Detection Of Hydroxyl Radicals And Regulation The Self-assembly Of Guanosine Derivatives

Hydroxyl radical possesses high reactivity, and directly leads to apoptosis and oxidative damage to DNA, which are associated with a series of physiological and pathological processes, including carcinogenesis and neurodegenerative diseases. So it’s very important to detect hydroxyl radicals in the living cells. Telomeres, locating at the end of eukaryotic chromosomes, can protect chromosome from fusion and degradation. Many studies have shown that the telomere guanine-rich DNA strand can form G-quadruplex structure under certain conditions, which is considered to be a new target for anti-cancer drug. This thesis focuses on DNA oxidative damage and the self-assembly structure regulation of guanosine derivatives. A high selective and sensitive fluorescent probe of hydroxyl radicals in living cells was exploited; the conversions between G-quartets and G-ribbons regulated by solvent, concentration, ultrasound and light were achieved. The study includes the following parts:1. A ratiometric fluorescent probe for the detection of hydroxyl radicals in living cellsBased on the excellent spectral properties of 1,8-naphthalimide and 7-methyl-naphthyridine, a novel naphthalimide-naphthyridine derivative has been designed and synthesized. It exhibits high selectivity and sensitivity, can clearly distinguish hydroxyl radicals from other reactive oxygen species. Moreover, it shows excellent photostability, low cytotoxicity, and can be used for intracellular detection of hydroxyl radicals, which is very significant to follow the tracks of hydroxyl radicals in physiological and pathological processes.2. Concentration and ultrasound regulation on self-assembled structures of guanosine derivativesAmphiphilic guanosine derivatives obtained by modification of glycosyl with a hydrophobic group not only possess the intrinsic properties of guanine itself, but also an additional hydrophobic interaction, which may be exploited to manipulate molecular self-assembly behavior by adjusting the micro-environment. In this work, we have designed and synthesized two amphiphilic guanosine derivatives by modifying the glycosyl group of guanosine with an adamantane moiety. The influence of concentration and ultrasound on the self-assembly behaviour have been extensively investigated. Surprisingly, we found that G-quartet was transformed into a G-ribbon gel at concentrations higher than the CGC. The exploration of the conversion between G-quartets and other self-assembled forms of guanosine has provided insight into the formation and stability of DNA G-quadruplexes.3. Light regulation on self-assembled structures of guanosine derivativesWe further introduced azobenzene group on the basis of the previous chapter work, and synthesized two azobenzene-modified guanosine derivatives. By means of CD, UV, NMR, the self-assembly behavior of the two compounds in chloroform under the presence of potassium ion were studied.The results showed that potassium ion can stabilize the G-quartet structure, light has short influence on the G-quartet structure.4. Detection and regulation of DNA mismatch by diarylethylene derivativesBased on the molecular recognition between naphthyridine and guanine groups, we designed and synthesized two diarylethylene compounds, which contained naphthalimide fluorophore and naphthyridine molecular recognition group. By means of UV-visible and fluorescence emission spectroscopies, photochromic properties and fluorescence lifetime of the two compounds were studied. The excellent photochromic behaviors make them hopeful in the detection and regulation of the configuration of guanine-mismatch DNA sequences.