Biosynthesis is a necessary process to maintain life. In recent years, research has fully shown that three kinds of biothiols (Cys, Hcy, GSH) mainly play the role in oxidative stress and maintaining cell homeostasis in cells, and that abnormal concentrations will lead to the occurrence of cardiovascular diseases, cancers, etc. Various fluorescent probes have shown unprecedented advantages in detecting their concentrations and studying their biological functions. As a matter of fact, these three kinds of biothiols are generated in the process of biosynthesis in vivo. It is of great significance to understand their biosynthetic pathways and elucidate their synthetic relationships. In this work, to α,β-unsaturated ketones conjugated ethylenediamine coumarin and pyrandione was introduced boron fluoride and, through its strong electron deficiency effect, afforded a molecule having near-infrared emission and regulated the rigidity of molecules. At the same time, the conjugated double bond is used to respond to molecular rigidity. The rapid response of the probe to biothiols and the slow dissociation aggregation of the probe itself through the response environment could monitor the absence of biothiols in cells. In addition, based on the difference in sensitivity of response of Cys and GSH to the probe, this work studied the interaction between biosynthetic pathways of Cys and GSH in cells through enzyme inhibition for the first time. The relationship of restriction and regulation of biosynthesis in vivo was revealed.
Norepinephrine (NE) is synthesized in the locus coeruleus
and widely
projected throughout the brain and spinal cord. It regulates various
actions and consciousness linked to a variety of neurological diseases.
A “hunting–shooting” strategy was proposed in
this work to improve the specificity and response rate of an NE fluorescent
probe: 2-(cyclohex-2-en-1-ylidene)malononitrile derivatives were chosen
as a fluorophore. To create a dual-site probe, an aldehyde group was
added to the ortho of the ester group (or benzene
sulfonate). Because of its excellent electrophilic activity, the aldehyde
group could rapidly “hunt” the amino group and then
form an intramolecular five-membered ring via the
nucleophilic reaction with the β-hydroxyl group. The −NH–
in the five-membered ring “shoots” the adjacent ester
group, releasing the fluorophore and allowing for rapid and specific
NE detection. The NE release and reuptake ″emetic″–″swallow″
transient process is captured and visualized under the action of the
primary NE receptor drug. Furthermore, by introducing halogen into
the fluorophore to lengthen the absorption wavelength, improve lipid
solubility, and adjust the pK
a appropriately,
the probe successfully penetrated the blood–brain barrier (BBB). In situ synchronous probe imaging was used to detect the
NE level in the brains of epileptic and normal mice, and abnormal
expression of NE in the brain was discovered during epilepsy. Brain
anatomy was used to examine the distribution and level changes of
NE in various brain regions before and after epilepsy. This research
provides useful tools and a theoretical foundation for diagnosing
and treating central nervous system diseases early.
The excellent water solubility of hydrazine (N2H4) easily invades the human body through the skin and respiratory tract, thereby damaging human organs and central nervous system. To realize the monitoring...
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