Rational Design of Fluorophores for In Vivo Applications - Progress in Molecular Biology and Translational Science - page 68

which alter their optical properties. Cyanines in solution are prone to pho-
tobleaching, oxidation, solvatochromic effects, and nonspecific interactions
with plasma proteins (see Refs. 27, 28 , and introduction to Ref. 80 and
references cited therein). Cyanine itself has a low fluorescence quantum
yield because of the competitive internal conversion and
photoisomerization. 33 In addition, in aqueous solutions, cyanines undergo
different types of aggregation, 45 and in a biological environment, they
nonspecifically interact with biomolecules. 28 All of these effects cause
diminishing of the fluorescence quantum yield and altering of the
maxima of both absorption and emission bands of cyanines in vivo .
Hence, much effort has been devoted to improving the chemical and
photochemical stability of cyanines; minimizing the nonspecific
interactions of cyanines with blood, plasma, or cellular components;
diminishing their aggregation in aqueous solution; and increasing their
quantum yields of fluorescence. Many of the reported methods
collectively improve the optical properties, stability and water solubility,
or aggregation behavior, so all of them will be discussed here in the same
subchapter. Two general directions have been followed to improve the
stability and fluorescence properties of cyanines: chemical modification of
the cyanine structure and encapsulation of cyanines inside dendrimers,
cyclodextrines, or nanoparticles.
2.3.1 Chemical modifications
Improvement of chemical stability and moderate increase in quantum yields
of fluorescence have been observed for cyanines with a polymethine chain
rigidified by the cyclohexene ring. 31 However, cycloheptamethine deriva-
tives substituted at cyclohexene ring with electron-donating amine groups
exhibit significantly reduced stability. 81,82 It has been subsequently
demonstrated that installing an acetyl substituent on the nitrogen, which
reduces electron density on the cyanine scaffold, significantly stabilizes
the N- acyl-substituted derivatives. 82,83
An another strategy to improve chemical stability has been pursued by
Armitage and coworkers, who observed that polyfluorinated pentamethine
cyanine having benzothiazolium units at both termini exhibits increased
fluorescence quantum yield, reduced tendency to aggregate in aqueous
solution, higher chemical stability, and greater resistance toward photo-
bleaching compared to its nonfluorinated analog. 84 The authors pointed
out that fluorination might be a general strategy for the improvement of