Diverse and unexpected outcomes from oxidation of the platinum(II) anticancer agent [Pt{(p-BrC6F4)NCH2CH2NEt2}Cl(py)] by hydrogen peroxide.

Oxidation of the anti-tumour agent [Pt{(p-BrC6F4)NCH2CH2NEt2}Cl(py)], 1 (py = pyridine) with hydrogen peroxide under a variety of conditions yields a range of organoenamineamidoplatinum(II) compounds [Pt{(p-BrC6F4)NCH=C(X)NEt2}Cl(py)] (X = H, Cl, Br) as well as species with shared occupancy involving H, Cl and Br. Thus, oxidation of the -CH2-CH2- backbone (dehydrogenation) occurs, often accompanied by substitution. Oxidation of 1 with H2O2 in acetone yielded 1:1 co-crystallized [Pt{(p-BrC6F4)NCH=CHNEt2}Cl(py)], 1H and [Pt{(p-BrC6F4)NCH=C(Cl)NEt2}Cl(py)], 1Cl. The former was obtained pure in low yield from the oxidation of 1 with (NH4)2[Ce(NO3)6] in acetone, and the latter was obtained from 1 and H2O2 in CH2Cl2 at near reflux. From the latter reaction under vigorous refluxing [Pt{(p-BrC6F4)NCH=C(Br)NEt2}Cl(py)], 1Br was isolated. In refluxing acetonitrile, oxidation of 1 with H2O2 yielded [Pt{(p-BrC6F4)NCH=C(H0.25Br0.75)NEt2}Cl(py)], 1H0.25Br0.75, in which the alkene is mainly substituted by Br in a dual occupancy. Treatment of 1 with H2O2 and tetrabutylammonium hydroxide in acetone at room temperature formed [Pt{(p-HC6F4)NCH2CH2NEt2}Cl(py)], 2. Oxidation of [Pt{(p-HC6F4)NCH2CH2NEt2}Br(py)], 3 with H2O2 in boiling acetonitrile gave the ligand oxidation product [Pt{(p-HC6F4)NCH=C(Br)NEt2}Br(py)], 3Br. All major products were identified by X-ray crystallography as well as by 1H and 19F NMR spectra. In cases of mixed crystals or dual occupancy compounds, the 19F and 1H NMR spectra showed dissociation into the components in the solution in the same proportions as in isolated crystalline material.

Developing a virus-microRNA interactome using cytoscape.

It is currently difficult to determine the effect of oncogenic viruses on the global function and regulation of pathways within mammalian cells. A thorough understanding of the molecular pathways and individual genes altered by oncogenic viruses is needed for the identification of targets that can be utilised for early diagnosis, prevention, and treatment methods. We detail a logical step-by-step guide to uncover viral-protein-miRNA interactions using publically available datasets and the network building program, Cytoscape. This method may be applied to identify specific pathways that are altered in viral infection, and contribute to the oncogenic transformation of cells. To demonstrate this, we constructed a gene regulatory interactome encompassing Human Papillomavirus Type 16 (HPV16) and its control of specific miRNAs. This approach can be broadly applied to understand and map the regulatory functions of other oncogenic viruses, and determine their role in altering the cellular environment in cancer. Availability and Implementation Cytoscape (Shannon et al. (2003), Smoot et al. (2010)) is freely available at https://cytoscape.org/. •This method allows for the analysis and visualization of large datasets to generate an interactome that integrates key players of molecular biology•This approach may be applied to any oncogenic virus to map its regulatory functions, and its secondary impact on gene regulation via microRNAs.

Systematic differences in electrochemical reduction of the structurally characterized anti-cancer platinum(IV) complexes [Pt{((p-HC6F4)NCH2)2}-(pyridine)2Cl2], [Pt{((p-HC6F4)NCH2)2}(pyridine)2(OH)2], and [Pt{((p-HC6F4)NCH2)2}(pyridine)2(OH)Cl].

The putative platinum(IV) anticancer drugs, [Pt{((R)NCH(2))(2)}(py)(2)XY] (X,Y=Cl, R=p-HC(6)F(4) (1a), C(6)F(5) (1b); X,Y=OH, R=p-HC(6)F(4) (2); X=Cl, Y=OH, R=p-HC(6)F(4) (3), py = pyridine) have been prepared by oxidation of the Pt(II) anticancer drugs [Pt{((R)NCH(2))(2)}(py)(2)] (R=p-HC(6)F(4) (4a) or C(6)F(5) (4b)) with PhICl(2) (1a,b), H(2)O(2) (2) and PhICl(2)/Bu(4)NOH (3). NMR spectroscopy and the X-ray crystal structures of 1b, 2 and 3 show that they have octahedral stereochemistry with the X,Y ligands in the trans-position. The net two electron electrochemical reduction of 1a, 2 and 3 has been studied by voltammetric, spectroelectrochemical and bulk electrolysis techniques in acetonitrile. NMR and other data reveal that reduction of 1a gives pure 4a via the elimination of both axial chloride ligands. In the case of 2, one end of the diamide ligand is protonated and the resulting -NH(p-HC(6)F(4)) group dissociated giving a [Pt{N(p-HC(6)F(4))CH(2)CH(2)NH(p-HC(6)F(4))}] arrangement, one pyridine ligand is lost and a hydroxide ion retained in the coordination sphere. Intriguingly, in the case of reduction of 3, a 50% mixture of the reduction products of pure 1a and 2 is formed. The relative ease of reduction is 1>3>2. Testing of 1a, 2 and 3 against L1210 and L1210(DDP) (DDP = cis-diamine-dichloroplatinum(II)) mouse leukaemia cells shows all to be cytotoxic with IC(50) values of 1.0-3.5 µM. 2 and 3 are active in vivo against AHDJ/PC6 tumor line when delivered in peanut oil despite being hard to reduce electrochemically, and notably are more active than 4a delivered in this medium whilst comparable with 4a delivered in saline/Tween.