Heterobimetallic Base Pair Programming in Designer 3D DNA Crystals

Abstract

Metal-mediated DNA (mmDNA) presents a pathway toward engineering bioinorganic and electronic behavior into DNA devices. Many chemical and biophysical forces drive the programmable chelation of metals between pyrimidine base pairs. Here, we developed a crystallographic method using the three-dimensional (3D) DNA tensegrity triangle motif to capture single- and multi-metal binding modes across granular changes to environmental pH using anomalous scattering. Leveraging this programmable crystal, we determined 28 biomolecular structures to capture mmDNA reactions. We found that silver­(I) binds with increasing occupancy in T–T and U–U pairs at elevated pH levels, and we exploited this to capture silver­(I) and mercury­(II) within the same base pair and to isolate the titration points for homo- and heterometal base pair modes. We additionally determined the structure of a C–C pair with both silver­(I) and mercury­(II). Finally, we extend our paradigm to capture cadmium­(II) in T–T pairs together with mercury­(II) at high pH. The precision self-assembly of heterobimetallic DNA chemistry at the sub-nanometer scale will enable atomistic design frameworks for more elaborate mmDNA-based nanodevices and nanotechnologies.