Selective Assembly between Cu ²⁺ and β-Nicotinamide Mononucleotide (NMN)

Nucleotides contain abundant N/O coordination sites, thus enabling versatile assembly with various metal ions. Here, we reported an unexpected discovery that β-nicotinamide mononucleotide (NMN) could selectively assemble with Cu²⁺ to generate blue-green precipitation, while the reduced form of NMN, namely, NMNH, does not exhibit such selectivity. For NMN-containing nicotinamide adenine dinucleotide (NAD⁺), similar selective assembly with Cu²⁺ was also observed, but disappeared for NADH. Further investigation revealed that the N⁺ site in the pyridine moiety is indispensable for the selective assembly. Isothermal titration calorimetry revealed that Cu²⁺ bears better binding with NMN over other divalent metal ions, but it is smaller than trivalent metal ions (e.g., Ln³⁺). Probably, the electrostatic repulsion between the N⁺ of NMN and Cu²⁺ eventually balances with their binding, thus leading to a selective assembly. This work reveals a unique finding in the coordination chemistry of nucleotides.