Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3

Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age. Detailed morphological analyses of the explanted heart tissue showed intracytoplasmic inclusions, aggregation of BAG3 and desmin, disintegration of myofibers and Z-disk alterations. The presence of undegraded autophagosomes, seen by electron microscopy, as well as increased levels of p62, LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses, indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were not altered. These findings indicate that altered autophagy plays a role in the pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu mutation, which could have implications for future therapeutic strategies

A family of superhelicenes - easily tunable, chiral nanographenes by merging helicity with planar π-systems

Incorporating helicity into large polycyclic aromatic hydrocarbons (PAHs) constitutes a new field of research at the interface between chemistry and material sciences. Lately, interest in the design of π-extended helicenes has surged. This new class of twisted, chiral nanographenes not only reveals unique characteristics but also finds its way into emerging applications such as spintronics. Insights into their structure-property relationships and on-demand tuning are scarce. To close these knowledge gaps, we designed a straightforward synthetic route towards a full-fledged family of π-extended helicenes: superhelicenes. Common are two hexa-peri-hexabenzocoronenes (HBCs) connected via a central 5-membered ring. By means of structurally altering this 5-membered ring, we realized a versatile library of molecular building blocks. Not only the superhelicene structure, but also their features are tuned with ease. In-depth physico-chemical characterizations served as a proof of concept thereof. The superhelicene enantiomers were separated, their circular dichroism was measured in preliminary studies and concluded with an enantiomeric assignment. Our work was rounded-off by crystal structure analyses. Mixed stacks of M- and P-isomers led to twisted molecular wires. Using such stacks, charge-carrier mobilities were calculated, giving reason to expect outstanding hole transporting properties

On the photophysics of nanographene – investigation of functionalized hexa-peri-hexabenzocoronenes as model systems

In the current study, we report on hexa-peri-hexabenzocoronenes (HBCs) as a representative model for nanographene. To this end, we synthesized a family of functionalized HBCs and investigated the impact of the substituents on the π-extended system of the HBCs. DFT and TD-DFT calculations suggested a charge transfer character, which intensifies as the electron density withdrawing effects of the substituents (–M-effect) increase. Unambiguous corroboration of the charge transfer character in the case of the NO2-substituents was realized with steady-state absorption and fluorescence experiments, which focused on the dependencies on solvent polarity and temperature featuring. Going beyond HBCs with NO2-substituents time-correlated single photon counting, femtosecond and nanosecond transient absorption spectroscopy unveil long-lived singlet and triplet excited states. As a complement, we performed electrochemical and spectroelectrochemical measurements. These were carried out to shed light onto the nature of functionalized HBCs as electron acceptors and/or donors, on one hand, and their corresponding spectroscopic signatures, on the other hand. All of the aforementioned enabled intermolecular charge separation assays with, for example, suitable electron acceptors by steady-state and time-resolved spectroscopies

Panchromatic light funneling through the synergy in hexabenzocoronene–(metallo)porphyrin–fullerene assemblies to realize the separation of charges

Here, we present a novel butadiyne-linked HBC-ethynyl-porphyrin dimer, which exhibits in the ground state strong absorption cross sections throughout the UV and visible ranges of the solar spectrum. In short, a unidirectional flow of excited state energy from the HBC termini to the (metallo)porphyrin focal points enables concentrating light at the latter. Control over excitonic interactions within, for example, the electron-donating porphyrin dimers was realized by complexation of bidentate ligands to set up panchromatic absorption that extends all the way into the near-infrared range. The bidentate binding motif was then exploited to create a supramolecular electron donor–acceptor assembly based on a HBC-ethynyl-porphyrin dimer and an electron accepting bis(aminoalkyl)-substituted fullerene. Of great relevance is the fact that charge separation from the photoexcited HBC-ethynyl-porphyrin dimer to the bis(aminoalkyl)-substituted fullerene is activated not only upon photoexciting the HBCs in the UV as well as the (metallo)porphyrins in the visible but also in the NIR. Implicit is the synergetic interplay of energy and charge transfer in a photosynthetic mimicking manner. The dimer and bis-HBC-ethynyl-porphyrin monomers, which serve as references, were probed by means of steady-state as well as time-resolved optical spectroscopies, including global target analyses of the time-resolved transient absorption data