Binaphthalene-Assisted Axial Chirality in Porphyrins: Toward Solid-State Circularly Polarized Luminescence from Self-Assembled Nanostructures.

Circularly polarized luminescence (CPL) is emerging as an effective tool to study the excited-state optical activity in molecules and their self-assembled nanostructures. Chiral porphyrins are a class of optically active molecules wherein the ground-state chirality has been extensively studied in recent times using circular dichroism (CD) spectroscopy. However, obtaining CPL from porphyrin nanostructures, which would have vast implications in biological applications, has remained an uphill task. In this work, we design and synthesize a pair of chiral porphyrin enantiomers functionalized by axially chiral binaphthalene units at the four meso-positions. The molecule undergoes self-assembly following an isodesmic polymerization model, leading to the formation of a spherical nanostructure possessing opposite chirality. Favorable thermodynamic parameters achieved through the controlled experimental conditions helped drive the self-assembly in the forward direction. The limitations imposed by a large nonradiative decay constant arising due to the aggregation-induced quenching could be overcome by fabricating self-standing polymeric films of the nanostructures. The films exhibited relatively high radiative decay and, more interestingly, good CPL activity with clear mirror image spectra for the nanostructures with opposite chirality. The work on CPL-active solid-state materials opens avenue for the design and synthesis of a variety of porphyrin-based chromophoric systems and their nanoaggregates that can find potential application in the field of chiral biosensing and bioimaging, security tags, and display devices.

Picolyl Porphyrin Nanostructures as a Functional Drug Entrant for Photodynamic Therapy in Human Breast Cancers.

The major challenge in photodynamic therapy (PDT) is to discover versatile photosensitizers (PSs) that possess good solubility in biological media, enhanced singlet oxygen generation efficacy, and photodynamic activity. Working in this direction, we synthesized a picolylamine-functionalized porphyrin conjugate, compound 1, and its zinc complex compound 2. Compound 1 forms spherical structures in methanol, whereas compound 2 exhibited vesicular structures. Compared to the existing PSs like foscan and photofrin, compound 2 exhibited a high singlet oxygen generation efficiency and triplet quantum yield. The complex also showed good water solubility, and its PDT activity was demonstrated through in vitro studies using MDA-MB 231 breast cancer cells. The mechanism of biological activity evaluated using various techniques proved that the active compound 2 induced predominantly singlet oxygen-triggered apoptosis-mediated cancerous cell death. Our results demonstrate that zinc insertion in the picolyl porphyrin induces an enhanced triplet excited state, and the singlet oxygen yields quantitatively and imparts excellent in vitro photodynamic activity, thereby demonstrating their pertinence as a nanodrug in future photobiological applications.

In Vitro and In Vivo Demonstration of Human-Ovarian-Cancer Necrosis through a Water-Soluble and Near-Infrared-Absorbing Chlorin.

With the objective of developing efficient sensitizers for therapeutic applications, we synthesized a water-soluble 5,10,15,20-tetrakis(3,4-dihydroxyphenyl)chlorin (TDC) and investigated its in vitro and in vivo biological efficacy, comparing it with the commercially available sensitizers. TDC showed high water solubility (6-fold) when compared with that of Foscan and exhibited excellent triplet-excited-state (84%) and singlet-oxygen (80%) yields. In vitro photobiological investigations in human-ovarian-cancer cell lines SKOV-3 showed high photocytotoxicity, negligible dark toxicity, rapid cellular uptake, and specific localization of TDC in neoplastic cells as assessed by flow-cytometric cell-cycle and propidium iodide staining analysis. The photodynamic effects of TDC include confirmed reactive-oxygen-species-induced mitochondrial damage leading to necrosis in SKOV-3 cell lines. The in vivo photodynamic activity in nude-mouse models demonstrated abrogation of tumor growth without any detectable pathology in the skin, liver, spleen, or kidney, thereby demonstrating TDC application as an efficient and safe photosensitizer.

Chiral supramolecular polymerization leading to eye differentiable circular polarization in luminescence.

This work demonstrates a simple methodology to tune the chiroptical properties of chiral europium(iii) complexes by supramolecular polymerization. Helical aggregation of the cesium derivative has updated the highest luminescence dissymmetry factor to date leading to naked eye visualization of circular polarized luminescence using circularly polarized filters.

Optimization of triplet excited state and singlet oxygen quantum yields of picolylamine-porphyrin conjugates through zinc insertion.

We synthesized a new class of picolylamine-porphyrin conjugates 1-3 and have investigated the effect of heavy atom insertion on their intersystem crossing efficiency through spin-orbit perturbations. By incorporating zinc ions in the core as well as periphery positions of the porphyrin ring, we have successfully optimized their triplet excited state quantum yields and their efficiency to generate singlet oxygen. Uniquely, the picolylamine-porphyrin conjugate 3 having five zinc ions exhibited a triplet excited state quantum yield of ca. 0.97 and a sensitized singlet oxygen generation yield of ca. 0.92. In contrast, the free base porphyrin derivative 1 exhibited ca. 0.64 and 0.5 of the triplet excited state and singlet oxygen quantum yields, respectively. Our results demonstrate that the insertion of zinc metal ions in the picolylamine-porphyrin conjugates not only quantitatively enhances the triplet excited state and singlet oxygen yields but also imparts hydrophilicity, thereby their potential use as sensitizers in photodynamic therapy and green photooxygenation reactions.

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.