Enhanced Conductivity In Multi-Copper-Mediated Thieno-Expanded and Sulfur-Substituted Purine Base Pairs

Functional DNA modifications hold promise for nanoelectronics, yet achieving stable and conductive systems remains challenging. This work introduces thieno-expanded sulfur-substituted purine bases (tth-/ttz-G/A) and constructs Cu-modified base pairs by replacing protons in Watson-Crick regions with copper(I) (^tthG_3CuC, ^tthA_2CuT, ^ttzG_3CuC, ^ttzA_2CuT, ^tthG_3CuT, ^tthA_2CuC, ^ttzG_3CuT, and ^ttzA_2CuC). It reveals a synergistic strategy combining thieno-expanded backbone modification with multicopper(I) coordination to overcome this challenge. Density functional theory (DFT) calculations reveal that the expanded framework provides a stable π-conjugated platform and intrinsically narrows the HOMO-LUMO gap, while multicopper substitution introduces strong σ-type Cu-N/O coordination bonds that dramatically enhance binding energies by an order of magnitude. Critically, copper coordination synergistically modulates the frontier orbitals, raising both the HOMO and LUMO levels, with a more pronounced HOMO upshift. This significantly lowers the ionization potential, narrows the energy gap, reduces the electron affinity, and enhances hole transport capability while suppressing electron capture. Red-shifted absorption spectra and increased charge-transfer transitions confirm facilitated charge migration. In triple stacks, copper modification consistently reduces the energy gap, with the extent of narrowing depending on both base identity and sequence topology (crossover versus repeat). These findings establish multicopper-modified, thieno-expanded purine base pairs as promising theoretical candidates for DNA-based molecular wires and provide a rational guideline/design principles for designing functional nucleic acid nanomaterials through the orthogonal combination of scaffold expansion and metal coordination.