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.

Synthesis, characterization, theoretical, molecular docking and in vitro biological activity studies of Ru(II) (η6-p-cymene) complexes with novel aniline substituted aroyl selenoureas.

A sequence of aroyl selenourea ligands (L1-L3) substituted by aniline and their Ru(II) (η6-p-cymene) complexes (1-3), [Ru(II) (η6-p-cymene) L] (L = monodentate aroyl selenourea ligand) have been synthesized and characterized the composition of the ligands and their metal complexes. The molecular structures of ligand L1 and complex 3 were also confirmed by single XRD crystal method. The single-crystal XRD study showed that aroyl selenourea ligand coordinates with Ru via Se novel neutral monodentate atom. In vitro DNA interaction studies were investigated by Fluorescence and UV-Visible spectroscopic methods which showed that the intercalative mode of binding is in the order of 1 > 2 > 3 with Ru(II) (η6-p-cymene) complexes. Spectroscopic methods have been used for measuring the binding affinity of bovine serum albumin to complex. Moreover, the cytotoxic study of complexes (1-3) were evaluated against HeLa S3, A549, and IMR90 cells, resulting in complexes 1 and 2 showed promising cytotoxic activity against HeLa S3 cell with IC50 values of 24 and 26 µM, respectively. Also, the morphological changes of HeLa S3 and A549 cells were confirmed by fluorescence microscope in the presence of complexes 1 and 2 using AO (acridine orange, 200 µM) and EB (ethidium bromide, 100 µM). In addition, the docking results strongly support the protein binding studies of the complexes.Communicated by Ramaswamy H. Sarma.

Analytical and computational investigation on host-guest interaction of cyclohexyl based thiosemicarbazones: Construction of molecular logic gates using multi-ion detection.

Two novel cyclohexyl based thiosemicarbazones, H2L1 and H3L2, are synthesized and characterized. The anion and cation sensing properties of the two receptors has been unveiled as an effective ratiometric and colorimetric sensor for selective and rapid detection of fluoride, copper and cobalt ions. The H2L1 shows selective sensing towards F- and Cu2+ at 429 and 393 nm, whereas, H3L2 can detect F-, Cu2+ and Co2+ at 350, 393 and 408 nm respectively. The fluoride-sensing mechanism of the receptors has been investigated by means of the DFT and TD-DFT methods. The experimental UV-vis and fluorescence spectra are well reproduced by the calculated vertical excitation energies in the ground state and the first singlet excited state. The present theoretical study indicates that the deportation was taken from the 'NH' proton which is closer to the imine group, which has been confirmed by natural bond orbital (NBO) analysis and the potential energy curve (PES) of ground state for the function of NH bond. The absorption and emission response for receptors with and without F-, Co2+ and Cu2+ ions can mimic multiple logic gate such as NOR, XNOR, OR and TRANSFER gates.

Colorimetric and fluorimetric response of salicylaldehyde dithiosemicarbazone towards fluoride, cyanide and copper ions: Spectroscopic and TD-DFT studies.

The sensing mechanism of salicylaldehyde phenyldithiosemicarbazone (SDTSC) chemosensor has been investigated by spectroscopic and TD-DFT methods. The SDTSC shows colourimetric and spectral changes towards fluoride, cyanide and copper ions. The interaction between SDTSC with fluoride, cyanide and copper ions was examined through their absorption and fluorescence behaviour, and found that SDTSC has more sensing ability towards Cu2+ ion than CN- and F- ions. The 1H NMR titration with SDTSC and F- gives the structural changes in the sensing process. The reversibility of SDTSC was also evaluated and thus it is confirmed as a reusable chemosensor which can be clarified by the "Read-Erase-Read-Write" logic system. The DFT and TD-DFT calculations give the detailed sensing mechanism of SDTSC towards fluoride ion. The potential energy surface (PES) analysis confirms the excited state electron transfer mechanism.

Multi-ion detection and molecular switching behaviour of reversible dual fluorescent sensor.

The selective chemosensing behaviour of imidazole bisthiocarbohydrazone (IBTC) towards F- and Cu2+ are studied via colorimetric, UV-Visible, fluorescence spectra studies, and binding constants were calculated. The 1H NMR titration study strongly support that the deprotonation of IBTC followed by the hydrogen bond formation via N1H1 and N2H2 protons with fluoride ion. The fluorescence inactive IBTC-Cu complex became fluorescence active in the presence of perchlorate (ClO4-) ion. The selective detection of perchlorate ion was also explained. The F- sensing mechanism of IBTC has been investigated by Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) methods. The theoretical outcomes well reproduce the experimental results. And it concluded the NH protons, nearby the imine group was first captured by the added F- ion and then deprotonation happened followed by the formation of hydrogen bond. The IBTC found good reversibility character with the alternative addition of Ca2+ and F-. The multi-ion detection of IBTC was used to construct the NOR, OR and INHIBITION molecular logic gates.

Spectroscopic and TDDFT investigation on highly selective fluorogenic chemosensor and construction of molecular logic gates.

1,5-Bis(2-fluorene)thiocarbohydrazone (FBTC) was designed and synthesized for selective sensing of fluoride and copper ions. The binding constants of FBTC towards fluoride and copper ions have been calculated using the Benesi-Hildebrand equation, and FBTC has more binding affinity towards copper ion than fluoride ion. The 1H NMR and 13C NMR titration studies strongly support the deprotonation was taken from the N-H protons followed by the formation of hydrogen bond via N-H…F. To understand the fluoride ion sensing mechanism, theoretical investigation had been carried out using the density functional theory and time-dependent density functional theory. The theoretical data well reproduced the experimental results. The deprotonation process has a moderate transition barrier (481.55kcal/mol). The calculated ΔE and ΔG values (-253.92 and -192.41kcal/mol respectively) suggest the feasibility of sensing process. The potential energy curves give the optimized structures of FBTC-F complex in the ground state and excited state, which states the proton transition occurs at the excited state. The excited state proton transition mechanism was further confirmed with natural bond orbital analysis. The reversibility of the sensor was monitored by the alternate addition of F- and Cu2+ ions, which was explained with "Read-Erase-Write-Read" behaviour. The multi-ion detection of sensor used to construct the molecular logic gate, such as AND, OR, NOR and INHIBITION logic gates.

Crystal structure of 3-[(E)-(2-hy-droxy-3-meth-oxy-benzyl-idene)amino]-1-methyl-1-phenyl-thio-urea.

In the asymmetric unit of the title compound, C16H17N3O2S, there are two independent mol-ecules (A and B), which show an E conformation with respect to the C=N bond. An intra-molecular O-H⋯N hydrogen bond with an S(6) motif stabilizes the mol-ecular structure. The terminal phenyl and benzene rings are almost orthogonal to each other, the dihedral angle being 87.47 (13)° for mol-ecule A and 89.86 (17)° for mol-ecule B. In the crystal, weak bifurcated N-H⋯(O,O) hydrogen bonds link the two independent mol-ecules, forming a supra-molecular chain with a C (2) 1(14)[R (2) 1(5)] motif along the b axis. A weak C-H⋯O inter-action is also observed in the chain.

A tetracoordinated rhodium aminyl radical complex.

A [16 + 1] valence electron configured rhodium aminyl radical complex could be synthesized and characterized in detail by pulse EPR spectroscopy and DFT calculations. The unpaired electron is delocalized over the metal center and two adjacent nitrogens. H-abstraction reactions from thiols and triethylsilane show that the spin density is predominantly localized on both nitrogens.

Spectral characterization of iron(III) complexes of 2-benzoylpyridine N(4)-substituted thiosemicarbazones.

Three iron(III) complexes (1-3) of 2-benzoylpyridine N(4)-phenyl thiosemicarbazone (HL1) and one iron(III) complex (4) of 2-benzoylpyridine N(4)-cyclohexyl thiosemicarbazone (HL2) were synthesized and characterized by means of different physicochemical techniques viz., molar conductivity measurements, magnetic susceptibility studies and electronic, infrared and EPR spectral studies. The analytical data and the molar conductance measurements of the complexes reveal that two molecules of the ligand and the anion are coordinated to the metal atom in all the four complexes. The magnetic moments of the complexes suggest that they are of low spin. From the infrared spectra of the ligands and the complexes it is confirmed that the ligands coordinate to iron(III) as an anion coordinating via the azomethine nitrogen, pyridyl nitrogen, and the thiolate sulphur. The EPR spectra of the complexes in the polycrystalline state at 298 and 110 K and in DMF solution at 110 K were recorded and all the spectra show three g values indicating that these complexes have rhombic distortion. All the iron(III) complexes in DMF solution at 110 K have similar anisotropic spectra with almost the same gav values, indicating that the bonding in all the complexes is similar and is unaffected by the coordination of the anion.