Paola Bergamini

Induction of erythroid differentiation of human K562 cells by cisplatin analogs

Human leukemic K562 cells can be induced in vitro to erythroid differentiation by a variety of chemical compounds, including hemin, butyric acid, 5-azacytidine, and cytosine arabinoside. Differentiation of K562 cells is associated with an increase in the expression of embryo-fetal globin genes, such as the zeta-, epsilon-, and gamma-globin genes. Therefore, the K562 cell line has been proposed as a very useful in vitro model system for determining the therapeutic potential of new differentiating compounds as well as for studying the molecular mechanism(s) regulating changes in the expression of embryonic and fetal human globin genes. Inducers of erythroid differentiation that stimulate gamma-globin synthesis could be considered for possible use in the experimental therapy of hematological diseases associated with a failure in the expression of adult beta-globin genes. In this paper, we analyzed the effects of a series of cisplatin analogs on both cell growth and differentiation of K562 cells. Among seven cisplatin analogs studied, three were found to be potent inducers of erythroid differentiation. Erythroid differentiation was associated with an increase in the accumulation of (a) hemoglobins Gower 1 and Portland and (b) gamma-globin mRNA.

Photocatalytic oxidation of cyclohexane by (nBu4N)4W10O32Fe(III)prophyrins integrated systems

Abstract The oxidation of cyclohexane by photoexcited (nBu4N)4W10O32 has been investigated in the presence of iron meso-tetraarylporphyrins bearing different substituents in the β-pyrrole positions and/or in the meso-aryl groups. Irradiation at 325 nm leads to the reduction of the polyoxotungstate with the simultaneous oxidation of cyclohexane to cyclohexyl radicals which can be detected by the ESR spin trapping technique. In oxygen-free solutions, the photoreduced polyoxotungstate is able to transfer one electron to the Fe(III)porphyrin to give the ferrous complex. The subsequent reaction between this species and cyclohexyl radicals leads to the formation of σ-alkyl-Fe(III)porphyrin complexes, as demonstrated by UV-VIS and NMR spectroscopy. In the presence of oxygen, the photoreduced polyoxotungstate has the role of initiating the activation of O2 through its reduction to O2 and H2O2. As a consequence, cyclohexane is converted to cyclohexanone and cyclohexanol in a cyclic way. The Fe(III)porphyrin complex strongly affects the product distribution probably through its hydrogen peroxide and alkyl-hydroperoxide-dependent oxidation. In comparison with (nBu2N4)W10O32 alone, a higher selectivity is obtained with the formation of cyclohexanol as a major product.

Radical-forming electron-transfer; photoreactions involving iron group metallocenes

Abstract Iron group metallocenes Cp2M (Cp = C5H5, M = Fe, Ru, Os) and chlorocarbon solvents RCl (CCl4, CHCl3, CH2Cl2, C2Cl4) form electron donor-acceptor (EDA) complexes. During irradiation of EDA complexes in the presence of spin traps, nitroxide radical adducts of chlorocarbon radicals ·R have been detected, and on this basis a mechanism for the photolysis of EDA complexes is suggested. The ability of metallocenes, particularly Cp2Fe, to trap transient radicals ·R in electron transfer processes has been demonstrated.

Unsymmetrical bridging of an acetylide ligand in the cation [Pt2(CCBut)3(µ-dppm)2]+(dppm = Ph2PCH2PPh2): X-ray structure determination of the tetraphenylborate salt

Treatment of [PtCl2(dppm-PP′)](dppm = Ph2PCH2PPh2) with LiCCBut in tetrahydrofuran gives [Pt2(CCBut)3(µ-dppm)2]Cl in 59% yield. The X-ray crystal structure of the BPh4 salt shows that the cation has an unsymmetrically bridged (σ,π bonded) acetylide ligand in the solid state; in solution, fluxional behaviour is indicated by the time averaging of the 31P and 1H n.m.r. spectra.

Acetylcholine-like and trimethylglycine-like PTA (1,3,5-triaza-7-phosphaadamantane) derivatives for the development of innovative Ru- and Pt-based therapeutic agents.

The PTA N-alkyl derivatives (PTAC2H4OCOMe)X (1X: 1a, X = Br; 1b, X = I; 1c, X = PF6; 1d, X = BPh4), (PTACH2COOEt)X (2X: 2a, X = Br; 2b, X = Cl; 2c, X = PF6), and (PTACH2CH2COOEt)X (3X: 3a, X = Br; 3c, X = PF6), presenting all the functional groups of the natural cationic compounds acetylcholine or trimethylglycine combined with a P-donor site suitable for metal ion coordination, were prepared and characterized by NMR, ESI-MS, and elemental analysis. The X-ray crystal structures of 1d and 2c were determined. Ligands 1c, 2b, and 3c were coordinated to Pt(II) and Ru(II) to give the cationic complexes cis-[PtCl2(L)2]X2 and [RuCpCl(PPh3)(L)]X (L = 1, 2, 3, X = Cl or PF6) designed with a structure targeted for anticancer activity. The X-ray crystal structure of [CpRu(PPh3)(PTAC2H4OCOMe)Cl]PF6 (1cRu) was determined. The antiproliferative activity of the ligands and the complexes was evaluated on three human cancer cell lines.

Cleavage of the P–C bond in [PtCl2(Ph2PCH2PPh2-P,P′)] under mild conditions

Treatment of [PtCl2PCH2PPh2-P,P′)] with an excess of NaOH in NH3 at –50 °C gives, in >80% yield, the cis and trans isomers of [(Ph2MeP)(Ph2PO)Pt(µ-NH2)2Pt((POPh2)(PMePh2)], the structure of the trans from being confirmed by X-ray crysallography; both the structure and the proposed mechanism display highly novel features.

Bis(8-hydroxyquinolinato)platinum 7,7,8,8-tetracyanoquinodimethane, Pt(QNL)2·TCNQ. Synthesis, structure and spectroscopic properties

Abstract The title complex, Pt(QNL) 2 ·TCNQ, was prepared by the reaction of Pt(QNL) 2 with TCNQ in acetonitrile. This complex consists of stacks of alternating, parallel Pt(QNL) 2 and TCNQ molecules. The molecules of Pt(QNL) 2 and TCNQ in the stack are planar and nearly parallel. The angle between the mean plane defined by the phenyl ring in TCNQ and the mean plane defined by the atoms Pt, O 1 , O′ 1 , N 1 and N′ 1 is 3.57°. The Pt(QNL) 2 ·TCNQ is diamagnetic. The visible spectrum exhibits a charge transfer band at 10 100 cm −1 indicating that there is some charge- transfer interaction in the complex. Spectroscopic data and the analysis of the bond distances in the TCNQ moiety indicates that the degree of charge- transfer in Pt(QNL) 2 ·TCNQ is small.

[PtOTf(triphos)]OTf and [PtMe2(triphos-P,P′)] as versatile synthons of platinum(II)-triphos species

The new complex [PtOTf(triphos)]OTf (triphos=bis(2-diphenylphosphinoethyl)phenyl-phosphine, OTf=CF3SO3) (1) can be most efficiently prepared by adding triflic acid to the known complex [PtMe2(triphos-P,P′)] (5) where triphos acts as a bidentate ligand. The fluxional behaviours of 1 and 5 in solution and their reactivity have been investigated by NMR: [PtOTf(triphos)]OTf is a very electrophilic complex and its reactivity is dominated by the tendency of the labile ligand OTf to be replaced by a variety of nucleophiles, while the chemistry of [PtMe2(triphos-P,P′)] is controlled by the proclivity of the third phosphorus to coordinate to platinum, as soon as a vacancy is created via Pt–Me protonolysis.

Preparation, solution behaviour and X-ray crystal structure of [PtOTf(triphos)]OTf

Abstract The lability of the coordinated triflate in the new complex [PtOTf(triphos)]OTf both in the solid state and in solution is pointed out by the X-ray crystal structure, by NMR observations and by some examples of nucleophilic substitution at platinum.

Reactivity of [Pt(CH2X)2(Ph2PCH2PPh2-PP′)](X = Cl, Br, or I): four- to five-membered ring expansions. Crystal structure of [bis(diphenylphosphino)-methane-PP′]bis(chloromethyl)platinum(II)

Addition of CH2N2 to the chelates [PtX2(dppm-PP′)](X = Cl, Br, or I; dppm = Ph2PCH2PPh2) gives the complexes [Pt(CH2X)2(dppm-PP′)](2a)–(2c) which have been fully characterised. The X-ray crystal structure of [Pt(CH2Cl)2(dppm-PP′)](2a) has been determined in confirmation of its chemical identity (orthorhombic, space group Pbca, R= 0.053 for 2 499 observed reflections [I/σ(I) 2.0]. Addition of HCl to complex (2a) gives [PtCl(CH2Cl)(dppm-PP′)](3). Treatment of (2a) with phosphines or pyridine leads to a ring-expansion reaction to give [PtL(CH2Cl)(CH2PPh2CH2PPh2)]Cl [L = pyridine (4a), PPh3(4b), or PPh2H (4c)]. With dppm, (2a) gives the bis chelate [Pt(CH2PPh2CH2PPh2)2]Cl2(5). The mechanism of these ligand-promoted ring expansions is discussed. The products have been fully characterised by a combination of elemental analysis, i.r., 1H, and 31P-{1H} n.m.r. spectroscopy.