good uptake and localization of 2 in live cells as well as isolated chromosomes. The observed shortening of the excited-state lifetime of 2 when internalized in cell chromosomes is consistent with DNA binding and luminescent quenching due to guanine photo-oxidation.

Dual Photoreactive Ternary Ruthenium(II) Terpyridyl Complexes: A Comparative Study on Visible-Light-Induced Single-Step Dissociation of Bidentate Ligands and Generation of Singlet Oxygen.

The versatile and tunable ligand-exchange dynamics in ruthenium(II)-polypyridyl complexes imposed by the modulation of the steric and electronic effects of the coordinated ligands provide an unlimited scope for developing phototherapeutic agents. The photorelease of a bidentate ligand from the Ru-center is better suited for potent Ru(II)-based photocytotoxic agents with two available labile sites for cross-linking with biological targets augmented with possible phototriggered 1O2 generation. Herein, we introduced a phenyl-terpyridine (ptpy) ligand in the octahedral Ru(II) core of [Ru(ptpy)(L-L)Cl]+ to induce structural distortion for the possible photorelease of electronically distinct bidentate ligands (L-L). For a systematic study, we designed four Ru(II) polypyridyl complexes: [Ru(ptpy)(L-L)Cl](PF6), ([1]-[4]), where L-L = 1,2-bis(phenylthio)ethane (SPH) [1], N,N,N',N'-tetramethylethylenediamine (TMEN) [2], N1,N2-diphenylethane-1,2-diimine (BPEDI) [3], and bis[2-(diphenylphosphino)phenyl]ether (DPE-Phos) [4]. The detailed photochemical studies suggest a single-step dissociation of L-L from the bis-thioether (SPH) complex [1] and diamine (TMEN) complex [2], while no photosubstitution was observed for [3] and [4]. Complex [1] and [2] demonstrated a dual role, involving both photosubstitution and 1O2 generation, while [3] and [4] solely exhibited poor to moderate 1O2 production. The interplay of excited states leading to these behaviors was rationalized from the lifetimes of the 3MLCT excited states by using transient absorption spectroscopy, suggesting intricate relaxation dynamics and 1O2 generation upon excitation. Therefore, the photolabile complexes [1] and [2] could potentially act as dual photoreactive agents via the phototriggered release of L-L (PACT) and/or 1O2-mediated PDT mechanisms, while [4] primarily can be utilized as a PDT agent.

Anti-Cancer Stem Cell Cobalt(III)-Polypyridyl Complexes Containing Salicylic Acid

Metal-containing compounds are an important class of chemotherapeutics used to treat various manifestations of cancer. Despite the widespread clinical use and success of metallopharmaceuticals, they are ineffective towards a sub-population of tumours called cancer stem cells (CSCs). CSCs evade current chemotherapeutic regimens (including metallopharmaceuticals) and promote cancer relapse and metastasis. Here, we report the synthesis, characterisation and anti-breast CSCs properties of a series of cobalt(III)-polypyridyl complexes with salicylic acid. The lead cobalt(III) complex 6 (containing 3,4,7,8-tetramethyl-1,10-phenanthroline) displayed low micromolar potency towards breast CSCs, significantly lower than the gold-standard anti-breast CSC agent, salinomycin, and the clinically used metallodrug, cisplatin. Mechanistic studies indicate that the cobalt(III) complex 6 induces its anti-breast CSC effect by entering breast CSCs, penetrating the nuclei, damaging nuclear DNA and triggering caspase-dependent apoptosis. The cytotoxic mechanism of action of the cobalt(III) complex 6 is also dependent on the modulation of cyclooxygenase-2 (COX-2) expression. This work highlights the anti-breast CSC properties of cobalt(III) coordination complexes with non-steroidal anti-inflammatory drugs (NSAIDs) and more widely spotlights the importance of metallopharmaceuticals in the development of new anticancer agents that can tackle chemotherapeutic-resistant sub-populations.

Triton X-100 Mediated Electron Transfer Reactions between Iron(III) Polypyridyl Complexes and Phenylsulfinylacetic Acids

Triton X-100 Mediated Electron Transfer Reactions between Iron(III) Polypyridyl Complexes and Phenylsulfinylacetic Acids

Ligand Characterization and DNA Intercalation of Ru(II) Polypyridyl Complexes: A Local Vibrational Mode Study.

We investigated in this work ruthenium-ligand bonding across the RuN framework in 12 Ru(II) polypyridyl complexes in the gas phase and solution for both singlet and triplet states, in addition to their affinity for DNA binding through π-π stacking interactions with DNA nucleobases. As a tool to assess the intrinsic strength of the ruthenium-ligand bonds, we determined local vibrational force constants via our local vibrational mode analysis software. We introduced a novel local force constant that directly accounts for the intrinsic strength of the π-π stacking interaction between DNA and the intercalated Ru(II) complex. According to our findings, [Ru(phen)2(dppz)]2+ and [Ru(phen)2(11-CN-dppz)]2+ provide an intriguing trade-off between photoinduced complex excitation and the strength of the subsequent π-π stacking interaction with DNA. [Ru(phen)2(dppz)]2+ displays a small singlet-triplet splitting and a strong π-π stacking interaction in its singlet state, suggesting a favorable photoexcitation but potentially weaker interaction with DNA in the excited state. Conversely, [Ru(phen)2(11-CN-dppz)]2+ exhibits a larger singlet-triplet splitting and a stronger π-π stacking interaction with DNA in its triplet state, indicating a less favorable photoinduced transition but a stronger interaction with DNA postexcitation. We hope our study will inspire future experimental and computational work aimed at the design of novel Ru-polypyridyl drug candidates and that our new quantitative measure of π-π stacking interactions in DNA will find a general application in the field.