High Singlet Oxygen Quantum Yield Research Articles

Dual action of asymmetrical zinc(II) phthalocyanines conjugated to silver tungstate nanoparticles towards photodegradation of tetracycline and inactivation of Staphylococcus aureus bacteria

Asymmetric (A3B) Zn(II) phthalocyanines containing dimethoxy phenoxy as the dominant substituent and (phenoxy) propanoic acid (1), (phenoxy) acetic acid (2), and (phenoxy) acrylic acid (3) as the other substituents were synthesized and linked to silver tungstate nanoparticles (Ag2WO4 NPs). The photocatalytic activities of the prepared complexes 1–3 and nanoconjugates were evaluated for the photodegradation of tetracycline (TC) under visible-light irradiation and for photodynamic antimicrobial chemotherapy (PACT) activity against S. aureus. The results revealed that complex 3 had the best photocatalytic and PACT performance compared to 1 and 2, corresponding to the higher singlet oxygen quantum yield of the former in dimethyl sulfoxide. The photodegradation reaction was also examined using EPR and a mechanism for generation of singlet oxygen under visible light was confirmed. Photoinactivation of S. aureus improved in the presence of TC, when the two are applied together.

The bromoporphyrins as promising anti-tumor photosensitizers in vitro.

The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I1-6) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I2) and stronger phototoxicity (except I4) against Eca-109 tumor cells than HMME. Among them, I3 possessed the highest singlet oxygen quantum yield (ΦΔ = 0.205), the lower dark toxicity and the strongest phototoxicity (IC50 = 3.5μM) in vitro. The findings indicated the compounds I3 had the potential to become anti-tumor agents for PDT.

Multifunctional porphyrin-ionic liquid aggregate for highly sensitive electrochemical detection of protein

Herein, this paper describes a novel label-free and extensibility electrochemical sensing platform based on porphyrin-ionic liquid (Por-IL) aggregate for the detection of antibody. The Por-IL was synthesized with water-soluble porphyrins Zn(II) meso-tetrakis (4-sulfonatophenyl)porphyrin (ZnTPPS)) and the ionic liquid 1-decyl-alkyl-3-methylimidazolium bromide (C10mimBr) under room temperature, which exhibited high singlet oxygen (1O2) quantum yields and electrocatalytic activity toward hydrogen peroxide (H2O2). In the presence of antibody, the antibody could be introduced on the surface of the electrode on the basis of antigen-antibody biorecognition. Under light illumination, the 1O2 formed, then water and the formed 1O2 could be catalyzed by antibody via the antibody catalyzed water oxidation pathway to produce H2O2 which could be detected by the electrode, leading to the electrochemical signal for readout. Using anti-carcinoembryonic antigen (anti-CEA) as a model target, this method displayed a wide linear detection range and a lower detection limit. In particular, Por-IL demonstrated lower detection limit of 1.67 fg/mL. Furthermore, the Por-IL sensors were able to detect antibody in complex samples. The immunosensor platform has the features of label-free, sensitivity, only with air and on/off light switching and could be used to detect of a variety of antibody by using corresponding antigen, showing potential application in medical diagnosis.

Photodynamic properties of lysine and arginine derivatives of bacteriopurpurinimide.

Background: O-propyloxime-N-propoxybacteriopurpurinimide methyl ester (3) is a near-infrared photosensitizer with confirmed in vivo anticancer activity. Methods: Conjugates of 3 with arginine (1) or lysine attached at an ε-amino group (2a) or α-amino group (2b) were studied as anticancer and antibacterial photosensitizers and compared with 3. Results: The new conjugates preserve advanced spectral characteristics of 3 and high singlet oxygen quantum yield. They demonstrated tenfold higher photocytotoxicity for cancer cells, due to their enhanced intracellular accumulation and altered localization. Though they showed threefold decreased antibacterial photodynamic effect compared with 3, they kill planktonic Staphylococcus aureus bacteria, and 1 destroys bacterial biofilms. Conclusion: Conjugates 1 and 2b are near-infrared photosensitizers with high anticancer and limited antibacterial activity.

Isomer Engineering of Lepidine-Based Iridophosphors for Far-Red Hypoxia Imaging and Photodynamic Therapy.

The development of highly efficient cyclometalated phosphorescent iridium(III) complexes is greatly promoted by their rational molecular design. Manipulating the excited states of iridophosphors could endow them with appealing photophysical properties, which play vital roles in triplet state-related photofunctional applications (e.g., electroluminescence, photodynamic therapy, etc.). In general, the most effective approach for decreasing the emission energies of iridophosphors is to extend the π-skeleton of ligands. However, the π-extension strategy often results in decreased solubility, lower synthetic yield, decreased photoluminescence quantum yield, and so forth. In this work, a simple yet efficient strategy is proposed for the effective excited-state manipulation of 2-phenyllepidine-based iridophosphors. Surprisingly, dramatic tuning of phosphorescence wavelength (∼70 nm) is achieved by simply controlling the position of a single methoxyl substituent on these iridophosphors. An oxygen-responsive iridophosphor featuring far-red emission (660 nm), long emission lifetime (1.60 μs), and high singlet oxygen quantum yield (0.73) is employed to realize accurate oxygen sensing in vitro and in vivo, and it also shows efficient photodynamic therapy in cancer cells, making it a promising candidate for the efficient image-guided photodynamic therapeutic agent. This molecular design strategy clearly demonstrates the advantages of designing novel long-wavelength emissive iridophosphors without increasing the π-conjugation of the ligand.

Development of AB3-Type Novel Phthalocyanine and Porphyrin Photosensitizers Conjugated with Triphenylphosphonium for Higher Photodynamic Efficacy.

There are a number of lipophilic cations that can be chosen; the triphenylphosphonium (TPP) ion is particularly unique for mitochondrion targeting, mainly due to its simplicity in structure and ease to be linked to the target molecules. In this work, mitochondrion-targeted AB3-type novel phthalocyanine and porphyrin photosensitizers (PSs) were synthesized and their photophysical photochemical properties were defined. Fluorescence quantum yields (ΦF) are 0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields (ΦΔ) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB 3 TPP-Pc, AB 3 TPP-Por-C4, and AB 3 TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated PS cell viabilities of A549 and BEAS-2B lung cells were comparatively measured and IC-50 values were determined. AB 3 TPP-Por-C4, AB 3 TPP-Por-C6, and AB 3 TPP-Pc compounds compared to the reference molecules ZnPc and H 2 TPP were found to be highly cytotoxic (sub-micromolar concentration) under the light. LuPcPox(OAc) is the most effective molecule regarding cell killing (the activity). The cell killing of the TPP-conjugated porphyrin derivatives exhibits a similar response compared to LuPcPox(OAc) when the light absorbing factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins absorb less light (lower extinction coefficient) but produce more radical species (higher singlet-oxygen quantum yield) and therefore effectively kill the cells. The singlet oxygen-producing capacity of AB 3 TPP-Pc is almost 3 times higher compared to LuPcPox(OAc) and 50% more efficient with respect to ZnPc, suggesting that TPP-conjugated phthalocyanine may serve as a good photosensitizer for photodynamic therapy (PDT). The high singlet oxygen generation capacity of these novel TPP-conjugated porphyrin and phthalocyanine PS suggests that they might be useful for PDT requiring lower photosensitizer concentration and reduced energy deposited through less light exposure.

A Selenium-Substituted Heptamethine Cyanine Photosensitizer for Near-Infrared Photodynamic Therapy.

Photodynamic therapy (PDT) is a relatively safe approach to cancer treatment without significant systemic side effects or drug resistance. However, the current PDT efficiency is unsatisfactory due to the lack of near-infrared (NIR) photosensitizers. Heptamethine cyanine (Cy7) dyes are well-known NIR fluorophores and are also used as photosensitizers. But their singlet oxygen quantum yields (ΦΔ ) are not ideal. Herein, we developed an NIR photosensitizer with a long-lived excited triplet state (τ=4.3 μs) by introducing a selenium atom into the structure of a Cy7 dye. The new NIR photosensitizer exhibits a significantly high singlet oxygen quantum yield (ΦΔ =0.11). Its good PDT effect was demonstrated in the living cells. Considering that the selenium-substituted photosensitizer has a very low dark cytotoxicity and good chemical stability, we conclude that it will have a promising future in biomedical and clinical applications.

Photodynamic antimicrobial chemotherapy with asymmetrical cationic or neutral metallophthalocyanines conjugated to amino-functionalized zinc oxide nanoparticles (spherical or pyramidal) against planktonic and biofilm microbial cultures

The synthesis and characterization of neutral zinc and indium substituted mercaptobenzothiazole substituted phthalocyanines (Pcs) and their respective cationic derivatives are presented. The phthalocyanines were further covalently linked to two differently shaped amino-functionalized ZnO nanoparticles (ZnONPs): namely nanospheres (NH2-ZnONSp), and nanopyramids (NH2-ZnONPy), to form corresponding nanoconjugates. The photophysicochemical properties of each nanocomposite were determined, and the Pc-ZnONPs produced high singlet oxygen quantum yields. The photodynamic antimicrobial chemotherapy activity was determined using planktonic and biofilm cells of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Candida albicans (C. albicans). The conjugates of the cationic Pc derivatives with ZnONPy produced the highest log reduction values (∼ 8 and above) with the complete elimination of all planktonic cells at 0.45 kJ/cm2 for S. aureus and at 0.9 kJ/cm2 for E. coli, and C. albicans. For biofilms log reduction values >3 for both S. aureus and E. coli were obtained. The conjugates of the cationic Pc derivatives with NH2-ZnONPy showed great potential in eradicating mixed microbial biofilms.

Aptamer-modified carbon dots for enhancement of photodynamic therapy of cancer cells

Carbon dots (CDs) have emerged as promising materials for photodynamic therapy (PDT) because of their intriguing photochemical properties, high stability, and low toxicity. However, achieving accurate delivery of CDs based photosensitizers into tumor sites remains a grand challenge. Herein, AS1411 aptamer, a short oligonucleotide sequence with high binding specificity to tumor cells, was chemically decorated to the surface of Asp-CDs to obtain Asp-CDs@AS1411. The aptamer modified Asp-CDs@AS1411 not only retains the excellent properties of Asp-CDs such as high singlet oxygen quantum yield (up to 50%), bright photoluminescence, and good stability, but also features specific recognition and markedly enhanced phototoxicity (4 times) to tumor cells. These combined attributes make Asp-CDs@AS1411 a promising PDT agent for efficient tumor treatment. More importantly, the reported strategy paves a new avenue for developing high performance PDT materials from surface functionalized CDs featuring high photosensitivity and targeting ability.

Bichromophoric BODIPY and Biotin Tagged Terpyridyl Ruthenium(II) Complexes for Cellular Imaging and Photodynamic Therapy

AbstractA perceived drawback of ruthenium(II) polypyridyl photosensitizers for phototherapeutic applications is their inadequate absorption in the visible region. Ru(II) dyads attached to light‐harvesting organic chromophores are studied to address this issue. Biotin‐appended compounds having one chromophore, namely BODIPY (boron‐dipyrromethene) (1) and Ru(II)‐(tpy)2 (2), or a dyad system containing BODIPY linked to Ru(II)‐(tpy)2 via a diphenylacetylene linker (3) were prepared and studied as photodetection agent and photosensitizes for Photodynamic Therapy (PDT) applications. The bichromophoric 3 with a strong absorption profile (ϵ≈71000 M−1 cm−1 at λmax=503 nm) and high singlet oxygen quantum yield (ΦΔ=0.63 in DMSO) was studied for PDT activity. This complex produced a superoxide anion radical via type‐I and singlet oxygen via type‐II photosensitization processes on light exposure, as evidenced from DNA photo‐cleavage experiments and in vitro DCFDA assay using reactive oxygen species scavengers/quenchers. Dyad 3 displayed an apoptotic photo‐cytotoxic effect against HeLa and H1299 cancer cells with a photocytotoxicity index (PI) value of >625 in HeLa cells with a PDT efficacy much superior to those of its monochromophoric analogs 1 and 2. The intrinsic emission of complex 3, utilized for cellular imaging, showed selectivity towards lysosomes. Finally, the remarkable potential of complex 3 was evidenced using a clinically relevant 3D multicellular tumor spheroid model.

Rational Modulation of BODIPY Photosensitizers to Design Metal-Organic Framework-Based NIR Nanocomposites for High-Efficiency Photodynamic Therapy in a Hypoxic Environment.

Photodynamic therapy (PDT) is a promising noninvasive treatment that has drawn great attention. However, the hypoxic environment in tumors seriously limits the therapeutic effect of oxygen-dependent chemicals and PDT. Herein, a versatile nanocomposite DF-BODIPY@ZIF-8 with oxygen-generating ability was developed based on zeolitic imidazolate framework-8 (ZIF-8) by loading the near-infrared photosensitizer DF-BODIPY to overcome hypoxia-induced drug resistance in cancer therapy. ZIF-8 can catalyze the decomposition of hydrogen peroxide in tumors and increase the dissolved oxygen concentration, resulting in a significant improvement in PDT efficacy. Additionally, we found that enhancing the electronegativity of substituents can effectively reduce the energy level difference (ΔEst) between the minimum singlet state (S1) and the lowest triplet state (T1), leading to the enhancement of the singlet oxygen quantum yield. In vitro experiments suggested that DF-BODIPY@ZIF-8 indeed had a higher singlet oxygen quantum yield and better tumor cell phototoxicity than free DF-BODIPY. In vivo experiments also demonstrated that DF-BODIPY@ZIF-8 could effectively eliminate 4T1 tumors under light irradiation. Thus, we conclude that increasing the electronegativity of substituents and introducing a ZIF-8 material can effectively improve the singlet oxygen quantum yield and overcome the hypoxia limitations for high-efficiency PDT.

Photodynamic antitumor activity of Gallium(III) and Phosphorus(V) complexes of trimethoxyl A2B triaryl corrole

Two new trimethoxyl A2B triaryl corroles 10-(2,4,6-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)- corrole (1) and 10-(3,4,5-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)-corrole (2) and their gallium(III) and phosphorus(V) (1-Ga, 1-P, 2-Ga and 2-P) complexes had been prepared and well characterized by UV–vis, NMR and HR-MS. Among all compounds, 2-Ga, 1-P and 2-P showed excellent in vivo photodynamic activity against the MDA-MB-231, A549, Hela and HepG2 cell lines upon light irradiation at 625 nm. And 2-P even exhibited higher phototoxicity than the clinical photosensitizer temoporfin. Also, 2-P exhibited the highest singlet oxygen quantum yield and photostability. The preliminary investigation revealed that 2-P could be rapidly absorbed by tumor cells and mainly located in the cytoplasm. After photodynamic therapy (PDT) treatment with 2-P, mitochondrial membrane potential destruction, intracellular ROS level increasing and nuclear fragmentation of cancer cells could be observed. Cell cycle analysis demonstrated that the 2-P PDT may cause tumor cell arrest at sub-G1 stage and induce early and late apoptosis of cells. These results suggest that 2-P is a promising candidate as a photosensitizer for photodynamic therapy.

Photodynamic antitumor activity of tetrahydroxyl-methyl pyropheophorbide-a with improved water-solubility and depth of treatment

Methyl pyropheophorbide-a (MPPa) is a chlorophyll degradation product that possesses excellent photophysical and photochemical properties, yet poor water solubility limits its clinical application. In this paper, a novel MPPa derivative, 31,32,7,8-tetrahydroxy-4 H-MPPa (HMPPa) was synthesized by oxidative hydrolysis of MPPa with potassium osmate. The four hydrophilic hydroxyl groups endow HMPPa with better water solubility (lipid water partition coefficient logP = −0.16), which solve the problem of MPPa aggregation in water. HMPPa has a long-wavelength near-infrared absorption at 740 nm that can achieve a deeper penetration depth in biological tissues, which allows HMPPa to be applied in deep tumor therapy. Moreover, HMPPa possesses a higher singlet oxygen quantum yield (62.65 %) than that of MPPa (56 %). MTT assay verified that HMPPa had a strong ability to inhibit the growth of HepG-2 cells and 4T1 cells, and the PDT effect was superior to that of MPPa. Cell morphology experiments and flow cytometry analysis showed that HMPPa could induce apoptosis via a mitochondrial pathway. In vivo study of HMPPa showed a significant PDT antitumor effect on 4T1 tumor-bearing mice (Balb/C). The tumor cells followed by treatment of HMPPa could be clearly observed under fluorescence microscopy, implying a good fluorescence imaging function of HMPPa.

Locked and Loaded: β-Galactosidase Activated Photodynamic Therapy Agent Enables Selective Imaging and Targeted Treatment of Glioblastoma Multiforme Cancer Cells.

Selective detection and effective therapy of brain cancer, specifically, the very aggressive glioblastoma multiforme (GBM), remains one of the paramount challenges in clinical settings. While radiotherapy combined surgery is proposed as the main treatment course, it has several drawbacks such as complexity of the operation and common development of recurrent tumors in this course of patient care. Unique opportunities presented by photodynamic therapy (PDT) offer promising, effective, and precise therapy against GBM cells along with simultaneous imaging opportunities. However, activatable, theranostic molecular systems in PDT modality for GBM remained scarce. Specifically, even though elevated β-galactosidase (β-gal) activity in glioblastoma cells is well-documented, targeted, activatable therapeutic PDT agents have not been realized. Herein, we report a β-galactosidase (β-gal) activatable phototheranostic agent based on an iodinated resorufin core (RB-1) which was realized in only three steps with commercial reagents in 29% overall yield. RB-1 showed very high singlet oxygen (1O2) quantum yield (54%) accompanied by a remarkable turn-on response in fluorescence upon enzymatic activation. RB-1 was tested in different cell lines and revealed selective photocytotoxicity in U-87MG glioblastoma cells. Additionally, thanks to almost 7% fluorescence quantum yield (ΦF) despite extremely high 1O2 generation yield, RB-1 was also demonstrated as a successful agent for fluorescence imaging of U-87MG cells. Due to significantly lower (β-gal) activity in healthy cells (NIH/3T3), RB-1 stayed in a passive state and showed minimal photo and dark toxicity. RB-1 marks the first example of a β-gal activatable phototheranostic agent toward effective treatment of glioblastoma.

Synthesis and Photophysical Characterizations of Pyrroloquinolone Photosensitizers for Singlet Oxygen Production†.

A series of pyrroloquinolone photosensitizers bearing different halogen substituents (Cl, Br, I) on the heterocyclic framework was studied. These structures were readily prepared through a multi-step synthetic sequence involving an oxidative protocol as an important step to access the quinolone framework. Spectroscopic characterizations and computational investigations were carried out to study the dyes before and after the oxidative step. Interestingly, the fluorescence emission was significantly reduced upon oxidation. In spite of a low photostability under UV light, the pyrroloquinolone photosensitizers proved effective to produce singlet oxygen. Higher singlet oxygen quantum yields were obtained with photosensitizers bearing halogen atoms with a higher atomic number.

The implications of ortho-, meta- and para- directors on the in-vitro photodynamic antimicrobial chemotherapy activity of cationic pyridyl-dihydrothiazole phthalocyanines

Cationic Zn phthalocyanine complexes were derived by alkylation reaction of tetra-(pyridinyloxy) phthalocyanines (Pcs) at the ortho, meta, and para positions to form Zn (II) tetrakis 3-(4-(2-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (2), Zn (II) tetrakis 3-(4-(3-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (4) and Zn (II) tetrakis 3-(4-(4-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (6). The photophysicochemical behaviors of the Pc complexes were assessed. The meta and para-substituted complexes gave high singlet oxygen quantum yields. The cationic Pcs demonstrated good planktonic antibacterial activity against Staphylococcus aureus and Escherichia coli with the high log reduction values of 9.29 and 8.55, respectively. The cationic complexes also showed a significant decrease in the viability of in vitro biofilms after photo-antimicrobial chemotherapy at 100 µM for both Staphylococcus aureus and Escherichia coli biofilms.

New soluble 4-(4-formyl-2,6-dimethoxyphenoxy) substituted phthalocyanines: Synthesis, characterization, photophysical and photochemical properties

This work describes the synthesis, spectral and fluorescence properties of bis 4-(4-formyl-2,6-dimethoxyphenoxy) substituted zinc (ZnPc) and magnesium (MgPc) phthalocyanines. The new compounds have been characterized by elemental analysis, UV-Vis, FT-IR, 1H-NMR and mass spectra. Afterward, the effects of including metal ion on the photophysicochemical properties of the complexes were studied in biocompatible solvent DMSO to analyze their potential to use as a photosensitizer in photodynamic therapy (PDT). The fluorescence and singlet oxygen quantum yields were calculated as 0.04–0.15 and 0.70–0.52 for ZnPc and MgPc, respectively. According to the results, MgPc has higher fluorescence quantum yield than ZnPc, while ZnPc has higher singlet oxygen quantum yield than MgPc. The results show that the synthesized complexes can have therapeutic outcomes for cancer treatment.

Photodynamic Antitumor and Antimicrobial Activities of Free-Base Tetra(4-methylthiolphenyl)chlorin and Its Tin(IV) Complex.

Meso-tetra(4-methylthiolphenyl)chlorin (3) and its Sn(IV) complex (3-Sn) have been synthesized and characterized. The heavy atom effects of the Sn(IV) ion and sulfur atoms result in relatively high singlet oxygen quantum yield values of 0.40 and 0.48. The photodynamic activities against MCF-7 breast cancer cells were determined through irradiation with a Thorlabs 660 nm LED for 30 min (280 mW.cm-2 ). IC50 values of 7.8 and 3.9 μM were obtained, respectively. 3-Sn was found to have significant photodynamic antimicrobial activity against both gram-(+) S. aureus and gram-(-) E. coli bacteria upon irradiation with a Thorlabs 660 nm LED for 75 min.

NIR-I region absorbing halogenated phenylamino zinc (II) phthalocyanines: Synthesis and photophysical properties

NIR-I region absorbing dyes with higher tissue penetration, lower auto-fluorescence, minimum photodamage to living tissues, and higher detection sensitivity are attracted great interesting in biological applications. In this paper, three novel NIR I absorbing halogenated phenylamino zinc (II) phthalocyanines have been firstly synthesized through a simple and practical method. They were obtained by condensation of corresponding halogenated phenylamino phthalonitriles. Halogenated phenylamino phthalonitriles were prepared by direct amination of halogenated boronic acids with nitro-phthalonitriles through a reductive molybdenum catalyzed method. The UV/Vis and fluorescence spectra of three halogenated phenylamino zinc phthalocyanines are within NIR-I region because of electron-donating conjugation effect of amine groups. In addition, the effect of substitution terminal halogen atoms as well as α/β substitution position on the UV/Vis and fluorescence spectra of three phthalocyanines were compared. Of three phthalocyanines, 3-BrZnPc with bromo-phenylamino substitution at α position possessed the longest Q-band absorption at 767 nm and fluorescence emission wavelength at 785 nm as well as the highest singlet oxygen quantum yield.

Cobalt(III) Complexes for Light-Activated Delivery of Acetylacetonate-BODIPY, Cellular Imaging, and Photodynamic Therapy.

Cobalt(III) complexes [Co(TPA)(L1)](ClO4)2 (1), [Co(4-COOH-TPA)(L1)](ClO4)2 (2), [Co(TPA)(L2)]Cl2 (3), and [Co(4-COOH-TPA)(L2)]Cl2 (4) having acetylacetonate-linked boron-dipyrromethene ligands (L1, acac-BODIPY; L2, acac-diiodo-BODIPY) were prepared and characterized, and their utility as bioimaging and phototherapeutic agents was evaluated (TPA, tris-(2-pyridylmethyl)amine; 4-COOH-TPA, 2-((bis-(2-pyridylmethyl)amino)methyl)isonicotinic acid). HL1, HL2, and complex 1 were structurally characterized by X-ray crystallography. Complexes 1 and 2 on photoactivation or in a reducing environment (excess GSH, ascorbic acid, and 3-mercaptopropionic acid) released the acac-BODIPY ligand. They exhibited strong absorbance near 501 nm (ε ∼ (5.2-5.8) × 104 M-1 cm-1) and emission bands near 513 nm (ΦF ∼ 0.13, λex = 490 nm) in dimethyl sulfoxide (DMSO). Complexes 3 and 4 with absorption maxima at ∼536 and ∼538 nm (ε ∼ (1.2-1.8) × 104 M-1 cm-1), respectively, afforded high singlet oxygen quantum yield (ΦΔ ∼ 0.79) in DMSO. Complexes 1-4 showed Co(III)-Co(II) redox responses near -0.2 V versus saturated calomel electrode (SCE) in dimethylformamide (DMF)-0.1 M tetrabutylammonium perchlorate (TBAP). The photocleavage of pUC19 DNA by complex 4 revealed the formation of both singlet oxygen and superoxide anion radicals as the reactive oxygen species (ROS). Confocal fluorescence microscopy showed the selective accumulation of complex 1 in the endoplasmic reticulum (ER) in A-549 cells. Complex 4 exhibited a high phototherapeutic index value (PI > 7000) in HeLa cancer cells (IC50 ∼ 0.007 μM in visible light of 400-700 nm, total dose ∼5 J cm-2). The ancillary ligands in the complexes demonstrated a structure-activity relationship and modulated the Co(III)-Co(II) redox potential, the complex solubility, acac-BODIPY ligand release kinetics, and phototherapeutic efficacy.