Elucidating the mechanism of the considerable mechanical stiffening of DNA induced by the couple Zn/Calix[4]arene-1,3-O-diphosphorous acid.

The couple Calix[4]arene-1,3-O-diphosphorous acid (C4diP) and zinc ions (Zn) acts as a synergistic DNA binder. Silicon NanoTweezer (SNT) measurements show an increase in the mechanical stiffness of DNA bundles by a factor of >150, at Zn to C4diP ratios above 8, as compared to Zinc alone whereas C4diP alone decreases the stiffness of DNA. Electroanalytical measurements using 3D printed devices demonstrate a progression of events in the assembly of C4diP on DNA promoted by zinc ions. A mechanism at the molecular level can be deduced in which C4diP initially coordinates to DNA by phosphate-phosphate hydrogen bonds or in the presence of Zn by Zn bridging coordination of the phosphate groups. Then, at high ratios of Zn to C4diP, interdigitated dimerization of C4diP is followed by cross coordination of DNA strands through Zn/C4diP inter-strand interaction. The sum of these interactions leads to strong stiffening of the DNA bundles and increased inter-strand binding.