Coordination features of ditopic oxa-azamacrocycles toward Ni(II) and Co(II). Dioxygen uptake by their dinuclear Co(II) complexes

The coordination properties of the ditopic oxa-aza macrocycles L1-L3 toward Ni(II) and Co(II) have been investigated by means of potentiometric and UV-vis spectrophotometric measurements. L1-L3 contain two triamine and/or tetraamine chains separated by two dioxa chains and form both mono- and dinuclear complexes in aqueous solution. In the [ML]2+ complexes, the metal ion is coordinated by one of the two polyamine moieties, while the other does not participate in the coordination. In the dinuclear complexes each metal ion is coordinated, almost independently, to a single polyamine moiety. Under aerobic conditions the binuclear Co(II) complexes of the ligands L1-L3 are able to bind molecular oxygen, with a bridging coordination of O2 between the two metals.     

Molecular structure of η5-[Pd(CH2CHCMeCH2CH2CHCMe2)-(MeCN)](BF4), A cationic π-allylpalladium complex with an almost in-plane intramolecular olefin coordination

The complex η⁵-[Pd(CH₂CHCMeCH₂CH₂CHCMe₂)-(MeCN)](BF₄), a model for a key intermediate in diene polymerization, crystallizes in the monoclinic space group P2₁/c, a 11.362(2), b 13.655(4), c 10.046(2) Å, β 134.80(1)°. The structure was solved by conventional Patterson and Fourier syntheses and refined by full matrix least squares techniques to a final discrepancy index R = 0.058 for 1710 independent reflections. The palladium and nitrogen atoms, the center of gravity of the allyl triangle, and the middle point of the coordinated double bond are coplanar. The side chain of the organic moiety is located in the syn position with respect to the η³-allyl group. The orientation of the coordinated double bond, which forms an angle of 26° with the coordination plane, is novel for palladium(II) complexes.     

New tetracyclic compounds containing the β-carboline moiety

Oxidation of 1-methyl-3-methoxycarbonyl-β-carboline with selenium dioxide gave 1-formyl-3-methoxycarbonyl-β-carboline II . Compound II reacted with acetic or propionic anhydride to give easily the 2-methoxycarbonyl-6H-indolo[3,2,1-d,e][1,5]naphthyridin-6-ones III ; reaction of II with some primary amines led to the formation of the Schiff bases IV , which were reduced to the 1-aminomethyl-3-methoxycarbonyl-β-carbolines V with sodium borohydride. Cyclization of V with aqueous formaldehyde led to the pyrimido[3,4,5-lm]pyrido[3,4-b]indoles VI . Analogously, cyclization with formaldehyde, acetone or 1,1′-carbonyldiimidazole of the 3-aminomethyl- 1,2,3,4-tetrahydro-β-carbolines VIII , obtained by reaction of 3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline VII with amines followed by lithium aluminium hydride reduction of the resulting amides, gave the imidazo[1′,5′-1,6]pyrido[3,4-b]indoles IX and X . Dieckmann cyclization of 3-methoxycarbonyl-2-[(3-ethoxycarbonyl)-1-propyl]-1,2,3,4-tetrahydro-β-carboline XI led to a 1:1 mixture of the β-ketoesters XII and XIII , which underwent deethoxycarbonylation to 5,6,8,9,10,11,11a,12-octahydroindolo[3,2-b]quinolizin-11-one XIV . Finally, the polyphosphoric acid (or esters) catalyzed cyclization of the N-acyl derivatives XVI of 3-hydrazinocarbonyl-β-carboline XV led smoothly to the 3-(1,3,4-oxadiazol-2-yl)-β-carbolines XVII .     

Synthesis of [1,2,4]triazoloquinazoline and [1,2,4]-triazolo-1,4-benzodiazepine derivatives

Some [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-ones 7 , the corresponding isomers [1,2,4]triazolo[4,3-c]quinazo-lin-5(6H)-ones and the 5-amino derivatives 8, 9 and 11 have been synthesized starting from the acylamidrazones 5 . The preparation of 5H-[1,2,4]triazolo[1,5-d]-1,4-benzodiazepin-6(7H)-ones 15 and of 5-cyclicaminomethyl-[1,2,4]triazolo[1,5-c]quinazolines 16 and 17 is also reported.     

Inhibition of Interleukin-6-Induced Matrix Metalloproteinase-2 Expression and Invasive Ability of Lemon Peel Polyphenol Extract in Human Primary Colon Cancer Cells

Among matrix metalloproteinases (MMPs), MMP-9/2 are key enzymes involved in the proteolysis of extracellular matrices in the inflammatory process and in cancer. Since MMP-9/2 expression levels, activity, and secretion is up-regulated during inflammation in response to pro-inflammatory cytokines, such as interleukin-6 (IL-6), many efforts have been devoted to identifying factors that could inhibit the IL-6-induced MMP-9/2 expression. Up to now, several reports indicated that polyphenols from fruits and vegetables are among the major components of health promotion for their antioxidant properties and also for their anti-inflammatory and anti-cancer agents. Among plant derived polyphenols, lemon (Citrus limon) peel extract (LPE) shows anti-cancer properties in various cancer types. In our previous work, we demonstrated that LPE can reduce IL-6-induced migration/invasiveness and MMP-9/2 up-regulation in some gastric cancer cell lines. This study aims to exploit the anti-cancer properties of LPE using an in vitro system model of inflammation, consisting of IL-6-exposed human primary colon cancer cells. We first analyzed the effect of LPE on IL-6-induced cell migration and invasiveness by wound healing and Boyden chamber assay, respectively. The MMP-2 mRNA expression levels and gelatinolytic activity in the cell culture media were determined by q-PCR analysis and gelatin zymography, respectively, and finally, the effects of LPE on IL-6-induced JAK2/STAT3 signaling pathways have been investigated by Western blotting analysis. Our results show that LPE is able to inhibit the IL-6-dependent cell migration and invasiveness associated with the up-regulation of MMP-2 expression levels and that these effects are correlated to the STAT3 phosphorylation in human primary T88 and T93 colon cancer cells.     

Synthesis of New 3′-Deoxyribonucleosides Employing the Acid-Catalyzed Fusion Method

Coupling of 4,6-dichloro-1H-imidazo[4,5-c]pyridine (2,6-dichloro-3-deaza-9H-purine) ( 1 ) with 1,2-O-di-acetyl-5-O-benzoyl-3-deoxy-β-D -ribofuranose ( 2 ), employing the acid-catalyzed fusion method, is reported (Scheme 1). The condensation reaction was regioselective and gave the three N¹-glycosylation products 3 – 5 , whereas no N³-nucleosides were detected. Treatment of 3 – 5 with methanolic ammonia afforded the corresponding deprotected nucleosides 6 – 8 . Compounds 6 and 7 were assigned the structure of the β-D - and α-D -anomeric N¹-(3′-deoxyribo)nucleosides, respectively. The third derivative 8 proved to be the α-D -anomer of a 3′-deoxyarabinonucleoside deriving from epimerization at C(2) of the sugar. The 2-chloro- and N⁶-substituted derivatives 9 , 11 , and 13 of 3′-deoxy-3-deazaadenosine ( 10 ) and of its α-D -anomer 12 can be obtained from these versatile synthons (Schemes 2 and 3).     

Investigating the underlying Markovian dynamics of ECG rhythms by information flow

Several approaches have been recently introduced to characterize and classify signals based on the underlying hidden dynamic. Markov models represent a natural choice for describing the dynamic evolution of a signal. However, the right selection of the memory of the process is essential for the correctness of the Markov model and a mathematically well-founded criterion is necessary to establish when the Markov model is a good approximation of the process. We review an information-theoretic based method that introduces the concept of information flow as such a criterion. The information flow describes the progressive loss of statistical dependence between the entire past and a point ahead in the future, which is indirectly related with the hidden dynamic of the signal. An approximated measure of information flow can be used as the discriminating statistic for selecting the optimal Markov model in terms of the shortest memory required. This technique is applied to investigate the underlying Markovian dynamics of the heart rate variability (HRV) for subjects in different patho-physiological conditions. Markov models with different memories seem to be associated with the circadian cycle and with different pathologies. Furthermore, the precursor character of the information flow for predicting ventricular tachycardia (VT) is discussed.