Monomeric copper(II) complexes with unsymmetrical salen environment: Synthesis, characterization and study of biological activities.

Three new ONNO-donor tetradentate unsymmetrical salen ligands were synthesized by using o-phenyl diamine with substituted salicylaldehydes followed by a two-step reaction methodology. These three ligands by reaction with Cu(OAc)2.4H2O produced three new monomeric Cu(II) complexes, [CuII(L1-3)] (1-3). Elemental analysis, IR, UV-vis, NMR, and HR-ESI-MS techniques were used to analyze and characterize all the synthesized ligands and their corresponding metal complexes. Molecular structures of 1-3 were confirmed by the single-crystal-XRD analysis. Furthermore, the DNA binding ability of these complexes was checked through UV-vis, fluorescence spectroscopy, and also by circular dichroism studies. All the complexes were found to show an intercalation mode of binding with the Kb value in the range of 104-105 M-1. Finally, 1-3 was tested against two malignant (HeLa and A549) and non-cancerous (NIH-3T3) cell lines to check their in vitro antiproliferative activities. Among all, 1 is the most cytotoxic of the series having IC50 values of 5.7 ± 0.9 and 6.0 ± 0.3 µM against HeLa and A549 cell lines, respectively. This result is also consistent with the DNA binding order. Furthermore, the apoptotic mode of cell death of all the complexes was also evaluated by DAPI, AO/EB, and Annexin V-FITC/PI double staining assays.

Recent advancements of fluorescent tin(IV) complexes in biomedical molecular imaging.

In the last few years, tin(IV) complexes have emerged as very attractive candidates in the field of molecular imaging due to their unique photophysical properties. Despite the few reviews published to date covering the chemistry of organotin and tin complexes and their cytotoxic potential, there are no reviews devoted to their live cell imaging properties. Therefore, this feature article summarizes the discussion of the fundamental photophysical properties of fluorescent tin metal complexes focusing on their recent advances in "biomedical molecular imaging". A debate on the design of tin complexes as cellular imaging agents relating to their chemical, electronic and photophysical properties is enclosed. This paper also discusses the imaging applications of tin complexes in cells, tissues, and organisms via confocal and multiphoton imaging for sensing mechanisms in cellular media, bioimaging, and therapeutic labeling. In addition, it explores and explains the current challenges and prospects associated with these tin complexes as emerging luminescent cellular agents for potential clinical use.

LVVO-Ethyl Maltol-Based Metallodrugs (L2- = Tridentate ONO Ligands): Hydrophobicity, Hydrolytic Stability, and Cytotoxicity via ROS-Mediated Apoptosis.

Four new oxidovanadium [VVOL1-4(ema)] complexes (1-4) have been synthesized using tridentate binegative ONO donor ligands H2L1-4 [H2L1: (E)-N'-(2-hydroxybenzylidene)furan-2-carbohydrazide; H2L2: (E)-N'-(4-(diethylamino)-2-hydroxybenzylidene)thiophene-2-carbohydrazide; H2L3: (E)-2-(4-(diethylamino)-2-hydroxybenzylideneamino)-4-methylphenol; H2L4: (E)-2-(3-ethoxy-2-hydroxybenzylideneamino)-4-methylphenol] and ethyl maltol (Hema) as a bidentate uninegative coligand and characterized by CHNS analysis, IR, UV-vis, NMR, and HR-ESI-MS methods. The structures of 1, 3, and 4 are confirmed by single-crystal X-ray analysis. The hydrophobicity and hydrolytic stability of the complexes are tested using NMR and HR-ESI-MS and correlated with their observed biological activities. It is observed that 1 hydrolyzed into a penta-coordinated vanadium-hydroxyl species (VVOL1-OH) with the release of ethyl maltol, whereas 2-4 are found quite stable under the investigated time period. The biomolecular interaction of 1-4 with DNA and BSA was performed using absorbance, fluorescence, and circular dichroism techniques. The in vitro cytotoxicity activities of H2L1-4 and 1-4 were tested against A549, HT-29, and NIH-3T3 cell lines. Among complexes, 2 with an IC50 value of 4.4 ± 0.1 µM displayed maximum anticancer activity against the HT-29 cell line. Complexes induce cell cycle arrest at the G2/M phase and subsequently trigger dose-dependent cell apoptosis, which is obtained by the cell apoptosis analysis via flow cytometry and confocal microscopy assays. Being fluorescence active, 1-4 were observed to target the mitochondria and exhibit disruption of the mitochondrial membrane potential, which consequently causes overproduction of intracellular reactive oxygen species and induced cell apoptosis.

Mitochondria-Targeted Luminescent Organotin(IV) Complexes: Synthesis, Photophysical Characterization, and Live Cell Imaging.

Five fluorescent ONO donor-based organotin(IV) complexes, [SnIV(L1-5)Ph2] (1-5), were synthesized by the one-pot reaction method and fully characterized spectroscopically including the single-crystal X-ray diffraction studies of 2-4. Detailed photophysical characterization of all compounds was performed. All the compounds exhibited high luminescent properties with a quantum yield of 17-53%. Additionally, the results of cellular permeability analysis suggest that they are lipophilic and easily absorbed by cells. Confocal microscopy was used to examine the live cell imaging capability of 1-5, and the results show that the compounds are mostly internalized in mitochondria and exhibit negligible cytotoxicity at imaging concentration. Also, 1-5 exhibited high photostability as compared to the commercial dye and can be used in long-term real-time tracking of cell organelles. Also, it is found that the probes (1-5) are highly tolerable during the changes in mitochondrial morphology. Thus, this kind of low-toxic organotin-based fluorescent probe can assist in imaging of mitochondria within living cells and tracking changes in their morphology.

Dithiocarbazate based oxidomethoxidovanadium(V) and mixed-ligand oxidovanadium(IV) complexes: Study of solution behavior, DNA binding, and anticancer activity.

In this work, one oxidomethoxidovanadium(V) [VVO(L)(OMe)] (1) and two mixed-ligand oxidovanadium(IV) [VIVO(L)(phen)] (2), and [VIVO(L)(bipy)] (3) complexes have been synthesized using a tridentate bi-negative ONS donor dithiocarbazate as main ligand, H2L [where, H2L = S-benzyl-3-(2-hydroxy-3-ethoxyphenyl)methylenedithiocarbazate] along with 1,10-phenanthroline (phen) (for 2) and 2,2'-bipyridine (bipy) (for 3) as co-ligands. The ligand and complexes have been characterised by FT-IR, UV-vis, NMR, and HR-ESI-MS techniques. Distorted square pyramidal for 1, and distorted octahedral geometry for 2 and 3 was confirmed by single crystal X-ray crystallography. The behavior of 1-3 in solution medium has been investigated through various physicochemical techniques. It is observed that 1 completely and 2-3 partially decomposes and converts into a penta-coordinated species, [VIVO(L)(DMSO/H2O)] after the release of the methoxido group (1) or breaking of the diimine based co-ligands (2 and 3) in DMSO/aqueous solution. Interestingly, in DMSO/aqueous solution, 1 gets completely reduced and converted into the corresponding oxidovanadium(IV) species. Interaction of 1-3 with calf thymus DNA (CT-DNA) was investigated and the results show, complex 2 exhibited the maximum binding constants, Kb = 7.12 × 104 M-1. The anticancer potential of 1-3 was evaluated by cell viability assay against human breast carcinoma cell, MCF-7, and noncancerous mouse embryonic cell, NIH-3T3 and 2 was found to be the most cytotoxic complex (IC50 = 6.73 ± 0.36 µM) in the series. In addition, 2 selectively inhibit colony formation compared to the rest complexes. Also, the cell cycle studies of the complexes were performed using flow cytometry analysis.