Modulation of drug activation profiles through carboxylate ligand modification in cytotoxic trans-platinum planar amine compounds

Transplatinum planaramine (TPA) compounds possessing carboxylate ligands in the trans position have been shown to be potential antitumor drugs in a variety of cell types, including cisplatin and oxaliplatin-resistant cell lines. In this work, we ask whether the nature and stability of the carboxylate ligand can be tuned in an attempt to manipulate the extent of serum protein binding; and consequently influence cytotoxicity, cellular drug accumulation and DNA adduct formation. Monitoring the interactions of selected TPAs with N-acetyl-methionine (NAM) by (1)H and (195)Pt NMR spectroscopy shows significant differences in the rate of sulfur binding. TPA-containing acetate ligands show a much lower sulfur binding rate than those possessing formate leaving groups. The same trend was seen when acetate and formate TPA compounds were incubated with human serum albumin and the reaction monitored for 24 h. To understand whether these results could be translated into a cellular medium, MTT cytotoxicity assays were conducted for each compound, before and after incubation with whole serum. Both the formate and acetate compounds, t-[Pt(4-pic)NH(3)(OFm)(2)] and t-[Pt(4-pic)NH(3)(OAc)(2)], showed minimal losses in cytotoxic efficacy and outperformed cisplatin after pre-incubation with serum. The same trends were seen when monitoring the effects of protein binding on cellular uptake and DNA platination. The rate of protein binding/drug deactivation was shown to be directly related to the stability of the leaving group (OAc(-) > OFm(-) > Cl(-)). Thus, our results suggest that utilization of the 'carboxylate strategy' substantially enhances the cellular efficacy of TPA compounds over cisplatin by allowing for an optimal balance between cytotoxic and metabolic efficiency.     

Nanoemulsions for the Determination of the Antioxidant Capacity of Oils by an Electrochemical Method

The paper describes a rapid and simple method for the evaluation of the antioxidant capacity in oil in water nanoemulsion. This procedure does not require extensive sample treatment and, most important, does not use any organic solvent for dissolution of the fatty matrix. The nanoemulsions were directly injected in a flow injection (FI) system with an electrochemical detector equipped with a glassy carbon working electrode operating amperometrically at a potential of +0.8 V (vs. Ag/AgCl). Results obtained were compared with those obtained by the Oxygen Radical Absorbance Capacity (ORAC) assay.     

The effect of pressure on CD spectra of the chiral octahedral transition metal complexes Λ-, Δ- and (Λ,Δ){Cr[(+)(S)(S)Mebdtp]3}

Abstract

The effect of pressure on circular dichroism (CD) spectra of the octahedral chiral Λ-, Δ- and (Λ, Δ)trisO, O'-bis[(+)(S)-2-methylbutyl]dithiophosphate Cr(III) complexes, have been studied in the pressure range 0-2.5GPa. Results on polycrystalline samples dispersed in nujol show a pressure-induced A to A inversion of configuration at the metal center above 1.2 GPa. The high pressure stability of the A-form is explained in terms of most favoured crystal packing among different ligand conformations of the chiral complex.     

On maximum likelihood estimation of a Pareto mixture

In this paper we deal with maximum likelihood estimation (MLE) of the parameters of a Pareto mixture. Standard MLE procedures are difficult to apply in this setup, because the distributions of the observations do not have common support. We study the properties of the estimators under different hypotheses; in particular, we show that, when all the parameters are unknown, the estimators can be found maximizing the profile likelihood function. Then we turn to the computational aspects of the problem, and develop three alternative procedures: an EM-type algorithm, a Simulated Annealing and an algorithm based on Cross-Entropy minimization. The work is motivated by an application in the operational risk measurement field: we fit a Pareto mixture to operational losses recorded by a bank in two different business lines. Under the assumption that each population follows a Pareto distribution, the appropriate model is a mixture of Pareto distributions where all the parameters have to be estimated.     

F-Divergences and Cost Function Locality in Generative Modelling with Quantum Circuits

Generative modelling is an important unsupervised task in machine learning. In this work, we study a hybrid quantum-classical approach to this task, based on the use of a quantum circuit born machine. In particular, we consider training a quantum circuit born machine using f-divergences. We first discuss the adversarial framework for generative modelling, which enables the estimation of any f-divergence in the near term. Based on this capability, we introduce two heuristics which demonstrably improve the training of the born machine. The first is based on f-divergence switching during training. The second introduces locality to the divergence, a strategy which has proved important in similar applications in terms of mitigating barren plateaus. Finally, we discuss the long-term implications of quantum devices for computing f-divergences, including algorithms which provide quadratic speedups to their estimation. In particular, we generalise existing algorithms for estimating the Kullback–Leibler divergence and the total variation distance to obtain a fault-tolerant quantum algorithm for estimating another f-divergence, namely, the Pearson divergence.     

Solid-state Reactions of Mercury with Pure Noble Metals Part 2. Mercury–iridium system

Thermogravimetry, cyclic voltammetry and other analytical techniques were used to study the reactions of mercury with pure iridium. The results allowed to suggest when subjected to heat or anodic stripping voltammetry an electrodeposited mercury film reacts with Ir substrate and at least three mass loss steps and three peaks appear in the mercury desorption process. The first two were attributed to Hg(0)species removal like a mercury bulk and a mercury monolayer. The last can be ascribed to the mercury removal from a solid solution with iridium. This revised version was published online in July 2006 with corrections to the Cover Date.     

Molecular interactions in the poly(vinyl chloride)-di-n-butylphthalate system determined by infrared spectroscopy

Infrared studies of the poly(vinyl chloride) (PVC)/di-n-butylphthalate (DBP) system are reported. Spectra of DBP in different solvents seem to be indicative of the ability of DBP to interact with PVC chains in the same way as with polyesters and of competitive interactions between DBP molecules and DBP with PVC. Plots of the width at half-height of the carbonyl stretching vibration, measured at 25 and at ?180°C, as a function of composition, show a sudden change of slope at about 60% PVC concentration by weight, indicating that above this polymer composition interaction between DBP and PVC dominates that between DBP molecules. This change corresponds to a “singularity” observed in the dependence of the glass transition temperature on composition.     

Determination of 3'-deamino-3'-[2(S)-methoxy-4-morpholinyl]doxorubicin, a new morpholinyl anthracycline, in plasma by high-performance liquid chromatography with fluorescence detection.

A sensitive and selective high-performance liquid chromatographic method for the determination of 3'-deamino-3'-[2(S)-methoxy-4-morpholinyl]doxorubicin and its possible 13-dihydro metabolite in human plasma has been developed. The plasma samples were buffered and the drugs and internal standard (doxorubicin) were extracted with diethyl ether-n-butanol, back-extracted into 0.3 M phosphoric acid, then analysed by reversed-phase liquid chromatography. Quantitation was achieved by fluorescence detection of the eluate. The linearity, precision and accuracy of the method were evaluated. No interference from blank plasma sample was observed. The suitability of the method for in vivo samples was checked by analysis of plasma samples drawn from female rats that had received repeated intravenous doses of the test compound.