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1. Multifaceted Ru( II ) arene systems for phototherapy display activity in lung cancer and melanoma

   https://doi.org/10.1111/php.70038  

   Spiconardi, Joseph; Havrylyuk, Dmytro; Shi, Ge; Talgatov, Alisher; Cameron, Colin G; Heidary, David K; McFarland, Sherri A; Glazer, Edith C (October 2025, Photochemistry and Photobiology)

   Abstract Phototherapy approaches include photodynamic therapy (PDT), which utilizes chemically stable photocatalysts to sensitize the conversion of endogenous molecules such as oxygen (O₂) to form transient reactive species such as¹O₂, and photopharmacology, a complementary approach that relies on molecules that undergo self‐modifying photochemistry, such as bond cleavage reactions or isomerization, for the creation of biologically active products. While Ru(II) polypyridyl systems have demonstrated utility for both approaches, related organometallic systems are relatively less explored. Here, the photochemistry and photobiological responses were compared for five Ru(II) arene compounds containing photolabile monodentate azine ligands and the π‐expansive bidentate ligands dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz), 4,5,9,16‐tetraaza‐dibenzo[a,c]naphthacene (dppn), and α‐terthienyl‐appended imidazo[4,5‐f][1,10]phenanthroline (IP‐3T). The compounds demonstrated significant light‐mediated photocytotoxicity in lung cancer and melanoma cell lines, with up to 6000‐fold increases in cytotoxicity upon irradiation. The arene systems were capable of partitioning between different excited state relaxation pathways, both releasing the monodentate ligand and generating¹O₂, but with notably low yields that did not correlate with the photocytotoxicity of the systems. The organometallic compounds exhibit less mixing of the metal‐associated and ligand‐centered excited states than analogous polypyridyl coordination compounds, providing a structurally, photochemically, and photobiologically distinct class of compounds that can support both metal‐ and ligand‐centered reactivity. 

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2. Light‐responsive and Protic Ruthenium Compounds Bearing Bathophenanthroline and Dihydroxybipyridine Ligands Achieve Nanomolar Toxicity towards Breast Cancer Cells ^†

   https://doi.org/10.1111/php.13508  

   Oladipupo, Olaitan E.; Brown, Spenser R.; Lamb, Robert W.; Gray, Jessica L.; Cameron, Colin G.; DeRegnaucourt, Alexa R.; Ward, Nicholas A.; Hall, James Fletcher; Xu, Yifei; Petersen, Courtney M.; et al (November 2021, Photochemistry and Photobiology)

   ABSTRACT We report new ruthenium complexes bearing the lipophilic bathophenanthroline (BPhen) ligand and dihydroxybipyridine (dhbp) ligands which differ in the placement of the OH groups ([(BPhen)₂Ru(n,n′‐dhbp)]Cl₂withn = 6 and 4 in 1_Aand 2_A, respectively). Full characterization data are reported for 1_Aand 2_Aand single crystal X‐ray diffraction for 1_A. Both 1_Aand 2_Aare diprotic acids. We have studied 1_A, 1_B, 2_A, and 2_B(B = deprotonated forms) by UV‐vis spectroscopy and 1 photodissociates, but 2 is light stable. Luminescence studies reveal that the basic forms have lower energy³MLCT states relative to the acidic forms. Complexes 1_Aand 2_Aproduce singlet oxygen with quantum yields of 0.05 and 0.68, respectively, in acetonitrile. Complexes 1 and 2 are both photocytotoxic toward breast cancer cells, with complex 2 showing EC₅₀light values as low as 0.50 μM with PI values as high as >200vs. MCF7. Computational studies were used to predict the energies of the³MLCT and³MC states. An inaccessible³MC state for 2_Bsuggests a rationale for why photodissociation does not occur with the 4,4′‐dhbp ligand. Low dark toxicity combined with an accessible³MLCT state for¹O₂generation explains the excellent photocytotoxicity of 2. 

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3. Crystal structures of [Cu(phen)(H 2 O) 3 ( M F 6 )]·H 2 O ( M = Ti, Zr, Hf) and [Cu(phen)(H 2 O) 2 F] 2 [HfF 6 ]·H 2 O

   https://doi.org/10.1107/S2056989021000645  

   Nisbet, Matthew L.; Poeppelmeier, Kenneth R. (February 2021, Acta Crystallographica Section E Crystallographic Communications)

   null (Ed.)

   The crystal structures of three bridged bimetallic molecular compounds, namely, triaqua-2κ 3 O -μ-fluorido-pentafluorido-1κ 5 F -(1,10-phenanthroline-2κ 2 N , N ′)copper(II)titanium(IV) monohydrate, [Cu(TiF 6 )(phen)(H 2 O) 3 ]·H 2 O (phen is 1,10-phenanthroline, C 12 H 8 N 2 ), (I), triaqua-2κ 3 O -μ-fluorido-pentafluorido-1κ 5 F -(1,10-phenanthroline-2κ 2 N , N ′)copper(II)zirconium(IV) monohydrate, [Cu(ZrF 6 )(phen)(H 2 O) 3 ]·H 2 O, (II), and triaqua-2κ 3 O -μ-fluorido-pentafluorido-1κ 5 F -(1,10-phenanthroline-2κ 2 N , N ′)copper(II)hafnium(IV) monohydrate, [Cu(HfF 6 )(phen)(H 2 O) 3 ]·H 2 O, (III), and one molecular salt, bis[diaquafluorido(1,10-phenanthroline-κ 2 N , N ′)copper(II)] hexafluoridohafnate(IV) dihydrate, [CuF(phen)(H 2 O) 2 ] 2 [HfF 6 ]·2H 2 O, (IV), are reported. The bridged bimetallic compounds adopt Λ-shaped configurations, with the octahedrally coordinated copper(II) center linked to the fluorinated early transition metal via a fluoride linkage. The extended structures of these Λ-shaped compounds are organized through both intra- and intermolecular hydrogen bonds and intermolecular π–π stacking. The salt compound [Cu(phen)(H 2 O) 2 F] 2 [HfF 6 ]·H 2 O displays an isolated square-pyramidal Cu(phen)(H 2 O) 2 F + complex linked to other cationic complexes and isolated HfF 6 2− anions through intermolecular hydrogen-bonding interactions. 

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4. Photocytotoxicity and photoinduced phosphine ligand exchange in a Ru( ii ) polypyridyl complex

   https://doi.org/10.1039/d1sc05647f  

   Steinke, Sean J.; Gupta, Sayak; Piechota, Eric J.; Moore, Curtis E.; Kodanko, Jeremy J.; Turro, Claudia (February 2022, Chemical Science)

   Two new tris-heteroleptic Ru( ii ) complexes with triphenylphosphine (PPh 3 ) coordination, cis -[Ru(phen) 2 (PPh 3 )(CH 3 CN)] 2+ (1a, phen = 1,10-phenanthroline) and cis -[Ru(biq)(phen)(PPh 3 )(CH 3 CN)] 2+ (2a, biq = 2,2′-biquinoline), were synthesized and characterized for photochemotherapeutic applications. Upon absorption of visible light, 1a exchanges a CH 3 CN ligand for a solvent water molecule. Surprisingly, the steady-state irradiation of 2a followed by electronic absorption and NMR spectroscopies reveals the photosubstitution of the PPh 3 ligand. Phosphine photoinduced ligand exchange with visible light from a Ru( ii ) polypyridyl complex has not previously been reported, and calculations reveal that it results from a trans -type influence in the excited state. Complexes 1a and 2a are not toxic against the triple negative breast cancer cell line MDA-MB-231 in the dark, but upon irradiation with blue light, the activity of both complexes increases by factors of >4.2 and 5.8, respectively. Experiments with PPh 3 alone show that the phototoxicity observed for 2a does not arise from the released phosphine ligand, indicating the role of the photochemically generated ruthenium aqua complex on the biological activity. These complexes represent a new design motif for the selective release of PPh 3 and CH 3 CN for use in photochemotherapy. 

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5. Unlocking the Potential of Ru(II) Dual‐action Compounds with the Power of the Heavy‐atom Effect ^†

   https://doi.org/10.1111/php.13573  

   Toupin, Nicholas P.; Steinke, Sean J.; Herroon, Mackenzie K.; Podgorski, Izabela; Turro, Claudia; Kodanko, Jeremy J. (December 2021, Photochemistry and Photobiology)

   ABSTRACT We report the synthesis, photochemical and biological characterization of two new Ru(II) photoactivated complexes based on [Ru(tpy)(Me₂bpy)(L)]²⁺(tpy = 2,2':6',2''‐terpyridine, Me₂bpy = 6,6'‐dimethyl‐2,2'‐bipyridine), where L = pyridyl‐BODIPY (pyBOD). Two pyBOD ligands were prepared bearing flanking hydrogen or iodine atoms. Ru(II)‐bound BODIPY dyes show a red‐shift of absorption maxima relative to the free dyes and undergo photodissociation of BODIPY ligands with green light irradiation. Addition of iodine into the BODIPY ligand facilitates intersystem crossing, which leads to efficient singlet oxygen production in the free dye, but also enhances quantum yield of release of the BODIPY ligand from Ru(II). This represents the first report of a strategy to enhance photodissociation quantum yields through the heavy‐atom effect in Ru(II) complexes. Furthermore, Ru(II)‐bound BODIPY dyes display fluorescence turn‐on once released, with a lead analog showing nanomolar EC₅₀values against triple negative breast cancer cells, >100‐fold phototherapeutic indexes under green light irradiation, and higher selectivity toward cancer cells as compared to normal cells than the corresponding free BODIPY photosensitizer. Conventional Ru(II) photoactivated complexes require nonbiorthogonal blue light for activation and rarely show submicromolar potency to achieve cell death. Our study represents an avenue for the improved photochemistry and potency of future Ru(II) complexes. 

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