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Suitable designed photoswitches based on azobenzenes are essential structural features for photopharmacological compounds. Optimized azobenzenes are important for serving as building blocks in "azo extension" strategies, and for designing photodrugs with tailored properties. Herein we present the synthesis and characterization of a variety of asymmetric azobenzenes by addressing selected structural features of the diazene core, such as polarity, steric demand, and electronic properties. Systematic exploration led to photoswitches with a relaxation half-life of seconds, minutes, hours, or days. Furthermore, the influence of different substitution patterns on the photophysical properties was charted. For analysis of all switches, robust characterization as well as examination under near-to physiological conditions was established, in order to assist with photoswitch choice for specific biological applications.

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS.Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1).Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p < 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p < 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p < 0.049, interaction effect).Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS.

Ruthenium(II) polypyridyl complexes are commonly applied as photosensitizers in the fields of artificial photosynthesis and light harvesting. Their immobilization on gold surfaces is also of interest for sensing and biological applications. Here, we report the self-assembly of [Ru(dmbpy)

The first total synthesis of the actin‐stabilizing marine natural product geodiamolide H was achieved. Solid‐phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring‐closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by docking on the F‐actin target and property computation in silico, for a better understanding of structure‐activity relationships (SAR). A non‐natural analogue of geodiamolide H was discovered to be most potent in the series, suggesting significant potential for tool compound design., The F‐actin stabilizing natural product geodiamolide H and its analogues were comprehensively investigated. The first total synthesis of geodiamolide H was enabled by optimized, scalable building block synthesis, improved couplings, and by a ring‐closing metathesis as a key step. Biological profiling of the synthesized library in cells, on target, and in silico uncovered potent and simplified non‐natural analogues. Additional structure‐activity relationship information was extracted for the whole class, useful for tool compound design.