Silica grafted polyethylenimine as heterogeneous catalyst for condensation reactions

Primary amine groups were attached to a silica surface by using α,ω-diamines derivatives and (3-glycidyloxypropyl)-trimethoxysilane activation. The same activation was used to graft polyethylenimine, which also contains secondary and tertiary amine groups. These silica aminated structures were tested as heterogeneous catalysts in nitroaldol condensation with nitromethane, the derivative with the polyethylenimine moiety being the more active catalyst. This catalyst also showed efficiency in the Knoevenagel condensation of benzaldehydes with ethyl cyanoacetate under very mild reaction conditions and showed much the same efficiency when used in consecutive reaction runs. A reaction mechanism with participation of the several amine groups of the catalysts is discussed

Diclofenac-β-cyclodextrin for colonic drug targeting: in vivo performance in rats

The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral administration, using sulfapyridine (a metabolite of sulfasalazine) as a marker of colonic absorption. Two groups of rats were used; the test rats received a suspension containing the two prodrugs, diclofenac-β-cyclodextrin and sulfasalazine, while the control rats received a suspension containing the corresponding free drugs, sodium diclofenac and sulfapyridine. The rats were fasted overnight with free access to water before and throughout the first 12 hours of the study. Blood was collected from the tail vein at pre-determined time points and the plasma analyzed for the concentrations of diclofenac and sulfapyridine. Following the oral administration of the two prodrugs, a more extended absorption profile was observed and Cmax was achieved 10 hours post-dose, in contrast to rapid absorption of the free drugs (tmax of diclofenac being 1.3 h, and that of sulfapyridine being 2.1 h) . In addition to a later tmax, conjugation of diclofenac to β-cyclodextrin also resulted in a reduced Cmax and a reduced AUC. The same tmax for diclofenac-β-cyclodextrin as for sulfasalazine confirms the colonic metabolism of diclofenac-β-cyclodextrin. This study shows the potential of this new cyclodextrin-based prodrug to target and release diclofenac specifically in the colon following oral administration

Influence of feeding regimens on rat gut fluids and colonic metabolism of diclofenac-β-cyclodextrin

Feeding states may affect the performance of colonic prodrugs. The aim is to investigate the influence of feeding regimen in Wistar rats on: (i) distribution and pH contents along the gut and (ii) metabolism of two colonic prodrugs, diclofenac-β-cyclodextrin and a commercially available control, sulfasalazine, within the caecal and colonic contents. Male Wistar rats were subject to four different feeding regimens, the gut contents characterized (mass and pH) and the metabolism of prodrugs investigated. The feeding regimen affects gut contents (mass and pH), more specifically in the stomach and lower intestine, and affects the rate of metabolism of diclofenac-β-cyclodextrin, but not that of sulfasalazine. The latter's degradation is much faster than that of diclofenac-β-cyclodextrin while the metabolism of both prodrugs is faster in colonic (versus caecal) contents. Fasting results in most rapid degradation of diclofenac-β-cyclodextrin, possibly due to lack of competition (absence of food) for microbial enzymatic activity

Reactivity of a-Oxophosphonium Ylides: A Contribution to the Mechanistics

Ylides 1f and 1g react with chlorine, with bromine and with N-chlorosuccinimide in the presence of a range of nucleophiles. The 2,3-disubstitutedbutenedioates obtained in this way allow us to gather more information about the mechanism involved. Ylide 1c was also studied showing similar reactivity and leading to the highly selective synthesis of 2,3- disubstituted-3-phenylpropenoate

On the mechanism of carboxylic acid co-catalyst assisted metalloporphyrin oxidations

The role of the carboxylic acid as co-catalyst in metalloporphyrin catalytic hydrogen peroxide oxidations is discussed, taking into account its dependence on the ratio relatively to the catalyst. The catalytic efficiency and stability of the catalyst in the presence of an excess of carboxylic acid suggests that a metallo-acylperoxo complex can be the effective oxidation intermediate.http://www.sciencedirect.com/science/article/B6TGM-42G6XGY-4/1/0ef5cfc94471f6985d77385ef339282

A nonionic porphyrin as a noninterfering DNA antibacterial agent

The increasing interest in clinical bacterial photodynamic inactivation has led to the search for photosensitizers with higher bactericidal efficiency and less side effects on the surrounding tissues. We present a novel nonionic porphyrin, the 5,10,15‐tris(2,6‐dichlorophenyl)‐20‐[4‐N‐(6‐amino‐hexyl)sulfonamido)phenyl]‐porphyrin (ACS769F4) with substantial improvements in the efficiency of nonionic sensitizers. This porphyrin causes eradication of both Escherichia coli and Staphylococcus aureus by the photodynamic effect but in higher concentrations compared with 5,10,15,20‐tetrakis (4‐N,N,N‐trimethylammoniumphenyl)‐porphyrin p‐tosylate (TTAP4+), a known bactericidal tetracationic porphyrin. More important, under such conditions, ACS769F4 proved to be harmless to two mammalian cells lines (human embryonic and baby hamster kidney), causing no reduction in their viability or negative impact on their cytoskeleton, despite its accumulation in cellular structures. On the contrary, TTAP4+ is shown to accumulate in the nucleus of mammalian cells, in association to DNA, causing chromatin condensation after exposure to light. Furthermore, dark incubation with TTAP4+ was shown to have a deleterious effect on the microtubule network. Based on its bactericidal efficiency, also observed without exposure to light, and on the low tendency to be harmful or genotoxic to mammalian cells, ACS769F4 should be looked at as an interesting photosensitizer to be evaluated for clinical purposes.info:eu-repo/semantics/publishedVersio