In this work a photosubstitution strategy is presented that can be used for the isolation of chiral organometallic complexes. A series of five cyclometalated complexes Ru(phbpy)(N−N)(DMSO-κS)](PF6)... Show moreIn this work a photosubstitution strategy is presented that can be used for the isolation of chiral organometallic complexes. A series of five cyclometalated complexes Ru(phbpy)(N−N)(DMSO-κS)](PF6) ([1]PF6-[5]PF6) were synthesized and characterized, where Hphbpy = 6′-phenyl-2,2′-bipyridyl, and N–N = bpy (2,2′-bipyridine), phen (1,10-phenanthroline), dpq (pyrazino[2,3-f][1,10]phenanthroline), dppz (dipyrido[3,2-a:2′,3′-c]phenazine, or dppn (benzo[i]dipyrido[3,2-a,2′,3′-c]phenazine), respectively. Due to the asymmetry of the cyclometalated phbpy– ligand, the corresponding [Ru(phbpy)(N–N)(DMSO-κS)]+complexes are chiral. The exceptional thermal inertness of the Ru–S bond made chiral resolution of these complexes by thermal ligand exchange impossible. However, photosubstitution by visible light irradiation in acetonitrile was possible for three of the five complexes ([1]PF6-[3]PF6). Further thermal coordination of the chiral sulfoxide (R)-methyl p-tolylsulfoxide to the photoproduct [Ru(phbpy)(phen)(NCMe)]PF6, followed by reverse phase HPLC, led to the separation and characterization of the two diastereoisomers of [Ru(phbpy)(phen)(MeSO(C7H7))]PF6, thus providing a new photochemical approach toward the synthesis of chiral cyclometalated ruthenium(II) complexes. Full photochemical, electrochemical, and frontier orbital characterization of the cyclometalated complexes [1]PF6-[5]PF6 was performed to explain why [4]PF6 and [5]PF6 are photochemically inert while [1]PF6-[3]PF6 perform selective photosubstitution. Show less
The long-term fate of biomedical nanoparticles after endocytosis is often only sparsely addressed in vitro and in vivo, while this is a crucial parameter to conclude on their utility. In this study... Show moreThe long-term fate of biomedical nanoparticles after endocytosis is often only sparsely addressed in vitro and in vivo, while this is a crucial parameter to conclude on their utility. In this study, dual-fluorescent polyisobutylene-polyethylene glycol (PiB-PEG) polymersomes were studied for several days in vitro and in vivo. In order to optically track the vesicles' integrity, one fluorescent probe was located in the membrane and the other in the aqueous interior compartment. These non-toxic nanovesicles were quickly endocytosed in living A549 lung carcinoma cells but unusually slowly transported to perinuclear lysosomal compartments, where they remained intact and luminescent for at least 90 h without being exocytosed. Fluorescence-assisted flow cytometry indicated that after endocytosis, the nanovesicles were eventually degraded within 7–11 days. In zebrafish embryos, the polymersomes caused no lethality and were quickly taken up by the endothelial cells, where they remained fully intact for as long as 96 h post-injection. This work represents a novel case-study of the remarkable potential of PiB-PEG polymersomes as an in vivo bio-imaging and slow drug delivery platform. Show less
Ruthenium polypyridyl complexes have received widespread attention as potential chemotherapeutics in photodynamic therapy (PDT) and in photochemotherapy (PACT). Here, we investigate a series of... Show moreRuthenium polypyridyl complexes have received widespread attention as potential chemotherapeutics in photodynamic therapy (PDT) and in photochemotherapy (PACT). Here, we investigate a series of sixteen ruthenium polypyridyl complexes with general formula [Ru(tpy)(N−N)(L)]+/2+ (tpy=2,2′:6′,2′′‐terpyridine, N−N=bpy (2,2′‐bipyridine), phen (1,10‐phenanthroline), dpq (pyrazino[2,3‐f][1,10]phenanthroline), dppz (dipyrido[3,2‐a:2′,3′‐c]phenazine, dppn (benzo[i]dipyrido[3,2‐a:2′,3′‐c]phenazine), pmip (2‐(4‐methylphenyl)‐1H‐imidazo[4,5‐f][1,10]phenanthroline), pymi ((E)‐N‐phenyl‐1‐(pyridin‐2‐yl)methanimine), or azpy (2‐(phenylazo)pyridine), L=Cl− or 2‐(2‐(2‐(methylthio)ethoxy)ethoxy)ethyl‐β‐d‐glucopyranoside) and their potential for either PDT or PACT. We demonstrate that although increased lipophilicity is generally related to increased uptake of these complexes, it does not necessarily lead to increased (photo)cytotoxicity. However, the non‐toxic complexes are excellent candidates as PACT carriers. Show less
Ruthenium complexes are promising prodrugs in photoactivated chemotherapy (PACT): to prevent systemic therapeutic side-effects, a non-toxic version of the drug is introduced in the body and is... Show moreRuthenium complexes are promising prodrugs in photoactivated chemotherapy (PACT): to prevent systemic therapeutic side-effects, a non-toxic version of the drug is introduced in the body and is only activated at the place of the tumor by means of visible light irradiation. However, most of these PACT compounds are only sensitive for UV or blue light, while this light does not permeate the body very well, in contrast to red or near-infrared light. To circumvent this problem, the principle of light-upconversion can be used to "upgrade" red light to blue light in a drug carrier such as a nanovesicle: the tumor is irradiated with red light, after which blue light is generated locally and used to activate the prodrug. Among the various methods of light-upconversion, triplet-triplet annihilation upconversion (TTA-UC) was selected as the most promising. In this thesis it is described that green-to-blue and red-to-blue upconverting nanovesicles were prepared. The red-to-blue upconverted light was successfully used to activate a ruthenium polypyridyl complex that was anchored to the same vesicle. Finally, the inherent oxygen-sensitivity of TTA-UC was greatly mitigated by the addition of water-soluble and biocompatible anti-oxidants. We expect that the results of this thesis will lead to exciting applications in PACT. Show less
Red-to-blue triplet–triplet annihilation upconversion was obtained in giant unilamellar vesicles. The upconverted light was homogeneously distributed across the membrane and could be utilized for... Show moreRed-to-blue triplet–triplet annihilation upconversion was obtained in giant unilamellar vesicles. The upconverted light was homogeneously distributed across the membrane and could be utilized for the imaging of individual giant vesicles in three dimensions. These results show the great potential of TTA-UC for imaging applications under anoxic conditions. Show less
