A Noncovalent Fluorescence Turn‐on Strategy for Hypoxia Imaging

Abstract

Hypoxia plays crucial roles in many diseases and is a central target for them. Present hypoxia imaging is restricted to the covalent approach, which needs tedious synthesis. In this work, a new supramolecular host–guest approach, based on the complexation of a hypoxia‐responsive macrocycle with a commercial dye, is proposed. To exemplify the strategy, a carboxyl‐modified azocalix[4]arene (CAC4A) was designed that binds to rhodamine 123 (Rho123) and quenches its fluorescence. The azo groups of CAC4A were selectively reduced under hypoxia, leading to the release of Rho123 and recovery of its fluorescence. The noncovalent strategy was validated through hypoxia imaging in living cells treated with the CAC4A–Rho123 reporter pair.

Indicator displacement assays (IDAs): the past, present and future

“…This ''domino tandem assay'' was performed in the same solution with a single reporter pair (CB [7] rhodamine 123. 36 Rhodamine 123 (Rho123) was shown to bind within the azocalix [4]arene (CAC4A) host with a 1 : 1 binding stoichiometry with attendant fluorescence quenching. In hypoxic environments, bioreductive enzymes capable of reducing a variety of organic functionalities are over-expressed.…”

On the encapsulation and assembly of anticancer drugs in a cooperative fashion

“…To further quantify the inclusion complexation, we noted that incremental addition of basket 1 6– to 2 + (Fig. 3A) quenched the emission from doxorubicin;36 the quenching was static,37 since in the absence of the complex formation the emission from the drug remained steady (Fig. S7†).…”

A Cofactor‐Substrate‐Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions

“…The direct modulation of cofactor mimics into the backbone of the capsules is postulated to be a promising approach to enforce active sites into close proximity with substrates and promote the electron transfer process between reactants efficiently. The encapsulation of a substrate‐based luminescent probe in stoichiometric cofactor‐backbone “molecular containers” would be an important tool for distinguishing and quantitatively detecting different degrees of the enzymatic activity between healthy and diseased states. The new host–guest cofactor‐substrate‐based supramolecular probe approach enabled the redox reaction of luminescent substrate, cofactor and enzyme to occur efficiently with excellent compatibility between kinetics and reaction intermediates …”

“…To echo the remarkable properties of enzymes for achieving efficient chemical conversions,c hemists have used metal-organic cages with defined hydrophobic cavities as unique hosts to catalyze unique chemical transformations. [14,15] Thed irect modulation of cofactor mimics into the backbone of the capsules is postulated to be ap romising approach to enforce active sites into close proximity with substrates [16] and promote the electron transfer process between reactants efficiently.T he encapsulation of as ubstrate-based luminescent probe in stoichiometric cofactorbackbone "molecular containers" [17] would be an important tool for distinguishing and quantitatively detecting different degrees of the enzymatic activity between healthy and diseased states.T he new host-guest cofactor-substrate-based supramolecular probe approach enabled the redox reaction of luminescent substrate,c ofactor and enzyme to occur efficiently with excellent compatibility between kinetics and reaction intermediates. [18] By incorporating the NADH mimics,t he most common cofactor [19] in the hypoxia-related enzymes,into the backbone of am etal-organic capsule Zn-MPB,w eh erein present ac ofactor-substrate-based supramolecular probe (Zn-MPB'L-NO 2 )f or biochemical imaging of enzyme nitroreductase (NTR) under hypoxia in aqueous solution and living systems.…”