Detergent-induced self-assembly and controllable photosensitizer activity of diester phenylene ethynylenes

Abstract

Photodynamic therapy, in which malignant tissue is killed by targeted light exposure following administration of a photosensitizer, can be a valuable treatment modality but currently relies on passive transport and local irradiation to avoid off-target oxidation. We present a system of excited-state control for truly local delivery of singlet oxygen. An anionic phenylene ethynylene oligomer is initially quenched by water, producing minimal fluorescence and no measurable singlet oxygen generation. When presented with a binding partner, in this case an oppositely charged surfactant, changes in solvent microenvironment result in fluorescence unquenching, restoration of intersystem crossing to the triplet state, and singlet oxygen generation, as assayed by transient absorption spectroscopy and chemical trapping. This solvation-controlled photosensitizer model has possible applications as a theranostic agent for, for example, amyloid diseases.photosensitizer | self-assembly | conjugated oligomers | photodynamic therapy | excited states G eneration of reactive oxygen species as a product of photoexcited electronic states in organic molecules can be a useful tool in a variety of applications. The possibilities of spatially localized generation of reactive oxygen species (ROS) in response to irradiation are only just beginning to be explored, despite the more than 100-y history of phototherapy in modern medicine (1), and are already in the clinic in the form of photodynamic therapy (PDT) for cancers of the skin, esophagus, and organ linings, actinic keratosis, and acne (2, 3). Photodynamic destruction of pathogenic bacteria, viruses, and fungi is also under investigation for antibiowarfare applications, passive sanitization of hospital surfaces under room light, and active sanitization of medical devices such as catheters (4-8). A major drawback of systemically dosed PDT photosensitizers, which are primarily porphyrins or their prodrugs (9), is their accumulation in the skin and eyes leading to long-lasting (weeks to months) posttherapeutic photosensitivity (10). Generation of ROS outside the target area can have multiple deleterious effects by overwhelming endogenous ROS-dependent signaling cascades (11). A solution to these issues would be a localized photosensitizer whose ROS-generating properties can be controllably activated, for example, in response to the binding to a target.The motivation of the current study is to develop a tool for local delivery of singlet oxygen using binding and self-assemblymediated control of excited states. Under intra-or intercellular conditions, 99% of singlet oxygen cannot travel more than 300 nm from the site of its generation before it decays through the transfer of its electronic energy to vibrational modes of water (12); the presence of redox sites will reduce this effective distance further. This less than 300-nm radius, being less than a cellular length, indicates that an active photosensitizer in or at a target cell will have minimal effect on adjacent cells. Previous investiga...

A Portrait of the OPE as a Biological Agent

“…In particular, the cationic 18d and the anionic 19c ( Table 1 ) can represent selective sensors for fibrils. Almost all active probe compounds showed a common terminal ethyl ester group, which guarantees, as demonstrated elsewhere [ 37 ], a fluorescence unquenching after interaction with hydrophobic molecules (such as amphiphiles or proteins), due to the removal of water molecules from a hydration shell. Among the positive ethyl ester terminated dyes, 18e and 18f showed an increased fluorescence intensity and thus a better selectivity for lysozyme fibrils over the monomeric form of HEWL.…”

“…Two groups of OPEs were analyzed, i.e., OPEs 18d - f ( Table 1 ) with positive alkyl ammonium pendants and different repeating units and an anionic OPE 19c , which possesses sulfonated chain groups and a single repeating unit. The selected OPEs were achiral, amphiphilic, and water soluble, and as demonstrated previously [ 37 ], they enhanced their fluorescence when bounded to a hydrophobic surface because of a reduced water solvation quenching. All OPEs shown an increase in fluorescence intensity in the presence of amyloid and no fluorescence changes in presence of the monomeric form, except for OPE 19c .…”

Highly Effective Inactivation of SARS-CoV-2 by Conjugated Polymers and Oligomers

“…This quenching may reduce the ability of the compound to sensitize reactive oxygen species. 48,49 For the two polymers used in this study, irradiation with either near UV or visible light results in inactivation of the SARS-CoV-2 virus as shown in It is worth considering the practical applications of these materials. We can envision that these materials can be used in the prevention of Covid-19 and other virus-based diseases as well as for future virus threats.…”

Well-defined Conjugated Macromolecules in Sensing

“…Those changes caused by the presence of individual charged molecules may reveal a unique response in the photophysical properties of the conjugated chromophore. The resulting fluorescence quenching or enhanced emission can indicate presence of ions [68], oxygen [69], surfactants [68,70,73,77,90], detergents [74,77], MV 2+ ions [66], solvent polarity [78], anionic biopolymer carboxymethylcellulose [75,76], biomolecules [91] and bacteria [67]. The oligomers were used for processes monitoring of e.g.…”