Rational Design and Synthesis of Activity Based Fluorescent Probes for Sensing of Reactive Carbonyl Species RCSs and their Applications

Abstract

Reactive carbonyl species (RCSs) such as formaldehyde (FA), glyoxal (GO), methylglyoxal (MGO), and glyoxylate (GA) are reactive aldehydes, which are widely used in food preservative, paint and cosmetic industries, and medical science. For example, FA is used to preserve fruits, milk, meat, fish etc. Similarly, GO and MGO is mainly used in the process of caramelization and microbial fermentation and can also be found in dry food and beverages. These reactive species are also produced endogenously via various enzymatic and metabolic pathways in physiology. These RCSs are prone to react with multiple bio-molecules leading to advanced glycation end products (AGEs), stable mutagenic DNA adducts, DNA-protein crosslinks (DPCs). These adducts are caused by harmful effects and lead to cellular dysfunctions and disease progression. Thus, elevated levels of RCSs are associated with several diseases, such as type 2 diabetes, cardiovascular, kidney dysfunctions, chronic inflammation, and cancer. Hence, monitoring of these RCSs in an inexpensive way is very much necessary for affordable disease diagnosis. newline newlineDue to the simplicity, cost-effectiveness, ease of access, high sensitivity, fast and non-invasive fluorescence technique has gained enormous attention in the scientific communities in the last two decades. This doctoral work has reported four efficient fluorescent probes which are capable of detecting different RCSs by turn-on fluorescence response. The rational design, synthesis of activity-based fluorescence probes (ABFP), and their sensing mechanism are well explained using different spectroscopy and quantum chemical calculations. By tuning the intramolecular charge transfer (ICT) process, mono-carbonyl can be discriminated from di-carbonyls for the first time. These ABFP were also applied in food and body fluid analysis. Interestingly, GA, a biomarker of type 2 diabetes, can also be efficiently detected using developed probes that may lead to the early diagnosis of diabetes. Furthermore, fluorescence imaging of endogen