To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.

Fluorescent probes 1 and 2 were prepared directly from tetramethyl-BODIPY via palladium-mediated C-H functionalization reactions.

Four systems 1a – d were prepared to investigate the optical properties of copolymers comprised of polyfluorene doped with BODIPY-based fluors. The underlying hypothesis was energy harvested via the strong absorptivity of the major component, fluorine, would be primarily emitted from the BODIPY parts at much higher wavelengths. Optimization of the polymerization process as a function of the mol % of BODIPY, indicated that the brightest polymers were formed when approximately 4 fluorene units were co-polymerized with every BODIPY precursor. These polymers were cast into nanoparticles of ca 40 nm diameter. Treatment of clone 9 rat liver cells with suspensions of these particles resulted in uptake without encapsulation in lysosomes, or organelle targeting.

Photophysical data and orbital energy levels (from electrochemistry) were compared for molecules with the same BODIPY acceptor part (red) and perpendicularly oriented xanthene or BODIPY donor fragments (green). Transfer of energy, hence the photophysical properties of the cassettes, including the pH dependant fluorescence in the xanthene containing molecules, correlates with the relative energies of the frontier orbitals in these systems. Intracellular sensing of protons is often achieved via sensors that switch off completely at certain pH values, but probes of this type are not easy to locate inside cells in their “off-state”. A communication from these laboratories (J. Am. Chem. Soc., 2009, 131, 1642 – 3) described how the energy transfer cassette 1 could be used for intracellular imaging of pH. This probe is fluorescent whatever the pH, but its exact photophysical properties are governed by the protonation-states of the xanthene donors. This work was undertaken to further investigate correlations between structure, photophysical properties, and pH for energy transfer cassettes. To achieve this, three other cassettes 2 – 4 were prepared another one containing pH-sensitive xanthene donors (2), and two “control cassettes” that each have two BODIPY-based donors (3 and 4). Both the cassettes 1 and 2 with xanthene-based donors fluoresce red under slightly acidic conditions (pH < ca 6), and green when the medium is more basic (> ca 7), whereas the corresponding cassettes with BODIPY donors give almost complete energy transfer regardless of pH. The cassettes that have BODIPY donors by contrast, show no significant fluorescence from the donor parts, but the overall quantum yields of the cassettes when excited at the donor (observation of acceptor fluorescence) are high (ca 0.6 and 0.9). Electrochemical measurements were performed to elucidate orbital energy level differences between the pH-fluorescence profiles of cassettes with xanthene donors, relative to the two with BODIPY donors. These studies confirm energy transfer in the cassettes is dramatically altered by analytes that perturb relative orbital levels. Energy transfer cassettes with distinct fluorescent donor and acceptor units provide a new, and potentially useful, approach to sensors for biomedical applications.

Key indicators: single-crystal X-ray study; T = 293 K; mean (C-C) = 0.002 A ˚ ; R factor = 0.041; wR factor = 0.126; data-to-parameter ratio = 14.3. In the title compound, C 13 H 15 BF 2 N 2 , the two pyrrole rings are almost coplanar, with a dihedral angle of 3.08 (10). The BF 2 plane is almost perpendicular to the boron-dipyrromethene ring plane, with a dihedral angle of 89.99 (7). Related literature For related literature, see: Bergströ m et al. (2002); Koll-mannsberger et al. (1998); Kuhn et al. (1990); Trieflinger et al. (2005). Experimental Crystal data C 13 H 15 BF 2 N 2 M r = 248.08 Monoclinic, P2 1 =c a = 7.6909 (8) A ˚ b = 14.3392 (15) A ˚ c = 11.8334 (10) A ˚ = 111.108 (5) V = 1217.4 (2) A ˚ 3 Z = 4 Mo K radiation = 0.10 mm À1 T = 293 (2) K 0.30 Â 0.20 Â 0.20 mm Data collection Rigaku Mercury2 diffractometer Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) T min = 0.961, T max = 0.974 6540 measured reflections 2396 independent reflections 1963 reflections with I > 2(I) R int = 0.019 Refinement R[F 2 > 2(F 2)] = 0.040 wR(F 2) = 0.126 S = 1.06 2396 reflections 167 parameters H-atom parameters constrained Á max = 0.27 e A ˚ À3 Á min = À0.24 e A ˚ À3