Helen Hölzel

A new halogenated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative was designed as a singlet-oxygen photosensitizer (PS) for use as a photodynamic therapy (PDT) agent, and its photophysical properties were characterized. The PS, having two iodine atom substituents, exhibited a low fluorescence quantum yield (Φ_FL) of 0.02 and high singlet-oxygen-generation quantum yield (Φ_Δ) of 0.93. Furthermore, in vitro photodynamic activities were evaluated to assess the potential of using the PS for PDT. A propidium iodide (PI) fluorescence assay and live-cell imaging of Lewis lung carcinoma (LLC) cells demonstrated that the cellular damage is induced by the photosensitization of the BODIPY dye, which subsequently leads to cell death by necrosis.q

Facile synthesis of an iodinated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative exhibited highly efficient singlet-oxygen sensitization. Photodynamic-therapy activity experiments showed photo-induced necrotic cell death in Lewis lung carcinoma cells.

BODIPY is a highly versatile fluorophore for biological imaging with a tunable fluorescence emission (500–800 nm) that overlaps the optically transparent window for tissue (600–1300 nm). Herein, we describe the synthesis of optically distinct BODIPY-based profluorescent probes bearing meso- and β-substituted isoindoline nitroxides and their corresponding methoxyamine derivatives. These profluorescent nitroxide probes possess strongly suppressed fluorescence, which can be revealed upon reduction or reaction with other radicals. Examination of the pentafluorophenylhydrazine reduction of the prepared probes by using tandem electron paramagnetic resonance (EPR) and fluorescence spectroscopy demonstrated that the asymmetric bis-β-substituted probe 9 (λ_em = 603 nm) was reduced the fastest; however, the greatest difference in fluorescence emission between the nitroxide and its reduced hydroxylamine analogue was observed for probe 7 (λ_em = 570 nm). The significant difference in fluorescence output between the nitroxides and their corresponding diamagnetic derivatives makes these probes ideal tools for imaging reactive oxygen species in biological systems.

Profluorescent nitroxide probes bearing isoindoline nitroxides substituted at the meso or β positions of the BODIPY core were synthesised. Reduction of the probes to their corresponding hydroxylamine analogues revealed a substantial fluorescence increase which demonstrates their potential as tools for imaging reactive oxygen species in biological systems.

A scalable and efficient method for the synthesis of pyrene-4,5-dione has been developed. The addition of N-methylimidazole (NMI, 5 mol-%) to a known oxidation reaction was shown to marginally improve the yield and dramatically improve the ease of the workup and thus the amount of product isolable in a day by using regular laboratory equipment.

The addition of N-methylimidazole (NMI, 5 mol-%) to the ruthenium-mediated K-region oxidation of pyrene has a dramatic effect on the workup procedure. The previously very messy and laborious workup that limited the scale of the reaction has thus become much easier to perform, which enables the comfortable synthesis of up to 15 g of pyrene-4,5-dione.

Hexaarylbenzene–porphyrin scaffolds were prepared by means of a Diels-Alder reaction. In the cover image, the mountains and shooting stars represent the statistical product distribution, which is a useful calibrant for mass spectrometry. The strong red luminescence of the conjugates is highlighted by the red moon. The graphene landscape stands for the conversion to π–extended porphyrin conjugates. More information can be found in the Communication by T. Drewello, N. Jux, et al. (DOI: 10.1002/chem.201603789).

A series of air-stable boron complexes 1–5 were prepared by using N-aryl iminopyrrolide ligands. Designed as minimalist structural mimics of the privileged BODIPY motif, these new BOIMPY (BOron complexes of IMinoPYrrolide ligands) fluorophores feature low molecular symmetry that promotes emission from CT-type excited states with large Stokes shifts and little self-quenching. Through comparative studies on the homologous set of compounds 1–4, we have confirmed that a delicate interplay between conformational twisting and donor–acceptor interaction dictates the mechanism of de-excitation, which responds sensitively to solvent polarity as well as protonation states. Over a wide visible spectral range, the structure-dependent light-emitting properties of BOIMPY molecules are well manifested, even in the solid-state. In order to exploit the environment-sensitive nature of CT-type emission, the BOIMPY motif was elaborated further into a bioprobe molecule 5. Live-cell fluorescence imaging studies have established that 5 is localized exclusively at lipid droplets to produce well-resolved staining patterns without affecting cell viability. These findings promise future elaboration of BOIMPY-based functional molecules for applications in biological imaging, chemical sensing, and molecular switching.

Desymmetrized light-emitters: Air-stable boron complexes of π-conjugated N,N-bidentate ligands promote emission from charge-separated excited state with large Stokes shifts and little self-quenching, which allow for solid-state emission and live-cell fluorescence imaging (see figure).

Herein, we report two new types of twisted polycyclic arenes (2 a, b and 3 a, b) with constitutionally isomeric π-backbones, which are synthesized by controlling the Scholl reaction of 1,2,4,5-tetra(naphth-2-yl)-3,6-diphenylbenzene (1) with properly positioned electron-donating substituents. With a polycyclic backbone containing two [5]helicene and four [4]helicene moieties, 2 a and b are new members of multiple helicenes with interesting stereochemistries. The as-synthesized 2 a and b are the twisted isomers, and thermal isomerization of twisted-2 b results in anti-2 b, a more stable stereoisomer. Both twisted- and anti-2 b have been fully characterized, and the thermal isomerization of twisted-2 b has been studied with ¹H NMR spectroscopy and DFT calculations. Compounds 3 a and b are new members of twistacenes, the benzannulated pentacene backbone of which exhibits an end-to-end twist as found from the crystal structure. Twisted- and anti-2 b are also found to function as p-type semiconductors in solution-processed thin film transistors, whereas the thin films of 3 b appear insulating presumably due to the lack of π–π interactions.

Let's twist again: Two new types of twisted polycyclic arenes (2 a, b and 3 a, b) with constitutionally isomeric π-backbones are synthesized by controlling the Scholl reaction of 1,2,4,5-tetra(naphth-2-yl)-3,6-diphenylbenzene with properly positioned electron-donating substituents (see scheme).

By taking advantage of an unexpected regioselectivity of intramolecular Scholl reactions on pentaphenylene compounds that favors distorted [5]helicenes over their flat counterparts, a new synthetic approach to twisted graphene nanoribbons has been designed based on side-fused di-tert-butyl-[5]helicene fragments. Syntheses of both small monomers and dimers have been achieved and their structures have been studied. An iterative synthetic strategy has been developed for the formation of longer flexible precursors, which relies on the step-by-step elongation of mono-functionalized oligomeric chains. The flexible trimer and tetramer have, thus, been synthesized and submitted to intramolecular Scholl reactions, which revealed important purification and characterization issues.

Do the twist! By taking advantage of the unexpected ability of the Scholl reaction to form highly hindered [5]helicenes, several syntheses of linear poly(phenylene-naphthylene) chains with different lengths have been achieved. The Scholl reaction on these compounds leads to fused poly(helicenes) that can be seen as very soluble twisted graphene nanoribbons (see figure).

Axially Chiral BODIPY DYEmers display intense fluorescence and circularly polarized luminescence (CPL) spectra. Due to exciton coupling between the BODIPY rings the π* states split into two energy levels, giving strong ECD couplets. The strongly emitting excited state is the low-lying exciton-coupled level. TD-DFT and CC2 calculations elucidated the photophysics behind the CPL of these systems. More information can be found in the Full Paper by L. Di Bari, G.  Pescitelli, et al. (DOI: 10.1002/chem.201602684).

A feasible two-step synthesis and characterization of a full series of hexaarylbenzene (HAB) substituted porphyrins and tetrabenzoporphyrins is presented. Key steps represent the microwave-assisted porphyrin condensation and the statistical Diels–Alder reaction to the desired HAB-porphyrins. Regarding their applications, they proved to be easily accessible and effective high molecular mass calibrants for (MA)LDI mass spectrometry. The free-base and zinc(II) porphyrin systems, as well as the respective tetrabenzoporphyrins, demonstrate in solid state experiments strong red- and near-infrared-light emission and are potentially interesting for the application in “truly organic” light-emitting devices. Lastly, they represent facile precursors to large polycyclic aromatic hydrocarbon (PAH) substituted porphyrins. We prepared the first tetra-hexa-peri-hexabenzocoronene substituted porphyrin, which represents the largest prepared PAH-porphyrin conjugate to date.

Hexaarylbenzene (HAB)-substituted (tetrabenzo)porphyrins were found to have useful properties for various applications, such as calibrants for (MA)LDI instruments, as strong red- and near- infrared light emitters, and as precursors to large superbenzene-porphyrin light-harvesting architectures.