Modified Nucleosides,Nucleotides and Nucleic Acids via Click Azide-Alkyne Cycloaddition for Pharmacological Applications

The click azide = alkyne 1,3-dipolar cycloaddition (click chemistry) has become the approach of choice for bioconjugations in medicinal chemistry, providing facile reaction conditions amenable to both small and biological molecules. Many nucleoside analogs are known for their marked impact in cancer therapy and for the treatment of virus diseases and new targeted oligonucleotides have been developed for different purposes. The click chemistry allowing the tolerated union between units with a wide diversity of functional groups represents a robust means of designing new hybrid compounds with an extraordinary diversity of applications. This review provides an overview of the most recent works related to the use of click chemistry methodology in the field of nucleosides, nucleotides and nucleic acids for pharmacological applications.     

Unusual behavior of the aqueous solutions of gemini bispyridinium surfactants: apparent and partial molar enthalpies of the dimethanesulfonates

Apparent and partial molar enthalpies at 298 K of the aqueous solutions of cationic gemini surfactants 1,1'-didodecyl-2,2'-dimethylenebispyridinium dimethanesulfonate (12-Py(2)-2-(2)Py-12 MS); 1,1'-didodecyl-2,2'-trimethylenebispyridinium dimethanesulfonate (12-Py(2)-3-(2)Py-12 MS); 1,1'-didodecyl-2,2'-tetramethylenebispyridinium dimethanesulfonate (12-Py(2)-4-(2)Py-12 MS); 1,1'-didodecyl-2,2'-octamethylenebispyridinium dimethanesulfonate (12-Py(2)-8-(2)Py-12 MS); 1,1'-didodecyl-2,2'-dodecamethylenebispyridinium dimethanesulfonate (12-Py(2)-12-(2)Py-12 MS) were measured as a function of concentration and are here reported for the first time. They show a very peculiar behavior as a function of the spacer length, not allowing for the determination of a -CH 2- group contribution when this group is added to the spacer. The curve of the compound with a four-carbon-atom-long spacer lies between those of the compound with a spacer of 2 and 3 carbon atoms, instead of that below the latter, as expected. This surprising behavior, never found before in the literature and different from that found for the more popular m- s- m-type bisquaternary ammonium gemini surfactants, could be explained by a conformation change of the molecule, caused by stacking interactions between the two pyridinium rings, mediated by the counterion and appearing at an optimum length of the spacer. The hypothesis is also supported by the data obtained from the surface tension vs log c curves, showing that A min, the minimum area taken at the air-water interface by the molecule, is significantly lower for 12-Py(2)-4-(2)Py-12 MS than that of the other compounds of the same homologous series, and that the same compound has a greater tendency to form micelles instead of adsorbing at the air/water interface. The evaluation of the micellization enthalpies, by means of a pseudophase transition model, agrees with the exposed trends. These results confirm the great crop of information that can be derived from the study of the solution thermodynamics of aggregate systems and in particular from the curves of apparent and molar enthalpies vs concentration.     

Amplified fluorescence response of chemosensors grafted onto silica nanoparticles

In conventional fluorescent chemosensors, the recognition of the target by the receptor unit affects the fluorescence properties of a single covalently coupled fluorescent moiety. Here we show for the first time that when a suitable TSQ derivative is densely grafted onto the surface of preformed silica nanoparticles electronic interactions between the individual chemosensor units enable the free units to recognize the state of the surrounding complexed ones. As a result, the fluorescence transduction is not limited to the local site where binding occurs, but it involves a wider region of the fluorophore network that is able to transfer its excitation energy to the complexed units. Such behavior leads to an amplification of the fluorescence signal. What we report here is the first example of amplification in the case an off-on chemosensor due to its organization onto the surface of silica nanoparticles. We also describe a simple general model to approach amplification in multifluorophoric systems based on the localization of the excited states, which is valid for assemblies such as the supramolecular ones where molecular interactions are weak and do not significantly perturb the individual electronic states. The introduction of an amplification factor f in particular allows for a simple quantitative estimation of the amplification effects.     

NMR studies on the novel heterobimetallic complexes [M(dppm)(Ph(2)PCH(2)PPh(2)PPPP) {Pt(PPh3)2}]OTf (M = Rh, Ir) derived from the stepwise activation of white phosphorus

The solution structures of the novel heterobimetallic complexes [Ir(dppm)(Ph(2)PCH(2)PPh(2)PPPP){Pt(PPh(3))2}]OTf and [Rh(dppm)(Ph(2)PCH(2)PPh(2)PPPP){Pt(PPh(3))(2)}]OTf derived from the reaction of Rh and Ir--P(5) precursors with [Pt(C2H4)(PPh3)2] have been unambiguously assigned on the basis of 1H NMR and 31P{1H} NMR data. The results are in agreement with the regio-selective insertion of the {Pt(PPh3)2} moiety resulting in a new pentaphosphorus topology which agrees with the formal formation of a unique phosphonium(+)-tetraphosphabutadienide(2-) ligand.     

Unusual cycloartane glycosides from Astragalus eremophilus

Eleven new cycloartane-type glycosides, named eremophilosides A-K have been isolated from the aerial parts of Astragalus eremophilus. Their structures were elucidated by MS and NMR experiments and the relative configurational analysis of eremophilosides C and D was carried out on the basis of the recently reported J-based method. Additionally, the cytotoxic activity of these compounds in MCF7 and U937 cell lines was evaluated. All tested compounds, except eremophilosides B, C, and J were found to inhibit slightly the growth (controlling the cell cycle) and/or to induce death processes in U937 cell line, the most susceptible cell line. Eremophilosides A and K resulted the most effective to induce cell death, the first by necrosis while the latter by apoptosis.     

Towards Green Reductions in Bio-Derived Solvents

The hydrogenation processes, and all the reactions that formally add two hydrogen atoms to an unsaturated bond, are among the most used transformations in the manufacture of bulk and fine chemicals. Although their potential as powerful tool for the sustainable synthesis of organic compounds, hydrogenations, and more generally the reductions, have been typically carried out in volatile organic solvents deriving from petroleum; indeed, all studies and fascinating advances related to the catalysts’ activity or the reducing agents’ reactivity have been limited to such volatile and often toxic reaction media. In this review, recent advances in the reducing methodologies with an improved degree of sustainability have been described. In particular, a series of examples have been reported to highlight the chance to reduce an organic compound by using a benign solvent deriving from renewable sources, without waiving to the process efficiency and selectivity. Some important key points of green chemistry, such as the easiness of catalyst recovery or the simplicity of product isolation, have been considered in the choice of the described studies.     

On the wave-cancelling nature of boundary layer flow control

This work deals with the feedforward active control of Tollmien–Schlichting instability waves over incompressible 2D and 3D boundary layers. Through an extensive numerical study, two strategies are evaluated; the optimal linear–quadratic–Gaussian (LQG) controller, designed using the Eigensystem realization algorithm, is compared to a wave-cancellation scheme, which is obtained using the direct inversion of frequency-domain transfer functions of the system. For the evaluated cases, it is shown that LQG leads to a similar control law and presents a comparable performance to the simpler, wave-cancellation scheme, indicating that the former acts via a destructive interference of the incoming wavepacket downstream of actuation. The results allow further insight into the physics behind flow control of convectively unstable flows permitting, for instance, the optimization of the transverse position for actuation. Using concepts of linear stability theory and the derived transfer function, a more efficient actuation for flow control is chosen, leading to similar attenuation of Tollmien–Schlichting waves with only about 10% of the actuation power in the baseline case.     

Oxazoline functionalization of polyethylenes and their blends with polyamides and polyesters

The compatibilization of blends of polyamide‐6 (PA6) with linear low density polyethylene (LLDPE) and of poly(ethylene terephthalate) (PET) with high density polyethylene (HDPE), by functionalization of the polyethylenes with oxazoline groups was investigated. Chemical modification of LLDPE and HDPE was carried out by melt free radical grafting with ricinoloxazoline maleinate. Blends preparation was made either with a two‐steps procedure comprising functionalization and blending, and in a single step in which the chemical modification of polyethylene with the oxazoline monomer was realized in situ, during blending. The characterization of the products was carried out by FTIR spectroscopy and scanning electron microscopy (SEM). The rheological and mechanical properties of the blends were also investigated. The results show that functionalization of the polyethylenes can be achieved by melt blending with ricinoloxazoline maleinate even in the absence of free radical initiators. The compatibilization of the blends enhances the dispersion of the minor phase significantly, increases the melt viscosity, and improves the mechanical properties. The one‐step preparation of the compatibilized blends was also found to be effective, and is thought to be even more promising in view of commercial application.     

Torsion and homogeneity on contact metric three-manifolds

We show that a three-dimensional contact metric manifold is locally homogeneous if and only if it is ball-homogeneous and satisfies the condition ∇_ξτ=2aτϕ, with a constant. Then, we relate the condition ∇_ξτ=0 with the existence of taut contact circles on a compact three-dimensional contact metric manifold. Entrata in Redazione il 20 gennaio 1999. Supported by funds of the University of Lecce and the M.U.R.S.T. Work made within the program of G.N.S.A.G.A.-C.N.R.