Light-activated compounds are powerful tools and potential agents for medical applications, as biological effects can be controlled in space and time. Ruthenium polypyridyl complexes can induce cytotoxic effects through multiple mechanisms, including acting as photosensitizers for singlet oxygen (1O2) production, generating other reactive oxygen species (ROS), releasing biologically active ligands, and creating reactive intermediates that form covalent bonds to biological molecules. A structure–activity relationship (SAR) study was performed on a series of Ru(II) complexes containing isomeric tetramethyl-substituted bipyridyl-type ligands. Three of the ligand systems studied contained strain-inducing methyl groups and created photolabile metal complexes, which can form covalent bonds to biomolecules upon light activation, while the fourth was unstrained and resulted in photostable complexes, which can generate 1O2. The compounds studied included both bis-heteroleptic complexes containing two bipyridine ligands and a third, substituted ligand and tris-homoleptic complexes containing only the substituted ligand. The photophysics, electrochemistry, photochemistry, and photobiology were assessed. Strained heteroleptic complexes were found to be more photoactive and cytotoxic then tris-homoleptic complexes, and bipyridine ligands were superior to bipyrimidine. However, the homoleptic complexes exhibited an enhanced ability to inhibit protein production in live cells. Specific methylation patterns were associated with improved activation with red light, and photolabile complexes were generally more potent cytotoxic agents than the photostable 1O2-generating compounds.

A family of 28 mononuclear Ru(II) complexes have been prepared and characterized by 1H NMR, electronic absorption, and cyclic voltammetry. These complexes are studied as catalysts for water oxidation. All the catalysts possess one tridentate ligand, closely related to 2,2′;6,2″-terpyridine (tpy) and may be divided into two basic types. In the type-1 catalyst, the three remaining coordination sites are occupied by a bidentate closely related to 2,2′-bipyridine (bpy) and a monodentate halogen (Br, Cl, or I) or water molecule. In the type-2 catalyst, the three remaining coordination sites are occupied by two axial 4-picoline molecules and an equatorial halogen or water. In general the type-2 catalysts are more reactive than the type-1. The type-2 iodo-catalyst shows first-order behavior and, unlike the bromo- and chloro-catalysts, does not require water–halogen exchange to show good activity. The importance of steric strain and hindrance around the metal center is examined. The introduction of three t-butyl groups at the 4, 4′, and 4″ positions of tpy sometimes improves catalyst activity, but the effect does not appear to be additive.

In the evaluation of systems designed for catalytic water oxidation, ceric ammonium nitrate (CAN) is often used as a sacrificial electron acceptor. One of the sources of failure for such systems is oxidative decay of the catalyst in the presence of the strong oxidant CAN (Eox = +1.71 V). Little progress has been made in understanding the circumstances behind this decay. In this study we show that a 2-(2′-hydroxphenyl) derivative (LH) of 1,10-phenanthroline (phen) in the complex [Ru(L)(tpy)]+ (tpy = 2,2′;6′,2″-terpyridine) can be oxidized by CAN to a 2-carboxy-phen while still bound to the metal. This complex is, in fact, a very active water oxidation catalyst. The incorporation of a methyl substituent on the phenol ring of LH slows down the oxidative decay and consequently slows down the catalytic oxidation. An analogous system based on bpy (2,2′-bipyridine) instead of phen shows much lower activity under the same conditions. Water molecule association to the Ru center of [Ru(L)(tpy)]+ and carboxylate donor dissociation were proposed to occur at the trivalent state. The resulting [RuIII–OH2] was further oxidized to [RuIV═O] via a PCET process.Keywords: 2-carboxyphenanthroline; anionic ligands; ligand decay; mononuclear Ru catalysts; water oxidation;

Two new formamidinate-bridged Rh2II,II complexes, cis-[Rh2II,II(μ-DTolF)2(μ-np)2]2+ (3; DTolF = N,N′-di-p-tolylformamidinate; np = 1,8-naphthyridine) and cis-[Rh2II,II(μ-DTolF)2(κ2-dap)2]2+ (4; dap = 1,12-diazaperylene), were synthesized from cis-[Rh2II,II(μ-DTolF)2(CH3CN)6](BF4)2 (1), and their properties were compared to those of cis-[Rh2II,II(μ-DTolF)2(phen)2](BF4)2 (2). Density functional theory (DFT) and electrochemical analyses support the description of the highest occupied molecular orbitals (HOMOs) of 3 and 4 as possessing contributions from the metals and formamidinate bridging ligands, with Rh2/form character, and lowest unoccupied molecular orbitals (LUMOs) localized on the respective diimine ligand np and dap π∗ orbitals. Both 3 and 4 display strong, low energy Rh2/form → diimine(π∗) metal/ligand-to-ligand charger transfer (1ML–LCT) transitions with maxima at 566 nm (ε = 3600 M−1 cm−1) for 3 and at 630 nm (ε = 2900 M−1 cm−1) for 4 in CH3CN. Time dependent-DFT (TD-DFT) calculations support these assignments. The ability of both the bridging np and chelating dap diimine ligands to produce strong absorption of these Rh2II,II complexes throughout the visible region is potentially useful for the development of new photocatalysts for H2 production and photochemotherapeutics.The variation of the coordinated diimine ligand between bridging and bidentate chelating modes impacts the light absorbing and electronic properties of formamidinate-bridged Rh2II,II complexes. The two new complexes exhibit broad, strong absorption throughout the UV–visible range which can be useful for the efficient absorption of solar energy.

The tetradentate ligand, 2-(pyrid-2′-yl)-8-(1″,10″-phenanthrolin-2″-yl)-quinoline (ppq) embodies a quaterpyridine backbone but with the quinoline C8 providing an additional sp2 center separating the two bipyridine-like subunits. Thus, the four pyridine rings of ppq present a neutral, square planar host that is well suited to first-row transition metals. When reacted with FeCl3, a μ-oxo-bridged dimer is formed having a water bound to an axial metal site. A similar metal-binding environment is presented by a bis-phenanthroline amine (dpa) which forms a 1:1 complex with FeCl3. Both structures are verified by X-ray analysis. While the FeIII(dpa) complex shows two reversible one-electron oxidation waves, the FeIII(ppq) complex shows a clear two-electron oxidation associated with the process H2O–FeIIIFeIII → H2O–FeIVFeIV → O═FeVFeIII. Subsequent disproportionation to an Fe═O species is suggested. When the FeIII(ppq) complex is exposed to a large excess of the sacrificial electron-acceptor ceric ammonium nitrate at pH 1, copious amounts of oxygen are evolved immediately with a turnover frequency (TOF) = 7920 h–1. Under the same conditions the mononuclear FeIII(dpa) complex also evolves oxygen with TOF = 842 h−1.

A series of tetradentate 2,2′:6′,2″:6″,2‴-quaterpyridine-type ligands related to ppq (ppq = 8-(1″,10″-phenanthrol-2″-yl)-2-(pyrid-2′-yl)quinoline) have been synthesized. One ligand replaces the 1,10-phenanthroline (phen) moiety of ppq with 2,2′-bipyridine and the other two ligands have a 3,3′-polymethylene subunit bridging the quinoline and pyridine. The structural result is that both the planarity and flexibility of the ligand are modified. Co(II) complexes are prepared and characterized by ultraviolet–visible light (UV-vis) and mass spectroscopy, cyclic voltammetry, and X-ray analysis. The light-driven H2-evolving activity of these Co complexes was evaluated under homogeneous aqueous conditions using [Ru(bpy)3]2+ as the photosensitizer, ascorbic acid as a sacrificial electron donor, and a blue light-emitting diode (LED) as the light source. At pH 4.5, all three complexes plus [Co(ppq)Cl2] showed the fastest rate, with the dimethylene-bridged system giving the highest turnover frequency (2125 h–1). Cyclic voltammograms showed a significant catalytic current for H2 production in both aqueous buffer and H2O/DMF medium. Combined experimental and theoretical study suggest a formal Co(II)-hydride species as a key intermediate that triggers H2 generation. Spin density analysis shows involvement of the tetradentate ligand in the redox sequence from the initial Co(II) state to the Co(II)-hydride intermediate. How the ligand scaffold influences the catalytic activity and stability of catalysts is discussed, in terms of the rigidity and differences in conjugation for this series of ligands.

An approximately planar tetradentate polypyridine ligand, 8-(1″,10″-phenanthrol-2″-yl)-2-(pyrid-2′-yl)quinoline (ppq), has been prepared by two sequential Friedländer condensations. The ligand readily accommodates Co(II) bearing two axial chlorides, and the resulting complex is reasonably soluble in water. In DMF the complex shows three well-behaved redox waves in the window of 0 to −1.4 V (vs SHE). However in pH 7 buffer the third wave is obscured by a catalytic current at −0.95 V, indicating hydrogen production that appears to involve a proton-coupled electron-transfer event. The complex [Co(ppq)Cl2] (6) in pH 4 aqueous solution, together with [Ru(bpy)3]Cl2 and ascorbic acid as a sacrificial electron donor, in the presence of blue light (λmax = 469 nm) produces hydrogen with an initial TOF = 586 h–1.

A series of seven dyad molecules have been prepared utilizing a [Ru(tpy)(NN)I]+ type oxidation catalyst (NN = 2,5-di(pyrid-2′-yl) pyrazine (1), 2,5-di-(1′,8′-dinaphthyrid-2′-yl) pyrazine (2), or 4,6-di-(1′,8′-dinaphthyrid-2′-yl) pyrimidine (3). The other bidentate site of the bridging ligand was coordinated with 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), or a substituted derivative. These dinuclear complexes were characterized by their 1H NMR spectra paying special attention to protons held in the vicinity of the electronegative iodide. In one case, 10a, the complex was also analyzed by single crystal X-ray analysis. The electronic absorption spectra of all the complexes were measured and reported as well as emission properties for the sensitizers. Oxidation and reduction potentials were measured and excited state redox properties were calculated from this data. Turnover numbers, initial rates, and induction periods for oxygen production in the presence of a blue LED light and sodium persulfate as a sacrificial oxidant were measured. Similar experiments were run without irradiation. Dyad performance correlated well with the difference between the excited state reduction potential of the photosensitizer and the ground state oxidation potential of the water oxidation dyad. The most active system was one having 5,6-dibromophen as the auxiliary ligand, and the least active system was the one having 4,4′-dimethylbpy as the auxiliary ligand.

In this study, ultrafast optical transient absorption and X-ray transient absorption (XTA) spectroscopy are used to probe the excited-state dynamics and structural evolution of copper(I) bicinchoninic acid ([Cu(I)(BCA)2]+), which has similar but less frequently studied biquinoline-based ligands compared to phenanthroline-based complexes. The optical transient absorption measurements performed on the complex in a series of polar protic solvents demonstrate a strong solvent dependency for the excited lifetime, which ranges from approximately 40 ps in water to over 300 ps in 2-methoxyethanol. The XTA experiments showed a reduction of the prominent 1s → 4pz edge peak in the excited-state X-ray absorption near-edge structure (XANES) spectrum, which is indicative of an interaction with a fifth ligand, most likely the solvent. Analysis of the extended X-ray absorption fine structure (EXAFS) spectrum shows a shortening of the metal–ligand bond in the excited state and an increase in the coordination number for the Cu(II) metal center. A flattened structure is supported by DFT calculations that show that the system relaxes into a flattened geometry with a lowest-energy triplet state that has a dipole-forbidden transition to the ground state. While the short excited-state lifetime relative to previously studied Cu(I) diimine complexes could be attributed to this dark triplet state, the strong solvent dependency and the reduction of the 1s → 4pz peak in the XTA data suggest that solvent interaction could also play a role. This detailed study of the dynamics in different solvents provides guidance for modulating excited-state pathways and lifetimes through structural factors such as solvent accessibility to fulfill the excited-state property requirements for efficient light harvesting and electron injection.

Members of a family of Ru(II)-appended pyrenylethynylene dyads were synthesized, characterized according to their photophysical and photobiological properties, and evaluated for their collective potential as photosensitizers for metal–organic photodynamic therapy. The dyads in this series possess lowest-lying 3IL-based excited states with lifetimes that can be tuned from 22 to 270 μs in fluid solution and from 44 to 3440 μs in glass at 77 K. To our knowledge, these excited-state lifetimes are the longest reported for Ru(II)-based dyads containing only one organic chromophore and lacking terminal diimine groups. These excited states proved to be extremely sensitive to trace amounts of oxygen, owing to their long lifetimes and very low radiative rates. Herein, we demonstrate that 3IL states of this nature are potent photodynamic agents, exhibiting the largest photocytotoxicity indices reported to date with nanomolar light cytotoxicities at very short drug-to-light intervals. Importantly, these new agents are robust enough to maintain submicromolar PDT in pigmented metastatic melanoma cells, where the presence of melanin in combination with low oxygen tension is known to compromise PDT. This activity underscores the potential of metal–organic PDT as an alternate treatment strategy for challenging environments such as malignant melanoma.

Some metal ion complexing properties of DPP (2,9-Di(pyrid-2-yl)-1,10-phenanthroline) are reported with a variety of Ln(III) (Lanthanide(III)) ions and alkali earth metal ions, as well as the uranyl(VI) cation. The intense π–π* transitions in the absorption spectra of aqueous solutions of 10–5 M DPP were monitored as a function of pH and metal ion concentration to determine formation constants of the alkali-earth metal ions and Ln(III) (Ln = lanthanide) ions. It was found that log K1(DPP) for the Ln(III) ions has a peak at Ln(III) = Sm(III) in a plot of log K1 versus 1/r+ (r+ = ionic radius for 8-coordination). For Ln(III) ions larger than Sm(III), there is a steady rise in log K1 from La(III) to Sm(III), while for Ln(III) ions smaller than Sm(III), log K1 decreases slightly to the smallest Ln(III) ion, Lu(III). This pattern of variation of log K1 with varying size of Ln(III) ion was analyzed using MM (molecular mechanics) and DFT (density functional theory) calculations. Values of strain energy (∑U) were calculated for the [Ln(DPP)(H2O)5]3+ and [Ln(qpy)(H2O)5]3+ (qpy = quaterpyrdine) complexes of all the Ln(III) ions. The ideal M–N bond lengths used for the Ln(III) ions were the average of those found in the CSD (Cambridge Structural Database) for the complexes of each of the Ln(III) ions with polypyridyl ligands. Similarly, the ideal M–O bond lengths were those for complexes of the Ln(III) ions with coordinated aqua ligands in the CSD. The MM calculations suggested that in a plot of ∑U versus ideal M–N length, a minimum in ∑U occurred at Pm(III), adjacent in the series to Sm(III). The significance of this result is that (1) MM calculations suggest that a similar metal ion size preference will occur for all polypyridyl-type ligands, including those containing triazine groups, that are being developed as solvent extractants in the separation of Am(III) and Ln(III) ions in the treatment of nuclear waste, and (2) Am(III) is very close in M–N bond lengths to Pm(III), so that an important aspect of the selectivity of polypyridyl type ligands for Am(III) will depend on the above metal ion size-based selectivity. The selectivity patterns of DPP with the alkali-earth metal ions shows a similar preference for Ca(II), which has the most appropriate M–N lengths. The structures of DPP complexes of Zn(II) and Bi(III), as representative of a small and of a large metal ion respectively, are reported. [Zn(DPP)2](ClO4)2 (triclinic, P1, R = 0.0507) has a six-coordinate Zn(II), with each of the two DPP ligands having one noncoordinated pyridyl group appearing to be π-stacked on the central aromatic ring of the other DPP ligand. [Bi(DPP)(H2O)2(ClO4)2](ClO4) (triclinic, P1, R = 0.0709) has an eight-coordinate Bi, with the coordination sphere composed of the four N donors of the DPP ligand, two coordinated water molecules, and the O donors of two unidentate perchlorates. As is usually the case with Bi(III), there is a gap in the coordination sphere that appears to be the position of a lone pair of electrons on the other side of the Bi from the DPP ligand. The Bi-L bonds become relatively longer as one moves from the side of the Bi containg the DPP to the side where the lone pair is thought to be situated. A DFT analysis of [Ln(tpy)(H2O)n]3+ and [Ln(DPP)(H2O)5]3+ complexes is reported. The structures predicted by DFT are shown to match very well with the literature crystal structures for the [Ln(tpy)(H2O)n]3+ with Ln = La and n = 6, and Ln = Lu with n = 5. This then gives one confidence that the structures for the DPP complexes generated by DFT are accurate. The structures generated by DFT for the [Ln(DPP)(H2O)5]3+ complexes are shown to agree very well with those generated by MM, giving one confidence in the accuracy of the latter. An analysis of the DFT and MM structures shows the decreasing O--O nonbonded distances as one progresses from La to Lu, with these distances being much less than the sum of the van der Waals radii for the smaller Ln(III) ions. The effect that such short O--O nonbonded distances has on thermodynamic complex stability and coordination number is then discussed.

The complexation of 2,9-dicarboxy-1,10-phenanthroline (DPA) with [Ru(tpy)Cl3] (tpy = 2,2′;6,2″-terpyridine) provides a six-coordinate species in which one carboxyl group of DPA is not bound to the Ru(II) center. A more soluble tri-t-butyl tpy analogue is also prepared. Upon oxidation, neither species shows evidence for intramolecular trapping of a seven-coordinate intermediate. The role of the tpy ligand is revealed by the preparation of [Ru(tpy)(phenq)]2+ (phenq = 2-(quinol-8′-yl)-1,10-phenanthroline) that behaves as an active water oxidation catalyst (TON = 334). This activity is explained by the expanded coordination geometry of the phenq ligand that can form a six-membered chelate ring that better accommodates the linear arrangement of axial ligands required for optimal pentagonal bipyramid geometry. When a 1,8-naphthyidine ring is substituted for each of the two peripheral pyridine rings on tpy, increased crowding in the vicinity of the metal center impedes acquisition of the prerequisite reaction geometry.

Two mononuclear Ru(II) complexes, [Ru(ttbt)(pynap)(I)]I and [Ru(tpy)(Mepy)2(I)]I (tpy = 2,2′;6,2″-terpyridine; ttbt = 4,4′,4″-tri-tert-butyltpy; pynap = 2-(pyrid-2′-yl)-1,8-naphthyridine; and Mepy = 4-methylpyridine), are effective catalysts for the oxidation of water. This oxidation can be driven by a blue (λmax = 472 nm) LED light source using [Ru(bpy)3]Cl2 (bpy = 2,2′-bipyridine) as the photosensitizer. Sodium persulfate acts as a sacrificial electron acceptor to oxidize the photosensitizer that in turn drives the catalysis. The presence of all four components, light, photosensitizer, sodium persulfate, and catalyst, are required for water oxidation. A dyad assembly has been prepared using a pyrazine-based linker to join a photosensitizer and catalyst moiety. Irradiation of this intramolecular system with blue light produces oxygen with a higher turnover number than the analogous intermolecular component system under the same conditions.

The reaction of 2,9-di(pyrid-2′-yl)-1,10-phenanthroline (dpp) with [RuCl3·3H2O] or [Ru(DMSO)4Cl2] provides the reagent trans-[RuII(dpp)Cl2] in yields of 98 and 89%, respectively. This reagent reacts with monodentate ligands L to replace the two axial chlorides, affording reasonable yields of a ruthenium(II) complex with dpp bound tetradentate in the equatorial plane. The photophysical and electrochemical properties of the tetradentate complexes are strongly influenced by the axial ligands with electron-donating character to stabilize the ruthenium(III) state, shifting the metal-to-ligand charge-transfer absorption to lower energy and decreasing the oxidation potential. When the precursor trans-[RuII(dpp)Cl2] reacts with a bidentate (2,2′-bipyridine), tridentate (2,2′;6,2″-terpyridine), or tetradentate (itself) ligand, a peripheral pyridine on dpp is displaced such that dpp binds as a tridentate. This situation is illustrated by an X-ray analysis of [Ru(dpp)(bpy)Cl](PF6).

Some metal-ion-complexing properties of the ligand 2-(pyrid-2′-yl)-1,10-phenanthroline (MPP) are reported. MPP is of interest in that it is a more preorganized version of 2,2′;6,2″-terpyridine (tpy). Protonation constants (pK1 = 4.60; pK2 = 3.35) for MPP were determined by monitoring the intense π–π* transitions of 2 × 10–5 M solutions of the ligand as a function of the pH at an ionic strength of 0 and 25 °C. Formation constants (log K1) at an ionic strength of 0 and 25 °C were obtained by monitoring the π–π* transitions of MPP titrated with solutions of the metal ion, or 1:1 solutions of MPP and the metal ion were titrated with acid. Large metal ions such as CaII or LaIII showed increases of log K1 of about 1.5 log units compared to that of tpy. Small metal ions such as ZnII and NiII showed little increase in log K1 for MPP compared to the tpy complexes, which is attributed to the presence of five-membered chelate rings in the MPP complexes, which favor large metal ions. The structure of [Cd(MPP)(H2O)(NO3)2] (1) is reported: monoclinic, P21/c, a = 7.4940(13) Å, b = 12.165(2) Å, c = 20.557(4) Å, β = 96.271(7)°, V = 1864.67(9) Å3, Z = 4, and final R = 0.0786. The Cd in 1 is seven-coordinate, comprising the three donor atoms of MPP, a coordinated water, a monodentate, and a bidentate NO3–. CdII is a fairly large metal ion, with r+ = 0.96 Å, slightly too small for coordination with MPP. The effect of this size matching in terms of the structure is discussed. Fluorescence spectra of 2 × 10–7 M MPP in aqueous solution are reported. The nonprotonated MPP ligand fluoresces only weakly, which is attributed to a photoinduced-electron-transfer effect. The chelation-enhanced-fluorescence (CHEF) effect induced by some metal ions is presented, and the trend of the CHEF effect, which is CaII > ZnII > CdII ∼ LaIII > HgII, is discussed in terms of factors that control the CHEF effect, such as the heavy-atom effect.

Selective reduction of 2-nitro-3-methoxybenzaldehyde provides 2-amino-3-methoxybenzaldehyde that undergoes the Friedländer condensation with a variety of acetyl-substituted derivatives of pyridine and 1,10-phenanthroline. After cleavage of the methyl ether, the resulting polydentate analogues of 8-hydroxyquinoline are excellent ligands for ruthenium. The resulting oxidation state of the metal center depends on the anionic character of the ligands. The presence of two electron donating anionic ligands results in a Ru(III) complex as evidenced by paramagnetic NMR behavior. The electronic absorption and redox properties of the complexes were measured and found to be consistent with the anionic character of the 8-HQ moieties. A planar pentadentate ligand provides two Ru–O and two Ru–N bonds in the equatorial plane. An X-ray structure shows that the central pyridine of the ligand is oriented toward the metal but held at a distance of 2.44 Å.

DPA (dipyrido[4,3-b;5,6-b]acridine) may be considered as a tridentate homologue of phen (1,10-phenanthroline). In this paper some of the metal ion complexing properties of DPA in aqueous solution are reported. Using UV−visible spectroscopy to follow the intense π−π* transitions of DPA as a function of pH gave protonation constants at ionic strength (μ) = 0 and 25 °C of pK1 = 4.57(3) and pK2 = 2.90(3). Titration of 10−5 M solutions of DPA with a variety of metal ions gave log K1 values as follows: Zn(II), 7.9(1); Cd(II), 8.1(1); Pb(II), 8.3(1); La(III), 5.23(7); Gd(III), 5.7(1); Ca(II), 3.68; all at 25 °C and μ = 0. Log K1 values at μ = 0.1 were obtained for Mg(II), 0.7(1); Sr(II), 2.20(1); Ba(II), 1.5(1). The log K1 values show that the high level of preorganization of DPA leads to complexes 3 log units more stable than the corresponding terpyridyl complexes for large metal ions such as La(III) or Ca(II), but that for small metal ions such as Mg(II) and Zn(II) such stabilization is minimal. Molecular mechanics calculations (MM) are used to show that the best-fit M−N length for coordination with DPA is 2.60 Å, accounting for the high stability of Ca(II) or La(III) complexes of DPA, which are found to have close to this M−N bond length in their phen complexes.

The pH-dependent mechanism of the reduction of the nicotinamide adenine dinucleotide (NADH) model complex [Ru(bpy)2(5)]2+ (5 = 3-(pyrid-2′-yl)-4-azaacridine) was compared to the mechanism of the previously studied geometric isomer [Ru(bpy)2(pbn)]2+ (pbn = 2-(pyrid-2′-yl)-1-azaacridine, previously referred to as 2-(pyrid-2′-yl)-benzo[b]-1,5-naphthyridine) in aqueous media. The exposure of [Ru(bpy)2(5)]2+ to CO2•− leads to the formation of the one-electron reduced species (k = 4.4 × 109 M−1 s−1). At pH < 11.2, the one-electron reduced species can be protonated, k = 2.6 × 104 s−1 in D2O. Formation of a C−C bonded dimer is observed across the pH range of 5−13 (k = 4.5 × 108 M−1 s−1). At pH < 11, two protonated radical species react to form a stable C−C bonded dimer. At pH > 11, dimerization of two one-electron reduced species is followed by disproportionation to one equivalent starting complex [Ru(bpy)2(5)]2+ and one equivalent [Ru(bpy)2(5HH)]2+. The structural difference between [Ru(bpy)2(pbn)]2+ and [Ru(bpy)2(5)]2+ dictates the mechanism and product formation in aqueous medium. The exchange of the nitrogen and carbon atoms on the azaacridine ligands alters the accessibility of the dimerization reactive site, thereby changing the mechanism and the product formation for the reduction of the [Ru(bpy)2(5)]2+ compound.

Several mononuclear Ru(II) dyads possessing 1,10-phenanthroline-appended pyrenylethynylene ligands were synthesized, characterized, and evaluated for their potential in photobiological applications such as photodynamic therapy (PDT). These complexes interact with DNA via intercalation and photocleave DNA in vitro at submicromolar concentrations when irradiated with visible light (λirr ≥ 400 nm). Such properties are remarkably sensitive to the position of the ethynylpyrenyl substituent on the 1,10-phenanthroline ring, with 3-substitution showing the strongest binding under all conditions and causing the most deleterious DNA damage. Both dyads photocleave DNA under hypoxic conditions, and this photoactivity translates well to cytotoxicity and photocytotoxicity models using human leukemia cells, where the 5- and 3-substituted dyads show photocytotoxicity at 5−10 μM and 10−20 μM, respectively, with minimal, or essentially no, dark toxicity at these concentrations. This lack of dark cytotoxicity at concentrations where significant photoactivity is observed emphasizes that agents with strong intercalating units, previously thought to be too toxic for phototherapeutic applications, should not be excluded from the arsenal of potential photochemotherapeutic agents under investigation.

A series of six tetradentate polypyridine-type ligands (L) have been used to prepare the corresponding Eu(III) complexes [Eu(L)2(S)]n+ (n = 2, 3) where S = H2O or CF3SO3−. Two of the ligands, 2,9-di(pyrid-2′-yl)-1,10-phenanthroline (4) and its dipyridophenazine analogue (6) are symmetrical around a central phenanthroline ring. The other four ligands are 2,2′-bi-1,10-phenanthroline and its 3,3′-di-, tri-, and tetramethylene-bridged analogues (5a-d) whose conformations are governed by the length of the polymethylene bridge. 1H NMR and X-ray analysis indicate that all of the complexes have a C2v symmetry. The biphenanthroline series shows a strong correlation of the conjugation between the two halves of the ligand, as governed by the bridge, with the absorption and emission properties of the Eu(III) complex. The complex having the most distorted, tetramethylene-bridged ligand exhibits a weak, high energy π−π* absorption and low sensitization efficiency. The luminescence decays are monoexponential for complexes of 4 and either monoexponential or biexponential for the complexes of 5 depending on its solution concentration and the length of the bridge. The complexes of 4 exhibit much longer lifetime, higher overall quantum yield, and higher sensitization efficiency than complexes of 5 while the complex of 6 emits very weakly. The Eu(5D0) lifetime for [Eu(4)2(H2O)](ClO4)3 is shorter than for [Eu(4)2(CF3SO3)](CF3SO3)2, reflecting the effect of the coordinated water. The complexes are examined for stability in the presence of water and found to retain most of their luminescent properties even in the presence of a large excess of water.

Density functional theory calculations were performed on a series of six ruthenium complexes possessing tridentate ligands: [Ru(tpy)2]2+ (1; tpy = [2,2′;6′,2′′]-terpyridine), [Ru(tpy)(pydppx)]2+ (2; pydppx = 3-(pyrid-2′-yl)-11,12-dimethyldipyrido[3,2-a: 2′,3′-c]phenazine), [Ru(pydppx)2]2+ (3), [Ru(tpy)(pydppn)]2+ (4; pydppn = 3-(pyrid-2′-yl)-4,5,9,16-tetraazadibenzo[a,c]naphthacene), [Ru(pydppn)2]2+ (5), and [Ru(tpy)(pydbn)]+ (6; pyHdbn = 3-pyrid-2′-yl-4,9,16-triazadibenzo[a,c]naphthacene). The calculations were compared to experimental data, including electrochemistry and electronic absorption spectra. The theoretical results reveal that the lowest-lying singlet and triplet states in 4 and 5 are pydppn-based ππ* in character, which are remarkably different from the lowest-lying metal-to-ligand charge transfer (MLCT) states in 1−3. The calculated lowest triplet states in 4 and 5 are consistent with the 3ππ* states observed experimentally. However, although the extended π-system of pydbn− is similar to that of pydppn, the HOMO of 6 lies above those of 4 and 5, resulting in strikingly different spectroscopic properties. Calculations show that the lowest triplet excited state of 6 is a combination of 3MLCT and 3ππ*. This work demonstrates that the electronic structure of the tridentate ligand has a pronounced effect on the photophysical properties of ruthenium(II) complexes and that DFT and TD-DFT methods are a useful tool that can be used to predict photophysical and redox properties of transition metal complexes.

Ru(II) complexes possessing new tridentate ligands with extended π systems, pydppx (3-(pyrid-2′-yl)-11,12-dimethyl-dipyrido[3,2-a:2′,3′-c]phenazine) and pydppn (3-(pyrid-2′-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene), were synthesized and characterized. The investigation of the photophysical properties of the series [Ru(tpy)n(L)2−n]2+ (L = pydppx, pydppn, n = 0−2) reveals markedly different excited state behavior among the complexes. The Ru(II) complexes possessing the pydppx ligand are similar to the pydppz (3-(pyrid-2′-yl)dipyrido[3,2-a:2′,3′-c]phenazine) systems, with a lowest energy metal-to-ligand charge transfer excited state with lifetimes of 1−4 ns. In contrast, the lowest energy excited state in the [Ru(tpy)n(pydppn)2−n]2+ (n = 0, 1) complexes is a ligand-centered 3ππ* localized on the pydppn ligand with lifetimes of ∼20 μs. The [Ru(tpy)n(pydppn)2−n]2+ (n = 0, 1) complexes are able to generate 1O2 with ∼100% efficiency. Both [Ru(tpy)(pydppn)]2+ and [Ru(pydppn)2]2+ bind to DNA, however, the former exhibits a ∼10-fold greater DNA binding constant than the latter. Efficient DNA photocleavage is observed for [Ru(tpy)(pydppn)]2+, owing to its ability to photosensitize the production of 1O2, which can mediate the reactivity. Such high quantum yields of 1O2 photosensitization of transition metal complexes may be useful in the design of new systems with long-lived excited states for photodynamic therapy.

The 1,5-naphthyridine (1,5-nap) molecule has been elaborated into a series of new bidentate and tridentate ligands using Stille coupling or Friedländer condensation methodologies. Thus 2-(tri-n-butylstannyl)pyridine was coupled with 2-chloro, 4-chloro, or 2,6-dichloro 1,5-nap to prepare the analogous bidentate ligands. The condensation of 2-aminonicotinaldehyde or 8-amino-7-quinolinecarbaldehyde with a variety of acetyl derivatives of 1,5-nap produced ligands incorporating 1,8-naphthyrid-2-yl or 1,10-phenanthrolin-2-yl groups, respectively. These ligands were treated with either [Ru(bpy-d8)2Cl2] or [Ru(tpy)Cl3] to prepare the corresponding heteroleptic mono- and dinuclear Ru(II) complexes. The NMR spectra of these complexes were simplified by the use of bpy-d8 as an auxiliary ligand, allowing straightforward product identification. The long wavelength absorption of both the ligands and the complexes are shifted to lower energy with increasing delocalization or the incorporation of a second metal. Protonation of a remote uncomplexed nitrogen leads to the red-shifting of the absorption band. The degree of communication between the metal centers in dinuclear complexes can be evaluated from the comproportionation constant measured by electrochemistry. When compared to the pyrazine linker, communication through the 1,5-nap linker appears to be somewhat less efficient.

Octahedral ruthenium complexes, capable of photodynamic singlet oxygen production at near 100% efficiency, were shown to cause light-dependent covalent crosslinking of p53 and PCNA subunits in mammalian cells and cell lysates. Azide, a singlet oxygen quencher, greatly reduced the p53 photocrosslinking, consistent with the idea that singlet oxygen is the reactive oxygen species involved in p53 photocrosslinking. A photodynamically inactive ruthenium complex, [Ru(tpy)2]2+ (tpy = [2,2′;6′,2′′]-terpyridine), had no effect on p53 or PCNA photocrosslinking. Photodynamic damage to p53 has particular relevance since p53 status is an important determinant of phototoxicity and the effectiveness of photodynamic cancer therapy. The two photodynamic complexes studied, [Ru(tpy)(pydppn)]2+, where pydppn = (3-(pyrid-2′-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene, and [Ru(pydppn)2]2+, differed in their efficiency of p53 and PCNA photocrosslinking in cells, but showed similar efficiency of photocrosslinking in cell lysates, suggesting that they differ in their ability to enter cells. Photocrosslinking of PCNA by [Ru(tpy)(pydppn)]2+ increased linearly with concentration, time of uptake, or light exposure. Both [Ru(tpy)(pydppn)]2+ and [Ru(pydppn)2]2+ caused photodynamic protein-DNA crosslinking in cells, but [Ru(tpy)(pydppn)]2+ was more efficient. The efficiency of photodynamic protein-DNA crosslinking by [Ru(tpy)(pydppn)]2+ in cells increased with increasing levels of photodynamic damage. Photodynamic damage by [Ru(tpy)(pydppn)]2+ caused inhibition of DNA replication in a classical biphasic response, suggesting that DNA damage signaling and cell cycle checkpoint pathways were still operative after significant damage to nuclear proteins.

Two series of mononuclear ruthenium(II) complexes involving polypyridine-type ligands have been prepared, and their ability to act as catalysts for water oxidation has been examined. One series is of the type [Ru(tpy)(NN)Cl](PF6) (tpy = 2,2′; 6,2′′-terpyridine), where NN is one of 12 different bidentate ligands, and the other series includes various combinations of 4-picoline, 2,2′-bipyridine (bpy), and tpy as well as the tetradentate 2,9-dipyrid-2′-yl-1,10-phenanthroline (dpp). The electronic absorption and redox data for these compounds have been measured and reported. The long-wavelength metal-to-ligand charge-transfer absorption and the first oxidation and reduction potentials are found to be consistent with the structure of the complex. Of the 23 complexes, 14 catalyze water oxidation and all of these contain a tpy or dpp. Kinetic measurements indicate a first-order reaction and together with a catalyst recovery experiment argue against the involvement of RuO2. A tentative mechanism is proposed that involves a seven-coordinate RuVI═O species that is attacked by water to form the critical O−O bond. Density functional theory calculations, which support the proposed mechanism, are performed.

An approach is developed for the four-electron oxidation of water to provide dioxygen that involves the juxtaposition of two Ru(II) centers such that a metal-bound water molecule might interact with one or both of the metals. The key element in this approach is an appropriate bridging ligand that will hold the metal assembly intact through the full redox cycle. Various synthetic approaches to such ligands are described with the ultimate preparation of four closely related bis-tridentate polypyridine-type systems in which the bridging and distal portions of the ligand are varied. All of these ligands self-assemble with two Ru(II) centers bridged by a Cl ion in the equatorial plane and four axial monodentate substituted pyridines or N-methylimidazoles to form the well-organized catalyst complexes. These complexes are characterized by their distinctive 1H NMR spectra as well as an X-ray structure of one representative species. The photophysical and electrochemical features of these complexes are consistent with electronegativity and delocalization effects in the equatorial and axial ligands. Of the 14 complexes studied, all but 2, which each contain four axial N-methylimidazole ligands, catalyze the decomposition of water in the presence of excess Ce(IV) as a sacrificial oxidant at pH = 1. Both the rates of oxygen evolution and the catalyst turnover numbers (TNs) are measured. For the active catalysts, the relative rates vary from 1 to 51 and the TNs measure from 80 to 689. Various analytical methods for making these measurements are discussed, and it is found that there is an approximately linear relationship between the rate and TN. Future work will involve optimization of these systems and studies aimed at a better understanding of the mechanism.

The ligand 2-(8′-quinolinyl)-1,10-phenanthroline (1) was prepared in 79% yield by the Friedländer condensation of 8-amino-7-quinolinecarbaldehyde and 8-acetylquinoline. The complex [Pt(1)Cl]+ was prepared and compared with the isomeric 2-(2′-quinolinyl)-1,10-phenanthroline (2) complex. An X-ray analysis indicated that the six-membered chelate ring in the tridentate complex resulted in a relief of angle strain as well as some non-planarity in the bound ligand 1. The control system for photophysical studies is [Pt(3)Cl]+ where 3 denotes 2-(2′-pyridyl)-1,10-phenanthroline. Relative to the complex of 3, in dichloromethane solution [Pt(1)Cl]+ exhibits noticeably higher energy charge-transfer absorption but slightly lower energy emission. The gap between the onset of absorption and emission is larger because the emission from [Pt(1)Cl]+ originates from a triplet excited state with substantial intra-ligand character. At room temperature in deoxygenated dichloromethane, [Pt(1)Cl]+ has an excited-state lifetime of 310 ns vs. 230 ns for [Pt(3)Cl]+. Within the series, [Pt(1)Cl]+ also exhibits the largest activation barrier for thermally induced quenching at 2730 cm−1 in fluid dichloromethane solution. However, the barrier is only about 50% larger than that found for [Pt(3)Cl]+. There is reduced ring strain in [Pt(1)Cl]+, but inter-ligand steric interactions weaken the ligand field.

Dual fluorescence is observed in water and water-containing solutions of 1H-pyrrolo[3,2-h]quinoline and dipyrido[2,3-a:3′,2′-i]carbazole. The low energy band is assigned to a product of excited state double proton transfer reaction, occurring in cyclic 1:1 complexes with water. Such complexes constitute only a small fraction of the ground state population. The majority of water complexes are not prone to phototautomerization, but are deactivated via a process that is not efficient in a non-hydrogen-bonded chromophore.

A family of 28 mononuclear Ru(II) complexes have been prepared and characterized by 1H NMR, electronic absorption, and cyclic voltammetry. These complexes are studied as catalysts for water oxidation. All the catalysts possess one tridentate ligand, closely related to 2,2′;6,2″-terpyridine (tpy) and may be divided into two basic types. In the type-1 catalyst, the three remaining coordination sites are occupied by a bidentate closely related to 2,2′-bipyridine (bpy) and a monodentate halogen (Br, Cl, or I) or water molecule. In the type-2 catalyst, the three remaining coordination sites are occupied by two axial 4-picoline molecules and an equatorial halogen or water. In general the type-2 catalysts are more reactive than the type-1. The type-2 iodo-catalyst shows first-order behavior and, unlike the bromo- and chloro-catalysts, does not require water–halogen exchange to show good activity. The importance of steric strain and hindrance around the metal center is examined. The introduction of three t-butyl groups at the 4, 4′, and 4″ positions of tpy sometimes improves catalyst activity, but the effect does not appear to be additive.

Octahedral ruthenium complexes, capable of photodynamic singlet oxygen production at near 100% efficiency, were shown to cause light-dependent covalent crosslinking of p53 and PCNA subunits in mammalian cells and cell lysates. Azide, a singlet oxygen quencher, greatly reduced the p53 photocrosslinking, consistent with the idea that singlet oxygen is the reactive oxygen species involved in p53 photocrosslinking. A photodynamically inactive ruthenium complex, [Ru(tpy)2]2+ (tpy = [2,2′;6′,2′′]-terpyridine), had no effect on p53 or PCNA photocrosslinking. Photodynamic damage to p53 has particular relevance since p53 status is an important determinant of phototoxicity and the effectiveness of photodynamic cancer therapy. The two photodynamic complexes studied, [Ru(tpy)(pydppn)]2+, where pydppn = (3-(pyrid-2′-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene, and [Ru(pydppn)2]2+, differed in their efficiency of p53 and PCNA photocrosslinking in cells, but showed similar efficiency of photocrosslinking in cell lysates, suggesting that they differ in their ability to enter cells. Photocrosslinking of PCNA by [Ru(tpy)(pydppn)]2+ increased linearly with concentration, time of uptake, or light exposure. Both [Ru(tpy)(pydppn)]2+ and [Ru(pydppn)2]2+ caused photodynamic protein-DNA crosslinking in cells, but [Ru(tpy)(pydppn)]2+ was more efficient. The efficiency of photodynamic protein-DNA crosslinking by [Ru(tpy)(pydppn)]2+ in cells increased with increasing levels of photodynamic damage. Photodynamic damage by [Ru(tpy)(pydppn)]2+ caused inhibition of DNA replication in a classical biphasic response, suggesting that DNA damage signaling and cell cycle checkpoint pathways were still operative after significant damage to nuclear proteins.