Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, NO and cGMP levels, as well as regulate MAPK signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca2+-sensitive K+ channels. More recent studies have revealed the ability of CO to inhibit T-type Ca2+ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.
[11C]Carbon monoxide (11CO) is a versatile building block for the synthesis of Positron Emission Tomography (PET) radioligands. However, the difficulty of trapping 11CO in a small solvent volume has limited its utility. We here report an evaluation of a simple, fully automated high‐pressure synthesizer prototype for the use in 11C‐carbonylation reactions. [11C]Carbon monoxide was easily prepared by online reduction of [11C]carbon dioxide using either Mo(s) or Zn(s) as the reducing agent. The conversion yield of 11CO was >99% when zinc was used as the reducing agent, and the corresponding value for Mo was approximately 71%. When the Zn or Mo column was constantly kept under inert atmosphere, no significant decrease in reducing properties was observed for more than 100 11CO productions. However, in our hands, Mo reductant was much easier to service. A total of nine functional groups were successfully radiolabeled using the 11CO synthesizer prototype. All measured radiochemical yields exceeded 37%, and the 11CO trapping efficiency was generally above 90%, except for the Suzuki coupling where the trapping efficiency was 80%. This high‐pressure synthesizer using [11C]carbon monoxide as the labeling precursor is easy to operate allowing for 11C‐carbonylation reactions to be performed in a high yield and in a routinely fashion. 相似文献
Two potent glucocorticoid receptor agonists were prepared labeled with carbon‐14 and with stable isotopes to perform drug metabolism, pharmacokinetics, and bioanalytical studies. Carbon‐14 labeled (1) was obtained from an enantiopure alkyne (5) via a Sonogashira coupling to a previously reported 5‐amino‐4‐iodo‐[2‐14C]pyrimidine [14C]‐(6), followed by a base‐mediated cyclization (1) in 72% overall radiochemical yield. Carbon‐14 labeled (2) was prepared in five steps employing a key benzoic acid intermediate [14C]‐(13), which was synthesized in one pot from enolization of trifluoromethylketone (12), followed by bromine–magnesium exchange and then electrophile trapping reaction with [14C]‐carbon dioxide. A chiral auxiliary (S)‐1‐(4‐methoxyphenyl)ethylamine was then coupled to this acid to give [14C]‐(15). Propargylation and separation of diastereoisomers by crystallizations gave the desired diastereomer [14C]‐(17) in 34% yield. Sonogashira coupling to iodopyridine (10) followed by cyclization to the azaindole [14C]‐(18) and finally removal of the chiral auxiliary gave [14C]‐(2) in 7% overall yield. For stable isotope syntheses, [13C6]‐(1) was obtained in three steps using [13C4]‐(6) and trimethylsilylacetylene‐[13C2] in 26% yield, while [2H5]‐(2) was obtained by first preparing the iodopyridine [2H5]‐(10) in five steps. Then, Sonogashira coupling to chiral alkyne (24) and cyclization gave [2H5]‐(2) in 42% overall yield. 相似文献
Highly expanded nanocomposite foams of polypropylene and carbon nanotubes (PP/CNT) are formed using supercritical carbon dioxide (scCO2) technology. The foaming parameters (temperature, pressure) are investigated to establish their influence on the morphology of the resulting foams and their impact on the electrical conductivity. As promising electromagnetic‐interference (EMI) absorbers, the EMI shielding performance of the foams is determined, and a preliminary relationship is established between foam morphology and the EMI shielding performance. The best candidates are highly expanded foams with a volume expansion of >25, containing 0.1 vol% CNTs; they are able to absorb more than 90% of the incident radiation between 25 and 40 GHz.
下载免费PDF全文