Synergistic Tuning of Active Sites and π-Conjugation in 2D Conductive MOFs Boosts Uric Acid Electrosensing

Uric acid (UA) detection is critical for human health monitoring, necessitating the development of electrochemical sensing electrodes suitable for physiological environments. This study evaluated four 2D conductive metal–organic frameworks (2D c-MOFs), namely Cu-HHTP, Ni-HHTP, Cu-HAB, and Ni-HAB, which share identical graphene-like 2D sheet structures but differ in π-conjugation extent and catalytic active centers [MX4] (M = Cu or Ni; X = O or NH) as electrosensing electrodes. Electrochemical sensing performance was compared by detecting UA in phosphate-buffered saline (PBS). Herein, the Ni-HHTP electrode demonstrated superior sensitivity (6.79 μA·μM−1·cm−2), the lowest oxidation potential (0.272 V), and the lowest detection limit (0.44 μM). Langmuir adsorption isotherm analysis revealed that the Ni-HHTP electrode possesses the highest surface coverage (ΓA) (5061.16 pmol cm−2) and the most favorable Gibbs adsorption free energy (ΔG°) (−18.775 kJ mol−1), indicating its strongest UA adsorption capacity and molecular interaction. This enhanced performance is attributed to the optimal synergy between [NiO4] catalytic centers and extended ligand π-conjugation, facilitating greater analyte adsorption and electron transfer efficiency. This work establishes clear structure–performance relationships for 2D c-MOF electrodes in UA detection, providing key insights for designing advanced electrosensing materials.