Solid-state structure and conformation of (Z)-2-(phenylbenzylidene)-3-quinuclidinone,an intermediate in the synthesis of quinuclidine derivatives

(Z)-2-(2-phenylbenzylidene)-3-quinuclidinone, C₂₀H₁₉NO,M _r =300.47D crystallizes in the monoclinicP2₁/c space group witha = 6.9809(2) Å,b=19.0523(2) Å,c = 11.7733(1) Å,=100.92(2)°,V=1537.5(3) ų,Z=4,D _c = 1.298 g/cm³,D _x =1.29 g/cm³ (flotation). Diffractometric data, using CuK radiation,=1.54178 Å, were collected on plate-like crystals. The structure, solved by direct methods was refined to a final R value of 0.037 for the 2645 observed reflections withF _o >3.0(F _o ). The molecule shows a trans conformation around the double bond. The quinuclidine and the diphenyl moieties present deformations in their geometric and conformational parameters due to the need of releasing intramolecular strains and/or nonbonded interactions.     

Plant-Derived Stilbenoids as DNA-Binding Agents: From Monomers to Dimers

Stilbenoids are natural compounds endowed with several biological activities, including cardioprotection and cancer prevention. Among them, (±)-trans-δ-viniferin, deriving from trans-resveratrol dimerization, was investigated in its ability to target DNA duplex and G-quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy and molecular docking. (±)-trans-δ-Viniferin proved to bind both the minor and major grooves of duplexes, whereas it bound the 3’- and 5’-ends of a G-quadruplex by stacking on the outer quartets, accompanied by rearrangement of flanking residues. Specifically, (±)-trans-δ-viniferin demonstrated higher affinity for the investigated DNA targets than its monomeric counterpart. Additionally, the methoxylated derivatives of (±)-trans-δ-viniferin and trans-resveratrol, i. e. (±)-pterostilbene-trans-dihydrodimer and trans-pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities and stoichiometries with the DNA targets as their parent analogues. All tested compounds were cytotoxic at μM concentration on several cancer cell lines, showing DNA damaging activity consistent with their ability to tightly interact with duplex and G-quadruplex structures.     

Synthetic studies toward bicyclic endoperoxides presenting polar side chains

We developed a synthetic strategy for the preparation of tetrahydrofuro[2,3-c][1,2]dioxane and 2,3,8-trioxa[3,3,1]nonanes bearing polar functional groups at C3 and C4, respectively. The synthetic strategy has been applied to the synthesis of 2,3,8-trioxa[3,3,1]nonanes bearing various amides and amines at C3 useful for structure-activity relationships investigation as antiplasmodial compounds. The synthesis of 1 and the reaction conditions identified for its conversion to amides and amines could pose the basis for the use of this class of endoperoxides also in conjugation with other drugs for polypharmacology approaches.     

The effect of solvent on the morphology of ZnO nanostructure assembly by dielectrophoresis and its device applications

Different zinc oxide nanostructured morphologies were grown on photolithographically patterned silicon/silicon dioxide substrates by dielectrophoresis technique using different solvents, such as water and ethanol, obtaining rod-like and net-like nanostructures, respectively. The formation of continuous nanostructures was confirmed by scanning electron microscopic, atomic force microscopic images, and electrical characterizations. The rod-like zinc oxide nanostructures were observed in the 10 μm gap between the fingers in the pattern, whereas net-like nanostructures were formed independently of microgap. A qualitative study about the mechanism for the assembly of zinc oxide continuous nanostructures was presented. Devices were electrically characterized, at room temperature, in controlled environment to measure the conductance behavior in ultraviolet and humidity environment. Devices based on zinc oxide nanostructures grown in ethanol medium show better responses under both ultraviolet and humidity, because of the net-like structure with high surface-to-volume ratio.     

A cardinality-constrained robust model for the assignment problem in Home Care services

Home Care includes medical, paramedical and social services which are delivered to patients at their domicile rather than in hospital. Managing human and material resources in Home Care services is a difficult task, as the provider has to deal with peculiar constraints (e.g., the continuity of care, which imposes that a patient is always cared for by the same nurse) and to manage the high variability of patients’ demands. One of the main issues encountered in planning Home Care services under continuity of care requirement is the nurse-to-patient assignment. Despite the importance of this topic, the problem is only marginally addressed in the literature, where continuity of care is usually treated as a soft-constraint rather than as a hard one. Uncertainty is another relevant feature of nurse-to-patient assignment problem, and it is usually managed adopting stochastic programming or analytical policies. However, both these approaches proved to be limited, even if they improve the quality of the assignments upon those actually provided in practice. In this paper, we develop a cardinality-constrained robust assignment model, which allows exploiting the potentialities of a mathematical programming model without the necessity of generating scenarios. The developed model is tested on real-life instances related to a relevant Home Care provider operating in Italy, in order to evaluate its capability of reducing the costs related to nurses’ overtimes.     

Breaking the Dogma of the Metal‐Coordinating Carboxylate Group in Integrin Ligands: Introducing Hydroxamic Acids to the MIDAS To Tune Potency and Selectivity

A suitable substitute : All integrin receptors bind their ligands, which contain an aspartate residue, in the metal‐ion‐ dependent adhesion site (MIDAS). So far all attempts to replace the carboxyl group of aspartate with other, pharmacologically favorable isosteric groups have failed. Now it has been shown that a hydroxamic acid group can replace the carboxyl group; the resulting ligand retains its high binding activity. The picture shows one such ligand in the binding site of αvβ3.