Design strategies for small molecular fluorophores and their applications in detection of fluoride and copper ions

Chemosensing, an area of increasing importance, has received considerable attention in recent years. The relevance of chemosensing can be observed in a wide range of on-site real-time applications such as in the areas of medical diagnostics, environmental monitoring, and toxicological analysis. The cationic and anionic analytes have potential roles in various fields of biological and environmental chemistry. Amongst the most important analytes are fluoride anion and copper cations, which need to be monitored due to their effects on physiology. Fluoride anions prevent dental cavities and are also used to treat osteoporosis. This anion is also essential for the refinement of waste generated from the manufacture of weapons-grade uranium. The human body can absorb fluoride anions quite easily, however the excretion out of the body is rather slow and therefore overexposure of these anions often cause acute kidney and gastric problems. Furthermore, overexposure to fluoride can also adversely affect the brain, thyroid gland, pineal gland and bones. Although numerous techniques have been developed to measure the level of fluoride ions involving the use of sophisticated instrumental methods, such as titrimetric, voltammetric, potentiometric, and electrochemical techniques, as well as ion-exchange chromatography, these techniques are relatively time-consuming, and often exhibit high detection limits. Method development for high sensitivity and selectivity towards fluoride anions thus still remains a challenge, and the use of optical sensors that rely on either change of colour or fluorescence intensity is an active research area, and the topic of this thesis. This thesis is divided into five chapters, the first chapter narrates different detection techniques and presents a literature survey on sensors in general. The second chapter reports on a highly selective isophorone-boronate ester based chemosensor (1) containing a dicyanovinyl moiety as a convenient colorimetric probe. The behaviour of (1) towards different anionic analytes (CH3COO-, ClO4-, Cl-, F-, PF6-, Br- and HSO4-) was investigated, and only the highly nucleophilic F- anion elicited a significant response towards the sensor. In solution, the coordination of the fluoride anion to the boron atom in (1) disrupts the pi-conjugation in the sensor, thereby shifting the absorption wavelength towards the red region due to a decrease in the HOMO-LUMO energy gap, resulting in a colour change from yellow to blue, observed under visible light conditions. From absorption titration studies, the binding constant and detection limit of this probe for fluoride ions were calculated and found to be 1.73 × 105 M-1 and 3.25 × 10-8 M, respectively. Silica gel TLC strips dip-coated in (1) underwent a colour change from yellow to brick red, observable with the naked eye, upon immersion in solutions containing fluoride ions. The molecular sensor (1) was found to be highly sensitive towards air and moisture and unstable due to the reactive boronate ester functionality present on it, hence in order to explore a stable and more reliable structural scaffold for fluoride sensing, the design and development of a tetraphenylethylene (TPE) based molecular sensor DTITPE was undertaken. The third chapter discusses the molecular sensor 4, 5-di(thien-2-yl)-2-(4-(1,2,2-triphenylvinyl)-phenyl)-1H-imidazole, DTITPE, which has been synthesized for the detection of fluoride ions. Detection limits of 1.37 x 10-7 M and 2.67 x 10-13 M were obtained as determined by UV-vis and fluorescence spectroscopy, respectively. The variation in the optical properties of the molecular sensor in the presence of fluoride ions was explained by an intermolecular charge transfer (ICT) process between the bis(thienyl) and tetraphenylethylene (TPE) moieties through the formation of an NH-F- hydrogen bond of the imidazole ring. The sensing mechanism exhibited by DTITPE for fluoride ions was confirmed by 1H NMR spectroscopic studies and density functional theory (DFT) calculations. Test strips coated with the molecular sensor could detect fluoride ions in THF, which can be observed with the naked eye showcasing their potential real-world application. Cu(II) ions are a crucial component of some metalloenzymes, including tyrosinase and superoxide dismutase. Cu(II) is also an essential micronutrient for plants and animals, however at elevated concentrations it can act as a toxin by effecting nutrient transport across cell walls. Because of the potentially deleterious effects, copper pollution is of significant concern. Cu(II) ions can enter the environment from many sources, particularly from industrial and agricultural processes, and contamination of drinking water is a major problem. In humans, overexposure to Cu(II) can cause liver and kidney damage, high blood pressure and is harmful to the central nervous system. Furthermore, the imbalance of Cu(II) metabolism has been linked to various diseases, including Wilson, Menkes, Alzheimer, Parkinson's and prion's diseases. Therefore, the selective detection of Cu(II) at the micromolar level is essential. In this thesis I have designed a thiophene derivative for Cu(II) cation sensing, and the fourth chapter describes the ultrasensitive detection of Cu(II) cations in water using a surface-enhanced Raman spectroscopy (SERS) technique. A bis(thienyl)imidazole-based fluorescent molecular sensor (TIBIT) was prepared and fully characterized by NMR spectroscopy, mass spectrometry and single-crystal X-ray diffraction. The sensing application of TIBIT towards metal ions in solution was investigated using UV-vis, fluorescence, and SERS. In organic solvents (ethanol, THF), TIBIT showed excellent sensitivity towards Cu(II) with a detection limit of 10 pM, whereas in aqueous media, aggregation-caused quenching (ACQ) was observed. Using a SERS substrate consisting of Au-deposited long-range ordered crystals (Au-LROCs) of polystyrene colloids, and uniform deposition of TIBIT as a Raman marker, ACQ was overcome and the detection of trace amounts of Cu(II) in aqueous media was achieved. Using this approach, a detection limit of 1.3 nM was found, considerably lower than the recommended safe level of 20 µM regulated by the United States Environmental Protection Agency for Cu2+ in drinking water, thus demonstrating the potential of TIBIT for monitoring Cu(II) levels in water samples. This thesis offers a strategic approach to develop highly selective and sensitive molecular sensors for detection of anionic/cationic analytes in both organic and aqueous media. We provide brief information about improving the stability and activity of the molecular sensor by changing the receptor, signalling units and pi-conjugate system which exist between both moieties. The detailed studies also provide an in-depth understanding of the sensing mechanism of the molecular sensor when binding with analytes. This research opens up a new opportunity for the development of a new method for SERS, by using Au-deposited long-range ordered crystals (Au-LROCs) substrate, enabling sensing with molecular sensors which do not display activity in aqueous media using traditional optical studies.