Selenium- and tellurium-containing fluorescent molecular probes for the detection of biologically important analytes.

Abstract

As scientists in recent decades have discovered, selenium is an important trace element in life. The element is now known to play an important role in biology as an enzymatic antioxidant. In this case, it sits at the active site and converts biological hydrogen peroxides to water. Mimicking this reaction, chemists have synthesized several organoselenium compounds that undergo redox transformations. As such, these types of compounds are important in the future of both medicinal and materials chemistry. One main challenge for organochalcogen chemists has been to synthesize molecular probes that are soluble in water where a selenium or tellurium center can best modify electronics of the molecule based on a chemical oxidation or reduction event. In this Account, we discuss chemists' recent efforts to create chalcogen-based chemosensors through synthetic means and current photophysical understanding. Our work has focused on small chromophoric or fluorophoric molecules, in which we incorporate discrete organochalcogen atoms (e.g., R-Se-R, R-Te-R) in predesigned sites. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively oxidize compounds and to study the level of analyte selectivity by way of their optical responses. All the reports we discussed here deal with well-defined and small synthetic molecular systems. With a large number of reports published over the last few years, many have notably originated from the laboratory of K. Han (P. R. China). This growing body of research has given chemists new ideas for the previously untenable reversible reactive oxygen species detection. While reversibility of the probe is technically important from the stand-point of the chalcogen center, facile regenerability of the probe using a secondary analyte to recover the initial probe is a very promising avenue. This is because (bio)chalcogen chemistry is extremely rich and bioinspired and continues to yield important developments across many scientific fields. Organochalcogen (R-E-R) chemistry in such chemical recognition and supramolecular pursuits is a fundamental tool to allow chemists to explore stable organic-based probe modalities of interest to develop better spectroscopic tools for (neuro)biological applications. Chalcogen donor sites also provide sites where metals can coordinate, and facile oxidation may extend to the sulfone analogues (R-EO2-R) or beyond. Consequently, chemists can then make use of reliable reversible chemical probing platforms based on the chemical redox properties valence state switching principally from 2 to 4 (and back to 2) of selenium and tellurium atoms. The main organic molecular skeletons have involved chemical frames including boron-dipyrromethene (BODIPY) systems, extended cyanine groups, naphthalimide, rhodamine, and fluorescein cores, and isoselenazolone, pyrene, coumarin, benzoselenadiazole, and selenoguanine systems. Our group has tested many such molecular probe systems in cellular milieu and under a series of conditions and competitive environments. We have found that the most important analytes have been reactive oxygen species (ROS) such as superoxide and hypochlorite. Reactive nitrogen species (RNS) such as peroxynitrite are also potential targets. In addition, we have also considered Fenton chemistry systems. Our research and that of others shows that the action of ROS is often reversible with H2S or biothiols such as glutathione (GSH). We have also found that a second class of analytes are the thiols (RSH), in particular, biothiols. Here, the target group might involve an R-Se-Se-R group. The study of analytes also extends to metal ions, for example, Hg(2+), and anions such as fluoride (F(-)), and we have developed NIR-based systems as well. These work through various photomechanisms, including photoinduced electron transfer (PET), twisted internal charge transfer (TICT), and internal charge transfer (ICT). The growing understanding of this class of probe suggests that there is much room for creative thinking regarding modular designs or unexpected organic chemical synthesis designs, interplay between analytes, new analyte selectivity, biological targeting, and chemical switching, which can also serve to further the neurological probing and molecular logic gating frontiers.