Trimethine cyanines

In this last case, the main skeleton considered could be the cationic trimethine cyanine and the third ring with its independent chain could be named as a substituent at the a or j3 position. When this substituent is of an ionic nature, it could be named after the corresponding ring, for... 

When a quinaldinium salt and 2-unsubstituted thiazolium are condensed together in the presence of a basic agent, the resulting bis-(methylquinoline-2)trimethine cyanine is issued from the cleavage of the thiazolium ring of the anhydrobase (25). It is induced by the -CHj attack of quinaldinium according to a process already described (Scheme 28). 

As an illustration of the real complexity of Mill s reaction, when two molecules of heterocycloammoniums of different nature, one of them being thiazolium (2-substituted or not), are put together in a basic medium, nine dyes theoretically can be produced (depending on the nature of the substituent in the ring) three thiazolomonomethine cyanines (two symmetrical, one asymmetrical) and six trimethine cyanines (two symmetrical, two symmetrical mesosubstituted. one unsymmetrical, one unsymmetrical mesosubstituted). One cannot separate such a mixture by usual chromatographic means. 

A mesophenyl-substituted trimethine cyanine has been identified as a by-product in syntheses leading to styryl dyes it is also obtained when the anhydrobase reacts with the styryl dye (26). 

Anilino vinyl derivatives of thiazolium (30, R = H) or acetanilido (30, R = C0CH3), as well as formyl methylene 30b (methods E-G), give asymmetrical dyes when condensed with a methyl reactive group of another species (Scheme 42). Mesosubstituted symmetrical or unsymmet-rical thiazolocyanines are obtainable via /S-alkylmercaptovinyl thiazolium derivatives (32) (methods H and I) (Scheme 43). a or /S carbon atoms of the trimethine chain can be substituted by acetyl when a dye is treated with acetic anhydride (method L). The hydrolysis of neocyanines lead to trimethine cyanine by fractional elimination of a composant chain (method K). 

For example, when N-ethylrhodanine is condensed with (quino)ine-4)(4-methylthiazole-2)trimethine cyanine or (pyridine-2)(4-methylthia-zole-2)trimethine cyanine, the yields obtained for neutrothiazolo-dimethine dye are 25 and 75%, respectively (53). 

The easier elimination of pyridine compared to quinoline-4 may be related to the pK value of 4-methylthiazole, which is between those of lepidine and 2-picoline (25. 55). This reaction explains also why a neutrodimethine cyanine is obtained with such good yields when reacting together a quaternary salt, ketomethylene, and o-ester in a basic medium. As the reaction proceeds, the trimethine cyanine is attacked by the ketomethylene. The resulting 2-methyl quaternary salt is transformed into trimethine cyanine, consuming the totality of the ketomethylene (1, p. 512 661). The mesosubstituted neutrodimethine cyanine is practically pure. 

TABLE 2I21A. SYMMETRICAL UNSUBSTITUTED TRIMETHINE CYANINES... 

Quaternary salts, pKa value of, 7] polarographic reduction potentials, 71 Quinaldinium salts, in Mills reaction, 37,45 Quinoline-4)(4-methvlthiazole-2) trimethine cyanine, 62... 

Rhodanine, A-ethyl. attack on trimethine cyanines. 62 for neutrocyanines, 27 in synthesis of dimethine neutrocyanine. 60... 

Ketomethylene, 4-(4-anilinobu tadienyli-dene), in the synthesis of tetra-methine neutrocyanines, 63 Ketomethylene compounds, attack on trimethine cyanines, 62 in synthesis of zeromethine cyanines,... 

Various hybrid compounds comprised of two types of nitroxide radicals and either a pentamethine (Cy5) or trimethine cyanine (Cy3) were synthesized by Sato and co-workers [32]. These compounds seem to be promising fluorescent chemo-sensors for the measurement of reducing species such as Fe2+, ascorbic acid, and hydroxyl radicals. 

Presently, the only commercially available dyes that are applied because of then-ability to form fluorescent aggregates are trimethine cyanines JC-1 and JC-9 (Fig. 11) [25], the first one being studied much more extensively than the second one. The dye JC-1 is known to form red-fluorescent (emission maximum at 590 nm) J-aggregates in mitochondria possessing strong intramitochondrial negative potential, while upon depolarization of the mitochondrial membrane, the dye monomer green emission (maximum at 527 nm) is observed [25]. JC-9 demonstrates similar properties [25]. Such properties permit the application of these dyes for, e.g., detection of apoptotic electrical depolarization of mitochondria [25]. 

Closely related are the cyanine dyes, for example cyanine (62) itself, which is formed from the ethiodide salts of lepidine and 4-iodoquinoline in the presence of base (Scheme 51). Analogous monomethine cyanines can have the quinoline nuclei linked 2,2 (pseudocyanines) and 2,4 (isocyanines). Quinaldine ethiodide on condensation With ethyl orthoformate gives the 2,2 -linked trimethine cyanine (carbocyanine) (63), known as pinacyanol (Scheme 51). 

Reaction of the quaternized salts of 4-ethoxycarbonyl-3,5-dimethyl-f-phenylpyttolo(furo or thieno)[2,3-c]pyrazole 34 with the iodomethane quaternary salts of pyridine, quinoline, and isoquinoline in ethanol with catalytic piperidine gave 3-[4(f)]-monomethine cyanine dyes (e.g., 35). Additionally, 3-[2(4)]-trimethine cyanine dyes and 4-[2(4)]-di-3[2(4)]-tri-mixed methine cyanine dyes (e.g., 36 and 37, respectively) were similarly prepared from the intermediates derived by reaction of 34 with triethyl orthoformate in the presence of piperidine (Scheme 8) <2002CCS106f>. 

Non-tellurium-containing type-123 trimethine dyes have been found recently to be susceptible to a reaction with chlorine and bromine (93MI1 94MI1). In this case, however, the reaction is rather slow and occurs at the trimethine bridges. For the formation of dihalogenides 124, halogens must be present in at least 2.5-fold excess to the initial trimethine cyanine 122. 

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