Fabio Marchetti

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-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.

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.

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.

Inhibitory effect of β-diketones and their metal complexes on TNF-α induced expression of ICAM-1 on human endothelial cells

Recent reports show that the natural beta-diketone curcumin displays important biological properties regarding the intercellular adhesion molecule-1 (ICAM-1), which plays a critical role in the immune responses and inflammation. In this study the ICAM-1 inhibitory activity of beta-diketone compounds, which are curcumin models lacking aromatic peripheral hydroxyl and methoxy groups, along with some metal derivatives is investigated. Beta-diketones are systematically more active than metal complexes and the best obtained inhibition is 75% for both groups. The best inhibitors are 4-benzoyl-3-methyl-1-phenyl-pyrazol-5-one (HQ(Ph)) among the ligands, and sodium benzoylacetonato among metal derivatives. These results appear in line with the reported antitumor activity of related species. Since 4-acyl-5-pyrazolones posses four tautomeric forms, those corresponding to HQ(Ph) were investigated using density functional theory. Docking of all HQ(Ph) tautomers on ICAM-1 protein was performed suggesting one keto-enol form favored to act in biological environment.

Characterization of diorganotin(IV) complexes with captopril. The first crystallographically authenticated metal complex of this anti-hypertensive agent.

Diorganotin(IV) complexes R(2)Sn(cap) (capH(2)=N-[(S)-3-mercapto-2-methylpropionyl]-L-proline; R=Me, Et, n-Bu and t-Bu) were prepared and characterised. The FTIR and Raman spectra demonstrated that the organotin(IV) moieties interact with the [S] atom of the ligand, while the other coordination sites are the carboxylate and the amide -CO groups. Mössbauer Delta data showed that the diorganotin(IV) compounds adopt slightly distorted trigonal-bipyramidal (tbp) geometry. A single-crystal X-ray study was performed on the compound Me(2)Sn(cap): the Sn atom is five-coordinated in a distorted tbp environment, with two [O] atoms in the axial positions and the [S] and two [C] atoms in the equatorial (eq) plane. Each cap ligand coordinates to two different Sn atoms, and infinite zigzag chains are formed, directed parallel to each other and to the b axis of the unit cell. NMR (CDCl(3)) of the Me(2)Sn(IV) and n-Bu(2)Sn(IV) complexes indicated the presence of different oligomeric species.

Organotin(IV) derivatives containing bis(diphenylphosphine)- and bis(diphenylphosphineoxo)alkanes

Abstract Di-organotin(IV)halides R2SnCl2 (R=Me or Ph) react with bis(diphenylphosphine)methane (DPPM) and bis(diphenylphosphine)ethane (DPPE) in ethanol in aerobic conditions yielding 1:1 adducts [R2SnCl2(DPPM–O2)] and [R2SnCl2(DPPE–O2)], respectively, containing the bis(diphenylphosphine) in oxidized form. The 1:1 adduct [SnMe2Cl2(DPPM–O2)] is composed of separate molecules containing six-coordinate tin, with the ligands coordinated in the bidentate O2-fashion, whereas [SnMe2Cl2(DPPE–O2)] is polymeric, with octahedral and centrosymmetric (all trans) tin atoms. In inert atmosphere, the interaction between R2SnCl2 and DPPM or DPPE does not take place. Mono-organotin halides RSnCl3 (R=Me, Bun or Ph) react with DPPM and DPPE yielding 1:1 adducts [RSnCl3(DPPM)] (R=Me, Bun or Ph) and [RSnCl3(DPPE)] (R=Bun or Ph).

(1-Phenyl-3-methyl-4-acetylpyrazolon-5-ato)rhodium(I) complexes, synthesis, structural and spectroscopical characterization: Reactivity of diolefin- and dicarbonyl-rhodium complexes toward N-, P- and O-donors

Novel complexes of rhodium(I) [Rh(diolefin)(Q″)] (where HQ″=1-phenyl-3-methyl-4-acetylpyrazol-5-one and diolefin=cycloocta-1,5-diene (COD), bicyclo[2.2.1]hepta-2,5-diene (NBD) or 1,5-hexadiene (HEX)) were synthesized and characterized by analytical and spectral data. [Rh(COD)(Q″)] interacts with 4,5-dimethyl-1,10-phenanthroline (Me 2 Phen) and 2,2′-bipyridil (Bipy) yielding the cationic derivatives [Rh(COD)(Me 2 Phen)](Q″)(H 2 O), [Rh(COD)(Bipy)](Q″)(H 2 O) upon displacement of the (Q″) − donor from the coordination sphere of the metal center. Whereas [Rh(COD)(Q″)] interacts with 2-benzoylpyridine (Bzpy) yielding the 1:1 adduct [Rh(COD)(Bzpy)(Q″)] in which Bzpy acts as N-monodentate donor. On the other hand the monodentate P-donors triphenylphosphine, triphenylphosphite, tricyclohexylphosphine and the bidentate bis(diphenylphosphino)ethane (DPPE) displace the COD ligand from [Rh(COD)(Q″)] giving the neutral derivatives [Rh(PR 3 ) 2 (Q″)] (PR 3 =PPh 3 , or P(OPh) 3 ) and [Rh(DPPE)(Q″)](H 2 O). HQ″ reacts with the dinuclear [Rh(CO) 2 Cl] 2 . The tetradentate cycloocto-tetraene (COT) reacts with [Rh(CO) 2 (Q″)] yielding the derivative [Rh(CO) 2 (HQ″)Cl] in which HQ″ acts as neutral monodentate O-donor ligand. Whereas in presence of NEt 3 HQ″ reacts with [Rh(CO) 2 Cl] 2 yielding [Rh(CO) 2 (Q″)]. In this complex, one molecule of CO can be replaced by one mole of Phen and Bipy or by two moles of PPh 3 and AsPh 3 yielding the derivatives [Rh(CO)(L) n (Q″)]·x(H 2 O) (L=Me 2 Phen or Bipy, n =1; L=PPh 3 or AsPh 3 , n =2) whereas one mole of DPPE displaces both the molecules of CO, yielding [Rh(DPPE)(Q″)] yielding the derivative [Rh(COT)(Q″)]. The X-ray crystal structure determination of [Rh(COD)(Q″)] establishes that the rhodium atom is in a square planar configuration with two adjacent sites occupied by the (Q″) − ligand in the O 2 -bidentate form (Rh–O distances=2.054(2) and 2.061(2) A). The COD ring has a twisted boat conformation with Rh–C distances in the range 2.101(3)–2.110(3) A. Comparison was made with structural data reported for several related tetracoordinated (COD)Rh(I) adducts.

Tris(4-bromo-1H-pyrazol-1-yl)borato derivatives of first-row transition and group 12 and 14 metals. X-ray crystal structure of [HB(4-Brpz)3]2 Cd. 113Cd solution NMR study of bis[poly(pyrazolyl)borato]cadmium complexes

Abstract A series of metal complexes M[HB(4-Brpz)3]2 [HB(4-Brpz)3 = hydridotris(4-bromo-1H-pyrazol-1-yl)borate and M = Mn, Fe, Co, Ni, Cu, Zn, Cd, Pb] were obtained from reaction of K[HB(4-Brpz)3] and the appropriate metal salt in aqueous solution. These air-stable complexes are sparingly soluble in most common solvents; they have been investigated through elemental analysis, conductivity measurements, IR, UV-vis and, in the case of diamagnetic compounds, 1H and 13C NMR spectroscopy. The X-ray crystal structure of cadmium(II) bis[hydridotris(4-bromo-1H-pyrazol-1-yl)borate] has been resolved. Six-coordinate cadmium is present in a slightly distorted octahedron with the axes not linear [angles 176.8(3), 177.2(3) and 178.7(3)°]. The ‘bite’ of the ligand, i.e. NCdN angle, lies in the range 81.6(2)–84.1(3)° (weighted average 82.4(4)°). The CdN distances vary from 2.298(8) to 2.329(8) A (weighted average 2.317(5) A). The geometry around the B atom is tetrahedral. The NBN angles range from 105.8(8) to 110.5(7)° (weighted average 108.5(7)°); the BN bond distances vary from 1.53(2) to 1.62(1) A (weighted average 1.58(1) A). We report and discuss also the 113Cd NMR solution data of several cadmium poly(pyrazol-1-yl)borates).

Mechanochemical and solution synthesis, X-ray structure and IR and 31P solid state NMR spectroscopic studies of copper(I) thiocyanate adducts with bulky monodentate tertiary phosphine ligands

A number of adducts of copper(I) thiocyanate with bulky tertiary phosphine ligands, and some nitrogen-base solvates, were synthesized and structurally and spectroscopically characterised. CuSCN:PCy3 (1:2), as crystallized from pyridine, is shown by a single crystal X-ray study to be a one-dimensional polymer ...(Cy3P)2CuSCN(Cy3P)2CuSCN... (1) with the four-coordinate copper atoms linked end-on by S-SCN-N bridging thiocyanate groups. A second form (2), obtained from acetonitrile, was also identified and shown by IR and 31P CPMAS NMR spectroscopy to be mononuclear, with the magnitude of the dν(Cu) parameter measured from the 31P CPMAS and the ν(CN) value from the IR clearly establishing this compound as three-coordinate [(Cy3P)2CuNCS]. Two further CuSCN/PCy3 compounds CuSCN:PCy3 (1:1) (3), and CuSCN:PCy3:py (1:1:1) (4) were also characterized spectroscopically, with the dν(Cu) parameters indicating three- and four-coordinate copper sites, respectively. Attempts to obtain a 1:2 adduct with tri-t-butylphosphine have yielded, from pyridine, the 1:1 adduct as a dimer [(Bu(t)3P)((SCN)(NCS))Cu(PBu(t)3)] (5), while similar attempts with tri-o-tolylphosphine (from acetonitrile and pyridine (= L)) resulted in solvated 1:1:1 CuSCN:P(o-tol)3:L forms as dimeric [{(o-tol)3P}LCu((SCN)(NCS))CuL{P(o-tol)3}] (6 and 8). The solvent-free 1:1 CuSCN:P(o-tol)3 adduct (7), obtained by desolvation of 6, was characterized spectroscopically and dν(Cu) measurements from the 31P CPMAS NMR data are consistent with the decrease in coordination number of the copper atom from four (for 6) (P,N(MeCN)Cu,S,N) to three (for 7) (PCuS,N) upon loss of the acetonitrile of solvation. These results are compared with those previously reported for mononuclear and binuclear PPh3 adducts which demonstrate a clear tendency for the copper centre to remain four-coordinate. The IR spectroscopic measurements on these compounds show that bands in the far-IR spectra provide a much more definitive criterion for distinguishing between bridging and terminal bonding than does an often-used empirical rule based on ν(CN) in the mid-IR, which leads to the wrong conclusion in some cases.