Polypropylene and all industrially produced polyolefins are linear molecules containing chain ends. Employing a tungsten catalyst, Veige and co-workers polymerize propyne to give cyclic polypropyne followed by hydrogenation to produce atactic polypropylene. Evidence for a cyclic topology comes from dynamic and static light-scattering techniques and rheology. Compared with linear polypropylene, the atactic cyclic polypropylene exhibits a >20 C increase in its glass transition temperature (T g ).
Circular bivalent aptamers (cb-apt) comprise an emerging class of chemically engineered aptamers with substantially improved stability and molecular recognition ability. Its therapeutic application, however, is challenged by the lack of functional modules to control the interactions of cb-apt with therapeutics. We present the design of a β-cyclodextrin-modified cb-apt (cb-apt-βCD) and its supramolecular interaction with molecular therapeutics via host-guest chemistry for targeted intracellular delivery. The supramolecular ensemble exhibits high serum stability and enhanced intracellular delivery efficiency compared to a monomeric aptamer. The cb-apt-βCD ensemble delivers green fluorescent protein into targeted cells with efficiency as high as 80%, or cytotoxic saporin to efficiently inhibit tumor cell growth. The strategy of conjugating βCD to cb-apt, and subsequently modulating the supramolecular chemistry of cb-apt-βCD, provides a general platform to expand and diversify the function of aptamers, enabling new biological and therapeutic applications.
This report describes the synthesis and characterization of novel N-heterocyclic carbene (NHC) gold(I) complexes and their bioconjugation to the CCRF-CEM leukemia specific aptamer sgc8c. Confirmation of successful bioconjugation was achieved by using fluorescent tags on both the NHC-Au(I) complex and the aptamer. Cell viability assays indicate the NHC-Au(I)-aptamer conjugate is more cytotoxic than the NHC-gold complex alone. A combination of flow cytometry, confocal microscopy, and cell viability assays provide clear evidence that the NHC-Au(I)-aptamer conjugate is selective for targeted CCRF-CEM leukemia cells.
Cyclic polymers possess properties
that are significantly different
from their linear analogs, such as higher densities, smaller hydrodynamic
volumes, and higher glass transition temperatures. Poly(4-methyl-1-pentene)
(PMP), a linear polyolefin, is a commercial transparent
thermoplastic and has applications in packaging materials and release
membranes. Polymerizing 4-methyl-1-pentyne with a tungsten alkylidyne
catalyst and subsequent hydrogenation (>99%) provided cyclic poly(4-methyl-1-pentene)
(
c-PMP). Evidence of a cyclic topology
comes from rheology/viscosity studies, light scattering measurements,
and size-exclusion chromatography. Importantly, atactic
c-PMP exhibits a T
g (39
°C) 10 °C higher than the linear analog. A 15 g-scale cyclic
polymerization was also achieved with 1-pentyne. Subsequent hydrogenation
yielded 10 g of cyclic poly(1-pentene). Measurements of initial rates
during the polymerization of 1-pentyne reveal a catalyst activity
of 180,000,000 g/molcat/h.
This work describes several synthetic approaches to append organic functional groups to gold and silver N-heterocyclic carbene (NHC) complexes suitable for applications in biomolecule conjugation. Carboxylate appended NHC ligands (3) lead to unstable AuI complexes that convert into bis-NHC species (4). A benzyl protected carboxylate NHC-AuI complex 2 was synthesized but deprotection to produce the carboxylic acid functionality could not be achieved. A small library of new alkyne functionalized NHC proligands were synthesized and used for subsequent silver and gold metalation reactions. The alkyne appended NHC gold complex 13 readily react with benzyl azide in a copper catalyzed azide-alkyne cycloaddition reaction to form the triazole appended NHC gold complex 14. Cell cytotoxicity studies were performed on DLD-1 (colorectal adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MCF-7 (breast adenocarcinoma), CCRF-CEM (human T-Cell leukemia), and HEK (human embryonic kidney). Complete spectroscopic characterization of the ligands and complexes was achieved using 1H and 13C NMR, gHMBC, ESI-MS, and combustion analysis.
A novel cationic NHC-Au(i) complex was synthesized and studied for its antitumor activity. For all the cell lines tested, cationic NHC-Au(i) complex 2 shows much higher cytotoxicity than its neutral analogue 1. To achieve selective cancer cell targeting, complex 2 was covalently conjugated to aptamer AS1411, a DNA aptamer with strong binding affinity for nucleolin. The successful conjugation was confirmed by HPLC, gel electrophoresis, fluorescence spectroscopy and UV-Vis absorption. Conjugate AS1411-2 was then examined for its specific targeting and binding ability towards cancer cells over human normal cells using flow cytometry analysis and confocal microscopy. The cytotoxicity of AS1411-2 was then estimated by MTS assay. It was found that AS1411-2 exhibits higher activity than complex 2 towards targeted cells. Importantly, AS1411-2 exhibits much lower cytotoxicity towards healthy normal cell lines. Concurrently, the control groups without the AS1411 aptamer or without the NHC-Au(i) complex do have significant impact on cancer cell viability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.