Colorimetric and Fluorimetric Detection of Fe(III) Using a Rhodamine-Imidazole Hydrazone Based Chemosensor: Photophysical Properties, DFT, TGA, and DSC Studies.

Rhodamine-imidazole hydrazones (RIH-1 & RIH-2) based chemosensors have been synthesized. These are characterised and evaluated by FT-IR spectroscopy, 1H-NMR, 13C-NMR, LCMS, absorption and fluorescence spectroscopy. These chemosensors exhibit enhanced sensitivity and selectivity in detecting the biologically significant Fe3+ metal ion through both colorimetric and fluorescence changes. The optical properties have been investigated using binary acetonitrile-water (7:3 v/v) semi-aqueous solution. The probe RIH-1 can be deployed as a fluorescent and colorimetric probe for the detection of Fe3+ ion. It shows an absorption band at 559 nm and an intensity band at 579 nm increasing up to 50-fold with the increase in the concentration of Fe3+ with the detection limit as low as 11nM. In the visible light, RIH-1 helps in the detection of Fe3+ ion through the naked eye, while the addition of Fe3+ to the probe RIH-1 results in a colour change from colourless to pink. This is primarily due to the opening of the lactone ring in RIH-1. Notably, RIH-1 probe displays a high quantum yield of 0.51, after binding with Fe3+ ions. Indeed, it has been found that sensor RIH-1 is very effective in sensing Fe3+ ions through both fluorescence based and visual detection methods. Additionally, DFT studies of these chemosensors have been evaluated, TGA and DSC analysis showed good thermal stability.

Unique development of a new dual application probe for selective detection of antiparallel G-quadruplex sequences.

G-Quadruplex (G4) structures play vital roles in many biological processes; consequently, they have been implicated in various human diseases like cancer, Alzheimer's disease etc. The selective detection of G4 DNA structures is of great interest for understanding their roles and biological functions. Hence, development of multifunctional fluorescent probes is indeed essential. In this investigation, we have synthesized a quinolinium based dual application probe (QnMF) that presents molecular rotor properties. This dual application molecular rotor is able to detect selectively antiparallel G4 sequences (22AG in 100 mM NaCl) through a turn-on response over other G4 topologies. The QnMF also contains a distinct fluorine-19 that undergoes a significant chemical shift in response to microenvironmental changes around the molecule when bound to G4 structures. The probe QnMF exhibits significantly brighter fluorescence emissions in glycerol (ε × Ï• = 2800 cm-1 M-1) and relatively less brighter fluorescence emissions in methanol (ε × Ï• = 40.5 cm-1 M-1). The restricted rotation inherent property of the QnMF molecular rotor is responsible for brighter fluorescence and leads to enhancement in the fluorescence upon binding to the G4 structure. Overall, the probe's dual detection method makes it useful for monitoring the G4 structures that are abundant and plays a vital role in living organisms.

A matrix targeted fluorescent probe to monitor mitochondrial dynamics.

Mitochondria are an indispensable organelle for energy production and regulation of cellular metabolism. The structural and functional alterations to mitochondria instigate pathological conditions of cancer, and aging-associated and neurodegenerative disorders. The normal functioning of mitochondria is maintained by quality control mechanisms involving dynamic fission, fusion, biogenesis and mitophagy. Under conditions of mitophagy and neurodegenerative diseases, mitochondria are exposed to different acidic environments and high levels of reactive oxygen species (ROS). Therefore stable molecular tools and methods are required to monitor the pathways linked to mitochondrial dysfunction and disease conditions. Herein, we report a far-red fluorescent probe (Mito-TG) with excellent biocompatibility, biostability, photostability, chemical stability and turn on emission for selective targeting of the mitochondrial matrix in different live cells. The probe was successfully employed for monitoring dynamic processes of mitophagy and amyloid beta (Aß) induced mitochondrial structural changes.

Small Molecule Inhibits Metal-Dependent and -Independent Multifaceted Toxicity of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most devastating forms of dementia, without reliable treatments to cure, delay the onset, or prevent the disease progression. The proposed toxic mechanisms of AD include amyloidogenesis of amyloid ß (Aß), metal ion dyshomeostasis, redox active metal-Aß inclusion complex formation, and generation of excessive reactive oxygen and nitrogen species (ROS and RNS). The imbalance in redox homeostasis causes oxidative stress, DNA damage, mitochondrial dysfunction, and inflammation, which collectively become a major hurdle in the development of effective therapeutic agents for multifactorial AD. This necessitates a multifunctional strategy to develop effective therapeutic agents to inhibit multifaceted toxicity. In this context, we report a rational design, synthesis, and detailed study to identify a small molecule multifunctional modulator (MFM) inspired by the human origin tripeptide. The lead, MFM 4, chelates and sequesters metal ions, disrupts their redox cycles, prevents excessive ROS production and oxidative stress, ameliorates oxidative DNA damage and mitochondrial dysfunction, and modulates Nrf2 protein signaling under oxidative stress conditions by eliminating the toxic stress elements. The MFM 4 was found to inhibit metal-dependent and -independent Aß aggregation and qualified as a suitable candidate to inhibit Aß-induced neuronal toxicity. The NMR spectroscopy study revealed molecular-level interactions of 4 with Aß42, which explain the mechanism of aggregation inhibition. Furthermore, 4 effectively inhibited inflammation as revealed by reduction in nitric oxide (NO) production in LPS-activated glial cells. These key features make 4 a potential MFM platform to develop therapeutic agents for metal (Cu, Zn and Fe)-dependent and -independent multifaceted Aß toxicity of AD.