Catalysis of Michael Additions by Covalently Modified G-Quadruplex DNA.

Enantioselective catalysis utilizing G-quadruplex DNA-based artificial metalloenzymes has emerged as a new approach in the field of aqueous-phase homogeneous catalysis. Recently, a catalytic asymmetric Michael addition employing a covalently modified G-quadruplex in combination with CuII ions has been reported. Here we assess, by systematic chemical variation and using various spectrometric techniques, a variety of parameters that govern rate acceleration and stereoselectivity of the reaction, such as the position of modification, the topology of the quadruplex, the nature of the ligand, the length of the linker between ligand and DNA, the chemical identity of monovalent ions and transition metal complexes. The DNA quadruplex modified at position 10 (dU10) with hexynyl-linked bpy ligand showed twice the initial reaction rate as compared with the DNA strand derivatized at position 12 (dU12). The strikingly different dependence of the stereoselectivity on the linker length, and their different spectroscopic properties indicate large differences in the architecture of the catalytic centers between the dU10-derivatized and the dU12-modified quadruplexes. Upon addition of CuII , both types of bpy-derivatized DNA strands form defined 1:1 Cu-DNA complexes stable enough for mass spectrometric analysis, while the underivatized strands exhibit weak and unspecific binding, correlated with much lower catalytic rate acceleration. Both dU10- and dU12-derivatized quadruplexes could be reused ten times without reduction of stereoselectivity.

Zwitterionic Modification of Ultrasmall Iron Oxide Nanoparticles for Reduced Protein Corona Formation.

Polyacrylic-acid-coated ultra-small super-paramagnetic iron oxide nanoparticles were surface-modified with low-molecular-weight sulfobetaines or 3-(diethylamino)propylamine in order to generate nanoparticles with zwitterionic character (ZW-NPs). The ZW-NPs proved highly resistant to serum protein corona formation in vitro, as revealed by atomic force microscopy, SDS-PAGE and proteomics analysis, and exhibited low cytotoxicity towards A431 and HEK293 cells. The presence of unreacted carboxylic acid groups enabled additional functionalization with fluorescent (Cy5) and radioactive [64 Cu-dmptacn; dmptacn=1,4-bis(2-pyridinylmethyl)-1,4,7-triazacyclononane] moieties. Overall, the ZW-NPs represent promising platforms for the development of new multimodal diagnostic/therapeutic agents possessing "stealth" properties.

Cu(II)-selective bispidine-dye conjugates.

The substitution of tetradentate bispidine ligands with rhodamine and cyanine dye molecules, coupled to an amine donor, forming an amide as potential fifth donor, is described. Bispidines are known to lead to very stable Cu(II) complexes, and the coordination to Cu(II) was expected to efficiently quench the fluorescence of dye molecules. However, at physiological pH the amide is not coordinated, as shown by titration experiments and crystallographic structural data of three possible isomers of these complexes. This may be due to the specific cavity shape of bispidines and the Jahn-Teller lability of the Cu(II) center. While Cu(II) coordination in aqueous solution leads to efficient fluorescence quenching, experiments show that the complex stabilities are not large enough for Cu(II) sensing in biological media, and possibilities are discussed, how this may be achieved by optimized bispidine-dye conjugates.