Design, synthesis, and conformational analysis of trispyrimidonamides as α-helix mimetics.

The straightforward synthesis of trispyrimidonamides as a new class of α-helix mimetics is reported. Because of the versatility of our synthetic protocol, a variety of side chains including aliphatic, basic, aromatic, and heteroaromatic residues were included. A comprehensive conformational analysis revealed that in polar solvents a trimeric compound adopts conformations that can lead to i, i + 4, i + 8, or i, i + 8 patterns of side chain orientation. This suggests that trispyrimidonamides could be promising α-helix mimetics to target hot spots that are distributed over a wider angular range of an α-helix interface than in the classical i, i + 4, i + 7 case.

Morphological Insights into the Degradation of Perovskite Solar Cells under Light and Humidity.

Perovskite solar cells (PSCs) have achieved competitive power conversion efficiencies compared with established solar cell technologies. However, their operational stability under different external stimuli is limited, and the underlying mechanisms are not fully understood. In particular, an understanding of degradation mechanisms from a morphology perspective during device operation is missing. Herein, we investigate the operational stability of PSCs with CsI bulk modification and a CsI-modified buried interface under AM 1.5G illumination and 75 ± 5% relative humidity, respectively, and concomitantly probe the morphology evolution with grazing-incidence small-angle X-ray scattering. We find that volume expansion within perovskite grains, induced by water incorporation, initiates the degradation of PSCs under light and humidity and leads to the degradation of device performance, in particular, the fill factor and short-circuit current. However, PSCs with modified buried interface degrade faster, which is ascribed to grain fragmentation and increased grain boundaries. In addition, we reveal a slight lattice expansion and PL redshifts in both PSCs after exposure to light and humidity. Our detailed insights from a buried microstructure perspective on the degradation mechanisms under light and humidity are essential for extending the operational stability of PSCs.

Picosecond Charge-Transfer-State Dynamics in Wide Band Gap Polymer-Non-Fullerene Small-Molecule Blend Films Investigated via Transient Infrared Spectroscopy.

Organic solar cells based on wide band gap polymers and nonfullerene small-molecule acceptors have demonstrated remarkably good device performances. Nevertheless, a thorough understanding of the charge-transfer process in these materials has not been achieved yet. In this study, we use Fano resonance signals caused by the interaction of broad electronic charge carrier absorption and the molecular vibrations of the electron acceptor molecule to monitor the charge-transfer state dynamics. In our time-resolved infrared spectroscopy experiments, we find that in the small-molecule acceptor, they have additional dynamics on the order of a few picoseconds. A change in the solvent used in thin film deposition, leading to different morphologies, influences this time further. We interpret our findings as the dynamics of the charge-transfer state at the interface of the electron donor and the electron- acceptor. The additional mid-infrared transient signal is generated in this state, as both electron and hole polarons can interact with small-molecule acceptor vibrational modes.

Development of a First-in-Class Small-Molecule Inhibitor of the C-Terminal Hsp90 Dimerization.

Heat shock proteins 90 (Hsp90) are promising therapeutic targets due to their involvement in stabilizing several aberrantly expressed oncoproteins. In cancerous cells, Hsp90 expression is elevated, thereby exerting antiapoptotic effects, which is essential for the malignant transformation and tumor progression. Most of the Hsp90 inhibitors (Hsp90i) under investigation target the ATP binding site in the N-terminal domain of Hsp90. However, adverse effects, including induction of the prosurvival resistance mechanism (heat shock response or HSR) and associated dose-limiting toxicity, have so far precluded their clinical approval. In contrast, modulators that interfere with the C-terminal domain (CTD) of Hsp90 do not inflict HSR. Since the CTD dimerization of Hsp90 is essential for its chaperone activity, interfering with the dimerization process by small-molecule protein-protein interaction inhibitors is a promising strategy for anticancer drug research. We have developed a first-in-class small-molecule inhibitor (5b) targeting the Hsp90 CTD dimerization interface, based on a tripyrimidonamide scaffold through structure-based molecular design, chemical synthesis, binding mode model prediction, assessment of the biochemical affinity, and efficacy against therapy-resistant leukemia cells. 5b reduces xenotransplantation of leukemia cells in zebrafish models and induces apoptosis in BCR-ABL1+ (T315I) tyrosine kinase inhibitor-resistant leukemia cells, without inducing HSR.