The synthesis, electrochemistry, and photophysical characterization of a 10,10-dimethyl-5,15-bis(pentafluorophenyl)-biladiene (DMBil1) linear tetrapyrrole supporting PdII or PtII centers is presented. Both of these nonmacrocyclic tetrapyrrole platforms are robust and easily prepared via modular routes. X-ray diffraction experiments reveal that the Pd[DMBil1] and Pt-[DMBil1] complexes adopt similar structures and incorporate a single PdII and PtII center, respectively. Additionally, electrochemical experiments revealed that both Pd[DMBil1] and Pt[DMBil1] can undergo two discrete oxidation and reduction processes. Spectroscopic experiments carried out for Pd[DMBil1] and Pt[DMBil1] provide further understanding of the electronic structure of these systems. Both complexes strongly absorb light in the UV–visible region, especially in the 350–600 nm range. Both Pd[DMBil1] and Pt[DMBil1] are luminescent under a nitrogen atmosphere. Upon photoexcitation of Pd[DMBil1], two emission bands are observed; fluorescence is detected from ~500–700 nm and phosphorescence from ~700–875 nm. Photoexcitation of Pt[DMBil1] leads only to phosphorescence, presumably due to enhanced intersystem crossing imparted by the heavier PtII center. Phosphorescence from both complexes is quenched under air due to energy transfer from the excited triplet state to ground state oxygen. Accordingly, irradiation with light of λ ≥ 500 nm prompts Pd[DMBil1] and Pt[DMBil1] to photosensitize the generation of 1O2 (singlet oxygen) with impressive quantum yields of 80% and 78%, respectively. The synthetic accessibility of these complexes coupled with their ability to efficiently photosensitize 1O2 may make them attractive platforms for development of new agents for photodynamic therapy.

Photodynamic therapy (PDT) represents a minimally invasive and highly localized treatment strategy to ablate tumors with few side effects. In PDT, photosensitizers embedded within tumors are activated by light and undergo intersystem crossing, followed by energy transfer to molecular oxygen, resulting in the production of toxic singlet oxygen (O). Previously, we reported a robust, linear tetrapyrrole palladium(II) complex, Pd[DMBil1], characterized by its facile and modular synthesis, broad absorption profile, and efficient O quantum yield of Φ = 0.8 in organic media. However, the insolubility of this porphyrinoid derivative in aqueous solution prevents its use under biologically relevant conditions. In this work, we report the synthesis of Pd[DMBil1]-PEG, a water-soluble dimethylbiladiene derivative that is appended with a poly(ethylene) glycol (PEG) functionality. Characterization of this complex shows that this PEGylated biladiene architecture maintains the attractive photophysical properties of the parent complex under biologically relevant conditions. More specifically, the absorption profile of Pd[DMBil1]-PEG closely matches that of Pd[DMBil1] and obeys the Beer-Lambert Law, suggesting that the complex does not aggregate under biologically relevant conditions. Additionally, the emission spectrum of Pd[DMBil1]-PEG retains the fluorescence and phosphorescence features characteristic of Pd[DMBil1]. Importantly, the PEGylated photosensitizer generates O with Φ = 0.57, which is well within the range to warrant interrogation as a potential PDT agent for treatment of cancer cells. The Pd[DMBil1]-PEG is biologically compatible, as it is taken up by MDA-MB-231 triple negative breast cancer (TNBC) cells and has an effective dose (ED) of only 0.354 μM when exposed to λ > 500 nm light for 30 min. Impressively, the lethal dose (LD) of Pd[DMBil1]-PEG without light exposure was measured to be 1.87 mM, leading to a remarkably high phototoxicity index of ∼5300, which is vastly superior to existing photosensitizers that form the basis for clinical PDT treatments. Finally, through flow cytometry experiments, we show that PDT with Pd[DMBil1]-PEG induces primarily apoptotic cell death in MDA-MB-231 cells. Overall these results demonstrate that Pd[DMBil1]-PEG is an easily prepared, biologically compatible, and well-tolerated photochemotherapeutic agent that can efficiently drive the photoinduced apoptotic death of TNBC cells.

Light-activated therapies are ideal for treating cancer because they are non-invasive and highly specific to the area of light application. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two types of light-activated therapies that show great promise for treating solid tumors. In PTT, nanoparticles embedded within tumors emit heat in response to laser light that induces cancer cell death. In PDT, photosensitizers introduced to the diseased tissue transfer the absorbed light energy to nearby ground state molecular oxygen to produce singlet oxygen, which is a potent reactive oxygen species (ROS) that is toxic to cancer cells. Although PTT and PDT have been extensively evaluated as independent therapeutic strategies, they each face limitations that hinder their overall success. To overcome these limitations, we evaluated a dual PTT/PDT strategy for treatment of triple negative breast cancer (TNBC) cells mediated by a powerful combination of silica core/gold shell nanoshells (NSs) and palladium 10,10-dimethyl-5,15-bis(pentafluorophenyl)biladiene-based (Pd[DMBil1]-PEG750) photosensitizers (PSs), which enable PTT and PDT, respectively. We found that dual therapy works synergistically to induce more cell death than either therapy alone. Further, we determined that low doses of light can be applied in this approach to primarily induce apoptotic cell death, which is vastly preferred over necrotic cell death. Together, our results show that dual PTT/PDT using silica core/gold shell NSs and Pd[DMBil1]-PEG750 PSs is a comprehensive therapeutic strategy to non-invasively induce apoptotic cancer cell death.

Photodynamic therapy (PDT) is a treatment in which photoactive compounds delivered to cancerous tissues are excited with light and then transfer the absorbed energy to adjacent tissue oxygen molecules to generate toxic singlet oxygen ( 1 O 2 ). As 1 O 2 is produced only where light and photosensitizers (PSs) are combined, PDT holds promise as a minimally invasive, highly selective treatment for certain cancers. The practical application of PDT requires easily synthesized, water-soluble PSs that have low dark toxicities, high 1 O 2 quantum yields, and efficient absorption of 650−850 nm near-infrared (NIR) light, which deeply penetrates tissue. We recently developed a linear tetrapyrrole metal complex, Pd[DMBil1]−PEG 750 , that meets most of these criteria. This complex is remarkably effective as a PS for PDT against triple-negative breast cancer (TNBC) cells but, critically, it does not absorb NIR light, which is necessary to treat deeper tumors. To enable NIR activation, we synthesized a new derivative, Pd[DMBil1]−PEG 5000 −SH, which bears a thiol functionality that facilitates conjugation to NIR-absorbing gold nanoshells (NSs). Upon excitation with pulsed 800 nm light, NSs emit two-photon-induced photoluminescence spanning 500− 700 nm, which can sensitize the attached PSs to initiate PDT. Additionally, NSs produce heat upon 800 nm irradiation, endowing the NS−PS conjugates with an auxiliary photothermal therapeutic (PTT) capability. Here, we demonstrate that NS− PS conjugates are potent mediators of NIR-activated tandem PDT/PTT against TNBC cells in vitro. We show that Pd[DMBil1]−PEG 5000 −SH retains the photophysical properties of the parent Pd[DMBil1] complex, and that NS−PS generate 1 O 2 under pulsed 800 nm irradiation, confirming activation of the PSs by photoluminescence emitted from NSs. TNBC cells readily internalize NS PS conjugates, which generate reactive oxygen species in the cells upon pulsed NIR irradiation to damage DNA and induce apoptosis. Together, these findings demonstrate that exploiting photoluminescent NSs as carriers of efficient Pd[DMBil1] PSs is an effective strategy to enable NIR light-activated tandem PDT/PTT.

Two new Re(I)bipyridyltricarbonylchloride complexes, Re(BB3)(CO) 3 Cl, and Re(BB4)(CO) 3 Cl, featuring BODIPY groups appended to the 5,5'-, or 6,6'-positions of the bipyridine ligand respectively, have been synthesized as structurally isomeric compliments to a previously reported 4,4'-substituted homologue, Re(BB2)(CO) 3 Cl. X-ray crystal structures of the compounds show that the 4,4'-, 5,5'-and 6,6'-substitution patterns place the BODIPY groups at progressively shorter distances of 9.43 Å, 8.39 Å and 5.56 Å, respectively, from the complexes' Re centers. The photophysical properties of the isomeric complexes were investigated to ascertain the manner in which the heavy rhenium atom might induce intersystem crossing of the pendant BODIPY moieties positioned at progressively shorter through-space distances. Electronic absorption spectroscopy revealed that the three metal complexes retain the strong visible absorption features characteristic of the bpy-BODIPY (BB2-BB4) ligands, however, the fluorescence of the parent borondipyrromethane appended ligands is attenuated by more than an order of magnitude in Re(BB2)(CO) 3 Cl and Re(BB3)(CO) 3 Cl, and by more than two orders of magnitude in Re(BB4) (CO) 3 Cl. Furthermore, phosphorescence from Re(BB4)(CO) 3 Cl is observed under a nitrogen atmosphere, consistent with highly efficient ISC to the triplet-excited state. Singlet oxygen sensitization studies confirm that all three complexes produce singlet oxygen with quantum yields that increase as the distance of the BODIPY groups to the heavy rhenium center is decreased. The trends observed across the series of rhenium complexes with respect to emission and 1 O 2 sensitization properties can be rationalized in terms of the varied distal separation between the metal center and BODIPY groups in each system.

Four new molecular Co(II)tetrapyridyl complexes were synthesized and evaluated for their activity as catalysts for proton reduction in aqueous environments. The pyridine groups around the macrocycle were substituted for either one or two pyrazine groups. Single crystal X-ray analysis shows that the pyrazine groups have minimal impact on the Co(II)–N bond lengths and molecular geometry in general. X-band EPR spectroscopy confirms the Co(II) oxidation state and the electronic environment of the Co(II) center are only very slightly perturbed by the substitution of pyrazine groups around the macrocycle. The substitution of pyrazine groups has a substantial impact on the observed metal- and ligand-centered reduction potentials as well as the overall H2 catalytic activity in a multimolecular system using the [Ru(2,2′-bipyridine)3]Cl2 photosensitizer and ascorbic acid as a sacrificial electron donor. The results reveal interesting trends between the H2 catalytic activity for each catalyst and the driving force for electron transfer between either the reduced photosensitizer to catalyst step or the catalyst to proton reduction step. The work presented here showcases how even the difference of a single atom in a molecular catalyst can have an important impact on activity and suggests a pathway to optimize the photocatalytic activity and stability of molecular systems.

The effect of molecular weight on the rate and extent of melt-infiltration of polystyrene into mesoporous silicon-based photonic crystals is investigated as a function of polymer molecular weight. Polymer viscosity and chain end-to-end (Ree) distance correlate with the rate and extent of infiltration. High molecular weight (Mw) polystyrene (200 or 400 kDa) infiltrates the mesoporous material in two distinct phases: a rapid phase where the larger pores of the template are filled, followed by a slower phase during which the smaller pores fill. Low molecular weight polystyrene (20 and 35 kDa) fills the pores more uniformly, progressing into the film as a single, relatively distinct front of liquid polymer. Scanning electron microscope (SEM) analyses of cross sections of the films are consistent with the optical measurements, showing a lower extent of infiltration for the higher molecular weight polymers. Removal of the porous Si templates by soaking in a chemical etchant generates free-standing films of nanostructured polymer. The low molecular weight samples display better replication. Partial removal of the template enables tuning of the hydrophobicity of the free-standing polymer films, which is demonstrated with a flexible and chemically stable polyvinylidene fluoride polymer

Facilitating photoinduced electron transfer (PET) while minimizing rapid charge-recombination processes to produce a long-lived charge-separated (CS) state represents a primary challenge associated with achieving efficient solar fuel production. Natural photosynthetic systems employ intermolecular interactions to arrange the electron-transfer relay in reaction centers and promote a directional flow of electrons. This work explores a similar tactic through the synthesis and ground- and excited-state characterization of two Cu(I)bis(phenanthroline) chromophores with homoleptic and heteroleptic coordination geometries and which are functionalized with negatively charged sulfonate groups. The addition of sulfonate groups enables solubility in pure water, and it also induces assembly with the dicationic electron acceptor methyl viologen (MV2+) via bimolecular, dynamic electrostatic interactions. The effect of the sulfonate groups on the ground- and excited-state properties was evaluated by comparison with the unsulfonated analogues in 1:1 acetonitrile/water. The excited-state lifetimes for all sulfonated complexes are similar to what we expect from previous literature, with the exception of the sulfonated heteroleptic complex whose metal-to-ligand charge-transfer (MLCT) lifetime in water has two components that are fit to 10 and 77 ns. For the sulfonated complexes, we detected reduced MV+• in both solvent environments following MLCT excitation, but control measurements in 1:1 acetonitrile/water with the unsulfonated analogues showed no PET to MV2+, indicating that electrostatically driven supramolecular assemblies of the sulfonated complexes with MV2+ facilitate the observed PET. Additionally, the strength of the intermolecular interactions driving the formation of these assemblies changes drastically with the solvent environment. In 1:1 acetonitrile/water, PET occurred from both sulfonated complexes with quantum yields (ΦET) of 2–3% but increased to a remarkable 98% for the sulfonated heteroleptic complex with a 3 μs CS-state lifetime in water.