Elucidating the mechanism of the considerable mechanical stiffening of DNA induced by the couple Zn(2+)/Calix[4]arene-1,3-O-diphosphorous acid

The couple Calix[4]arene-1,3-O-diphosphorous acid (C4diP) and zinc ions (Zn(2+)) 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(2+) 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(2+) by Zn(2+) bridging coordination of the phosphate groups. Then, at high ratios of Zn(2+) to C4diP, interdigitated dimerization of C4diP is followed by cross coordination of DNA strands through Zn(2+)/C4diP inter-strand interaction. The sum of these interactions leads to strong stiffening of the DNA bundles and increased inter-strand binding.