Rational Design of Fluorophores for In Vivo Applications - Progress in Molecular Biology and Translational Science - page 75

that illustrate the design strategies to shift the absorption/emission bands to-
ward longer wavelengths are given in Chart 3.3 . Substitution on the pyrrole
subunits with conjugated substituents, such as styryl or arylethynyl, with
electron-donating groups shifts absorption/emission above 800 nm (e.g.,
compounds ). 126,132-134 BDP derivatives

with a fused benzene or naphthalene ring at the pyrrole subunits exhibit
absorption/emission bands around 700 nm (e.g., compounds

BDP-I , BDP-II ,and BDP-III

BDP-IV and

). 127,135,136 Replacement of meso carbon atom with nitrogen
leads to the formation of aza-BDP derivatives whose absorption and
emission bands are shifted toward longer wavelengths by about 150 nm
compared to the corresponding BDP analogs. 128 Aza-BDP derivatives
substituted at the a -pyrrolic position with aromatic substituents possessing
an electron-donating group exhibit absorption/emission at

BDP-V

688/715 nm

). 128,137,138 An additional bathochromic shift of about 50 nm
and an increase in extinction coefficient have been achieved by rigidifying
the aryl

( aza-BDP-VI

substituents, either by embedding the aryl substituent into a

) 129 cyclohexane ring ( aza-BDP-VII or by the formation of a

). 130 Fusing of the benzo ring on the
pyrrole moieties allows shifting of the absorption/emission bands above
800 nm. 139,140
BDP derivatives with fused furan rings and p- methoxyphenyl substituents
absorb and emit in the red or near-IR spectral window, depending on the
substituent present at the meso position (BDP-IX and BDP-X). 131 The lat-
ter derivatives exhibit exceptionally high extinction coefficients and high
quantum yield of fluorescence, both of which make them probably the
brightest near-IR organic fluorophores. 131
An inspection of the literature data, exemplified in Chart 3.3 , indicates
that the optical properties of BDP can be broadly tuned and optimized by
careful molecular design, whereby derivatives with long absorption wave-
length and high extinction coefficient and quantum yield of fluorescence
can be obtained.
Another problem associated with use of BDPs for in vivo imaging is
their inherent hydrophobic character and the lack of water solubility of their
simple derivatives. Water solubility, however, can be imparted by the
attachment of hydrophilic groups to the BDP core. Several water-soluble,
highly fluorescent BDP derivatives have been prepared containing
hydrophilic groups,

boron-oxygen bond ( aza-BDP-VIII

sulfonates, 141,142 carboxylates, 141,143,144 such as

phosphonates, 145 ammonium salts, 141

quarternary di(hydroxyethyl)

amine, 146 oligoethylene glycol chains, 134,147-150 sulfonated peptides, 151