ABSTRACT
A metal-free N-hydroxyphthalimide (NHPI) catalyzed aerobic oxidative cleavage of olefins has been developed. Molecular oxygen is used as the oxidant and reagent for this oxygenation reaction. This methodology has prevented the use of toxic metals or overstoichiometric amounts of traditional oxidants, showing good economical and environmental advantages. Based on the experimental observations, a plausible mechanism is proposed.
Subject(s)
Alkenes/chemistry , Oxidants/chemistry , Oxygen/chemistry , Phthalimides/chemistry , Catalysis , Molecular Structure , Oxidation-ReductionABSTRACT
Although siRNA techniques have been broadly applied as a tool for gene knockdown, substantial challenges remain in achieving efficient delivery and in vivo efficacy. In particular, the low efficiency of target gene silencing in vivo is a critical limiting step to the clinical application of siRNA therapies. Poly(amidoamine) (PAMAM) dendrimers are widely used as carriers for drug and gene delivery; however, in vivo siRNA delivery by PAMAM dendrimers remains to be carefully investigated. In this study, the effectiveness of G5 and G6 PAMAM dendrimers with 8% of their surface amines conjugated to MPEG-5000 was studied for siRNA delivery in vitro and for intramuscular in vivo delivery in mice. The results from the PEG-modified dendrimers were compared to the results from the parent dendrimers as well as Lipofectamine 2000 and INTERFERin. Both PEG-modifed dendrimers protect the siRNA from being digested by RNase and gave high transfection efficiency for FITC-labeled siRNA in the primary vascular smooth muscle cells (VSMC) and mouse peritoneal macrophages. The PEG-modified dendrimers achieved knockdown of both plasmid (293A cells) and adenovirus-mediated green fluorescence protein (GFP) expression (Cos7 cells) in vitro with efficiency similar to that shown for Lipofectamine 2000. We further demonstrated in vivo that intramuscular delivery of GFP-siRNA using PEG-modified dendrimer significantly suppressed GFP expression in both transiently adenovirus infected C57BL/6 mice and GFP transgenic mice.
Subject(s)
Dendrimers/chemistry , Gene Silencing/physiology , Polyethylene Glycols/chemistry , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Animals , Animals, Newborn , COS Cells , Cell Line , Cricetinae , Female , Fluorescein-5-isothiocyanate/chemistry , Green Fluorescent Proteins/genetics , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Myocytes, Smooth Muscle/metabolism , RNA, Small Interfering/chemistryABSTRACT
An efficient difluorohydroxylation of substituted indoles leading to 3,3-difluoroindolin-2-ols with good yields by using Selectfluor as the electrophilic fluorinating reagent has been developed. In this methodology, the indole rings were difluorinated highly regioselectively at the C3 carbon site. This protocol is practically convenient, easily handled under mild conditions, and provides an efficient way to produce the unique difluorinated indolin-2-ol structure. When alcohols were used as the nucleophiles instead of H(2)O, the corresponding products were obtained in moderate yields. Based on the experimental observations, a plausible mechanism is proposed.
Subject(s)
Hydrocarbons, Fluorinated/chemistry , Indoles/chemistry , Crystallography, X-Ray , Hydroxylation , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
A Fe-catalytic highly selective ring expansion reaction of alkynylcyclopropyl alkanols to alkynylcyclobutanols via a 1,2-carbon shift under mild conditions was developed. A new class of homogeneous FeCl(2)/O(2) catalytic system was employed in these novel transformations.
