Photoelimination of nitrogen from cyclic azo alkanes. An exceptionally labile and an exceptionally reluctant diazabicyclo[2.2.2]octene

The photochemistry of an unusually reactive diazabicyclo[2.2.2]octene has been found to be extremely solvent and temperature dependent; an exceptionally stable diazabicyclo[2.2.2]octene has been found to undergo a novel fragmentation as a result of vapor phase photoexcitation.     

Intercalation is not required for DNA light-switch behavior

The DNA light-switch complex [Ru(bpy)2(tpphz)]2+ (1, bpy = 2,2'-bipyridine, tpphz = tetrapyrido[3,2-a:2',3'-c:3',2'-h:2',3'-j]phenazine) is luminescent when bound to DNA and in organic solvents and weakly emissive in water. To date, light-switch behavior by transition metal complexes has generally been regarded as confirmation of DNA intercalation. In contrast, the present work demonstrates that the nonintercalating bimetallic complex [(bpy)2Ru(tpphz)Ru(bpy)2]4+ (2) behaves as a DNA light-switch. Weak emission from the 3MLCT excited state of 2 is observed in water with lambda(em) = 623 nm (phi(em) = 1.4 x 10(-4)), and a red shift (lambda(em) = 702 nm) and 40-fold increase in intensity are observed upon addition of 100 microM calf thymus DNA (ct-DNA). Addition of increasing concentrations of 2 to 1 mM herring sperm DNA does not result in an increase in the viscosity of the solution, indicating that the complex is not an intercalator. Additionally, experiments were conducted to ensure that the emission enhancement did not arise from threading intercalation of the complex. The in situ generation of 2 intercalated between the base pairs of ct-DNA in a threading fashion, however, exhibits emission maximum at 685 nm, which is blue-shifted from that of surface-bound 2. DFT calculations show low-lying orbitals in 2 that are expected to exhibit nonemissive character when contributing to the MLCT state, in accord with the lower emission intensity observed for 2 relative to that for 1. To our knowledge, the present work is the first example of a nonintercalating light-switch metal complex, thus showing that light-switch behavior cannot be used exclusively as confirmation of intercalation.     

Pyrene excimer signaling molecular beacons for probing nucleic acids

Molecular beacon DNA probes, containing 1-4 pyrene monomers on the 5' end and the quencher DABCYL on the 3' end, were engineered and employed for real-time probing of DNA sequences. In the absence of a target sequence, the multiple-pyrene labeled molecular beacons (MBs) assumed a stem-closed conformation resulting in quenching of the pyrene excimer fluorescence. In the presence of target, the beacons switched to a stem-open conformation, which separated the pyrene label from the quencher molecule and generated an excimer emission signal proportional to the target concentration. Steady-state fluorescence assays resulted in a subnanomolar limit of detection in buffer, whereas time-resolved signaling enabled low-nanomolar target detection in cell-growth media. It was found that the excimer emission intensity could be scaled by increasing the number of pyrene monomers conjugated to the 5' terminal. Each additional pyrene monomer resulted in substantial increases in the excimer emission intensities, quantum yields, and excited-state lifetimes of the hybridized MBs. The long fluorescence lifetime ( approximately 40 ns), large Stokes shift (130 nm), and tunable intensity of the excimer make this multiple-pyrene moiety a useful alternative to traditional fluorophore labeling in nucleic acid probes.     

EPR characterization of gadolinium(III)-containing-PAMAM-dendrimers in the absence and in the presence of paramagnetic probes

Gd(III)-containing dendrimers are promising contrast agents for magnetic resonance imaging (MRI). An important issue in the effectiveness and toxicity of a Gd(III) based MRI contrast agent is knowledge of the relative locations and concentrations of Gd(III) in dendrimer drug delivery hosts. In order to provide experimental information on this issue, we have investigated the electron paramagnetic resonance (EPR) of a stable Gd(III) complex with diethylenetriaminepentaacetic acid (DTPA) in various polyammidoamine (PAMAM) dendrimers as a function of dendrimer generation (G2, G4, and G6), dendrimer core (ethylenediamine = EDA, and cystamine = cys), and dendrimer surface functionality (NH(2), 5-oxo-3-pyrrolidinecarboxylic acid methyl ester = pyr, and tris(hydroxymethyl) methylamine = tris). The dendrimer systems were investigated in the presence and absence of paramagnetic probes, that is, Cu(II) and nitroxide radicals (4-(trimethylammonium and dodecyl-dimethylammonium) 2,2,6,6-tetramethylpiperidine 1-oxyl bromide = CAT1 and CAT12, respectively). The analysis of the EPR spectra revealed anisotropic locations of Gd-DTPA inside the dendrimer. Computer analysis of the EPR spectra of the probes identified the interactions of the Gd-dendrimers with ions and organic molecules. The interaction between the probes and the dendrimer internal and external surface depends on the type of core, the composition of the external surface and the generation of the dendrimer. The negatively charged Gd-DTPA complex attracts the positively charged species and this provokes spin-spin interactions between Gd and the probes, which increases with a decrease in generation, mainly from G6 to G4, and with an increase in both the Gd-dendrimer concentration and the probe concentration. The cys core increases the internal volume and decreases the packing of the branches.     

Interactions of a hydrophobically modified polymer with oppositely charged surfactants

The interaction of a hydrophobically modified anionic polymer (PMAOVE) with a cationic surfactant (DTAB) was studied using a multi-technique approach: turbidity, surface tension, and viscosity measurements, as well as EPR (5-doxyl stearic acid) and fluorescence (pyrene) probe techniques were used. In the investigated pH range (4-10), the cationic surfactant headgroups interact with the anionic carboxylic groups of the polymer backbone. In addition, nonpolar interactions of the surfactant chains with the n-octyl chains of PMAOVE stabilize the PMAOVE-DTAB complexes. Charge neutralization of the anionic polymer by the cationic surfactant leads to precipitation of the PMAOVE-DTAB complex at a certain DTAB concentration range. Further addition of DTAB causes a charge reversal of the complex and, subsequently, resolubilization of the precipitate. At an acidic pH (pH = 4), a second precipitation was observed, which is probably caused by conformational changes in the PMAOVE-DTAB complex. This second precipitate can be resolubilized by further addition of surfactant. At a neutral and basic pH, this second precipitation is absent. EPR analysis indicates that the surfactants form an ordered structure at the extended polymer chain at a neutral and basic pH, whereas at an acidic pH, a less ordered surfactant layer is formed on the coiled polymer with more hydrophobic microdomains.     

Steric and Electronic Factors Associated with the Photoinduced Ligand Exchange of Bidentate Ligands Coordinated to Ru(II)

In an effort to create a molecule that can absorb low energy visible or near‐infrared light for photochemotherapy (PCT), the new complexes [Ru(biq)₂(dpb)](PF₆)₂ (1, biq = 2,2′‐biquinoline, dpb = 2,3‐bis(2‐pyridyl)benzoquinoxaline) and [(biq)₂Ru(dpb)Re(CO)₃Cl](PF₆)₂ (2) were synthesized and characterized. Complexes 1 and 2 were compared to [Ru(bpy)₂(dpb)](PF₆)₂ (3, bpy = 2,2′‐bipyridine) and [Ru(biq)₂(phen)](PF₆)₂ (4, phen = 1,10‐phenanthroline). Distortions around the metal and biq ligands were used to explain the exchange of one biq ligand in 4 upon irradiation. Complex 1, however, undergoes photoinduced dissociation of the dpb ligand rather than biq under analogous experimental conditions. Complex 3 is not photoactive, providing evidence that the biq ligands are crucial for ligand photodissociation in 1. The crystal structures of 1 and 4 are compared to explain the difference in photochemistry between the complexes. Complex 2 absorbs lower energy light than 1, but is photochemically inert although its crystal structure displays significant distortions. These results indicate that both the excited state electronic structure and steric bulk play key roles in bidentate photoinduced ligand dissociation. The present work also shows that it is possible to stabilize sterically hindered Ru(II) complexes by the addition of another metal, a property that may be useful for other applications.     

Theory and spectroscopy of an incarcerated quantum rotor: The infrared spectroscopy,inelastic neutron scattering and nuclear magnetic resonance of H2@C60 at cryogenic temperature

The supramolecular complex, H₂@C₆₀, represents a model of a quantum rotor in a nearly spherical box. In providing a real example of a quantum particle entrapped in a small space, the system cuts to the heart of many important and fundamental quantum mechanical issues. This review compares the predictions of theory of the quantum behaviour of H₂ incarcerated in C₆₀ with the results of infrared spectroscopy, inelastic neutron scattering and nuclear magnetic resonance. For H₂@C₆₀, each of these methods supports the quantization of translational motion of H₂ and the coupling of the translational motion with rotational motion and provides insights to the factors leading to breaking of the degeneracies of states expected for a purely spherical potential. Infrared spectroscopy and inelastic neutron scattering experiments at cryogenic temperatures provide direct evidence of a profound quantum mechanical feature of H₂ predicted by Heisenberg based on the Pauli principle: the existence of two nuclear spin isomers, a nuclear spin singlet (para-H₂) and a nuclear triplet (ortho-H₂). Nuclear magnetic resonance is capable of probing the local lattice environment of H₂@C₆₀ through analysis of the H₂ motional effects on the ortho-H₂ spin dynamics (para-H₂, the nuclear singlet state, is NMR silent). In this review we will show how the information obtained by three different forms of spectroscopy join together with quantum theory to create a complementary and consistent picture which strikingly shows the intrinsically quantum nature of H₂@C₆₀.     

Insight into the photoinduced ligand exchange reaction pathway of cis-[Rh2(μ-O2CCH3)2(CH3CN)6]2+ with a DNA model chelate

We previously showed that [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) binds to dsDNA only upon irradiation with visible light and that photolysis results in a 34-fold enhancement of its cytotoxicity toward Hs-27 human skin fibroblasts, making it potentially useful for photodynamic therapy (PDT). With the goal of gaining further insight on the photoinduced binding of DNA to the complex, we investigated by NMR spectroscopy the mechanism by which 2,2'-bipyridine (bpy), a model for biologically relevant bidentate nitrogen donor ligands, binds to [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) upon irradiation in D(2)O. The photochemical results are compared to the reactivity in the dark in D(2)O and CD(3)CN. The photolysis of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) with equimolar bpy solutions in D(2)O with visible light affords [Rh(2)(O(2)CCH(3))(2)(eq/eq-bpy)(CH(3)CN)(2)(D(2)O(ax))(2)](2+) (eq/eq) with the reaction reaching completion in ~8 h. Only vestiges of eq/eq are observed at the same time in the dark, however, and the reaction is ~20 times slower. Conversely, the dark reaction of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) with an equimolar amount of bpy in CD(3)CN affords [Rh(2)(O(2)CCH(3))(2)(η(1)-bpy(ax))(CH(3)CN)(5)](2+) (η(1)-bpy(ax)), which remains present even after 5 days of reaction. The photolysis results in D(2)O are consistent with the exchange of one equiv CH(3)CNeq for solvent, and the resulting species quickly reacting with bpy to generate eq/eq; the initial eq ligand dissociation is assisted by absorption of a photon, thus greatly enhancing the reaction rate. The photolytic reaction of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+):bpy in a 1:2 ratio in D(2)O affords the eq/eq and (eq/eq)(2) adducts. The observed differences in the reactivity in D(2)O vs CD(3)CN are explained by the relative ease of substitution of eq D(2)O vs CD(3)CN by the incoming bpy molecule. These results clearly highlight the importance of dissociation of an eq CH(3)CN molecule from the dirhodium core to attain high reactivity and underscore the importance of light for the reactivity of these compounds, which is essential for PDT agents.     

Effect of electronic structure on the photoinduced ligand exchange of Ru(II) polypyridine complexes

The series of complexes [Ru(bpy)(2)(L)](2+), where bpy = 2,2'-bipyridine and L = 3,6-dithiaoctane (bete, 1), 1,2-bis(phenylthio)ethane (bpte, 2), ethylenediamine (en, 3), and 1,2-dianilinoethane (dae, 4), were synthesized, and their photochemistry was investigated. Photolysis experiments show that the bisthioether ligands in 1 and 2 are more easily photosubstituted by chloride ions, bpy, and H(2)O than the corresponding diammine complexes in 3 and 4 to generate the bis-substituted products. Electronic structure calculations show that bond elongation in the lowest energy triplet metal-to-ligand charge transfer ((3)MLCT) state compared to the ground state is greater for complexes containing bisthioether ligands than those with coordinated bidentate nitrogen atoms. This elongation in the excited state is attributed to Ru-S π-bonding character of the highest occupied molecular orbitals, which is not present in the diamine complexes. In the Ru→bpy (3)MLCT state, the lower electron density on the metal-centered highest occupied molecular orbital (HOMO) weakens the Ru-S bond and results in the greater photoreactivity of 1 and 2 relative to that of 3 and 4. The more efficient photoinduced ligand exchange of the complexes possessing thioether ligands results in binding of 1 and 2 to DNA upon irradiation.     

Infrared spectroscopy of endohedral HD and D2 in C60

We report on the dynamics of two hydrogen isotopomers, D(2) and HD, trapped in the molecular cages of a fullerene C(60) molecule. We measured the infrared spectra and analyzed them using a spherical potential for a vibrating rotor. The potential, vibration-rotation Hamiltonian, and dipole moment parameters are compared with previously studied H(2)@C(60) parameters [M. Ge, U. Nagel, D. Hüvonen, T. R??m, S. Mamone, M. H. Levitt, M. Carravetta, Y. Murata, K. Komatsu, J. Y.-C. Chen, and N. J. Turro, J. Chem. Phys. 134, 054507 (2011)]. The isotropic part of the potential is similar for all three isotopomers. In HD@C(60), we observe mixing of the rotational states and an interference effect of the dipole moment terms due to the displacement of the HD rotation center from the fullerene cage center.