Rational Design of Fluorophores for In Vivo Applications - Progress in Molecular Biology and Translational Science - page 84

600 nm). 186
Both chlorins and bacteriochlorins are present in the natural photosynthetic
apparatus in plants (chlorophyll a and b , chlorin derivatives) and in bacteria
(bacteriochlorophyll a , bacteriochlorin derivative). 187 Hence, nature is a
convenient and rich source of chlorin and bacteriochlorin derivatives.
The chemically modified chlorophyll and bacteriochlorophyll derivatives
have been used for in vivo imaging of cancer 188,191 or, as conjugates with
the

of fluorescence up to 0.70) at somewhat shorter wavelengths (

fluorescence quencher, have been used in vivo to monitor

phospholipase activity. 189,190
Naturally occurring chlorophylls and bacteriochlorophylls are attractive
because of their availability, but their use imposes certain problems and lim-
itations. First, naturally occurring derivatives have a full complement of sub-
stituents on the macrocycle periphery, and their chemical modification to
tune their optical and chemical properties, although possible, is limited.
Moreover, naturally occurring bacteriochlorophylls are rather unstable,
and outside their natural environment, they undergo oxidation to the more
conjugated derivatives with substantially different optical properties. There-
fore, a chief effort has been dedicated to developing stable synthetic chlorin
and bacteriochlorin analogs that would retain the optical properties of nat-
urally occurring compounds and would be amenable for synthetic modifi-
cations and fine-tuning of their physicochemical properties.
The routes developed for fully synthetic hydroporphyrins entail either
derivatization of porphyrins (which are usually much easier to prepare) 192
or de novo synthesis of the hydroporphyrin macrocycle. 193-200 The latter
approach, though more synthetically challenging, is more versatile and
enables full control of the position and numbers of substituents on the
periphery of the macrocycle (thus allowing also the extensive tuning of the
chemical and optical properties of hydroporphyrins). De novo routes enable
also preparation of more stable hydroporphyrins resistant to oxidation to
more conjugated porphyrins. Installation of geminal alkyl groups on the
partially saturated pyrroline rings in hydroporphyrins prevents oxidation of
chlorins and bacteriochlorins to more conjugated congeners. 193-195
Synthetic hydroporphyrins display a range of unique photochemical prop-
erties, which make them very attractive platforms to develop fluorophores
for in vivo applications. Both synthetic chlorins and bacteriochlorins exhibit
narrow and tunable absorption and emission bands. Their absorption and
emission maxima can be broadly tuned by simple substitution on the
periphery of the macrocycle, spanning the range of about 635-715 nm
for chlorins 183,185,199,200 and 715-823 nm for bacteriochlorins. 184 The
wavelengths of absorption and emission can be tuned virtually with