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Building on the preceding structural analysis and a structure–activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA2AAR antagonist 2a, we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. The SAR findings indicated that such inversions significantly modulated hA3AR binding affinities depending on the type of ribose, whereas removal of ribose altered the functional efficacy via hA2AAR. Among the synthesized derivatives, 2-aryl-8-hexynyl adenine 4ademonstrated the highest selectivity for hA2AAR (Ki,hA2A= 5.0 ± 0.5 nM, Ki,hA3/Ki,hA2A= 86) and effectively blocked cAMP production and restored IL-2 secretion in PBMCs. Favorable pharmacokinetic properties and a notable enhancement of anticancer effects in combination with an mAb immune checkpoint blockade were observed upon oral administration of 4a. These findings establish 4aas a viable immune-oncology therapeutic candidate.

In this study, we investigated how the catalytic redox cycle occurs over a lanthanum manganese oxide (LaMnO3) catalyst when applied to the ozone-induced oxidation of soot. This was accomplished by tracking the catalysis using O3/O2temperature-programmed desorption coupled with X-ray photoelectron spectroscopy (XPS). We prepared the catalyst by the citric acid sol–gel method to obtain a catalyst with a uniform perovskite phase and improved specific surface area. The catalyst was remarkably active in promoting ozone-induced soot oxidation within the temperature range of 25–125 °C. The active oxygen species were superoxide ions combined with Mn4+ions on the catalyst surface. It was presumed the superoxide ion migrates over the surface Mn4+sites and either desorbs as molecular oxygen or oxidizes the soot particles if it reaches the interface between soot and catalyst particles. The redox cycle was completed by the Mn4+-to-Mn3+transition, which accompanied the detachment of superoxide ions. No evidence was found to support the involvement of the bulk phase of the catalyst with the redox cycle. The ozone-induced redox cycle was presumed to exclusively occur on the surface of the catalyst.