Studies on the Electronic Effect on Chemosensors and Sensing Platforms

Abstract

Practical use for the electronic effect on a sensing system can produce innovative approaches that can solve previous questions. Part I describes a new prototype of flavin sensing strategy based on a photo-oxidation mechanism. A synthetic probe, consisted of a coumarin unit and a bis(diethylamino)-[9H]xanthene ring linked through a phenyl spacer, showed high brightness (ε × ΦF = 6.5 × 103 M−1cm−1) at long wavelength (λem = 600 nm) upon oxidation, assisted by flavins strong electron accepting ability. The oxidation process was promoted upon photoirradiation (λirr = 450 nm), which is termed photo-oxidation. Moreover, the probe exhibited high selectivity for flavins over other biological oxidants, remarkable photostability, and most importantly, mitochondria localized ability. Therefore, the probe enabled a fluorescence monitoring of mitochondrial flavins in live cells and tissues. Subsequently, an electric field effect on the redox probes was described. Zn2+–dipicolyamine complex (ZnII-DPA) was introduced to the coumarin unit to make probe 1-Zn, which decreased in the autooxidation rate exerting attractive Coulombic force on the [9H]xanthene ring. The positive charge of ZnII-DPA lowered electronic density of the vicinal [9H]xanthene ring, and thereby stabilizing probe 1-Zn. On the other hand, the positive charge increased in the flavin-mediated photo-oxidation rate. The positive charge lowered the reduction potential of isoalloxazine and promoted intermolecular electron transfer from the reduced xanthene to isoalloxazine. Consequently, the probe was successfully applied to various flavin-linked studies such as eosinophils imaging and differential diagnosis of eosinophilia using human blood cell lysate. Part II describes a new sensing strategy for pyrophosphate (PPi) utilizing electrostatic interactions between negatively charged graphene oxide (GO) and a positively charged synthetic probe that is consisted of phenoxo-bridged binuclear Zn2+–dipicolylamine complex (bisZnDPA) ligand. The combination of the well-known surface characteristics of GO and the selective recognition ability of the bisZnDPA-containing probe resulted in improved selectivity toward PPi even in excess amount of nucleoside triphosphates (NTPs). Consequently, the GO-probe conjugate was successfully applied to polymerase chain reaction monitoring that requires highly selective and sensitive detection of PPi. Part III describes push-pull π-conjugation effect on small molecular probes. In Section I, paper strip for cyanide (CN−) detection was prepared by utilizing a synthetic probe, consisted of 6-(dimethylamino)-1,3-benzothiazole linked to a vinyl malononitrile group. A nucleophilic attack of CN− on an electron deficient site of probe altered π-conjugation length and dipole moment of the probe, and thereby giving a large spectral shift accompanied by color change, which are desired for naked eye detection. Further, the internal referencing system allowed compensation of measurement errors, which is indispensable for quantitative analysis in point-of-care testing. The paper strip test showed selective response to CN− with a linear correlation in a range of 0–25 mM in a simple and cost-effective manner. In Section II, a synthetic probe, bearing a benzothiazolium hemicyanine fluorophore and the bisZnDPA ligand, facilitated cellular imaging of PPi by means of its long wavelength emission (λem ≈ 560 nm). The probe allowed highly selective fluorescent detection for PPi over other potential competitors except for ATP. Despite the response to ATP, the probe was successfully applied to fluorescence imaging of PPi in the C2C12 myoblast cell line.