DNA Droplet Formation and Nucleic Acid–Binding Properties of a Cationic Dinuclear Platinum(II) Complex for the Construction of Biological Metal–Organic Frameworks

We investigated the cationic dinuclear Pt(II) complex AMPZ ([{<i>cis</i>-Pt(NH₃)₂}₂(μ-OH)(μ-pyrazolato)](NO₃)₂) as a tool for constructing biological metal-organic frameworks (bio-MOFs) via liquid-liquid phase separation (LLPS). AMPZ efficiently induced LLPS in 44- or 45-mer single-stranded DNA (ssDNA) fragments, generating droplets whose properties depended on the relative abundance of nucleobase and the presence or absence of coordination interactions with AMPZ. In guanine-rich ssDNA, AMPZ promoted droplet gelation through cross-linking and formation of a coordination-bonded network, whereas adenine-rich, guanine-deficient ssDNA did not undergo gelation. ¹H nuclear magnetic resonance analysis of reactions between AMPZ and mononucleosides or mononucleotides revealed that nucleobase-dependent differences in droplet properties arise from distinct reaction mechanisms and kinetics. Notably, AMPZ and adenine form a unique 1:1 complex in which the N7 nitrogen and deprotonated N6-NH of adenine coordinate to the two Pt(II) ions of AMPZ, forming an eight-membered chelate. This chelate prevents cross-linking of adenine-rich ssDNA and the subsequent gel transition. AMPZ and cytosine also provide a similar 1:1 chelate complex. These findings demonstrate that AMPZ modulates droplet formation and properties in a nucleobase-dependent manner. The mechanistic insights uncovered here provide a new strategy for constructing bio-MOFs via LLPS, exploiting the two-step interactions between AMPZ and DNA.