Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(I/II) complexes of thiosemicarbazone: special emphasis on their interactions with DNA.

4-(p-X-phenyl)thiosemicarbazone of napthaldehyde {where X = Cl (HL¹) and X = Br (HL²)}, thiosemicarbazone of quinoline-2-carbaldehyde (HL³) and 4-(p-fluorophenyl)thiosemicarbazone of salicylaldehyde (H2L4) and their copper(I) {[Cu(HL¹)(PPh3)2Br]·CH3CN (1) and [Cu(HL²)(PPh3)2Cl]·DMSO (2)} and copper(II) {[(Cu2L³2Cl)2(µ-Cl)2]·2H2O (3) and [Cu(L4)(Py)] (4)} complexes are reported herein. The synthesized ligands and their copper complexes were successfully characterized by elemental analysis, cyclic voltammetry, NMR, ESI-MS, IR and UV-Vis spectroscopy. Molecular structures of all the Cu(I) and Cu(II) complexes have been determined by X-ray crystallography. All the complexes (1-4) were tested for their ability to exhibit DNA-binding and -cleavage activity. The complexes effectively interact with CT-DNA possibly by groove binding mode, with binding constants ranging from 104 to 105 M⁻¹. Among the complexes, 3 shows the highest chemical (60%) as well as photo-induced (80%) DNA cleavage activity against pUC19 DNA. Finally, the in vitro antiproliferative activity of all the complexes was assayed against the HeLa cell line. Some of the complexes have proved to be as active as the clinical referred drugs, and the greater potency of 3 may be correlated with its aqueous solubility and the presence of the quinonoidal group in the thiosemicarbazone ligand coordinated to the metal.

Synthesis and characterization of a series of structurally and electronically diverse Fe(II) complexes featuring a family of triphenylamido-amine ligands.

A family of triphenylamido-amine ligands of the general stoichiometry L(x)H(3) = [R-NH-(2-C(6)H(4))](3)N (R = 4-t-BuPh (L(1)H(3)), 3,5-t-Bu(2)Ph (L(2)H(3)), 3,5-(CF(3))(2)Ph (L(3)H(3)), CO-t-Bu (L(4)H(3)), 3,5-Cl(2)Ph (L(5)H(3)), COPh (L(6)H(3)), CO-i-Pr (L(7)H(3)), COCF(3) (L(8)H(3)), and i-Pr (L(9)H(3))) has been synthesized and characterized, featuring a rigid triphenylamido-amine scaffold and an array of stereoelectronically diverse aryl, acyl, and alkyl substituents (R). These ligands are deprotonated by potassium hydride in THF or DMA and reacted with anhydrous FeCl(2) to afford a series of ferrous complexes, exhibiting stoichiometric variation and structural complexity. The prevalent [(L(x))Fe(II)-solv](-) structures (L(x) = L(1), L(2), L(3), L(5), solv = THF; L(x) = L(8), solv = DMA; L(x) = L(6), L(8), solv = MeCN) reveal a distorted trigonal bipyramidal geometry, featuring ligand-derived [N(3,amido)N(amine)] coordination and solvent attachment trans to the N(amine) atom. Specifically for [(L(8))Fe(II)-DMA](-), a N(amido) residue is coordinated as the corresponding N(imino) moiety (Fe-N(Ar) horizontal lineC(CF(3))-O(-)). In contrast, compounds [(L(4))Fe(II)](-), [(L(6))(2)Fe(II)(2)](2-), [K(L(7))(2)Fe(II)(2)](2)(2-), and [K(L(9))Fe](2) are all solvent-free in their coordination sphere and exhibit four-coordinate geometries of significant diversity. In particular, [(L(4))Fe(II)](-) demonstrates coordination of one amidato residue via the O-atom end (Fe-O-C(t-Bu) horizontal lineN(Ar)). Furthermore, [(L(6))(2)Fe(II)(2)](2-) and [K(L(7))(2)Fe(II)(2)](2)(2-) are similar structures exhibiting bridging amidato residues (Fe-N(Ar)-C(R) horizontal lineO-Fe) in dimeric structural units. Finally, the structure of [K(L(9))Fe](2) is the only example featuring a minimal [N(3,amido)N(amine)] coordination sphere around each Fe(II) site. All compounds have been characterized by a variety of physicochemical techniques, including Mossbauer spectroscopy and electrochemistry, to reveal electronic attributes that are responsible for a range of Fe(II)/Fe(III) redox potentials exceeding 1.0 V.

Synthesis, structure, and electrochemical properties of a family of 2-(arylazo)phenolate complexes of ruthenium with unusual C-C coupling and N=N cleavage.

Reaction of 2-(4'-R-phenylazo)-4-methylphenols (R = OCH3, CH3, H, Cl, and NO2) with [Ru(dmso)(4)Cl2]affords a family of five ruthenium(III) complexes, containing a 2-(arylazo)phenolate ligand forming a six-membered chelate ring and a tetradentate ligand formed from two 2-(arylazo)phenols via an unusual C-C coupling linking the two ortho carbons of the phenyl rings in the arylazo fragment. A similar reaction with 2-(2'-methylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl2] has afforded a similar complex, in which one 2-(2'-methylphenylazo)-4-methylphenolate ligand is coordinated forming a six-membered chelate ring, and the other two ligands have undergone the C-C coupling reaction, and the coupled species is coordinated as a tetradentate ligand forming a five-membered N,O-chelate ring, a nine-membered N,N-chelate ring, and another five-membered chelate ring. Reaction of 2-(2',6'-dimethylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl2] has afforded a complex in which two 2-(2',6'-dimethylphenylazo)-4-methylphenols are coordinated as bidentate N,O-donors forming five- and six-membered chelate rings, while the third one has undergone cleavage across the N=N bond, and the phenolate fragment, thus generated, remains coordinated to the metal center in the iminosemiquinonate form. Structures of four selected complexes have been determined by X-ray crystallography. The first six complexes are one-electron paramagnetic and show rhombic ESR spectra. The last complex is diamagnetic and shows characteristic 1H NMR signals. All the complexes show intense charge-transfer transitions in the visible region and a Ru(III)-Ru(IV) oxidation on the positive side of SCE and a Ru(III)-Ru(II) reduction on the negative side.

Rhodium assisted C-H activation of benzaldehyde thiosemicarbazones and their oxidation via activation of molecular oxygen.

The benzaldehyde thiosemicarbazones are found to undergo oxidation at the sulfur center upon reaction with [Rh(PPh3)3Cl] in refluxing ethanol in the presence of a base (NEt3). A group of organorhodium complexes are obtained from such reactions, in which the oxidized thiosemicarbazones are coordinated to rhodium as tridentate CNS donors, along with two triphenylphosphines and a hydride. From the reaction with para-nitrobenzaldehyde thiosemicarbazone, a second organometallic complex is obtained, in which the thiosemicarbazone is coordinated to rhodium as a tridentate CNS donor, along with two triphenylphosphines and a hydride. Reaction of the benzaldehyde thiosemicarbazones with [Rh(PPh3)3Cl] in refluxing ethanol in the absence of NEt3 affords another group of organorhodium complexes, in which the thiosemicarbazones are coordinated to rhodium as tridentate CNS donors, along with two triphenylphosphines and a chloride. Structures of representative complexes of each type of complexes have been determined by X-ray crystallography. In all of the complexes, the two PPh3 ligands are trans. All of the complexes show intense MLCT transitions in the visible region. Cyclic voltammetry on these complexes shows a Rh(III)-Rh(IV) oxidation on the positive side of SCE. Redox responses of the coordinated thiosemicarbazones are also displayed by all of the complexes.

Iridium(III) complexes formed by O-H and/Or C-H activation of 2-(arylazo)phenols.

Reaction of 2-(arylazo)phenols with [Ir(PPh(3))(3)Cl] in refluxing ethanol in the presence of a base (NEt(3)) affords complexes of three different types, viz. [Ir(PPh(3))(2)(NO-R)(H)Cl] (R = OCH(3), CH(3), H, Cl and NO(2)), [Ir(PPh(3))(2)(NO-R)(H)(2)] and [Ir(PPh(3))(2)(CNO-R)(H)]. Structures of the [Ir(PPh(3))(2)(NO-Cl)(H)Cl], [Ir(PPh(3))(2)(NO-Cl)(H)(2)] and [Ir(PPh(3))(2)(CNO-Cl)(H)] complexes have been determined by X-ray crystallography. In the [Ir(PPh(3))(2)(NO-R)(H)Cl] and [Ir(PPh(3))(2)(NO-R)(H)(2)] complexes, the 2-(arylazo)phenolate ligands are coordinated to the metal center as monoanionic bidentate N,O-donors, whereas in the [Ir(PPh(3))(2)(CNO-R)(H)] complexes, they are coordinated to iridium as dianionic tridentate C,N,O-donors. In all three products formed in ethanol, the two PPh(3) ligands are trans. Reaction of 2-(arylazo)phenols with [Ir(PPh(3))(3)Cl] in refluxing toluene in the presence of NEt(3) affords complexes of two types, viz. [Ir(PPh(3))(2)(CNO-R)(H)] and [Ir(PPh(3))(2)(CNO-R)Cl]. Structure of the [Ir(PPh(3))(2)(CNO-Cl)Cl] complex has been determined by X-ray crystallography, and the 2-(arylazo)phenolate ligand is coordinated to the metal center as a dianionic tridentate C,N,O-donor and the two PPh(3) ligands are cis. All of the iridium(III) complexes show intense MLCT transitions in the visible region. Cyclic voltammetry shows an Ir(III)-Ir(IV) oxidation on the positive side of SCE and an Ir(III)-Ir(II) reduction on the negative side for all of the products.

An unprecedented oxidative migration of a methyl group from 2-(2',6'-dimethylphenylazo)-4-methylphenol mediated by ruthenium and osmium.

An unprecedented chemical transformation of 2-(2',6'-dimethylphenylazo)-4-methylphenol has been observed upon its reaction with [M(PPh(3))(3)X(2)] (M = Ru, Os; X = Cl, Br) whereby one methyl group from the phenyl ring of the arylazo fragment migrates to the metal center via oxidation to CO.