Fluoroionophores

A cartoon of a fluorescent switch , turned on or off (quenched) depending on the absence or presence of a metal ion. The ionophore (the cyclic polyether) is the metal-binding component, the fluorophore (the fused-ring aromatic unit) is the component activated by light. Complexation stops electron transfer that otherwise quenches fluorescence. 

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Rurack K, Koval chuck A, Bricks JL et al (2001) A Simple bifunctional fluoroionophore signaling different metal ions either independently or cooperatively. J Am Chem Soc 123 6205-6206... 

Yang JS, Hwang CY, Hsieh CC et al (2004) Spectroscopic correlations between supermolecules and molecules. Anatomy of the ion-modulated electronic properties of the nitrogen donor in monoazacrown-derived intrinsic fluoroionophores. J Org Chem 69 719-726... 

Rurack K, Kollmannsberger M, Resch-Genger U et al (2000) A selective and sensitive fluoroionophore for Hgll, Agl, and Cull with virtually decoupled fluorophore and receptor units. J Am Chem Soc 122 968-969... 

Fig. 10.9. Main aspects of fluorescent molecular sensors for cation recognition (fluoroionophores).

More than one ionophore and/or more than one fluorophore may be involved in the structure of fluoroionophores. Figure 10.10 illustrates some of the structures that have been designed. 

When a fluoroionophore contains two fluorophores whose mutual distance is affected by cation complexation, recognition of this cation can be monitored by the monomer/excimer fluorescence-intensity ratio (see Chapter 4, Section 4.4.1 for ex-rimer formation). Cation binding may favor or hinder exrimer formation. In any case, such a ratiometric method allowing self-calibration measurement is of great interest for practical applications. 

The examples described above illustrate the immense variety of fluoroionophores that have been designed for cation recognition. Emphasis was put on the understanding of cation-induced photophysical changes, which should help the user and the designer of this kind of sensor. 

The methods of anion detection based on fluorescence involve quenching, complex formation, redox reactions and substitution reactions (Fernandez-Gutierrez and Munoz de la Pena, 1985). This chapter will be restricted to anion molecular sensors based on collisional quenching (in general, they exhibit a poor selectivity) and on recognition by an anion receptor linked to a fluorophore (fluoroionophore). 

In particular, for a ditopic receptor that can bind successively two cations (see previous section), the criterion for cooperativity is Kn/Ku > 1/4, i.e. complexation of a second cation is made easier by the presence of a bound cation. For instance, a cooperative effect was observed with fluoroionophore E-l (see Section 10.3.4). 

The discovery of crown ethers and cryptands in the late sixties opened new possibilities of cation recognition with improvement of selectivity, especially for alkali metal ions for which there is a lack of selective chelators. Then, the idea of coupling these ionophores to chromophores or fluorophores, leading to so-called chromoionophores and fluoroionophores, respectively, emerged some years later l9) As only fluorescent probes are considered in this chapter, chromoionophores will not be described. 

In the design of a fluoroionophore, much attention is to be paid to the characteristics of the ionophore moiety and to the expected changes in fluorescence characteristics of the fluorophore moiety on binding. The complexing ability of the ionophore will be considered first. 

Figure 2.1. Schematic illustration of various structures of fluoroionophores. (a) Chelators and podands (b) coronands (c) cryptands (d) other structures.

Figure 2.5. Spectral displacement of fluoroionophores based on cation control of photoinduced charge transfer in conjugated donor-acceptor systems.

Figure 2.6. Examples of donor-acceptor fluoroionophores in which the electron-donating character of the donor (nitrogen atom of the crown) is cation-controlled.

Figure 2.8, Schematic illustration of photoejection of cation from a donor-acceptor fluoroionophore,...

Figure 2.9. Examples of donor-acceptor fluoroionophores designed for the recognition of cytosolic calcium, magnesium, and sodium ions.

Figure 2.10. Example of a donor-acceptor fluoroionophore in which the electron-withdrawing character of the acceptor (carbonyl group of the coumarine) is cation-controlled. Absorption and fluorescence spectra of ClS3-crown(Oj) and its complexes with perchlorate salts in acetonitrile. (Adapted from Ref. SO.)...

Table 2.1. Effect of the Nature of the Fluorophore on the Stability Constants (Ks = [ML]/[M][L]) of Complexes with Fluoroionophores Containing Monoaza-15-crown-5 in Acetonitrile...

Figure 2.11. Examples of fluoroionophores consisting of two donor-acceptor fluorophores.

The importance of solvent effects has been outlined in Section 2.2.1. An illustration with some of the fluoroionophores described in this section is given in Table 2.2. For alkali and alkaline-earth metal ions, the stability constants are higher in acetonitrile than in methanol these cations are indeed hard and have a stronger affinity for oxygen atoms (hard) than for nitrogen atoms (soft). In contrast, the soft silver atom has a strong affinity for nitrogen atoms and no complexation is observed in acetonitrile, whereas complexes in methanol, ether, and 1,2-dichloromethane are formed. 

Figure 2.16. Various fluoroionophores undergoing particular changes in some of their photophysical properties on cation binding.

Figure 2.17. Examples of fluoroionophores for recognition of anions (Adapted from Refs. 72 and 73.)...

In analytical chemistry, detection of metal ions is of major importance. In particular, the development of simple and reliable methods for continuous control in situ of metal ions in the environment is the object of much attention. For instance, the detection of lead, mercury, cadmium, and iron ions in sea water will be performed in the near future by optodes associated with suitable fluoroionophores, thus allowing continuous monitoring by instruments on ships. 

S. Fery-Forgues, M.-T. Le Bris, J.-P. Guette, and B. Valeur, First crown ether derivative of benzoxazinone anew fluoroionophore for alkaline earth metals recognition, J. Chem, Soc., Chem, Commun. 5, 384-385 (1988). 

Other Fluoroionophores with Enhanced Fluorescence in the Presence of Cations... 

For this type of integrated fluoroionophores, the photochemical processes can be accelerated and can lead to very fast and reversible photochemical ion release or ion takeup. One example has been described recently 140 where Ca2+ or Li+ is ejected in some picoseconds. By this way, the application of biologically useful chelators, which have their binding constant altered by an irreversible photoreaction taking at best some milliseconds, 141 can be extended to ultrashort time scales. 

Structurally the fluoroionophores are made up of a fluorophore and a receptor chelate, sometimes linked by a spacer. Three different ways of connecting the fluorophores with the receptors are shown in Eigure 3.17. ... 

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