Physiology and Pathophysiology of Oxygen Sensitivity

Oxygen is an essential requirement for metabolism in mammals and many other animals. Therefore, pathways that sense a reduction in available oxygen are critical for organism survival. Higher mammals developed specialized organs to detect and respond to changes in O2 content to maintain gas homeostasis by balancing oxygen demand and supply. Here, we summarize the various oxygen sensors that have been identified in mammals (carotid body, aortic bodies, and astrocytes), by what mechanisms they detect oxygen and the cellular and molecular aspects of their function on control of respiratory and circulatory O2 transport that contribute to maintaining normal physiology. Finally, we discuss how dysregulation of oxygen availability leads to elevated signalling sensitivity in these systems and may contribute to the pathogenesis of chronic cardiovascular and respiratory diseases and many other disorders. Hence, too little oxygen, too much oxygen, and a malfunctioning sensitivity of receptors/sensors can create major pathophysiological problems for the organism.

Modulation of Optical Oxygen Sensing Properties of Iridium (III) Complexes By Changing Their Substitution Groups

The series of bis-cyclometalated iridium (III) complexes bearing different substituents (-H, -OCH3, -F, -CH3) at the aryl moiety (Ir-1, Ir-2, Ir-3 and Ir-4) have been synthesized and characterized by MASS and 1H NMR spectrometries, and IR, absorption and emission spectroscopies. The effects of the substituents on their oxygen sensing properties as well as optical properties and decay kinetics have been investigated systematically in tetrahydrofuran (THF) and ethyl cellulose (EC) thin films. The Ir (III) complexes embedded in EC-based thin films showed more advanced sensor dynamics, higher oxygen sensitivity, and superior relative signal changes when compared with their solution phase. The I0/I100 values of Ir-1, Ir-2, Ir-3 and Ir-4 immobilized in EC thin film were calculated as 11.3, 5.2, 7.0 and 25.6 for the concentration range of 0-100% pCO2, respectively. These results show that the weak electron-donating properties of the methyl groups at the aryl moiety improve remarkably the optical oxygen sensing abilities of the Ir (III) complexes.

Oxygen-Sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension

Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs. the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.

Mechanistic basis of oxygen sensitivity in titanium

One of the most potent examples of interstitial solute strengthening in metal alloys is the extreme sensitivity of titanium to small amounts of oxygen. Unfortunately, these small amounts of oxygen also lead to a markedly decreased ductility, which in turn drives the increased cost to purify titanium to avoid this oxygen poisoning effect. Here, we report a systematic study on the oxygen sensitivity of titanium that provides a clear mechanistic view of how oxygen impurities affect the mechanical properties of titanium. The increased slip planarity of Ti-O alloys is caused by an interstitial shuffling mechanism, which is sensitive to temperature, strain rate, and oxygen content and leads to the subsequent alteration of deformation twinning behavior. The insights from our experimental and computational work provide a rationale for the design of titanium alloys with increased tolerance to variations in interstitial content, with notable implications for more widespread use of titanium alloys.

Genetic basis of oxygen sensing in the carotid body: HIF2α and an isoform switch in cytochrome c oxidase subunit 4

The mechanistic basis of the marked oxygen sensitivity of glomus cells in the carotid body has long puzzled physiologists. In this issue of Science Signaling, Moreno-Domínguez et al. show the critical importance of high levels of hypoxia-inducible factor, HIF2α/EPAS1, and the nuclear-encoded mitochondrial cytochrome c oxidase subunit, COX4I2, in glomus cell sensitivity to hypoxia.

Reactivation of sulfide-protected [FeFe] hydrogenase in a redox-active hydrogel

[FeFe] hydrogenases are highly active hydrogen conversion catalysts, whose oxygen sensitivity prevents their widespread application. Here, an oxygen-stable inactive form was reactivated in a redox hydrogel enabling its practical use under air.

Oxygen sensing and OLED applications of di-tert-butyl-dimethylacridinyl disubstituted oxygafluorene exhibiting long-lived deep-blue delayed fluorescence

Optical sensors with high oxygen sensitivity and efficient deep-blue OLEDs with CIEy of 0.08 was developed using the simplicity in molecular design of di-tert-butyl-dimethylacridanyl disubstituted oxygafluorene.