Heterobimetallic Base Pair Programming in Designer 3D DNA Crystals

• Published in: Journal of the American Chemical Society Vol. 145; no. 32; pp. 17945 - 17953
• Main Authors: Lu, Brandon, Ohayon, Yoel P., Woloszyn, Karol, Yang, Chu-fan, Yoder, Jesse B., Rothschild, Lynn J., Wind, Shalom J., Hendrickson, Wayne A., Mao, Chengde, Seeman, Nadrian C., Canary, James W., Sha, Ruojie, Vecchioni, Simon
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.08.2023; American Chemical Society (ACS)
• Subjects: Base Pairing; Chemistry; DNA - chemistry; Mercury - chemistry; Silver - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.3c05478

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.