4-4-difluoro-4-bora-3a-4a-diaza-s-indacene and anthracene

The facile synthesis and in vitro activity of a library of heavy atom-free BODIPY-anthracene, -pyrene dyads (BAD-13-BPyrD-19) and a control (BODIPY 20) are reported. We demonstrate that singlet oxygen produced from dyad triplet states formed from charge-separated states is sufficient to induce cytotoxicity in human breast cancer cells (MDA-MB-468) at micromolar concentrations. The compounds in this series are promising candidates for photodynamic therapy, especially BAD-17 which displays significant photocytotoxicity (15% cell viability) at a concentration of 5 × 10-7 M, with minimal toxicity (89% cell viability) in the absence of light.

Topics: Anthracenes; Boron Compounds; Cell Line; Cell Survival; Photochemotherapy; Photosensitizing Agents; Pyrenes; Singlet Oxygen

The Diels-Alder reaction is one of the most important C-C bond-forming reactions in organic chemistry, and much effort has been devoted to controlling its enantio- and diastereoselectivity. The Diels-Alderase ribozyme (DAse) catalyses the reaction between anthracene dienes and maleimide dienophiles with multiple-turnover, stereoselectivity, and up to 1100-fold rate acceleration. Here, a new generation of anthracene-BODIPY-based fluorescent probes was developed to monitor catalysis by the DAse. The brightness of these probes increases up to 93-fold upon reaction with N-pentylmaleimide (NPM), making these useful tools for investigating the stereochemistry of the ribozyme-catalysed reaction. With these probes, we observed that the DAse catalyses the reaction with >91% de and >99% ee. The stereochemistry of the major product was determined unambiguously by rotating-frame nuclear Overhauser NMR spectroscopy (ROESY-NMR) and is in agreement with crystallographic structure information. The pronounced fluorescence change of the probes furthermore allowed a complete kinetic analysis, which revealed an ordered bi uni type reaction mechanism, with the dienophile binding first.

Topics: Anthracenes; Boron Compounds; Catalysis; Cycloaddition Reaction; Fluorescent Dyes; Models, Molecular; Molecular Probes; RNA, Catalytic; Stereoisomerism; Substrate Specificity

An anthracene unit was successfully fused to the zigzag edge of a boron dipyrromethene (BODIPY) core by an FeCl(3)-mediated oxidative cyclodehydrogenation reaction. Meanwhile, a dimer was also formed by both intramolecular cyclization and intermolecular coupling. The anthracene-fused BODIPY monomer 7a and dimer 7b showed small energy gaps (∼1.4 eV) and near-infrared absorption/emission. Moreover, they exhibited high photostability.

Topics: Anthracenes; Boron Compounds; Dimerization; Fluorescent Dyes; Models, Molecular; Molecular Structure; Photochemical Processes; Spectroscopy, Near-Infrared

Fluorescence spectroscopy is a powerful, extremely sensitive technique for the investigation of enzyme and ribozyme mechanisms. Herein, we describe the synthesis and characterization of water-soluble fluorescence probes for studying biocatalytic Diels-Alder reactions. These probes consist of anthracene and sulfonated BODIPY fluorophores fused by conjugated phenylacetylenyl bridges. Intact anthracene efficiently quenches BODIPY fluorescence, likely by photoinduced electron transfer. Upon destruction of the aromatic system by the Diels-Alder reaction, the fluorescence emission increases 20-fold. Binding in the catalytic pocket of a Diels-Alderase ribozyme yields a further approximately 2-fold increase in the fluorescence intensity of both the anthracene-BODIPY and the Diels-Alder-product-BODIPY probes. Therefore, a fluorescence-based distinction of free substrate, bound substrate, bound product, and free product is possible. With these all-in-one reporters, we monitored RNA-catalyzed Diels-Alder reactions under both single- and multiple-turnover conditions down to the nanomolar concentration range. Burst analysis at the single-molecule level revealed blinking of the dyads between an on state and an off state, presumably due to rotation around the phenylacetylenyl bridge. Binding to the ribozyme does not increase the intensity of the individual fluorescence bursts, but rather increases the average time spent in the on state. Variations in the quantum yields of the different probes correlate well with the degree of conjugation between anthracene and the phenylacetylenyl bridge.

Topics: Anthracenes; Biocatalysis; Boron Compounds; Fluorescent Dyes; RNA, Catalytic; Spectrometry, Fluorescence; Water