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

Unraveling the reaction mechanism, enantio and diastereoselectivities of selenium ylide promoted epoxidation

1001-1009The reaction between chiral selenium ylide and benzaldehyde leads to the formation of (2S,3S)-trans-epoxide with high enantio- and diastereoselectivity. Density functional theory and Hartree-Fock calculations using 6-31G(d) basis set have been performed to understand the reaction mechanism and factors associated with enantio- and diastereoselectivities. Conformation of chiral selenium ylide has been found to have a strong influence on the stability of the initial addition transition state between ylide and benzaldehyde. Calculated enantio- and diastereoselectivities from the energy differences between B3LYP/6-31G(d) addition TSs are in good agreement with the experimental data. The rate and diastereoselectivity are controlled by the <i style="mso-bidi-font-style: normal">cisoid-transoid rotational transition state. Analysis of transition state geometries clearly reveals that unfavorable eclipsing interaction between phenyl groups of the benzaldehyde and ylidic substituents mainly governs the energy differences between the enantio and diastereomeric transition states. The favourable reactivity is also explained through Fukui function calculations

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