Controllable construction of base pairing and chirality study in supramolecular assemblies based on guanine nucleotides

Abstract

A detailed understanding and investigation of mismatched bases in non-B DNA structures can help reveal the pathogenesis of hereditary genetic diseases and provide a theoretical foundation for the development of gene therapy technologies. Accordingly, this study successfully designed and synthesized three nucleotide-based assemblies using guanosine 5′-monophosphate (GMP) as a building block. The synthesis leveraged a synergistic assembly strategy involving transition metal ions and the auxiliary ligand bpe, controlled by pH modulation. The assemblies are: {[M(GMP)(bpe)(H₂O)₃]·9H₂O}_n (M = Mn(II), Ni(II)) (1 and 2) and (HGMP)₂(H₂bpe)·7H₂O (3) (bpe = 1,2-bis(4-pyridyl)ethylene). Comprehensive characterization of 1–3 was conducted through infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV-vis), X-ray powder diffraction (PXRD) and single-crystal X-ray diffraction. Crystallographic studies revealed that 1 and 2 exist as coordination polymers, while 3 forms an ionic co-crystal. In 3, the bpe ligand serves as a “scaffolding” through multiple π–π stacking interactions, successfully constructing a guanine–guanine base mismatch pattern with high anti–anti glycosidic bond torsion angles. These validate that the strategy exhibits certain general applicability and effectiveness. Furthermore, combining single-crystal structure analysis and solid-state circular dichroism (CD) spectroscopy, the processes of chiral transfer, chiral induction, and chiral amplification in the three assemblies were investigated. It was found that in assembly 3 containing base mismatches, the system energy increases and the chiral signal undergoes a blue shift. This study not only develops a new assembly paradigm for nucleotide-based functional materials, but also provides important chemical model references for deepening the understanding of the molecular mechanism of base mismatches and designing targets in gene therapy.