Chemotherapeutic Activities of New η6-p-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands.

A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (3ai, 3aii, 3aiii, 3bii/4aiii, 4bi, 4bii), and the tridentate (SNS) pyridine-2,6-diylimidazole-2-thione-Ru(II)/Os(II) complexes (5bi, 5civ/6bi, 6ci, 6civ) in the forms [MII(cym)(L)Cl]PF6 and [MII(cym)(L)]PF6 (M = Ru or Os, cym = η6-p-cymene, and L = heterocyclic derivatives of thiourea) respectively, were successfully synthesized. Spectroscopic and analytical methods were used to characterize the complexes and their ligands. Solid-state single-crystal X-ray diffraction analyses revealed a "piano-stool" geometry around the Ru(II) or Os(II) centers in the respective complexes. The complexes were investigated for in vitro chemotherapeutic activities against human cervical carcinoma (HeLa) and the non-cancerous cell line (Hek293) using the MTT assay. The compounds 3aii, 5civ, 5bi, 4aiii, 6ci, 6civ, and the reference drug, 5-fluorouracil were found to be selective toward the tumor cells; the compounds 3ai, 3aiii, 3bii, 4bi, 4bii, and 6bi, which were found not to be selective between normal and tumor cell lines. The IC50 value of the tridentate half-sandwich complex 5bi (86 ± 9 µM) showed comparable anti-proliferative activity with the referenced commercial anti-cancer drug, 5-fluorouracil (87 ± 15 µM). The pincer (SNS) osmium complexes 6ci (36 ± 10 µM) and 6civ (40 ± 4 µM) were twice as effective as the reference drug 5-fluorouracil at the respective dose concentrations. However, the analogous pincer (SNS) ruthenium complex 5civ was ineffective and did not show anti-proliferative activity, even at a higher concentration of 147 ± 1 µM. These findings imply that the higher stability of the chelating (SS) and the pincer (SNS) ligand architectures in the complexes improves the biological (anti-proliferative) activity of the complexes by reducing the chance of ligand dissociation under physiological conditions. In general, the pincer (SNS) osmium complexes were found to be more cytotoxic than their ruthenium analogues, suggesting that the anti-proliferative activity of the imidazole-2-thione-Ru/Os complexes depends on the ligand's spatial coordination, the nature of the metal center, and the charge of the metal complex ions.

Oxidation of Styrene to Benzaldehyde Catalyzed by Schiff Base Functionalized Triazolylidene Ni(II) Complexes.

Four new Schiff base functionalized 1,2,3-triazolylidene nickel complexes, [Ni-(L1NHC)2](PF6)2; 3, [Ni-(L2NHC)2](PF6)2; 4, [Ni-(L3NHC)](PF6)2; 7 and [Ni-(L4NHC)](PF6)2; 8, (where L1NHC = (E)-3-methyl-1-propyl-4-(2-(((2-(pyridin-2-yl)ethyl)imino)methyl)phenyl)-1H-1,2,3-triazol-3-ium hexafluorophosphate(V), 1, L2NHC = (E)-3-methyl-4-(2-((phenethylimino)methyl)phenyl)-1-propyl-1H-1,2,3-triazol-3-ium hexafluorophosphate(V), 2, L3NHC = 4,4'-(((1E)-(ethane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(2,1-phenylene))bis(3-methyl-1-propyl-1H-1,2,3-triazol-3-ium) hexafluorophosphate(V), 5, and L4NHC = 4,4'-(((1E)-(butane-1,4-diylbis(azanylylidene))bis(methanylylidene))bis(2,1-phenylene))bis(3-methyl-1-propyl-1H-1,2,3-triazol-3-ium) hexafluorophosphate(V), 6), were synthesised and characterised by a variety of spectroscopic methods. Square planar geometry was proposed for all the nickel complexes. The catalytic potential of the complexes was explored in the oxidation of styrene to benzaldehyde, using hydrogen peroxide as a green oxidant in the presence of acetonitrile at 80 °C. All complexes showed good catalytic activity with high selectivity to benzaldehyde. Complex 3 gave a conversion of 88% and a selectivity of 70% to benzaldehyde in 6 h. However, complexes 4 and 7-8 gave lower conversions of 48-74% but with higher (up to 90%) selectivity to benzaldehyde. Results from kinetics studies determined the activation energy for the catalytic oxidation reaction as 65 ± 3 kJ/mol, first order in catalyst and fractional order in the oxidant. Results from UV-visible and CV studies of the catalytic activity of the Ni-triazolylidene complexes on styrene oxidation did not indicate any clear possibility of generation of a Ni(II) to Ni(III) catalytic cycle.

1-(4-Nitro-phen-yl)-1H-imidazol-3-ium chloride.

In the title salt, C9H8N3O2(+)·Cl(-), the least-squares planes of the imidazolium and benzene rings are almost coplanar, making a dihedral angle of 4.59 (1)°. In the crystal, the chloride anion links the organic mol-ecules through N-H⋯Cl hydrogen bonds, forming chains that run diagonally across the bc face, which compliment strong C-H⋯O hydrogen bonds between neighbouring mol-ecules. These chains are connected to adjacent chains through two weak C-H⋯Cl inter-actions, resulting in hydrogen-bonded sheets extending along the b and c axes. The absolute structure of the title compound was determined using a Flack x parameter of 0.00 (6) and a Hooft y parameter of 0.03 (2).

Recent Literature Review on Coumarin Hybrids as Potential Anticancer Agents.

Cancer is considered one of the leading causes of death globally, especially patients with lung, pancreatic, or brain tumors are most likely to die of cancer, and patients with prostate and breast cancer are at a high risk of noncancer death. As a result, there is ongoing research regarding developing new, safe, and efficient anticancer agents. Coumarin-based naturally occurring compounds possess a broad spectrum of activity in medicinal chemistry, such as anticancer, anti-inflammatory, antimicrobial, antioxidant agents, etc. Many researchers have synthesized coumarinbased novel therapeutic agents via molecular hybridization technique, which offers an excellent opportunity to develop novel compounds with improved biological activities by incorporating two or more pharmacophores. This review aims to shed light on the recent developments of coumarin-based anticancer hybrid derivatives and their Structure-Activity Relationships (SAR). This review serves as a medium that medicinal chemists could utilize to design and synthesize coumarin derivatives with significant pharmacological value as future anticancer agents.

1-[4-(1H-imidazol-1-yl)phen-yl]ethanone monohydrate.

In the crystal structure of the title compound, C(11)H(10)N(2)O·H(2)O, the solvent water mol-ecule links the organic mol-ecules through O-H⋯O and O-H⋯N hydrogen bonds, forming chains that run diagonally across the bc face. These chains are connected to adjacent chains through weak C-H⋯O inter-actions, resulting in hydrogen-bonded sheets extending along the b and c axes. The sheets are connected along the a axis through π-π inter-actions, with centroid-centroid distances of 3.7571 (9) and 3.7231 (9) Å.

(2,4,6-Trimethyl-phen-yl){2-[N-(2,4,6-trimethyl-phen-yl)formamido]-eth-yl}ammonium chloride.

In the title salt, C21H29N2O(+)·Cl(-), the benzene rings form a dihedral angle of 6.13 (1)°. In the crystal, N-H⋯Cl hydrogen bonds link the cations and anions into chains extending along the c axis.

4,6-Bis(diphenyl-phosphan-yl)-2,8-di-methyl-phenoxathiin dichloro-methane monosolvate.

The title compound, C(38)H(30)OP(2)S·CH(2)Cl(2), belongs to the xanthene family of ligands containing S- and O-donor atoms in the central heterocylic ring. Positions 2 and 8 on the xanthene backbone are functionalized with methyl groups to allow for the selective functionalization of the backbone at positions 4 and 6 with diphenyl-phosphanyl units. The title compound shows a significant 'roof-like' bending along the axis of planarity involving the O- and S-donor atoms and the benzene rings, resulting in a dihedral angle between the mean planes of the benzene rings of 32.88 (13)°.

4,6-Bis(diphenyl-phosphan-yl)dibenzo[b,d]furan.

The asymmetric unit of the title compound, C(36)H(26)OP(2), comprises two mol-ecules which have slightly different conformations of the phenyl ring substituents. In both mol-ecules, the dibenzofuran unit is close to being planar, with dihedral angles of 3.20 (3) and 1.86 (2)° for the two mol-ecules. Its planarity affects the intra-molecular distances between P atoms, with P⋯P distances of 5.574 (2) and 5.485 (2) Šfor the two mol-ecules.

Dicarbon-yl(η-cyclo-penta-dien-yl)[2-(phenyl-sulfan-yl)eth-yl]iron(II).

The title compound, [Fe(C(5)H(5))(C(8)H(9)S)(CO)(2)], is a three-legged piano-stool iron(II) complex that is characterized by a thio-ethyl-linked phenyl ring and a cyclo-penta-dienyl moiety that occupies the apical coordination site. The two aromatic rings are essentially planar with the same maximum deviation of 0.009 Å. The mean planes of the phenyl and cyclo-penta-dienyl rings bis-ect at an acute angle of 50.08°.

2,6-Bis(tosyl-oxymeth-yl)pyridine.

The title compound, C(21)H(21)NO(6)S(2), is organized around a twofold axis parallel to the crystallographic c axis and containing the N atom and a C atom of the pyridine ring. The tosyl moiety and the pyridine ring are both essentially planar [maximum deviations 0.028 (2) and 0.020 (3) Å, respectively]; their mean planes form a dihedral angle of 33.0 (2)°.

6-Hy-droxy-2H-1,3-benzodioxole-5-carbaldehyde.

The title compound, C(8)H(6)O(4), crystallizes with two independent mol-ecules in the asymmetric unit. The benzodioxole ring system is almost planar in each mol-ecule, with maximum deviations of 0.008 (1) and 0.007 (1) Å. The mol-ecular structure is characterized by strong electrostatic intra-molecular O⋯O contacts [2.649 (3) Å] and intra-molecular O-H⋯O hydrogen-bonding inter-actions. Inter-molecular O⋯O inter-actions [3.001 (2) Å] are observed in the crystal structure.

Acetonitrile-dicarbon-yl(η-penta-methyl-cyclo-penta-dien-yl)iron(II) tetra-fluorido-borate.

In the structure of the title compound, [Fe{η(5)-C(5)(CH(3))(5)}(NCCH(3))(CO)(2)]BF(4), the arrangement of ligands around the Fe atom is in a pseudo-octa-hedral three-legged piano-stool fashion in which the penta-methyl-cyclo-penta-dienyl (Cp*) ligand occupies three apical coordination sites, while the two carbonyl and one acetonitrile ligands form the basal axes of the coordination. The Fe-N bond length is 1.924 (3) Šand the Fe-Cp* centroid distance is 1.722 Å.

[1,4-Phenyl-enebis(methyl-ene)]bis-(tri-phenyl-phospho-nium) bis-(tetra-fluoro-borate).

The crystal structure of the title salt, C(44)H(38)P(2) (2+)2BF(4) (-), consists of discrete dications inter-laced with the BF(4) (-) counter-ions. In each cation, both phospho-nium groups lie on the same side of the plane of the central benzene ring. The tetra-fluoro-borate anions are involved in intensive thermal motion, thus some B-F bond lengths [range 1.329 (6) to 1.391 (6) Å] deviate significantly from their standard values.

1,3-Bis(1-adamant-yl)imidazolium tetra-chloridoferrate(III).

The crystal structure of the title compound, (C(23)H(33)N(2))[FeCl(4)], consists of 1,3-bis-(1-adamant-yl)imidazolium (BAIM) cations and tetra-hedral tetra-chloridoferrate(III) (TCF) anions. The BAIM cation possesses m symmetry, with the central imidazole ring and four C atoms of each terminal adamantyl group located on a mirror plane. The Fe and two Cl atoms of the TCF anion are also located on the mirror plane. The cyclo-hexane rings of the adamantyl groups adopt normal chair conformations.

1,3-Bis(2,6-diisopropyl-phen-yl)-4,5-dihydro-1H-imidazol-3-ium triiodide.

In the crystal structure of the title compound, C(27)H(39)N(2) (+)·I(3) (-), the imidazolidinium ring is perpendicular to a mirror plane which bis-ects the cation. The dihedral angle between the imidazolidinium ring and the benzene ring is 89.0 (2)°. The triiodide anion also lies on a mirror plane and is almost linear with an I-I-I bond angle of 178.309 (18)°.

1-(6-Ferrocenylhex-yl)-1H-imidazole.

The title compound, [Fe(C(5)H(5))(C(14)H(19)N(2))], is characterized by a ferrocenyl group separated from an imidazole functionality by a straight-chain hexyl unit. The two cyclo-penta-dienyl rings of the ferrocenyl group show a marginal inward tilt of 2.17 (2)°. The imidazole unit, which is essentially planar (with a maximum deviation of 0.007 A for one of the N atoms) and tilted away from the ferrocenyl group [dihedral angle between the substituted ferrocenyl ring and the imidazole = 122.6 (1)°], is involved in inter-molecular C-H⋯N inter-actions.

cis-N-(2-Hydroxy-cyclo-hexyl)-p-toluene-sulfonamide.

There are two symmetry-independent mol-ecules in the asymmetric unit of the title compound, C(13)H(19)NO(3)S. The cyclo-hexane rings in the two mol-ecules adopt chair configurations. The hydr-oxy and amino groups on the cyclo-hexane ring assume axial and equatorial orientations, respectively, with respect to the plane of the ring. The crystal structure is stabilized by two inter-molecular N-H⋯O and O-H⋯O hydrogen bonds from the two symmetry-independent mol-ecules.

Transfer Hydrogenation of Ketones Catalyzed by Symmetric Imino-N-heterocyclic Carbene Co(III) Complexes.

The synthesis of new moisture-sensitive imine-functionalized N-heterocyclic carbene (NHC) precursor salts [1-(2-[(hydroxyl-benzylidene)-amino]-ethyl)-3-R-3H-imidazole-1-ium bromide; R = methyl (1a), ethyl (1b), and benzyl (1c)] is reported. Subsequent deprotonation of 1a-c and coordination of the in situ generated NHC ligands to CoBr2 led to the isolation of air-stable six-coordinate Co(III) complexes 2a-c, respectively. All the salts and complexes were fully characterized. Single-crystal X-ray analysis of 2a and 2c showed octahedral Co centers hexacoordinated to two NHC carbons, two imine nitrogen atoms, and two phenolate oxygens in the form [C^N^O(Co3+)C^N^O]. The complexes were used in the catalytic transfer hydrogenation (CTH) of a range of ketones in 2-propanol as the solvent and hydrogen donor. Based on a low catalyst concentration of 0.4 mol %, significant conversions in the range of 70-99% were recorded at high turnover frequencies up to 1635 h-1. A mechanism to account for the steps involved in the CTH of cyclohexanone by complex 2a is proposed and supported by data from cyclic voltammetry, low-resolution mass spectrometry, UV, and IR spectroscopic techniques.

2,8-Dimethyl-10-p-tolyl-10H-phenoxaphosphine.

THE TITLE COMPOUND (SYSTEMATIC NAME: 3,6-dimethyl-10-p-tolyl-9-oxa-10-phosphaanthracene), C(21)H(19)OP, is a precursor for the preparation of a bidentate xanthene-based ligand, in which the dihedral angle between the toluene ring and the phenoxaphosphine ring system is 83.26 (3)°. The geometry at the P atom is pyramidal, resulting in a longer C-P bond length as compared to the two ring C-P bonds.

1-(4-Bromo-phen-yl)ferrocene.

In the title compound, [Fe(C(5)H(5))(C(11)H(8)Br)], the distance of the Fe atom from the centroids of the unsubstituted and substituted cyclo-penta-dienyl (Cp) rings is 1.644 (1) and 1.643 (1) Å, respectively. The ferrocenyl moiety deviates from an eclipsed geometry, with marginally tilted Cp rings and an inter-planar angle between the Cp and benzene rings of 13.0 (4)°. The crystal structure is stabilized by C-H⋯π inter-actions between a cyclo-penta-dienyl H atom and the cyclo-penta-dienyl ring of a neighbouring mol-ecule.