Danaboyina Ramaiah

Tuning Photosensitized Singlet Oxygen Generation Efficiency of Novel Aza-BODIPY Dyes

Novel aza-BODIPY derivatives substituted with heavy atoms such as bromine and iodine were synthesized, and their triplet and singlet oxygen generation efficiencies have been investigated. These derivatives showed absorption in the NIR region with high molar extinction coefficients. The dye substituted with four iodine atoms showed yields of Φ(T) = 0.78 and Φ((1)O(2)) = 0.70, which are the highest values so far obtained for the aza-BODIPY derivatives.

Fluorescence Ratiometric Selective Recognition of Cu2+ Ions by Dansyl-Naphthalimide Dyads

Chimeric dyads 1a and 1b based on dansyl and naphthalimide units linked through the polymethylene group were synthesized, and their photophysical and interactions with various metal ions were investigated under different conditions. These dyads showed dual emission centered at around 375 and 525 nm, respectively, due to the locally excited state of the naphthalimide chromophore and energy-transfer-mediated emission (FRET) from the dansyl moiety. When titrated with various metal ions, these systems exhibited unusual selectivity for Cu(2+) ions as compared to Na(+), Li(+), K(+), Zn(2+), Pb(2+), Hg(2+), Co(2+), Fe(2+), Cd(2+), Mg(2+), and Ba(2+) ions and signaled the binding event through inhibition of FRET mediated emission at 525 nm with concurrent enhancement in the emission intensity of the naphthalimide chromophore at 375 nm. The uniqueness of these dyads is that they form stable 2:1 stoichiometric complexes involving sulfonamide functionality and act as visual fluorescence ratiometric probes for the selective recognition of Cu(2+) ions.

Aza‐BODIPY Derivatives: Enhanced Quantum Yields of Triplet Excited States and the Generation of Singlet Oxygen and their Role as Facile Sustainable Photooxygenation Catalysts

A new series of aza-BODIPY derivatives (4 a-4 c, 5 a,c, and 6 b,c) were synthesized and their excited-state properties, such as their triplet excited state and the yield of singlet-oxygen generation, were tuned by substituting with heavy atoms, such as bromine and iodine. The effect of substitution has been studied in detail by varying the position of halogenation. The core-substituted dyes showed high yields of the triplet excited state and high efficiencies of singlet-oxygen generation when compared to the peripheral-substituted systems. The dye 6 c, which was substituted with six iodine atoms on the core and peripheral phenyl ring, showed the highest quantum yields of the triplet excited state (Φ(T) =0.86) and of the efficiency of singlet-oxygen generation (Φ(Δ) =0.80). Interestingly, these dyes were highly efficient as photooxygenation catalysts under artificial light, as well as under normal sunlight conditions. The uniqueness of these aza-BODIPY systems is that they are stable under irradiation conditions, possess strong red-light absorption (620-680 nm), exhibit high yields of singlet-oxygen generation, and act as efficient and sustainable catalysts for photooxygenation reactions.

Squaraine Dyes for Photodynamic Therapy: Mechanism of Cytotoxicity and DNA Damage Induced by Halogenated Squaraine Dyes Plus Light (>600 nm)¶

Halogenated squaraine dyes 1 and 2 possess favorable photophysical and in vitro photobiological properties that make these new class of molecules interesting for photodynamic therapeutic applications. For a better understanding of the mechanism of their photobiological activity, we have analyzed the DNA damage and the cytotoxicity induced by these photosensitizers in mammalian cells and cell‐free systems in the presence and absence of various additives and scavengers. Both photoactivated squaraines were found to be similar efficient in inducing single‐strand breaks (SSB) in cell‐free DNA when compared with the cellular DNA. Superoxide dismutase and catalase did not show any influence. However, the presence of tert‐butanol and glutathione inhibited the formation of the DNA SSB, indicating an indirect (possibly squaraine radical mediated) mechanism under cell‐free conditions. Replacing H2O in the buffer by D2O resulted in a five‐ to six‐fold increase in the number of the SSB in cell‐free DNA and a significant enhancement of the photocytotoxicity in mouse lymphoma cells. The results demonstrate that singlet oxygen is the major reactive species under cell‐free and cellular conditions and confirm that squaraine‐based sensitizers 1 and 2 can have potential applications in photodynamic therapy.

Halogenated Squaraine Dyes as Potential Photochemotherapeutic Agents. Synthesis and Study of Photophysical Properties and Quantum Efficiencies of Singlet Oxygen Generation

Abstract— We describe the synthesis and photophysical studies, including measurements of quantum yields of triplet excited states and singlet oxygen generation of bis(3,5‐dibromo‐2,4,6‐trihydroxyphenyl)squaraine (2) and bis(3,5‐diiodo‐2,4,6‐trihydroxyphenyl)squaraine (3). These dyes exist in solution in the protonated, neutral, single and double depro‐tonated forms, depending on pH. The pKa values of these dyes were found to be relatively lower than those of the parent bis(2,4,6‐trihydroxyphenyl)squaraine (1). Only the single deprotonated forms (Sq) of 2 and 3 showed measurable fluorescence. In microheterogeneous media such as in the presence of β‐cyclodextrin, cetyltrunethylammonium bromide and polyvinylpyrrolidone), bathochromic shifts in the absorption and emission spectra of Sq were observed with a substantial enhancement in their fluorescence yields. Triplet excited states are the main transient intermediates obtained upon 532 nm laser excitation of the various forms of 2 and 3 in methanol. These triplets have lifetimes in the range from 0.061 to 132 μs. The triplet quantum yields of double deprotonated forms are low (φT = <0.01), whereas the neutral and Sq−forms of 2 (φr = 0.12 and 0.22) and 3 (φT= 0.24 and 0.5), respectively, exhibited significant triplet yields. Quantum yields of singlet oxygen generation by Sq−forms of 2 and 3 were determined in methanol and were found to be 0.13 and 0.47, respectively, which are in good agreement with the triplet yields obtained in these systems.

Squaraine Dyes for Photodynamic Therapy: Study of Their Cytotoxicity and Genotoxicity in Bacteria and Mammalian Cells¶,‡

Abstract Halogenated squaraine dyes are characterized by long wavelength absorption (>600 nm) and high triplet yields and therefore represent new types of photosensitizers that could be useful for photodynamic therapy. We have analyzed the cytotoxicity and genotoxicity of the bromo derivative 1, the iodo derivative 2 and the corresponding nonhalogenated dye 3 in the absence and presence of visible light. At concentrations of 1–2 μM, 1 and 2 reduced the cloning efficiency of AS52 Chinese hamster ovary cells to less than 1% under conditions that were well tolerated in the dark. Similarly, the proliferation of L5178Y mouse lymphoma cells was inhibited by photoexcited 1 and 2 with high selectivity. The squaraine 3 was much less efficient. Both 1 and 2 induced only few mutations in the gpt locus of the AS52 cells in the presence of light and were not mutagenic in the dark. No mutagenicity with and without irradiation was observed in Salmonella typhimurium TA100 and TA2638. However, both 1 and 2 plus light increased the frequency of micronuclei in AS52 cells. The results indicate that halogenated squaraines exhibit photobiological properties in vitro that are favorable for photodynamic therapeutical applications.

meso-Tetrakis(p-sulfonatophenyl)N-Confused Porphyrin Tetrasodium Salt: A Potential Sensitizer for Photodynamic Therapy

A water-soluble derivative of N-confused porphyrin (NCP) was synthesized, and the photodynamic therapeutic (PDT) application was investigated by photophysical and in vitro studies. High singlet oxygen quantum yield in water at longer wavelength and promising IC(50) values in a panel of cancer cell lines ensure the potential candidacy of the sensitizer as a PDT drug. Reactive oxygen species (ROS) generation on PDT in MDA-MB 231 cells and the apoptotic pathway of cell death was illustrated using different techniques.

Efficient Reaction Based Colorimetric Probe for Sensitive Detection, Quantification, and On-Site Analysis of Nitrite Ions in Natural Water Resources

We have developed a novel aza-BODIPY probe for the sensitive colorimetric detection of the nitrite ions in the aqueous medium by a simple and direct method. This probe selectively recognizes the nitrite ions through a distinct visual color change from bright blue to intense green with a sensitivity of 20 ppb. Uniquely, this probe can be coated on a glass surface to fabricate a simple solid-state dipstick device that can be used for the visual detection of the nitrite ions in the presence of other competing anions in distilled as well as natural water resources like a sea, lake, and river. Furthermore, this probe can be used for the sensitive detection of the nitrate ions when coupled to a reduction step. Our results demonstrate that this probe not only can be used for the on-site analysis and quantification but also can replace the conventional spot test carried out for the nitrite ions in the laboratory practical experiments.

Sensitive naked eye detection of hydrogen sulfide and nitric oxide by aza-BODIPY dyes in aqueous medium.

With an objective to develop optical probes for biologically important anions and neutral molecules, we synthesized three novel NIR absorbing aza-BODIPY derivatives, 3a-3c, and have systematically tuned their photophysical properties by changing the peripheral substitution. A profound red-shift was observed in the absorption and fluorescence spectra of the aza-BODIPY dyes with the change in substitution from azido (3a) to amino (3b) to dimethylamino (3c) groups. Theoretical calculations of 3a-3c showed a consistent decrease in bandgap, which supports the observed spectral changes. The study of their interactions with various analytes revealed that the azido-aza-BODIPY 3a selectively interacts with hydrogen sulfide (H2S) when compared to other molecules. Uniquely, the detection of H2S can be visualized through a change in color from bright blue to purple with a detection limit of 0.5 ppm. The sensitivity of the probe was observed to be ~20-fold higher than the allowed exposure limits of H2S as defined by EPA (10 ppm). The aza-BODIPY derivative 3b, on the other hand, exhibited selective interactions with nitrite ions (NO2(-)) and nitric oxide (NO) in aqueous medium through a visible color change from blue to green with a sensitivity of 20 and 0.15 ppb, respectively. In contrast, the dimethylamino-aza-BODIPY derivative, 3c, showed negligible affinity for the anions and neutral molecules tested. By tuning the photophysical properties through the judicious functionalization, the aza-BODIPY dyes thus synthesized can be utilized for the sensitive on-site detection and analysis of H2S, NO2(-), and NO in the aqueous medium.

In vitro demonstration of apoptosis mediated photodynamic activity and NIR nucleus imaging through a novel porphyrin.

We synthesized a novel water-soluble porphyrin THPP and its metalated derivative Zn-THPP having excellent triplet excited state quantum yields and singlet oxygen generation efficiency. When compared to U.S. Food and Drug Administration approved and clinically used sensitizer Photofrin, THPP showed ca. 2-3-fold higher in vitro photodynamic activity in different cell lines under identical conditions. The mechanism of the biological activity of these porphyrin systems has been evaluated through a variety of techniques: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, comet assay, poly(ADP-ribose)polymerase (PARP) cleavage, CM-H(2)DCFDA assay, DNA fragmentation, flow cytometric analysis, fluorescence, and confocal microscopy, which confirm the apoptotic cell death through predominantly reactive oxygen species (ROS). Moreover, THPP showed rapid cellular uptake and are localized in the nucleus of the cells as compared to Hoechst dye and Photofrin, thereby demonstrating its use as an efficient sensitizer in photodynamic therapy and live cell NIR nucleus imaging applications.