Giancarlo Gioia Lobbia

In vitro antitumor activity of the water soluble copper(I) complexes bearing the tris(hydroxymethyl)phosphine ligand.

Monocationic hydrophilic complexes [Cu(thp)4](+) 3 and [Cu(bhpe)2](+) 4 were synthesized by ligand exchange reactions starting from the labile [Cu(CH3CN)4][PF6] precursor in the presence of an excess of the relevant hydrophilic phosphine. Complexes 3 and 4 were tested against a panel of several human tumor cell lines. Complex 3 has been shown to be about 1 order of magnitude more cytotoxic than cisplatin. Chemosensitivity tests performed on cisplatin and multidrug resistance phenotypes suggested that complex 3 acts via a different mechanism of action than the reference drug. Different short-term proliferation assays suggested that lysosomal damage is an early cellular event associated with complex 3 cytotoxicity, probably mediated by an increased production of reactive oxygen species. Cytological stains and flow cytometric analyses indicated that the phosphine copper(I) complex is able to inhibit the growth of tumor cells via G2/M cell cycle arrest and paraptosis accompanied with the loss of mitochondrial transmembrane potential.

Organotin derivatives of 4-acyl-5-pyrazolones. Crystal structure of trans-di(t-butyl)bis(1-phenyl-3-methyl-4-benzoyl-pyrazolon-5-ato)tin(IV)

Abstract Stable, six-coordinated Q 2 SnRX compounds have been prepared where QH is 1-phenyl-3-methyl-4-R′C(O)-pyrazol-5-one (R′ = Me, Ph) X = Cl or R, and R = Cl, Me, Et, i-Pr, n- and t-Bu, vinyl, benzyl or phenyl. They are not fluxional when X = Cl or Ph or X = R = t-Bu. The 119 Sn NMR chemical shift is a function of the number of chloride groups. Owing to crowding of the ligands, in the title molecule the CSnC axis is bent (150.0(5)°) and the SnC bonds and two of the four SnO bonds are long; 2.20(1) for the SnC, 2.381(7) and 2.461(6) vs. 2.145(5) and 2.135(6) A for SnO.

Sulfonate- or carboxylate-functionalized N-heterocyclic bis-carbene ligands and related water soluble silver complexes

New N-heterocyclic carbene ligand precursors {H(2)C(HTz(R))(2)} and {H(2)C(HIm(R))(2)} (HTz = 1,2,4-triazole; HIm = imidazole; R = PrSO(3) or EtCOO) were obtained starting from the compounds bis(1,2,4-triazol-1-yl)methane and bis(imidazol-1-yl)methane. The related silver(i) carbene complexes were prepared in degassed water solution by treatment of the triazolium or imidazolium species with Ag(2)O, resulting in well-characterized and water soluble bimetallic complexes of general formula {Na(2)[H(2)C(Tz(R))(2)](2)Ag(2)} and {Na(2)[H(2)C(Im(R))(2)](2)Ag(2)}. In these metallacycles every silver atom is coordinated to two triazolin- or imidazolin-2-ylidene rings, belonging to two different dicarbene units.

Synthesis, characterization and antioxidant activity of new copper(I) complexes of scorpionate and water soluble phosphane ligands

New copper(I) complexes have been synthesised from the reaction of CuCl with potassium hydrotris(4-bromo-1H-pyrazol-1-yl)borate, KTp4Br or lithium bis(3,5-dimethylpyrazol-1-yl)acetate, Li[L2CO2] ligands and 4- or 2-(diphenylphosphane)benzoic acid or tris(m-sulfonatophenyl)posphine trisodium salt (TPPTS) coligands. The complexes obtained have been characterized by elemental analyses and FT-IR in the solid state, and by NMR (1H and 31P[1H]) and electrospray mass spectrometry (ESI-MS) in solution. Single crystal structural characterisation was undertaken for the [Cu[PPh2(4-C6H4COOH)](Tp4Br)] derivative, an interesting dimeric supramolecular assembly. A chemiluminescence study has demonstrated the superoxide scavenging activity of these new copper complexes. The Comet assay was used to evaluate the impairment of DNA in rat epithelial cells exposed to different reactive nitrogen species. In addition, the same complexes were included in this study to determine their efficacy as antioxidants in mitigating oxidative DNA damage. The parameter tail moment, used as an index of DNA damage, showed that the complex [Cu[PPh2(4-C6H4COOH)](Tp4Br)] remarkably inhibited DNA strand breaks induced by the different nitrogen oxide species. The other copper complexes under study showed a different ability to reduce tail moment values depending on the type of RNOS donor used.

Organotin(IV) polypyrazolylborates. III, Tris(3,5-dimethylpyrazolyl)borates

Abstract The compounds RnSnX3-nQ where R = Me, Et, Bu or Ph; X = Cl or Br: n = 0, 1, or 2 and Q is the sterically demanding title ligand have been shown to be stable and non-fluxional and to contain six-coordinated tin(IV) and the tridentate ligand Q.

Synthesis, characterization and X-ray structural studies of novel dinuclear silver(I) complexes of poly(azolyl)borate ligands

Abstract A series of Ag(I) complexes of tris- and tetrakis-(pyrazolyl)hydroborates, tetrakis(imidazol-1-yl)borate, and hydrotris(3-methyl-1-imidazolyl-2-thione)borate, namely the previously recorded [Ag{HB(pz) 3 }] 2 , [Ag{HB(3,5-Me 2 pz) 3 }] 2 , [Ag{B(pz) 4 }] n , together with [Ag{HB(4-Brpz) 3 }] 2 , [Ag{B(3-Mepz) 4 }] n , [Ag{B(im) 4 }] n (Him=imidazole) and [Ag{Tm}] 2 (Tm=hydrotris(3-methyl-2-thioxo-1-imidazolyl)borate) have been synthesized and further characterized by elemental analysis, IR, Far–IR, 1 H, 13 C NMR spectroscopy, and in the case of [Ag{Tm}] 2 , also by a single-crystal X-ray study. Variable-temperature 1 H NMR spectra indicate that [Ag{HB(3,5-Me 2 pz) 3 }] 2 , [Ag{HB(4-Brpz) 3 }] 2 , and [Ag{B(pz) 4 }] n are fluxional, with a pyrazolyl ring exchange process occurring rapidly at 293 but not at 193 K, whereas [Ag{HB(pz) 3 }] 2 and the crystalline form of [Ag{HB(3,5-Me 2 pz) 3 }] 2 are not fluxional, even at room temperature. The reactions between K[HB(pz) 3 ], K[HB(3,5-Me 2 pz) 3 ], K[B(pz) 4 ] or K[Tm] and AgNO 3 in presence of N -and S -donor, unidentate or bidentate ligands such as pyrazole, imidazole, 1-10-phenanthroline and 1-methylimidazoline(2,3 H )thione (Hmimt) were investigated. We also report the results of positive ion FAB MS studies carried out for selected derivatives.

Tin(IV) and organotin(IV) adducts of bis(1-pyrazolyl)methane

Abstract Bis(pyrazol-1-yl)methane, (L-L), reacts with tin(IV) or organotin(IV) halides yielding (L-L)SnX m R −m (X = Cl, Br, I; m = 4,3 or 2 but not 1; R = methyl or phenyl). NMR spectra show that the compounds are fluxional, while combined molecular weight determinations and conductivity data show that in acetone solution the molecules obtained dissociate readily into the starting materials.

Synthesis and characterization of copper(I) derivatives with N-donor ligands—III. Hydridotris (1H-pyrazol-1-yl)borate. The X-ray crystal structure of [HB-(μ-pz)3-Cu(PPh3)]

Abstract (Triarylphosphine)copper(I) derivatives containing anionic tris(1 H -pyrazol-1-yl)borato have been prepared from (Ar 3 P) 2 CuNO 3 and KTp, KTp ∗ , KTp Me and KTp ∗Cl and characterized through IR and 1 H, 13 C and 31 P NMR spectra. The complexes contain tetrahedral Cu I and a tridentate ligand. The X-ray single crystal analysis of the (PPh 3 )CuTp complex is reported. Four-coordinate Cu 1 is present in a distorted tetrahedral configuration owing to the bulky PPh 3 and Tp groups: NCuN angles range from 88.4(2) to 91.8(2)°; NCuP angles range from 120.6(2) to 127.3(1)°. The CuN distances are 2.081(5), 2.065(5) and 2.083(5) A and the CuP distance is 2.153(2) A.

Triorganotin(IV) derivatives of several 4-acyl-5-pyrazolonato ligands: synthesis, spectroscopic characterization and behavior in solution. Crystal structure of aquotrimethyl(4-p-methoxybenzoyl-1-phenyl-3-methyl-pyrazolon-5-ato)tin(IV).

New triorganotin(IV) derivatives [(Q)SnR3 · x(H2O)] (x = 0, R  Ph; x = 1, R  Me and nBu) (in general QH  1-R′-3-methyl-4-R″ (CC)-pyrazol-5-one; in detail Q′H: R′ = C6H5, R″ = C6H5; QAH:R′ = C6H5, R″ = p-CH3OC6H4; QNH: R′ C6H5, R″  p-NO2C6H4; QBrH:R′ = C6H5, R″ = p -BrC6H4; Q″H: R′ = C6H5,R″ = CH3; QClH: R′ = C6H5, R″ = CCl3; QFH: R′ = C6H5, R″ = CF3; QMH: R′ = CH3 R″ = C6H5; QDH: R′ = CH3, R″ = CH3) have been synthesized and characterized by analysis and spectral (IR and 1H, 13C and 119Sn NMR) data. The (Q)SnPh3 derivatives are five-coordinated in the solid state, with a likely skewed cis-trigonal bipyramidal (cis-TBP) geometry around the tin center and the ligand (Q)− acting in the bidentate form. In [(Q)SnR3 · (H2O)] derivatives (R = nBu or Me) a coordination site is occupied by water, with the ligand (Q)− coordinating in a monodentate fashion. The crystal structure of [(QASnMe3 · (H2O)] has been determined: the tin atom is found in a distorted TBP environment, with the methyl in the equatorial positions. Two of the SnC bond lengths are normal (2.11(1) and 2.08(2) A) whereas the third is longer (2.18(2) A); the ligand binds the metal atom through one carbonyl oxygen in the apical position (SnO = 2.10(1) A). The bond lenght between H2O and Sn is longer (2.41(2) A), and the OSnO angle is 174.9(5)°. H atoms of water are involved in an intermolecular H-bond network with uncoordinated carbonyl and the pyridinic N atom of the ligand. In chloroform solution the[(Q)Snr3 · (H2O)] derivatives (R = Me or nBu) lost the molecule of water and adopt a tetrahedral arrangement. They also give rise to a slow disproportionation, yielding SnR4 and [(Q)2SnR2] derivatives.

Adducts from mercury(I) and mercury(II) compounds with Bispyrazolylalkanes.X-Ray crystal structure of Bis(3,5-dimethylpyrazol-l-yl)methane(dicyano)-mercury(II)

Abstract The 1:1 adducts between thebis(3,5-dimethylpyrazol-1-yl)methane (L′-L′) or 2,2′-bis(pyrazol- 1-yl)propane (L″L″) ligand and HgX 2 (with X = Cl, CN or CO 2 CF 3 ) have been obtained as well as [(L′L′) 2 ]Hg(ClO 4 ) 2 and the mercury(I) derivative (ligand) 2 Hg 2 (ClO 4 ) 2 . The adducts have been characterized from analytical and spectral data (IR, proton and 13 C NMR). Four-coordinated mercury is present in (L′L′)Hg(CN) 2 , in which the metal-(NN) 2 C ring adopts an asymmetric boat form. The molecular parameters are significantly different for the two independent molecules, the CHgC angles and the two Hg-N distances being 163.1(9)°and 2.55(1) plus 2.70(1) A in the one case, and 148.2(8)° and 2.40(1) plus 2.51(1) A, in the other; correspondingly the N-Hg-N angle, the ‘bite’ of the ligand, ranges from 79.0(5)° to 71.7(4)°, a value outside the range previously reported.