Selective DNA Recognition and Cytotoxicity of Water-Soluble Helical Metallosupramolecular Polymers

Abstract

Water-soluble helical Fe(II)-based metallosupramolecular polymers ((P)- and (M)-polyFe) were synthesized by 1:1 complexation of Fe(II) ions and bis(terpyridine)s bearing a (R)- and (S)-BINOL spacer, respectively. The binding affinity to calf thymus DNA (ct-DNA) was investigated by titration measurements. (P)-PolyFe with the same helicity as B-DNA showed 40-fold higher binding activity (K = 13.08 × 10 M) to ct-DNA than (M)-polyFe. The differences in binding affinity were supported by electrochemical impedance spectroscopy analysis. The charge-transfer resistance (R) of (P)-polyFe increased from 2.5 to 3.9 kΩ upon DNA binding, while that of (M)-polyFe was nearly unchanged. These results indicate that ionically strong binding of (P)-polyFe to DNA chains decreased the mobility of ions in the conjugate. Unique rod-like images were obtained by atomic force microscopy measurement of the DNA conjugate with (P)-polyFe, likely because of the rigid binding between DNA chains and the polymer. Differences in polymer chirality lead to significantly different cytotoxicity levels in A549 cells. (P)-PolyFe showed higher binding affinity to B-DNA and much higher cytotoxicity than (M)-polyFe. The helicity in metallosupramolecular polymer chains was important not only for chiral recognition of DNA but also for coordination to a biological target in the cellular environment.

Characterization and Inception of a Triterpenoid Astrakurkurol, as a Cytotoxic Molecule on Human Hepatocellular Carcinoma Cells, Hep3B

“…Several research groups further added that any triterpene compound with helicity will enumerate their anticancer activity . Higuchi and co-workers reported the cytotoxic behavior of helical metallosupramolecular polymers and highlighted the importance of the presence of helicity in a potent anticancer compound for chiral recognition of DNA …”

“…39 Higuchi and co-workers reported the cytotoxic behavior of helical metallosupramolecular polymers and highlighted the importance of the presence of helicity in a potent anticancer compound for chiral recognition of DNA. 40 Our recent work emphasized to look into the X-ray crystal structure of this natural lanostane-type triterpenoid, which reveals appealing cooperative non-covalent interactions. DFT calculations of the compound indicate that in the solid state, non-covalent interactions have a crucial role in stabilizing the structure of astrakurkurol.…”

Helical Fe(II)-Based Metallo-Supramolecular Polymers: Effect of Crown Ether Groups Located outside the Helix on Hydrous Proton Channel Formation

“…PolyFe-H was prepared previously and characterized thoroughly in our earlier report. 6 Instrumentation. 1 H and 13 C NMR spectra were obtained by a JEOL AL 300/BZ instrument (300 and 75 MHz, respectively).…”

“…A helical MSP can be synthesized using an axially chiral ligand. 6 As for the helical MSP, the selective chemical modification inside or outside the helix is expected to supply a new function. Here, we report the helical Fe(II)-based MSPs with crown ether groups located outside the helix as a new proton-conductive polymer.…”

Increase in the apparent intercalation ability of a platinum complex via multivalency by installation into the sidechain of a graft copolymer and observation of structural changes in the intercalated DNA

“…Polymerized metal complexes prepared through the formation of coordinate bonds by mixing metal and ligand monomers have been reported in the literature. 15,16 Compared to these types, it is more feasible to evaluate the required intercalator density in the polymer chain for the multivalency by polymer graing the ligand units into a sidechain. This is because the number of intercalators per polymer chain can be controlled by adjusting the metal/polymer molar ratio without changing the main chain of the polymer segment.…”