Structure and Reactivity of Pd Complexes in Various Oxidation States in Identical Ligand Environments with Reference to C–C and C–Cl Coupling Reactions: Insights from Density Functional Theory

Bonding and reactivity of [(^RN4)­Pd^<i>n</i>CH₃X]^{(<i>n</i>−2)+} complexes have been investigated at the M06/BS2//B3LYP/BS1 level. Feasible mechanisms for the unselective formation of ethane and methyl chloride from mono-methyl Pd^III complexes and selective formation of ethane or methyl chloride from Pd^IV complexes are reported here. Density functional theory (DFT) results indicate that Pd^IV is more reactive than Pd^III and Pd in different oxidation states that follow different mechanisms. Pd^III complexes react in three steps: (i) conformational change, (ii) transmetalation, and (iii) reductive elimination. In the first step a five-coordinate Pd^III intermediate is formed by the cleavage of one Pd–N_ax bond, and in the second step one methyl group is transferred from the Pd^III complex to the above intermediate via transmetalation, and subsequently a six-coordinate Pd^IV intermediate is formed by disproportion. In this step, transmetalation can occur on both singlet and triplet surfaces, and the singlet surface is lying lower. Transmetalation can also occur between the above intermediate and [(^RN4)­Pd^II(CH₃)­(CH₃CN) ]⁺, but this not a feasible path. In the third step this Pd^IV intermediate undergoes reductive elimination of ethane and methyl chloride unselectively, and there are three possible routes for this step. Here axial–equatorial elimination is more facile than equatorial–equatorial elimination. Pd^IV complexes react in two steps, a conformational change followed by reductive elimination, selectively forming ethane or methyl chloride. Thus, Pd^III complex reacts through a six-coordinate Pd^IV intermediate that has competing C–C and C–Cl bond formation, and Pd^IV complex reacts through a five-coordinate Pd^IV intermediate that has selective C–C and C–Cl bond formation. Free energy barriers indicate that iPr, in comparison to the methyl substituent in the ^RN4 ligand, activates the cleaving of the Pd–N_ax bond through electronic and steric interactions. Overall, reductive elimination leading to C–C bond formation is easier than the formation of a C–Cl bond

Surfactant–copper(II) Schiff base complexes: synthesis, structural investigation, DNA interaction, docking studies, and cytotoxic activity

<div><p>A series of surfactant–copper(II) Schiff base complexes (<b>1–6</b>) of the general formula, [Cu(sal-R₂)₂] and [Cu(5-OMe-sal-R₂)₂], {where, sal = salicylaldehyde, 5-OMe-sal = 5-methoxy- salicylaldehyde, and R₂ = dodecylamine (DA), tetradecylamine (TA), or cetylamine (CA)} have been synthesized and characterized by spectroscopic, ESI-MS, and elemental analysis methods. For a special reason, the structure of one of the complexes (<b>2</b>) was resolved by single crystal X-ray diffraction analysis and it indicates the presence of a distorted square-planar geometry in the complex. Analysis of the binding of these complexes with DNA has been carried out adapting UV-visible-, fluorescence-, as well as circular dichroism spectroscopic methods and viscosity experiments. The results indicate that the complexes bind via minor groove mode involving the hydrophobic surfactant chain. Increase in the length of the aliphatic chain of the ligands facilitates the binding. Further, molecular docking calculations have been performed to understand the nature as well as order of binding of these complexes with DNA. This docking analysis also suggested that the complexes interact with DNA through the alkyl chain present in the Schiff base ligands via the minor groove. In addition, the cytotoxic property of the surfactant–copper(II) Schiff base complexes have been studied against a breast cancer cell line. All six complexes reduced the visibility of the cells but complexes 2, 3, 5, and 6 brought about this effect at fairly low concentrations. Analyzed further, but a small percentage of cells succumbed to necrosis. Of these complexes (<b>6</b>) proved to be the most efficient aptotoxic agent.</p></div

Water-Soluble Mono- and Binuclear Ru(η⁶‑<i>p</i>‑cymene) Complexes Containing Indole Thiosemicarbazones: Synthesis, DFT Modeling, Biomolecular Interactions, and <i>In Vitro</i> Anticancer Activity through Apoptosis

Indole thiosemicarbazone ligands were prepared from indole-3-carboxaldehyde and <i>N</i>-(un)­substituted thiosemicarbazide. The Ru­(η⁶-<i>p</i>-cymene) complexes [Ru­(η⁶-<i>p</i>-cymene)­(HL1)­Cl]Cl (<b>1</b>) and [Ru­(η⁶-<i>p</i>-cymene)­(L2)]₂Cl₂ (<b>2*</b>) were exclusively synthesized from thiosemicarbazone (TSC) ligands HL1 and HL2, and [RuCl₂(<i>p-</i>cymene)]₂. The compounds were characterized by analytical and various spectroscopic (electronic, FT-IR, 1D/2D NMR, and mass) tools. The exact structures of the compounds (HL1, HL2, <b>1</b>, and <b>2*</b>) were confirmed by single-crystal X-ray diffraction technique. In complexes <b>1</b> and <b>2*</b>, the ligand coordinated in a bidentate neutral (<b>1</b>)/monobasic (<b>2*</b>) fashion to form a five-membered ring. The complexes showed a piano-stool geometry around the Ru ion. While <b>2*</b> existed as a dimer, <b>1</b> existed as a monomer, and this was well explained through free energy, bond parameter, and charge values computed at the B3LYP/SDD level. The intercalative binding mode of the complexes with calf thymus DNA (CT DNA) was revealed by spectroscopic and viscometric studies. The DNA (pUC19 and pBR322 DNA) cleavage ability of these complexes evaluated by an agarose gel electrophoresis method confirmed significant DNA cleavage activity. Further, the interaction of the complexes with bovine serum albumin (BSA) was investigated using spectroscopic methods, which disclosed that the complexes could bind strongly with BSA. A hemolysis study with human erythrocytes revealed blood biocompatibility of the complexes. The <i>in vitro</i> anticancer activity of the compounds (HL1, HL2, <b>1</b>, and <b>2*</b>) was screened against two cancer cell lines (A549 and HepG-2) and one normal cell line (L929). Interestingly, the binuclear complex <b>2*</b> showed superior activity with IC₅₀ = 11.5 μM, which was lower than that of cisplatin against the A549 cancer cell line. The activity of the same complex (IC₅₀ = 35.3 μM) was inferior to that of cisplatin in the HepG-2 cancer cell line. Further, the apoptosis mode of cell death in the cancer cell line was confirmed by using confocal microscopy and DNA fragmentation analysis