Synthesis and DNA Cleavage Properties of Triazacrown Derivatives

Abstract

New metal-free DNA cleaving reagent 1, 1,4,7-triazacrown (TACN) both with aminoethyl, hydroxyethyl side arms and a planar anthraquinone linked by an alkyl (1,6-hexamethylene) spacer has been synthesized and characterized by NMR and MS spectrometry. For comparison, the corresponding aminoethyl, hydroxyethyl triazacrown derivative 2 without the anthraquinone has also been synthesized. DNA-binding properties via fluorescence and CD spectroscopy indicate that the binding affinity of 1 with DNA is much stronger than that of 2. Agarose gel electrophoresis was used to assess plasmid pUC19 DNA cleavage. Kinetic data of DNA cleavage promoted by 1, 2 and parent triazacrown (TACN) 3 under physiological condition give the 15-fold and 234-fold rate acceleration of compound 1 over 2 and parent triazacrown 3. Radical scavenger inhibition study suggests that DNA cleavage promoted by 1 may be a non-oxidative pathway through the transphosphorylation and then hydrolysis. The dramatic rate acceleration is due not only to the anthraquinone moiety of compound 1 intercalating into DNA base pairs via stacking interaction, but also the cooperative catalysis of the nucleophilic hydroxyl and the electrophilic ammonium group for the cleavage of phosphodiester of DNA.

meso-Mono-[4-(1,4,7-triazacyclononanyl)]-tri(phenyl)]porphyrin and the respective zinc(ii)-complex: complete characterization and biomolecules binding abilities

“…Transition metal complexes of TACN have found application as sensors, 23 metalloenzyme models 24 as well as hydrolytic agents capable of the non-oxidative cleavage of a range of substrates, including activated esters 25 and DNA. 26,27 Thorough literature search revealed that heterocycles containing an N-donor atom ring system, such as 1,4,8,11-tetraazacyclotetradecane (cyclam), 28 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) 29 and 1,4,7-triazacyclononane (TACN), 30 exhibit a wide spectrum of medical and biomimetical activities, for example, acting as a chelator for image contrast, 31,32 nucleic acids delivery, 33 DNA cleavage 34 or therapeutic agents for cancer. 35,36 By considering the biological significance of these two classes of molecules, it was contemplated to construct new triazacyclononane-substituted porphyrins combining the porphyrin and TACN moieties, using 2-chloromethyl-4-methyl-6-formylphenol (Cmff ) as a spacer, in a single molecular framework.…”

Label‐Free DNA Sensors Based on Field‐Effect Transistors with Semiconductor of Carbon Materials

“…DNA can constitute genetic instructions to guide biological development and operation of vital functions. [1][2][3] Double-stranded DNA (dsDNA) consists of pairs of bonded complementary single-stranded DNA (ssDNA) to form the well-known DNA double helix. DNA fragment with the genetic information is called a gene.…”