Biomolecular Interactions and Anticancer Mechanisms of Ru(II)-Arene Complexes of Cinnamaldehyde-Derived Thiosemicarbazone Ligands: Analysis Combining In Silico and In Vitro Approaches.

Our study focuses on synthesizing and exploring the potential of three N-(4) substituted thiosemicarbazones derived from cinnamic aldehyde, alongside their Ru(II)-(η6 -p-cymene)/(η6-benzene) complexes. The synthesized compounds were comprehensively characterized using a range of analytical techniques, including FT-IR, UV-visible spectroscopy, NMR (1H, 13C), and HRMS. We investigated their electronic and physicochemical properties via density functional theory (DFT). X-ray crystal structures validated structural differences identified by DFT. Molecular docking predicted promising bioactivities, supported by experimental observations. Notably, docking with EGFR suggested an inhibitory potential against this cancer-related protein. Spectroscopic titrations revealed significant DNA/BSA binding affinities, particularly with DNA intercalation and BSA hydrophobic interactions. RuPCAM displayed the strongest binding affinity with DNA (Kb = 6.23 × 107 M-1) and BSA (Kb = 9.75 × 105 M-1). Assessed the cytotoxicity of the complexes on cervical cancer cells (HeLa), and breast cancer cells (MCF-7 and MDA-MB 231), revealing remarkable potency. Additionally, selectivity was assessed by examining MCF-10a normal cell lines. The active complexes were found to trigger apoptosis, a vital cellular process crucial for evaluating their potential as anticancer agents utilizing staining assays and flow cytometry analysis. Intriguingly, complexation with Ru(II)-arene precursors significantly amplified the bioactivity of thiosemicarbazones, unveiling promising avenues toward the creation of powerful anticancer agents.

Targeting Glioblastoma: Efficacy of Ruthenium-Based Drugs.

Ruthenium compounds offer improved selectivity and fewer side effects compared to platinum-based drugs in glioblastoma treatment. Insights into their interactions with transferrin suggest targeted drug delivery, while photoactivated chemotherapy is a novel cytotoxic approach in tumor tissues.

Copper-mediated cyclization of thiosemicarbazones leading to 1,3,4-thiadiazoles: Structural elucidation, DFT calculations, in vitro biological evaluation and in silico evaluation studies.

Cancer's global impact necessitates innovative and less toxic treatments. Thiosemicarbazones (TSCs), adaptable metal chelators, offer such potential. In this study, we have synthesized N (4)-substituted heterocyclic TSCs from syringaldehyde (TSL1, TSL2), and also report the unexpected copper-mediated cyclization of the TSCs to form thiadiazoles (TSL3, TSL4), expanding research avenues. This work includes extensive characterization and studies such as DNA/protein binding, molecular docking, and theoretical analyses to demonstrate the potential of the as-prepared TSCs and thiadiazoles against different cancer cells. The DFT results depict that the thiadiazoles exhibit greater structural stability and reduced reactivity compared to the corresponding TSCs. The docking results suggest superior EGFR inhibition for TSL3 with a binding constant value of - 6.99 Kcal/mol. According to molecular dynamics studies, the TSL3-EGFR complex exhibits a lower average RMSD (1.39 nm) as compared to the TSL1-EGFR complex (3.29 nm) suggesting that both the thiadiazole and thiosemicarbazone examined here can be good inhibitors of EGFR protein, also that TSL3 can inhibit EGFR better than TSL1. ADME analysis indicates drug-likeness and oral availability of the thiadiazole-based drugs. The DNA binding experiment through absorption and emission spectroscopy discovered that TSL3 is more active towards DNA which is quantitatively calculated with a Kb value of 4.74 × 106 M-1, Kq value of 4.04 × 104 M-1and Kapp value of 5 × 106 M-1. Furthermore, the BSA binding studies carried out with fluorescence spectroscopy showed that TSL3 shows better binding capacity (1.64 × 105 M-1) with BSA protein. All the compounds show significant cytotoxicity against A459-lung, MCF-7-breast, and HepG2-liver cancer cell lines; TSL3 exhibits the best cytotoxicity, albeit less effective than cisplatin. Thiadiazoles demonstrate greater cytotoxicity than the TSCs. Overall, the promise of TSCs and thiadiazoles in cancer research is highlighted by this study. Furthermore, it unveils unexpected copper-mediated cyclization of the TSCs to thiadiazoles.

Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications.

A novel Coumarin-based 1,2-pyrazole, HCPyTSC is synthesised and characterized. The chemosensor has been shown to have efficient colourimetric and fluorescence sensing capabilities for the quick and selective detection of fluoride and copper ions. At 376 and 430 nm, the HCPyTSC exhibits selective sensing for Cu2+ and F- ions. By examining the natural bond orbital (NBO) analysis and the potential energy curve (PES) of the ground state for the function of the C-H bond, it has been determined from the theoretical study at hand that the deprotonation was taken from the 'CH' proton of the pyrazole ring. For F- and Cu2+, the HCPyTSC detection limits were 4.62 nM and 15.36 nM, respectively. Similarly, the binding constants (Kb) for F- and Cu2+ ions in acetonitrile medium were found to be 2.06 × 105 M-1 and 1.88 × 105 M-1. Chemosensor HCPyTSC with and without F- and Cu2+ ions have an emission and absorption response that can imitate a variety of logic gates, including the AND, XOR, and OR gates. Additionally, a paper-based sensor strip with the HCPyTSC was created for use in practical, flexible F- sensing applications. The paper-based sensor was more effective in detecting F- than other anions. The effectiveness of HCPyTSC for the selective detection of F- in living cells as well as its cell permeability were examined using live-cell imaging in T24 cells.

Cadmium Exposure and Cardiovascular Diseases.

Cadmium lurks in our food, water, and air silently wreaking havoc on human health. It accumulates in plants and mammals, lasting 25-30 years. Herein, we highlight the potential link between cadmium exposure and cardiovascular disorders in humans.

Pilot Study on the Visualization of Latent Fingerprints and Naked Eye Detection of Hg2+ and Zn2+ Ions in Aqueous Media Using Ninhydrin-Based Thiosemicarbazone.

Here, we described a cheap and effective chemosensor (NHPyTSC) that can distinguish Hg2+ and Zn2+ ions from other metal ions and evaluated this phenomenon using several spectroscopy techniques. With the addition of mercury and zinc ions, the proposed chemosensor in particular showed noticeable changes in color and absorption spectra. Additionally, by including EDTA in the NHPyTSC-Hg2+ and NHPyTSC-Zn2+ solutions, colorimetry readings can be reversed. We developed a molecular-scale sequential information processing circuit and presented the "writing-reading-erasing-reading" and "multiwrite" behaviors in the form of binary logic based on the great reversibility of this process. Moreover, by sequentially adding Hg2+, Zn2+, and EDTA, NHPyTSC imitates a molecular keypad lock and molecular logic gates. Density functional theory (DFT) investigations provided more evidence of the Hg2+ and Zn2+ ions' ability to attach to NHPyTSC. The most interesting part of this work is that a study on the latent fingerprint detection of the powder compound revealed that NHPyTSC exhibits good adherence and finger ridge features without background stains. When compared to black and white fingerprint powders, it is discovered that the NHPyTSC powder produces results that are remarkably clear on the majority of surfaces. This demonstrated their potential for real-world use, particularly in the area of criminal investigations.

Simple Fluorescence Sensing Approach for Selective Detection of Fe3+ Ions: Live-Cell Imaging and Logic Gate Functioning.

A pyrene-based fluorescent chemosensor APSB [N-(pyrene-1-ylmethylene) anthracen-2-amine] was designed and developed by a simple condensation reaction between pyrene carboxaldehyde and 2-aminoanthracene. The APSB fluorescent sensor selectively binds Fe3+ in the presence of other metal ions. Apart from this, APSB shows high selectivity and sensitivity toward Fe3+ ion detection. The detection limit for APSB was 1.95 nM, and the binding constant (K b) was obtained as 8.20 × 105 M-1 in DMSO/water (95/5, v/v) medium. The fluorescence quantum yields for APSB and APSB-Fe3+ were calculated as 0.035 and 0.573, respectively. The function of this fluorescent sensor APSB can be explained through the photo-induced electron transfer mechanism which was further proved by density functional theory studies. Finally, a live-cell image study of APSB in HeLa cells was also carried out to investigate the cell permeability of APSB and its efficiency for selective detection of Fe3+ in living cells.

An Effective Selenium-Based Fluorescence Chemosensor for Selective Recognition of Hg2+ in Aqueous Medium: Experimental and Theoretical Studies.

We introduce a novel selenium-based compound [N-(Phenylcarbamoselenoyl) furan-2-carboxamide] for the optical and fluorimetric detection of Hg in an aqueous medium. The synthesized compound was characterized by different spectroscopic methods. The designed chemosensor FSU has shown a significant fluorescence quenching when Hg2+ ions were added to the sensing medium. Furthermore, Hg2+ ions provoked a 2:1 complex formation with the chemosensor FSU. It is found that the compound offers high selectivity over a variety of cations such as Co2+, Cr3+, Ni2+, Zn2+, Cu2+, Mg2+, Hg2+, Cd2+, Ca2+, Mn2+, Ga3+, Pb2+, Na+, Fe2+ and K+. The detection limit was calculated as 7.35 × 10-7 M. Also, FSU shows appreciable binding affinity towards Hg2+ ions with a binding constant value of 1.413 × 103 M-1. The ICT mechanism of mercury sensing was confirmed with spectroscopic techniques and DFT studies. Density functional theory was also implemented to investigate the structure of the Hg2+ complex and its electronic distribution in the aqueous medium. Finally, an MEP study was also carried out to obtain detailed information about the surface characteristics of the chemosensor FSU. Effectively, we have reported a potent chemosensor for Hg2+ in the aqueous medium.

A Highly Fluorescent Pyrene-Based Sensor for Selective Detection Of Fe3+ Ion in Aqueous Medium: Computational Investigations.

In this work, we introduce a highly selective and sensitive fluorescent sensor based on pyrene derivative for Fe(III) ion sensing in DMSO/water media. 2-(pyrene-2-yl)-1-(pyrene-2-ylmethyl)-1H-benzo[d]imidazole (PEBD) receptor was synthesized via simple condensation reaction and confirmed by spectroscopic techniques. The receptor exhibits fluorescence quenching in the presence of Fe(III) ions at 440 nm. ESI-MS and Job's method were used to confirm the 1:1 molar binding ratio of the receptor PEBD to Fe(III) ions. Using the Benesi-Hildebrand equation the binding constant value was determined as 8.485 × 103 M-1. Furthermore, the limit of detection (LOD, 3σ/K) value was found to be 1.81 µM in DMSO/water (95/5, v/v) media. According to the Environmental Protection Agency (EPA) of the United States, it is lower than the acceptable value of Fe3+ in drinking water (0.3 mg/L). The presence of 14 other metal ions such Co2+, Cr3+, Cu2+, Fe2+, Hg2+, Pb2+, K+, Ni2+, Mg2+, Cd2+, Ca2+, Mn2+, Al3+, and Zn2+ did not interfere with the detection of Fe(III) ions. The fluorescence life-time of the receptor PEBD with and without Fe3+ ion was found to be 1.097 × 10-9 s and 0.9202 × 10-9 s respectively. Similarly, the quantum yield of the receptor PEBD with Fe3+ and without Fe3+ ion was calculated, and found as 0.05 and 0.25 respectively. Computational studies of the receptor PEBD were carried out with density functional theory (DFT) using B3LYP/ 6-311G (d, p), LANL2DZ level of theory.