Ni(II) complexes of His2 peptides as multi-responsive electrochemical probes for anion sensing

Peptides possessing a histidine residue at the second position (His2) exhibit distinctive coordination properties, effectively binding transition metal cations. The resulting complexes, with labile binding sites, offer advantageous features as potential molecular receptors. In this work, a His2 peptide library was designed to select a sequence that, upon binding Ni(II) ions, would exhibit the most promising properties for anion sensing. Electrochemical techniques were used to characterize the redox properties of the studied Ni(II)-His2 peptide complexes. Subsequently, voltammetric responses of the complexes in the presence of various biologically relevant anions (chlorides, sulfates, acetates, lactates and phosphates) were collected and analyzed using Principal Component Analysis, providing effective anion discrimination based on electrochemical fingerprints. Finally, a simple methodology was proposed to differentiate varying lactate and phosphate concentrations in complex, multi-ion samples, simulating physiological and pathological blood plasma conditions. The results confirm the high application potential of the proposed class of molecular receptors and provide insights into novel anion-sensing strategies utilizing metal-peptide complexes as multi-responsive electrochemical probes.