PMMA/PC Blends: Effect of Mixing Conditions on Compatibility

In this work the effect of melt mixing condition and of a trans-esterification catalyst on miscibility of poly(methyl methacrylate) (PMMA)/polycarbonate of bisphenol A (PC) blends is studied. In particular, at high temperature chemical reactions between PMMA and PC phases can take place; these strongly change the compatibility in the blend and materials having single T_g can be obtained. FT-IR analyses, coupled with solvent extraction, suggest that a grafting reaction of PC on PMMA is involved. SEC and DSC data are consistent with spectroscopic results, and some decrement of the molar weight distribution (MWD) of PC phase is observed. On the other hand, the presence of a fraction of modified material having higher MWD of starting PMMA is also noticed. The single T_g characteristic of some materials has been confirmed by experimental data of structural relaxation performed by differential scanning calorimetry (DSC). These materials showed optical clarity and the morphological analysis performed by scanning electron microscopy (SEM) confirm the homogeneity of these materials.     

31P NMR studies on the interaction of morpholinyl anthracyclines and related compounds with d(CGTACG)2. Thermodynamic and kinetic parameters

³¹P NMR spectroscopy has been used to study the intercalation of the anthracyclines doxorubicin1, daunorubicin2, 4-demethoxydaunorubicin3, morpholinodoxorubicin4, methoxymorpholinodoxorubicin5 and 9-deoxydaunorubicin6 with the DNA fragment d(CGTACG)₂. The individual phosphate resonances of the oligonucleotide were assigned in the free as well as in the intercalated species. The³¹P chemical shift variations allowed us to identify the intercalation sites, which resulted to be the same for all compoundsi.e. between the terminal CG base-pairs of the helix (two molecules of drugper duplex). The binding constants, the dissociation rate constants and ΔG ^# values have been determined in different conditions of ionic strength and temperature. The kinetic constant (k _off) of the slow step of the anthracycline/duplex intercalation process has been directly measured by NOE exchange techniques. Binding constants depend on the ionic strength and on the self-association process so greatly, that their use to study by NMR anthracycline/DNA interactions is questionable. On the contrary, thek _off are not affected by these phenomena and present an interesting trend for1–6, thus showing that the average lifetime of the drug in the intercalation site appears to be important for determining the cytotoxicity and the antimitotic activity.     

Regiospecific total synthesis of 6-deoxyanthracyclines

Regiospecific approaches to 6-deoxyanthracyclinones, which have resulted in the synthesis of the novel anthracyclines 4-demethoxy-6-deoxydaunorubicin (2) and 6-deoxycarminomycin (3), are reported. The construction of the aglycone 4 is based on the coupling of l,4-dimethoxy-2-lithionaphthalene (10) to 1 formyl-2-carbomethoxy-4-acetylcyclohexane thioketal (11). A new improved regioselective route, which allows the preparation of 6-deoxyanthracyclinones bearing also substituents in ring Das illustrated by 5, 'a based on the coupling of 10a and of l,4,5-trimethoxy-3-lithionaphthalene (10b) to lactone 28.     

Thermal degradation of two classes of block copolymers based on poly(lactic-glycolic acid) and poly(ϵ-caprolactone) or poly(ethylene glycol)

Thermodegradative investigations of two classes of multi-block copolymers containing poly(D,L-lactic-glycolic acid) (PLGA) and either poly(ethylene glycol) (PEG) or poly(ϵ-caprolactone) diol-terminated (PCDT) segments were performed. In particular, the influence of the type and length of the segments as well as of the molar ratio between the D,L-lactic acid (LA) and glycolic acid (GA) residues was investigated at 180°C in air by viscometry, FT-IR analysis and isothermal thermogravimetry. The thermal oxidative degradation of these materials is largely affected by the LA/GA ratio, a higher LA content generally imparting higher stability. The FT-IR analysis suggests that, depending on the composition of the PLGA segments, degradative processes are triggered which can lead to a preferential degradation of the blocks.     

Stereospecific epoxidation of anthracyclinones: a route to 8(r)-methoxydaunomycinone

Stereoselective epoxidation of $\text{1}$, the 7,8-unsaturated derivative of daunomycinone, followed by $\text{trans}$ opening of the epoxide $\text{2}$, afforded 8(R)-methoxydaunomycinone $\text{6a}$; its configuration at C-8 was determined by chemical correlation and PMR studies.     

A Novel LC–MS/MS-Based Method for the Diagnosis of ADA2 Deficiency from Dried Plasma Spot

Adenosine Deaminase 2 Deficiency (DADA2) (OMIM: 607575) is a monogenic, autoinflammatory disease caused by the loss of functional homozygous or heterozygous mutations in the ADA 2 gene (previously CECR1, Cat Eye Syndrome Chromosome Region 1). A timely diagnosis is crucial to start Anti-TNF therapies that are efficacious in controlling the disease. The confirmation of DADA2 is based on DNA sequencing and enzymatic assay. It is, thus, very important to have robust and reliable assays that can be rapidly utilized in specialized laboratories that can centralize samples from other centers. In this paper, we show a novel enzymatic assay based on liquid chromatography-tandem mass spectrometry that allows the accurate determination of the ADA2 enzyme activity starting from very small amounts of plasma spotted on filter paper (dried plasma spot). The method allows significantly distinguishing healthy controls from affected patients and carriers and could be of help in implementing the diagnostic workflow of DADA2.     

Optical properties of Yeast Cytochrome c monolayer on gold: an in situ spectroscopic ellipsometry investigation

The adsorption of Yeast Cytochrome c (YCC) on well defined, flat gold substrates has been studied by Spectroscopic Ellipsometry (SE) in the 245-1000 nm wavelength range. The investigation has been performed in aqueous ambient at room temperature, focusing on monolayer-thick films. In situ δΨ and δΔ difference spectra have shown reproducibly well-defined features related to molecular optical absorptions typical of the so-called heme group. The data have been reproduced quantitatively by a simple isotropic optical model, accounting for the molecular absorption spectrum and film-substrate interface effects. The simulations allowed a reliable estimate of the film thickness and the determination of the position and the shape of the so-called Soret absorption peak that, within the experimental uncertainty, is the same found for molecules in liquid. These findings suggest that YCC preserves its native structure upon adsorption. The same optical model was able to reproduce also ex situ results on rinsed and dried samples, dominated by the spectral features associated to the polypeptide chain that tend to overwhelm the heme absorption features.