Conjugation of testosterone modifies the interaction of mono-functional cationic platinum(II) complexes with DNA, causing significant alterations to the DNA helix

Previously a range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of enhancing cellular delivery, and which have shown increased cytotoxic activity compared with non-steroidal compounds (M. J. Hannon et al., Dalton Trans., 2010, DOI: 10.1039/c0dt00838a). To further study this, the complexes have been assessed for their ability to bind to and alter the structure of DNA. All platinum(II) complexes studied herein bind to model nucleo-bases and DNA, but to our surprise, testosterone-based complexes caused the DNA helix to undergo significant unwinding and bending, whereas non-steroidal control complexes caused minimal structural alterations. These effects are similar to those cisplatin induces on DNA structure despite the fact that these compounds produce a monofunctional lesion. This ability attributed to interactions between the DNA helix and bulky steroidal skeleton of testosterone, coupled with the enhanced cellular delivery induced by the steroid make the steroid approach an exciting way to explore non-conventional platinum drug delivery.     

In Vitro Evaluation of Non‐Protein Adsorbing Breast Cancer Theranostics Based on 19F‐Polymer Containing Nanoparticles

Eight fluorinated nanoparticles (NPs) are synthesized, loaded with doxorubicin (DOX), and evaluated as theranostic delivery platforms to breast cancer cells. The multifunctional NPs are formed by self‐assembly of either linear or star‐shaped amphiphilic block copolymers, with fluorinated segments incorporated in the hydrophilic corona of the carrier. The sizes of the NPs confirm that small circular NPs are formed. The release kinetics data of the particles reveals clear hydrophobic core dependence, with longer sustained release from particles with larger hydrophobic cores, suggesting that the DOX release from these carriers can be tailored. Viability assays and flow cytometry evaluation of the ratios of apoptosis/necrosis indicate that the materials are non‐toxic to breast cancer cells before DOX loading; however, they are very efficient, similar to free DOX, at killing cancer cells after drug encapsulation. Both flow cytometry and confocal microscopy confirm the cellular uptake of NPs and DOX‐NPs into breast cancer cells, and in vitro ¹⁹F‐MRI measurement shows that the fluorinated NPs have strong imaging signals, qualifying them as a potential in vivo contrast agent for ¹⁹F‐MRI.     

A simple characterization of tightness for convex solid sets of positive random variables

We show that for a convex solid set of positive random variables to be tight, or equivalently bounded in probability, it is necessary and sufficient to be is radially bounded, i.e. that every ray passing through one of its elements eventually leaves the set. The result is motivated by problems arising in mathematical finance.     

A dichotomy in the enantioselective oxidation of aryl benzyl sulfides: A combined experimental and computational work

Pentafluorobenzyl pentafluorophenyl sulfide is oxidised with moderate e.e. value and a low yield by the usually highly successful oxidation protocol based upon tert-butyl hydroperoxide (TBHP) in the presence of a titanium/hydrobenzoin complex. This disappointing result resisted until the present work, in which the switch of the oxidation agent (from TBHP to cumene hydroperoxide), suggested by our previous computations, yielded the enantiopure sulfoxide. This valuable chiral compound was obtained in good yields (76%) without resorting to a chromatographic separation. DFT computations uncovered that this favourable reactivity was originated by a stabilizing π?π?stacking between the phenyl group of the oxidant and the pentafluorophenyl moiety of the substrate.     

Concerning the reactivity of dioxiranes. Observations from experiments and theory

The challenging hypothesis of a "biphilic" (i.e., electrophilic vs nucleophilic) character for dioxirane reactivity, which envisages that electron-poor alkenes are attacked by dioxiranes in a nucleophilic fashion, could not be sustained experimentally. Rate data, which estimate Hammett "rho" values for the epoxidation of 3- or 4-substituted cinnamonitriles X x Ph-CH=CH-CN, unequivocally allow one to establish that dioxiranes epoxidize electrophilically even alkenes carrying electron-withdrawing groups. The greater propensity of methyl(trifluoromethyl)dioxirane TFDO (1b) to act as an electrophilic oxidant with respect to dimethyldioxirane DDO (1a) parallels the cathode reduction potentials for the two dioxiranes, as measured by cyclic voltammetry. A simple FMO approach for alkene epoxidation is helpful to conceive a likely rationale for the greater oxidizing power of TFDO as compared to DDO.     

Gas chromatography-mass spectrometry characterization of the varnish and glue of an ancient 18th century double bass

A GC-MS investigation is conducted on the double bass "Panormus", property of Conservatorio di Musica "Vincenzo Bellini" in Palermo. The most important components of the varnish (fatty acids) and of the glue (proteinaceous amino acids), with which the musical instrument was treated in the past, are determined. The analyses are carried out by prior derivatization of fatty acids by acidic methanol and of amino acids by acidic methanol and trifluoroacetic anhydride (TFAA). Analytes identification is achieved by direct comparison with several reference materials and the use of a digitized library.     

Characterisation by liquid chromatography-electrospray tandem mass spectrometry of anthocyanins in extracts of Myrtus communis L. berries used for the preparation of myrtle liqueur

Anthocyanins in extracts of berries of Myrtus communis, prepared following a typical Sardinia myrtle liqueur recipe, were identified and quantified by HPLC coupled with electrospray/tandem mass spectrometry using, respectively, an ion trap and a triple quadrupole mass analyser. The fragmentation patterns of the anthocyanidins were dependent on the MS technique employed, and differed considerably from those previously reported. The anthocyanin profile of five anthocyanin glucosides and four anthocyanin arabinosides, the latter not previously identified in this specie, was specific for myrtle berry extracts. The quantitative compositions of extracts of myrtle berries derived from different geographical areas in Italy were compared.     

DNA Binding Studies and Cytotoxicity of a Dinuclear Pt(II) Diazapyrenium-Based Metallo-supramolecular Rectangular Box

The interaction with native DNA of a 2,7-diazapyrenium-based ligand 1 and its Pt(II) rectangular metallacycle 2 is explored through circular and linear dichroism and fluorescence spectroscopies. The metal-free ligand 1 binds through intercalation, with a binding constant of approximately 5×10(5) M(-1) , whereas the metallacycle 2 binds and bends the DNA with a binding constant of 7×10(6) M(-1) . PCR assays show that metallo-supramolecular box 2 interferes with DNA transactions in vitro whereas the intercalator 1 does not. The metallacycle is active against four human cancer cell lines, with IC(50) values ranging between 3.1 and 19.2?μM and shows similar levels of efficacy, but a different spectrum of activity, to cisplatin.     

The quest for new mild and selective modifications of natural structures: laccase-catalysed oxidation of ergot alkaloids leads to unexpected stereoselective C-4 hydroxylation

Laccase-catalysed oxidation of ergot alkaloids in the absence of chemical mediators allowed the unexpected isolation of the mono-hydroxylated derivatives of compounds 2-7. Structure determination by NMR techniques clearly indicated that hydroxylation took place at the C-4 benzylic position. Quite notably, the proposed protocol allowed, for the first time, functionalisation at the C-4 position of the ergoline skeleton. Depending on the absence or on the presence of a C-10 α-methoxy substituent, hydroxylation was either stereoselective (furnishing C-4α OH derivatives) or gave rise to a C-4α/C-4β OH mixture in a 2:1 ratio, respectively.     

Local Unit Roots and Global Stationarity of TARMA Models

In this paper the (strict and weak) stationarity of threshold autoregressive moving average models is discussed. After examining the strict stationarity, mainly based on the random coefficient autoregressive representation of the model, we provide sufficient conditions for its weak stationarity that allow to obtain a wider stationarity region with respect to some previous results given in the literature. These conditions are discussed to distinguish between global and local stationarity, whose relation has been considered in detail. The threshold process has been further evaluated to face the problem related to the so called existence of a threshold structure in the data generating process that is strictly related to the stationarity and has significant relevance when the parameters of the model have to be estimated.