A sustainable strategic approach for N-alkylation of amines with activation of alcohols triggered via a hydrogen auto-transfer reaction using a Pd(II) complex: evidence for metal-ligand cooperativity.

This work describes a new well-defined, air-stable, phosphine free palladium(II) [Pd(L)Cl] (1) catalyst. This catalyst was utilized for N-alkylation of amines and indole synthesis where H2O was found to be the by-product. A broad range of aromatic amines were alkylated using this homogeneous catalyst with a catalyst loading of 0.1 mol%. Greener aromatic and aliphatic primary alcohols were utilized and a hydrogen auto-transfer strategy via a metal-ligand cooperative approach was investigated. The precursor of the antihistamine-containing drug molecule tripelennamine was synthesized on a gram scale for large-scale applicability of the current synthetic methodology. A number of control experiments were performed to investigate the possible reaction pathway and the outcomes of these experiments indicated the azo-chromophore as a hydrogen reservoir during the catalytic cycle.

Catalytic, Antifungal, and Antiproliferative Activity Studies of a New Family of Mononuclear [VIVO]/[VVO2] Complexes.

Ligands derived from 2-(1-phenylhydrazinyl)pyridine and salicylaldehyde (HL1), 3-methoxysalicylaldehyde (HL2), 5-bromosalicylaldehyde (HL3), and 3,5-di-tert-butylsalicylaldehyde (HL4) react with [VIVO(acac)2] in MeOH followed by aerial oxidation to give [VVO2(L1)] (1), [VVO2(L2)] (2), [VVO2(L3)] (3), and [VVO2(L4)] (4). Complex [VIVO(acac)(L1)] (5) is also isolable from [VIVO(acac)2] and HL1 in dry MeOH. Structures of all complexes were confirmed by single-crystal X-ray and spectroscopic studies. They efficiently catalyze benzyl alcohol and its derivatives' oxidation in the presence of H2O2 to their corresponding aldehydes. Under optimized reaction conditions using 1 as a catalyst precursor, conversion of benzyl alcohol follows the order: 4 (93%) > 2 (90%) > 1 (86%) > 3 (84%) ≈ 5 (84%). These complexes were also evaluated for antifungal and antiproliferative activities. Complex 3 with MIC50 = 16 µg/mL, 4 with MIC50 = 12 µg/mL, and 5 with MIC50 = 16 µg/mL are efficient toward planktonic cells of Candida albicans and Candida tropicalis. On Michigan cancer foundation-7 (MCF-7) cells, they show comparable cytotoxic effects and exhibit IC50 in the 27.3-33.5 µg/mL range, and among these, 4 exhibits the highest cytotoxicity. A similar study on human embryonic kidney cells (HEK293) confirms their less toxicity at lower concentrations (4 to 16 µg/mL) compared to MCF-7.

Turn-on detection of Al3+ and Zn2+ ions by a NSN donor probe: reversibility, logic gates and DFT calculations.

An efficient dual functional naphthalene-derived Schiff base NpSb probe has been synthesised and evaluated for its fluorescence and chromogenic response towards metal ions. The NpSb probe was capable of selectively recognising Al3+ and Zn2+ ions when they were excited at the same wavelength in an aqueous organic solvent system. Almost non-fluorescent NpSb displayed a 'turn-on' fluorescence response when treated with Zn2+ (λem = 416 nm) and Al3+ (λem = 469 nm) ions due to the chelation-enhanced fluorescence (CHEF) effect. The limit of detection (LoD) values for Al3+ and Zn2+ have been determined to be 38.0 nM and 43.0 nM, respectively. The binding constants for Al3+ and Zn2+ were found to be 1.18 × 106 M-1 and 3.5 × 105 M-1, respectively. The NpSb also acted as a colorimetric sensor for Al3+ as the colour of the probe's solution turned to pale green from colourless upon Al3+ addition. The binding mechanism between NpSb and Zn2+/Al3+ was supported by the ESI-MS, Job's plot, NMR, and DFT studies. The reversibility experiments were carried out with an F- ion and EDTA with the development of corresponding logic gates. Moreover, NpSb could be applied to detect Al3+ ions in real samples such as tap water, distilled water and soil samples.

Inhibition of amyloid ß1-42 peptide aggregation by newly designed cyclometallated palladium complexes.

Uncontrolled amyloid aggregation is a frequent cause of neurodegenerative disorders such as prions and Alzheimer's disease (AD). As a result, many drug development approaches focus on evaluating novel molecules that can alter self-recognition pathways. Herein, we designed and synthesized the cyclometallated pyrene (Pd-1 and Pd-3) and anthracene (Pd-2) based palladium complexes ([Pd((L1)Cl] Pd-1, [Pd(L2)Cl](Pd-2), and [Pd(L3)Cl] (Pd-3)). This study explores the effect of these complexes on the aggregation, fibrillation, and amyloid formation of bovine serum albumin (BSA) and Aß1-42 peptide. Several spectroscopic methods were used to characterize all the Pd-complexes, and the molecular structure of Pd-3 was determined by X-ray crystallography. The secondary structures were studied using circular dichroism (CD) and transmission electron microscopy (TEM), while amyloid aggregation and inhibitory activities were investigated using the Thioflavin-T (ThT) fluorescence assay. Molecular docking of the Pd-complex (Pd-3) was done using fibril (PDB: 2BEG) and monomeric (PDB: 1IYT) peptides using Auto-dock Vina. As a result, the hydrogen bonding and hydrophobic interaction between the aromatic rings of the Pd-complexes and the amino acids of amyloid-ß peptides significantly reduced the production of ordered ß-sheets of amyloid fibrils and protein aggregation in the presence of Pd-2 and Pd-3 complexes.

Design and synthesis of piano-stool ruthenium(II) complexes and their studies on the inhibition of amyloid ß (1-42) peptide aggregation.

Misfolding and protein aggregation have been linked to numerous human neurodegenerative disorders such as Alzheimer's, prion, and Parkinson's diseases. Ruthenium (Ru) complexes have received considerable attention in studying protein aggregation due to their interesting photophysical and photo properties. In this study, we have synthesized the novel Ru complexes ([Ru(p-cymene)Cl(L-1)][PF6](Ru-1), and [Ru(p-cymene)Cl(L-2)][PF6](Ru-2)) and investigated their inhibitory activity against the bovine serum albumin (BSA) aggregation and the Aß1-42 peptides amyloid formation. Several spectroscopic methods were used to characterize these complexes, and the molecular structure of the complex was determined by X-ray crystallography. Amyloid aggregation and inhibition activities were examined using the Thioflavin-T (ThT) assay, and the secondary structures of the protein were analyzed by circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). The cell viability assay was carried out on the neuroblastoma cell line, revealing that the complex Ru-2 showed better protective effects against Aß1-42 peptide toxicity on neuro-2a cells than the complex Ru-1. Molecular docking studies elucidate the binding sites and interactions between the Ru-complexes and Aß1-42 peptides. The experimental studies revealed that these complexes significantly inhibited the BSA aggregation and Aß1-42 amyloid fibril formation at 1:3 and 1:1 molar concentrations, respectively. Antioxidant assays demonstrated that these complexes act as antioxidants, protecting from amyloid-induced oxidative stress. Molecular docking studies with the monomeric Aß1-42 (PDB: 1IYT) show hydrophobic interaction, and both complexes bind preferably in the central region of the peptide and coordinate with two binding sites of the peptide. Hence, we suggest that the Ru-based complexes could be applied as a potential agent in metallopharmaceutical research against Alzheimer's disease.

DNA binding, antitubercular, antibacterial and anticancer studies of newly designed piano-stool ruthenium(II) complexes.

The chemotherapeutic potential of ruthenium(II) complexes has recently attracted researchers' interest as antibacterial and anticancer agents. In this study, two novel half-sandwich imine-based Ru complexes ([Ru(p-cymene)Cl(L-1)][PF6] (Ru-1) and [Ru(p-cymene)Cl(L-2)][PF6] (Ru-2)) were reported for their deoxyribonucleic acid (DNA) binding and antitubercular, antibacterial, and anticancer activities. The molecular structure of Ru-2 was obtained by single-crystal X-ray crystallography. DNA interaction studies were conducted by UV-Vis absorbance and fluorescence spectral titration which gave rise to DNA binding constants (Kb) of 1.32 × 106 and 1.82 × 106 for Ru-1 and Ru-2, respectively and the Stern-Volmer binding constant (KSV) values for Ru-1 and Ru-2 were 1.7763 × 104 M-1 and 7.6 × 103 M-1, respectively. The in vitro antitubercular activity was evaluated against Mycobacterium tuberculosis H37Ra. The antibacterial potential of both the Ru-complexes was examined against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. The half-maximal inhibitory concentration (IC50) values for the antitubercular activity of Ru-1 and Ru-2 were 4.87 ± 1.32 µM and 5.78 ± 0.54 µM, respectively. A cytotoxic study of these complexes was performed against the human breast cancer cell line (MCF-7) and the human embryonic kidney cell line (HEK293) (normal cells). The study revealed meaningful activity of the Ru-1 complex against (cancer) MCF-7 cells, while the viability of HEK293 (normal) cells in the presence of Ru-2 was higher as compared to a reference drug 5FU. We suggest that these kinds of Ru-complexes could have potential for application in metallopharmaceuticals.

Photodissociation of nitric oxide from designed ruthenium nitrosyl complex: Studies on wound healing and antibacterial activity.

A photoactivable NO releasing complex [Ru(L1-2)(PPh3)(NO)Cl2](PF6)(1a) have been synthesized by complex [RuL1-2(PPh3)2Cl2](1). Newly designed bidentate ligands, i.e., 4-methoxy-N'-phenyl-N'-(pyridin-2-ylmethyl)benzohydrazide(L1) and 4-nitro-N'-phenyl-N'-(pyridin-2-ylmethyl)benzohydrazide (L2) were utilized to synthesize complex (1). Complex (1) was characterized by ESI-MS, and the solid structure of the complex [1a](PF6) was acquired by X-ray crystallography. Different spectroscopic techniques were employed for the identification of ligands (L1 and L2) and complexes (1 and [1a](PF6)). Calculations employing DFT and TD-DFT were made better to understand the electronic properties of the complex [1a](PF6). The photo liberation experiments were screened in the presence of visible light lamp. Griess assay experiment was used to quantify the photo released amount to NO. The photo liberated NO was successfully transferred to reduced myoglobin (Mb). The complex [1a](PF6) at 50 µg/mL concentration was used for wound healing and antimicrobial activity on B16F1 mouse skin cells and Escherichia coli bacteria, respectively. In results, we observed a considerable wound healing activity of [1a](PF6) complex after 36 h of incubation in the light-treated cells compared to the control medium, and also it shows more than 99% inhibition of bacterial cells after 1.5 h of treatment in the presence of light. These study suggested that this complex 1a](PF6) could be utilized for topical delivery of NO for combating several dermatological infections.