Riccardo Pettinari

Synthesis and characterisation of tin(IV) and organotin(IV) derivatives 2-{((2-hydroxyphenyl)imino)methyl}phenol

Abstract From the interaction of 2-{[(2-hydroxyphenyl)imino]methyl}phenol(salopH2) with tin and organotin(IV) acceptors, the derivatives [SnR3(salopH)] (R=Me or Bun), [SnR2(salop)] (R=Me, Bun, But, Vin or Ph), [SnRX(salop)(solvent)] (R=Me, Bun, Ph or X; X=Cl, Br or I; solvent=CH3OH or H2O), [Sn(salop)2], [R2SnCl2(salopH2)] (R=Me or Bun) have been obtained and characterised. The chelates, containing the Schiff base in mono or dianionic form, are generally stable both in the solid state and in solution, whereas the [SnR2Cl2(salopH2)] adducts slowly decompose in acetone or DMSO yielding [SnR2(salop)] and releasing HCl. All the [SnR2(salop)] and [SnRX(salop)(solvent)] complexes are fluxional in solution. The 119Sn NMR chemical shift is a function of the number of R groups. The X-ray single crystal diffraction study of [SnVin2(salop)] shows the metal to be five-coordinate in a distorted square pyramidal environment, SnC distances being 2.112(2) and 2.113(2) A, SnO 2.117(2) and 2.125(2) A and SnN 2.227(2) A. The whole structure consists of molecular units connected by weak intermolecular SnO interactions. In the complexes [SnX2(salop)(CH3OH)]·CH3OH complexes (X=Cl or Br), the tin atom is found in a strongly distorted octahedral environment with the SnO bond ranging from 1.995(3) to 2.055(2) A. The SnN bond is 2.116(4) A in the bromide and 2.171(3) A in the chloride complex.

Ruthenium-arene complexes of curcumin: X-ray and density functional theory structure, synthesis, and spectroscopic characterization, in vitro antitumor activity, and DNA docking studies of (p-cymene)Ru(curcuminato)chloro.

The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon-rectal tumor HCT116, IC(50) = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxy-curcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20° between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru-N7(guanine) interaction is detected. This Ru-N7(guanine) interaction is also seen with ESI-MS on a Ru-complex-guanosine derivative.

Group 12 metal complexes of tetradentate N2O2–Schiff-base ligands incorporating pyrazole: Synthesis, characterisation and reactivity toward S-donors, N-donors, copper and tin acceptors

Abstract New [M(Q)2(X)] derivatives (where M=Zn, Cd or Hg; Q=1-phenyl-3-methyl-4-R(C=O)-pyrazolon-5-ato; in detail: QL, R=C6H5; QB, R=CH2C(CH3)3; QS, R=CH(C6H5)2; X=EtOH or H2O) have been synthesised and characterised. These compounds undergo a condensation reaction with the appropriate diamine in ethanol, affording novel Schiff-base metal derivatives [M(diaquo)bis(1-phenyl-3methyl-4-R(C=N)-pyrazolone)(CH2)ndiimmine] (LnH2, R=C6H5, n=2, 3 or 4; BnH2, R=CH2C(CH3)3, n=2, 3 or 4; SnH2, R=CH(C6H5)2, n=2 or 3; M=Zn, Cd or Hg). These compounds possess a six-coordinate metal environment. A 113Cd NMR study has been carried out on cadmium derivatives. The derivative [Zn(L2)(H2O)2] reacted with CuCl2 and with Cu(ClO4)2 affording [Cu(QL)2] and [Cu(en)2](ClO4)2 (en=ethylendiamine), respectively, upon breaking of the C=N bond in the Schiff-base donor. In addition [Zn(L2)(H2O)2] reacted with 1,10-phenanthroline (phen), yielding the derivative [Zn(QL)2(phen)]. Whereas when [Zn(L2)(H2O)2] reacted with CdCl2, formation of [Cd(L2)(H2O)2] due to exchange of the metal centre was observed. Finally the derivative [Zn(L2)(Hmimt)], likely containing a five-coordinate ZnN2O2S central core, has been obtained from the exchange reaction between [Zn(L2)(H2O)2] and 1-methylimidazolin-2-thione (Hmimt).

Mixed-ligand Cu(II)–vanillin Schiff base complexes; effect of coligands on their DNA binding, DNA cleavage, SOD mimetic and anticancer activity

SOD mimics with varying coligand are momentous in developing potential chemotherapeutic drugs. Cu(II) based SOD mimics 1-4 [CuLH(OAc)(H(2)O)Y)] (LH = 2-((E)-(1,3-dihydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol, OAc = CH(3)COO, 1: Y = H(2)O; 2: Y = phen (1,10-phenanthroline), 3: Y = tpimH (2,4,5-triphenylimidazole); 4: Y = tfbimH (2-(trifluoromethyl)benzimidazole) were synthesized and thoroughly characterized. Their interaction with CT-DNA showed different non-covalent binding behaviour. SOD activity of 2 was highest among 1-4 which was further validated by gel electrophoresis. The pBR322 plasmid strand break offered by 2 + O₂·⁻ system reveals oxidative cleavage mechanism. In vitro antimicrobial activity of 1-4 was shown by percent inhibition data while in vitro anticancer activity of 1-4 was screened using 16 human carcinoma cell lines of different histological origin. Complex 2 showed higher efficacy towards 14 cell lines.

Arene-ruthenium(II) acylpyrazolonato complexes: apoptosis-promoting effects on human cancer cells.

A series of ruthenium(II) arene complexes with the 4-(biphenyl-4-carbonyl)-3-methyl-1-phenyl-5-pyrazolonate ligand, and related 1,3,5-triaza-7-phosphaadamantane (PTA) derivatives, has been synthesized. The compounds have been characterized by NMR and IR spectroscopy, ESI mass spectrometry, elemental analysis, and X-ray crystallography. Antiproliferative activity in four human cancer cell lines was determined by MTT assay, yielding dose- and cancer cell line-dependent IC50 values of 9-34 μM for three hexamethylbenzene-ruthenium complexes, whereas the other metal complexes were much less active. Apoptosis was the mechanism involved in the anticancer activity of such compounds. In fact, the hexamethylbenzene-ruthenium complexes activated caspase activity, with consequent DNA fragmentation, accumulation of pro-apoptotic proteins (p27, p53, p89 PARP fragments), and the concomitant down-regulation of antiapoptotic protein Bcl-2. Biosensor-based binding studies indicated that the ancillary ligands were critical in determining the DNA binding affinities, and competition binding experiments further characterized the nature of the interaction.

Arene-Ru(II) complexes of curcumin exert antitumor activity via proteasome inhibition and apoptosis induction.

Organometallic ruthenium(II) complexes of general formula [(η6‐arene)Ru(curcuminato)Cl], with arene being p‐iPrC6H4Me (1), C6H6 (2), and C6Me6 (3), were synthesized, characterized, and evaluated for their antitumor effects. Specifically, we explored their ability to regulate the proteasome, a validated pharmacological target in cancer treatment. Ruthenium complexes inhibited isolated proteasomes to various extents, with the biological activity of these complexes depending on the nature of the bound arene; in particular, [(η6‐arene)Ru(curcuminato)Cl] 2 suppressed proteasomal activities more potently than 1, 3, or free curcumin. Each complex also inhibited proteasomes in cultured colon cancer cells and consequently triggered apoptosis, with the [(η6‐benzene)Ru(curcuminato)Cl] complex 2 being the most active. The influence on the oxidative status of HCT116 cells and the DNA binding ability of the [(η6‐arene)Ru(curcuminato)Cl] complexes were studied. Complex 2 showed the highest antioxidant capacity; moreover, complexes 1 and 2 were shown to bind isolated DNA with higher affinity (up to threefold) than free curcumin. Collectively, our results demonstrate that the complexation of curcumin with ruthenium(II) is a promising starting point for the development of curcumin‐based anticancer drugs.

Synthesis, Structure, and Antiproliferative Activity of Ruthenium(II) Arene Complexes with N,O-Chelating Pyrazolone-Based β-Ketoamine Ligands

Novel ruthenium half-sandwich complexes containing (N,O)-bound pyrazolone-based β-ketoamine ligands have been prepared, and the solid-state structures of one ligand and five complexes have been determined by single-crystal X-ray diffraction. Some of the complexes display moderate cytotoxicity toward the human ovarian cancer cell lines A2780 and A2780cisR, the latter line having acquired resistance to cisplatin.

Organotin(IV) derivatives of novel β-diketones ☆: Part V. Synthesis and characterization of di- and triorganotin(IV) derivatives of 4-acyl-5-pyrazolones modified in position 3 of the pyrazole. Crystal structure of (1,3-diphenyl-4-benzoyl-pyrazolon-5-ato)triphenyltin(IV)

Abstract The interaction between R 3 SnCl, (R 3 Sn) 2 O, R 2 SnO or R 2 SnCl 2 acceptors (R=Me, n Bu or Ph) and the two novel β-diketone proligands (LH=1,3-diphenyl-4-R 4 (CO)-pyrazol-5-one: L 1 H, R 4 =Ph; L 2 H, R 4 =Me) yields complexes [SnR 3 (L)(H 2 O)] (R=Me or n Bu, L=L 1 or L 2 ), [SnPh 3 (L)] and [SnR 2 (L) 2 ] (L=L 1 or L 2 ). The phenyl substituent on position 3 induces instability of the triorganotin derivatives in solution with the formation of SnR 2 (L) 2 and SnR 4 compounds. Moreover, diorganotin derivatives partially dissociate in solution yielding [SnR 2 (L)(solvent)] 2+ species. When compared with the related 3-methyl species, the crystal structure of (1,3-diphenyl-4-benzoyl-pyrazolon-5-ato)triphenyltin(IV) is not modified by the 3-phenyl substitution. The chemical instability generated by the Ph in position 3 is greater than in positions 1 and 4. In addition, the Ph in position 3 of the pyrazole influences the solution behavior of the free neutral 4-acyl-5-pyrazolones stabilizing a novel amino-diketo tautomeric form.

Synthesis, Characterization, and Antitumor Activity of Water-Soluble (Arene)ruthenium(II) Derivatives of 1,3-Dimethyl-4-acylpyrazolon-5-ato Ligands. First Example of Ru(arene)(ligand) Antitumor Species Involving Simultaneous Ru−N7(guanine) Bonding and Ligand Intercalation to DNA

We report on the synthesis of novel water-soluble [(arene)Ru(II)(Q)Cl] and [(arene)Ru(II)(Q)(X)]BF4 compounds (arene = p-cymene, benzene, hexamethylbenzene; HQ = 1,3-dimethyl-4-R-(C═O)-5-pyrazolone, HQ(Me), R = methyl, HQ(Ph), R = phenyl, HQ(Naph), R = naphthyl; X = H2O, 9-ethylguanine), and their in vitro antitumor activity toward the cell lines MCF7 (HTB-22, human breast adenocarcinoma), HCT116 (CCL-247, human colorectal carcinoma), A2780 (human ovarian carcinoma), A549 (CCL-185, human lung carcinoma), and U87 MG (HTB-1, human glioblastoma). The X-ray crystal structures of two complexes were determined. One of them, {chlorido-(p-cymene)-[(1,3-dimethyl-4-(1-naphthoyl)-pyrazolon-5-ato]ruthenium(II)}, was also studied with density functional theory methods and was selected for docking on a DNA octamer showing intercalation between DNA bases by the naphthyl moiety and for Ru-N7(guanine) bonding.

Structure and volatility of copper complexes containing pyrazolyl-based ligands

Abstract Volatility studies, electrospray mass spectra and IR in vapour phase were carried out for a series of Cu(I) and Cu(II) complexes containing anionic pyrazole-based ligands such as 4-acyl-5-pyrazolonates and poly(pyrazolyl)borates. The volatility has been related to structural features and molecular parameters of the copper complexes. The crystal structures of [Cu(Q′)2(bipy)]·(acetone)1.5 (Q′=1-phenyl-3-methyl-4-benzoyl-pyrazolon-5-ato, bipy=2,2′-bipyridyl) and [Cu(QF)2(phen)]·EtOH (QF=1-phenyl-3-methyl-4-trifluoroacetyl-pyrazolon-5-ato, phen=1,10-phenanthroline), have been also determined. In these complexes the copper atom is in a tetragonally distorted octahedral arrangement of the four O-atoms of pyrazolones with N2-donor ligand in equatorial position. Two sets of CuO distances, the longer being in axial positions, have been found. XRD data of films obtained from metal organic chemical vapour deposition MOCVD experiments on [Cu(poly(pyrazolyl)borate)(PR3)] complexes have also been reported.