Quinone-Methide Species, A Gateway to Functional Molecular Systems: From Self-Immolative Dendrimers to Long-Wavelength Fluorescent Dyes
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- 作者：Samer Gnaim ; Doron Shabat
- 刊名：Accounts of Chemical Research
- 出版年：2014
- 出版时间：October 21, 2014
- 年：2014
- 卷：47
- 期：10
- 页码：2970-2984
- 全文大小：857K
- ISSN：1520-4898
文摘
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鈥搕wo-acceptors molecular structure. This intramolecular charge transfer produces a new fluorochrome with an extended conjugation of 蟺-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.
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鈥搕wo-acceptors molecular structure. This intramolecular charge transfer produces a new fluorochrome with an extended conjugation of 蟺-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.