Lipid bilayers decorated with photosensitive ruthenium complexes

In this thesis the thermal- and photo-substitution behavior of polypyridyl ruthenium complexes is described at the surface of lipid bilayers and in homogeneous solutions. It is shown that the successive thermal binding and light-induced unbinding of the cationic ruthenium complex at the surface of the lipid bilayer requires negatively charged liposomes and ruthenium complexes containing moderately hindered N-N bidentate ligands. Our results in homogeneous solution show that changing the steric hindrance of the bidentate ligand influences both the photo- and thermal reactivities of these complexes, by altering the mechanism of the Ru-S bond formation. It is also shown that the Ru-S bond formation at the surface of negative lipid bilayers is faster than the same reaction in homogenous aqueous solutions, and a two-steps mechanism is proposed for the thermal coordination of ruthenium aqua complexes at membrane-embedded ligands. Furthermore, the application of ruthenium-functionalized liposomes in drug delivery is discussed. In vitro tests on cancer cell lines show that neutral liposomes functionalized with ruthenium compounds are more readily taken up by cancer cells than ruthenium-free liposomes. The liposome samples with ruthenium compounds are shown to be poorly cytotoxic in the dark. After light irradiation, the cytotoxicity increased at least up to five times for ruthenium complexes supported on non-PEGylated liposomes. Finally, the photoactivation of polypyridyl complexes with low-energy photons was studied using a photosensitization approach. A photosubstitution reaction was made faster upon yellow light irradiation than upon blue light irradiation by covalently linking a rhodamine B dye to the ruthenium complex.Metals in Catalysis, Biomimetics & Inorganic Material

Dielectric‐modulated biosensing with ultrahigh‐frequency‐operated graphene field‐effect transistors

Supramolecular & Biomaterials Chemistr

Ruthenium Polypyridyl Complexes Hopping at Anionic Lipid Bilayers through a Supramolecular Bond Sensitive to Visible Light

The new ruthenium complex [Ru(terpy)(dcbpy)(Hmte)](PF(6) )(2) ([2](PF(6) )(2) ; dcbpy=6,6'-dichloro-2,2'-bipyridine, terpy=2,2';6',2"-terpyridine, Hmte=2-(methylthio)ethanol) was synthesized. In the crystal structure, this complex is highly distorted, revealing steric congestion between dcbpy and Hmte. In water, [2](2+) forms spontaneously by reacting Hmte and the aqua complex [Ru(terpy)(dcbpy)(OH(2) )](2+) ([1](2+) ), with a second-order rate constant of 0.025 s(-1)  M(-1) at 25 °C. In the dark, the RuS bond of [2](2+) is thermally unstable and partially hydrolyzes; in fact, [1](2+) and [2](2+) are in an equilibrium characterized by an equilibrium constant K of 151 M(-1) . When exposed to visible light, the RuS bond is selectively broken to release [1](2+) , that is, the equilibrium is shifted by visible-light irradiation. The light-induced equilibrium shifts were repeated four times without major signs of degradation; the RuS coordination bond in [2](2+) can be described as a robust, light-sensitive, supramolecular bond in water. To demonstrate the potential of this system in supramolecular chemistry, a new thioether-cholesterol conjugate (4), which inserts into lipid bilayers through its cholesterol moiety and coordinates to ruthenium through its sulfur atom, was synthesized. Thioether-functionalized, anionic, dimyristoylphosphatidylglycerol (DMPG), lipid vesicles, to which aqua complex [1](2+) efficiently coordinates, were prepared. Upon exposure of the Ru-decorated vesicles to visible light, the RuS bond is selectively broken, thus releasing [1](2+) that stays at the water-bilayer interface. When the light is switched off, the metal complex spontaneously coordinates back to the membrane-embedded thioether ligands without a need to heat the system. This process was repeated four times at 35 °C, thus achieving light-triggered hopping of the metal complex at the water-bilayer interface

Targeted anion transporter delivery by coiled-coil driven membrane fusion

Supramolecular & Biomaterials Chemistr

Spontaneous Formation in the Dark, and Visible Light-Induced Cleavage, of a Ru–S Bond in Water: A Thermodynamic and Kinetic Study

In this work the thermal and photochemical reactivity of a series of ruthenium complexes [Ru­(terpy)­(N–N)­(L)]­(X)₂ (terpy = 2,2′;6′,2″-terpyridine, L = 2-(methylthio)­ethanol (Hmte) or water, and X is Cl^– or PF₆^–) with four different bidentate chelates N–N = bpy (2,2′-bipyridine), biq (2,2′-biquinoline), dcbpy (6,6′-dichloro-2,2′-bipyridine), or dmbpy (6,6′-dimethyl-2,2′-bipyridine), is described. For each chelate N–N the thermodynamic constant of the dark equilibrium between the aqua- and Hmte- complexes, the Hmte photosubstitution quantum yield, and the rate constants of the thermal interconversion between the aqua and Hmte complexes were measured at room temperature. By changing the steric hindrance and electronic properties of the spectator N–N ligand along the series bpy, biq, dcbpy, dmbpy the dark reactivity clearly shifts from a nonlabile equilibrium with N–N = bpy to a very labile thermal equilibrium with N–N = dmbpy. According to variable-temperature rate constant measurements in the dark near pH = 7 the activation enthalpies for the thermal substitution of H₂O by Hmte are comparable for all ruthenium complexes, whereas the activation entropies are negative for bpy and biq, and positive for dcbpy and dmbpy complexes. These data are indicative of a change in the substitution mechanism, being interchange associative with nonhindered or poorly hindered chelates (bpy, biq), and interchange dissociative for more bulky ligands (dcbpy, dmbpy). For the most labile dmbpy system, the thermal equilibrium is too fast to allow significant modification of the composition of the mixture using light, and for the nonhindered bpy complex the photosubstitution of Hmte by H₂O is possible but thermal binding of Hmte to the aqua complex does not occur at room temperature. By contrast, with N–N = biq or dcbpy the thermodynamic and kinetic parameters describing the formation and breakage of the Ru–S bond lie in a range where the bond forms spontaneously in the dark, but is efficiently cleaved under light irradiation. Thus, the ratio between the aqua and Hmte complex in solution can be efficiently controlled at room temperature using visible light irradiation

Spontaneous Formation in the Dark, and Visible Light-Induced Cleavage, of a Ru–S Bond in Water: A Thermodynamic and Kinetic Study

In this work the thermal and photochemical reactivity of a series of ruthenium complexes [Ru­(terpy)­(N–N)­(L)]­(X)₂ (terpy = 2,2′;6′,2″-terpyridine, L = 2-(methylthio)­ethanol (Hmte) or water, and X is Cl^– or PF₆^–) with four different bidentate chelates N–N = bpy (2,2′-bipyridine), biq (2,2′-biquinoline), dcbpy (6,6′-dichloro-2,2′-bipyridine), or dmbpy (6,6′-dimethyl-2,2′-bipyridine), is described. For each chelate N–N the thermodynamic constant of the dark equilibrium between the aqua- and Hmte- complexes, the Hmte photosubstitution quantum yield, and the rate constants of the thermal interconversion between the aqua and Hmte complexes were measured at room temperature. By changing the steric hindrance and electronic properties of the spectator N–N ligand along the series bpy, biq, dcbpy, dmbpy the dark reactivity clearly shifts from a nonlabile equilibrium with N–N = bpy to a very labile thermal equilibrium with N–N = dmbpy. According to variable-temperature rate constant measurements in the dark near pH = 7 the activation enthalpies for the thermal substitution of H₂O by Hmte are comparable for all ruthenium complexes, whereas the activation entropies are negative for bpy and biq, and positive for dcbpy and dmbpy complexes. These data are indicative of a change in the substitution mechanism, being interchange associative with nonhindered or poorly hindered chelates (bpy, biq), and interchange dissociative for more bulky ligands (dcbpy, dmbpy). For the most labile dmbpy system, the thermal equilibrium is too fast to allow significant modification of the composition of the mixture using light, and for the nonhindered bpy complex the photosubstitution of Hmte by H₂O is possible but thermal binding of Hmte to the aqua complex does not occur at room temperature. By contrast, with N–N = biq or dcbpy the thermodynamic and kinetic parameters describing the formation and breakage of the Ru–S bond lie in a range where the bond forms spontaneously in the dark, but is efficiently cleaved under light irradiation. Thus, the ratio between the aqua and Hmte complex in solution can be efficiently controlled at room temperature using visible light irradiation