[Pt(cur)(NH3)2](NO3) (1), a curcumin-bound cis-diammineplatinum(II) complex, nicknamed Platicur, as a novel photoactivated chemotherapeutic agent releases photoactive curcumin and an active platinum(II) species upon irradiation with visible light. The hydrolytic instability of free curcumin reduces upon binding to platinum(II). Interactions of 1 with 5'-GMP and ct-DNA indicated formation of platinum-bound DNA adducts upon exposure to visible light (λ=400-700 nm). It showed apoptotic photocytotoxicity in cancer cells (IC50 ≈ 15 μM), thus forming (⋅)OH, while remaining passive in the darkness (IC50 >200 μM). A comet assay and platinum estimation suggest Pt-DNA crosslink formation. The fluorescence microscopic images showed cytosolic localization of curcumin, thus implying possibility of dual action as a chemo- and phototherapeutic agent.

Platinum(II) complexes [Pt(L)(R-BODIPY)]Cl (1) and [Pt(L)(R-BODIPY)]Cl (2), where R-BODIPY is 8-(4-ethynylphenyl)-distyryl-4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3, L is 4'-phenyl-2,2':6',2″-terpyridine, and L is (2,2':6',2″-terpyridin-4'-oxy)ethyl-β-d-glucopyranoside, were synthesized and characterized, and their photocytotoxicity was studied. The phenylacetylide complex [Pt(L)(C≡CPh)]Cl (3) was prepared and used as a control. Complexes 1 and 2 showed near-IR absorption bands at 713 nm (ε = 3.47 × 10 M cm) and 715 nm (3.2 × 10 M cm) in 10% dimethyl sulfoxide (DMSO)-Dulbecco's Modified Eagle's Medium (DMEM) (pH 7.2). The BODIPY complexes are emissive in 10% DMSO-DMEM at pH 7.2 with λ (λ, Φ) = 822 nm (710 nm, 0.022) for complex 1 and λ (λ, Φ) = 825 nm (710 nm, 0.026) for complex 2. They generated singlet oxygen (O) in red light as evidenced from 1,3-diphenylisobenzofuran (DPBF) titration experiments. The singlet oxygen quantum yield (Φ) values for 1 and 2 were ∼0.6 signifying their photosensitizing ability. They were remarkably photodynamic therapy (PDT) active in red light showing significant red light-induced cytotoxicity in cervical HeLa, lung cancer A549, and breast cancer MCF-7 cells (IC: 2.3-24.7 μM in light) with negligible dark toxicity (IC > 100 μM). A significant enhancement in cellular uptake was observed for 2 having glucose-appended terpyridine ligand compared to 1. The confocal microscopy showed significant mitochondrial localization of the complexes as evidenced from the JC-1 assay. The complexes released the photoactive R-BODIPY ligand upon red light-irradiation as evidenced from the mass and H NMR spectral studies. Complex 2 is remarkable in satisfying the essential requirements of targeted PDT in red light.

Monofunctional pyriplatin analogues cis-[Pt-(NH 3 ) 2 (L)Cl](NO 3 ) (1−3) having boron-dipyrromethene (BODIPY) pendants (L) with 1,3,5,7-tetramethyl-8-(4-pyridyl)-4,4′-difluoroboradiazaindacene moieties were designed and synthesized, and their photocytotoxic properties were studied. The Pt-BODIPY conjugates displayed an absorption band within 505−550 nm and a green emissive band near 535 nm in 1% DMSO/DMEM (Dulbecco's modified Eagle's medium) buffer. Complex cis-[Pt(NH 3 ) 2 (4-Me-py)Cl](NO 3 ) (4) was used as a control for determining the structural aspects by X-ray crystallography. The mono-and diiodinated BODIPY complexes 2 and 3 showed generation of singlet oxygen on light activation as evidenced from the 1,3-diphenylisobenzofuran (DPBF) titration experiments. The cytotoxicity of the BODIPY complexes was tested against A549 (human lung cancer), MCF-7 (human breast cancer), and HaCaT (human skin keratinocyte) cells in dark and visible light (400−700 nm, 10 J cm −2 ). While complexes 2 and 3 showed excellent photocytotoxicity (IC 50 ≈ 0.05 μM), they remained essentially nontoxic in the dark (IC 50 > 100 μM). The emissive bands of 1 and 2 were used for cellular imaging by confocal microscopy study, which showed their mitochondrial localization. This was further supported by platinum estimation from isolated mitochondria and mitochondrial depolarization through a JC-1 assay. The photomediated apoptotic cell death was evidenced from flow cytometric assays, annexin-V/FITC-PI (fluorescein isothiocyanate-propidium iodide) and cell cycle arrest in sub-G1 and G2/M phases. The complexes bind to 9-ethylguanine as a model nucleobase to form monoadducts. A mechanistic study on DNA photocleavage activity using pUC19 DNA showed singlet oxygen as the reactive oxygen species (ROS). The combination of photodynamic therapy with DNA cross-linking property enhanced the anticancer potential of the monofunctional BODIPY-conjugates of pyriplatins.

Three platinum(II) complexes of curcumin, [Pt(NH 3 ) 2 -(cur)](NO 3 ) (1), [Pt(en)(cur)](NO 3 ) (2) and [Pt(dach)(cur)](NO 3 ) (3), where Hcur is curcumin, en is ethylenediamine and dach is 1R,2R-(-)-1,2-diaminocyclohexane, were synthesized, characterized and their photocytotoxic properties were explored. The acetylacetone (Hacac) analogue of 1, [Pt(NH 3 ) 2 (acac)]NO 3 (4), was prepared to investigate the role of photoactive curcumin. The crystal structure of [Pt(NH 3 ) 2 (acac)]CF 3 SO 3 (4a) revealed square-planar geometry of the platinum(II) centre. Complexes 1-3 displayed an intense absorption band at 450 nm (ε = 22500 M -1 cm -1 ). The curcumin in metal-bound form showed

Monofunctional platinum(II) complexes of formulation cis-[Pt(NH)(L)Cl](NO), where L is an imidazole base conjugated to 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with emissive (L in 1) and nonemissive (L in 2) moieties were prepared and characterized, and their singlet oxygen-mediated photoinduced cytotoxicity was studied. The 1-methylimidazole (1-MeIm) complex 3 was prepared as a control and for structural characterization by X-ray crystallography. Complexes 1 and 2 showed strong visible absorption bands at 500 nm (ε = 2.7 × 10 M cm) and 540 nm (1.4 × 10 M cm). Complex 1 is emissive with a band at 510 nm (Φ = 0.09) in 1% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (pH 7.2). Singlet oxygen generation upon photoirradiation with visible light (400-700 nm) was evidenced from 1,3-diphenylisobenzofuran titration experiments showing significant photosensitizing ability of the BODIPY complexes. Both 1 and 2 were remarkably photocytotoxic in visible light (400-700 nm, 10 J cm) in skin keratinocyte HaCaT and breast cancer MCF-7 cells giving IC values in nanomolar concentration. The complexes were, however, essentially nontoxic to the cells in the dark (IC > 80 μM). Complex 2 having a diiodo-BODIPY unit is nonemissive but an efficient photosensitizer with high singlet oxygen generation ability in visible light (400-700 nm). Confocal microscopy using the emissive complex 1 showed significant mitochondrial localization of the complex. Cell death via apoptotic pathway was observed from the Annexin-V-FITC/PI assay. The formation of Pt-DNA adducts was evidenced from the binding experiments of the complexes 1 and 2 with 9-ethylguanine as a model nucleobase from H NMR and mass spectral studies.

The binuclear platinum(II) boron-dipyrromethene (BODIPY) complex [{Pt(dach)} 2 (μ-Dcrb)] (DP), where dach is 1,2-diaminocyclohexane and H 4 Dcrb is a morpholine-conjugated BODIPY-linked dicatechol bridging ligand, was prepared for lysosome organelle targeting and near-IR (NIR) light (600−720 nm) induced photocytotoxic activity. The platinum complex [Pt(dach)(cat)] (CP), where H 2 cat is catechol, was synthesized and used as a control complex without bearing the BODIPY unit. The complex DP displayed a band at 660 nm (ε = 2.1 × 10 4 M −1 cm −1 ) in the red region of the UV−visible spectrum recorded in 10% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (DMSO/DMEM, pH 7.2). The complex DP and the BODIPY ligand displayed emission in 10% DMSO−DMEM (pH 7.2) giving an λ em value of 668 nm (λ ex = 650 nm) with a Φ F value of 0.02 for DP and 0.16 for H 4 Dcrb (Φ F , fluorescence quantum yield). Titration experiments using 1,3-diphenylisobenzofuran (DPBF) indicated that the complex DP and H 4 Dcrb on irradiation with near-IR light of 600−720 nm generated singlet oxygen ( 1 O 2 ) as the ROS (reactive oxygen species). The complex DP showed significant lysosomal localization and remarkable apoptotic photodynamic therapy (PDT) effects, giving half-maximal inhibitory concentration values (IC 50 ) within 0.6−3.4 μM in HeLa cervical cancer, A549 lung cancer, and MDA-MB231 multidrug resistant cancer cells, while being essentially nontoxic in the dark and in the HPL1D immortalized lung epithelial normal cells. The acridine orange assay using A549 cells showed lysosomal membrane permeabilization by the complex DP under near-IR light (600−720 nm). This complex on near-IR light (600−720 nm) activation in A549 cells induced apoptotic cell death, as observed from an Annexin-V FITC assay.

[Pt(cur)(NH 3 ) 2 ](NO 3 )( 1), ac urcumin-bound cisdiammineplatinum(II) complex, nicknamed Platicur,a s anovel photoactivated chemotherapeutic agent releases photoactive curcumin and an active platinum(II) species upon irradiation with visible light. The hydrolytic instability of free curcumin reduces upon binding to platinum(II). Interactions of 1 with 5'-GMP and ct-DNAi ndicated formation of platinum-bound DNAa dducts upon exposure to visible light (l = 400-700 nm). It showed apoptotic photocytotoxicity in cancer cells (IC 50 % 15 mm), thus forming · OH, while remaining passive in the darkness (IC 50 > 200 mm). Ac omet assaya nd platinum estimation suggest Pt-DNAcrosslink formation. The fluorescence microscopic images showed cytosolic localization of curcumin, thus implying possibility of dual action as ac hemo-and phototherapeutic agent.

Platinum(II) complexes of the type [Pt(L)(cat)] (1 and 2), in which H2 cat is catechol and L represents two 2-(2-pyridyl)benzimidazole ligands with 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) pendants, were synthesized to achieve mitochondria-targeted photocytotoxicity. The complexes showed strong absorptions in the range λ=510-540 nm. Complex 1 exhibited intense emission at λ=525 nm in 1 % DMSO/water solution (fluorescence quantum yield of 0.06). Nanosecond transient absorption spectral features indicated an enhanced population of the triplet excited state in di-iodinated complex 2. The generation of singlet oxygen by complex 2 upon exposure to visible light, as evidenced from experiments with 1,3-diphenylisobenzofuran, is suitable for photodynamic therapy because of the remarkable photosensitizing ability. The complexes resulted in excellent photocytotoxicity in HaCaT cells (half maximal inhibitory concentration IC50 ≈3 μm, λ=400-700 nm, light dose=10 J cm(-2) ), but they remained non-toxic in the dark (IC50 >100 μm). Confocal microscopy images of 1 and Pt estimation from isolated mitochondria showed colocalization of the complexes in the mitochondria. Complex 2 displayed generation of reactive oxygen species induced by visible light, disruption of the mitochondrial membrane potential, and apoptosis.