BODIPY dyes

Fluorophores containing 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene as a core skeleton are commonly designated as BODIPY fluorophores. Due to their useful photophysical properties including high fluorescence quantum yields, high molar absorption coefficient, narrow absorption and emission band width, and their high photostability [50], BODIPY dyes are proven to be extremely versatile and useful in many biological applications Fig. 11 [68]. 

The first BODIPY fluorophore was synthesized by Treibs and Kreuzer in 1968 [69]. As described in recent review article [70], BODIPY dyes can be categorized into... 

Symmetrically substituted BODIPY dyes are relatively easy to be synthesized via the condensation of pyrroles with carbonyl electrophiles, such as acyl chlorides,... 

Fig. 12 Synthetic scheme for symmetrically substituted BODIPY dyes (a) and unsymmetrically substituted BODIPY dyes (b)...

On the other hand, the introduction of halide substituents at the C-2 and C-6 position decreases fluorescence quantum yields and gives a bathochromic shift of emission maxima. For example, bromine at the C-2 and C-6 position in compound 14b deteriorates fluorescence quantum yields from 0.95 (14a) to 0.45 and the emission maximum is red-shifted by 42 nm. Moreover, iodine at the C-2,6 position in compound 14d gives the similar bathochromic shift to bromine (14b, 44 nm) and more dramatic reduction in quantum yields (almost nonfluorescent, photophysical properties were interpreted as the heavy atom effect of halides on a BODIPY core skeleton. The bathochromic shift of BODIPY dyes without dramatic decrease in quantum yield was observed by the introduction of vinyl substituents at the C-2 and C-6 position. The extension of conjugation... 

Loudet A, Burgess K (2007) BODIPY dyes and their derivatives syntheses and spectroscopic properties. Chem Rev 107 4891 1932... 

BODIPY is a short for 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, the basic structure of this type of fluorophore (see Fig. 6.5). Derivatives of this dye have been created by modification of positions 1, 3, 5, 7, and 8, generating an array of fluorophores with very distinct excitation and emission properties [38]. Molecular Probes has synthesized a wide number of BODIPY dyes whose excitation... 

FRET probes have not only been generated to measure the phospholipase activity but to study its substrate specificity as well. Several substrates of PLA2 with a variety of head groups and labeled with a BODIPY dye and a Dabcyl quencher were created by Rose et al. and tested against different PLAs in cells to determine substrate specificity and intracellular localization [137], The specificity of PLA2 isoforms towards the number of double bonds in the sn2 position was evaluated with a small series of PENN derivatives. It was demonstrated that the cytosolic type V PLA2 preferred substrates with a single double bond [138],... 

Rohand, T, Baruah, M, Qin, W. W, Boens, N. and Dehaen, W. (2006). Functionalisation of fluorescent BODIPY dyes by nucleophilic substitution. Chem. Commun. 266-268. 

Using 2-bromopyrrole 72, Burgess has synthesized 2-arylpyrroles 73 in excellent yield [61], The resulting hydrolyzed pyrroles 74 were used to prepare 3,5-diaryl BODIPY dyes. 

The optical properties of organic dyes (Fig. ld-f, Table 1) are controlled by the nature of the electronic transition(s) involved [4], The emission occurs either from an electronic state delocalized over the whole chromophore (the corresponding fluorophores are termed here as resonant or mesomeric dyes) or from a charge transfer (CT) state formed via intramolecular charge transfer (ICT) from the initially excited electronic state (the corresponding fluorophores are referred to as CT dyes) [4], Bioanalytically relevant fluorophores like fluoresceins, rhodamines, most 4,4 -difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY dyes), and cyanines (symmetric... 

Jones LJ, Upson RH, Haugland RP, Panchuk-Voloshina N, Zhou M, Haugland RP. Quenched BODIPY dye-labeled casein substrates for the assay of protease activity by direct fluorescence measurement. Anal Biochem 1997 251(2) 144-152. 

Benzo[4,5]furo[3,2- ]pyrrole 86 and benzo[4,5]thieno[3,2- ]pyrrole 87 were used for the synthesis of new constrained aryl-substituted 4,4-difluoro-4-bora-3a,4a-diaza-r-indacene (BODIPY) dyes 86 and 89 <2000JOC2900>. Their fluorescence characteristics were investigated and compared with the unconstrained systems published by Burghart and co-workers (Scheme 8) <199881276, 1999JOC7813>. 

Direct labeling of a biomolecule involves the introduction of a covalently linked fluorophore in the nucleic acid sequence or in the amino acid sequence of a protein or antibody. Fluorescein, rhodamine derivatives, the Alexa, and BODIPY dyes (Molecular Probes [92]) as well as the cyanine dyes (Amersham Biosciences [134]) are widely used labels. These probe families show different absorption and emission wavelengths and span the whole visible spectrum (e.g., Alexa Fluor dyes show UV excitation at 350 nm to far red excitation at 633 nm). Furthermore, for differential expression analysis, probe families with similar chemical structures but different spectroscopic properties are desirable, for example the cyanine dyes Cy3 and Cy5 (excitation at 548 and 646 nm, respectively). The design of fluorescent labels is still an active area of research, and various new dyes have been reported that differ in terms of decay times, wavelength, conjugatibility, and quantum yields before and after conjugation [135]. New ruthenium markers have been reported as well [136]. 

Due to space constraints, only a few review articles that discuss the synthesis and chemistry of novel classes of pyrrole materials will be discussed here. A comprehensive review of the important class of dyes, known collectively as BODIPY dyes (difluoro-4-bora-3a,4a-diaza-.s-indacene 79), appeared <07CRV4891>. Reviews of carboporphyrins <07EJO5461> and acyclic oligopyrroles <07EJO5313> were also published. 

Figure 4.31 BODIPY Dyes. Normalized fluorescence emission spectra of (1) BODIPY FL (2) BODIPY R6G (3) BODIPY TMR (4) BODIPY 581/591 (5) BODIPY TR (6) BODIPY 630/650 (7) BODIPY 650/665 fluorophores in methanol (Reproduced from Molecular Probes Handbook, Fig. 1.37).

Syntheses and spectroscopic properties of BODIPY dyes and their derivatives (BODIPY is4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) 07CRV4891. 

Bis(trifluoroacetoxy)iodo]benzene in conjunction with a Lewis acid promotes C—C coupling of Bodipy (4,4 -difluoro-4-bora-3a,4a-diaza- -indacene) monomers 331 leading to mixtures of dimers 332 (when X = I orp-tolyl) (Scheme 3.133) and higher oligomers when X = H [386], Bodipy dyes have attracted significant interest in recent years due to their outstanding optical properties. 

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