Self-immolative dendritic probe for direct detection of triacetone triperoxide.

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv, 69978, Israel.
Chemical Communications (Impact Factor: 6.72). 12/2008; DOI: 10.1039/b814855d
Source: PubMed

ABSTRACT A new self-immolative dendritic probe directly detects triacetone triperoxide through amplification of a single cleavage event initiated by one molecule of hydrogen peroxide into multiple-release of fluorogenic end-groups.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reactive oxygen species (ROS) play key roles in many physiological processes, such as cell signaling and host innate immunity. However, when they are overproduced, ROS may damage biomolecules in vivo and cause diseases such as cardiovascular or neurodegenerative diseases, cancer, and so forth. Oxidative stress is usually implicated in various inflammatory tissues, representing an important target for the development of various therapeutic strategies. Therefore, various probes for the in vitro detection of ROS or the in vivo diagnosis of the oxidative stress-relevant diseases have been developed. Oxidation-responsive polymers have also attracted great interest due to their potential applications in biomedical fields. In this feature article, we summarize six types of oxidation-responsive polymers based on different oxidation-responsive motifs. Poly(propylene sulfide)s, selenium-based polymers, aryl oxalate- and phenylboronic ester-containing polymers are discussed in detail, while poly(thioketal)s and proline-containing polymeric scaffolds are briefly introduced.
    05/2014; 2(22). DOI:10.1039/C3TB21725F
  • [Show abstract] [Hide abstract]
    ABSTRACT: Conspectus Over the last 30 years, the quinone-methide elimination has served as a valuable tool for achieving various important molecular functions. Molecular adaptors based on quinone-methide or aza-quinone-methide reactivity have been designed, synthesized, and used in diagnostic probes, molecular amplifiers, drug delivery systems, and self-immolative dendritic/polymeric molecular systems. These unique adaptors function as stable spacers between an enzyme- or reagent-responsive group and a reporter moiety and can undergo 1,4-, 1,6-, or 1,8-type elimination reactions upon cleavage of the triggering group. Such reactivity results in the release of the reporter group through formation of a quinone-methide species. This type of elimination was applied to design distinct molecular adaptors capable of multiple quinone-methide eliminations. Using this chemistry, we have developed unique molecular structures that are known today as self-immolative dendrimers. These dendrimers disassemble upon a single triggering event in a domino-like manner from the focal point to their periphery with the consequent release of multiple end-groups. Such molecular structures are used in self-immolative dendritic prodrugs and in diagnostic probes to obtain a significant amplification effect. To further enhance amplification, we have developed the dendritic chain reaction, which uses simple molecules to achieve functionality of high-generation virtual self-immolative dendrimers. In addition, we harnessed the quinone-methide elimination reactivity to design polymers that disassemble from head-to-tail initiated by an analyte-responsive event. Following this example, other chemical reactivities were demonstrated by scientists to design such polymeric molecules. In a manner analogous to the quinone-methide elimination, electron rearrangement can lead to formation of conjugated quinone-methide-type dyes with long-wavelength emission of fluorescence. We have recently applied an intramolecular charge transfer to form a unique kind of quinone-methide type derivative based on a donor-two-acceptors molecular structure. This intramolecular charge transfer produces a new fluorochrome with an extended conjugation of π-electron system that is used for the design of long-wavelength fluorogenic probes with a turn-ON option. The rapidly expanding use of quinone-methide species, reflected in the increased number of examples reported in the literature, indicates the importance of this tool in chemistry. These species provide a useful gateway to functional molecular structures with distinct reactivities and spectroscopic characteristics.
    Accounts of Chemical Research 09/2014; 47(10). DOI:10.1021/ar500179y · 24.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reactive oxygen species (ROS) play important roles in the development and progression of cancer and other diseases, motivating the development of translatable technologies for biological ROS imaging. Here we report Peroxy-Caged-[(18)F]Fluorodeoxy thymidine-1 (PC-FLT-1), an oxidatively immolative positron emission tomography (PET) probe for H2O2 detection. PC-FLT-1 reacts with H2O2 to generate [(18)F]FLT, allowing its peroxide-dependent uptake and retention in proliferating cells. The relative uptake of PC-FLT-1 was evaluated using H2O2-treated UOK262 renal carcinoma cells and a paraquat-induced oxidative stress cell model, demonstrating ROS-dependent tracer accumulation. The data suggest that PC-FLT-1 possesses promising characteristics for translatable ROS detection and provide a general approach to PET imaging that can be expanded to the in vivo study of other biologically relevant analytes.
    Journal of the American Chemical Society 10/2014; 136(42). DOI:10.1021/ja509198w · 11.44 Impact Factor